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1. Molecular pathways identified from single nucleotide polymorphisms demonstrate mechanistic differences in systemic lupus erythematosus patients of Asian and European ancestry.

Author

Owen, Katherine A, Bell, Kristy A, Price, Andrew, Bachali, Prathyusha, Ainsworth, Hannah, Marion, Miranda C, Howard, Timothy D, Langefeld, Carl D, Shen, Nan, Yazdany, Jinoos, Dall'era, Maria, Grammer, Amrie C, and Lipsky, Peter E

Subjects
Humans, Lupus Erythematosus, Systemic, Genetic Predisposition to Disease, Case-Control Studies, Genotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Lupus, Clinical Research, Autoimmune Disease, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system
Abstract

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE.

Published
2023

2. Characterization of HIV risks in a Brazilian sickle cell disease population.

Author

de Almeida-Neto, C, Blatyta, P, Kelly, S, Goncalez, T, Carneiro-Proietti, A, Salomon, T, Miranda, C, Sabino, E, Preiss, L, Maximo, C, Loureiro, P, and Custer, Brian

Subjects
HIV, HIV risk factors, Sickle cell disease, Transfusion transmitted infections, Adolescent, Adult, Aged, Anemia, Sickle Cell, Blood Transfusion, Brazil, Case-Control Studies, Cohort Studies, Female, HIV Infections, Health Risk Behaviors, Humans, Male, Middle Aged, Prevalence, Sexual Partners, Substance Abuse, Intravenous
Abstract

BACKGROUND: A low prevalence of HIV in sickle cell disease (SCD) patients has been reported in the literature though mechanisms for this are not understood. METHODS: HIV risk behaviors were compared between SCD cases and non-SCD controls using a self-administered audio computer-assisted self-interview. SCD cases were recruited from a multi-center SCD cohort established in Brazil; controls were recruited from SCD social contacts. Categorical variables were analyzed using Chi-Square or Fisher exact test. Continuous variables were compared using the Mann-Whitney U test. RESULTS: There were 152 SCD cases and 154 age/location matched controls enrolled at three participating Brazilian centers during 2016-17. No significant differences in number of sexual partners (lifetime or previous 12 months), male-to-male sex partners or intravenous drug use were observed. Cases received more transfusions, surgeries, and acupuncture treatment. CONCLUSIONS: Besides the risk of transfusion-transmitted HIV, which is now exceedingly rare, SCD and non-SCD participants demonstrated similar HIV risk behaviors. Causes other than risk behaviors such as factors inherent to SCD pathophysiology may explain the reported low prevalence of HIV in SCD.

Published
2020

3. The peri-Sylvian cortical network underlying single word repetition revealed by electrocortical stimulation and direct neural recordings

Author

Leonard, Matthew K, Cai, Ruofan, Babiak, Miranda C, Ren, Angela, and Chang, Edward F

Subjects
Biological Psychology, Cognitive and Computational Psychology, Biomedical and Clinical Sciences, Psychology, Basic Behavioral and Social Science, Behavioral and Social Science, Neurosciences, Clinical Research, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Acoustic Stimulation, Adult, Aged, Brain Mapping, Cerebral Cortex, Cognition, Cohort Studies, Electric Stimulation, Electrocorticography, Female, Humans, Male, Middle Aged, Nerve Net, Speech, Speech Perception, Electrocortical stimulation, Verbal repetition, Peri-Sylvian cortex, Neurosurgery, Speech perception, Speech production, Medical and Health Sciences, Psychology and Cognitive Sciences, Language, Communication and Culture, Experimental Psychology, Biomedical and clinical sciences, Language, communication and culture
Abstract

Verbal repetition requires the coordination of auditory, memory, linguistic, and motor systems. To date, the basic dynamics of neural information processing in this deceptively simple behavior are largely unknown. Here, we examined the neural processes underlying verbal repetition using focal interruption (electrocortical stimulation) in 58 patients undergoing awake craniotomies, and neurophysiological recordings (electrocorticography) in 8 patients while they performed a single word repetition task. Electrocortical stimulation revealed that sub-components of the left peri-Sylvian network involved in single word repetition could be differentially interrupted, producing transient perceptual deficits, paraphasic errors, or speech arrest. Electrocorticography revealed the detailed spatio-temporal dynamics of cortical activation, involving a highly-ordered, but overlapping temporal progression of cortical high gamma (75-150Hz) activity throughout the peri-Sylvian cortex. We observed functionally distinct serial and parallel cortical processing corresponding to successive stages of general auditory processing (posterior superior temporal gyrus), speech-specific auditory processing (middle and posterior superior temporal gyrus), working memory (inferior frontal cortex), and motor articulation (sensorimotor cortex). Together, these methods reveal the dynamics of coordinated activity across peri-Sylvian cortex during verbal repetition.

Published
2019

4. Transancestral mapping and genetic load in systemic lupus erythematosus.

Author

Langefeld, Carl D, Ainsworth, Hannah C, Cunninghame Graham, Deborah S, Kelly, Jennifer A, Comeau, Mary E, Marion, Miranda C, Howard, Timothy D, Ramos, Paula S, Croker, Jennifer A, Morris, David L, Sandling, Johanna K, Almlöf, Jonas Carlsson, Acevedo-Vásquez, Eduardo M, Alarcón, Graciela S, Babini, Alejandra M, Baca, Vicente, Bengtsson, Anders A, Berbotto, Guillermo A, Bijl, Marc, Brown, Elizabeth E, Brunner, Hermine I, Cardiel, Mario H, Catoggio, Luis, Cervera, Ricard, Cucho-Venegas, Jorge M, Dahlqvist, Solbritt Rantapää, D'Alfonso, Sandra, Da Silva, Berta Martins, de la Rúa Figueroa, Iñigo, Doria, Andrea, Edberg, Jeffrey C, Endreffy, Emőke, Esquivel-Valerio, Jorge A, Fortin, Paul R, Freedman, Barry I, Frostegård, Johan, García, Mercedes A, de la Torre, Ignacio García, Gilkeson, Gary S, Gladman, Dafna D, Gunnarsson, Iva, Guthridge, Joel M, Huggins, Jennifer L, James, Judith A, Kallenberg, Cees GM, Kamen, Diane L, Karp, David R, Kaufman, Kenneth M, Kottyan, Leah C, Kovács, László, Laustrup, Helle, Lauwerys, Bernard R, Li, Quan-Zhen, Maradiaga-Ceceña, Marco A, Martín, Javier, McCune, Joseph M, McWilliams, David R, Merrill, Joan T, Miranda, Pedro, Moctezuma, José F, Nath, Swapan K, Niewold, Timothy B, Orozco, Lorena, Ortego-Centeno, Norberto, Petri, Michelle, Pineau, Christian A, Pons-Estel, Bernardo A, Pope, Janet, Raj, Prithvi, Ramsey-Goldman, Rosalind, Reveille, John D, Russell, Laurie P, Sabio, José M, Aguilar-Salinas, Carlos A, Scherbarth, Hugo R, Scorza, Raffaella, Seldin, Michael F, Sjöwall, Christopher, Svenungsson, Elisabet, Thompson, Susan D, Toloza, Sergio MA, Truedsson, Lennart, Tusié-Luna, Teresa, Vasconcelos, Carlos, Vilá, Luis M, Wallace, Daniel J, Weisman, Michael H, Wither, Joan E, Bhangale, Tushar, Oksenberg, Jorge R, Rioux, John D, Gregersen, Peter K, Syvänen, Ann-Christine, Rönnblom, Lars, Criswell, Lindsey A, Jacob, Chaim O, Sivils, Kathy L, Tsao, Betty P, Schanberg, Laura E, and Behrens, Timothy W

Subjects
Humans, Lupus Erythematosus, Systemic, HLA Antigens, Logistic Models, Case-Control Studies, Mutagenesis, Insertional, Age of Onset, Sequence Deletion, Genetic Load, Multifactorial Inheritance, Polymorphism, Single Nucleotide, African Continental Ancestry Group, American Native Continental Ancestry Group, European Continental Ancestry Group, Hispanic Americans, Lupus Erythematosus, Systemic, Mutagenesis, Insertional, Polymorphism, Single Nucleotide
Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P

Published
2017

5. Phonological Processing in Primary Progressive Aphasia

Author

Henry, Maya L, Wilson, Stephen M, Babiak, Miranda C, Mandelli, Maria Luisa, Beeson, Pelagie M, Miller, Zachary A, and Gorno-Tempini, Maria Luisa

Subjects
Biological Psychology, Cognitive and Computational Psychology, Psychology, Clinical Research, Rare Diseases, Brain Disorders, Neurodegenerative, Frontotemporal Dementia (FTD), Alzheimer's Disease Related Dementias (ADRD), Aphasia, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Dementia, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Aphasia, Primary Progressive, Brain, Female, Humans, Language Tests, Logistic Models, Male, Middle Aged, Organ Size, Phonetics, Reading, Speech, Writing, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

Individuals with primary progressive aphasia (PPA) show selective breakdown in regions within the proposed dorsal (articulatory-phonological) and ventral (lexical-semantic) pathways involved in language processing. Phonological STM impairment, which has been attributed to selective damage to dorsal pathway structures, is considered to be a distinctive feature of the logopenic variant of PPA. By contrast, phonological abilities are considered to be relatively spared in the semantic variant and are largely unexplored in the nonfluent/agrammatic variant. Comprehensive assessment of phonological ability in the three variants of PPA has not been undertaken. We investigated phonological processing skills in a group of participants with PPA as well as healthy controls, with the goal of identifying whether patterns of performance support the dorsal versus ventral functional-anatomical framework and to discern whether phonological ability differs among PPA subtypes. We also explored the neural bases of phonological performance using voxel-based morphometry. Phonological performance was impaired in patients with damage to dorsal pathway structures (nonfluent/agrammatic and logopenic variants), with logopenic participants demonstrating particular difficulty on tasks involving nonwords. Binary logistic regression revealed that select phonological tasks predicted diagnostic group membership in the less fluent variants of PPA with a high degree of accuracy, particularly in conjunction with a motor speech measure. Brain-behavior correlations indicated a significant association between the integrity of gray matter in frontal and temporoparietal regions of the left hemisphere and phonological skill. Findings confirm the critical role of dorsal stream structures in phonological processing and demonstrate unique patterns of impaired phonological processing in logopenic and nonfluent/agrammatic variants of PPA.

Published
2016

6. Transient aphasias after left hemisphere resective surgery.

Author

Wilson, Stephen M, Lam, Daniel, Babiak, Miranda C, Perry, David W, Shih, Tina, Hess, Christopher P, Berger, Mitchel S, and Chang, Edward F

Subjects
Brain, Humans, Glioma, Brain Neoplasms, Epilepsy, Aphasia, Neurosurgical Procedures, Brain Mapping, Prospective Studies, Language, Neuropsychological Tests, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Functional Laterality, Young Adult, ADC = apparent diffusion coefficient, AQ = Aphasia Quotient, BNT = Boston Naming Test, BTLA = basal temporal language area, DWI = diffusion-weighted imaging, MNI = Montreal Neurological Institute, ROI = region of interest, VLSM = voxel-based lesion-symptom mapping, WAB = Western Aphasia Battery, aphasia, resective surgery, voxel-based lesion-symptom mapping, Patient Safety, Neurosciences, Stroke, Brain Disorders, Aging, Clinical Sciences, Neurology & Neurosurgery
Abstract

ObjectTransient aphasias are often observed in the first few days after a patient has undergone resection in the language-dominant hemisphere. The aims of this prospective study were to characterize the incidence and nature of these aphasias and to determine whether there are relationships between location of the surgical site and deficits in specific language domains.MethodsOne hundred ten patients undergoing resection to the language-dominant hemisphere participated in the study. Language was evaluated prior to surgery and 2-3 days and 1 month postsurgery using the Western Aphasia Battery and the Boston Naming Test. Voxel-based lesion-symptom mapping was used to identify relationships between the surgical site location assessed on MRI and deficits in fluency, information content, comprehension, repetition, and naming.ResultsSeventy-one percent of patients were classified as aphasic based on the Western Aphasia Battery 2-3 days postsurgery, with deficits observed in each of the language domains examined. Fluency deficits were associated with resection of the precentral gyrus and adjacent inferior frontal cortex. Reduced information content of spoken output was associated with resection of the ventral precentral gyrus and posterior inferior frontal gyrus (pars opercularis). Repetition deficits were associated with resection of the posterior superior temporal gyrus. Naming deficits were associated with resection of the ventral temporal cortex, with midtemporal and posterior temporal damage more predictive of naming deficits than anterior temporal damage. By 1 month postsurgery, nearly all language deficits were resolved, and no language measure except for naming differed significantly from its presurgical level.ConclusionsThese findings show that transient aphasias are very common after left hemisphere resective surgery and that the precise nature of the aphasia depends on the specific location of the surgical site. The patient cohort in this study provides a unique window into the neural basis of language because resections are discrete, their locations are not limited by vascular distribution or patterns of neurodegeneration, and language can be studied prior to substantial reorganization.

Published
2015

7. Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression

Author

Lu, Xiaoming, Zoller, Erin E, Weirauch, Matthew T, Wu, Zhiguo, Namjou, Bahram, Williams, Adrienne H, Ziegler, Julie T, Comeau, Mary E, Marion, Miranda C, Glenn, Stuart B, Adler, Adam, Shen, Nan, Nath, Swapan K, Stevens, Anne M, Freedman, Barry I, Tsao, Betty P, Jacob, Chaim O, Kamen, Diane L, Brown, Elizabeth E, Gilkeson, Gary S, Alarcón, Graciela S, Reveille, John D, Anaya, Juan-Manuel, James, Judith A, Sivils, Kathy L, Criswell, Lindsey A, Vilá, Luis M, Alarcón-Riquelme, Marta E, Petri, Michelle, Scofield, R Hal, Kimberly, Robert P, Ramsey-Goldman, Rosalind, Bin Joo, Young, Choi, Jeongim, Bae, Sang-Cheol, Boackle, Susan A, Graham, Deborah Cunninghame, Vyse, Timothy J, Guthridge, Joel M, Gaffney, Patrick M, Langefeld, Carl D, Kelly, Jennifer A, Greis, Kenneth D, Kaufman, Kenneth M, Harley, John B, and Kottyan, Leah C

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Biotechnology, Lupus, Autoimmune Disease, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Alleles, Animals, Asian People, Bayes Theorem, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Lupus Erythematosus, Systemic, Mice, Protein Binding, Proto-Oncogene Protein c-ets-1, STAT1 Transcription Factor, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been associated with systemic lupus erythematosus (SLE), or lupus, in independent cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a critical driver of immune cell function and differentiation, and mice deficient in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of 14,551 subjects from multi-ancestral cohorts by starting with genotyped variants and imputing to all common variants spanning ETS1. By constructing genetic models via frequentist and Bayesian association methods, we identified 16 variants that are statistically likely to be causal. We functionally assessed each of these variants on the basis of their likelihood of affecting transcription factor binding, miRNA binding, or chromatin state. Of the four variants that we experimentally examined, only rs6590330 differentially binds lysate from B cells. Using mass spectrometry, we found more binding of the transcription factor signal transducer and activator of transcription 1 (STAT1) to DNA near the risk allele of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed that the risk allele increased binding to the active form of STAT1. Analysis with expression quantitative trait loci indicated that the risk allele of rs6590330 is associated with decreased ETS1 expression in Han Chinese, but not other ancestral cohorts. We propose a model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1.

Published
2015

8. Handedness and language learning disability differentially distribute in progressive aphasia variants

Author

Miller, Zachary A, Mandelli, Maria Luisa, Rankin, Katherine P, Henry, Maya L, Babiak, Miranda C, Frazier, Darvis T, Lobach, Iryna V, Bettcher, Brianne M, Wu, Teresa Q, Rabinovici, Gil D, Graff-Radford, Neill R, Miller, Bruce L, and Gorno-Tempini, Maria Luisa

Subjects
Biological Psychology, Cognitive and Computational Psychology, Psychology, Aphasia, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Acquired Cognitive Impairment, Neurodegenerative, Dementia, Aging, Neurosciences, Rare Diseases, Frontotemporal Dementia (FTD), Clinical Research, Brain Disorders, Mental Health, Behavioral and Social Science, 2.1 Biological and endogenous factors, Mental health, Neurological, Aged, Aphasia, Primary Progressive, Cohort Studies, Comorbidity, Female, Functional Laterality, Humans, Language Development Disorders, Learning Disabilities, Magnetic Resonance Imaging, Male, Middle Aged, Primary Progressive Nonfluent Aphasia, Alzheimer's disease, frontotemporal dementia, dementia aphasia, case control study, risk factors in epidemiology, Alzheimer’s disease, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Abstract

Primary progressive aphasia is a neurodegenerative clinical syndrome that presents in adulthood with an isolated, progressive language disorder. Three main clinical/anatomical variants have been described, each associated with distinctive pathology. A high frequency of neurodevelopmental learning disability in primary progressive aphasia has been reported. Because the disorder is heterogeneous with different patterns of cognitive, anatomical and biological involvement, we sought to identify whether learning disability had a predilection for one or more of the primary progressive aphasia subtypes. We screened the University of California San Francisco Memory and Aging Center's primary progressive aphasia cohort (n = 198) for history of language-related learning disability as well as hand preference, which has associations with learning disability. The study included logopenic (n = 48), non-fluent (n = 54) and semantic (n = 96) variant primary progressive aphasias. We investigated whether the presence of learning disability or non-right-handedness was associated with differential effects on demographic, neuropsychological and neuroimaging features of primary progressive aphasia. We showed that a high frequency of learning disability was present only in the logopenic group (χ(2) = 15.17, P < 0.001) and (χ(2) = 11.51, P < 0.001) compared with semantic and non-fluent populations. In this group, learning disability was associated with earlier onset of disease, more isolated language symptoms, and more focal pattern of left posterior temporoparietal atrophy. Non-right-handedness was instead over-represented in the semantic group, at nearly twice the prevalence of the general population (χ(2) = 6.34, P = 0.01). Within semantic variant primary progressive aphasia the right-handed and non-right-handed cohorts appeared homogeneous on imaging, cognitive profile, and structural analysis of brain symmetry. Lastly, the non-fluent group showed no increase in learning disability or non-right-handedness. Logopenic variant primary progressive aphasia and developmental dyslexia both manifest with phonological disturbances and posterior temporal involvement. Learning disability might confer vulnerability of this network to early-onset, focal Alzheimer's pathology. Left-handedness has been described as a proxy for atypical brain hemispheric lateralization. As non-right-handedness was increased only in the semantic group, anomalous lateralization mechanisms might instead be related to frontotemporal lobar degeneration with abnormal TARDBP. Taken together, this study suggests that neurodevelopmental signatures impart differential trajectories towards neurodegenerative disease.

Published
2013

9. Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups

Author

Kaufman, Kenneth M, Zhao, Jian, Kelly, Jennifer A, Hughes, Travis, Adler, Adam, Sanchez, Elena, Ojwang, Joshua O, Langefeld, Carl D, Ziegler, Julie T, Williams, Adrienne H, Comeau, Mary E, Marion, Miranda C, Glenn, Stuart B, Cantor, Rita M, Grossman, Jennifer M, Hahn, Bevra H, Song, Yeong Wook, Yu, Chack-Yung, James, Judith A, Guthridge, Joel M, Brown, Elizabeth E, Alarcón, Graciela S, Kimberly, Robert P, Edberg, Jeffrey C, Ramsey-Goldman, Rosalind, Petri, Michelle A, Reveille, John D, Vilá, Luis M, Anaya, Juan-Manuel, Boackle, Susan A, Stevens, Anne M, Freedman, Barry I, Criswell, Lindsey A, Group, Bernardo A Pons-Estel on behalf of the Argentine Collaborative, Lee, Joo-Hyun, Lee, Ji-Seon, Chang, Deh-Ming, Scofield, R Hal A, Gilkeson, Gary S, Merrill, Joan T, Niewold, Timothy B, Vyse, Timothy James, Bae, Sang-Cheol, network, Marta E Alarcón-Riquelme on behalf of the BIOLUPUS, Jacob, Chaim O, Sivils, Kathy Moser, Gaffney, Patrick M, Harley, John B, Sawalha, Amr H, and Tsao, Betty P

Subjects
Human Genome, Autoimmune Disease, Lupus, Genetics, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Base Sequence, Chromosome Mapping, Chromosomes, Human, X, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Interleukin-1 Receptor-Associated Kinases, Lupus Erythematosus, Systemic, Methyl-CpG-Binding Protein 2, Molecular Sequence Data, Polymorphism, Single Nucleotide, Racial Groups, Real-Time Polymerase Chain Reaction, Risk Factors, Argentine Collaborative Group, BIOLUPUS network, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology
Abstract

ObjectivesThe Xq28 region containing IRAK1 and MECP2 has been identified as a risk locus for systemic lupus erythematosus (SLE) in previous genetic association studies. However, due to the strong linkage disequilibrium between IRAK1 and MECP2, it remains unclear which gene is affected by the underlying causal variant(s) conferring risk of SLE.MethodsWe fine-mapped ≥136 SNPs in a ∼227 kb region on Xq28, containing IRAK1, MECP2 and seven adjacent genes (L1CAM, AVPR2, ARHGAP4, NAA10, RENBP, HCFC1 and TMEM187), for association with SLE in 15 783 case-control subjects derived from four different ancestral groups.ResultsMultiple SNPs showed strong association with SLE in European Americans, Asians and Hispanics at p

Published
2013

10. Association of two independent functional risk haplotypes in TNIP1 with systemic lupus erythematosus

Author

Adrianto, Indra, Wang, Shaofeng, Wiley, Graham B, Lessard, Christopher J, Kelly, Jennifer A, Adler, Adam J, Glenn, Stuart B, Williams, Adrienne H, Ziegler, Julie T, Comeau, Mary E, Marion, Miranda C, Wakeland, Benjamin E, Liang, Chaoying, Kaufman, Kenneth M, Guthridge, Joel M, Alarcón‐Riquelme, Marta E, Networks, BIOLUPUS and GENLES, Alarcón, Graciela S, Anaya, Juan‐Manuel, Bae, Sang‐Cheol, Kim, Jae‐Hoon, Bin Joo, Young, Boackle, Susan A, Brown, Elizabeth E, Petri, Michelle A, Ramsey‐Goldman, Rosalind, Reveille, John D, Vilá, Luis M, Criswell, Lindsey A, Edberg, Jeffrey C, Freedman, Barry I, Gilkeson, Gary S, Jacob, Chaim O, James, Judith A, Kamen, Diane L, Kimberly, Robert P, Martín, Javier, Merrill, Joan T, Niewold, Timothy B, Pons‐Estel, Bernardo A, Scofield, R Hal, Stevens, Anne M, Tsao, Betty P, Vyse, Timothy J, Langefeld, Carl D, Harley, John B, Wakeland, Edward K, Moser, Kathy L, Montgomery, Courtney G, and Gaffney, Patrick M

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Research, Human Genome, Lupus, Autoimmune Disease, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Adaptor Proteins, Signal Transducing, Black or African American, Asian, B-Lymphocytes, Cell Line, Transformed, DNA-Binding Proteins, Female, Genetic Markers, Genetic Predisposition to Disease, Haplotypes, Hispanic or Latino, Humans, Intracellular Signaling Peptides and Proteins, Lupus Erythematosus, Systemic, Male, Neoplasm Proteins, Polymorphism, Single Nucleotide, Risk Factors, United States, White People, BIOLUPUS and GENLES Networks, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and altered type I interferon expression. Genetic surveys and genome-wide association studies have identified >30 SLE susceptibility genes. One of these genes, TNIP1, encodes the ABIN1 protein. ABIN1 functions in the immune system by restricting NF-κB signaling. The present study was undertaken to investigate the genetic factors that influence association with SLE in genes that regulate the NF-κB pathway.MethodsWe analyzed a dense set of genetic markers spanning TNIP1 and TAX1BP1, as well as the TNIP1 homolog TNIP2, in case-control populations of diverse ethnic origins. TNIP1, TNIP2, and TAX1BP1 were fine-mapped in a total of 8,372 SLE cases and 7,492 healthy controls from European-ancestry, African American, Hispanic, East Asian, and African American Gullah populations. Levels of TNIP1 messenger RNA (mRNA) and ABIN1 protein in Epstein-Barr virus-transformed human B cell lines were analyzed by quantitative reverse transcription-polymerase chain reaction and Western blotting, respectively.ResultsWe found significant associations between SLE and genetic variants within TNIP1, but not in TNIP2 or TAX1BP1. After resequencing and imputation, we identified 2 independent risk haplotypes within TNIP1 in individuals of European ancestry that were also present in African American and Hispanic populations. Levels of TNIP1 mRNA and ABIN1 protein were reduced among subjects with these haplotypes, suggesting that they harbor hypomorphic functional variants that influence susceptibility to SLE by restricting ABIN1 expression.ConclusionOur results confirm the association signals between SLE and TNIP1 variants in multiple populations and provide new insight into the mechanism by which TNIP1 variants may contribute to SLE pathogenesis.

Published
2012

11. Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian–European populations

Author

Sánchez, Elena, Rasmussen, Astrid, Riba, Laura, Acevedo‐Vasquez, Eduardo, Kelly, Jennifer A, Langefeld, Carl D, Williams, Adrianne H, Ziegler, Julie T, Comeau, Mary E, Marion, Miranda C, La Torre, Ignacio García‐De, Maradiaga‐Ceceña, Marco A, Cardiel, Mario H, Esquivel‐Valerio, Jorge A, Rodriguez‐Amado, Jacqueline, Moctezuma, José Francisco, Miranda, Pedro, Perandones, Carlos E, Castel, Cecilia, Laborde, Hugo A, Alba, Paula, Musuruana, Jorge L, Goecke, I Annelise, Anaya, Juan‐Manuel, Kaufman, Kenneth M, Adler, Adam, Glenn, Stuart B, Brown, Elizabeth E, Alarcón, Graciela S, Kimberly, Robert P, Edberg, Jeffrey C, Vilá, Luis M, Criswell, Lindsey A, Gilkeson, Gary S, Niewold, Timothy B, Martín, Javier, Vyse, Timothy J, Boackle, Susan A, Ramsey‐Goldman, Rosalind, Scofield, R Hal, Petri, Michelle, Merrill, Joan T, Reveille, John D, Tsao, Betty P, Orozco, Lorena, Baca, Vicente, Moser, Kathy L, Gaffney, Patrick M, James, Judith A, Harley, John B, Tusié‐Luna, Teresa, Pons‐Estel, Bernardo A, Jacob, Chaim O, and Alarcón‐Riquelme, Marta E

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Health Sciences, Genetics, Autoimmune Disease, Clinical Research, Lupus, Kidney Disease, American Indian or Alaska Native, Inflammatory and immune system, Adolescent, Adult, Child, Female, Genetic Predisposition to Disease, Genotype, Humans, Indians, North American, Indians, South American, Lupus Erythematosus, Systemic, Lupus Nephritis, Male, Middle Aged, Morbidity, Prevalence, Risk Factors, Socioeconomic Factors, White People, Young Adult, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveAmerican Indian-Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian-European SLE patients.MethodsA total of 2,116 SLE patients of American Indian-European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry-informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs).ResultsThe average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41-0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement.ConclusionIn general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age.

Published
2012

12. Targeting an alternate Wilms' tumor antigen 1 peptide bypasses immunoproteasome dependency

Author

Miranda C. Lahman, Thomas M. Schmitt, Kelly G. Paulson, Nathalie Vigneron, Denise Buenrostro, Felecia D. Wagener, Valentin Voillet, Lauren Martin, Raphael Gottardo, Jason Bielas, Julie M. McElrath, Derek L. Stirewalt, Era L. Pogosova-Agadjanyan, Cecilia C. Yeung, Robert H. Pierce, Daniel N. Egan, Merav Bar, Paul C. Hendrie, Sinéad Kinsella, Aesha Vakil, Jonah Butler, Mary Chaffee, Jonathan Linton, Megan S. McAfee, Daniel S. Hunter, Marie Bleakley, Anthony Rongvaux, Benoit J. Van den Eynde, Aude G. Chapuis, Philip D. Greenberg, and UCL - SSS/DDUV/GECE - Génétique cellulaire

Subjects
Epitopes, Leukemia, Myeloid, Acute, Mice, Proteasome Endopeptidase Complex, Antigens, Neoplasm, HLA-A2 Antigen, Receptors, Antigen, T-Cell, Animals, Humans, General Medicine, Peptides, WT1 Proteins, Article
Abstract

Designing effective antileukemic immunotherapy will require understanding mechanisms underlying tumor control or resistance. Here, we report a mechanism of escape from immunologic targeting in an acute myeloid leukemia (AML) patient, who relapsed 1 year after immunotherapy with engineered T cells expressing a human leukocyte antigen A*02 (HLA-A2)–restricted T cell receptor (TCR) specific for a Wilms’ tumor antigen 1 epitope, WT1126–134(TTCR-C4). Resistance occurred despite persistence of functional therapeutic T cells and continuous expression of WT1 and HLA-A2 by the patient’s AML cells. Analysis of the recurrent AML revealed expression of the standard proteasome, but limited expression of the immunoproteasome, specifically the beta subunit 1i (β1i), which is required for presentation of WT1126–134. An analysis of a second patient treated with TTCR-C4demonstrated specific loss of AML cells coexpressing β1i and WT1. To determine whether the WT1 protein continued to be processed and presented in the absence of immunoproteasome processing, we identified and tested a TCR targeting an alternative, HLA-A2–restricted WT137–45epitope that was generated by immunoproteasome-deficient cells, including WT1-expressing solid tumor lines. T cells expressing this TCR (TTCR37–45) killed the first patients’ relapsed AML resistant to WT1126–134targeting, as well as other primary AML, in vitro. TTCR37–45controlled solid tumor lines lacking immunoproteasome subunits both in vitro and in an NSG mouse model. As proteasome composition can vary in AML, defining and preferentially targeting these proteasome-independent epitopes may maximize therapeutic efficacy and potentially circumvent AML immune evasion by proteasome-related immunoediting.

Published
2023

13. Body Mass Index Recovery after Lung Transplant for Cystic Fibrosis

Author

Joseph B. Pryor, Miranda C. Bradford, Ann L. Jennerich, Travis Y. Hee Wai, Joseph M. Pilewski, Siddhartha G. Kapnadak, Moira L. Aitken, Christopher H. Goss, and Kathleen J. Ramos

Subjects
Pulmonary and Respiratory Medicine, Cystic Fibrosis, Humans, Body Mass Index, Lung Transplantation, Proportional Hazards Models, Retrospective Studies, Original Research
Abstract

RATIONALE: Many lung transplant recipients with cystic fibrosis (CF) have low preoperative body mass index (BMI); however, post-transplant BMI recovery is not well understood. OBJECTIVES: To evaluate BMI recovery (⩾18.5 kg/m(2)) among CF lung transplant recipients with low preoperative BMI and to investigate the association of survival with BMI recovery. METHODS: The United Network for Organ Sharing and CF Foundation patient registries (June 2005–December 2016) were used to identify CF lung transplant recipients. Among recipients surviving ⩾1 year, Cox modeling compared post-transplant 1-year conditional survival between recipients with low (

Published
2023

14. Exploring the Criterion Validity of Pragmatic Person-Centered Care/Culture Change Measures

Author

Miranda C. Kunkel, Caroline Madrigal, Reese Moore, John R. Bowblis, Jane Straker, Matt Nelson, Kimberly Van Haitsma, and Katherine M. Abbott

Subjects
Logistic Models, Nursing Assistants, Patient-Centered Care, Humans, Geriatrics and Gerontology, Gerontology, Nursing Homes, Ohio
Abstract

Background Nursing homes (NHs) are required to provide person-centered care, efforts often folded into broader culture change initiatives. Despite the known benefits of culture change, it is difficult to measure. This study aims to assess the criterion validity of the Preferences for Everyday Living Inventory (PELI) Implementation Indicator with other culture change measures. Methods Using data from Ohio-based NHs ( n = 771), logistic regression techniques demonstrated the relationship between the PELI Implementation Indicator and two validated culture change measures, the Resident Preferences for Care (RPC) and Certified Nursing Assistant (CNA) Empowerment scales. Results There was a significant relationship between the two scales and complete PELI implementation holding all other variables constant. The RPC and CNA Empowerment scales were significantly associated with complete PELI implementation. Discussion Findings suggest that the PELI Implementation Indicator can be used as a pragmatic indicator of a community’s adoption of person-centered care and culture change.

Published
2022

15. Molecular pathways identified from single nucleotide polymorphisms demonstrate mechanistic differences in systemic lupus erythematosus patients of Asian and European ancestry

Author

Katherine A. Owen, Kristy A. Bell, Andrew Price, Prathyusha Bachali, Hannah Ainsworth, Miranda C. Marion, Timothy D. Howard, Carl D. Langefeld, Nan Shen, Jinoos Yazdany, Maria Dall’era, Amrie C. Grammer, and Peter E. Lipsky

Subjects
Multidisciplinary, Lupus Erythematosus, Genotype, Inflammatory and immune system, Systemic, Human Genome, Lupus, Single Nucleotide, Autoimmune Disease, Clinical Research, Case-Control Studies, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Polymorphism, Aetiology, Genome-Wide Association Study
Abstract

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE.

Published
2023

16. The European Particle Therapy Network (EPTN) consensus on the follow-up of adult patients with brain and skull base tumours treated with photon or proton irradiation

Author

De Roeck, Laurien, van der Weide, Hiska L, Eekers, Daniëlle B P, Kramer, Miranda C, Alapetite, Claire, Blomstrand, Malin, Burnet, Neil G, Calugaru, Valentin, Coremans, Ida E M, Di Perri, Dario, Harrabi, Semi, Iannalfi, Alberto, Klaver, Yvonne L B, Langendijk, Johannes A, Romero, Alejandra Méndez, Paulsen, Frank, Roelofs, Erik, de Ruysscher, Dirk, Timmermann, Beate, Vitek, Pavel, Weber, Damien C, Whitfield, Gillian A, Nyström, Petra Witt, Zindler, Jaap, Troost, Esther G C, Lambrecht, Maarten, work package 1 of the taskforce 'European Particle Therapy Network' of ESTRO, UCL - (SLuc) Centre du cancer, and UCL - (SLuc) Service de radiothérapie oncologique

Subjects
Adult, Consensus, Toxicity, Skull base tumour, Follow-up, Medizin, Particle therapy, Brain, Brain tumour, Hematology, Skull Base Neoplasms, Oncology, Central nervous system, European Particle Therapy Network, Proton Therapy, Humans, Radiology, Nuclear Medicine and imaging, Protons, 610 Medicine & health, Follow-Up Studies
Abstract

PURPOSE Treatment-related toxicity after irradiation of brain tumours has been underreported in the literature. Furthermore, there is considerable heterogeneity on how and when toxicity is evaluated. The aim of this European Particle Network (EPTN) collaborative project is to develop recommendations for uniform follow-up and toxicity scoring of adult brain tumour patients treated with radiotherapy. METHODS A Delphi method-based consensus was reached among 24 international radiation-oncology experts in the field of neuro-oncology concerning the toxicity endpoints, evaluation methods and time points. RESULTS In this paper, we present a basic framework for consistent toxicity scoring and follow-up, using multiple levels of recommendation. Level I includes all recommendations that are considered minimum of care, whereas level II and III are optional evaluations in the advanced clinical or research setting, respectively. Per outcome domain, the clinical endpoints and evaluation methods per level are listed. Where relevant, the organ at risk threshold doses for recommended referral to specific organ specialists are defined. CONCLUSION These consensus-based recommendations for follow-up will enable the collection of uniform toxicity data of brain tumour patients treated with radiotherapy. With adoptation of this standard, collaboration will be facilitated and we can further propel the research field of radiation-induced toxicities relevant for these patients. An online tool to implement this guideline in clinical practice is provided at www.cancerdata.org.

Published
2022

17. An aggressive lactotroph pituitary tumor in a young male

Author

Roelandt-Schumann, Friederike E, Vergeer, Rob A, Korsten-Meijer, Astrid G W, Kramer, Miranda C A, Westerlaan, Henriëtte E, Pott, Jan W R, Nuver, Janine, van den Berg, Gerrit, den Dunnen, Wilfred F A, and Molecular Neuroscience and Ageing Research (MOLAR)

Subjects
Adult, Male, Vascular Endothelial Growth Factor A, Cabergoline, Lactotrophs, General Medicine, Pathology and Forensic Medicine, Prolactin, Ki-67 Antigen, Neurology, Receptors, Estrogen, Humans, Pituitary Neoplasms, Neurology (clinical), Tumor Suppressor Protein p53
Abstract

This case report concerns a 31-year-old male with an aggressive pituitary tumor who presented initially with bitemporal hemianopsia and slightly elevated prolactin. On magnetic resonance imaging of the brain, there was a sellar mass with parasellar invasion to the lateral aspects of the internal carotid arteries, compressing the optic chiasm. On histopathological analysis, the diagnosis was made of a densely granulated lactotroph pituitary tumor with a Ki67 proliferation rate of 15%, a mitotic count of 6/10 high-power fields, and p53 positivity. Based on these features, the tumor was classified as a grade 2b tumor according to the Trouillas classification, and a more aggressive behavior of the tumor could be expected. In order to anticipate a future need for alternative drug treatments, the following analyses were undertaken: MGMT methylation (present) as well as the expression of estrogen receptor (negative), programmed-death ligand 1 (60 - 70% positive tumor cells), vascular endothelial growth factor-A and somatostatin receptor 2 (both positive). There was regrowth of residual tumor tissue, and the treatment consisted thus far of repeat surgery, cabergoline, pasireotide, and radiotherapy. Chemotherapy with temozolomide could not yet be initiated due to a concurrent infertility treatment. This case is unique because the tumor displays atypical characteristics, both in terms of morphology and behavior. It also illustrates how pathologists can play an important role in determining the diagnosis, prognosis, and possibilities for targeted therapy.

Published
2022

18. Parent Perspectives after the PRISM-P Randomized Trial: A Mixed-Methods Analysis

Author

Abby R. Rosenberg, Chuan Zhou, J. Nicholas Dionne-Odom, Krysta S. Barton, Miranda C. Bradford, Joyce P. Yi-Frazier, Courtney C. Junkins, J. Randall Curtis, Mallory Taylor, and Erin K. Kross

Subjects
Adult, Counseling, Parents, Palliative care, Adolescent, media_common.quotation_subject, Mixed methods analysis, law.invention, Young Adult, Randomized controlled trial, law, Neoplasms, Humans, Medicine, Child, General Nursing, media_common, business.industry, Original Articles, General Medicine, Psychotherapy, Distress, Anesthesiology and Pain Medicine, Child, Preschool, Psychological resilience, business, Stress, Psychological, Clinical psychology
Abstract

BACKGROUND: Parents experience high distress following their child's diagnosis of cancer. We previously tested two delivery models (group and one-on-one) of the “Promoting Resilience in Stress Management for Parents” (PRISM-P) intervention in a randomized trial: one-on-one delivery improved resilience and benefit finding at three months when compared to usual care (UC). OBJECTIVE: The objective of this analysis was to evaluate quantitative and qualitative outcomes at six months. DESIGN: In this single-center, phase 2, parallel, 1:1:1 randomized trial conducted December 2016 to December 2018, English-speaking parents with a 2–24 year-old child diagnosed with new cancer were randomly assigned to UC, one-on-one, or group PRISM-P, a brief, skill-based curriculum targeting stress management, goal setting, cognitive reframing, and meaning making. We collected parent-reported outcomes (resilience, benefit finding, and psychological distress) at baseline and three and six months. We applied linear mixed-effects regression models to examine six-month outcomes among all participants and conducted directed content analyses of exit interviews with the first 12 parents to complete each study arm. RESULTS: The 94 participating parents were median aged 35–38 years and predominantly white, college-educated mothers. At six months, there was no statistically significant difference in parent-reported outcomes. Exit interviews (n = 36) suggested that PRISM-P was highly valued: 100% of interviewed recipients recommended it for other parents. Most suggested more coaching would help them retain skills, and almost all endorsed a combined one-on-one and group program. CONCLUSIONS: Although the PRISM-P benefits observed at three months were not sustained for six months, all interviewed parents found it valuable. Additional opportunities to strengthen and sustain resilience resources include longer follow-up, flexible format, and skill reinforcement. TRIAL REGISTRATION: NCT02998086.

Published
2021

19. Improving Food-Related Quality of Life in Inflammatory Bowel Disease through a Novel Web Resource: A Feasibility Randomised Controlled Trial

Author

Selina R. Cox, Wladyslawa Czuber-Dochan, Catherine L. Wall, Hazel Clarke, Candice Drysdale, Miranda C. Lomer, James O. Lindsay, and Kevin Whelan

Subjects
Nutrition and Dietetics, inflammatory bowel disease, food-related quality of life, eHealth, Crohn Disease, Chronic Disease, Quality of Life, Humans, Feasibility Studies, Colitis, Ulcerative, Inflammatory Bowel Diseases, Food Science
Abstract

Food-related quality of life (FR-QoL) is impaired in inflammatory bowel disease (IBD) and education and support on food-related issues in IBD is needed. This feasibility trial aimed to investigate the effectiveness and acceptability of a web resource in enhancing FR-QoL in newly diagnosed IBD. Patients diagnosed with Crohn’s disease or ulcerative colitis in the preceding 12 months, with an impaired FR-QoL, were recruited and randomised to either receive access to the web resource (covering IBD-specific diet concerns) or no access (control group) for 12 weeks, while receiving usual clinical care. FR-QoL, health-related quality of life, psychological outcomes, and clinical disease activity were assessed. Web resource usage was assessed, and patients’ experiences of the web resource were investigated in semi-structured interviews. Of 81 patients screened, 50 participants were randomised, 30 to the web resource and 20 to control. FR-QoL increased more in the web resource (+11.7 SD 18.2) than control group (+1.4 SD 20.4) (p = 0.067), while IBD distress reduced in the web resource (−6.8 SD 26.6) and increased in the control group (+8.3 SD 25.5) (p = 0.052), albeit not statistically significantly. End of trial Crohn’s disease clinical activity (PRO-2) was significantly lower in the web resource than control group (p = 0.046). Participants most frequently accessed web resource content discussing dietary management of gut symptoms and in semi-structured interviews, reported the website to contain relevant information. This feasibility study demonstrates potential effectiveness of the web resource on improving FR-QoL and psychological outcomes in IBD. An adequately powered effectiveness RCT is feasible to conduct and is now warranted. NCT03884686.

Published
2022

20. Gender Discrimination and Sexual Harassment in a Department of Pediatrics

Author

Anne C. Slater, Anita A. Thomas, Linda Quan, Shaquita Bell, Miranda C. Bradford, Leslie Walker-Harding, and Abby R. Rosenberg

Subjects
Male, Gender Equity, Sexual Harassment, Pregnancy, Pediatrics, Perinatology and Child Health, Sexism, Humans, Female, Child, Faculty, Pediatrics
Abstract

The last substantial description of gender discrimination and harassment described in the journal Pediatrics was in 2019. It is unclear whether the field has made progress toward its goal of equity. We aimed to describe: (1) the recent gender-equity climate according to women and men faculty in the department of pediatrics at a single, large academic center, and (2) institutional efforts to address persistent gender discrimination and harassment. In late 2020, we distributed an anonymous survey to all department faculty that included demographic data, a modified version of the Overt Gender Discrimination at Work Scale, questions about experiences/witnessed discriminatory treatment and sexual harassment, and if those experiences negatively affected career advancement. Of 524 pediatrics faculty, 290 (55%) responded. Compared with men, women more commonly reported gender discrimination (50% vs. 4%, P < .01) and that their gender negatively affected their career advancement (50% vs 9%, P < .01). More than 50% of women reported discriminatory treatment at least annually and 38% recognized specific sexist statements; only 4% and 17% of men reported the same (P < .01 for both). We concluded that a disproportionately low number of male faculty recognized the harassment female faculty experienced. In the 18 months since, our department and university have made efforts to improve salary equity and parity in leadership representation, created an anonymous bias-reporting portal, mandated bias training, and implemented new benchmarks of “professionalism” that focus on diversity. Although we acknowledge that culture change will take time, we hope our lessons learned help promote gender equity in pediatrics more broadly.

Published
2022

21. Rectal suction biopsy versus incisional rectal biopsy in the diagnosis of Hirschsprung disease

Author

Nicole, Green, Caitlin A, Smith, Miranda C, Bradford, Lusine, Ambartsumyan, and Raj P, Kapur

Subjects
Biopsy, Rectum, Humans, Infant, Hirschsprung Disease, Suction, Child, Retrospective Studies
Abstract

Hirschsprung disease is one of the most common congenital anomalies that affect colorectal function. Rectal biopsy demonstrating the absence of ganglion cells in the affected bowel is the gold standard for diagnosis. Suction and incisional rectal biopsies are appropriate methods for obtaining diagnostic tissue. The goal of this study is to determine if any differences in adequacy exist between suction and incisional rectal biopsies at our institution.We conducted a retrospective review of suction and incisional rectal biopsies for inadequacy per procedure at a tertiary pediatric hospital. Each procedure for rectal biopsy was also evaluated by a number of biopsies per procedure. We used a two-sample test of proportions to compare the inadequacy of suction vs. incisional biopsies.133 rectal suction biopsy procedures (227 biopsies) and 125 incisional biopsy procedures (140 biopsies) were analyzed. In patients 6 months of age and older, the percentage of inadequate procedures was substantially higher in the suction biopsy group (24.1% vs 0.9%, p 0.01).A substantially higher proportion of inadequacy was found in the suction rectal biopsy group compared to the incisional cohort among the older patient cohort, suggesting incisional biopsies should be strongly considered as the primary rectal biopsy method in patients older than 6 months.

Published
2022

22. Effectiveness and costs of a new framework for selecting absorbent urinary incontinence products compared with current practice

Author

Miranda C Schreuder, Henk van der Worp, Beate Balkestein, Alec GGA Malmberg, Tine van den Bos, Janny H Dekker, Michiel R de Boer, Karin M Vermeulen, Marco H Blanker, Life Course Epidemiology (LCE), and Value, Affordability and Sustainability (VALUE)

Subjects
IMPACT, QUESTIONNAIRE, General Medicine, Urinary incontinences, Health policy, Cohort Studies, Urinary Incontinence, Treatment Outcome, QUALITY-OF-LIFE, Surveys and Questionnaires, Quality of Life, Humans, Health economics, ICIQ
Abstract

ObjectivesTo improve continence care in the Netherlands, a new framework has been developed in which a shift has been made from incontinence severity as the sole criterion for selecting incontinence products to a focus on patient need for daily life activities. The impact of the framework on daily care has not been assessed. We aimed to compare treatment effectiveness and costs between participants who did and did not undergo re-evaluation according to the new framework.DesignCohort studySettingTwelve pharmacies in the NetherlandsParticipantsExisting users of absorbent incontinence materials for urinary incontinence.InterventionsParticipants were offered the option to have their incontinence products re-evaluated within the new framework at their pharmacy.Primary and secondary outcome measuresEffectiveness and cost outcomes were assessed at 3 and 6 months through questionnaires. These questionnaires included the International Consultation on Incontinence Questionnaire (ICIQ) Lower Urinary Tract Symptoms Quality of Life Module, ICIQ Urinary Incontinence Short Form, ICIQ Absorbent Pads, questions about satisfaction and the iPCQ and iMCQ.Results303 users consented and 279 completed the baseline questionnaire. Of these participants, 72 agreed to a re-evaluation of their incontinence materials. There was a small improvement at 3 months in the re-evaluation group compared with the other group on most outcomes. However, these improvements were not clinically relevant. Moreover, these differences did not change much from 3 to 6 months. Small differences were also observed in the changes in costs, but with very wide CIs on both sides of zero (€99.38; 95% CI −633.48 to 832.23).ConclusionsThe current study showed no clinically relevant effect of a newly implemented framework for selecting incontinence materials in pharmacies when compared with an existing method. Given that the study also showed no differences in effectiveness and costs, introducing the new framework in pharmacies may not lead to better incontinence care.

Published
2022

23. Event-related potential (ERP) measures of error processing as biomarkers of externalizing disorders

Author

Miranda C. Lutz, Rianne Kok, Ingmar H.A. Franken, LEARN! - Child rearing, APH - Mental Health, Clinical Developmental Psychology, Clinical Psychology, and Clinical Child and Family Studies

Subjects
Behavioral addiction, Substance-Related Disorders, Affect (psychology), 050105 experimental psychology, Error-related negativity, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Event-related potential, Physiology (medical), medicine, Humans, ADHD, Error processing, 0501 psychology and cognitive sciences, Externalizing disorders, Evoked Potentials, Substance use disorders, General Neuroscience, 05 social sciences, Electroencephalography, Biomarker, medicine.disease, Comorbidity, Neuropsychology and Physiological Psychology, Attention Deficit Disorder with Hyperactivity, Error positivity, Etiology, Biomarker (medicine), medicine.symptom, Psychology, 030217 neurology & neurosurgery, Biomarkers, Clinical psychology
Abstract

Previous studies have shown that electrophysiological measures of error processing are affected in patients at risk or diagnosed with internalizing disorders, hence, suggesting that error processing could be a suitable biomarker for internalizing disorders. In this narrative review, we will evaluate studies that address the role of event-related potential (ERP) measures of error-processing in externalizing disorders and discuss to what extend these can be considered a biomarker for externalizing disorders. Currently, there is evidence for the notion that electrophysiological indices of error processing such as the error-related negativity (ERN) and error positivity (Pe) are reduced in individuals with substance use disorders, attention-deficit/hyperactivity disorder, and in forensic populations. However, it remains unclear whether this is also the case for other understudied disorders such as behavioral addiction. Furthermore, to fully understand how these deficits affect day to day behavior, we encourage research to focus on testing current theories and hypotheses of ERN and Pe. In addition, we argue that within an externalizing disorder, individual differences in error processing deficits may be related to prognosis and gender of the patient, methodological issues and presence of comorbidity. Next, we review studies that have related treatment trajectories with ERP measures of error processing, and we discuss the prospect of improving error processing as a treatment option. We conclude that ERP measures of error processing are candidate biomarkers for externalizing disorders, albeit we strongly urge researchers to continue looking into the predictive value of these measures in the etiology and treatment outcome through multi-method and longitudinal designs.

Published
2021

24. Impact of Implementing the Preferences for Everyday Living Inventory on Nursing Home Survey Deficiencies

Author

Miranda C. Kunkel, John R. Bowblis, Jane Straker, Kimberly Van Haitsma, and Katherine M. Abbott

Subjects
Logistic Models, Health Policy, Surveys and Questionnaires, Patient-Centered Care, Humans, General Medicine, Geriatrics and Gerontology, General Nursing, Nursing Homes, Skilled Nursing Facilities
Abstract

The purpose of this study is to expand on previous work testing the relationship between person-centered care (PCC) and quality outcomes in the nursing home (NH) setting. We explore if the Preferences for Everyday Living Inventory (PELI) implementation is a predictor of NH quality, as defined by deficiencies.Secondary data analysis of repeated cross-sections.Data from 6 sources on Ohio NHs were merged to examine 1300 NH-year observations.Logistic regression techniques were used to evaluate the relationship between PELI implementation and 3 survey deficiency outcomes: whether the NH had a 4- or 5- deficiency star rating, deficiency score, and whether the NH had a deficiency score of 0.NHs with complete PELI implementation increased the probability of having a 4- or 5- deficiency star rating by 6 percentage points (P = .039). Results also show complete PELI implementation is related to lower deficiency scores and an increased probability of having a deficiency score of 0, but only a 0 deficiency score was marginally significant.The findings indicate PCC stands to improve quality outcomes; however, benefits take time to show. Future research should seek to help improve NHs level of commitment to PCC and buy-in from policymakers.

Published
2022

25. Gut dysbiosis and the clinical spectrum in anti-Ro positive mothers of children with neonatal lupus

Author

Robert M. Clancy, Miranda C. Marion, Hannah C. Ainsworth, Miao Chang, Timothy D. Howard, Peter M. Izmirly, Mala Masson, Jill P. Buyon, and Carl D. Langefeld

Subjects
Microbiology (medical), Infectious Diseases, Sjogren's Syndrome, Gastroenterology, Infant, Newborn, Dysbiosis, Humans, Lupus Erythematosus, Systemic, Mothers, Female, Child, Microbiology, Gastrointestinal Microbiome
Abstract

Anti-SSA/Ro antibodies, while strongly linked to fetal cardiac injury and neonatal rash, can associate with a spectrum of disease in the mother, ranging from completely asymptomatic to overt Systemic Lupus Erythematosus (SLE) or Sjögren's Syndrome (SS). This study was initiated to test the hypothesis that the microbiome, influenced in part by genetics, contributes to disease state. The stool microbiome of healthy controls (HC) was compared to that of anti-SSA/Ro positive women whose children had neonatal lupus. At the time of sampling, these women were either asymptomatic (Asym), had minor rheumatic symptoms or signs considered as an undifferentiated autoimmune syndrome (UAS), or were diagnosed with SLE or SS. Differences in microbial relative abundances among these three groups were tested assuming an ordering in clinical severity (HCAsym/UASSS/SLE) and then again without the ordinal assumption. Those taxa that showed differential relative abundances were then tested for whether the effect size differed depending on the women's HLA SLE-risk allele genotype (DRB1*03:01, DRB1*15:01, DQB1*02:01 and DQB1*06:02) or anti-SSA/Ro autoantibody levels. Multiple genera within the families

Published
2022

26. Impact of multiorgan and kidney-pancreas allocation policies on pediatric kidney-alone transplant candidates in the United States

Author

Rachel Engen, Danielle Shepherd, Miranda C. Bradford, Julia Foutz, Sharon M. Bartosh, and Jodi M. Smith

Subjects
Transplantation, Tissue and Organ Procurement, Policy, Waiting Lists, Pediatrics, Perinatology and Child Health, Humans, Child, Kidney, Kidney Transplantation, Pancreas, United States, Tissue Donors
Abstract

The United States organ allocation policies prioritize kidney-pancreas and other multiorgan candidates above pediatric kidney-alone candidates, but the effects of these policies are unclear.We used OPTN data to describe trends in multiorgan and kidney-pancreas transplantation and identify 377 next-sequential pediatric kidney-alone candidates between 4/1/2015 and 10/31/2019 for individual-level analysis.Eleven percent of all kidneys were allocated as part of a multiorgan or kidney-pancreas transplant and 6% of pediatric kidney candidates were impacted. Pediatric next-sequential candidates accrued a median of 118 days (IQR 97-135 days) of additional wait time, and this was significantly longer for children who were Hispanic (p = .02), blood type B or O (p = .01), or had a cPRA ≥20% (p .01). Eight pediatric next-sequential candidates (2%) were removed from the waitlist due to death or "too sick to transplant." 63% were transplanted with a kidney with a higher KDPI than the original multiorgan match (p .01). Donor service areas with higher volumes of kidney-pancreas transplants had significantly longer additional wait times for pediatric next-sequential candidates (p = .01).Current allocation policy results in longer waiting times and higher KDPI kidneys for pediatric kidney candidates. As multiorgan transplant volume is increasing, further consideration of allocation policy is necessary to maximize equality and utility.

Published
2022

27. Effects of Intensive Systolic Blood Pressure Control on All-Cause Hospitalizations

Author

Michael V. Rocco, Amret T. Hawfield, Miranda C. Marion, Carl D. Langefeld, Barry I. Freedman, and Mary E. Comeau

Subjects
Male, Blood pressure control, medicine.medical_specialty, Blood Pressure, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Post-hoc analysis, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Intervention trial, Antihypertensive Agents, Aged, business.industry, Blood Pressure Determination, Middle Aged, Hospitalization, Treatment Outcome, Blood pressure, Hypertension, Cardiology, Female, business, All cause mortality
Abstract

Intensive blood pressure control decreases the rate of cardiovascular events by >25% compared with standard blood pressure control. We sought to determine whether the decrease in cardiovascular events seen with intensive blood pressure control is associated with an increased rate of other causes of hospitalization. This is a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial) in 9361 adult participants with hypertension and elevated cardiovascular risk. Participants were randomly assigned to an intensive or standard systolic blood pressure goal (P =0.37). Equivalence testing shows that these hospitalization rates were statistically equivalent at the P =0.05 level. Of those with hospitalizations, >1 hospitalization was seen in 38.8% of intensive arm participants and 41.9% of standard arm participants ( P =0.08). The mean cumulative count of nonprimary event hospitalizations was comparable between the two arms. The most common causes of hospitalization were cardiovascular (23.6%) followed by injuries, including bone and joint therapeutic procedures (15.7%), infections (12.0%), and nervous systems disorders (10.7%). No categories of hospitalization were statistically more common in the intensive arm compared with the standard arm. Thus, the decrease in cardiovascular events seen with intensive blood pressure control is not associated with an increased rate of other causes of hospitalization. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01206062.

Published
2020

28. Quality of Life in Adolescents and Young Adults: The Role of Symptom Burden

Author

Angela Steineck, Miranda C. Bradford, Alison O'Daffer, Kaitlyn M. Fladeboe, Maeve B. O'Donnell, Samantha Scott, Joyce P. Yi-Frazier, and Abby R. Rosenberg

Subjects
Male, Adolescent, Young Adult, Anesthesiology and Pain Medicine, Neoplasms, Surveys and Questionnaires, Prevalence, Quality of Life, Humans, Female, Neurology (clinical), Child, General Nursing, Fatigue
Abstract

Adolescents and young adults (AYAs) with cancer report worse health-related quality of life (HRQOL) than other age groups. Symptom burden is a modifiable predictor of HRQOL.The objective of this study was to identify which symptoms are most burdensome to AYAs with advanced cancer.In this observational study, English-speaking individuals aged 12-25 years undergoing treatment for advanced cancer completed assessments of symptom burden (Memorial Symptom Assessment Scale) and HRQOL (Pediatric Quality of Life Inventory Generic Form and Cancer Module; minimal clinically important difference 4.4). We dichotomized participants as having low (7) or high (≥7) symptom prevalence. Mixed regression models estimated HRQOL differences between groups. For individual symptoms, unadjusted mixed models estimated HRQOL reductions.N = 58 AYAs completed baseline surveys. The median age was 17 years (IQR 15-19), 58% were male, 59% identified as white, and 44% were diagnosed with leukemia/lymphoma. High symptom prevalence was associated with a mean generic HRQOL 7 points lower (95% CI: -11, -3; P0.01) and cancer-specific HRQOL score 12 points lower (95% CI: -17, -7; P0.01) than low symptom prevalence. The most prevalent symptoms were fatigue (71%), pain (58%), and difficulty sleeping (58%). Fatigue (-8), difficulty concentrating (-7), and mouth sores (-6) were associated with the greatest generic HRQOL score reductions. Dysphagia (-12), difficulty concentrating (-12), and sadness (-11) were associated with the greatest cancer-specific HRQOL score reductions.The symptom experience among AYAs with advanced cancer is unique. Separate evaluation of AYA's symptoms may optimize management and improve HRQOL.

Published
2022

29. Anti-tumor treatment and healthcare consumption near death in the era of novel treatment options for patients with melanoma brain metastases

Author

Annemarie C. Eggen, Geke A. P. Hospers, Ingeborg Bosma, Miranda C. A. Kramer, Anna K. L. Reyners, Mathilde Jalving, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)

Subjects
Proto-Oncogene Proteins B-raf, Adult, Male, Cancer Research, Emergency Medical Services, Patient Acceptance of Health Care/statistics & numerical data, Terminal Care/statistics & numerical data, Antineoplastic Agents, Brain Neoplasms/drug therapy, Proto-Oncogene Proteins B-raf/genetics, Genetics, 80 and over, Humans, Melanoma/drug therapy, Melanoma, Aged, Hospitalization/statistics & numerical data, Netherlands, Retrospective Studies, Aged, 80 and over, Terminal Care, Brain Neoplasms, Emergency Medical Services/statistics & numerical data, Antineoplastic Agents/therapeutic use, Patient Acceptance of Health Care, Middle Aged, Hospitalization, Treatment Outcome, Oncology, Mutation, Female
Abstract

Background Effective systemic treatments have revolutionized the management of patients with metastatic melanoma, including those with brain metastases. The extent to which these treatments influence disease trajectories close to death is unknown. Therefore, this study aimed to gain insight into provided treatments and healthcare consumption during the last 3 months of life in patients with melanoma brain metastases. Methods Retrospective, single-center study, including consecutive patients with melanoma brain metastases diagnosed between June-2015 and June-2018, referred to the medical oncologist, and died before November-2019. Patient and tumor characteristics, anti-tumor treatments, healthcare consumption, presence of neurological symptoms, and do-not-resuscitate status were extracted from medical charts. Results 100 patients were included. A BRAF-mutation was present in 66 patients. Systemic anti-tumor therapy was given to 72% of patients during the last 3 months of life, 34% in the last month, and 6% in the last week. Patients with a BRAF-mutation more frequently received systemic treatment during the last 3 (85% vs. 47%) and last month (42% vs. 18%) of life than patients without a BRAF-mutation. Furthermore, patients receiving systemic treatment were more likely to visit the emergency room (ER, 75% vs. 36%) and be hospitalized (75% vs. 36%) than those who did not. Conclusion The majority of patients with melanoma brain metastases received anti-tumor treatment during the last 3 months of life. ER visits and hospitalizations occurred more often in patients on anti-tumor treatment. Further research is warranted to examine the impact of anti-tumor treatments close to death on symptom burden and care satisfaction.

Published
2022

31. Adverse childhood experiences (ACEs) and medically traumatic events (TEs) in adolescents and young adults (AYAs) with cancer: a report from the Promoting Resilience in Stress Management (PRISM) randomized controlled trial

Author

Miranda C. Bradford, Abby R. Rosenberg, Mallory Taylor, Joyce P. Yi-Frazier, Angela Steineck, Nancy Lau, Alison O'Daffer, Samantha Scott, and Kaitlyn Fladeboe

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Population, Article, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Randomized controlled trial, Adverse Childhood Experiences, law, Neoplasms, medicine, Humans, 030212 general & internal medicine, Young adult, Child, education, Depression (differential diagnoses), education.field_of_study, business.industry, Medical record, Resilience, Psychological, Pediatric cancer, humanities, Oncology, 030220 oncology & carcinogenesis, Quality of Life, Physical therapy, Wounds and Injuries, Anxiety, Female, medicine.symptom, business, Stress, Psychological
Abstract

OBJECTIVE: In Adolescents and Young Adults (AYAs) with cancer, we examined (1) the distribution and type of traumatic events (TEs) experienced prior to baseline assessment and (2) how a resilience intervention, Promoting Resilience in Stress Management (PRISM), impacted changes in patient-reported outcomes (PROs) for AYAs with and without TEs. METHODS: AYAs (12–25 years) within 1–10 weeks of diagnosis of new malignancy or ever diagnosed with advanced cancer were enrolled and randomly assigned to Usual Care (UC) with or without PRISM. To assess TEs, we screened medical records for traditionally-defined Adverse Childhood Experiences (ACEs) and medical traumatic events. Age-validated PROs assessed resilience, benefit-finding, hope, generic health-related quality of life (QoL), cancer-specific QoL, depression, and anxiety at enrollment and 6-months later. We calculated effect sizes (Cohen’s d) for PRISM vs UC effect on PRO-score change at 6-months for 1+ TEs and 0 TE groups. RESULTS: Ninety-two AYAs enrolled and completed baseline surveys (44-UC, 48-PRISM; N=74 at 6-months, 38-UC, 36-PRISM); 60% experienced 1+ TEs. PROs at baseline were similar across groups. PRISM’s effect on score-change was greater (Cohen’s d ≥ 0.5) for the 1+ TE group on domains of benefit-finding and hope; and similar (d < 0.5) on domains of resilience, depression, anxiety, and both generic and cancer-specific QoL. CONCLUSIONS: In AYAs with cancer, TEs occurred at similar rates as the general population. PRISM may be particularly helpful for improving benefit-finding and hope for those who have experienced TEs.

Published
2020

32. Analysis of Trans-Ancestral SLE Risk Loci Identifies Unique Biologic Networks and Drug Targets in African and European Ancestries

Author

Adam C. Labonte, Michelle D. Catalina, Peter E. Lipsky, James M. Dittman, Robert D. Robl, Hannah C. Ainsworth, Miranda C. Marion, Andrew Price, Kip D. Zimmerman, Bryce N. Aidukaitis, Timothy D. Howard, Katherine A. Owen, Carl D. Langefeld, Prathyusha Bachali, Amrie C. Grammer, and Kathryn M. Kingsmore

Subjects
0301 basic medicine, Lactams, Quantitative Trait Loci, Population, Protein Array Analysis, Black People, Gene Expression, Genome-wide association study, Disease, Biology, Polymorphism, Single Nucleotide, Article, White People, Bortezomib, Biological pathway, 03 medical and health sciences, Quantitative Trait, Heritable, 0302 clinical medicine, Heterocyclic Compounds, Genetics, medicine, Humans, Lupus Erythematosus, Systemic, Gene Regulatory Networks, Genetic Predisposition to Disease, education, Gene, Genetics (clinical), 030203 arthritis & rheumatology, B-Lymphocytes, education.field_of_study, Systemic lupus erythematosus, Genome, Human, Mechanism (biology), Molecular Sequence Annotation, Isoquinolines, medicine.disease, Enhancer Elements, Genetic, Gene Ontology, 030104 developmental biology, Expression quantitative trait loci, DNA, Intergenic, Interferons, Genome-Wide Association Study
Abstract

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of African ancestry (AA) experience the disease more severely and with an increased co-morbidity burden compared to European ancestry (EA) populations. We hypothesize that the disparities in disease prevalence, activity, and response to standard medications between AA and EA populations is partially conferred by genomic influences on biological pathways. To address this, we applied a comprehensive approach to identify all genes predicted from SNP-associated risk loci detected with the Immunochip. By combining genes predicted via eQTL analysis, as well as those predicted from base-pair changes in intergenic enhancer sites, coding-region variants, and SNP-gene proximity, we were able to identify 1,731 potential ancestry-specific and trans-ancestry genetic drivers of SLE. Gene associations were linked to upstream and downstream regulators using connectivity mapping, and predicted biological pathways were mined for candidate drug targets. Examination of trans-ancestral pathways reflect the well-defined role for interferons in SLE and revealed pathways associated with tissue repair and remodeling. EA-dominant genetic drivers were more often associated with innate immune and myeloid cell function pathways, whereas AA-dominant pathways mirror clinical findings in AA subjects, suggesting disease progression is driven by aberrant B cell activity accompanied by ER stress and metabolic dysfunction. Finally, potential ancestry-specific and non-specific drug candidates were identified. The integration of all SLE SNP-predicted genes into functional pathways revealed critical molecular pathways representative of each population, underscoring the influence of ancestry on disease mechanism and also providing key insight for therapeutic selection.

Published
2020

33. Creating a Resilient Research Program—Lessons Learned From a Palliative Care Research Laboratory

Author

Liam Comiskey, Abby R. Rosenberg, Samantha Scott, Angela Steineck, Nancy Lau, Miranda C. Bradford, Joyce P. Yi-Frazier, Courtney C. Junkins, and Krysta S. Barton

Subjects
Research program, Palliative care, media_common.quotation_subject, Psychological safety, Burnout, Article, 03 medical and health sciences, 0302 clinical medicine, Professional, Humans, Medicine, 030212 general & internal medicine, Burnout, Professional, Curriculum, General Nursing, media_common, Medical education, Staff, Operationalization, Resilience, business.industry, Palliative Care, Leadership, Anesthesiology and Pain Medicine, 030220 oncology & carcinogenesis, Hospice and Palliative Care Nursing, Needs assessment, Neurology (clinical), Psychological resilience, Research Team, Laboratories, business
Abstract

Conducting palliative care research can be personally and professionally challenging. Although limitations in funding and training opportunities are well described, a less recognized barrier to successful palliative care research is creating a sustainable and resilient team. In this special report, we describe the experience and lessons learned in a single palliative care research laboratory. In the first few years of the program, 75% of staff quit, citing burnout and the emotional tolls of their work. To address our sustainability, we translated resilience theory to practice. First, we identified and operationalized shared mission and values. Next, we conducted a resilience resource needs assessment for both individual team members and the larger team as a whole and created a workshop-based curriculum to address unmet personal and professional support needs. Finally, we changed our leadership approach to foster psychological safety and shared mission. Since then, no team member has left, and the program has thrived. As the demand for rigorous palliative care research grows, we hope this report will provide perspective and ideas to other established and emerging palliative care research programs.

Published
2020

34. Prevalence of Comorbid Spasticity and Urinary Incontinence in Residents of a Long-Term Care Facility

Author

Peter Hedera, Lea Sayce, Shelby Ploucher, Aaditi G. Naik, Maxim Turchan, Kelly Harper, Mallory L. Hacker, Miranda C. Tomaras, and David Charles

Subjects
medicine.medical_specialty, Activities of daily living, Gerontological nursing, Urinary incontinence, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Activities of Daily Living, Prevalence, medicine, Humans, 030212 general & internal medicine, Spasticity, General Nursing, 030504 nursing, business.industry, Medical record, Long-Term Care, Confidence interval, Cross-Sectional Studies, Urinary Incontinence, Relative risk, Quality of Life, Physical therapy, medicine.symptom, 0305 other medical science, business, Gerontology
Abstract

The current study evaluated the prevalence of comorbid spasticity and urinary incontinence (UI) in a long-term care facility. Medical history, presence of UI, and activities of daily living (ADL) dependency were obtained from medical records and Minimum Data Set 3.0. Quality of life was assessed with the EuroQoL-5D-5L (EQ-5D). Comorbid spasticity and UI presented in 29% of participants (14 of 49). Participants with spasticity and UI had higher ADL dependency and lower EQ-5D than participants without both conditions (4.9, 95% confidence interval [CI] [1.6, 80.], p = 0.003; −0.17, 95% CI [−0.33, 0.00], p = 0.044; respectively). More than one half of participants with lower limb spasticity had severe UI, compared to only 10% without lower limb spasticity (relative risk = 5.5; 95% CI [1.9, 15.9]; p = 0.006). Comorbid spasticity and UI may be common in the long-term care setting and negatively associated with ADL and quality of life. Further investigation is needed to confirm these findings. [ Journal of Gerontological Nursing, 46 (10), 35–42.]

Published
2020

35. Emergent Mental Health Visits to a Pediatric Hospital

Author

Jennifer Jensen, Neil G. Uspal, Kelly Schloredt, Bonnie Strelitz, Carolyn A. Paris, Chelsie Gallagher, Elizabeth Bennett, Luis Sanchez-Erebia, and Miranda C. Bradford

Subjects
Firearms, medicine.medical_specialty, Safe storage, Tertiary care, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Standard care, 030225 pediatrics, Pediatric hospital, Humans, Medicine, Child, business.industry, 030208 emergency & critical care medicine, General Medicine, Emergency department, Hospitals, Pediatric, Mental health, Suicide, Mental Health, Pediatrics, Perinatology and Child Health, Emergency medicine, Emergency Medicine, Safety, business, After treatment
Abstract

OBJECTIVE The aims of this study were to describe firearm storage practices in homes of patients evaluated for mental health (MH) complaints at a tertiary care children's hospital and to describe storage practice changes after treatment. METHODS We surveyed families of children with MH complaints presenting to the emergency department or psychiatry unit who stored firearms in their homes between February 12, 2016, and January 14, 2017. Patients and families received standard care, including routine counseling on limiting access to methods of suicide. Participants completed surveys at baseline, 7, and 30 days after discharge. The primary outcome was triple safe firearm storage-storage of firearms unloaded, locked, and with ammunition stored and locked separately. RESULTS Ninety-one household members of MH patients who stated they had firearms were enrolled at baseline. Seventy-seven (85%) completed at least 1 follow-up survey, and 63 (69%) completed both. At baseline, 21% (19/91) of participants reported engaging in triple safe firearm storage, 26% had an unlocked firearm, 23% had a loaded firearm, and 65% stored ammunition either unlocked or with their firearm. Triple safe storage rates increased to 31% at both 7 days and 30 days. Ten (17%) of 59 (P < 0.01) participants who did not report triple safe storage at baseline and completed a follow-up survey changed to reporting triple safe storage on follow-up. CONCLUSIONS The majority of firearm-storing family members of children with MH complaints do not follow triple safe storage practices. Storage practices modestly improved after an emergent MH visit, but over two thirds of participants reported unsecured or partially secured firearms 7 and 30 days later.

Published
2020

36. Influence of the 2012 European Guidelines in Diagnosis and Follow-up of Coeliac Children With Selective IgA Deficiency

Author

Román E, Cilleruelo Ml, Miranda C, Romero Rg, Vecino R, and Rodrigo G

Subjects
medicine.medical_specialty, Biopsy, Selective IgA deficiency, Coeliac disease, Serology, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Internal medicine, medicine, Humans, Child, Autoantibodies, Retrospective Studies, Transglutaminases, medicine.diagnostic_test, biology, business.industry, IgA Deficiency, Gastroenterology, HLA-DQ2, Hepatology, medicine.disease, Immunoglobulin A, Celiac Disease, Pediatrics, Perinatology and Child Health, Cohort, biology.protein, 030211 gastroenterology & hepatology, Antibody, business, Follow-Up Studies
Abstract

OBJECTIVES The aim of the study was to describe diagnostic criteria used in children with coeliac disease (CD) and selective IgA deficiency; to determine if the publication of the 2012 ESPGHAN criteria prompted any changes; to evaluate the evolution of serological markers. METHODS Multicenter, retrospective, descriptive study of a cohort of children under 15 years with selective IgA deficiency diagnosed with CD (January 2006 to December 2016). Demographic, clinical, genetic, histological and IgG-based antibodies were collected at diagnosis and follow-up. RESULTS Eighty-six children were included, 60 diagnosed after the guide. Two groups were established: G1 (n = 63) and G2 (n = 23) with or without diagnostic biopsy respectively. In G1: 87.3% were symptomatic, 87.3% had human leukocyte antigan (HLA) DQ2/DQ8 typing (all positive), all had IgG serology positive (71.5% ATG, 35% EMA, 19% DPG, 9.5% AGA), and all had villous atrophy (Marsh-Oberhuber 2-3). Follow-up data were available in 58 children, 34 after 2 years on a gluten-free diet. Fifty-two percentage remained ATG IgG-positive despite good dietary adherence and symptom remission. Regarding G2: all were diagnosed post-2012, had typical symptoms, HLA DQ2/DQ8 positive and ATG IgG × 10 ULN. Additionally, EMA IgG was performed in 14 (60%), all positive. CONCLUSIONS In our cohort of children with selective IgA deficiency and diagnosed with CD, children without a diagnostic biopsy suggests that IgG serology was considered the equivalent as IgA isotype, even when this is not addressed in the aforementioned guidelines. Great heterogeneity was observed in the IgG serology used at diagnosis. After 2 years of a gluten-free diet, half of children remained with a positive serology.

Published
2020

37. Primary care diagnostic and treatment pathways in Dutch women with urinary incontinence

Author

Miranda C. Schreuder, Nadine A. M. van Merode, Antal P. Oldenhof, Feikje Groenhof, Marlous F. Kortekaas, Hedy Maagdenberg, Johannes C. van der Wouden, Henk van der Worp, Marco H. Blanker, Life Course Epidemiology (LCE), Elderly care medicine, General practice, APH - Aging & Later Life, and APH - Quality of Care

Subjects
Male, Urinary Incontinence, Primary Health Care, General Practitioners, Urinary Incontinence, Stress, Public Health, Environmental and Occupational Health, Humans, Female, Retrospective Studies
Abstract

To investigate how GPs manage women with urinary incontinence (UI) in the Netherlands and to assess whether this is in line with the relevant Dutch GP guideline. Because UI has been an underreported and undertreated problem for decades despite appropriate guidelines being created for general practitioners (GPs). Retrospective cohort study. Routine primary care data for 2017 in the Netherlands. We included the primary care records of women aged 18–75 years with at least one contact registered for UI, and then extracted information about baseline characteristics, diagnosis, treatment, and referral to pelvic physiotherapy or secondary care. In total, 374 records were included for women aged 50.3 ± 15.1 years. GPs diagnosed 31.0%, 15.2%, and 15.0% women with stress, urgency, or mixed UI, respectively; no diagnosis of type was recorded in 40.4% of women. Urinalysis was the most frequently used diagnostic test (42.5%). Education was the most common treatment, offered by 17.9% of GPs; however, no treatment or referral was reported in 15.8% of cases. As many as 28.7% and 21.7% of women were referred to pelvic physiotherapy and secondary care, respectively. Female UI is most probably not managed in line with the relevant Dutch GP guideline. It is also notable that Dutch GPs often fail to report the type of UI, to use available diagnostic approaches, and to provide appropriate education. Moreover, GPs referred to specialists too often, especially for the management of urgency UI.Key pointsUrinary incontinence (UI) has been an underreported and undertreated problem for decades. Despite various guidelines, UI often lies outside the GPs comfort zone.•According to this study: general practitioners do not treat urinary incontinence according to guidelines.•The type of incontinence is frequently not reported and diagnostic approaches are not fully used.•We believe that increased awareness will help improve treatment and avoidable suffering. Urinary incontinence (UI) has been an underreported and undertreated problem for decades. Despite various guidelines, UI often lies outside the GPs comfort zone. •According to this study: general practitioners do not treat urinary incontinence according to guidelines. •The type of incontinence is frequently not reported and diagnostic approaches are not fully used. •We believe that increased awareness will help improve treatment and avoidable suffering.

Published
2022

38. Hand function development of children with hemiplegic cerebral palsy: A scoping review

Author

Miranda C. Ludovice, Derek G. Kamper, Catherine Elliott, and James V. McCall

Subjects
Hemiplegic cerebral palsy, medicine.medical_specialty, Hand function, business.industry, Cerebral Palsy, Rehabilitation, Physical Therapy, Sports Therapy and Rehabilitation, Hemiplegia, Hand, Biomechanical Phenomena, Upper Extremity, Physical medicine and rehabilitation, Pediatrics, Perinatology and Child Health, medicine, Humans, business, Child, Physical Therapy Modalities
Abstract

PURPOSE: Hemiplegic cerebral palsy (hCP) typically impacts sensorimotor control of the hand, but comprehensive assessments of the hands of children with hCP are relatively rare. This scoping review summarizes the development of hand function for children with hCP. METHODS: This scoping review focused on the development of hand function in children with hCP. Electronic databases (PubMed, PEDro, Web of Science, CINAHL, and SpringerLink) were searched to identify studies assessing hand function in children with hCP. The search was performed using keywords (e.g., “hemiplegia”). An iterative approach verified by two authors was used to select the studies. Articles which reported quantitative data for children with hCP on any items of a specified set of hand evaluations were included. Measures were sorted into three categories: quantitative neuromechanics, clinical assessments, and clinical functional evaluations. RESULTS: Initial searches returned 1536 articles, 131 of which were included in the final review. Trends between assessment scores and age were examined for both hands. CONCLUSION: While several studies have evaluated hand function in children with hCP, the majority relied on clinical scales, assessments, or qualitative descriptions. Further assessments of kinematics, kinetics, and muscle activation patterns are needed to identify the underlying impairment mechanisms that should be targeted for treatment.

Published
2021

39. Value of screening and follow-up brain MRI scans in patients with metastatic melanoma

Author

Geke A. P. Hospers, Thijs T Wind, Annemarie C Eggen, Ingeborg Bosma, Miranda C. A. Kramer, Mathilde Jalving, Hiska L. van der Weide, Peter Jan van Laar, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)

Subjects
Male, Cancer Research, Skin Neoplasms, IMPACT, medicine.medical_treatment, THERAPY, brain metastases, Mass Screening, FAILURE, Research Articles, RC254-282, Netherlands, neuroimaging, Brain Neoplasms, Melanoma, SALVAGE, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, OPEN-LABEL, Magnetic Resonance Imaging, DABRAFENIB, CANCER, Oncology, neuro‐oncology, Female, Radiology, medicine.symptom, neuro-oncology, Research Article, medicine.drug, early diagnosis, RADIOSURGERY, medicine.medical_specialty, Ipilimumab, Asymptomatic, Radiosurgery, Neuroimaging, medicine, melanoma, Humans, Radiology, Nuclear Medicine and imaging, Aged, Retrospective Studies, business.industry, IPILIMUMAB, Clinical Cancer Research, Cancer, Retrospective cohort study, Dabrafenib, medicine.disease, business
Abstract

Background Novel treatments make long‐term survival possible for subsets of patients with melanoma brain metastases. Brain magnetic resonance imaging (MRI) may aid in early detection of brain metastases and inform treatment decisions. This study aimed to determine the impact of screening MRI scans in patients with metastatic melanoma and follow‐up MRI scans in patients with melanoma brain metastases. Methods This retrospective cohort study included patients diagnosed with metastatic melanoma or melanoma brain metastases between June 2015 and January 2018. The impact of screening MRI scans was evaluated in the first 2 years after metastatic melanoma diagnosis. The impact of follow‐up MRI scans was examined in the first year after brain metastases diagnosis. The number of MRI scans, scan indications, scan outcomes, and changes in treatment strategy were analyzed. Results In total, 116 patients had no brain metastases at the time of the metastatic melanoma diagnosis. Twenty‐eight of these patients (24%) were subsequently diagnosed with brain metastases. Screening MRI scans detected the brain metastases in 11/28 patients (39%), of which 8 were asymptomatic at diagnosis. In the 96 patients with melanoma brain metastases, treatment strategy changed after 75/168 follow‐up MRI scans (45%). In patients treated with immune checkpoint inhibitors, the number of treatment changes after follow‐up MRI scans was lower when patients had been treated longer. Conclusion(s) Screening MRI scans aid in early detection of melanoma brain metastases, and follow‐up MRI scans inform treatment strategy. In patients with brain metastases responding to immune checkpoint inhibitors, treatment changes were less frequently observed after follow‐up MRI scans. These results can inform the development of brain imaging protocols for patients with immune checkpoint inhibitor sensitive tumors., This study demonstrates that screening magnetic resonance imaging (MRI) scans aid in the early detection of asymptomatic brain metastases. Furthermore, changes in treatment strategy often occur after follow‐up MRI scans in patients with melanoma brain metastases.

Published
2021

41. Exploring the Presence of Multiple Abnormal Non-Motor Features in Patients with Cervical Dystonia

Author

Nia Mitchell, Miranda C. Tomaras, David Ezana, Grace Cannard, Aaditi G. Naik, Jacqueline Meystedt, Lea Sayce, David Charles, and Mallory L. Hacker

Subjects
medicine.medical_specialty, business.industry, Spatial discrimination, Movement, General Medicine, Audiology, medicine.disease, Article, Neurology, Physiology (medical), Healthy control, medicine, Non motor, Humans, Surgery, In patient, Neurology (clinical), Cervical dystonia, business, Temporal discrimination, Torticollis
Abstract

This study’s aim was to investigate prevalence of four non-motor symptoms in patients with cervical dystonia and healthy controls to explore whether the presence of multiple non-motor features is associated with cervical dystonia diagnosis. Fifteen patients with cervical dystonia and 15 healthy controls underwent non-invasive testing of spatial discrimination threshold, temporal discrimination threshold, vibration-induced illusion of movement, and kinesthesia. All spatial discrimination threshold, temporal discrimination threshold, and vibration-induced illusion of movement measures were converted to standardized Z scores with scores >2.0 considered abnormal. Any incorrect kinesthesia response was considered abnormal. Prevalence of each abnormal non-motor feature was compared between groups using a chi-squared test. A higher proportion of patients with cervical dystonia had abnormal spatial discrimination threshold (p = 0.01) and abnormal kinesthesia (p = 0.03) scores compared to healthy control subjects. There were no significant differences between the proportion of patients with cervical dystonia versus healthy controls for abnormal temporal discrimination threshold (p = 0.07) or abnormal vibration-induced illusion of movement (p = 0.14). Forty-seven percent of patients with cervical dystonia (7/15) demonstrated one abnormal non-motor feature, 20% (3/15) displayed two abnormal features, and 13% (2/15) displayed three abnormal features. Kinesthesia was the only non-motor feature identified as abnormal in the control group (20%, 3/15). All four tests demonstrated high specificity (80–100%) and low-moderate sensitivity (13–60%). These findings suggest that non-motor feature testing, specifically for spatial discrimination threshold and kinesthesia, could be a highly specific diagnostic tool to inform cervical dystonia diagnosis. Further investigation is needed to confirm these findings.

Published
2021

42. Assessment of the Promoting Resilience in Stress Management Intervention for Adolescent and Young Adult Survivors of Cancer at 2 Years

Author

Rosenberg, Abby R., Zhou, Chuan, Bradford, Miranda C., Salsman, John M., Sexton, Katie, O’Daffer, Alison, and Yi-Frazier, Joyce P.

Subjects
Adult, Male, Adolescent, Research, Resilience, Psychological, United States, Online Only, Young Adult, Oncology, Cancer Survivors, Neoplasms, Adaptation, Psychological, Quality of Life, Humans, Female, Stress, Psychological, Original Investigation
Abstract

Key Points Question Is the Promoting Resilience In Stress Management (PRISM) psychosocial intervention associated with sustained well-being among adolescent and young adult cancer survivors? Findings In this secondary analysis of available 2-year long-term follow-up data on 57 participants from a phase 2 clinical randomized trial, adolescents and young adults who received PRISM reported sustained improvements in patient-reported cancer-related quality of life and hope compared with those who received usual care. Meaning The findings of this study suggest that positive psychology interventions such as PRISM may bolster durable well-being among adolescent and young adult survivors of cancer., This secondary analysis of long-term follow-up data from a randomized clinical trial examines the effectiveness of the Promoting Resilience In Stress Management intervention for the psychological well-being of adolescents and young adults who have survived cancer., Importance Adolescents and young adults (AYAs) with cancer have a high risk of poor psychosocial outcomes. The Promoting Resilience in Stress Management (PRISM) intervention is one of few psychosocial interventions targeting younger people with cancer that has demonstrated efficacy in a randomized clinical trial. Objective To explore 2-year trajectories of patient-reported well-being among AYA cancer survivors. The hypothesis was that AYAs who initially responded to PRISM would report sustained positive changes. Design, Setting, and Participants This secondary analysis of data from a single-center, parallel, phase 2 randomized clinical trial was conducted from January 2015 to October 2016. Eligible participants were English-speaking AYAs between ages 13 and 25 years with cancer treated at a single, quaternary children’s hospital in the US. Participants were randomly assigned (1:1) to PRISM or usual care. Data were analyzed between March 2021 and June 2021. Intervention PRISM is a brief, skills-based coaching program targeting 4 resilience resources (stress management, goal setting, cognitive reframing, and meaning making). Main Outcomes and Measures Patient-reported cancer-related quality of life (QoL) (PedsQL scale), hope (Hope scale), resilience (Connor-Davidson Resilience scale), and psychological distress (Kessler-6 scale) were collected at baseline, 6, 12, and 24 months. Data from AYAs who remained alive at 24 months were analyzed. Improvement was defined as a positive change in instrument scores between baseline and 6 months (ie, the end of the PRISM program) and used linear mixed effects regression to assess changes over time. Results A total of 57 AYAs were included in analysis at 24 months (62% of 92 randomized). Twenty-six participants (46%) were female; 36 (63%) were between ages 13 and 17 years; and 20 (35%) identified as part of a racial or ethnic minority group (4 [7%] Asian, 11 [19%] Hispanic or Latino, 16 [28%] mixed race or other). PRISM was associated with improved QoL, hope, resilience, and distress between baseline and 6 months, and these associations were sustained for QoL over 12 months (β = 7.4; 95% CI, 0.8 to 14; P = .03) and hope throughout the study period (12 months: β = 6.2; 95% CI, 2.7 to 9.6; P

Published
2021

43. ‘Minimal symptom expression’ in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab

Author

Vissing J., Jacob S., Fujita K. P., O'Brien F., Howard J. F., Mazia C. G., Wilken M., Barroso F., Saba J., Rugiero M., Bettini M., Chaves M., Vidal G., Garcia A. D., DeBleecker J., Vanden Abeele G., deKoning K., DeMey K., Mercelis R., Mahieu D., Wagemaekers L., VanDamme P., Depreitere A., Schotte C., Smetcoren C., Stevens O., VanDaele S., Vandenbussche N., Vanhee A., Verjans S., Vynckier J., D'Hont A., Tilkin P., Alves deSiqueira Carvalho A., DiasBrockhausen I., Feder D., Ambrosio D., Cesar P., Melo A. P., MartinsRibeiro R., Rocha R., Rosa B. B., Veiga T., daSilva L. A., SantosEngel M., GoncalvesGeraldo J., daPenha Ananias Morita M., NogueiraCoelho E., Paiva G., Pozo M., Prando N., MartineliTorres D. D., Butinhao C. F., Duran G., SurianeFialho T. A., Gomes daSilva T. C., MaiaGoncalves L. O., Pazetto L. E., CubasVolpe L. R., SouzaDuca L., GhellerFriedrich M. A., Guerreiro A., Mohr H., PereiraMartins M., daCruz Pacheco D., Ferreira L., Macagnan A. P., Pinto G., deCassia Santos A., Souza BulleOliveira A., Amaral deAndrade A. C., Annes M., DuarteSilva L., CavalcanteLino V., Pinto W., Assis N., Carrara F., Miranda C., Souza I., Fernandes P., Siddiqi Z., Phan C., Narayan J., Blackmore D., Mallon A., Roderus R., Watt E., Vohanka S., Bednarik J., Chmelikova M., Cierny M., Toncrova S., Junkerova BarboraKurkova J., Reguliova K., Zapletalova O., Pitha J., Novakova I., Tyblova M., Jurajdova I., Wolfova M., Andersen H., Harbo T., Vinge L., Krogh S., Mogensen A., Hojgaard J., Witting N., Mette OstergaardAutzen A., Pedersen J., Eralinna J. -P., Laaksonen M., Oksaranta O., Harrison T., Eriksson J., Rozsa C., Horvath M., Lovas G., Matolcsi J., Szabo G., Jakab G., Szabadosne B., Vecsei L., Dezsi L., Varga E., Konyane M., Antonini G., DiPasquale A., Garibaldi M., Morino S., Troili F., Fionda L., Sacca F., previous, Filla A., sub-investigators, Costabile T., Marano E., Fasanaro A., Marsili A., Puorro G., Mantegazza R., Antozzi C., Bonanno S., Camera G., Locatelli A., Maggi L., Pasanisi M., Campanella A., Evoli A., Alboini P. E., D'Amato V., Iorio R., Inghilleri M., Frasca V., Giacomelli E., Gori M., Lopergolo D., Onesti E., Gabriele M., Uzawa A., Kanai T., Kawaguchi N., Mori M., Kaneko Y., Kanzaki A., Kobayashi E., Murai H., Masaki K., Matsuse D., Matsushita T., Uehara T., Shimpo M., Jingu M., Kikutake K., Nakamura Y., Sano Y., Utsugisawa K., Nagane Y., Kamegamori I., Tsuda T., Fujii Y., Futono K., Ozawa Y., Mizugami A., Saito Y., Samukawa M., Suzuki H., Morikawa M., Kamakura S., Miyawaki E., Shiraishi H., Mitazaki T., Motomura M., Mukaino A., Yoshimura S., Asada S., Yoshida S., Amamoto S., Kobashikawa T., Koga M., Maeda Y., Takada K., Takada M., Tsurumaru M., Yamashita Y., Suzuki Y., Akiyama T., Narikawa K., Tano O., Tsukita K., Kurihara R., Meguro F., Fukuda Y., Sato M., Okumura M., Funaka S., Kawamura T., Makamori M., Takahashi M., Taichi N., Hasuike T., Higuchi E., Kobayashi H., Osakada K., Imai T., Tsuda E., Shimohama S., Hayashi T., Hisahara S., Kawamata J., Murahara T., Saitoh M., Suzuki S., Yamamoto D., Ishiyama Y., Ishiyama N., Noshiro M., Takeyama R., Uwasa K., Yasuda I., Kim B. -J., Lee C. N., Koo Y. S., Seok H. Y., Kang H. N., Ra H. J., Kim B. J., Cho E. B., Choi M. S., Lee H. L., Min J. -H., Seok J., Lee J. E., Koh D. Y., Kwon J. Y., Park S. A., Choi E. H., Hong Y. -H., Ahn S. -H., Koo D. L., Lim J. -S., Shin C. W., Hwang J. Y., Kim M., Kim S. M., Jeong H. -N., Jung J. W., Kim Y. -H., Lee H. S., Shin H. Y., Hwang E. B., Shin M., van derKooi A., deVisser M., Gibson T., Casasnovas C., AlbertiAguilo M. A., Homedes-Pedret C., Palacios N. J., DiezPorras L., VelezSantamaria V., Lazaro A., DiezTejedor E., GomezSalcedo P., Fernandez-Fournier M., LopezRuiz P., Rodriguez deRivera F. J., Sastre M., GamezCarbonell J., Sune P., SalvadoFigueras M., Gili G., Mazuela G., Illa I., CortesVicente E., Diaz-Manera J., QuerolGutierrez L. A., RojasGarcia R., Vidal N., Arribas-Ibar E., Piehl F., Hietala A., Bjarbo L., Sengun I., Meherremova A., Ozcelik P., Balkan B., Tuga C., Ugur M., Erdem-Ozdamar S., Bekircan-Kurt C. E., Acar N. P., Yilmaz E., Caliskan Y., Orsel G., Efendi H., Aydinlik S., Cavus H., Kutlu A., Becerikli G., Semiz C., Tun O., Terzi M., Dogan B., Onar M. K., Sen S., KirbasCavdar T., Veske A., Norwood F., Dimitriou A., Gollogly J., Mahdi-Rogers M., Seddigh A., Sokratous G., Maier G., Sohail F., Sadalage G., Torane P., Brown C., Shah A., Sathasivam S., Arndt H., Davies D., Watling D., Amato A., Cochrane T., Salajegheh M., Roe K., Amato K., Toska S., Wolfe G., Silvestri N., Patrick K., Zakalik K., Katz J., Miller R., Engel M., Forshew D., Bravver E., Brooks B., Sanjak M., Plevka S., Burdette M., Cunningham S., Kramer M., Nemeth J., Schommer C., Tinerney S., Juel V., Guptill J., Hobson-Webb L., Massey J., Beck K., Carnes D., Loor J., Anderson A., Pascuzzi R., Bodkin C., Kincaid J., Snook R., Guinrich S., Micheels A., Chaudhry V., Corse A., Mosmiller B., Kelley A., Ho D., Srinivasan J., Vytopil M., Jara J., Ventura N., Carter C., Donahue C., Herbert C., Scala S., Weiner E., Alam S., McKinnon J., Haar L., McKinnon N., Alcon K., McKenna K., Sattar N., Daniels K., Jeffery D., Freimer M., Hoyle J. C., Kissel J., Agriesti J., Chelnick S., Mezache L., Pineda C., Muharrem F., Karam C., Khoury J., Marburger T., Kaur H., Dimitrova D., Gilchrist J., Agrawal B., Elsayed M., Kohlrus S., Andoin A., Darnell T., Golden L., Lokaitis B., Seelbach J., Muppidi S., Goyal N., Sakamuri S., So Y. T., Paulose S., Pol S., Welsh L., Bhavaraju-Sanka R., TobonGonzalez A., Dishman L., Jones F., Gonzalez A., Padilla P., Saklad A., Silva M., Nations S., Trivedi J., Hopkins S., Kazamel M., Alsharabati M., Lu L., Nozaki K., Mumfrey-Thomas S., Woodall A., Mozaffar T., Cash T., Roy G., Mathew V., Maqsood F., Minton B., Jones H. J., Rosenfeld J., Garcia R., Echevarria L., Garcia S., Pulley M., Aranke S., Berger A. R., Shah J., Shabbir Y., Smith L., Varghese M., Gutmann L., Jerath N., Nance C., Swenson A., Olalde H., Kressin N., Sieren J., Barohn R., Dimachkie M., Glenn M., McVey A., Pasnoor M., Statland J., Wang Y., Liu T., Emmons K., Jenci N., Locheke J., Fondaw A., Johns K., Rico G., Walsh M., Herbelin L., Hafer-Macko C., Kwan J., Zilliox L., Callison K., Young V., DiSanzo B., Naunton K., Benatar M., Bilsker M., Sharma K., Cooley A., Reyes E., Michon S. -C., Sheldon D., Steele J., Howard J., Traub R., Chopra M., Vu T., Katzin L., McClain T., Harvey B., Hart A., Huynh K., Beydoun S., Chilingaryan A., Doan V., Droker B., Gong H., Karimi S., Lin F., Polaka K., Tran A., Akhter S., Malekniazi A., Tandan R., Hehir M., Waheed W., Lucy S., Weiss M., Distad J., Strom S., Downing S., Kim B., Bertorini T., Arnold T., Henderson K., Pillai R., Liu Y., Wheeler L., Hewlett J., Vanderhook M., Nowak R., Dicapua D., Keung B., Kumar A., Patwa H., Robeson K., Yang I., Nye J., Vu H., Vissing, J., Jacob, S., Fujita, K. P., O'Brien, F., Howard, J. F., Mazia, C. G., Wilken, M., Barroso, F., Saba, J., Rugiero, M., Bettini, M., Chaves, M., Vidal, G., Garcia, A. D., Debleecker, J., Vanden Abeele, G., Dekoning, K., Demey, K., Mercelis, R., Mahieu, D., Wagemaekers, L., Vandamme, P., Depreitere, A., Schotte, C., Smetcoren, C., Stevens, O., Vandaele, S., Vandenbussche, N., Vanhee, A., Verjans, S., Vynckier, J., D'Hont, A., Tilkin, P., Alves deSiqueira Carvalho, A., Diasbrockhausen, I., Feder, D., Ambrosio, D., Cesar, P., Melo, A. P., Martinsribeiro, R., Rocha, R., Rosa, B. B., Veiga, T., Dasilva, L. A., Santosengel, M., Goncalvesgeraldo, J., daPenha Ananias Morita, M., Nogueiracoelho, E., Paiva, G., Pozo, M., Prando, N., Martinelitorres, D. D., Butinhao, C. F., Duran, G., Surianefialho, T. A., Gomes daSilva, T. C., Maiagoncalves, L. O., Pazetto, L. E., Cubasvolpe, L. R., Souzaduca, L., Ghellerfriedrich, M. A., Guerreiro, A., Mohr, H., Pereiramartins, M., daCruz Pacheco, D., Ferreira, L., Macagnan, A. P., Pinto, G., deCassia Santos, A., Souza BulleOliveira, A., Amaral deAndrade, A. C., Annes, M., Duartesilva, L., Cavalcantelino, V., Pinto, W., Assis, N., Carrara, F., Miranda, C., Souza, I., Fernandes, P., Siddiqi, Z., Phan, C., Narayan, J., Blackmore, D., Mallon, A., Roderus, R., Watt, E., Vohanka, S., Bednarik, J., Chmelikova, M., Cierny, M., Toncrova, S., Junkerova BarboraKurkova, J., Reguliova, K., Zapletalova, O., Pitha, J., Novakova, I., Tyblova, M., Jurajdova, I., Wolfova, M., Andersen, H., Harbo, T., Vinge, L., Krogh, S., Mogensen, A., Hojgaard, J., Witting, N., Mette OstergaardAutzen, A., Pedersen, J., Eralinna, J. -P., Laaksonen, M., Oksaranta, O., Harrison, T., Eriksson, J., Rozsa, C., Horvath, M., Lovas, G., Matolcsi, J., Szabo, G., Jakab, G., Szabadosne, B., Vecsei, L., Dezsi, L., Varga, E., Konyane, M., Antonini, G., Dipasquale, A., Garibaldi, M., Morino, S., Troili, F., Fionda, L., Sacca, F., Previous, Filla, A., sub-investigators, Costabile, T., Marano, E., Fasanaro, A., Marsili, A., Puorro, G., Mantegazza, R., Antozzi, C., Bonanno, S., Camera, G., Locatelli, A., Maggi, L., Pasanisi, M., Campanella, A., Evoli, A., Alboini, P. E., D'Amato, V., Iorio, R., Inghilleri, M., Frasca, V., Giacomelli, E., Gori, M., Lopergolo, D., Onesti, E., Gabriele, M., Uzawa, A., Kanai, T., Kawaguchi, N., Mori, M., Kaneko, Y., Kanzaki, A., Kobayashi, E., Murai, H., Masaki, K., Matsuse, D., Matsushita, T., Uehara, T., Shimpo, M., Jingu, M., Kikutake, K., Nakamura, Y., Sano, Y., Utsugisawa, K., Nagane, Y., Kamegamori, I., Tsuda, T., Fujii, Y., Futono, K., Ozawa, Y., Mizugami, A., Saito, Y., Samukawa, M., Suzuki, H., Morikawa, M., Kamakura, S., Miyawaki, E., Shiraishi, H., Mitazaki, T., Motomura, M., Mukaino, A., Yoshimura, S., Asada, S., Yoshida, S., Amamoto, S., Kobashikawa, T., Koga, M., Maeda, Y., Takada, K., Takada, M., Tsurumaru, M., Yamashita, Y., Suzuki, Y., Akiyama, T., Narikawa, K., Tano, O., Tsukita, K., Kurihara, R., Meguro, F., Fukuda, Y., Sato, M., Okumura, M., Funaka, S., Kawamura, T., Makamori, M., Takahashi, M., Taichi, N., Hasuike, T., Higuchi, E., Kobayashi, H., Osakada, K., Imai, T., Tsuda, E., Shimohama, S., Hayashi, T., Hisahara, S., Kawamata, J., Murahara, T., Saitoh, M., Suzuki, S., Yamamoto, D., Ishiyama, Y., Ishiyama, N., Noshiro, M., Takeyama, R., Uwasa, K., Yasuda, I., Kim, B. -J., Lee, C. N., Koo, Y. S., Seok, H. Y., Kang, H. N., Ra, H. J., Kim, B. J., Cho, E. B., Choi, M. S., Lee, H. L., Min, J. -H., Seok, J., Lee, J. E., Koh, D. Y., Kwon, J. Y., Park, S. A., Choi, E. H., Hong, Y. -H., Ahn, S. -H., Koo, D. L., Lim, J. -S., Shin, C. W., Hwang, J. Y., Kim, M., Kim, S. M., Jeong, H. -N., Jung, J. W., Kim, Y. -H., Lee, H. S., Shin, H. Y., Hwang, E. B., Shin, M., van derKooi, A., Devisser, M., Gibson, T., Casasnovas, C., Albertiaguilo, M. A., Homedes-Pedret, C., Palacios, N. J., Diezporras, L., Velezsantamaria, V., Lazaro, A., Dieztejedor, E., Gomezsalcedo, P., Fernandez-Fournier, M., Lopezruiz, P., Rodriguez deRivera, F. J., Sastre, M., Gamezcarbonell, J., Sune, P., Salvadofigueras, M., Gili, G., Mazuela, G., Illa, I., Cortesvicente, E., Diaz-Manera, J., Querolgutierrez, L. A., Rojasgarcia, R., Vidal, N., Arribas-Ibar, E., Piehl, F., Hietala, A., Bjarbo, L., Sengun, I., Meherremova, A., Ozcelik, P., Balkan, B., Tuga, C., Ugur, M., Erdem-Ozdamar, S., Bekircan-Kurt, C. E., Acar, N. P., Yilmaz, E., Caliskan, Y., Orsel, G., Efendi, H., Aydinlik, S., Cavus, H., Kutlu, A., Becerikli, G., Semiz, C., Tun, O., Terzi, M., Dogan, B., Onar, M. K., Sen, S., Kirbascavdar, T., Veske, A., Norwood, F., Dimitriou, A., Gollogly, J., Mahdi-Rogers, M., Seddigh, A., Sokratous, G., Maier, G., Sohail, F., Sadalage, G., Torane, P., Brown, C., Shah, A., Sathasivam, S., Arndt, H., Davies, D., Watling, D., Amato, A., Cochrane, T., Salajegheh, M., Roe, K., Amato, K., Toska, S., Wolfe, G., Silvestri, N., Patrick, K., Zakalik, K., Katz, J., Miller, R., Engel, M., Forshew, D., Bravver, E., Brooks, B., Sanjak, M., Plevka, S., Burdette, M., Cunningham, S., Kramer, M., Nemeth, J., Schommer, C., Tinerney, S., Juel, V., Guptill, J., Hobson-Webb, L., Massey, J., Beck, K., Carnes, D., Loor, J., Anderson, A., Pascuzzi, R., Bodkin, C., Kincaid, J., Snook, R., Guinrich, S., Micheels, A., Chaudhry, V., Corse, A., Mosmiller, B., Kelley, A., Ho, D., Srinivasan, J., Vytopil, M., Jara, J., Ventura, N., Carter, C., Donahue, C., Herbert, C., Scala, S., Weiner, E., Alam, S., Mckinnon, J., Haar, L., Mckinnon, N., Alcon, K., Mckenna, K., Sattar, N., Daniels, K., Jeffery, D., Freimer, M., Hoyle, J. C., Kissel, J., Agriesti, J., Chelnick, S., Mezache, L., Pineda, C., Muharrem, F., Karam, C., Khoury, J., Marburger, T., Kaur, H., Dimitrova, D., Gilchrist, J., Agrawal, B., Elsayed, M., Kohlrus, S., Andoin, A., Darnell, T., Golden, L., Lokaitis, B., Seelbach, J., Muppidi, S., Goyal, N., Sakamuri, S., So, Y. T., Paulose, S., Pol, S., Welsh, L., Bhavaraju-Sanka, R., Tobongonzalez, A., Dishman, L., Jones, F., Gonzalez, A., Padilla, P., Saklad, A., Silva, M., Nations, S., Trivedi, J., Hopkins, S., Kazamel, M., Alsharabati, M., Lu, L., Nozaki, K., Mumfrey-Thomas, S., Woodall, A., Mozaffar, T., Cash, T., Roy, G., Mathew, V., Maqsood, F., Minton, B., Jones, H. J., Rosenfeld, J., Garcia, R., Echevarria, L., Garcia, S., Pulley, M., Aranke, S., Berger, A. R., Shah, J., Shabbir, Y., Smith, L., Varghese, M., Gutmann, L., Jerath, N., Nance, C., Swenson, A., Olalde, H., Kressin, N., Sieren, J., Barohn, R., Dimachkie, M., Glenn, M., Mcvey, A., Pasnoor, M., Statland, J., Wang, Y., Liu, T., Emmons, K., Jenci, N., Locheke, J., Fondaw, A., Johns, K., Rico, G., Walsh, M., Herbelin, L., Hafer-Macko, C., Kwan, J., Zilliox, L., Callison, K., Young, V., Disanzo, B., Naunton, K., Benatar, M., Bilsker, M., Sharma, K., Cooley, A., Reyes, E., Michon, S. -C., Sheldon, D., Steele, J., Howard, J., Traub, R., Chopra, M., Vu, T., Katzin, L., Mcclain, T., Harvey, B., Hart, A., Huynh, K., Beydoun, S., Chilingaryan, A., Doan, V., Droker, B., Gong, H., Karimi, S., Lin, F., Polaka, K., Tran, A., Akhter, S., Malekniazi, A., Tandan, R., Hehir, M., Waheed, W., Lucy, S., Weiss, M., Distad, J., Strom, S., Downing, S., Kim, B., Bertorini, T., Arnold, T., Henderson, K., Pillai, R., Liu, Y., Wheeler, L., Hewlett, J., Vanderhook, M., Nowak, R., Dicapua, D., Keung, B., Kumar, A., Patwa, H., Robeson, K., Yang, I., Nye, J., Vu, H., ANS - Neuroinfection & -inflammation, and Neurology

Subjects
0301 basic medicine, Male, Myasthenia gravi, Gastroenterology, 0302 clinical medicine, Quality of life, Activities of Daily Living, CYCLOPHOSPHAMIDE, Medicine and Health Sciences, Medicine, Receptors, Cholinergic, Acetylcholine receptor, Myasthenia gravis, Original Communication, Eculizumab, Minimal symptom expression, Refractory, Middle Aged, Acetylcholine receptor antibody, Tolerability, Neurology, Female, Life Sciences & Biomedicine, COMPLEMENT INHIBITOR ECULIZUMAB, medicine.drug, Adult, medicine.medical_specialty, Clinical Neurology, Placebo, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Double-Blind Method, Internal medicine, Humans, Immunologic Factors, Patient Reported Outcome Measures, Generalized myasthenia, Aged, Autoantibodies, Science & Technology, business.industry, Confidence interval, 030104 developmental biology, Quality of Life, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery
Abstract

Background The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension. Methods Attainment of ‘minimal symptom expression’ was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. ‘Minimal symptom expression’ was defined as MG-ADL total score of 0–1 or MG-QOL15 total score of 0–3. Results At REGAIN week 26, more eculizumab-treated patients achieved ‘minimal symptom expression’ versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved ‘minimal symptom expression’ increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved ‘minimal symptom expression’ (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports. Conclusions Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained ‘minimal symptom expression’ based on patient-reported outcomes. ‘Minimal symptom expression’ may be a useful tool in measuring therapy effectiveness in gMG. Trial registration ClinicalTrials.gov NCT01997229, NCT02301624.

Published
2020

44. Surgical site infection after gastrointestinal surgery in children: An international, multicentre, prospective cohort study

Author

Harrison E. M., Drake T. M., Ghosh D., Ademuyiwa A. O., Bhangu A., Fitzgerald J. E., Glasbey J., Borda-Luque G., Costas-Chavarri A., Ntirenganya F., Fergusson S. J., Ingabire J. C. A., Ismail L., Lilford R., Mihaljevic A. L., Morton D., Mutabazi A. Z., Adisa A. O., Ots R., Pinkney T., Poskus T., Shaw C. A., Verjee A., Runigamugabo E., Khatri C., Mohan M., Jaffry Z., Altamini A., Kirby A., Soreide K., Cornick J., Iyer D., King S., Arthur T., Nahar S. N., Waterman A., Lawini I., Rouse T., Correa J. C., Salem H. K., Worku M., Arnaud A., Kalles V., Aguilera M. L., Recinos G., Quek R., Altibi A., Whitaker J., Bent Z., Al-Slaibi I., Tahboub H., Alser O. H., Shu S., Mironescu A., Bratu M., Altwijri A., Alsaggaf M. U., Jubran A. F., Seisay S., Jeyakumar J., Senanayake K., Abdulbagi O., Raptis D., Kong C., Suresh S., Scott M., Grizhja B., Ymeri S., Galiqi G., Klappenbach R., Antezana D., Beleno A. E. M., Costa C., Sanchez B., Aviles S., Modolo M. M., Fermani C. G., Balmaceda R., Villalobos S., Carmona J. M., Hamill D., Deutschmann P., Sandler S., Cox D., Nataraja R., Sharpin C., Ljuhar D., Gray D., Haines M., Niranjan N., D'Amours S., Ashtari M., Franco H., Mitul A. R., Karim S., Aman N. F., Estee M. M., Salma U., Razzaque J., Hamidkanta T., Tori S., Alamin Md. S., Roy S., Al Amin Md. S., Haque M., Faruq A., Iftekhar F., O'Shea M., Padmore G., Jonnalagadda R., Litvin A., Filatau A., Paulouski D., Shubianok M., Shachykava T., Khokha D., Khokha V., Djivoh F., Lawani I., Dossou F., Seto D. M., Gbessi D. G., Noukpozounkou B., Souaibou Y. I., Keke K. R., Hodonou F., Ahounou E., Alihonou T., Denakpo M., Ahlonsou G., Bedada A. G., Nsengiyumva C., Kwizera S., Barendegere V., Choi P., Stock S., Jamal L., Firdouse M., Zani A., Azzie G., Kushwaha S., Agarwal A., Chen T. -L., Yip C., Montes I., Zapata F., Sierra S., Lanau M. I. V., Arango M. C. M., Restrepo I. M., Giraldo R. S. R., Mendozaarango M., Domini E., Karlo R., Mihanovic J., Youssef M., Elfeki H., Thabet W., Sanad A., Tawfik G., Zaki A., Abdel-Hameed N., Mostafa M., Omar M. F. W., Ghanem A., Abdallah E., Denewer A., Emara E., Rashad E., Sakr A., Elashry R., Emile S., Khafagy T., Elhamouly S., Elfarargy A., Mamdouhmohamed A., Saiednagy G., Esam A., Elwy E., Hammad A., Khallaf S., Ibrahim E., Saidbadr A., Moustafa A., Eldosoukymohammed A., Elgheriany M., Abdelmageed E., Al Raouf E. A., Elbanby E., Elmasry M., Morsyfarahat M., Yahyamansor E., Magdyhegazy E., Gamal E., Gamal H., Kandil H., Maherabdelrouf D., Moaty M., Gamal D., El-Sagheer N., Salah M., Magdy S., Salah A., Essam A., Ali A., Badawy M., Ahmed S., Mohamed M., Assal A., Sleem M., Ebidy M., Abdelrazek A., Zahran D., Adam N., Nazir M., Hassanein A. B., Ismail A., Elsawy A., Mamdouh R., Mabrouk M., Ahmed L. A. M., Hassabalnaby M., Magdy E., Abd-Elmawla M., Fahim M., Mowafy B., Mahmoud M. I., Allam M., Alkelani M., El Gendy N. H., Aboul-Naga M. S., Alaael-Din R., Elgendy A. H., Ismail M., Shalaby M., Elsharkawy A. A., Moghazy M. E., Elbisomy K. H., Shakshouk H. A. G., Hamed M. F., Ebidy M. M., Abdelkader M., Karkeet M., Ahmed H., Adel I., Omar M. E., Ibrahim M., Ghoneim O., Hesham O., Gamal S., Hilal K., Arafa O., Awad S. A., Salem M., Elsherif F. A., Elsabbagh N., Aboelsoud M. R., Rida A. H. E. F., Hossameldin A., Hany E., Asar Y. H., Anwar N., Gadelkarim M., Abdelhady S., Morshedy E. M., Saad R., Soliman N., Salama M., Ezzat E., Mohamed A., Ibrahim A., Fergany A., Mohammed S., Reda A., Allam Y., Saad H. A., Abdelfatah A., Fathy A. M., El-Sehily A., Kasem E. A., Hassan A. T. A., Mohammed A. R., Saad A. G., Elfouly Y., Elfouly N., Hassaan A., Mohammed M. M., Elhoseny G., Magdy M., Elkhalek E. A., Zakaria Y., Ezzat T., El Dahab A. A., Kelany M., Arafa S., Hassan O. M. M., Badwi N. M., Sleem A. S., Abdelbadeai K., Abdullah M. A., Lokman M., Bahar S., Radyabdelazeam A., Adelshone A., Hasnan M. B., Zulkifli A., Kamarulzamil S. N. A., Elhendawy A., Latif A., Adnan A. B., Shaharuddin S., Majid A. H. H. A., Amreia M., Al-Marakby D., Salma M., Basir E. R. M., Ali C. D. M., Ata A. Y., Nasr M., Rezq A., Sheta A., Tariq S., Sallam A., Darwish A. K. Z., Elmihy S., El Hadry S., Farag A., Hajah H., Seliem A., Aglan A., Zohair A., Essam M., Moussa O., El-Gizawy E., Samy M., Ali S., Elhalawany E., Ata A., Elhalawany M., Nashat M., Soliman S., Elazab A., Abdelaziz M. A., Ibrahim K., Ibrahim A. M., Gado A., Hantour U., Eldeen E. A., Loaloa M. R., Abouzaid A., Ahmedbahaaeldin M., Hashad E., Sroor F., Gamil D., Mahmoudabdulhakeem E., Zakaria M., Mohamed F., Abubakr M., Ali E., Magdy H., Ramadan M., Abdelatymohamed M., Mansour S., Abdulazizamin H., Rabiemohamed A., Saami M., Ahmedredaelsayed N., Tarek A., Mohyeldeenmahmoud S., El Sayed I. M., Yusufshawky M., Mousasalem M., El-Din S. A., Soliman N. A., Talaat M., Abdelmoenelhusseiny S. A. -D. A., Abdullah N., Elshaar M., Abdelfatahibraheem A., Abdulaziz H., Ismail M. K., Hamdymadkor M., Abdelaty M., Kader S. M., Mohamedsalah O., Eldafrawy M., Zakieldeeb A., Mahmoudeid M., Attia A., El-Dien K. S., Shwky A., Badenjki M. A., Soliman A., Al Attar S. M., Sayed F., Abdelsabour F., Azizeldine M. G., Shawqi M., Hashim A., Aamer A., Raouf A. M. A., Abdelshakour M., Mahmoud B., Mahmoud M. A., Qenawy M., Rashed A. M., Dahy A., Sayed M., Shamsedine A. W., Mohamed B., Hasan A., Saad M. M., Abdulbassit K., Khalidabdelatif N., Elzahed N., Elkashash A., Bekhet N. M., Hafez S., Gad A., Maher M. E., Abdelsameea A., Hafez M., Sabe A., Ahmed A., Shahine A., Dawood K., Gaafar S., Husseiny R., Aboelmagd O., Mesbah N., Emadeldin H., Almeligy A., Bekhet A. H., Hasan D., Alhady K., Sabe A. K., Elnajjar M. A., Aboelella M., Hamsho W., Hassan I., Saad H., Abdelazim G., Mahmoud H., Wael N., Kandil A. M., Magdy A., Saidelkholy S., Adel B., Dabbour K., Elsherbiney S., Mattar O., Abdrabou A. K., Aly M. Y. M., Geuoshy A., Elnagar A., Abdelmotaleb I., Saleh A. 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E., Leone N., Bondurri A., Maffioli A., Simioni A., de Boni D., Pasquali S., Goldin E., Vendramin E., Ciccioli E., Tedeschi U., Bortolasi L., Violi P., Campagnaro T., Conci S., Lazzari G., Iacono C., Guglielmi A., Manfreda S., Rinaldi A., Ringressi M. N., Brunoni B., Salamone G., Mangiapane M., de Marco P., la Brocca A., Tutino R., Silvestri V., Licari L., Fontana T., Cocorullo N. F. G., Sileri P., Arcudi C., Bsisu I., Aljboor K., Abusalem L., Alnusairat A., Qaissieh A., Al-Dakka E., Ababneh A., Halhouli O., Yusufali T., Mohammed H., Lando J., Parker R., Ndegwa W., Jokubauskas M., Gribauskaite J., Venskutonis D., Kuliavas J., Dulskas A., Samalavicius N. E., Jasaitis K., Parseliunas A., Nevieraite V., Montrimaite M., Slapelyte E., Dainius E., Riauka R., Subocius Z. D. A., Venclauskas L., Gulbinas A., Bradulskis S., Kasputyte S., Mikuckyte D., Kiudelis M., Zilinskas J., Jankus T., Petrikenas S., Pazusis M., Urniezius Z., Vilcinskas M., Banaitis V. J., Gaizauskas V., Grisin E., Mazrimas P., Rackauskas R., Drungilas M., Lagunavicius K., Lipnickas V., Majauskyte D., Jotautas V., Abaliksta T., Uscinas L., Simutis G., Ladukas A., Danys D., Laugzemys E., Mikalauskas S., Sruogiene E. Z., Visinskas P., Zilinskiene R., Dragatas D., Burmistrovas A., Tverskis Z., Vaicius A., Mazelyte R., Zadoroznas A., Kaselis N., Ziubryte G., Rahantasoa F. C. F. P., Samison L. H., Rasoaherinomenjanahary F., Tolotra T. E. C., Mukuzunga C., Msosa V., Kwatiwani C., Msiska N., Chai F. Y., Asilah S. M. D., Syibrah K. Z., Chin P. X., Salleh A., Riswan N. Z., Roslani A. C., Chong H. -Y., Aziz N. A., Poh K. -S., Chai C. -A., Taher M. M., Kosai N. R., Aziz D. N. A., Rajan R., Julaihi R., Jethwani D. L., Yahaya M. T., Abdullah N. A. N., Mathew S. W., Chung K. J., Nirumal M. K., Tze R. G. E., Ali S. A. W. E. W., Gan Y. Y., Ting J. R. S., Sii S. S. Y., Koay K. L., Tan Y. K., Cheah A. E. Z., Wong C. Y., Mat T. N. T., Chow C. Y. N., Har P. A. L., Der Y., Tew Y. Y., Henry F., Low X., Neo Y. T., Heng H. E., Kong S. N., Gan C., Mok Y. T., Tan Y. W., Palayan K., Devatata M., Cheong Y. J., Gunaseelan K., Nasir W. N. A. W. M., Yoganathan P., Lee E. X., Saw J. E., Yeang L. J., Koh P. Y., Lim S. Y., Teo S. Y., Grech N., Magri D., Cassar K., Mizzi C., Falzon M., Shaikh N., Scicluna R., Zammit S., Borg E., Mizzi S., Brincat S. D., Tembo T., Le V. T. H., Grima T., Sammut K., Carabott K., Farrugia A., Zarb C., Navarro A., Dimech T., Camilleri G., Bertuello I., Dalli J., Bonavia K., Corro-Diaz S., Manriquez-Reyes M., Ramos-De la Medina A., Abdelhamid A., Hrora A., Benammi S., Bachri H., Abbouch M., Boukhal K., Bennai R. M., Belkouchi A., Jabal M. S., Benyaiche C., Vermaas M., Duinhouwer L., Pastora J., Wood G., Merlo M. S., Ajao A., Ayandipo O., Lawal T., Abdurrazzaaq A., Habeeb O., Alada M., Nasir A., Adeniran J., Popoola A., Adeyeye A., Adebanjo A., Adesanya O., Adeniyi A., Mendel H., Bello B., Muktar U., Osinowo A., Olajide T. O., Oshati O., Ihediwa G., Adenekan B., Nwinee V., Alakaloko F., Ademuyiwa A., Elebute O., Lawal A., Bode C., Olugbemi M., Adesina A., Faturoti O., Odutola O., Adebola O., Onuoha C., Taiwo O., Williams O., Balogun F., Ajai O., Oludara M., Njokanma I., Osuoji R., Kache S., Ajah J., Makama J., Adamu A., Baba S., Aliyu M., Aliyu S., Ukwenya Y., Aliyu H., Sholadoye T., Daniyan M., Ogunsua O., Anyanwu L. -J., Sheshe A., Mohammad A., Olori S. D., Mshelbwala P., Odeyemi B., Samson G., Timothy O. K., Samuel S. A., Ajiboye A., Amole I., Abiola O., Olaolorun A., Veen T., Kanani A., Styles K., Herikstad R., Larsen J. W., Soreide J. A., Jensen E., Gran M., Aahlin E. K., Gaarder T., Monrad-Hansen P. W., Naess P. A., Lauzikas G., Wiborg J., Holte S., Augestad K., Banipal G., Monteleone M., Moe T., Schultz J., Al-Taher T., Hamdan A., Salman A., Saadeh R., Musleh A., Jaradat D., Abushamleh S., Hanoun S., Qumbos A. A., Hamarshi A., Taher A. A., Qawasmi I., Qurie K., Altarayra M., Ghannam M., Shaheen A., Herebat A., Abdelhaq A., Shalabi A., Abu-Toyour M., Asi F., Shamasneh A., Atiyeh A., Mustafa M., Zaatreh R., Dabboor M., Alaloul E., Baraka H., Meqbil J., Al-Buhaisi A., Elshami M., Afana S., Jaber S., Alyacoubi S., Abuowda Y., Idress T., Abuqwaider E., Al-Saqqa S. W., Bowabsak A., Eljamassi A., Hasanain D., Al-Farram H., Firwana A., Hamdan M., Awad I., Ashour A., Al Barrawi F. E., Al-Khatib A., Al-Faqawi M., Fares M., Elmashala A., Adawi M., Adawi I., Khreishi R., Ghaben A., Nadeem N., Saqlain M., Abbasy J., Alvi A. R., Gala T., Shahzad N., Bhopal K. F., Iftikhar Z., Butt M. T., Ul Razi S. A., Niazi A. K., Raza I., Baluch F., Raza A., Bani-Sadar A., Qureshi A. U., Adil M., Javaid M., Waqar M., Khan M., Arshad M., Amjad M., Vega G. M. M., Cardozo J. T., Roche M. O., Servin G. R. P., Lohse H. A. S., Lopez L. I. P., Cardozo R. A. M., Espinoza F., Rojas A. D. P., Sanchez D., Samaniego C. S., Torres S. G., Calua A. 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R., Negoi I., Beuran M., Ciubotaru C., Alphonse M., Uzabumwana N., Duhoranenayo D., Jovine E., Zanini N., Landolfo G., Aljiffry M., Idris F., Alghamdi M. S. A., Maghrabi A., Altaf A., Khalifah E., Gudal A., Albiety A., Alkaaki A., Alshareef R., Khoja A., Nawawi A., Najjar M., Turkustani S., Sahel S., Alzahrani A., Alghamdi A., Alhazmi W., Al Saied G., Alamoudi M., Riaz M. M., Hassanain M., Alhassan B., Altamimi A., Alyahya R., Alsubaie N., Albastawis F., Nouh T., Khan R., Radojkovic M., Jeremic L., Nestorovic M., Law J. H., Tan K. S. K., Tan R. C. K., Tan J. K., Joel L. W. L., Lieske B., Chan X. W., Leong F. Q. H., Chong C. S., Koh S., Lee K. Y., Lee K. C., Pluke K., Dedekind B., Nashidengo P., Hampton M. I., Joosten J., Sobnach S., Roodt L., Sander A., Pape J., Spence R., Maistry N., Ndwambi P., Kinandu K., Tun M., du Toit F., Ellison Q., Burger S., Grobler D. C., Khulu L. B., Moore R., Jennings V., Leusink A., Kariem N., Gouws J., Chu K., Bougard H., Noor F., Dell A., Rayne S., van Straten S., Khamajeet A., Tshisola S. K., Kabongo K., Kong V., Moodley Y., Anderson F., Madiba T., du Plooy F., Hartford L., Chilton G., Karjiker P., Mabitsela M., Ndlovu S., Badicel M., Jaich R., Ruiz-Tovar J., Garcia-Florez L., Otero-Diez J. L., Ramosperez V., Aguadosuarez N., Garcia J. M., Moreno S. C., Collado M. V., Carneros V. J., Septiem J. G., Gonzalez M., Picardo A., Esteban E., Ferrero E., Ortega I., Espin-Basany E., Blanco-Colino R., Andriola V., Lorena I., Contreras E., Garciabernardo C., Pagnozzi J., Sanz S., Miyardeleon A., Dorisme A., Rodicio J., Suarez A., Stuva J., Diazvico T., Fernandez-Vega L., Soldevila-Verdeguer C., Sena-Ruiz F., Pujol-Cano N., Diaz-Jover P., Garcia-Perez J. M., Segura-Sampedro J. J., Pineno-Flores C., Ambrona-Zafra D., Craus-Miguel A., Jimenez-Morillas P., Mazzella A., Jayathilake A. B., Thalgaspitiya S. P. B., Wijayarathna L. S., Wimalge P. M. S. N., Sanni H. A., Ndajiwo A., Okenabirhie O., Homeida A., Younis A., Omer O. A., Abdulaziz M., Mussad A., Gilani A. M., Cengiz Y., Bjorklund I., Ahlqvist S., Thorell A., Wogensen F., Sokratous A., Breistrand M., Thorarinsdottir H., Sigurdadottir J., Nikberg M., Chabok A., Hjertberg M., Elbe P., Saraste D., Rutkowski W., Forlin L., Niska K., Sund M., Oswald D., Peros G., Bluelle R., Reinisch K., Frey D., Palma A., Zumbuhl L., Zuber M., Schmid R., Werder G., Nocito A., Gerosa A., Mahanty S., Widmer L. W., Muller J., Gubeli A., Zuk G., Gulcicek O. B., Altinel Y., Vartanoglu T., Kose E., Karahan S. R., Aydin M. C., Sahbaz N. A., Halicioglu I., Alis H., Sapci I., Adiyaman C., Pektas A. M., Cengiz T. B., Tansoker I., Isler V., Cevik M., Mutlu D., Ozben V., Ozmen B. B., Bayram S., Yolcu S., Kobal B. B., Toto O. F., Cakaloglu H. C., Karabulut K., Mutlu V., Ozkan B. B., Celik S., Semiz A., Bodur S., Gul E., Murutoglu B., Yildirim R., Baki B. E., Arslan E., Ulusahin M., Guner A., Walker N., Shrimanker N., Stoddart M., Cole S., Breslin R., Srinivasan R., Elshaer M., Hunter K., Al-Bahrani A., Liew I., Mairs N. G., Rocke A., Dick L., Qureshi M., Chowdhury D., Wright N., Skerritt C., Ho A., Dissanayake T., Tennakoon A., Ali W., Lim S. J., Tan C., O'Neill S., Jones C., Knight S., Nassif D., Sharma A., Warren O., White R., Mehdi A., Post N., Kalakouti E., Dashnyam E., Stourton F., Mykoniatis I., Currow C., Wong F., Gupta A., Shatkar V., Luck J., Kadiwar S., Smedley A., Wakefield R., Herrod P., Blackwell J., Lund J., Cohen F., Bandi A., Giuliani S., Bond-Smith G., Pezas T., Farhangmehr N., Urbonas T., Perenyei M., Ireland P., Blencowe N., Bowling K., Bunting D., Longstaff L., Smart N., Keogh K., Jeon H., Iqbal M. R., Khosla S., Jeffery A., Perera J., Teasdale E., Ibrahem A. A., Alhammali T., Salama Y., Kabariti R., Oram S., Kidd T., Cullen F., Owen C., Wilson M., Chiu S., Sarafilovic H., Ploski J., Evans E., Abbas A., Kamya S., Ishak N., Bisset C., Andress C., Chin Y. R., Patel P., Evans D., Haslegrave A., Boggon A., Laurie K., Connor K., Mann T., Nepogodiev D., Mansuri A., Davies R., Griffiths E., Shahbaz A. R., Eng C., Din F., Heveder A. L., Park E. H. G., Ravishankar R., McIntosh K., Yau J. D., Chan L., McGarvie S., Tang L., Lim H., Yap S., Park J., Ng Z., Mirza S., Ang Y. L., Walls L., Roy C., Paterson-Brown S., Camilleri-Brennan J., McLean K., D'Souza M., Pronin S., Henshall D. E., Ter E., Fouad D., Minocha A., English W., Morgan C., Townsend D., Maciejec L., Mahdi S., Akpenyi O., Hall E., Caydiid H., Rob Z., Abbott T., Torrance H. D., Irwin G., Johnston R., Gani M., Gravante G., Rajmohan S., Majid K., Dindyal S., Smith C., Palliyil M., Patel S., Nicholson L., Harvey N., Baillie K., Shillito S., Kershaw S., Bamford R., Orton P., Reunis E., Tyler R., Soon W., Jama G. M., Dhillon D., Patel K., Nanthakumaran S., Heard R., Chen K. Y., Barmayehvar B., Datta U., Kamarajah S. K., Iftekhartani S., Monaghan E., Donnelly P., Walker M., Parakh J., Blacker S., Kaul A., Paramasivan A., Farag S., Nessa A., Awadallah S., Lim J., Cheankhunng J., Gash K., Kiran R. P., Murray A., Etchill E., Dasari M., Puyana J., Haddad N., Zielinski M., Choudhry A., Caliman C., Beamon M., Duane T., Narayanan R., Swaroop M., Myers J., Deal R., Schadde E., Hemmila M., Napolitano L., To K., Makupe A., Musowoya J., Maimbo M., van der Naald N., Kumwenda D., Reece-Smith A., Otten K., Verbeek A., Prins M., Suarez A. A. B., Deane C., Dijan E., Elfiky M., Koskenvuo L., Thollot A., Limoges B., Capito C., Alexandre C., Kotobi H., Leroux J., Pinnagoda K., Henric N., Azzis O., Rosello O., Francois P., Etienne S., Buisson P., Hmila S., Clegg-Lamptey J. -N., Imoro O., Abem O. E., Papageorgiou D., Soulou V., Asturias S., Pena L., Connor D. B. O., Luc A. R., Russo A. A., Ruzzenente A., Taddei A., Cona C., Bottini C., Pascale G., Rotunno G., Solaini L., Pascale M. M., Notarnicola M., Corbellino M., Sacco M., Ubiali P., Cautiero R., Bocchetti T., Muzio E., Guglielmo V., Morandi E., Mao P., de Luca E., Ali F. M., Strupas K., Kondrotas P., Baltrunas R., Kutkevicius J., Ignatavicius P., Tan C. L., Siaw J. Y., Yam S. Y., Wilson L., Aziz M. R. A., Bondin J., Zorrilla C. D., Majbar A., Sale D., Abdullahi L., Osagie O., Faboya O., Fatuga A., Taiwo A., Nwabuoku E., Bliksoen M., Khan Z. A., Coronel J., Miranda C., Vasquez I., Helguero-Santin L. M., Rickard J., Adedeji A., Alqahtani S., Rath M., van Niekerk M., Koto M. Z., Matos-Puig R., Israelsson L., Schuetz T., Yuksek M. A., Mericliler M., Wolf B., Fairfield C., Yong G. L., Whitehurst K., Redgrave N., Musyoka C. K., Olivier J., Lee K., Cox M., Farhan-Alanie M. M. H., Callan R., Chibuye C., Ali T. H. A., Rekhis S., Rommaneh M., Sam Z. H., Pugliesi T. B., Pardo G., Harrison, E. M., Drake, T. M., Ghosh, D., Ademuyiwa, A. O., Bhangu, A., Fitzgerald, J. E., Glasbey, J., Borda-Luque, G., Costas-Chavarri, A., Ntirenganya, F., Fergusson, S. J., Ingabire, J. C. A., Ismail, L., Lilford, R., Mihaljevic, A. L., Morton, D., Mutabazi, A. Z., Adisa, A. O., Ots, R., Pinkney, T., Poskus, T., Shaw, C. A., Verjee, A., Runigamugabo, E., Khatri, C., Mohan, M., Jaffry, Z., Altamini, A., Kirby, A., Soreide, K., Cornick, J., Iyer, D., King, S., Arthur, T., Nahar, S. N., Waterman, A., Lawini, I., Rouse, T., Correa, J. C., Salem, H. K., Worku, M., Arnaud, A., Kalles, V., Aguilera, M. L., Recinos, G., Quek, R., Altibi, A., Whitaker, J., Bent, Z., Al-Slaibi, I., Tahboub, H., Alser, O. H., Shu, S., Mironescu, A., Bratu, M., Altwijri, A., Alsaggaf, M. U., Jubran, A. F., Seisay, S., Jeyakumar, J., Senanayake, K., Abdulbagi, O., Raptis, D., Kong, C., Suresh, S., Scott, M., Grizhja, B., Ymeri, S., Galiqi, G., Klappenbach, R., Antezana, D., Beleno, A. E. M., Costa, C., Sanchez, B., Aviles, S., Modolo, M. M., Fermani, C. G., Balmaceda, R., Villalobos, S., Carmona, J. M., Hamill, D., Deutschmann, P., Sandler, S., Cox, D., Nataraja, R., Sharpin, C., Ljuhar, D., Gray, D., Haines, M., Niranjan, N., D'Amours, S., Ashtari, M., Franco, H., Mitul, A. R., Karim, S., Aman, N. F., Estee, M. M., Salma, U., Razzaque, J., Hamidkanta, T., Tori, S., Alamin, Md. S., Roy, S., Al Amin, Md. S., Haque, M., Faruq, A., Iftekhar, F., O'Shea, M., Padmore, G., Jonnalagadda, R., Litvin, A., Filatau, A., Paulouski, D., Shubianok, M., Shachykava, T., Khokha, D., Khokha, V., Djivoh, F., Lawani, I., Dossou, F., Seto, D. M., Gbessi, D. G., Noukpozounkou, B., Souaibou, Y. I., Keke, K. R., Hodonou, F., Ahounou, E., Alihonou, T., Denakpo, M., Ahlonsou, G., Bedada, A. G., Nsengiyumva, C., Kwizera, S., Barendegere, V., Choi, P., Stock, S., Jamal, L., Firdouse, M., Zani, A., Azzie, G., Kushwaha, S., Agarwal, A., Chen, T. -L., Yip, C., Montes, I., Zapata, F., Sierra, S., Lanau, M. I. V., Arango, M. C. M., Restrepo, I. M., Giraldo, R. S. R., Mendozaarango, M., Domini, E., Karlo, R., Mihanovic, J., Youssef, M., Elfeki, H., Thabet, W., Sanad, A., Tawfik, G., Zaki, A., Abdel-Hameed, N., Mostafa, M., Omar, M. F. W., Ghanem, A., Abdallah, E., Denewer, A., Emara, E., Rashad, E., Sakr, A., Elashry, R., Emile, S., Khafagy, T., Elhamouly, S., Elfarargy, A., Mamdouhmohamed, A., Saiednagy, G., Esam, A., Elwy, E., Hammad, A., Khallaf, S., Ibrahim, E., Saidbadr, A., Moustafa, A., Eldosoukymohammed, A., Elgheriany, M., Abdelmageed, E., Al Raouf, E. A., Elbanby, E., Elmasry, M., Morsyfarahat, M., Yahyamansor, E., Magdyhegazy, E., Gamal, E., Gamal, H., Kandil, H., Maherabdelrouf, D., Moaty, M., Gamal, D., El-Sagheer, N., Salah, M., Magdy, S., Salah, A., Essam, A., Ali, A., Badawy, M., Ahmed, S., Mohamed, M., Assal, A., Sleem, M., Ebidy, M., Abdelrazek, A., Zahran, D., Adam, N., Nazir, M., Hassanein, A. B., Ismail, A., Elsawy, A., Mamdouh, R., Mabrouk, M., Ahmed, L. A. M., Hassabalnaby, M., Magdy, E., Abd-Elmawla, M., Fahim, M., Mowafy, B., Mahmoud, M. I., Allam, M., Alkelani, M., El Gendy, N. H., Aboul-Naga, M. S., Alaael-Din, R., Elgendy, A. H., Ismail, M., Shalaby, M., Elsharkawy, A. A., Moghazy, M. E., Elbisomy, K. H., Shakshouk, H. A. G., Hamed, M. F., Ebidy, M. M., Abdelkader, M., Karkeet, M., Ahmed, H., Adel, I., Omar, M. E., Ibrahim, M., Ghoneim, O., Hesham, O., Gamal, S., Hilal, K., Arafa, O., Awad, S. A., Salem, M., Elsherif, F. A., Elsabbagh, N., Aboelsoud, M. R., Rida, A. H. E. F., Hossameldin, A., Hany, E., Asar, Y. H., Anwar, N., Gadelkarim, M., Abdelhady, S., Morshedy, E. M., Saad, R., Soliman, N., Salama, M., Ezzat, E., Mohamed, A., Ibrahim, A., Fergany, A., Mohammed, S., Reda, A., Allam, Y., Saad, H. A., Abdelfatah, A., Fathy, A. M., El-Sehily, A., Kasem, E. A., Hassan, A. T. A., Mohammed, A. R., Saad, A. G., Elfouly, Y., Elfouly, N., Hassaan, A., Mohammed, M. M., Elhoseny, G., Magdy, M., Elkhalek, E. A., Zakaria, Y., Ezzat, T., El Dahab, A. A., Kelany, M., Arafa, S., Hassan, O. M. M., Badwi, N. M., Sleem, A. S., Abdelbadeai, K., Abdullah, M. A., Lokman, M., Bahar, S., Radyabdelazeam, A., Adelshone, A., Hasnan, M. B., Zulkifli, A., Kamarulzamil, S. N. A., Elhendawy, A., Latif, A., Adnan, A. B., Shaharuddin, S., Majid, A. H. H. A., Amreia, M., Al-Marakby, D., Salma, M., Basir, E. R. M., Ali, C. D. M., Ata, A. Y., Nasr, M., Rezq, A., Sheta, A., Tariq, S., Sallam, A., Darwish, A. K. Z., Elmihy, S., El Hadry, S., Farag, A., Hajah, H., Seliem, A., Aglan, A., Zohair, A., Essam, M., Moussa, O., El-Gizawy, E., Samy, M., Ali, S., Elhalawany, E., Ata, A., Elhalawany, M., Nashat, M., Soliman, S., Elazab, A., Abdelaziz, M. A., Ibrahim, K., Ibrahim, A. M., Gado, A., Hantour, U., Eldeen, E. A., Loaloa, M. R., Abouzaid, A., Ahmedbahaaeldin, M., Hashad, E., Sroor, F., Gamil, D., Mahmoudabdulhakeem, E., Zakaria, M., Mohamed, F., Abubakr, M., Ali, E., Magdy, H., Ramadan, M., Abdelatymohamed, M., Mansour, S., Abdulazizamin, H., Rabiemohamed, A., Saami, M., Ahmedredaelsayed, N., Tarek, A., Mohyeldeenmahmoud, S., El Sayed, I. M., Yusufshawky, M., Mousasalem, M., El-Din, S. A., Soliman, N. A., Talaat, M., Abdelmoenelhusseiny, S. A. -D. A., Abdullah, N., Elshaar, M., Abdelfatahibraheem, A., Abdulaziz, H., Ismail, M. K., Hamdymadkor, M., Abdelaty, M., Kader, S. M., Mohamedsalah, O., Eldafrawy, M., Zakieldeeb, A., Mahmoudeid, M., Attia, A., El-Dien, K. S., Shwky, A., Badenjki, M. A., Soliman, A., Al Attar, S. M., Sayed, F., Abdelsabour, F., Azizeldine, M. G., Shawqi, M., Hashim, A., Aamer, A., Raouf, A. M. A., Abdelshakour, M., Mahmoud, B., Mahmoud, M. A., Qenawy, M., Rashed, A. M., Dahy, A., Sayed, M., Shamsedine, A. W., Mohamed, B., Hasan, A., Saad, M. M., Abdulbassit, K., Khalidabdelatif, N., Elzahed, N., Elkashash, A., Bekhet, N. M., Hafez, S., Gad, A., Maher, M. E., Abdelsameea, A., Hafez, M., Sabe, A., Ahmed, A., Shahine, A., Dawood, K., Gaafar, S., Husseiny, R., Aboelmagd, O., Mesbah, N., Emadeldin, H., Almeligy, A., Bekhet, A. H., Hasan, D., Alhady, K., Sabe, A. K., Elnajjar, M. A., Aboelella, M., Hamsho, W., Hassan, I., Saad, H., Abdelazim, G., Mahmoud, H., Wael, N., Kandil, A. M., Magdy, A., Saidelkholy, S., Adel, B., Dabbour, K., Elsherbiney, S., Mattar, O., Abdrabou, A. K., Aly, M. Y. M., Geuoshy, A., Elnagar, A., Abdelmotaleb, I., Saleh, A. A., Mohammedbakry, H., Saeed, M., Mahmoud, S., Tawfik, B., Ismail, S. A., Zakaria, E., Gad, M. O., Elhelbawy, M., Bassem, M., Khaledabdel-Latif, N., Maraie, N., Elhadary, N. M., Semeda, N., Rabiemohamed, S., Bakry, H. M., Essam, A. A., Tarek, D., Ashour, K., Elhadad, A., Abdel-Aty, A., Rakha, I., Matter, S. M., Abdelhamed, R., Abdelkader, O., Soliman, Y., Ghanem, S., Farouk, S. A. M., Ibrahim, E. M., El-Taher, E., Mahrousbadr, M., El-Sawy, R. E. A., Bakr, A., Al Rafati, A. A. R., Saar, S., Reinsoo, A., Talving, P., Seyoum, N., Worku, T., Fitsum, A., Tolonen, M., Leppaniemi, A., Sallinen, V., Parmentier, B., Peycelon, M., Irtan, S., Dardenne, S., Robert, E., Maillot, B., Courboin, E., Arnaud, A. P., Hascoet, J., Abbo, O., Kaci, A. A., Prudhomme, T., Ballouhey, Q., Grosos, C., Fourcade, L., Cecilia, T., Jean-Francois, C., Helene, F. -C., Delforge, X., Haraux, E., Dousset, B., Schiavone, R., Gaujoux, S., Marret, J. -B., Haffreingue, A., Rod, J., Renaux-Petel, M., Lecompte, J. -F., Breaud, J., Gastaldi, P., Taieb, C., Claire, R., Anis, E., Bustangi, N., Lopez, M., Scalabre, A., Grella, M. G., Mariani, A., Podevin, G., Schmitt, F., Hervieux, E., Broch, A., Muller, C., Tabiri, S., Kojo, A. T. T., Bandoh, D., Abantanga, F., Kyereh, M., Asumah, H., Appiah, E. K., Wondoh, P., Gyedu, A., Dally, C., Amoah, K. A. M., Yifieyeh, A., Agbedinu, K., Owusu, F., Amoako-Boateng, M., Dayie, M., Hagan, R., Debrah, S., Ohene-Yeboah, M., Clegg-Lampety, J. -N., Etwire, V., Dakubo, J., Essoun, S., Bonney, W., Glover-Addy, H., Osei-Nketiah, S., Amoako, J., Adu-Aryee, N., Appeadu-Mensah, W., Bediako-Bowan, A., Dedey, F., Ekow, M., Akatibo, E., Yakubu, M., Kordorwu, H. E. K., Asare-Bediako, K., Tackie, E., Aaniana, K., Acquah, E., Opoku-Agyeman, R., Avoka, A., Kusi, K., Maison, K., Gyamfi, F. E., Naabarnabas, G., Abdul-Latif, S., Taahamoako, P., Davor, A., Dassah, V., Dagoe, E., Kwakyeafriyie, P., Akoto, E., Ackom, E., Mensah, E., Atkins, E. T., Coompson, C. L., Ivros, N., Ferousis, C., Agalianos, C., Kyriazanos, I., Barkolias, C., Tselos, A., Tzikos, G., Voulgaris, E., Lytras, D., Bamicha, A., Psarianos, K., Stefanopoulos, A., Patoulias, I., Sfougaris, D., Valioulis, I., Balalis, D., Korkolis, D., Manatakis, D. K., Kyrou, G., Karabelias, G., Papaskarlatos, I. -A., Konstantina, K., Zampitis, N., Germanos, S., Papailia, A., Theodosopoulos, T., Gkiokas, G., Mitroudi, M., Panteli, C., Feidantsis, T., Farmakis, K., Kyziridis, D., Ioannidis, O., Parpoudi, S., Gemenetzis, G., Parasyris, S., Anthoulakis, C., Nikoloudis, N., Margaritis, M., Aguilera-Arevalo, M. -L., Coyoy-Gaitan, O., Rosales, J., Tale, L., Soley, R., Barrios, E., Rodriguez, S. T. T., Pazgalvez, C., Herreracruz, D., Rosenberg, G. S., Matheu, A., Cohen, D. M., Paul, M., Charles, A., Lam, J. C. Y., Yeung, M. H. A., Fok, C. Y. J., Li, K. H. G., Lai, A. C. -H., Cheung, Y. H. E., Wong, H. Y., Leung, K. W., Lee, T. S. B., Lam, W. H., Dao, W., Kwok, S. H. -W., Chan, T. -Y. K., Ng, Y. K., Liu, Q., Foo, C. C., Yang, J., Kumar, B., Bhatnagar, A., Upadhyaya, V., Kumar, S., Muddebihal, U., Dar, W., Kc, J., Alexander, P., Aruldas, N., Adella, F. J., Rulie, A. S., Iskandar, F., Setiawan, J., Evajelista, C. V., Natalie, H., Arlindawati, Gunawan, R., Karismaningtyas, H., Mata, L., Andika, F., Hasanah, A., Widiastini, T. A., Purwaningsih, N., Mukin, A. D. F., Rahmah, D., Nurqistan, H., Arsyad, H., Adhitama, N., Jeo, W., Sutandi, N., Clarissa, A., Gultom, P. A., Billy, M., Haloho, A., Amandito, R., Johanna, N., Lee, F., Dorani, R. M. N. R., Glynn, M., Alherz, M., Goh, W., Shiwani, H. A., Sproule, L., Conlon, K. 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M., Salusso, P., Perino, M., Mochet, S., Sasia, D., Riente, F., Migliore, M., Merlini, D., Basilico, S., Corbellini, C., Lazzari, V., Macchitella, Y., Bonavina, L., Angelieri, D., Coletta, D., Falaschi, F., Catani, M., Reali, C., Malavenda, M., Del Basso, C., Ribaldi, S., Coletti, M., Natili, A., Depalma, N., Iannone, I., Antoniozzi, A., Rossi, D., Gui, D., Perrotta, G., Ripa, M., Giardino, F. R., Foco, M., Vicario, E., Coccolini, F., Ansaloni, L., Nita, G. E., Leone, N., Bondurri, A., Maffioli, A., Simioni, A., de Boni, D., Pasquali, S., Goldin, E., Vendramin, E., Ciccioli, E., Tedeschi, U., Bortolasi, L., Violi, P., Campagnaro, T., Conci, S., Lazzari, G., Iacono, C., Guglielmi, A., Manfreda, S., Rinaldi, A., Ringressi, M. N., Brunoni, B., Salamone, G., Mangiapane, M., de Marco, P., la Brocca, A., Tutino, R., Silvestri, V., Licari, L., Fontana, T., Cocorullo, N. F. 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Shachykava, Tatsiana, Khokha, Dziani, Khokha, Vladimir, Djivoh, Fernande, Lawani, Ismaïl, Dossou, Franci, Morel Seto, Djifid, Gaspard Gbessi, Dansou, Noukpozounkou, Bruno, Imorou Souaibou, Yacoubou, René Keke, Kpèmahouton, Hodonou, Fred, Ahounou, Ernestyemalinstephane, Alihonou, Thierry, Dénakpo, Max, Ahlonsou, Germain, Ginbo Bedada, Alemayehu, Nsengiyumva, Carlo, Kwizera, Sandrine, Barendegere, Venerand, Choi, Philip, Stock, Simon, Jamal, Luai, Azzie, George, Kushwaha, Sameer, Chen, Tzu-Ling, Yip, Chingwan, Montes, Irene, Zapata, Felipe, Sierra, Sebastian, Youssef, Mohamed, Elfeki, Hossam, Thabet, Waleed, Sanad, Aly, Tawfik, Gehad, Zaki, Ahmed, Abdel-Hameed, Noran, Mostafa, Mohamed, Abd Elkhalek, Esraa, Zakaria, Yehia, Ezzat, Tarek, Abo ElDahab, Ali, Kelany, Mohamed, Arafa, Sara, Mohamed Hassan, Osamamokhtar, Mohamed Badwi, Nermin, Saber Sleem, Ahmad, Ahmed, Hussien, Abdelbadeai, Kholoud, Abozed Abdullah, Mohamed, Lokman, Muhammadamsyarauni, Bahar, Suraya, Radyabdelazeam, Anan, Adelshone, Abdelrahman, Bin Hasnan, Muhammad, Zulkifli, Athirah, NurAlia Kamarulzamil, Siti, Elhendawy, Abdelaziz, Latif, Aliang, Bin Adnan, Ahmad, Shaharuddin, Shahadatul, HanumHaji AbdulMajid, Aminah, Amreia, Mahmoud, Al-Marakby, Dina, Salma, Mahmoud, Ismail, Mohamadjeffreybin, Rifhan MohdBasir, Elissa, Dewi MohdAli, Citra, Yehia Ata, Aya, Nasr, Maha, Rezq, Asmaa, Sheta, Ahmed, Tariq, Sherif, Sallam, Abdelkhalek, Kz Darwish, Abdelrhman, Elmihy, Sohaila, El Hadry, Shady, Farag, Ahmed, Hajah, Haidar, Seliem, Abdelaziz, Aglan, Amro, Zohair, Ahmed, Essam, Mahitab, Moussa, Omar, El-Gizawy, Esraa, Samy, Mostafa, Ali, Safia, Elhalawany, Esraa, Ata, Ahmed, Elhalawany, Mohamed, Nashat, Mohamed, Soliman, Samar, Elazab, Alaa, Samy, Mostada, A Abdelaziz, Mohamed, Ibrahim, Khaled, Mohamed Ibrahim, Ahmed, Gado, Ammar, Hantour, Usama, Alm Eldeen, Esraa, Reda Loaloa, Mohamed, Abouzaid, Arwa, Ahmedbahaaeldin, Mostafa, Hashad, Eman, Sroor, Fathy, Gamil, Doaa, Mahmoudabdulhakeem, Eman, Zakaria, 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Zanini, Nicola, Landolfo, Giovanni, Aljiffry, Murad, Idris, Faisal, Saleh AAlghamdi, Mohammed, Maghrabi, Ashraf, Altaf, Abdulmalik, Khalifah, Eyad, Albiety, Adel, Alkaaki, Aroub, Alshareef, Reham, Khoja, Ahmad, Nawawi, Abrar, Najjar, Mohammed, Turkustani, Sondo, Sahel, Sarah, Alzahrani, Ahmed, Alghamdi, Ahmed, Alhazmi, Wedyan, Al Saied, Ghiath, Alamoudi, Mohammed, Masood Riaz, Muhammed, Hassanain, Mazen, Alhassan, Basmah, Altamimi, Abdullah, Alyahya, Reem, Alsubaie, Norah, Albastawis, Fatema, Altamimi, Afnan, Nouh, Thamer, Khan, Roaa, Radojkovic, Milan, Jeremic, Ljiljana, Nestorovic, Milica, Hao Law, Jia, Say Kwang Tan, Keith, Kin Tan, Joel, WenLiang Joel, Lau, Wei Chan, Xue, QiHui Leong, Faith, Seng Chong, Choon, Koh, Sharon, Yin Lee, Kai, Chung Lee, Kuok, Pluke, Kent, Dedekind, Britta, Nashidengo, Puyearashid, Ian Hampton, Mark, Joosten, Johanna, Sobnach, Sanju, Roodt, Liana, Sander, Anthony, Pape, Jame, Maistry, Niveshni, Ndwambi, Phumudzo, Kinandu, Kamau, Tun, Myint, Du Toit, 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Chibuye, Chali, Hassanein Ahmed Ali, Tebian, Rekhis, Syrine, Rommaneh, Muna, Hao Sam, Zi, Lawani, Ismail, Brunelli Pugliesi, Thay, Pardo, Gabriel, Blanco, Ruth, and GlobalSurg Collaborative: Aneel Bhangu, Adesoji O Ademuyiwa, Maria Lorena Aguilera, Philip Alexander, Sara W Al-Saqqa, Giuliano Borda-Luque, Ainhoa Costas-Chavarri, Thomas M Drake, Faustin Ntirenganya, J Edward Fitzgerald, Stuart J Fergusson, James Glasbey, Jc Allen Ingabire, Lawani Ismaïl, Hosni Khairy Salem, Anyomih Theophilus Teddy Kojo, Marie Carmela Lapitan, Richard Lilford, Andre L Mihaljevic, Dion Morton, Alphonse Zeta Mutabazi, Dmitri Nepogodiev, Adewale O Adisa, Riinu Ots, Francesco Pata, Thomas Pinkney, Tomas Poškus, Ahmad Uzair Qureshi, Antonio Ramos-De la Medina, Sarah Rayne, Catherine A Shaw, Sebastian Shu, Richard Spence, Neil Smart, Stephen Tabiri, Ewen M Harrison, Chetan Khatri, Midhun Mohan, Zahra Jaffry, Afnan Altamini, Andrew Kirby, Kjetil Søreide, Gustavo Recinos, Jen Cornick, Maria Marta Modolo, Dushyant Iyer, Sebastian King, Tom Arthur, Sayeda Nazmum Nahar, Ade Waterman, Michael Walsh, Arnav Agarwal, Augusto Zani, Mohammed Firdouse, Tyler Rouse, Qinyang Liu, Juan Camilo Correa, Peep Talving, Mengistu Worku, Alexis Arnaud, Vassilis Kalles, Basant Kumar, Sunil Kumar, Radhian Amandito, Roy Quek, Luca Ansaloni, Ahmed Altibi, Donatas Venskutonis, Justas Zilinskas, Tomas Poskus, John Whitaker, Vanessa Msosa, Yong Yong Tew, Alexia Farrugia, Elaine Borg, Zineb Bentounsi, Tanzeela Gala, Ibrahim Al-Slaibi, Haya Tahboub, Osaid H Alser, Diego Romani, Sebestian Shu, Piotr Major, Aurel Mironescu, Matei Bratu, Amar Kourdouli, Aliyu Ndajiwo, Abdulaziz Altwijri, Mohammed Ubaid Alsaggaf, Ahmad Gudal, Al Faifi Jubran, Sam Seisay, Bettina Lieske, Irene Ortega, Jenifa Jeyakumar, Kithsiri J Senanayake, Omar Abdulbagi, Yucel Cengiz, Dmitri Raptis, Yuksel Altinel, Chia Kong, Ella Teasdale, Gareth Irwin, Michael Stoddart, Rakan Kabariti, Sukrit Suresh, Katherine Gash, Ragavan Narayanan, Mayaba 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Souaibou, Kpèmahouton René Keke, Fred Hodonou, Ernest Yemalin Stephane Ahounou, Thierry Alihonou, Max Dénakpo, Germain Ahlonsou, Alemayehu Ginbo Bedada, Carlos Nsengiyumva, Sandrine Kwizera, Venerand Barendegere, Philip Choi, Simon Stock, Luai Jamal, Georges Azzie, Sameer Kushwaha, Tzu-Ling Chen, Chingwan Yip, Irene Montes, Felipe Zapata, Sebastian Sierra, Maria Isabel Villegas Lanau, Maria Clara Mendoza Arango, Ivan Mendoza Restrepo, Ruben Santiago Restrepo Giraldo, Edgar Domini, Robert Karlo, Jakov Mihanovic, Mohamed Youssef, Hossam Elfeki, Waleed Thabet, Aly Sanad, Gehad Tawfik, Ahmed Zaki, Noran Abdel-Hameed, Mohamed Mostafa, Muhammad Fathi Waleed Omar, Ahmed Ghanem, Emad Abdallah, Adel Denewer, Eman Emara, Eman Rashad, Ahmad Sakr, Rehab Elashry, Sameh Emile, Toqa Khafagy, Sara Elhamouly, Arwa Elfarargy, Amna Mamdouh Mohamed, Ghada Saied Nagy, Abeer Esam, Eman Elwy, Aya Hammad, Salwa Khallaf, Eman Ibrahim, Ahmed Said Badr, Ahmed Moustafa, Amany Eldosouky Mohammed, Mohammed Elgheriany, Eman Abdelmageed, Eman Abd Al Raouf, Esraa Samir Elbanby, Maha Elmasry, Mahitab Morsy Farahat, Eman Yahya Mansor, Eman Magdy Hegazy, Esraa Gamal, Heba Gamal, Hend Kandil, Doaa Maher Abdelrouf, Mohamed Moaty, Dina Gamal, Nada El-Sagheer, Mohamed Salah, Salma Magdy, Asmaa Salah, Ahmed Essam, Ahmed Ali, Mahmoud Badawy, Sara Ahmed, Mazed Mohamed, Abdelrahman Assal, Mohamed Sleem, Mai Ebidy, Aly Abd-Elrazek, Diaaaldin Zahran, Nourhan Adam, Mohamed Nazir, Adel B Hassanein, Ahmed Ismail, Amira Elsawy, Rana Mamdouh, Mohamed Mabrouk, Lopna Ahmed Mohamed Ahmed, Mohamed Hassab Alnaby, Eman Magdy, Manar Abd-Elmawla, Marwan Fahim, Bassant Mowafy, Moustafa Ibrahim Mahmoud, Meran Allam, Muhammad Alkelani, Noran Halim El Gendy, Mariam Saad Aboul-Naga, Reham Alaa El-Din, Alyaa Halim Elgendy, Mohamed Ismail, Mahmoud Shalaby, Aya Adel Elsharkawy, Mahmoud Elsayed Moghazy, Khaled Hesham Elbisomy, Hend Abdel Gawad Shakshouk, Mohamed Fouad Hamed, Mai Mohamed Ebidy, Mostafa Abdelkader, Mohamed 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Kholoud Abdelbadeai, Mohamed Abozed Abdullah, Muhammad Amsyar Auni Lokman, Suraya Bahar, Anan Rady Abdelazeam, Abdelrahman Adelshone, Muhammad Bin Hasnan, Athirah Zulkifli, Siti Nur Alia Kamarulzamil, Abdelaziz Elhendawy, Aliang Latif, Ahmad Bin Adnan, Shahadatul Shaharuddin, Aminah Hanum Haji Abdul Majid, Mahmoud Amreia, Dina Al-Marakby, Mahmoud Salma, Mohamad Jeffrey Bin Ismail, Elissa Rifhan Mohd Basir, Citra Dewi Mohd Ali, Aya Yehia Ata, Maha Nasr, Asmaa Rezq, Ahmed Sheta, Sherif Tariq, Abd Elkhalek Sallam, Abdelrhman Kz Darwish, Sohaila Elmihy, Shady Elhadry, Ahmed Farag, Haidar Hajeh, Abdelaziz Abdelaal, Amro Aglan, Ahmed Zohair, Mahitab Essam, Omar Moussa, Esraa El-Gizawy, Mostafa Samy, Safia Ali, Esraa El Halawany, Ahmed Ata, Mohamed El Halawany, Mohamed Nashat, Samar Soliman, Alaa Elazab, Mostada Samy, Mohamed A Abdelaziz, Khaled Ibrahim, Ahmed Mohamed Ibrahim, Ammar Gado, Usama Hantour, Esraa Alm Eldeen, Mohamed Reda Loaloa, Arwa Abouzaid, Mostafa Ahmed Bahaa Eldin, Eman Hashad, Fathy Sroor, Doaa Gamil, Eman Mahmoud Abdulhakeem, Mahmoud Zakaria, Fawzy Mohamed, Marwan Abubakr, Elsayed Ali, Hesham Magdy, Menna Tallah Ramadan, Mohamed Abdelaty Mohamed, Salma Mansour, Hager Abdul Aziz Amin, Ahmed Rabie Mohamed, Mahmoud Saami, Nada Ahmed Reda Elsayed, Adham Tarek, Sabry Mohy Eldeen Mahmoud, Islam Magdy El Sayed, Amira Reda, Martina Yusuf Shawky, Mohammed Mousa Salem, Shahinaz Alaa El-Din, Noha Abdullah Soliman, Muhammed Talaat, Shahinaz Alaael-Dein, Ahmed Abd Elmoen Elhusseiny, Noha Abdullah, Mohammed Elshaar, Aya Abdelfatah Ibraheem, Hager Abdulaziz, Mohammed Kamal Ismail, Mona Hamdy Madkor, Mohamed Abdelaty, Sara Mahmoud Abdel-Kader, Osama Mohamed Salah, Mahmoud Eldafrawy, Ahmed Zaki Eldeeb, Mostafa Mahmoud Eid, Attia Attia, Khalid Salah El-Dien, Ayman Shwky, Mohamed Adel Badenjki, Abdelrahman Soliman, Samaa Mahmoud Al Attar, Farrag Sayed, Fahd Abdel Sabour, Mohammed G Azizeldine, Muhammad Shawqi, Abdullah Hashim, Ahmed Aamer, Ahmed Mahmoud Abdelraouf, Mahmoud Abdelshakour, Amal Ibrahim, Basma Mahmoud, Mohamed Ali Mahmoud, Mostafa Qenawy, Ahmed M Rashed, Ahmed Dahy, Marwa Sayed, Ahmed W Shamsedine, Bakeer Mohamed, Ahmad Hasan, Mahmoud M Saad, Khalil Abdul Bassit, Nadia Khalid Abd El-Latif, Nada Elzahed, Ahmed El Kashash, Nada Mohamed Bekhet, Sarah Hafez, Ahmed Gad, Mahmoud Elkhadragy Maher, Ahmed Abd El-Sameea, Mohamed Hafez, Ahmad Sabe, Ataa Ahmed, Ahmed Shahine, Khaled Dawood, Shireen Gaafar, Reem Husseiny, Omnia Aboelmagd, Ahmed Soliman, Nourhan Mesbah, Hossam Emadeldin, Amgad Al Meligy, Amira Hassan Bekhet, Doaa Hasan, Khaled Alhady, Ahmad Khaled Sabe, Mahmoud A Elnajjar, Majed Aboelella, Ward Hamsho, Ihab Hassan, Hala Saad, Galaleldin Abdelazim, Hend Mahmoud, Noha Wael, Ahmedali M Kandil, Ahmed Magdy, Shimaa Said Elkholy, Badr Eldin Adel, Kareem Dabbour, Saged Elsherbiney, Omar Mattar, Abdulshafi Khaled AbdRabou, Mohammed Yahia Mohamed Aly, Abdelrahman Geuoshy, Ahmedglal Elnagar, Saraibrahim Ahmed, Ibrahem Abdelmotaleb, Amr Ahmed Saleh, Hesham Mohammed Bakry, Manar Saeed, Shady Mahmoud, Badreldin Adel Tawfik, Samar Adel Ismail, Esraay Zakaria, Mariam O Gad, Mohamed Salah Elhelbawy, Monica Bassem, Noha Maraie, Nourhan Medhat Elhadary, Nourhan Semeda, Shaza Rabie Mohamed, Hesham Mohammed Bakry, A A Essam, Dina Tarek, Khlood Ashour, Alaa Elhadad, Abdulrahman Abdel-Aty, Ibrahim Rakha, Sara Mamdouh Matter, Rasha Abdelhamed, Omar Abdelkader, Ayat Hassaan, Yasmin Soliman, Amna Mohamed, Sara Ghanem, Sara Amr Mohamed Farouk, Eman Mohamed Ibrahim, Esraa El-Taher, Merna Mostafa, Mohamed Fawzy Mahrous Badr, Rofida Elsemelawy, Aya El-Sawy, Ahmad Bakr, Ahmad Abdel Razaq Al Rafati, Sten Saar, Arvo Reinsoo, Nebyou Seyoum, Tewodros Worku, Agazi Fitsum, Matti Tolonen, Ari Leppäniemi, Ville Sallinen, Benogreît Parmentier, Matthieu Peycelon, Sabine Irtan, Sabrina Dardenne, Elsa Robert, Betty Maillot, Etienne Courboin, Alexis Pierre Arnaud, Juliette Hascoet, Olivier Abbo, Amir Ait Kaci, Thomas Prudhomme, Quentin Ballouhey, Céline Grosos, Laurent Fourcade, Tolg Cecilia, Colombani Jean-Francois, Francois-Coridon Helene, Xavier Delforge, Elodie Haraux, Bertrand Dousset, Roberto Schiavone, Sebastien Gaujoux, Jean-Baptiste Marret, Aurore Haffreingue, Julien Rod, Mariette Renaux-Petel, Jean-François Lecompte, Jean Bréaud, Pauline Gastaldi, Chouikh Taieb, Raquillet Claire, Echaieb Anis, Nasir Bustangi, Manuel Lopez, Aurelien Scalabre, Maria Giovanna Grella, Aurora Mariani, Guillaume Podevin, Françoise Schmitt, Erik Hervieux, Aline Broch, Cecile Muller, Dickson Bandoh, Francis Abantanga, Martin Kyereh, Hamza Asumah, Eric Kofi Appiah, Paul Wondoh, Adam Gyedu, Charles Dally, Kwabena Agbedinu, Michael Amoah, Abiboye Yifieyeh, Kwabena Agbedinu, Frank Owusu, Mabel Amoako-Boateng, Makafui Dayie, Richmond Hagan, Sam Debrah, Micheal Ohene-Yeboah, Joe-Nat Clegg-Lampety, Victor Etwire, Jonathan Dakubo, Samuel Essoun, William Bonney, Hope Glover-Addy, Samuel Osei-Nketiah, Joachim Amoako, Niiarmah Adu-Aryee, William 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Antanas Zadoroznas, Nerijus Kaselis, Greta Žiubrytė, Finaritra Casimir Fleur Prudence Rahantasoa, Luc Hervé Samison, Fanjandrainy Rasoaherinomenjanahary, Todisoa Emmanuella Christina Tolotra, Cornelius Mukuzunga, Chimwemwe Kwatiwani, Nelson Msiska, Feng Yih Chai, Siti Mohd Desa Asilah, Khuzaimah Zahid Syibrah, Pui Xin Chin, Afizah Salleh, Nur Zulaika Riswan, April Camilla Roslani, Hoong-Yin Chong, Nora Abdul Aziz, Keat-Seong Poh, Chu-Ann Chai, Sandip Kumar, Mustafa Mohammed Taher, Nik Ritza Kosai, Dayang Nita Abdul Aziz, Reynu Rajan, Rokayah Julaihi, Durvesh Lacthman Jethwani, Muhammad Taqiyuddin Yahaya, Nik Azim Nik Abdullah, Susan Wndy Mathew, Kuet Jun Chung, Milaksh Kumar Nirumal, R Goh Ern Tze, Syed Abdul Wahhab Eusoffee Wan Ali, Yiing Yee Gan, Jesse Ron Swire Ting, Samuel S Y Sii, Kean Leong Koay, Yi Koon Tan, Alvin Ee Zhiun Cheah, Chui Yee Wong, Tuan Nur'Azmah Tuan Mat, Crystal Yern Nee Chow, Prisca Al Har, Yishan Der, Fitjerald Henry, Xinwei Low, Ya Theng Neo, Hian Ee Heng, Shu Ning Kong, Cheewei Gan, Yi Ting Mok, Yee Wen Tan, Kandasami Palayan, Mahadevan Deva Tata, Yih Jeng Cheong, Kuhaendran Gunaseelan, Wan Nurul 'Ain Wan Mohd Nasir, Pigeneswaren Yoganathan, Eu Xian Lee, Jian Er Saw, Li Jing Yeang, Pei Ying Koh, Shyang Yee Lim, Shuang Yi Teo, Nicole Grech, Daniela Magri, Kristina Cassar, Christine Mizzi, Malcolm Falzon, Nihaal Shaikh, Ruth Scicluna, Stefan Zammit, Sean Mizzi, Svetlana Doris Brincat, Thelma Tembo, Vu Thanh Hien Le, Tara Grima, Keith Sammut, Kurt Carabott, Ciskje Zarb, Andre Navarro, Thea Dimech, Georgette Marie Camilleri, Isaac Bertuello, Jeffrey Dalli, Karl Bonavia, Samantha Corro-Diaz, Marisol Manriquez-Reyes, Amina Abdelhamid, Abdelmalek Hrora, Sarah Benammi, Houda Bachri, Meryem Abbouch, Khaoula Boukhal, Redouane Mammar Bennai, Abdelkader Belkouchi, Mohamed Sobhi Jabal, Chaymae Benyaiche, Maarten Vermaas, Lucia Duinhouwer, Javier Pastora, Greta Wood, Maria Soledad Merlo, Akinlabi Ajao, Omobolaji Ayandipo, Taiwo Lawal, Abdussemiu Abdurrazzaaq, Muslimat Alada, Abdulrasheed Nasir, James Adeniran, Olufemi Habeeb, Ademola Popoola, Ademola Adeyeye, Ademola Adebanjo, Opeoluwa Adesanya, Adewale Adeniyi, Henry Mendel, Bashir Bello, Umar Muktar, Adedapo Osinowo, Thomas Olagboyega Olajide, Oyindamola Oshati, George Ihediwa, Babajide Adenekan, Victor Nwinee, Felix Alakaloko, Olumide Elebute, Abdulrazzaq Lawal, Chris Bode, Mojolaoluwa Olugbemi, Alaba Adesina, Olubukola Faturoti, Oluwatomi Odutola, Oluwaseyi Adebola, Clement Onuoha, Ogechukwu Taiwo, Omolara Williams, Fatai Balogun, Olalekan Ajai, Mobolaji Oludara, Iloba Njokanma, Roland Osuoji, Stephen Kache, Jonathan Ajah, Jerry Makama, Ahmed Adamu, Suleiman Baba, Mohammad Aliyu, Shamsudeen Aliyu, Yahaya Ukwenya, Halima Aliyu, Tunde Sholadoye, Muhammad Daniyan, Oluseyi Ogunsua, Lofty-John Anyanwu, Abdurrahaman Sheshe, Aminu Mohammad, Samson Olori, Philip Mshelbwala, Babatunde Odeyemi, Garba Samson, Oyediran Kehinde Timothy, Sani Ali Samuel, Anthony Ajiboye, Isaac Amole, Olajide Abiola, Akin Olaolorun, Torhild Veen, Arezo Kanani, Kristian Styles, Ragnar Herikstad, Johannes Wiik Larsen, Jon Arne Søreide, Elisabeth Jensen, Mads Gran, Eirik Kjus Aahlin, Tina Gaarder, Peter Wiel Monrad-Hansen, Pål Aksel Næss, Giedrius Lauzikas, Joachim Wiborg, Silje Holte, Knut Magne Augestad, Gurpreet Singh Banipal, Michela Monteleone, Thomas Tetens Moe, Johannes Kurt Schultz, Najwa Nadeem, Muhammad Saqlain, Jibran Abbasy, Abdul Rehman Alvi, Noman Shahzad, Kamran Faisal Bhopal, Zainab Iftikhar, Muhammad Talha Butt, Syed Asaat Ul Razi, Asdaq Ahmed, Ali Khan Niazi, Ibrahim Raza, Fatima Baluch, Ahmed Raza, Ahmad Bani-Sadar, Muhammad Adil, Awais Raza, Mahnoor Javaid, Muhammad Waqar, Maryam Ali Khan, Mohammad Mohsin Arshad, Mohammad Asim Amjad, Taher Al-Taher, Ayah Hamdan, Ayman Salman, Rana Saadeh, Aseel Musleh, Dana Jaradat, Soha Abushamleh, Sakhaa Hanoun, Amjad Abu Qumbos, Aseel Hamarshi, Ayman And Taher, Israa Qawasmi, Khalid Qurie, Marwa Altarayra, Mohammad Ghannam, Alaa 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William English, Catrin Morgan, Dominic Townsend, Laura Maciejec, Shareef Mahdi, Onyinye Akpenyi, Elisabeth Hall, Hanaan Caydiid, Zakaria Rob, Tom Abbott, Hew D Torrance, Robin Johnston, Mohammed Aki Gani, Gianpiero Gravante, Shivanchan Rajmohan, Kiran Majid, Shiva Dindyal, Christopher Smith, Madanmohan Palliyil, Sanjay Patel, Luke Nicholson, Neil Harvey, Katie Baillie, Sam Shillito, Suzanne Kershaw, Rebecca Bamford, Peter Orton, Elke Reunis, Robert Tyler, Wai Cheong Soon, Guled M Jama, Dharminder Dhillon, Khyati Patel, Shayanthan Nanthakumaran, Rachel Heard, Kar Yan Chen, Behrad Barmayehvar, Uttaran Datta, Sivesh K Kamarajah, Sharad Karandikar, Sobhana Iftekhar Tani, Eimear Monaghan, Philippa Donnelly, Michael Walker, Jehangirshaw Parakh, Sarah Blacker, Anil Kaul, Arjun Paramasivan, Sameh Farag, Ashrafun Nessa, Salwa Awadallah, Jieqi Lim, James Chean Khun Ng, Ravi P Kiran, Alice Murray, Eric Etchill, Mohini Dasari, Juan Puyana, Nadeem Haddad, Martin Zielinski, Asad Choudhry, Celeste Caliman, Mieshia Beamon, Therese Duane, Mamta Swaroop, Jonathan Myers, Rebecca Deal, Erik Schadde, Mark Hemmila, Lena Napolitano, Kathleen To, Alex Makupe, Joseph Musowoya, Niels van der Naald, Dayson Kumwenda, Alex Reece-Smith, Kars Otten, Anna Verbeek, Marloes Prins, Alibeth Andres Baquero Suarez, Ruben Balmaceda, Chelsea Deane, Emilio Dijan, Mahmoud Elfiky, Laura Koskenvuo, Aurore Thollot, Bernard Limoges, Carmen Capito, Challine Alexandre, Henri Kotobi, Julien Leroux, Kalitha Pinnagoda, Nicolas Henric, Olivier Azzis, Olivier Rosello, Poddevin Francois, Sara Etienne, Philippe Buisson, Sophian Hmila, Joe-Nat Clegg-Lamptey, Osman Imoro, Owusu Emmanuel Abem, Dimitrios Papageorgiou, Vasiliki Soulou, Sabrina Asturias, Lenin Peña, Donal B O'Connor, Alberto Realis Luc, Alfio Alessandro Russo, Andrea Ruzzenente, Antonio Taddei, Camilla Cona, Corrado Bottini, Giovanni Pascale, Giuseppe Rotunno, Leonardo Solaini, Marco Maria Pascale, Margherita Notarnicola, Mario Corbellino, Michele Sacco, Paolo Ubiali, Roberto Cautiero, Tommaso Bocchetti, Elena Muzio, Vania Guglielmo, Eugenio Morandi, Patrizio Mao, Emilia de Luca, Farah Mahmoud Ali, Justas Žilinskas, Kestutis Strupas, Paulius Kondrotas, Robertas Baltrunas, Juozas Kutkevicius, Povilas Ignatavicius, Choy Ling Tan, Jia Yng Siaw, Sir Young Yam, Ling Wilson, Mohamed Rezal Abdul Aziz, John Bondin, Carmina Diaz Zorrilla, Anass Majbar, Danjuma Sale, Lawal Abdullahi, Olabisi Osagie, Omolara Faboya, Adedeji Fatuga, Agboola Taiwo, Emeka Nwabuoku, Marte Bliksøen, Zain Ali Khan, Jazmin Coronel, Cesar Miranda, Idelso Vasquez, Luis M Helguero-Santin, Jennifer Rickard, Adesina Adedeji, Saleh Alqahtani, Max Rath, Michael Van Niekerk, Modise Zacharia Koto, Roel Matos-Puig, Leif Israelsson, Tobias Schuetz, Mahmut Arif Yuksek, Meric Mericliler, Mehmet Ulusahin, Bernhard Wolf, Cameron Fairfield, Guo Liang Yong, Katharine Whitehurst, Natalie Redgrave, Caroluce K Musyoka, James Olivier, Kathryn Lee, Michael Cox, Muhamed M H Farhan-Alanie, Rory Callan, Chali Chibuye, Tebian Hassanein Ahmed Ali, Syrine Rekhis, Muna Rommaneh, Zi Hao Sam, Thays Brunelli Pugliesi, Gabriel Pardo, Ruth Blanco

Subjects
Male, paediatric, Cohort Studies, 0302 clinical medicine, Primary outcome, gastro-enterologic surgery, Risk Factors, Prospective Studies, 030212 general & internal medicine, paediatrics, Prospective cohort study, Child, Digestive System Surgical Procedures, Original Research, lcsh:R5-920, Paediatric surgery, Health Policy, Human development (humanity), 3142 Public health care science, environmental and occupational health, 3. Good health, CONGENITAL-ANOMALIES, 030220 oncology & carcinogenesis, Child, Preschool, surgical infection, Female, lcsh:Medicine (General), Surgical site infection, Cohort study, Human, AFRICA, medicine.medical_specialty, CARE-ASSOCIATED INFECTION, Adolescent, lcsh:Infectious and parasitic diseases, NO, 03 medical and health sciences, MIDDLE-INCOME COUNTRIES, medicine, Humans, Surgical Wound Infection, lcsh:RC109-216, In patient, Human Development Index, business.industry, Kirurgi, Risk Factor, Public Health, Environmental and Occupational Health, Infant, Newborn, Infant, Digestive System Surgical Procedure, GLOBAL BURDEN, 3126 Surgery, anesthesiology, intensive care, radiology, Surgery, Prospective Studie, Cohort Studie, business
Abstract

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p

Published
2020

45. Consistent improvement with eculizumab across muscle groups in myasthenia gravis

Author

Mantegazza, R., O'Brien, F. L., Yountz, M., Howard, J. F., Gabriel Mazia, C., Wilken, M., Barroso, F., Saba, J., Rugiero, M., Bettini, M., Chaves, M., Vidal, G., Dalila Garcia, A., De Bleecker, J., Van den Abeele, G., de Koning, K., De Mey, K., Mercelis, R., Mahieu, D., Wagemaekers, L., Van Damme, P., Depreitere, A., Schotte, C., Smetcoren, C., Stevens, O., Van Daele, S., Vandenbussche, N., Vanhee, A., Verjans, S., Vynckier, J., D'Hont, A., Tilkin, P., Alves de Siqueira Carvalho, A., Dias Brockhausen, I., Feder, D., Ambrosio, D., Cesar, P., Paula Melo, A., Martins Ribeiro, R., Rocha, R., Bezerra Rosa, B., Veiga, T., Augusto da Silva, L., Santos Engel, M., Goncalves Geraldo, J., da Penha Ananias Morita, M., Nogueira Coelho, E., Paiva, G., Pozo, M., Prando, N., Torres, D. D. M., Fernanda Butinhao, C., Duran, G., Augusto Suriane Fialho, T., Gomes da Silva, T. C., Goncalves, L. O. M., Eduardo Pazetto, L., Renata Cubas Volpe, L., Souza Duca, L., Friedrich, M. A. G., Guerreiro, A., Mohr, H., Pereira Martins, M., da Cruz Pacheco, D., Ferreira, L., Paula Macagnan, A., Pinto, G., de Cassia Santos, A., Souza Bulle Oliveira, A., Amaral de Andrade, A. C., Annes, M., Duarte Silva, L., Cavalcante Lino, V., Pinto, W., Assis, N., Carrara, F., Miranda, C., Souza, I., Fernandes, P., Siddiqi, Z., Phan, C., Narayan, J., Blackmore, D., Mallon, A., Roderus, R., Watt, E., Vohanka, S., Bednarik, J., Chmelikova, M., Cierny, M., Toncrova, S., Junkerova, J., Kurkova, B., Reguliova, K., Zapletalova, O., Pitha, J., Novakova, I., Tyblova, M., Jurajdova, I., Wolfova, M., Andersen, H., Harbo, T., Vinge, L., Krogh, S., Mogensen, A., Vissing, J., Hojgaard, J., Witting, N., Mette Ostergaard Autzen, A., Pedersen, J., Eralinna, J. -P., Laaksonen, M., Oksaranta, O., Harrison, T., Eriksson, J., Rozsa, C., Horvath, M., Lovas, G., Matolcsi, J., Szabo, G., Jakab, G., Szabadosne, B., Vecsei, L., Dezsi, L., Varga, E., Konyane, M., Antonini, G., Di Pasquale, A., Garibaldi, M., Morino, S., Troili, F., Fionda, L., Pasquale, A., Evoli, A., Emilio Alboini, P., D'Amato, V., Iorio, R., Inghilleri, M., Frasca, V., Giacomelli, E., Gori, M., Lopergolo, D., Onesti, E., Gabriele, M., Sacca, F., Filla, A., Costabile, T., Marano, E., Fasanaro, A., Marsili, A., Puorro, G., Antozzi, C., Bonanno, S., Camera, G., Locatelli, A., Maggi, L., Pasanisi, M., Campanella, A., Uzawa, A., Kanai, T., Kawaguchi, N., Mori, M., Kaneko, Y., Kanzaki, A., Kobayashi, E., Murai, H., Masaki, K., Matsuse, D., Matsushita, T., Uehara, T., Shimpo, M., Jingu, M., Kikutake, K., Nakamura, Y., Sano, Y., Utsugisawa, K., Nagane, Y., Kamegamori, I., Tsuda, T., Fujii, Y., Futono, K., Ozawa, Y., Mizugami, A., Saito, Y., Samukawa, M., Suzuki, H., Morikawa, M., Kamakura, S., Miyawaki, E., Okumura, M., Funaka, S., Kawamura, T., Nakamori, M., Takahashi, M., Taichi, N., Hasuike, T., Higuchi, E., Kobayashi, H., Osakada, K., Shiraishi, H., Miyazaki, T., Motomura, M., Mukaino, A., Yoshimura, S., Asada, S., Yoshida, S., Amamoto, S., Kobashikawa, T., Koga, M., Maeda, Y., Takada, K., Takada, M., Tsurumaru, M., Yamashita, Y., Suzuki, Y., Akiyama, T., Narikawa, K., Tano, O., Tsukita, K., Kurihara, R., Meguro, F., Fukuda, Y., Sato, M., Imai, T., Tsuda, E., Shimohama, S., Hayashi, T., Hisahara, S., Kawamata, J., Murahara, T., Saitoh, M., Suzuki, S., Yamamoto, D., Ishiyama, Y., Ishiyama, N., Noshiro, M., Takeyama, R., Uwasa, K., Yasuda, I., van der Kooi, A., de Visser, M., Gibson, T., Kim, B. -J., Nyoung Lee, C., Seo Koo, Y., Youl Seok, H., Nam Kang, H., Ra, H., Joon Kim, B., Bin Cho, E., Choi, M., Lee, H., Min, J. -H., Seok, J., Lee, J., Koh, D. Y., Kwon, J., Park, S., Haw Choi, E., Hong, Y. -H., Ahn, S. -H., Lim Koo, D., Lim, J. -S., Won Shin, C., Ye Hwang, J., Kim, M., Min Kim, S., Jeong, H. -N., Jung, J., Kim, Y. -H., Seok Lee, H., Young Shin, H., Bi Hwang, E., Shin, M., Casasnovas, C., Antonia Alberti Aguilo, M., Homedes-Pedret, C., Julia Palacios, N., Diez Porras, L., Velez Santamaria, V., Lazaro, A., Gamez Carbonell, J., Sune, P., Salvado Figueras, M., Gili, G., Mazuela, G., Illa, I., Cortes Vicente, E., Diaz-Manera, J., Antonio Querol Gutierrez, L., Rojas Garcia, R., Vidal, N., Arribas-Ibar, E., Diez Tejedor, E., Gomez Salcedo, P., Fernandez-Fournier, M., Lopez Ruiz, P., Rodriguez de Rivera, F. J., Sastre, M., Piehl, F., Hietala, A., Bjarbo, L., Sengun, I., Meherremova, A., Ozcelik, P., Balkan, B., Tuga, C., Ugur, M., Erdem-Ozdamar, S., Bekircan-Kurt, C., Pinar Acar, N., Yilmaz, E., Caliskan, Y., Orsel, G., Efendi, H., Aydinlik, S., Cavus, H., Kutlu, A., Becerikli, G., Semiz, C., Tun, O., Terzi, M., Dogan, B., Kazim Onar, M., Sen, S., Kirbas Cavdar, T., Veske, A., Norwood, F., Dimitriou, A., Gollogly, J., Mahdi-Rogers, M., Seddigh, A., Sokratous, G., Maier, G., Sohail, F., Jacob, S., Sadalage, G., Torane, P., Brown, C., Shah, A., Sathasivam, S., Arndt, H., Davies, D., Watling, D., Amato, A., Cochrane, T., Salajegheh, M., Roe, K., Amato, K., Toska, S., Wolfe, G., Silvestri, N., Patrick, K., Zakalik, K., Katz, J., Miller, R., Engel, M., Forshew, D., Bravver, E., Brooks, B., Sanjak, M., Plevka, S., Burdette, M., Cunningham, S., Kramer, M., Nemeth, J., Schommer, C., Scott, T., Juel, V., Guptill, J., Hobson-Webb, L., Massey, J., Beck, K., Carnes, D., Loor, J., Anderson, A., Pascuzzi, R., Bodkin, C., Kincaid, J., Snook, R., Guingrich, S., Micheels, A., Chaudhry, V., Corse, A., Mosmiller, B., Kelley, A., Ho, D., Srinivasan, J., Vytopil, M., Jara, J., Ventura, N., Carter, C., Donahue, C., Herbert, C., Scala, S., Weiner, E., Alam, S., Mckinnon, J., Haar, L., Mckinnon, N., Alcon, K., Mckenna, K., Sattar, N., Daniels, K., Jeffery, D., Freimer, M., Chad Hoyle, J., Kissel, J., Agriesti, J., Chelnick, S., Mezache, L., Pineda, C., Muharrem, F., Karam, C., Khoury, J., Marburger, T., Kaur, H., Dimitrova, D., Gilchrist, J., Agrawal, B., Elsayed, M., Kohlrus, S., Ardoin, A., Darnell, T., Golden, L., Lokaitis, B., Seelbach, J., Muppidi, S., Goyal, N., Sakamuri, S., Y. T., So, Paulose, S., Pol, S., Welsh, L., Bhavaraju-Sanka, R., Tobon Gonzalez, A., Dishman, L., Jones, F., Gonzalez, A., Padilla, P., Saklad, A., Silva, M., Nations, S., Trivedi, J., Hopkins, S., Kazamel, M., Alsharabati, M., Lu, L., Nozaki, K., Mumfrey-Thomas, S., Woodall, A., Mozaffar, T., Cash, T., Roy, G., Mathew, V., Maqsood, F., Minton, B., James Jones, H., Rosenfeld, J., Garcia, R., Echevarria, L., Garcia, S., Pulley, M., Aranke, S., Ross Berger, A., Shah, J., Shabbir, Y., Smith, L., Varghese, M., Gutmann, L., Jerath, N., Nance, C., Swenson, A., Olalde, H., Kressin, N., Sieren, J., Barohn, R., Dimachkie, M., Glenn, M., Mcvey, A., Pasnoor, M., Statland, J., Wang, Y., Liu, T., Emmons, K., Jenci, N., Locheke, J., Fondaw, A., Johns, K., Rico, G., Walsh, M., Herbelin, L., Hafer-Macko, C., Kwan, J., Zilliox, L., Callison, K., Young, V., Disanzo, B., Naunton, K., Benatar, M., Bilsker, M., Sharma, K., Cooley, A., Reyes, E., Michon, S. -C., Sheldon, D., Steele, J., Traub, R., Chopra, M., Vu, T., Katzin, L., Mcclain, T., Harvey, B., Hart, A., Huynh, K., Beydoun, S., Chilingaryan, A., Doan, V., Droker, B., Gong, H., Karimi, S., Lin, F., Polaka, K., Tran, A., Akhter, S., Malekniazi, A., Tandan, R., Hehir, M., Waheed, W., Lucy, S., Weiss, M., Distad, J., Strom, S., Downing, S., Kim, B., Bertorini, T., Arnold, T., Henderson, K., Pillai, R., Liu, Y., Wheeler, L., Hewlett, J., Vanderhook, M., Nowak, R., Dicapua, D., Keung, B., Kumar, A., Patwa, H., Robeson, K., Yang, I., Nye, J., Vu, H., Mantegazza, R., O'Brien, F. L., Yountz, M., Howard, J. F., Gabriel Mazia, C., Wilken, M., Barroso, F., Saba, J., Rugiero, M., Bettini, M., Chaves, M., Vidal, G., Dalila Garcia, A., De Bleecker, J., Van den Abeele, G., de Koning, K., De Mey, K., Mercelis, R., Mahieu, D., Wagemaekers, L., Van Damme, P., Depreitere, A., Schotte, C., Smetcoren, C., Stevens, O., Van Daele, S., Vandenbussche, N., Vanhee, A., Verjans, S., Vynckier, J., D'Hont, A., Tilkin, P., Alves de Siqueira Carvalho, A., Dias Brockhausen, I., Feder, D., Ambrosio, D., Cesar, P., Paula Melo, A., Martins Ribeiro, R., Rocha, R., Bezerra Rosa, B., Veiga, T., Augusto da Silva, L., Santos Engel, M., Goncalves Geraldo, J., da Penha Ananias Morita, M., Nogueira Coelho, E., Paiva, G., Pozo, M., Prando, N., Torres, D. D. M., Fernanda Butinhao, C., Duran, G., Augusto Suriane Fialho, T., Gomes da Silva, T. C., Goncalves, L. O. M., Eduardo Pazetto, L., Renata Cubas Volpe, L., Souza Duca, L., Friedrich, M. A. G., Guerreiro, A., Mohr, H., Pereira Martins, M., da Cruz Pacheco, D., Ferreira, L., Paula Macagnan, A., Pinto, G., de Cassia Santos, A., Souza Bulle Oliveira, A., Amaral de Andrade, A. C., Annes, M., Duarte Silva, L., Cavalcante Lino, V., Pinto, W., Assis, N., Carrara, F., Miranda, C., Souza, I., Fernandes, P., Siddiqi, Z., Phan, C., Narayan, J., Blackmore, D., Mallon, A., Roderus, R., Watt, E., Vohanka, S., Bednarik, J., Chmelikova, M., Cierny, M., Toncrova, S., Junkerova, J., Kurkova, B., Reguliova, K., Zapletalova, O., Pitha, J., Novakova, I., Tyblova, M., Jurajdova, I., Wolfova, M., Andersen, H., Harbo, T., Vinge, L., Krogh, S., Mogensen, A., Vissing, J., Hojgaard, J., Witting, N., Mette Ostergaard Autzen, A., Pedersen, J., Eralinna, J. -P., Laaksonen, M., Oksaranta, O., Harrison, T., Eriksson, J., Rozsa, C., Horvath, M., Lovas, G., Matolcsi, J., Szabo, G., Jakab, G., Szabadosne, B., Vecsei, L., Dezsi, L., Varga, E., Konyane, M., Antonini, G., Di Pasquale, A., Garibaldi, M., Morino, S., Troili, F., Fionda, L., Pasquale, A., Evoli, A., Emilio Alboini, P., D'Amato, V., Iorio, R., Inghilleri, M., Frasca, V., Giacomelli, E., Gori, M., Lopergolo, D., Onesti, E., Gabriele, M., Saccà, Francesco, Filla, Alessandro, Costabile, T., Marano, E., Fasanaro, A., Marsili, Angela, Puorro, Giorgia, Antozzi, C., Bonanno, S., Camera, G., Locatelli, A., Maggi, L., Pasanisi, M., Campanella, A., Uzawa, A., Kanai, T., Kawaguchi, N., Mori, M., Kaneko, Y., Kanzaki, A., Kobayashi, E., Murai, H., Masaki, K., Matsuse, D., Matsushita, T., Uehara, T., Shimpo, M., Jingu, M., Kikutake, K., Nakamura, Y., Sano, Y., Utsugisawa, K., Nagane, Y., Kamegamori, I., Tsuda, T., Fujii, Y., Futono, K., Ozawa, Y., Mizugami, A., Saito, Y., Samukawa, M., Suzuki, H., Morikawa, M., Kamakura, S., Miyawaki, E., Okumura, M., Funaka, S., Kawamura, T., Nakamori, M., Takahashi, M., Taichi, N., Hasuike, T., Higuchi, E., Kobayashi, H., Osakada, K., Shiraishi, H., Miyazaki, T., Motomura, M., Mukaino, A., Yoshimura, S., Asada, S., Yoshida, S., Amamoto, S., Kobashikawa, T., Koga, M., Maeda, Y., Takada, K., Takada, M., Tsurumaru, M., Yamashita, Y., Suzuki, Y., Akiyama, T., Narikawa, K., Tano, O., Tsukita, K., Kurihara, R., Meguro, F., Fukuda, Y., Sato, M., Imai, T., Tsuda, E., Shimohama, S., Hayashi, T., Hisahara, S., Kawamata, J., Murahara, T., Saitoh, M., Suzuki, S., Yamamoto, D., Ishiyama, Y., Ishiyama, N., Noshiro, M., Takeyama, R., Uwasa, K., Yasuda, I., van der Kooi, A., de Visser, M., Gibson, T., Kim, B. -J., Nyoung Lee, C., Seo Koo, Y., Youl Seok, H., Nam Kang, H., Ra, H., Joon Kim, B., Bin Cho, E., Choi, M., Lee, H., Min, J. -H., Seok, J., Lee, J., Koh, D. Y., Kwon, J., Park, S., Haw Choi, E., Hong, Y. -H., Ahn, S. -H., Lim Koo, D., Lim, J. -S., Won Shin, C., Ye Hwang, J., Kim, M., Min Kim, S., Jeong, H. -N., Jung, J., Kim, Y. -H., Seok Lee, H., Young Shin, H., Bi Hwang, E., Shin, M., Casasnovas, C., Antonia Alberti Aguilo, M., Homedes-Pedret, C., Julia Palacios, N., Diez Porras, L., Velez Santamaria, V., Lazaro, A., Gamez Carbonell, J., Sune, P., Salvado Figueras, M., Gili, G., Mazuela, G., Illa, I., Cortes Vicente, E., Diaz-Manera, J., Antonio Querol Gutierrez, L., Rojas Garcia, R., Vidal, N., Arribas-Ibar, E., Diez Tejedor, E., Gomez Salcedo, P., Fernandez-Fournier, M., Lopez Ruiz, P., Rodriguez de Rivera, F. J., Sastre, M., Piehl, F., Hietala, A., Bjarbo, L., Sengun, I., Meherremova, A., Ozcelik, P., Balkan, B., Tuga, C., Ugur, M., Erdem-Ozdamar, S., Bekircan-Kurt, C., Pinar Acar, N., Yilmaz, E., Caliskan, Y., Orsel, G., Efendi, H., Aydinlik, S., Cavus, H., Kutlu, A., Becerikli, G., Semiz, C., Tun, O., Terzi, M., Dogan, B., Kazim Onar, M., Sen, S., Kirbas Cavdar, T., Veske, A., Norwood, F., Dimitriou, A., Gollogly, J., Mahdi-Rogers, M., Seddigh, A., Sokratous, G., Maier, G., Sohail, F., Jacob, S., Sadalage, G., Torane, P., Brown, C., Shah, A., Sathasivam, S., Arndt, H., Davies, D., Watling, D., Amato, A., Cochrane, T., Salajegheh, M., Roe, K., Amato, K., Toska, S., Wolfe, G., Silvestri, N., Patrick, K., Zakalik, K., Katz, J., Miller, R., Engel, M., Forshew, D., Bravver, E., Brooks, B., Sanjak, M., Plevka, S., Burdette, M., Cunningham, S., Kramer, M., Nemeth, J., Schommer, C., Scott, T., Juel, V., Guptill, J., Hobson-Webb, L., Massey, J., Beck, K., Carnes, D., Loor, J., Anderson, A., Pascuzzi, R., Bodkin, C., Kincaid, J., Snook, R., Guingrich, S., Micheels, A., Chaudhry, V., Corse, A., Mosmiller, B., Kelley, A., Ho, D., Srinivasan, J., Vytopil, M., Jara, J., Ventura, N., Carter, C., Donahue, C., Herbert, C., Scala, S., Weiner, E., Alam, S., Mckinnon, J., Haar, L., Mckinnon, N., Alcon, K., Mckenna, K., Sattar, N., Daniels, K., Jeffery, D., Freimer, M., Chad Hoyle, J., Kissel, J., Agriesti, J., Chelnick, S., Mezache, L., Pineda, C., Muharrem, F., Karam, C., Khoury, J., Marburger, T., Kaur, H., Dimitrova, D., Gilchrist, J., Agrawal, B., Elsayed, M., Kohlrus, S., Ardoin, A., Darnell, T., Golden, L., Lokaitis, B., Seelbach, J., Muppidi, S., Goyal, N., Sakamuri, S., So, Y. T., Paulose, S., Pol, S., Welsh, L., Bhavaraju-Sanka, R., Tobon Gonzalez, A., Dishman, L., Jones, F., Gonzalez, A., Padilla, P., Saklad, A., Silva, M., Nations, S., Trivedi, J., Hopkins, S., Kazamel, M., Alsharabati, M., Lu, L., Nozaki, K., Mumfrey-Thomas, S., Woodall, A., Mozaffar, T., Cash, T., Roy, G., Mathew, V., Maqsood, F., Minton, B., James Jones, H., Rosenfeld, J., Garcia, R., Echevarria, L., Garcia, S., Pulley, M., Aranke, S., Ross Berger, A., Shah, J., Shabbir, Y., Smith, L., Varghese, M., Gutmann, L., Jerath, N., Nance, C., Swenson, A., Olalde, H., Kressin, N., Sieren, J., Barohn, R., Dimachkie, M., Glenn, M., Mcvey, A., Pasnoor, M., Statland, J., Wang, Y., Liu, T., Emmons, K., Jenci, N., Locheke, J., Fondaw, A., Johns, K., Rico, G., Walsh, M., Herbelin, L., Hafer-Macko, C., Kwan, J., Zilliox, L., Callison, K., Young, V., Disanzo, B., Naunton, K., Benatar, M., Bilsker, M., Sharma, K., Cooley, A., Reyes, E., Michon, S. -C., Sheldon, D., Steele, J., Traub, R., Chopra, M., Vu, T., Katzin, L., Mcclain, T., Harvey, B., Hart, A., Huynh, K., Beydoun, S., Chilingaryan, A., Doan, V., Droker, B., Gong, H., Karimi, S., Lin, F., Polaka, K., Tran, A., Akhter, S., Malekniazi, A., Tandan, R., Hehir, M., Waheed, W., Lucy, S., Weiss, M., Distad, J., Strom, S., Downing, S., Kim, B., Bertorini, T., Arnold, T., Henderson, K., Pillai, R., Liu, Y., Wheeler, L., Hewlett, J., Vanderhook, M., Nowak, R., Dicapua, D., Keung, B., Kumar, A., Patwa, H., Robeson, K., Yang, I., Nye, J., Vu, H., Neurology, and Amsterdam Neuroscience - Neuroinfection & -inflammation

Subjects
0301 basic medicine, Malalties neuromusculars, Activities of daily living, Autoimmune diseases, Severity of Illness Index, Complement inhibitor, 0302 clinical medicine, CYCLOPHOSPHAMIDE, Activities of Daily Living, Outcome Assessment, Health Care, Medicine and Health Sciences, Research Articles, Malalties autoimmunitàries, General Neuroscience, Eculizumab, myasthenia, Neuromuscular diseases, Life Sciences & Biomedicine, medicine.drug, RC321-571, Research Article, Adult, medicine.medical_specialty, Cyclophosphamide, Gross motor skill, Clinical Neurology, Neurosciences. Biological psychiatry. Neuropsychiatry, Placebo, Antibodies, Monoclonal, Humanized, ACETYLCHOLINE-RECEPTOR, 03 medical and health sciences, Refractory, Double-Blind Method, Internal medicine, Myasthenia Gravis, medicine, Humans, Muscle Strength, Patient Reported Outcome Measures, RC346-429, Muscle, Skeletal, Science & Technology, business.industry, Neurosciences, medicine.disease, Myasthenia gravis, 030104 developmental biology, Complement Inactivating Agents, ANTIBODY, Monoclonal antibodies, Neurosciences & Neurology, Neurology (clinical), Neurology. Diseases of the nervous system, business, Anticossos monoclonals, 030217 neurology & neurosurgery
Abstract

OBJECTIVE: To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. METHODS: Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed. RESULTS: Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension. INTERPRETATION: Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. ispartof: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY vol:7 issue:8 pages:1327-1339 ispartof: location:United States status: published

Published
2020

46. Feasibility and acceptability of a home‐based resistance training intervention in adolescent and young adult hematopoietic cell transplant survivors

Author

Sheri Ballard, K. Scott Baker, Matt Van Doren, Abby R. Rosenberg, Eric J. Chow, Kari Jenssen, Tyler G. Ketterl, Sam Myers, and Miranda C. Bradford

Subjects
Adult, medicine.medical_specialty, Adolescent, Coaching, Article, Young Adult, Prednisone, Intervention (counseling), medicine, Humans, Survivors, Young adult, business.industry, Hematopoietic Stem Cell Transplantation, Resistance Training, Hematology, Anthropometry, medicine.disease, Exercise Therapy, Transplantation, Oncology, Pediatrics, Perinatology and Child Health, Lean body mass, Physical therapy, Feasibility Studies, Metabolic syndrome, business, medicine.drug
Abstract

Background Adolescent and young adult (AYA) hematopoietic cell transplantation (HCT) survivors are at increased risk of metabolic syndrome and lean body mass (LBM) deficits. Resistance training (RT) is a potential intervention to improve LBM, metabolic fitness, and reduce risk of cardiovascular disease. Procedure Eligible participants ages 13-39 years, 80-120 days post-HCT, transfusion independent, and prednisone dose ≤1 mg/kg/day were approached. Baseline assessments of body composition (DXA), anthropometrics, and strength testing were completed and participants were taught a 12-week, home-based RT intervention with weekly remote coaching. Follow-up assessments were at day +200 (FU1) and +365 post-HCT (FU2). Feasibility targets were (a) 60% enrollment of approached patients, (b) 80% completion of weekly phone calls, and (c) 80% completion of the RT intervention and FU1 assessments. Acceptability was based on positive responses in qualitative interviews. Results Twenty of 31 (65%) eligible AYAs enrolled. Three participants failed to complete baseline measurements (2 = scheduling barriers, 1 = passive refusal) and four participants who completed baseline assessments did not receive the intervention (1 = medical reasons, 2 = no longer interested). Of those who completed baseline assessments, 13 received the intervention, completed 88.5% of coaching calls, and 11 (65%) completed FU1. LBM (kg) increased or remained unchanged in nine of nine participants with complete body composition data at FU1 (mean 1.1 kg; 95%CI: 0.4, 1.9). All participants who completed FU1 reported they would recommend the intervention to an AYA HCT survivor. Conclusions A home-based RT intervention in AYA HCT survivors early post HCT is both feasible and acceptable and may maintain or increase LBM.

Published
2021

47. Enhancing Performance of a Spasticity Screening Tool Using the Minimum Data Set

Author

Sandra F. Simmons, Miranda C. Tomaras, John F. Schnelle, Mallory L. Hacker, and David Charles

Subjects
medicine.medical_specialty, Minimum Data Set, Tool Use Behavior, business.industry, Health Policy, General Medicine, Long-Term Care, Physical medicine and rehabilitation, Muscle Spasticity, medicine, Humans, Mass Screening, Screening tool, Spasticity, Geriatrics and Gerontology, medicine.symptom, business, General Nursing
Published
2021

48. A novel combined resilience and advance care planning intervention for adolescents and young adults with advanced cancer: A feasibility and acceptability cohort study

Author

Abby R. Rosenberg, Kaitlyn Fladeboe, Joyce P. Yi-Frazier, Angela Steineck, Courtney C. Junkins, Miranda C. Bradford, Krysta S. Barton, and Maeve B O'Donnell

Subjects
Advance care planning, Adult, Male, Cancer Research, medicine.medical_specialty, Palliative care, Adolescent, Population, Article, Cohort Studies, Advance Care Planning, Young Adult, Neoplasms, Medicine, Humans, Young adult, education, Child, education.field_of_study, business.industry, Resilience, Psychological, humanities, Distress, Oncology, Family medicine, Anxiety, Feasibility Studies, Female, medicine.symptom, business, Psychosocial, Stress, Psychological, Cohort study
Abstract

BACKGROUND Few evidence-based psychosocial programs have been tested among adolescents and young adults (AYAs) with advanced cancer (AC), and early advance care planning (ACP) in this population is rare. The authors aimed to determine the feasibility and acceptability of 1) delivering an established resilience-coaching program, and 2) integrating ACP into that program, among AYAs with AC. METHODS Eligible AYAs were 12 to 24 years old, diagnosed with advanced cancer (recurrent/refractory disease or a diagnosis associated with

Published
2021

49. Aprosodia and prosoplegia with right frontal neurodegeneration

Author

H. Isabel Hubbard, Brianne M. Bettcher, Miranda C. Babiak, Christopher M. Filley, James R. Bateman, Peter Pressman, and Elliott D. Ross

Subjects
Male, medicine.medical_specialty, Apraxias, Neuropsychological Tests, Audiology, Functional Laterality, Speech Disorders, Article, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Arts and Humanities (miscellaneous), Aphasia, medicine, Humans, 0501 psychology and cognitive sciences, Prosody, Facial expression, 05 social sciences, Neurodegeneration, Middle Aged, medicine.disease, Temporal Lobe, Frontal Lobe, Facial Expression, Affective prosody, Clinical diagnosis, Neurology (clinical), Aprosodia, medicine.symptom, Psychology, 030217 neurology & neurosurgery
Abstract

Affective prosody and facial expression are essential components of human communication. Aprosodic syndromes are associated with focal right cerebral lesions that impair the affective-prosodic aspects of language, but are rarely identified because affective prosody is not routinely assessed by clinicians. Inability to produce emotional faces (affective prosoplegia) is a related and important aspect of affective communication has overlapping neuroanatomic substrates with affective prosody. We describe a patient with progressive aprosodia and prosoplegia who had right greater than left perisylvian and temporal atrophy with an anterior predominance. We discuss the importance of assessing affective prosody and facial expression to arrive at an accurate clinical diagnosis.

Published
2019

50. Evaluation of two distinct placental‐derived membranes and their effect on tenocyte responses in vitro

Author

Kelly A. Kimmerling, Katie C. Mowry, John P. McQuilling, and Miranda C. Staples

Subjects
Male, Proteomics, Placenta, medicine.medical_treatment, Basic fibroblast growth factor, Medicine (miscellaneous), 02 engineering and technology, hypothermically stored amniotic membrane (HSAM), Matrix (biology), Tendons, Extracellular matrix, chemistry.chemical_compound, Cell Movement, Pregnancy, Research Articles, Cells, Cultured, Aged, 80 and over, 0303 health sciences, Amnion, biology, Middle Aged, Extracellular Matrix, Tendon, Cell biology, medicine.anatomical_structure, Cytokines, Intercellular Signaling Peptides and Proteins, Female, Collagen, Inflammation Mediators, Research Article, regenerative healing, 0206 medical engineering, Biomedical Engineering, Biomaterials, 03 medical and health sciences, In vivo, tendon repair, medicine, Humans, Aged, Cell Proliferation, 030304 developmental biology, Wound Healing, amniotic membrane, Growth factor, Transforming growth factor beta, 020601 biomedical engineering, Tenocytes, chemistry, biology.protein, dehydrated amnion/chorion membrane (dACM)
Abstract

Tendon healing is a complex, multiphase process that results in increased scar tissue formation, leading to weaker tendons. The purpose of this study was to evaluate the response of tenocytes to both hypothermically stored amniotic membrane (HSAM) and dehydrated amnion/chorion membrane (dACM). Composition and growth factor release from HSAM and dACM were evaluated using proteomics microarrays. HSAM and dACM releasate was used to assess tenocyte proliferation, migration, gene expression, extracellular matrix (ECM) protein deposition, and response to inflammation. Additionally, tenocyte–ECM interactions were evaluated. HSAM and dACM contain and release growth factors relevant to tendon healing, including insulin‐like growth factor I, platelet‐derived growth factor, and basic fibroblast growth factor. Both dACM and HSAM promoted increased tenocyte proliferation and migration; tenocytes treated with dACM proliferated more robustly, whereas treatment with HSAM resulted in higher migration. Both dACM and HSAM resulted in altered ECM gene expression; dACM grafts alone resulted in increases in collagen deposition. Furthermore, both allografts resulted in altered tenocyte responses to inflammation with reduced transforming growth factor beta levels. Additionally, dACM treatment resulted in increased expression and production of matrix metalloprotease‐1 (MMP‐1), whereas HSAM treatment resulted in decreased production of MMP‐1. Tenocytes migrated into and remodeled HSAM only. These results indicate that both grafts have properties that support tendon healing; however, the results presented here suggest that the responses to each type of graft may be different. Due to the complex environment during tendon repair, additional work is needed to evaluate these effects using in vivo models.

Published
2019

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