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Health care teams are most effective at addressing complex problems and improving health outcomes for underserved populations when team members bring diverse life experiences and perspectives to the effort. With rates of visual impairment expected to increase in the United States by 2050, especially among minority populations, diversification of the ophthalmology workforce will be critical in reducing disparities in access to and quality of vision health care. Currently, ophthalmology is less diverse with respect to race, ethnicity, and gender than graduating medical classes and other medical specialties, as well as the general US population. In addition, data on diversity in sexual orientation and gender identity, socioeconomic status, and disability are lacking in ophthalmology. The Minority Ophthalmology Mentoring and Rabb-Venable Excellence in Ophthalmology Programs are examples of initiatives to increase racial and ethnic diversity in the workforce and can serve as models for increasing other aspects of inclusiveness. Other strategies for improving vision health care for all Americans include continuing to support existing diversity programs and creating new ones; addressing unconscious and implicit bias in medical school, residency, and faculty selections; conducting holistic reviews of medical school and residency applications; diversifying selection committees and leadership; and encouraging faculty development of underrepresented groups.

Objectives We present the results of our experience in the diagnosis and follow up of the positive cases for propionic, methylmalonic acidemias and cobalamin deficiencies (PA/MMA/MMAHC) since the Expanded Newborn Screening was implemented in Madrid Region. Methods Dried blood samples were collected 48 h after birth. Amino acids and acylcarnitines were quantitated by MS/MS. Newborns with alterations were referred to the clinical centers for follow-up. Biochemical and molecular genetic studies for confirmation of a disease were performed. Results In the period 2011–2020, 588,793 children were screened, being 953 of them were referred to clinical units for abnormal result (192 for elevated C3 levels). Among them, 88 were false positive cases, 85 maternal vitamin B12 deficiencies and 19 were confirmed to suffer an IEM (8 PA, 4 MMA, 7 MMAHC). Ten out 19 cases displayed symptoms before the NBS results (6 PA, 1 MMA, 3 MMAHC). C3, C16:1OH+C17 levels and C3/C2 and C3/Met ratios were higher in newborns with PA/MMA/MMAHC. Cases diagnosed with B12 deficiency had mean B12 levels of 187.6 ± 76.9 pg/mL and their mothers 213.7 ± 95.0; 5% of the mothers were vegetarian or had poor eating while 15% were diagnosed of pernicious anemia. Newborns and their mothers received treatment with B12 with different posology, normalizing their levels and the secondary alterations disappeared. Conclusions Elevated C3 are a frequent cause for abnormal result in newborn screening with a high rate of false positive cases. Presymptomatic diagnosis of most of PA and some MMA/MMAHC is difficult. Vitamin B12 deficiency secondary to maternal deprivation is frequent with an heterogenous clinical and biochemical spectrum.

Elena García Castillo,1– 4 Tamara Alonso Pérez,1– 4 Adrián Peláez,1– 3 Patricia Pérez González,1,2,4 Joan B Soriano,1– 3 Julio Ancochea1– 4 1Pulmonary Department, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain; 2School of Medicine, Universidad Autónoma de Madrid (UAM), Madrid, Spain; 3Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; 4Cátedra UAM-GSK “Respira Vida”, Madrid, SpainCorrespondence: Elena García Castillo, Pulmonology Department, Hospital Universitario La Princesa, C/ Diego de León, 62, Madrid, CP: 28006, Spain, Tel +34 91 520 22 77, Fax +91-520-26-72, Email elenagcs@gmail.comPurpose: The prevalence of Chronic obstructive pulmonary disease (COPD) in Spain has been evaluated in the last ten years by EPISCAN in 2007 and EPISCAN II in 2017. This study describes changes in the prevalence of COPD in an urban region of Spain in the last 10 years, its risk factors and underdiagnosis.Patients and Methods: Participants from the Autonomous Community of Madrid (Spain) were selected from both studies up to the age of 80 years. A descriptive analysis of their sociodemographic and clinical characteristics, as well as by gender, was conducted. COPD was defined by a post-bronchodilator ratio < 0.70.Results: The prevalence of COPD in the Autonomous Community of Madrid increased non-significantly from 11.0% (95% CI: 8.9– 13.5%) to 12.1% (95% CI: 9.6– 15.1, p=0.612). However, the prevalence by gender showed an increase in women (5.6% to 14.7%, p< 0.001) and a decrease in men (17.6% to 9.8%, p=0.08). Underdiagnosis was reduced from 81.0% to 67.9% (p=0.006), although with greater underdiagnosis in women (86.4% in EPISCAN and 100% in EPISCAN II). Smoking was higher in men than in women in EPISCAN (31.2% vs 23.0%, p< 0.01) but with no differences by gender in EPISCAN II (25.5% men vs 26.0% women, p=0.146). Age, smoking, low BMI, and a sedentary lifestyle were consistently associated with COPD.Conclusion: In 10 years in Madrid, there have been no changes in the global prevalence of COPD, but there have been important changes in women, with an increase in its prevalence, smoking habit and underdiagnosis.Keywords: COPD, prevalence, Madrid, spirometry

Objective. To detect serum IgG anti-SARS-CoV-2 in pre-and post- Covid-19 pandemic in Mexican asymptomatic subjects in order to know the degree of viral dispersion. Materials and methods. Association of serum IgG antibodies (determined by ELISA) to sociodemographic and clinical data or contact with Covid-19 cases in three groups of subjects: 1) Covid-19 pre-pandemic blood donors (n= 538); 2) Covid-19 post-pandemic blood donors (n= 243); 3) Covid-19 post-pandemic neurological patients (n= 312). None of the subjects studied had been vaccinated. Results. The positive rate of IgG anti-SARS-CoV-2 was notably higher in participants recruited during the pandemic (donors, 29.6%; neurological patients, 15.7%) than in those recruited pre-pan­demic (donors 0.6%) (p

SARS-CoV-2 specific T-cell response has been associated with disease severity, immune memory and heterologous response to endemic coronaviruses. However, an integrative approach combining a comprehensive analysis of the quality of SARS-CoV-2 specific T-cell response with antibody levels in these three scenarios is needed. In the present study, we found that, in acute infection, while mild disease was associated with high T-cell polyfunctionality biased to IL-2 production and inversely correlated with anti-S IgG levels, combinations only including IFN-γ with the absence of perforin production predominated in severe disease. Seven months after infection, both non-hospitalised and previously hospitalised patients presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only previously hospitalised patients showed a T-cell exhaustion profile. Finally, combinations including IL-2 in response to S protein of endemic coronaviruses were the ones associated with SARS-CoV-2 S-specific T-cell response in pre-COVID-19 healthy donors’ samples. These results could have implications for protective immunity against SARS-CoV-2 and recurrent COVID-19 and may help for the design of new prototypes and boosting vaccine strategies., NIH (contract to AS, DW), Grant/AwardNumber: 75N9301900065; “Contratación de Personal Investigador Doctor”supported by the European Social Fund and Junta de Andalucía (PAIDIDOCTOR- Convocatoria 2019-2020 toFJO, SB); Instituto de Salud Carlos III,Fondos FEDER. ERM was supported bythe Spanish Research Council (CSIC);Consejería de Transformación Económica, Industria, Conocimiento y Universidades Junta de Andalucía (research project to ERM), Grant/AwardNumber: CV20-85418; Red Temática de Investigación Cooperativa en SIDA, whichis included in the Acción Estratégica en Salud, Plan Nacional de InvestigaciónCientífica, Desarrollo e Innovación Tecnológica, 2008 to 2011 and 2013 to 2016,Grant/Award Numbers: RD16/0025/0020,RD16/0025/0026; Consejeria de Salud Junta de Andalucia (Research contract toJV), Grant/Award Number:RH-0037-2020; Instituto de Salud CarlosIII (PI19/01127 to ERM, CP19/00159 toAGV, FI17/00186 to MRJL, FI19/00083 toCGC, CM20/00243 to APG andCOV20/00698 to support COHVID-GS)

Public health measures (PHM) designed to contain the spread of COVID-19 pandemic have influenced the epidemiological characteristics of other viral infections. Its impact on acute RSV bronchiolitis in infants of ≤24 months old has not been systematically studied in our setting.To describe the monthly pattern of visits to the Paediatric Emergency Department (PED) of patients 0 to 14 years of age, the rate of patients diagnosed with RSV acute bronchiolitis per thousand inhabitants of 0 to 24 months, and the rate of them requiring hospital admission during the winter 2020-2021, in the context of local and national COVID-19 restrictions and compare them to the four previous seasons.Interrupted time series analysis of patients assisted in the PED and diagnosed with or admitted for RSV acute bronchiolitis in a tertiary University Hospital from January 2016 to February 2020 (pre-intervention period) and from March 2020 to June 2021 (post-intervention period).Preventive PHM implemented by the Spanish government weighted by the Containment and Health Index of the Oxford COVID-19 Government Response Tracker.The intervention was followed by an immediate reduction of the rate of visits to the PED of -19.5 (95% confidence interval [CI] -24.0, -14.9) per thousand, and the rate of diagnoses and admissions for RSV acute bronchiolitis of -44.3 (95% CI -73.8, -14.8) and -1.4 (95% CI -2.7, -0.1) per thousand, respectively, with a delayed rebound.After the implementation of PHM to prevent the spread of SARS-CoV-2 infection, an immediate and important decline in the visits to the PED was observed, with an upward change thereafter. There was also an initial reduction in the diagnoses of and admissions by RSV acute bronchiolitis. An upward trend was observed six to nine months after the usual time of the winter RSV epidemic, coinciding with the relaxation of the preventive PHM.

Altres ajuts: Huntington's Disease Society of America Female Huntington's disease (HD) patients have consistently shown a faster clinical worsening than male, but the underlying mechanisms responsible for this observation remain unknown. Here, we describe how sex modifies the impact of neurodegeneration on brain atrophy and clinical severity in HD. Cerebrospinal fluid neurofilament light chain (NfL) levels were used as a biological measure of neurodegeneration, and brain atrophy was assessed by structural magnetic resonance imaging. We found that larger NfL values in women reflect higher brain atrophy and clinical severity than in men (p < 0.05 for an interaction model). This differential vulnerability could have important implications in clinical trials.

Background The primary aim of this study was to analyze the survival of patients undergoing lung transplant (LT) with cytomegalovirus (CMV)-positive serologies at the time of transplantation, according to the presence of CMV events and according to the severity of these events. The secondary objective was to assess whether there are differences in the incidence of chronic lung allograft dysfunction (CLAD) according to the presence of these events. Methods This was an observational, single-center, retrospective study. The inclusion criterion for the study was having undergone LT at the Hospital Universitario 12 de Octubre from October 2008 to February 2019. Survival was calculated using the Kaplan-Meier method and compared using the log-rank test. The incidence of CLAD was compared using the χ2 test. Results Inclusion criteria were met by 239 LTs. In terms of survival, no difference was found between patients with and without CMV events (log-rank P = .52), with mean survival of 3223 ± 164 days and 3024 ± 146 days, respectively. Nor did we find a difference when stratifying patients according to no CMV events, infection, syndrome, and disease (log-rank P = .6). There was also no difference in the incidence of CLAD between patients with and without CMV events (P > .178). Conclusion In patients with positive CMV serology, the development of CMV events, including severe disease, does not seem to influence survival. The incidence of CLAD also is not increased by the presence of CMV events.

Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting cognitive and memory abilities and is believed to be linked to the formation and accumulation of neurotoxic aggregates of the Amyloid-β peptide (Aβ). In particular, it is the formation of soluble pre-fibrillar oligomers within the early stage of Aβ aggregation which is thought to represent a key step in the development of AD, thus underlining the interest in characterizing the aggregation process and the nature of these aggregates. In this context, fluorescence correlation spectroscopy (FCS) has emerged as a valuable alternative for the study of these systems in solution. Indeed, the use of FCS to study terminally labelled Aβ provides a means to detect changes in the size and concentration of initially monomeric Aβ samples by monitoring these fluorescently labelled species freely diffusing in solution with single-molecule resolution. Herein, we show how to employ FCS to study the early aggregation process of Aβ(1-42) and how this can be used to estimate the critical concentration for oligomer formation and to characterize the aggregates formed.

The treatment and outcomes of diabetic macular oedema (DMO) have improved with the introduction of intravitreal injections. However, real-world data reveal that the burden of DMO treatment causes large gaps in outcomes between randomized clinical trials and daily clinical practice. Long-lasting intravitreal drugs and devices for DMO might reduce this disparity by achieving optimal treatment due to more feasible injection regimens. In this manuscript, we cover pharmacodynamics, preliminary results from clinical trials, and safety behavior about brolucizumab, faricimab, conbercept, KSI-301, and port-delivery system WR42221. These treatments might present the first step to control the global epidemic of diabetic eye disease in real life.

Aim : To describe and synthesize scientific literature on nurse managers’ competencies. Background : The key strategy for the success of health organisations currently re-sides in the capacity of the nurse manager to develop advanced competencies in management. However, there is a lack of systematic reviews that synthesize knowl-edge about nurse managers’ competencies. Evaluation : A scoping review was conducted using electronic databases including Web of Science, Scopus, PubMed and Cumulative Index to Nursing and Allied Health Literature. Key issues : After the first analysis, 392 competencies were observed from 76 stud-ies. Finally, 53 competencies were grouped according to their characteristics. The two most- cited competencies were communication and finance. Conclusions : Knowing the competencies required by nurse managers can help or-ganisations create strategies to develop competent managers. In addition, from the results we can infer what might be the core competencies, since 22 main competen-cies from the total number were identified. Implications for Nursing Management : The competencies identified constitute the body of knowledge necessary for nurse managers. In addition, it is possible to gener-ate a pathway for learning and professional development for nurses before they work at the microlevel of management. The starting point for this pathway could be the 22 core competencies. SI

The Navachiste complex (NAV) is impacted by neighbored human activities and is located in the southwestern coastal zone of the Gulf of California. The study determines the trace metal (TM) and organochlorine pesticides (OCP) health risk content in the edible tissue of Sphoeroides spp. from NAV. The daily intakes (EDI), target hazard quotient (THQ), hazard index (HI), and carcinogenic and non-carcinogenic risks were calculated. Twenty OCP and seven TM were detected with the following trend for TM: Zn > Fe > Pb > Ni > Mn > Cu > Cd. Cd, Cu, Fe, Mn, Pb, and Zn were above MRLs. The γ‒Chlordane was the most frequent OCP. The highest average concentration was for α‒HCH, followed by γ‒chlordane. With the high ratios of γ‒HCH, p, p'‒ DDD and p, p'‒DDD, and the absence of p, p'‒ DDT, the higher ratios for dieldrin and endrin than for aldrin, α‒ chlordane, γ‒chlordane, heptachlor, and heptachlor epoxide indicates historical contamination. In contrast, the residual products of methoxychlor, endosulfan, and its isomers indicate endosulfan's recent use. The TM EDI, THQ > 1 (at 120 g day-1), and the ILCR (> 1 × 10-6) were above minimum levels, showing a high-risk potential for cancer development in the long term.

Extracellular vesicles (EVs) are biological nanoparticles secreted by all cells for cellular communication and waste elimination. They participate in a vast range of functions by acting on and transferring their cargos to other cells in physiological and pathological conditions. Given their presence in biofluids, EVs represent an excellent resource for studying disease processes and can be considered a liquid biopsy for biomarker discovery. An attractive aspect of EV analysis is that they can be selected based on markers of their cell of origin, thus reflecting the environment of a specific tissue in their cargo. However, one of the major handicaps related to EV isolation methods is the lack of methodological consensuses and standardized protocols. Astrocytes are glial cells with essential roles in the brain. In neurodegenerative diseases, astrocyte reactivity may lead to altered EV cargo and aberrant cellular communication, facilitating/enhancing disease progression. Thus, analysis of astrocyte EVs may lead to the discovery of biomarkers and potential disease targets. This protocol describes a 2-step method of enrichment of astrocyte-derived EVs (ADEVs) from human plasma. First, EVs are enriched from defibrinated plasma via polymer-based precipitation. This is followed by enrichment of ADEVs through ACSA-1-based immunocapture with magnetic micro-beads, where resuspended EVs are loaded onto a column placed in a magnetic field. Magnetically labeled ACSA-1+ EVs are retained within the column, while other EVs flow through. Once the column is removed from the magnet, ADEVs are eluted and are ready for storage and analysis. To validate the enrichment of astrocyte markers, glial fibrillary acidic protein (GFAP), or other specific astrocytic markers of intracellular origin, can be measured in the eluate and compared with the flow-through. This protocol proposes an easy, time-efficient method to enrich ADEVs from plasma that can be used as a platform to examine astrocyte-relevant markers.

Centrosome amplification, the presence of more than two centrosomes in a cell is a common feature of most human cancer cell lines. However, little is known about centrosome numbers in human cancers and whether amplification or other numerical aberrations are frequently present. To address this question, we have analyzed a large cohort of primary human epithelial ovarian cancers (EOCs) from 100 patients. We found that rigorous quantitation of centrosome number in tumor samples was extremely challenging due to tumor heterogeneity and extensive tissue disorganization. Interestingly, even if centrosome clusters could be identified, the incidence of centrosome amplification was not comparable to what has been described in cultured cancer cells. Surprisingly, centrosome loss events where a few or many nuclei were not associated with centrosomes were clearly noticed and overall more frequent than centrosome amplification. Our findings highlight the difficulty of characterizing centrosome numbers in human tumors, while revealing a novel paradigm of centrosome number defects in EOCs.

We replicated and extended studies showing that contextual cues for matching stimuli from 2 separate equivalence classes control the same derived relations as contextual cues for opposition frames in RFT studies. We conducted 2 experiments with 6 college students. In Phase 1, they received training in a conditional discrimination AB. Then, they received training for maintaining AB with X1 as context, and for reversing the sample-comparison relations of AB, with X2. In Phase 2, X1 functioned as context for matching same-class stimuli, and X2 functioned as context for matching separate-class stimuli. In Phase 3, X2 controlled the same derived arbitrary relations as cues for opposition frames in RFT studies. This functional equivalence may suggest that X2 functioned as a cue for opposition frames. In Phase 4, participants matched different stimuli with X2 as context, instead of matching most different (opposite) stimuli. In addition, Different, a cue for matching different stimuli, controlled the same derived arbitrary relations as X2. These results are incompatible with X2 being a cue for opposition frames. Contextual control over equivalence and responding by exclusion can explain these outcomes. The implications of these findings for RFT studies on opposition frames are discussed.

Objectives: To picture the psychological impact on the general population consulting the Emergency Medical System (EMS) of Catalonia for psychological assistance due to the COVID-19.Methods: Calls received to the 061 emergency phone number between the months of March and June 2020 (period of lockdown and de-escalation) were analyzed. The reason, most prevalent psychological symptoms, presence of psychological antecedents, and type of intervention that was carried out were analyzed.Results: A total of 2,516 calls were analyzed. Weeks 6, 7, 8 and 9 of lockdown saw the highest volume of calls (298, 314, 282 and 290 daily calls, respectively). The main profile of the affected person was women, under the age of 50 who are responsible for others. Psychologically, they present symptoms of depression (7.33%) and anxiety (39.44%). The greatest impacts on mental health throughout lockdown seem to be related to an increase of interpersonal conflict (8.8% < 11.2%), work-related problems (1.7% < 4.6%), and problems of psychological distress (6.5% < 17.0%).Conclusion: The information obtained enables us to better understand the possible evolution of the impacts on mental health derived from the lockdown.

Background: The impact of the new “borderline” hemodynamic class for pulmonary hypertension (PH) (mean pulmonary artery pressure [mPAP], 21–24 mm Hg and pulmonary vascular resistance, [PVR], ≥3 wood units, [WU]) in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) is unclear. Objectives: The aim of this study was to assess the effect of borderline PH (BLPH) on survival in COPD and ILD patients. Method: Survival was analyzed from retrospective data from 317 patients in 12 centers (Italy, Spain, UK) comparing four hemodynamic groups: the absence of PH (NoPH; mPAP 2), and severe PH (SPH; mPAP ≥35 mm Hg or mPAP ≥25 mm Hg and CI 2). Results: BLPH affected 14% of patients; hemodynamic severity did not predict survival when COPD and ILD patients were analyzed together. However, survival in the ILD cohort for any PH level was worse than in NoPH (3-year survival: NoPH 58%, BLPH 32%, MPH 28%, SPH 33%, p = 0.002). In the COPD cohort, only SPH had reduced survival compared to the other groups (3-year survival: NoPH 82%, BLPH 86%, MPH 87%, SPH 57%, p = 0.005). The mortality risk correlated significantly with mPAP in ILD (hazard ratio [HR]: 2.776, 95% CI: 2.057–3.748, p < 0.001) and notably less in COPD patients (HR: 1.015, 95% CI: 1.003–1.027, p = 0.0146). Conclusions: In ILD, any level of PH portends worse survival, while in COPD, only SPH presents a worse outcome.

[EN] BackgroundNurses capable of adequately developing their competencies in the management field are essential for the sustainability of health-care organizations. Such competencies should be included in a model of specific competencies.AimThe aim of this research is to propose a competency model for nurse executives.MethodsThe Delphi method was applied to reach a consensus on the required competencies, and Principal Component Analysis (PCA) was applied to determine the construct validity and reduce the data set's dimensionality. Consensus was defined based on at least 80% of the experts agreeing with the proposed competencies. For each competency, the development levels were beginner, advanced beginner, competent, highly competent and expert.ResultsFrom among the 51 competencies that were identified to define a model for nurse executives, decision-making, leadership and communication stood out. The PCA indicated the structural validity of the proposed model by saturation of the principal components (Cronbach's α > 0.631).ConclusionNurses wishing to develop their professional careers as nurse executives must first develop the competencies shown in the proposed model. Nurse executives should follow the educational programmes specified in this study, to adapt their knowledge to this role's requirements. SI Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCLE

Made available in DSpace on 2022-05-01T09:30:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 Background: DNA damage is accumulated in the cells over time as the result of both exogenous and endogenous factors. The objective of this study was to analyze the immunohistochemical expression of the repair proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). Materials and Methods: Paraffin blocks were selected from the archives of the Laboratory of Hospital Clinico Universitario de Santiago de Compostela, Spain. The sample was composed of 16 cases of OL without dysplasia, 14 cases of OL with dysplasia, and 15 cases of OSCC. The patients' clinical data were collected and immunohistochemical analysis was performed for MLH1, MSH2, MRE11, and XRCC1. The data were submitted to the χ2and the Kruskal-Wallis (P≤0.05) tests. Results: MSH2 was overexpressed in OSCC (P=0.020) and was positive in 100% of patients with OL with dysplasia or OSCC (P=0.019). Positivity for MLH1 was significantly associated with comorbidity (P=0.040), especially in patients who presented with 2 or more pathologies (P=0.028). XRCC1 positivity was also associated with comorbidity (P=0.039). No significant associations were found for the MRE11A expression. Although the simultaneous positivity for the 4 markers was observed in presence of comorbidities (P=0.006). Conclusions: This study supports the effect of the overexpression of MSH2 protein in samples of OL with dysplasia and OSCC, most notably in patients who present with comorbidities and negativity for OL without dysplasia. Oral Medicine Unit Technology Research Center (NPT) Mogi das Cruzes University Mogi das Cruzes, 200 Dr. C ndido Xavier de Almeida Souza Avenue Department of Pathology Clinical Hospital Santiago de Compostela Department of Forensic Sciences and Pathology University of Santiago de Compostela Translational Oncology Laboratory Idichus Foundation Santiago de Compostela School of Medicine Anhembi Morumbi University Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP) Department of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (UNESP)

Vascular occlusion has multiple, diverse clinical manifestations, some of which can have grave consequences for patients. It also has a wide variety of causes, including thrombi, which we recently addressed in partI of this review. In this second part, we look at additional causes of vascular occlusion.

The treatment of neovascular AMD (nAMD) has been revolutionized by the introduction of anti-vascular endothelial growth factor (VEGF) agents. Though, there is a tremendous gap between the outcomes in randomized clinical trials and real-world settings, where long-term outcomes are not as good as expected. This is due to undertreatment, i.e., fewer injection and low monitoring frequency. Treatment burden due to frequent injections remains a major limitation. Long-lasting treatments provide promising solutions for this unmet need by achieving better results with less mandatory injections. This review aims to cover the current state in this field and also discuss the mechanism of action, data from pivotal trials, and safety profile of long-acting treatments in present and future, going into details about the following agents: Brolucizumab, Faricimab, Abipicar, and Conbercept.摘要: 抗血管内皮生长因子 (VEGF) 药物的应用使新生血管性AMD (nAMD) 的治疗发生了革命性变化。但随机临床试验的结果与现实世界存在巨大差距, 临床实际的长期疗效远低于预期。这是由于治疗不足所致, 即注射次数较少以及随访频率低。其中频繁注射造成的治疗负担为主要的制约因素。而长效制剂通过减少注射次数以及获得的更好疗效, 为满足临床上述的需求提供了解决方案。本综述旨在阐述该领域的现状, 讨论长期治疗在目前和未来阶段的作用机制、重要临床试验数据和安全性, 并详细介绍以下药物: Brolucizumab、Faricimab、Abipicar和Conbercept。.

La patología vascular oclusiva es causante de diversas y variadas manifestaciones clínicas, algunas de las cuales son de catastróficas consecuencias para el paciente. Sin embargo, las causas de tal oclusión son muy variadas, extendiéndose desde trombos por acción descontrolada de los mecanismos de coagulación, hasta anomalías de los endotelios de los vasos u oclusión por materiales extrínsecos. En una serie de dos artículos hacemos una revisión de las principales causas de oclusión vascular, resumiendo sus manifestaciones clínicas principales y los hallazgos histopatológicos fundamentales. Esta primera parte corresponde a las oclusiones vasculares que cursan con trombos.

Background Hemolytic Uremic Syndrome (HUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, considered within the group of thrombocytic microangiopathies. Ocular complications in HUS are very rare. Here, we report an adult patient who suffered from acute onset of paracentral scotoma, caused by branch retinal artery occlusion (BRAO), as a leading symptom of atypical HUS. Case presentation A 39-year-old healthy male was lately diagnosed with essential hypertension and mild renal impairment. He complained about acute onset of central scotoma in his left eye. Fundus examination revealed marked narrowing of retinal vessels, cotton wool spots and few retinal hemorrhages in both eyes. The patient was diagnosed with bilateral ischemic retinal vasculopathy and acute macular BRAO in his left eye. Workup revealed thrombocytopenia, worsening renal failure. Renal biopsy showed signs of chronic thrombotic microangiopathy. The patient was diagnosed with atypical HUS (aHUS) and started on plasmapheresis, together with eculizumab. As his condition continued to worsen, he was put on renal replacement therapy. Due to a persistent monoclone of IgG1, the patient underwent bone marrow biopsy which revealed Monoclonal Gammopathy of renal significance, triggering a HUS and treatment was initiated accordingly. Two months after initial presentation, the patient developed neovascularization of the optic disc (NVD) in his left eye, and was treated with 3 monthly intravitreal bevacizumab injections with complete regression of the NVD. The patient suffered from myocardial infarction in the later course and was lost for follow-up. He returned 11 months after the last bevacizumab injection because of sudden loss of vision in his left eye caused by a dense vitreous hemorrhage. Biomicroscopy revealed a new NVD in his right eye. The patient underwent panretinal photocoagulation in both eyes with regression of neovascularization. Vision improved and remained 20/20 in both eyes. Conclusion We present a case report showing retinal ischemia can be linked with aHUS. As clinal diagnosis might be challenging, physicians should be aware of the rare ocular manifestations of this devastating multi-organ disease. In case of retinal ischemia, panretinal photocoagulation should be initiated soon to avoid blinding complications.

Analysis of male infertility by molecular methods has increased since recognition of genetic risk factors. The AZFa, AZFb, AZFc, and gr/gr regions on the Y-chromosome can cause male infertility. The aim of this study was to determine the prevalence of Y-chromosome microdeletions in these regions in infertile Mexican patients.We recruited 57 infertile patients with abnormal sperm count (26 azoospermic and 31 oligozoospermic) and 55 individuals with normal sperm count. Analysis of the regions of interest was performed by PCR.15.8% of infertile patients presented Y-chromosome microdeletions, whereas no deletions were found in the control group. Deletions were observed in all the analyzed regions except in AZFa. Additionally, the neural network model revealed a mild genotype-phenotype correlation between deletion of the sY1191, sY1291 and sY254 markers with oligozoospermia, azoospermia and cryptozoospermia, respectively.Our data show that AZFb, AZFc, and gr/gr microdeletions are significantly associated with infertility in Mexican population. In addition, the neural network model revealed a discrete genotype-phenotype correlation between specific deletions and a particular abnormality. Our results reinforce the importance of the analysis of AZF regions as part of the clinical approach of infertile men.La utilización de técnicas moleculares para estudiar la infertilidad masculina se ha incrementado desde el reconocimiento de factores genéticos. Las regiones AZFa, AZFb, AZFc, y gr/gr del cromosoma Y son causa de infertilidad masculina. El objetvo de este estudio fue determinar la prevalencia de microdeleciones en estas regiones en pacientes infértiles Mexicanos.Reclutamos 57 pacientes infértiles con cuentas espermáticas anormales (26 con azoospermia y 31 con oligozoospermia) y 55 individuos con cuentas espermáticas normales. El análisis de las regiones se realizó mediante PCR.15.8% de los pacientes infértiles presentó microdeleciones, no se encontraron microdeleciones en el grupo control. Las microdeleciones fueron observadas en todas las regiones excepto en AZFa. Adicionalmente, el modelo de red neuronal reveló una leve correlación genotipo-fenotipo entre microdeleciones de los marcadores sY1191, Sy1291 y sY254 con oligozoospermia, azoospermia y criptozoospermia, respectivamente.Nuestros datos muestran que las microdeleciones en AZFb, AZFc, y gr/gr se asocian significativamente con infertilidad en la población Mexicana. Además, el modelo de red neuronal reveló una discreta correlación genotipo-genotipo entre microdeleciones específicas con una anormalidad en particular. Nuestros resultados refuerzan la importancia del análisis de las regiones AZF en el abordaje de la infertilidad masculina.

Traditionally, the understanding of biological mechanisms has played a central role in clinical reasoning. With the rise of the evidence-based paradigm, however, this role has come under scrutiny. On the one hand, clinical guidelines now place less emphasis on the evidence of pathophysiological mechanisms, a shift motivated by the unreliability of our understanding of complex biological mechanisms. On the other hand, some scholars defend evidence of mechanisms as crucial for clinical practice. This article assesses the relevance of evidence of biological mechanisms in two types of clinical predictions: predictions about the efficacy and about the safety of a certain intervention for a particular patient. For each type of prediction, the article analyzes the two roles that evidence of mechanisms might have-confirming and disconfirming-depending on whether the evidence supports that certain epidemiological results apply to the single patient. The analysis shows that the "unreliability because of incompleteness" argument against the emphasis on mechanistic clinical thinking only applies to some of the considered cases. The article concludes by offering a model for a more granular view of the role that evidence of mechanisms should play in clinical practice.

Great efforts have been performed on the production of advanced biomaterials with the combination of self-healing and wound healing properties in implant/tissue engineering biomedical area. Inspired by this idea, chitosan (CHI) based hydrogels can be used to treat a less investigated class of harmful chronic wounds: ulcers or pressure ulcers. Thus, CHI was crosslinked with previously synthesized polyethylene glycol diacid (PEG-diacid) to obtain different CHI-PEG hydrogel formulations with high H-bonding tendency resulting in self-repair ability. Here presented results show biocompatible, antibacterial, anti-inflammatory, and self-healing CHI-PEG hydrogels with a promising future in the treatment of ulcerated wounds by a significant improvement in metabolic activity (94.51 ± 4.38 %), collagen and elastin quantities (2.12 ± 0.63 μg collagen and 4.97 ± 0.61 μg elastin per mg dermal tissue) and histological analysis. Furthermore, cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) antibiotics, and acetylsalicylic acid (ASA) anti-inflammatory agent were sustainedly released for enhancing antibacterial and anti-inflammatory activities of hydrogels.

The 2020 pandemic of SARS-CoV-2 causing COVID-19 disease is an unprecedented global emergency. COVID-19 appears to be a disease with an early phase where the virus replicates, coinciding with the first presentation of symptoms, followed by a later 'inflammatory' phase which results in severe disease in some individuals. It is known from other rapidly progressive infections such as sepsis and influenza that early treatment with antimicrobials is associated with a better outcome. The hypothesis is that this holds for COVID-19 and that early antiviral treatment may prevent progression to the later phase of the disease.Trial design: Phase IIA randomised, double-blind, 2 × 2 design, placebo-controlled, interventional trial.Participants will be randomised 1:1 by stratification, with the following factors: gender, obesity, symptomatic or asymptomatic, current smoking status presence or absence of comorbidity, and if the participant has or has not been vaccinated.Participants and investigators will both be blinded to treatment allocation (double-blind).We propose to conduct a proof-of-principle placebo-controlled clinical trial of favipiravir plus or minus nitazoxanide in health workers, their household members and patients treated at the Mexican Social Security Institute (IMSS) facilities. Participants with or without symptomatic COVID-19 or who tested positive will be assigned to receive favipiravir plus nitazoxanide or favipiravir plus nitazoxanide placebo. The primary outcome will be the difference in the amount of virus ('viral load') in the upper respiratory tract after 5 days of therapy. Secondary outcomes will include hospitalization, major morbidity and mortality, pharmacokinetics, and impact of antiviral therapy on viral genetic mutation rate. If favipiravir with nitazoxanide demonstrates important antiviral effects without significant toxicity, there will be a strong case for a larger trial in people at high risk of hospitalization or intensive care admission, for example older patients and/or those with comorbidities and with early disease.ClinicalTrials.gov NCT04918927 . Registered on June 9, 2021.

Mucinous tubularand spindle cell carcinomas (MTSC) are a relativelyrare subtype of renal cell carcinoma (RCC) . Thesetumors are composed by tubular and spindle cellareas within a mucinous stroma. They are generallylow-grade nuclei tumors and limited to the kidney, sothey usually have a favorable prognosis. We report twonew cases of MTSC treated at our institution. MATERIALS AND METHODS: We reviewed therenal tumors surgery database of our hospital from2008 to 2019, selecting patients diagnosed with CMTF.We evaluated clinicopathological data and evolution ofthe patients. We also reviewed the published literatureto compare it with our findings. RESULTS: Two patients were included in the study,a 50-year-old male (case 1) and a 55-year-old female(case 2). The diagnosis was made by ultrasound asan incidental fi nding in case 1 and during the studyof fl ank pain in case 2. Treatment was surgical withpartial and radical nephrectomy respectively. After amean follow-up of 70 months, both patients are aliveand disease-free. CONCLUSION: Mucinous tubular and spindle cellcarcinomas (MTSC) is a rare renal tumor, approximatelytwo hundred cases have been published. Thereare questions yet to be answered about their diagnosisand behaviour so it is of utmost importance to reportnew cases in order to increase our knowledge and improvepatient care.INTRODUCCIÓN: Los carcinomasmucinosos tubulares y de células fusiformes (CMTF)son un subtipo relativamente infrecuente de carcinomarenal (CCR). Están compuestos por célulastubulares y fusiformes con un estroma mucinoso.Generalmente son tumores de bajo grado y estánlimitados al riñón, por lo que habitualmente tienenbuen pronóstico. Reportamos dos nuevos casos deCMTF tratados en nuestra institución. MATERIAL Y MÉTODOS: Se realizó una revisiónde todos los tumores renales intervenidos en nuestrohospital desde el año 2008 has ta el año 2019, seleccionandolos pacientes diagnosticados de CMTF.Se evaluaron las características clinicopatológicasy la evolución de los pacientes. Así mismo, se realizóuna revisión exhaustiva de la literatura publicadapara comparar los hallazgos descritos con los denuestros casos. RESULTADOS: Dos pacientes fueron incluidos enel estudio, un varón de 50 años ( caso 1) y una mujer de55 años ( caso 2). El diagnóstico fue ecográfico, de forma incidental en el caso 1 y a partir del estudio de undolor en flanco, en el caso 2. El tratamiento fue quirúrgicomediante nefrectomía parcial y radical respectivamente.Tras un seguimiento medio de 70 meses ambospacientes están vivos y libres de enfermedad. CONCLUSIÓN: El carcinoma mucinoso tubular yde células fusiformes (CMTF) es un tumor renal infrecuente,habiéndose publicado aproximadamente doscentenares de casos. Aún hay incógnitas que resolversobre su diagnóstico y comportamiento, de ahí la importanciade reportar nuevos casos que nos permitanaumentar su conocimiento y mejorar el manejo denuestros pacientes.

To identify clinical, radiological, and histopathological characteristics that could be predictive factors of microinvasive/invasive breast carcinoma in patients with diagnosis of ductal carcinoma in situ (DCIS) by core-needle biopsy.This is a retrospective study conducted from 2006-2017, which included women ≥18 years of age with initial DCIS, and who were treated with surgery. Final diagnosis was divided in DCIS and microinvasive/invasive carcinoma.334 patients were included: 193 (57.8%) with DCIS and 141 (42.2%) with microinvasive/invasive carcinoma (microinvasive 5.1%, invasive 37.1%). Lymph node metastasis occurred in 16.3%. Differences between DCIS and microinvasive/invasive groups included the presence of palpable nodule (36.7% vs. 63.2%), radiological nodule (29% vs. 51%), bigger radiological-tumor size (1.2 cm vs. 1.7 cm), and larger microcalcification extension (2.5 cm vs. 3.1 cm), all of these variables p ≤0.05. Hormonal receptors and HER2 expression were similar. After logistic regression analysis, predictive factor of invasion was the presence of palpable nodule (OR = 4.072, 95%CI = 2.520-6.582, p0.001) and radiological multicentric disease (OR = 1.677, 95%CI = 1.036-2.716, p = 0.035).In patients with DCIS, palpable nodule, and radiological multicentric disease, upgrade to microinvasive/invasive is high, and sentinel lymph node is recommended.Identificar características clínicas, radiológicas e histopatológicas como factores predictivos de carcinoma mamario microinvasor/invasor en pacientes con Carcinoma Ductal In Situ (CDIS) diagnosticado mediante aguja de corte.Estudio retrospectivo de 2006–2017, en mujeres ≥18 años con CDIS diagnosticado con aguja de corte y tratadas con cirugía. Los diagnósticos finales fueron CDIS y carcinoma microinvasor/invasor.Se incluyeron 334 pacientes, 193 (57.8%) con CDIS y 141 (42.2%) con carcinoma microinvasor/invasor (microinvasor 5.1%, invasor 37.1%). Hubo 16.3% casos con afección ganglionar. Las diferencias entre el grupo de CDIS y carcinoma microinvasor/invasor fue la presencia de tumor palpable (36.7% vs. 63.2%), nódulo visto por imagen (29% vs. 51%), tumores más grandes (1.2 cm vs. 1.7 cm), y mayor extensión de microcalcificaciones (2.5 cm vs. 3.1 cm), estas variables con p ≤0.05. Los receptores hormonales y HER2 fueron similares. En el análisis de regresión logística, los factores predictivos de invasión fueron tumor palpable (OR = 4.072, IC95% = 2.520–6.582, p0.001) y multicentricidad radiológica (OR = 1.677, IC95% = 1.036–2.716, p = 0.035).En CDIS, tumor palpable y enfermedad multicéntrica radiológica, el escalamiento a carcinoma microinvasor/invasor es alto y es recomendable realizar ganglio centinela.

Objective To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients. Methods A retrospective, multicentric, observational study of VWD patients treated with Fanhdi®, a pdVWF/FVIII concentrate, from January 2011 to December 2017 was conducted at 14 centers in Spain. Efficacy and safety were evaluated for acute bleeding episodes, for prevention of bleeding in surgeries, and for secondary long-term prophylaxis. Results Seventy-two eligible patients, type 1, 2, 3 VWD (25%/38.9%/36.1%) were treated for spontaneous and traumatic bleeding (140 episodes, n = 41 patients), to prevent surgical bleeding (69 episodes, n = 43 patients); and for secondary long-term prophylaxis (18 programs, n = 13 patients). Replacement therapy with pdVWF/FVIII showed an excellent to good clinical efficacy in 96.7% of the bleeding episodes, 100% during surgical procedures and 100% during prophylaxis. No adverse events (AEs), nor serious AEs related to the product were observed. Conclusions Fanhdi® was effective, safe and well tolerated in the management of bleeding episodes, the prevention of bleeding during surgeries, and for secondary long-term prophylaxis in VWD patients.

To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients. Methods: A retrospective, multicentric, observational study of VWD patients treated with Fanhdi®, a pdVWF/FVIII concentrate, from January 2011 to December 2017 was conducted at 14 centers in Spain. Efficacy and safety were evaluated for acute bleeding episodes, for prevention of bleeding in surgeries, and for secondary long-term prophylaxis. Seventy-two eligible patients, type 1, 2, 3 VWD (25%/38.9%/36.1%) were treated for spontaneous and traumatic bleeding (140 episodes, n = 41 patients), to prevent surgical bleeding (69 episodes, n = 43 patients); and for secondary long-term prophylaxis (18 programs, n = 13 patients). Replacement therapy with pdVWF/FVIII showed an excellent to good clinical efficacy in 96.7% of the bleeding episodes, 100% during surgical procedures and 100% during prophylaxis. No adverse events (AEs), nor serious AEs related to the product were observed. Conclusions: Fanhdi® was effective, safe and well tolerated in the management of bleeding episodes, the prevention of bleeding during surgeries, and for secondary long-term prophylaxis in VWD patients, The author(s) disclosed receipt of the followingfinancial support forthe research, authorship, and/or publication of this article: This workwas supported by Grifols, manufacturer of the pdVWF/FVIII,Fanhdi®

Azathioprine is a drug widely used to treat patients with inflammatory bowel disease, with not an inconsiderable frequency of adverse events. Among these, myelotoxicity is one of the most serious. For some time, the existence of specific genetic variations of the gene encoding thiopurine-methyltransferase that affect enzymatic activity and produce alterations in thiopurine metabolism that translate into a higher frequency of adverse events in these patients has been known. It has recently been observed that patients carrying certain genetic variations in the nudix hydrolase gene also present a higher rate of adverse events induced by azathioprine, mainly related to leukopenia and alopecia, the latter behaving as an early clinical marker of myelotoxicity. These genetic variants are more common in the Asian population. We present the case of a European patient with azathioprine-induced alopecia and leukopenia whose genetic analysis confirmed that she had one of the genetic alterations associated with the appearance of these adverse events.

Introduction Surgical inferior alveolar nerve (IAN) reposition techniques offer an alternative approach to implant-based rehabilitation in patients with severe mandibular atrophy The aim of this systematic review, was to determine the complications associated with the technique and to determine which of two variants (lateralization or transposition) is less invasive. Materials and methods An electronic search was conducted in databases complimented by a manual search to identify clinical studies investigating complications derived from these surgical techniques. Only studies of adult humans, published in English during the last seven years were included. The initial search located 78 articles, of which seven were included in analysis on the basis of the following characteristics: four investigated inferior alveolar nerve lateralization (IANL), one inferior alveolar nerve transposition (IANT), and two investigated both reposition techniques. Results This review included data from 289 patients who were recruited for lateralization (N = 319) or transposition surgery (N = 33) making a total of 352 reposition procedures. Five patients (1.73%) suffered persistent damage to the IAN at the end of the follow-up periods. The overall implant survival rate was 99.26% of a total of 817 implants. The most common complications were neurosensory problems, mandibular fracture, infection, implant loss, and insufficient anatomical reconstruction of the atrophic mandible; neurosensory complications (hypoesthesia, paraesthesia, and hyperesthesia caused by traumatic damage to the nerve) were the most prevalent. Conclusions Lateralization of the inferior alveolar nerve would appear to be less invasive as it produces lower percentages of persistent neurosensory disorders (1.56%) than transposition (12.12%). Nevertheless, both techniques offer a viable approach to implant placement in edentulous atrophic mandibles, obtaining predictable clinical and radiological results after 5 years implant loading.

Introduction & objectives Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes. Methods A cross sectional, multicenter survey of hospitalized cirrhotic patients. Results 377 patients, (62% males; 58 ± 11 years) (BMI > 25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR + NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population > 500,000 (n = 45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n = 22). Conclusions The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.

Resumen: Introducción: Después de que la Organización Mundial de la Salud (OMS) declaró a la enfermedad por SARS-CoV-2 (COVID-19) pandemia, el número de pacientes con infección confirmada ha incrementado exponencialmente. Es muy probable que gastroenterólogos y otros especialistas se involucren en la atención de estos pacientes. Objetivo: Evaluar el conocimiento de gastroenterólogos y endoscopistas (adscritos y residentes) en Latinoamérica sobre las características de COVID-19 y las medidas de prevención durante procedimientos endoscópicos. Material y métodos: Realizamos un estudio transversal que incluyó a gastroenterólogos y endoscopistas de nueve países de Latinoamérica. Se aplicó un cuestionario electrónico diseñado para valorar conocimientos sobre síntomas, grupos de riesgo para enfermedad grave, medidas de prevención y reprocesamiento de endoscopios utilizados en pacientes con COVID-19. Resultados: Se obtuvo información de 133 médicos, 95% de los encuestados identificó correctamente los síntomas más frecuentes y 60% identificó los tres grupos de riesgo para enfermedad grave. El 66% no consideró necesario usar precauciones estándar durante procedimientos endoscópicos y 30% no consideró necesarias las precauciones de contacto. El 48% desconoció el protocolo para reprocesamiento de los endoscopios en pacientes con COVID-19. Conclusión: Los signos y síntomas de COVID-19 y las poblaciones de riesgo de complicaciones son conocidos por la mayoría de los gastroenterólogos y endoscopistas. El conocimiento sobre medidas de prevención (durante atención clínica y procedimientos endoscópicos), así como el reprocesamiento del equipo endoscópico son desconocidos por 70 y 48% de los encuestados respectivamente. Se deben realizar estrategias de difusión y enseñanza que incrementen el conocimiento sobre estos aspectos de bioseguridad. Abstract: Introduction: After the World Health Organization declared the COVID-19 outbreak a pandemic, the number of patients with confirmed SARS-CoV-2 infection (COVID-19) has increased exponentially, and gastroenterologists and other specialists most likely will be involved in the care of those patients. Aim: To evaluate the knowledge Latin American gastroenterologists and endoscopists (staff physicians and residents) have about the characteristics of COVID-19, as well as the prevention measures to be taken during endoscopic procedures. Materials and methods: We conducted a cross-sectional study that included gastroenterologists and endoscopists from 9 Latin American countries. An electronic questionnaire was applied that was designed to evaluate the knowledge of symptoms, risk groups for severe disease, prevention measures, and the reprocessing of endoscopes utilized in patients with COVID-19. Results: Information was obtained from 133 physicians. Ninety-five percent of them correctly identified the most frequent symptoms of the virus, and 60% identified the 3 risk groups for severe disease. Sixty-six percent of those surveyed did not consider it necessary to use standard precautions during endoscopic procedures, and 30% did not consider contact precautions necessary. Forty-eight percent of the participants surveyed were not familiar with the protocol for reprocessing the endoscopes utilized in patients with COVID-19. Conclusion: The majority of the gastroenterologists and endoscopists surveyed were familiar with the signs and symptoms of COVID-19 and the populations at risk for complications. There was a lack of knowledge about prevention measures (during clinical care and endoscopic procedures) and the reprocessing of endoscopic equipment by 70% and 48%, respectively, of those surveyed. Dissemination and teaching strategies that increase the knowledge of specific biosafety measures must be carried out.

Irreversible electroporation (IRE) is a non-thermic ablation therapy which has been proposed for locally advanced pancreatic adenocarcinoma (LAPC) as well as for the local control of other types of tumors (kidney or liver). Its use has been extended in the last few years worldwide. Its advantage over other ablation techniques is that it only affects the lipids bilayer of the cell membrane avoiding vascular damage. Safety and viability have been demonstrated in recent studies. Overall survival seems (OS) to improve when it is combined with chemotherapy compared to chemotherapy with or without radiotherapy. Clinical trials should confirm these encouraging data.

This work investigates the transfer of motor learning from the eye to the hand and its neural correlates by using functional magnetic resonance imaging (fMRI) and a sensorimotor task consisting of the continuous tracking of a virtual target. In pretraining evaluation, all the participants (experimental and control group) performed the tracking task inside an MRI scanner using their right hand and a joystick. After which, the experimental group practiced an eye‐controlled version of the task for 5 days using an eye tracking system outside the MRI environment. Post‐training evaluation was done 1 week after the first scanning session, where all the participants were scanned again while repeating the manual pretraining task. Behavioral results show that the training in the eye‐controlled task produced a better performance not only in the eye‐controlled modality (motor learning) but also in the hand‐controlled modality (motor transfer). Neural results indicate that eye to hand motor transfer is supported by the motor cortex, the basal ganglia and the cerebellum, which is consistent with previous research focused on other effectors. These results may be of interest in neurorehabilitation to activate the motor systems and help in the recovery of motor functions in stroke or movement disorder patients.

4-HNE-modified ankyrins have been described in diseases such as diabetes, renal failure, G6PD deficient, sickle cell trait, and P. falciparum infected erythrocytes with different AB0 blood groups. However, effects at the atomic level of this carbonylation on structure and function of modified protein are not yet fully understood. We present a study based on molecular dynamics simulations of nine 4-HNE modified residues of the ZU5-ANK ankyrin domain with β-spectrin and their binding energy profiles. Results show that 4-HNE induced local conformational changes over all protein systems evaluated, increased mobility in the modification sites, and localized structural changes between the positively charged patch of the ZU5-ANK domain. Carbonylation with 4-HNE on lysine residues decreased the affinity between ZU5-ANK and the 14-β-spectrin repeat by reducing electrostatic and van der Waals interactions. The presented work provides further insight into understanding the loss of human erythrocyte deformation capacity under conditions of oxidative stress in different diseases.

Purpose To determine the differences in short- and long-term mortality in elderly septic patients with multiorgan dysfunction syndrome and establish the factors related to non-survival. Materials and methods A retrospective cohort study was made of 206 patients over 65 years of age with septic and septic shock criteria admitted to the ICU of Rio Hortega Hospital between January 2011 and February 2017. Study variables were obtained from electronic database records. Results A total of 206 patients were included, divided into three groups of age (65–74, 75–85, >85 years). There were no significant differences in mortality according to age group after 28 days, 90 days or one year (28.6%, 32.1% and 45.2% in the 65–74 years age group; 32.5%, 38.6% and 45.8% in the 75–85 years age group, 41%, 48.7% and 56.4% in the >85 years age group). The factors related to mortality were: chronic heart failure, non-haematological cancer, liver dysfunction and central nervous system dysfunction. Conclusions The results indicate that there is no significant difference in mortality among the different age groups. About 50% of the elderly patients survive a septic process. There is a close relationship between the number of affected organs and days of dysfunction, the use of interventional techniques and long-term mortality.

Background Gastrointestinal complications after lung transplatation are associated with an increased risk of morbidity and mortality. This study aims to describe severe gastrointestinal complications (SGC) after lung transplantation. Methods We performed a prospective, observational study that included 136 lung transplant patients during a seven year period in a tertiary care universitary hospital. SGC were defined as any diagnosis related to the gastrointestinal or biliary tract leading to lower survival rates or an invasive therapeutic procedure. Early and late complications were defined as those occurring p Results There were 17 (12.5%) SGC in 17 patients. Five were defined as early. Twelve patients (70.6%) required surgical treatment. Mortality was 52.9% (n = 9). Patients with SGC had a lower overall survival rate compared to those who did not (14 vs 28 months, p = 0.0099). The development of arrhythmias in the first 48 h of transplantation was a risk factor for gastrointestinal complications (p = 0.0326). Conclusions SGC are common after lung transplantation and are associated with a considerable increase in morbidity-mortality. Early recognition is necessary to avoid delays in treatment, since a clear predictor has not been found in order to forecast this relevant comorbidity.

Cognitive dysfunction is a disabling complication in Parkinson's disease (PD). Accuracy of diagnosis of mild cognitive impairment in PD (PD-MCI) depends on the tests performed, which limits results generalization. Blood-based biomarkers could provide additional objective information for PD-MCI diagnosis and progression. Blood neurofilament light chain (NfL), a marker of neuronal injury, has shown good performance for PD disease stratification and progression. While NfL is not disease-specific, phosphorylated-tau at threonine-181 (p-tau181) in blood is a highly specific marker of concomitant brain amyloid-β and tau pathology.We investigated the potential of plasma NfL and p-tau181 levels as markers of cognitive impairment in a prospective cohort of 109 PD patients with and without PD-MCI (age 68.1 ± 7 years, education 12.2± 5 years), and 40 comparable healthy controls. After a follow-up of 4 years, we evaluated their predictive value for progression to dementia.Although NfL and p-tau181 levels were significantly increased in PD compared with healthy controls, only NfL levels were significantly higher in PD-MCI compared with PD with normal cognition (PD-NC) at baseline. After a follow-up of 4 years, only NfL predicted progression to dementia (HR 1.23, 95% CI 1.02-1.53; p = 0.038). Significant correlations between fluid biomarkers and neuropsychological examination were only found with NfL levels.Plasma NfL levels objectively differentiates PD-MCI from PD-NC patients, and may serve as a plasma biomarker for predicting progression to dementia in PD. Plasma levels of p-tau181 does not seem to help in differentiating PD-MCI or to predict future cognitive deterioration.

Helicobacter pylori (H. pylori) infection is associated with various gastrointestinal diseases and is the dominant microorganism in gastric microbiota. There are multiple therapeutic combinations used with uneven results for eradication. Studies have been carried out with some strains of Lactobacillus (L) that support its preponderant role in the treatment of infection and reduction of inflammation.

In Alzheimer’s disease, two fundamental aspects become important for caregivers: ambiguity and ambivalence. Thus, anticipatory grief is considered an active psychological process that is very different from the mere anticipation of death. The present study aims to determine which characteristics of family caregivers of people with dementia, such as age, gender, educational level, relationship with the person with dementia, years with dementia or years as a caregiver, are related to the presence of anticipatory grief. A cross-sectional design was employed. The sample consisted of a total of 129 subjects who cared for a family member with dementia. A sociodemographic data sheet and a battery of tests measure the presence of anticipatory grief, caregiver burden and/or psychopathology. The results obtained allowed us to confirm some of the hypotheses regarding the anticipatory grief construct, the importance of the care time factor, in years and per day, as well as the relevance of the previous demographic and psychopathological profile (being female, spouse function and possible depressive symptomatology). Likewise, from the prediction analyzes performed, it seems that these variables can predict anticipatory grief. These results propose interesting opportunities to formulate care proposals to professionals and family caregivers in relation to care tasks and caregiver skills.

Survivors to COVID-19 have described long-term symptoms after acute disease. These signs constitute a heterogeneous group named long COVID or persistent COVID. The aim of this study is to describe persisting symptoms 6 months after COVID-19 diagnosis in a prospective cohort in the Northwest Spain. This is a prospective cohort study performed in the COHVID-GS. This cohort includes patients in clinical follow-up in a health area of 569,534 inhabitants after SARS-CoV-2/COVID-19 diagnosis. Clinical and epidemiological characteristics were collected during the follow up. A total of 248 patients completed 6 months follow-up, 176 (69.4%) required hospitalization and 29 (10.2%) of them needed critical care. At 6 months, 119 (48.0%) patients described one or more persisting symptoms. The most prevalent were: extra-thoracic symptoms (39.1%), chest symptoms (27%), dyspnoea (20.6%), and fatigue (16.1%). These symptoms were more common in hospitalized patients (52.3% vs. 38.2%) and in women (59.0% vs. 40.5%). The multivariate analysis identified COPD, women gender and tobacco consumption as risk factors for long COVID. Persisting symptoms are common after COVID-19 especially in hospitalized patients compared to outpatients (52.3% vs. 38.2%). Based on these findings, special attention and clinical follow-up after acute SARS-CoV-2 infection should be provided for hospitalized patients with previous lung diseases, tobacco consumption, and women.

Epidemiological models have played a central role in the COVID-19 pandemic, particularly when urgent decisions were required and available evidence was sparse. They have been used to predict the evolution of the disease and to inform policy-making. In this paper, we address two kinds of epidemiological models widely used in the pandemic, namely, compartmental models and agent-based models. After describing their essentials—some real examples are invoked—we discuss their main strengths and weaknesses. Then, on the basis of this analysis, we make a comparison between their respective merits concerning three different goals: prediction, explanation, and intervention. We argue that there are general considerations which could favour any of those sorts of models for obtaining the aforementioned goals. We conclude, however, that preference for particular models must be grounded case-by-case since additional contextual factors, as the peculiarities of the target population and the aims and expectations of policy-makers, cannot be overlooked.