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Study Objective To study the progression of benign ovarian lesions to mucinous borderline ovarian tumors (mBOTs); analyze the clinicopathologic features, diagnosis, and management of mBOTs in pediatric and adolescent girls; and provide a review of the literature on mBOTs in this population. Design Retrospective chart review of female adolescents younger than age 18 years diagnosed with mBOTs between July 2017 and February 2021. Setting Yale New Haven Hospital, New Haven, Connecticut; and Yale New Haven Health Bridgeport Hospital, Bridgeport, Connecticut. Participants Three female patients diagnosed with mBOTs between ages 12 and 17 years. Interventions None. Main Outcome Measures Clinical presentation, preoperative characteristics, surgical technique, histology, tumor stage, treatment, progression, outcome, and rate of recurrence. Results Three adolescent patients were identified to have mBOTs. All three patients presented with a chief complaint of abdominal pain. One of the three patients was premenarchal at presentation. Two of the three patients were initially diagnosed with a mucinous cystadenoma and had recurrences of an ovarian cyst in the same ovary within five and 17 months. Pathology of the recurrent cyst was consistent with mBOT. Two of the three patients initially underwent cystectomy, and all ultimately had a unilateral salpingo-oophorectomy. Subsequent surveillance over two to four years was without evidence of disease recurrence. Conclusion mBOTs are rare in the pediatric and adolescent population and may arise from benign ovarian tumors.

Acute traumatic coagulopathy (ATC) occurs in approximately 30% of patients with trauma and is associated with increased mortality. Excessive generation of activated protein C (APC) and hyperfibrinolysis are believed to be driving forces for ATC. Two mouse models were used to investigate whether an engineered activated FV variant (superFVa) that is resistant to inactivation by APC and contains a stabilizing A2-A3 domain disulfide bond can reduce traumatic bleeding and normalize hemostasis parameters in ATC. First, ATC was induced by the combination of trauma and shock. ATC was characterized by activated partial thromboplastin time (APTT) prolongation and reductions of factor V (FV), factor VIII (FVIII), and fibrinogen but not factor II and factor X. Administration of superFVa normalized the APTT, returned FV and FVIII clotting activity levels to their normal range, and reduced APC and thrombin-antithrombin (TAT) levels, indicating improved hemostasis. Next, a liver laceration model was used where ATC develops as a consequence of severe bleeding. superFVa prophylaxis before liver laceration reduced bleeding and prevented APTT prolongation, depletion of FV and FVIII, and excessive generation of APC. Thus, prophylactic administration of superFVa prevented the development of ATC. superFVa intervention started after the development of ATC stabilized bleeding, reversed prolonged APTT, returned FV and FVIII levels to their normal range, and reduced TAT levels that were increased by ATC. In summary, superFVa prevented ATC and traumatic bleeding when administered prophylactically, and superFVa stabilized bleeding and reversed abnormal hemostasis parameters when administered while ATC was in progress. Thus, superFVa may be an attractive strategy to intercept ATC and mitigate traumatic bleeding.

BACKGROUND: Older adults are under-represented in cancer clinical trials. However, it remains unclear which types of trials under-enroll aging patients. We aimed to identify associations between trial characteristics and disparate enrollment of older adults onto trials sponsored by the Alliance for Clinical Trials in Oncology (Alliance). METHODS: Actual age ≥ 65 percentage and trial data were extracted from the Alliance closed study list. Each trial, based on its cancer type and years of enrollment, was assigned an expected age ≥ 65 percentage extracted from the Surveillance, Epidemiology, and End Results (SEER) US population-based database. Enrollment disparity difference (EDD), the difference between the expected age ≥ 65 percentage and the actual age ≥ 65 percentage, was calculated for each trial. Linear regression determined trial variables associated with larger EDDs and variables with an overall association p-value < 0.20 were included in a multivariable fixed-effects linear model. RESULTS: The median age of 66,708 patients across 237 trials was 60 years (range 18-102). The average actual age ≥ 65 percentage enrolled per trial was lower than each trial’s expected age ≥ 65 percentage average (39% vs. 58%; EDD 19, 95% CI 17.1-21.3%, p

Food system is a powerful concept for understanding and responding to nutrition and sustainability challenges. Food systems integrate social, economic, environmental and health aspects of food production through to consumption. Aquatic foods are an essential part of food systems providing an accessible source of nutrition for millions of people. Yet, it is unclear to what degree research across diverse disciplines concerning aquatic foods has engaged food systems, and the value this concept has added. We conducted a systematic review of fisheries, aquaculture and aquatic food literature (2017–2019) to determine the following: the characteristics of this research; the food systems components and interrelations with which research engaged; and the insights generated on nutrition, justice, sustainability and climate change. Sixty five of the 88 reviewed articles focussed on production and supply chains, with 23 considering human nutrition. Only 13% of studies examined low- and middle-income countries that are most vulnerable to undernutrition. One third of articles looked beyond finfish to other aquatic foods, which illuminated values of local knowledge systems and diverse foods for nutrition. When aggregated, reviewed articles examined the full range of food system drivers—biophysical and environmental (34%), demographic (24%) and socio-cultural (27%)—but rarely examined interactions between drivers. Future research that examines a diversity of species in diets, system-wide flows of nutrients, trade-offs amongst objectives, and the nutritional needs of vulnerable social groups would be nudging closer to the ambitions of the food systems concept, which is necessary to address the global challenges of equity, nutrition and sustainability.

PURPOSE: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. METHODS: Individual-level data was pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36-months after. Cognitive performance was assessed with objective (working memory, processing speed and executive functions) and subjective tests and physical, emotional and functional well-being was also assessed. RESULTS: One hundred and sixty-seven (M age = 67.3 years) women, with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36-months. Measures of well-being improved from prior to systemic therapy to 12-months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. CONCLUSION: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.

Religion and spirituality are important aspects of culture that can interact with mental health. They can also be central components of women's experiences during pregnancy and the postpartum period. This study aims to explore the role of religion and spirituality among women experiencing severe psychopathology during the perinatal period using qualitative interviews of women hospitalized during pregnancy or postpartum on an inpatient unit in the Southeast USA. The average age of participants was 34.2 and all identified as white, aside from one who identified as other. Though religious affiliation was varied, most participants were Christian. Each patient interviewed had a diagnosis of depressive disorder, among other comorbid diagnoses. Three main themes emerged in the subsequent analyses (1) spirituality providing a sense of healing and connectedness above and beyond religion, (2) patients seeking support from religious leaders, and (3) patients experiencing familial pressure to enact religion in a certain way, especially as it relates to child rearing. Clinical implications for each of the themes are explored.

Objective To retrospectively evaluate the outcomes of immediate artificial urinary sphincter (AUS) reactivation in patients after urethral cuff replacement. It is common practice to delay reactivation of an AUS for four to six weeks following surgery to replace a failed urethral cuff. This is due to concerns about local tissue edema risking obstruction and concerns for urethral erosion. Despite these concerns, there are no published data to support this practice. Methods Retrospective chart review of single surgeon procedures performed from 2005-2020. Patients with urethral cuff replacement for recurrent stress incontinence due to compression or mechanical failure were included. Results Thirty-four patients were identified who had immediate reactivation of the AUS following urethral cuff exchange. Thirty of these patients (88.2%) had radical prostatectomy and five patients also underwent further radiation therapy (14.7%). At 6 months follow-up, there was no reported events of erosion. Likewise, 32/34 (94%) of patients had no complications and reported expected urinary function of the AUS. Urinary retention was not observed. One patient required further re-exploration for a complication within his AUS system (2.9%), and another was ultimately unsatisfied with their unchanged baseline continence despite a fully functioning AUS (2.9%). Conclusion In this series, we observe that immediate reactivation of the AUS after urethral cuff exchange is a safe and reasonable management approach. Limitations of this analysis include a single institution, retrospective study. However, early AUS reactivation after device revision has not been reported in the literature and warrants further investigation given the impact on patient quality of life.

Background Diffuse intrinsic pontine glioma (DIPG) remains a clinico-radiologic diagnosis without routine tissue acquisition. Reliable imaging distinction between DIPG and other pontine tumors with potentially more favorable prognoses and treatment considerations is essential. Methods Cases submitted to the International DIPG registry (IDIPGR) with histopathologic and/or radiologic data were analyzed. Central imaging review was performed on diagnostic brain MRIs (if available) by two neuro-radiologists. Imaging features suggestive of alternative diagnoses included nonpontine origin, Results Among 286 patients with pathology from biopsy and/or autopsy, 23 (8%) had histologic diagnoses inconsistent with DIPG, most commonly nondiffuse low-grade gliomas and embryonal tumors. Among 569 patients with centrally-reviewed diagnostic MRIs, 40 (7%) were classified as non-DIPG, alternative diagnosis suspected. The combined analysis included 151 patients with both histopathology and centrally-reviewed MRI. Of 77 patients with imaging classified as characteristic of DIPG, 76 (99%) had histopathologic diagnoses consistent with DIPG (infiltrating grade II-IV gliomas). Of 57 patients classified as likely DIPG with some unusual imaging features, 55 (96%) had histopathologic diagnoses consistent with DIPG. Of 17 patients with imaging features suggestive of an alternative diagnosis, eight (47%) had histopathologic diagnoses inconsistent with DIPG (remaining patients were excluded due to nonpontine tumor origin). Association between central neuro-imaging review impression and histopathology was significant (p < 0.001), and central neuro-imaging impression was prognostic of overall survival. Conclusions The accuracy and important role of central neuro-imaging review in confirming the diagnosis of DIPG is demonstrated.

Objective To examine infertility-related fund-raising campaigns on a popular crowdfunding website and to compare campaign characteristics across states with and without legislative mandates for insurance coverage for infertility-related care. Design Retrospective cohort study. Setting Online crowdfunding platform (GoFundMe) between 2010 and 2020. Patient(s) GoFundMe campaigns in the United States containing the keywords “fertility” and “infertility.” Intervention(s) State insurance mandates for infertility treatment coverage. Main Outcome Measure(s) Primary outcomes included fund-raising goals, funds raised, campaign location, and campaigns per capita. Result(s) Of the 3,332 infertility-related campaigns analyzed, a total goal of $52.6 million was requested, with $22.5 million (42.8%) successfully raised. The average goal was $18,639 (standard deviation [SD] $32,904), and the average amount raised was $6,759 (SD $14,270). States with insurance mandates for infertility coverage had fewer crowdfunding campaigns per capita (0.75 vs. 1.15 campaigns per 100,000 population than states without insurance mandates. Conclusion(s) We found a large number of campaigns requesting financial assistance for costs associated with infertility care, indicating a substantial unmet financial burden. States with insurance mandates had fewer campaigns per capita, suggesting that mandates are effective in mitigating this financial burden. These data can inform future health policy legislation on the state and federal levels to assist with the financial burden of infertility.

Introduction and aims: The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period. Materials and methods: Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005–2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated. Results: A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn’s disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. Conclusions: Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications. Resumen: Introducción y objetivos: El objetivo primario fue explorar la tendencia epidemiológica de la enfermedad intestinal inflamatoria pediátrica en América Latina; los secundarios, obtener una visión general del enfoque diagnóstico/terapéutico de miembros de la SLAGHNP y explorar la relación entre la frecuencia de casos y los años del período evaluado. Material y métodos: Se realizó una encuesta en línea a pediatras gastroenterólogos de América Latina con la plataforma SurveyMonkey. Se preguntó la frecuencia anual de pacientes nuevos de 2005 a 2016, su variedad, los segmentos del tubo digestivo afectados, los métodos de diagnóstico y el tratamiento utilizado. Se evaluó la correlación entre la frecuencia anual y los años de estudio. Resultados: Se estudió a 607 pacientes; el diagnóstico de colitis ulcerativa se realizó en 475 (78.3%), de enfermedad de Crohn en 104 (17.1%) y de enfermedad intestinal inflamatoria no clasificable en 28 (4.6%). La tendencia de colitis ulcerativa tuvo un incremento lineal con coeficiente de correlación significativo entre la frecuencia de casos nuevos y el año de estudio; 67.6% tuvieron pancolitis. Los métodos de diagnóstico incluyeron datos clínicos, endoscopia y biopsias en más del 99% de los casos; los estudios de imagen se indicaron de manera selectiva. Los esquemas farmacológicos se circunscribieron a derivados del ácido 5-aminosalicílico, azatioprina, 6-mercaptopurina, infliximab y adalimumab. Conclusiones: La enfermedad intestinal inflamatoria pediátrica en América Latina parece incrementarse en el período estudiado con predominio de formas moderadas o graves de colitis ulcerativa; esta tendencia lineal puede indicar la posibilidad predictiva de incremento gradual en la próxima década, lo que es probable que tenga implicaciones epidemiológicas y clínicas.

Introduction: Although IgA nephropathy (IgAN) is the most common recurrent glomerulonephritis encountered in the kidney allograft, the clinical and immunogenetic characteristics remain poorly understood. We sought to study determinants and prognosis of recurrent IgAN with special focus on human leukocyte antigens (HLAs). Materials and Methods: Between 2005 and 2019, we identified 282 transplanted patients with failure secondary to IgAN from 2 North American and 1 European Medical Centers, including 80 with recurrent IgAN and 202 without recurrence. The prevalence of HLAs was compared to external healthy controls of European ancestry (n = 15,740). Graft survival was assessed by the Kaplan-Meier method and log rank test. Cox proportional hazards were used for multivariable analyses. Results: Compared to external controls of European ancestry, kidney transplant recipients of European ancestry with kidney failure secondary to IgAN had higher frequency of HLA-DQ5 (42% vs. 30%, OR = 1.68, p = 0.002) and lower frequency of HLA-DR15 (15% vs. 28%, OR = 0.46, p < 0.001) and HLA-DQ6 (32% vs. 45%, OR = 0.59, p = 0.003); however, the frequency of these HLAs were similar in recurrent versus nonrecurring IgAN. Younger recipient age at transplantation was an independent predictor of recurrence. HLA matching was an independent predictor for recurrent IgAN only in recipients of living-related but not deceased or living-unrelated transplants. Recurrent IgAN was an independent predictor of allograft failure, along with acute rejection. In patients with recurrent IgAN, serum creatinine at biopsy, degree of proteinuria, and concurrent acute rejection were associated with inferior allograft survival. Conclusion: Recurrent IgAN negatively affects allograft survival. Younger recipient age at transplantation is an independent predictor of recurrent IgAN, while the presence of HLAs associated with IgAN in the native kidney and HLA matching in recipients of deceased or living-unrelated transplants are not.

PurposeOlder cancer survivors required medical care during the COVID-19 pandemic despite infection risks, but there are limited data on medical care in this age group. Methods. We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors ages 60-98 from five US regions (n=321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included self-reported interruptions in ability to see doctors, receive treatment or supportive therapies, or fill prescriptions. Logistic regression models evaluated bivariate and multivariate associations between care disruptions and education, medical, psychosocial and COVID-19-related factors. Multivariate models included age, county COVID-19 rates, comorbidity and post-diagnosis time. Results. There was a high response rate (n=262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were significantly higher with more education (OR 1.23 per one-year increase, 95% CI 1.09-1.39, p =0.001) and greater depression (OR 1.04 per one-point increase in CES-D score, CI 1.003-1.08, p=0.033); tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99 per one-point increase, p=0.012). There was a trend for associations between disruptions and comorbidity (unadjusted OR 1.13 per 1 added comorbidity, 95% CI 0.99-1.29, p=0.07). Adjusting for covariates, only higher education (p=0.001) and tangible social support (p=0.006) remained significantly associated with having care disruptions. Conclusions. Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.

Introduction Treatment burden is emerging as an important patient-centered outcome for older adults with cancer who concurrently manage geriatric conditions. Our objective was to evaluate the contribution of geriatric conditions to treatment burden in older adults with non-muscle invasive bladder cancer (NMIBC). Methods We identified 73,395 Medicare beneficiaries age 66+ diagnosed with NMIBC (Stage Results At baseline, 64% had multimorbidity and median 3 conditions (IQR 0–5). Prevalence of other geriatric conditions ranged from 5.9%–15.2%. Adjusted mean health system contact was 8.9 days (95% CI 8.6–9.2). Multimorbidity had the largest effect size (adjusted mean 11.8 contact days (95% CI 8.3–8.8)). Each additional chronic condition conferred a 13% increased average number of health system contact (adjusted IRR 1.132, 95% CI 1.129–1.135). Regardless of number of chronic conditions, rural patients consistently had more treatment burden than urban counterparts. Discussion In this population-based cohort of older NMIBC patients, multimorbidity and rurality were strongly associated with treatment burden in the year following NMIBC diagnosis. These findings highlight the need for interventions that reduce treatment burden due to geriatric conditions among the growing population of older adults with cancer, particularly in rural areas.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Background High macular pigment optical density (MPOD) has been associated with improved eye health and better cognitive functions. Genetic variations have been associated with MPOD in adults. However, these associations between genetic variations and MPOD have not been studied in children. Objectives This was a secondary analysis of the FK2 (Fitness Improves Thinking in Kids 2) trial (n = 134, 41% male). The aim was to determine differences in MPOD among children (aged 7-9 y) based on genetic variants that either are biologically relevant to lutein (L) and zeaxanthin (Z) accumulation or have been associated with MPOD in adults. Methods MPOD was measured using customized heterochromatic flicker photometry via a macular densitometer. DXA was used to assess whole-body and visceral adiposity. DNA was extracted from saliva samples and was genotyped for 26 hypothesis-driven single nucleotide polymorphisms and 75 ancestry-informative markers (AIMs). Habitual diet history was obtained via 3-d food logs completed by parents (n = 88). General linear models were used to compare MPOD between different genotypes. Principal component analysis was performed for the AIMs to account for ethnic heterogeneity. Results Children carrying ≥1 minor allele on β-carotene-15,15'-monooxygenase (BCO1)-rs7501331 (T allele) (P = 0.045), cluster of differentiation 36(CD36)-rs1527483 (T allele) (P = 0.038), or CD36-rs3173798 (C allele) (P = 0.001) had significantly lower MPOD (range: 14.1%-26.4%) than those who were homozygotes for the major alleles. MPOD differences based on CD36-rs3173798 genotypes persisted after adjustment for dietary L and Z intake. Conclusions The findings indicate that genetic variations of CD36 and BCO1 contribute to MPOD in children. The influence of genetic variation in CD36-rs3173798 persisted after adjusting for variation in dietary intake.This trial was registered at clinicaltrials.gov as NCT01619826.

Allograft survival of deceased donor kidneys with suboptimal histology (DRTx/suboptimal histology: >10% glomerulosclerosis, >10% tubulointerstitial scarring, or >mild vascular sclerosis) is inferior to both DRTx with optimal histology (DRTx/optimal histology) and living donor kidneys irrespective of histologic changes (LRTx). In this report, we explored the reasons behind this guarded outcome with a special focus on the role of alloimmunity. We initially assessed gene expression in 39 time-zero allograft biopsies using the Nanostring 770 genes PanCancer Immune Profiling Panel. Subsequently, we studied 696 consecutive adult kidney allograft recipients that were grouped according to allograft type and histology at time-zero biopsy [DRTx/suboptimal histology (n = 194), DRTx/optimal histology (n = 166), and LRTx (n = 336)]. Part-1: Several immune pathways were upregulated in time-zero biopsies from DRTx/suboptimal histology (n = 11) compared to LRTx (n = 17) but not to DRTx/optimal histology (n = 11). Part-2: Amongst the three groups of recipients, DRTx/suboptimal histology had the highest incidence of acute rejection episodes, most of which occurred during the first year after transplantation (early rejection). This increase was mainly attributed to T cell mediated rejection, while the incidence of antibody-mediated rejection was similar amongst the three groups. Importantly, early acute T cell mediated rejection was a strong independent predictor for allograft failure in DRTx/suboptimal histology (adjusted HR: 2.13, P = 0.005) but not in DRTx/optimal histology nor in LRTx. Our data highlight an increased baseline immunogenicity in DRTx/suboptimal histology compared to LRTx but not to DRTx/optimal histology. However, our results suggest that donor chronic histologic changes in DRTx may help transfer such increased baseline immunogenicity into clinically relevant acute rejection episodes that have detrimental effects on allograft survival. These findings may provide a rationale for enhanced immunosuppression in recipients of DRTx with baseline chronic histologic changes to minimize subsequent acute rejection and to prolong allograft survival.

Shortage of organs for liver transplantation (LT) and the availability of highly efficient pan-genotypic direct-acting antivirals (DAAs) against hepatitis C virus (HCV) have allowed the use of livers from HCV-positive antibody/negative nucleic acid test donors (dHCV Ab+/NAT-) into aviremic HCV recipients over the last few years. We report the case of a patient who received an LT from an HCV Ab+/NAT- donor and, after HCV viremic conversion, developed a nephrotic syndrome due to a focal proliferative glomerulonephritis early after LT. Patient's renal function and proteinuria resolved after successful treatment with DAAs. Renal and hepatic function remain normal over 24 months of follow-up. This case restates the success of LT using livers from dHCV Ab+/NAT- in aviremic recipients in the context of DAAs while illustrating the risk for potential complications associated with the HCV transmission and reinforcing the importance of early initiation of anti-HCV therapy.

In response to the coronavirus disease-2019 (COVID-19) pandemic, we developed and launched a student-led telemedicine program in Chelsea. From April to November 2020, over 200 student volunteers contacted over 1000 patients to assess COVID-19 symptoms, provide counseling, and triage patients. Through a retrospective cohort study, we determined that student triage decision was associated with patient outcomes, including hospitalization status, COVID-19 test administration, and COVID-19 test result. These results quantify the outcomes of a student-led telemedicine clinic to combat the ongoing pandemic and may serve as a model for implementation of similar clinics to alleviate mounting health care system burden.

To determine the efficacy and safety of inferior vena cava (IVC) filters in preventing pulmonary embolism (PE) in high-risk patients undergoing hip or knee arthroplasty.2857 hip or knee arthroplasty procedures between January 2013 and December 2018 were retrospectively reviewed. Patients with a preoperative history of venous thromboembolism (VTE), either PE or deep venous thrombosis (DVT), were categorized as high-risk patients. The incidence of overall VTE, PE, and DVT were compared between patients with filters and those without. The subgroup analysis was also performed by patient risk, and filter status and the incidence of VTE, PE, and DVT were compared. Variables such as filter placement, history of hypercoagulability etcetra were evaluated as risk factors for the development of postoperative VTE.In the high-risk group, the use of IVC filters was significantly associated with a lower incidence of pulmonary embolism (0.8% vs 5.5%, P = .028). When compared with the low-risk group, the high-risk group had significantly higher incidence of PE (3.8% vs 2.0%, P = .038), DVT (11.6% vs 5.3%, P.001), and overall VTE (15.0% vs 6.8%, P.001). The history of VTE was associated with postoperative VTE (P.001), PE (P = .042), and DVT (P.001). There was no significant correlation between filter placement and postoperative VTE, DVT, or PE in the low-risk group. Filter retrieval was successful in 100% (96/96) of attempted patients with no complications.The use of IVC filters is significantly associated with a lower incidence in pulmonary embolism in high-risk arthroplasty patients. High-risk patients demonstrated an incidence of postoperative VTE over two times greater than other patients. Prophylactic placement of IVC filters in hip/knee arthroplasty is safe.

Background Cancer patients incur high care costs; however, there is a paucity of literature characterizing unmet financial obligations for patients with urologic cancers. Kidney cancer patients are particularly burdened by costs associated with novel systemic treatments. This study aimed to ascertain the characteristics of GoFundMe® crowdfunding campaigns for patients with kidney cancer, in order to better understand the financial needs of this population. Methods We performed a cross‐sectional, quantitative, and qualitative analysis of all kidney cancer GoFundMe® campaigns since 2010. Fundraising metrics such as goal funds and amount raised, were extracted. Eight independent investigators collected patient, disease and campaign‐level variables from campaign stories (κ = 0.72). In addition, we performed a content analysis of campaign narratives spotlighting the primary appeal of the patient's life story. Results A total of 486 GoFundMe® kidney cancer campaigns were reviewed. The median goal funds were 10,000USD [IQR = 5000, 20,000] and the median amount raised was 1450USD [IQR = 578, 4050]. Most campaigns were for adult males (53%) and 62% of adults had children. A minority were for pediatric patients (17%). Thirty‐seven percent of adult patients were primary wage earners and 43% reported losing their job or substantially reducing hours due to illness. Twenty‐nine percent reported no insurance or insufficient coverage. Campaigns most frequently sought funds for medical bills (60%), nonmedical bills (27%), and medical travel (23%). Qualitative campaign narratives mostly emphasized patients’ hardship (46.3%) or high moral character (35.2%). Only 8% of campaigns achieved their target funds. Conclusions Despite fundraising efforts, patients with kidney cancer face persistent financial barriers, incurring both medical and nonmedical cost burdens. This may be compounded by limited or no insurance. Cancer care providers should be aware of financial constraints placed on kidney cancer patients, and consider how these may impact treatment regimens., This work spotlights online crowdfunding campaigns for patients with kidney cancer. By elucidating patient and campaign characteristics, we are able to better understand the financial needs of this population.

Background: During pregnancy and in the postpartum period women are at increased risk of venous thromboembolism (VTE) owing to hypercoagulability and mechanical issues, as well as nonpregnancy conditions including inherited and acquired thrombophilia. Although guidelines exist for the use of thromboprophylaxis in this setting, there are differences in the specifics of the recommendations among expert societies. We assessed the current practice patterns of North American providers in the prevention of pregnancy-associated VTE in women with thrombophilia. Methods: A survey was created and distributed with case studies and questions addressing VTE prevention during the antepartum and postpartum periods. Results: Surveys were completed by 28% of adult providers queried, with broad geographic representation. There was consistent use of a prophylactic dose of low-molecular weight heparin (LMWH) ante- and postpartum for individuals with low-risk thrombophilia and past estrogen-provoked VTE but a lack of a consensus of anticoagulant (AC) use and dose in individuals with higher risk thrombophilia. There was variability in the dose selection and monitoring of AC when using induction versus spontaneous labor, with 47% of providers switching from LMWH to unfractionated heparin for those not having a scheduled delivery, and there were differences in the duration of postpartum prophylaxis based upon delivery mode. Conclusion: In this survey of North American experienced specialists' responses to a variety of commonly encountered scenarios of thrombophilia and pregnancy and the management of AC were not always consistent with published guidelines.

Background: Two primary care clinics implemented an opioid use disorder (OUD) treatment program that integrates behavioral health counseling with buprenorphine treatment and uses tiers. This project aimed to understand how patients moved through tiers in this program. Method: We purposively sampled 20 patients with at least 10 OUD-related treatment visits; we documented tier changes at all visits between September 1, 2016 and December 31, 2018 using a standard data collection instrument. These data were used to construct run-charts. Results: About 45% of sampled patients had at least one relapse noted and 60% of patients dropped in tier during the study. Reductions in tier often happened when the patient was navigating difficult psychosocial situations in their life, whereas increases in tier often accompanied positive life events. We also found variation in use of the tiers. Discussion: OUD treatment from two clinics by tier illustrates that recovery is an individualized process based on patient need that can fluctuate due to psychosocial triggers and significant life events. Having tiers can guide treatment and provide both clinicians and patients with information about what to expect during treatment while still allowing the flexibility to meet patients where they are. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS-CoV-2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS-CoV-2 infection who underwent antibody testing with a single commercially available anti-nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. Seventy SOT recipients were studied (56% kidney, 19% lung, 14% liver ± kidney, and 11% heart ± kidney recipients). Thirty-six (51%) had positive anti-nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared to those who did not receive a kidney (p = .04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p = .002) and baseline immunosuppression with more than two agents (OR 0.26, p = .03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51% of patients had detectable anti-nucleocapsid antibodies, and transplant-related variables including the level and nature of immunosuppression were important predictors. These findings raise the concern that SOT recipients with COVID-19 may be less likely to form SARS-CoV-2 antibodies.

Background The coronavirus disease 2019 (COVID‐19) pandemic has had wide‐ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic. Methods The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web‐based or telephone COVID‐19 survey, between May 27 and September 11, 2020. Mixed‐effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies–Depression [CES‐D] scale) from before to during the pandemic in survivors versus controls and to test survivor‐control differences in the associations between changes in loneliness and changes in mental health, including depression (CES‐D, excluding the loneliness item), anxiety (the State‐Trait Anxiety Inventory), and perceived stress (the Perceived Stress Scale). Models were adjusted for age, race, county COVID‐19 death rates, and time between assessments. Results Loneliness increased from before to during the pandemic (0.211; P = .001), with no survivor‐control differences. Increased loneliness was associated with worsening depression (3.958; P < .001) and anxiety (3.242; P < .001) symptoms and higher stress (1.172; P < .001) during the pandemic, also with no survivor‐control differences. Conclusions Cancer survivors reported changes in loneliness and mental health similar to those reported by women without cancer. However, both groups reported increased loneliness from before to during the pandemic that was related to worsening mental health, suggesting that screening for loneliness during medical care interactions will be important for identifying all older women at risk for adverse mental health effects of the pandemic., Older breast cancer survivors and matched noncancer controls experienced similar increases in loneliness from before to during the COVID‐19 pandemic. Women who reported increased loneliness also experienced worsening depression and anxiety symptoms and higher stress during the pandemic.

Infertility is a global health problem affecting 10-15% of couples in reproductive age. Recent studies have provided growing evidence supporting that lifestyle factors can affect male fertility through alterations in endocrine profiles, spermatogenesis and/or sperm function. One of these critical factors could be the change in the food intake behavior in modern societies that produces metabolic alterations. Regarding this, metabolic syndrome (MetS) prevalence has increased in epidemic in the last 40-50 years. Although MetS is associated with advanced age, changes in lifestyles have accelerated the appearance of symptoms in the reproductive age. We review herein the current understanding of the relationship between MetS and the male reproductive status. For this purpose, in this narrative review a comprehensive literature search was made in both animal models and men, allowing us to evaluate such relationship. This analysis showed a high variability in the reproductive phenotypes observed in patients and mice suffering MetS, including sperm parameters, fertility and offspring health. In view of this, we proposed that the reproductive effects, which are diverse and not robust, observed among MetS-affected males, might depend on additional factors not associated with the metabolic condition and contributed not only by the affected male but also by his partner. With this perspective, this review provides a more accurate insight of this syndrome critical for the identification of specific diagnostic indicators and treatment of MetS-induced fertility disorders.

Background Despite the prevalence of hypocoagulability after injury, the majority of trauma patients paradoxically present with elevated thrombin generation (TG). While several studies have examined plasma TG post-injury, this has not been assessed in whole blood. We hypothesize that whole blood TG is lower in hypocoagulopathy, and TG effectively predicts massive transfusion. Study Design Blood was collected from trauma activation patients at an urban Level-1 trauma center. Whole blood TG was performed with a prototype point-of-care device. Whole blood TG values in healthy volunteers were compared to trauma patients, and TG values were examined in trauma patients with shock and massive transfusion requirement (MT). Results Overall, 118 patients were included (Table 1). Compared to healthy volunteers, trauma patients overall presented with more robust TG; however, those arriving in shock (n=23) had a depressed TG, with significantly lower peak thrombin (88.3 versus 133.0 nM, p=0.01) and slower maximum rate of thrombin generation (27.4 versus 48.3 nM/min, p=0.04). Patients who required massive transfusion (n=26) had significantly decreased TG, with a longer lag time (median 4.8 min versus 3.9 min, p=0.04), decreased peak thrombin (median 71.4 nM versus 124.2 nM, p=0.0003), and lower maximum rate of TG (median 15.8 nM/min versus 39.4 nM/min, p=0.01). AUROC analysis revealed lag time (AUROC 0.6), peak thrombin (AUROC 0.7), and maximum rate of TG (AUROC 0.7) predict early MT. Conclusion These data challenge the prevailing bias that all trauma patients present with elevated TG and highlight that deficient thrombin contributes to the hypocoagulopathic phenotype of trauma-induced coagulopathy. Further, whole blood TG predicts massive transfusion, suggesting point of care whole blood TG may be a useful tool for diagnostic and therapeutic strategies in trauma.

To compare overall survival (OS) in patients who underwent surgery for early-stage pancreatic adenocarcinoma (rPca) based on sequence (NAT, neoadjuvant therapy and/or AT, adjuvant therapy) and type (SA, single-agent or MA, multi-agent) of chemotherapy received.Using the National Cancer Database, patients with clinical stage I/II rPca diagnosed between 2010 and 2014 were identified and five comparison matches (1: NAT vs. upfront resection (UR); 2: multi-agent neoadjuvant (MA NAT) vs. single-agent adjuvant therapy (SA AT), single-agent neoadjuvant therapy (SA NAT), multi-agent adjuvant therapy (MA AT); 3: MA NAT vs. MA AT; 4: NAT + AT vs NAT; 5: NAT + AT vs AT) were constructed using minimum distance matching strategy. Median OS (mOS) was analysed using Kaplan-Meier method, log-rank test and Cox proportional hazard model.A total of 18,470 patients with stage I/II rPca were eligible for analysis. NAT showed a 5 month (mo.) improved OS compared with UR (3271 patients/group, 28.1 vs 23.2 mo. P 0.0001 hazard ratio [HR]: 0.79). MA-NAT was shown to be superior to other chemotherapy approaches SA AT, SA NAT, and MA AT (1349 patients/group: 30 vs. 25.9 mo., P = 0.0001 [HR: 0.82]). MA NAT showed a survival advantage over MA-AT (1349 patients/group, 30 vs 26.1 mo., P = 0.0008 [HR: 0.86]). The combination of NAT and AT showed a better outcome when compared with NAT alone (1128 patients/group, 31.6 vs 27.4 mo., P = 0.0011 [HR: 0.81]) or AT alone (1128 patients/group, 31.6 vs. 25.2 mo., P 0.0001 [HR: 0.76]).In patients with stage I/II rPca, MA NAT showed improved mOS compared to UR and all other chemotherapy sequences except both NAT plus AT. These findings support the use of MA NAT in stage I/II rPca patients and warrant prospective trials evaluating MA NAT and post-resection maintenance therapies.

Therapy for medulloblastoma in patients

Upper urinary tract obstructions (UTOs) are blockages that inhibit the flow of urine through its normal course, leading to impaired kidney function. Imaging plays a significant role in the initial diagnosis of UTO, with anatomic imaging (primarily ultrasound (US) and non-contrast computed tomography (CT)) serving as screening tools for the detection of the dilation of the urinary collecting systems (i.e., hydronephrosis). Whether hydronephrosis represents UTO or a non-obstructive process is determined by functional imaging (typically nuclear medicine renal scintigraphy). If these exams reveal evidence of UTO but no discernable source, multiphase contrast enhanced CT urography and/or dynamic contrast enhanced MR urography (DCE-MRU) may be performed to delineate a cause. These are often performed in conjunction with direct ureteroscopic evaluation. While contrast-enhanced CT currently predominates, it can induce renal injury due to contrast induced nephropathy (CIN), subject patients to ionizing radiation and is limited in quantifying renal function (traditionally assessed by renal scintigraphy) and establishing the extent to which hydronephrosis is due to functional obstruction. Traditional MRI is similarly limited in its ability to quantify function. DCE-MRU presents concerns regarding nephrogenic systemic fibrosis (NSF), although decreased with newer gadolinium-based contrast agents, and regarding cumulative gadolinium deposition in the basal ganglia. DCE-MR CEST urography is a promising alternative, employing new MRI contrast agents and imaging schemes and allowing for concurrent assessment of renal anatomy and functional parameters. In this review we highlight clinical challenges in the diagnosis and management of UTO, identify key advances in imaging agents and techniques for DCE-MR CEST urography and provide perspective on how this technique may evolve in clinical importance.

Background Quinacrine plus a fluoropyrimidine has in vivo efficacy against metastatic colorectal cancer (mCRC). This phase 1b trial evaluated the combination of quinacrine plus capecitabine in patients with treatment-refractory mCRC. Patients and Methods Using a modified Simon accelerated titration design, adults with treatment-refractory mCRC were treated with capecitabine 1000 mg/m2 twice daily for 14/21-day cycle, and escalating doses of quinacrine 100 mg daily, 100 mg twice daily, and 200 mg twice daily for 21 days. The primary endpoint was identifying the maximum tolerated dose, determining tolerability and safety. In an expansion cohort, it was overall response rate and time to tumor progression (TTP). Results Ten patients (median age of 60 years) were treated in phase 1b. The first 2 quinacrine dosing levels were well tolerated. Dose-limiting toxicities were seen in 3 patients treated with quinacrine 200 mg twice daily. Five additional patients tolerated quinacrine 100 mg twice daily without further dose-limiting toxicities, thus establishing the maximum tolerated dose. Seven additional expansion-cohort patients enrolled onto the study before quinacrine manufacturing ceased within the United States. Five patients experienced stable disease, 1 partial response, and 10 disease progression. Median TTP overall was 2.12 months and median overall survival 5.22 months for the 17 patients. Conclusion Capecitabine and quinacrine can be safely administered at the maximum tolerated dose of capecitabine 1000 mg/m2 by mouth twice daily on days 1-14 and quinacrine 100 mg by mouth twice daily on days 1-21 of a 21-day cycle in mCRC patients. Although the expansion study was halted early, TTP was in line with other studies of refractory mCRC, suggesting activity of this regimen in heavily pretreated patients.

Purpose: Current literature reports increased incidence of postpancreaticoduodenectomy (PD) nonalcoholic fatty liver disease (NAFLD), a precursor for nonalcoholic steatohepatitis and cirrhosis. The incidence of and risk factors (RFs) for NAFLD in the PD population, however, are not well elucidated. Methods: A cohort of 421 patients from a single institution who underwent PD for carcinoma and followed for at least 6 months were assessed retrospectively for age, gender, pathology, surgical complications (operative blood loss and length of stay [LOS]), comorbidities (diabetes, hypertension, hyperlipidemia, obesity), tobacco use, pre- and postoperative nutritional status (albumin and body mass index [BMI]), use of pancreatic enzyme replacement, and perioperative laboratory values (hemoglobin and liver function test). Cox proportional hazards model was used to examine these potential RFs as predictors of time to development of post-PD NAFLD. Results: Sixty (14.3%) patients developed post-PD NAFLD. Patients with NAFLD were younger (61.10 vs. 65.01 years old) and had higher preoperative BMI (28.92 vs. 26.61). Multivariate Cox proportional hazard model identified higher preoperative BMI, shorter postoperative LOS, and female gender as RFs for post-PD NAFLD. After excluding 12 patients with rare histology, there was a lower unadjusted hazard of developing NAFLD (p-value = 0.018) in the adenocarcinoma group than in the neuroendocrine and periampullary tumor groups. There was no statistically significant association between post-PD NAFLD and other characteristics. Conclusion: Female gender, higher preoperative BMI, and shorter LOS deserve closer monitoring for earlier detection and management of NAFLD.

In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) resulted in fewer heart failure hospitalizations (HFHs) and lower mortality at 24 months in patients with heart failure (HF) with mitral regurgitation (MR) secondary to left ventricular dysfunction compared with guideline-directed medical therapy (GDMT) alone.This study determined if these benefits persisted to 36 months and if control subjects who were allowed to cross over at 24 months derived similar benefit.This study randomized 614 patients with HF with moderate-to-severe or severe secondary MR, who remained symptomatic despite maximally tolerated GDMT, to TMVr plus GDMT versus GDMT alone. The primary effectiveness endpoint was all HFHs through 24-month follow-up. Patients have now been followed for 36 months.The annualized rates of HFHs per patient-year were 35.5% with TMVr and 68.8% with GDMT alone (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.37 to 0.63; p 0.001; number needed to treat (NNT) = 3.0; 95% CI: 2.4 to 4.0). Mortality occurred in 42.8% of the device group versus 55.5% of control group (HR: 0.67; 95% CI: 0.52 to 0.85; p = 0.001; NNT = 7.9; 95% CI: 4.6 to 26.1). Patients who underwent TMVr also had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity. Among 58 patients assigned to GDMT alone who crossed over and were treated with TMVr, the subsequent composite rate of mortality or HFH was reduced compared with those who continued on GDMT alone (adjusted HR: 0.43; 95% CI: 0.24 to 0.78; p = 0.006).Among patients with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite GDMT, TMVr was safe, provided a durable reduction in MR, reduced the rate of HFH, and improved survival, quality of life, and functional capacity compared with GDMT alone through 36 months. Surviving patients who crossed over to device treatment had a prognosis comparable to those originally assigned to transcatheter therapy. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]; NCT01626079).

Background In low surgical risk patients with symptomatic severe aortic stenosis, the PARTNER 3 (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis) trial demonstrated superiority of transcatheter aortic valve replacement (TAVR) versus surgery for the primary endpoint of death, stroke, or re-hospitalization at 1 year. Objectives This study determined both clinical and echocardiographic outcomes between 1 and 2 years in the PARTNER 3 trial. Methods This study randomly assigned 1,000 patients (1:1) to transfemoral TAVR with the SAPIEN 3 valve versus surgery (mean Society of Thoracic Surgeons score: 1.9%; mean age: 73 years) with clinical and echocardiography follow-up at 30 days and at 1 and 2 years. This study assessed 2-year rates of the primary endpoint and several secondary endpoints (clinical, echocardiography, and quality-of-life measures) in this as-treated analysis. Results Primary endpoint follow-up at 2 years was available in 96.5% of patients. The 2-year primary endpoint was significantly reduced after TAVR versus surgery (11.5% vs. 17.4%; hazard ratio: 0.63; 95% confidence interval: 0.45 to 0.88; p = 0.007). Differences in death and stroke favoring TAVR at 1 year were not statistically significant at 2 years (death: TAVR 2.4% vs. surgery 3.2%; p = 0.47; stroke: TAVR 2.4% vs. surgery 3.6%; p = 0.28). Valve thrombosis at 2 years was increased after TAVR (2.6%; 13 events) compared with surgery (0.7%; 3 events; p = 0.02). Disease-specific health status continued to be better after TAVR versus surgery through 2 years. Echocardiographic findings, including hemodynamic valve deterioration and bioprosthetic valve failure, were similar for TAVR and surgery at 2 years. Conclusions At 2 years, the primary endpoint remained significantly lower with TAVR versus surgery, but initial differences in death and stroke favoring TAVR were diminished and patients who underwent TAVR had increased valve thrombosis. (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis [PARTNER 3]; NCT02675114 )

Background Improvements in health care innovations have resulted in an enhanced ability to extend patient viability. As a consequence, resources are being increasingly utilized at an unsustainable level. As we implement novel treatments, identifying futility should be a focus. The “death diamond” (DD) is a unique thrombelastography (TEG) tracing that is indicative of failure of the coagulation system, with a mortality rate exceeding 90%. The purpose of this study was to determine if the DD was a consistent marker of poor survival in a multicenter study population. We hypothesize that the DD, while an infrequent occurrence, predicts poor survival and can be used to stratify patients in whom resuscitation efforts are futile. Methods A retrospective multi-institutional study of trauma patients presenting with TEG DDs between 8/2008 and 12/2018 at four American College of Surgeons trauma centers was completed. Demographics, injury mechanisms, TEG results, management, and survival were examined. Results A total of 50 trauma patients presented with DD tracings, with a 94% (n = 47) mortality rate. Twenty-six (52%) patients received a repeat TEG with 10 patients re-demonstrating the DD tracing. There was 100% mortality in patients with serial DD tracings. The median use of total blood products was 18 units (interquartile range 6, 34.25) per patient. Discussion The DD is highly predictive of trauma-associated mortality. This multicenter study highlights that serial DDs may represent a possible biomarker of futility.

PURPOSE Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer. METHODS Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated. RESULTS In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively ( P < .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity ( P < .01). CONCLUSION The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.

The STS-ACC TVT Registry (Society of Thoracic Surgeons–American College of Cardiology Transcatheter Valve Therapy Registry) from 2011 to 2019 has collected data on 276,316 patients undergoing transcatheter aortic valve replacement (TAVR) at sites in all U.S. states. Volumes have increased every year, exceeding surgical aortic valve replacement in 2019 (72,991 vs. 57,626), and it is now performed in all U.S. states. TAVR now extends from extreme- to low-risk patients. This is the first presentation on 8,395 low-risk patients treated in 2019. In 2019, for the entire cohort, femoral access increased to 95.3%, hospital stay was 2 days, and 90.3% were discharged home. Since 2011, the 30-day mortality rate has decreased (7.2% to 2.5%), stroke has started to decrease (2.75% to 2.3%), but pacemaker need is unchanged (10.9% to 10.8%). Alive with acceptable patient-reported outcomes is achieved in 8 of 10 patients at 1 year. The Registry is a national resource to improve care and analyze TAVR’s evolution. Real-world outcomes, site performance, and the impact of coronavirus disease 2019 will be subsequently studied. (STS/ACC Transcatheter Valve Therapy Registry [TVT Registry]; NCT01737528 )

Objectives The aim of this study was to compare ticagrelor monotherapy with dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents. Background The role of abbreviated DAPT followed by an oral P2Y12 inhibitor after PCI remains uncertain. Methods Two randomized trials, including 14,628 patients undergoing PCI, comparing ticagrelor monotherapy with standard DAPT on centrally adjudicated endpoints were identified, and individual patient data were analyzed using 1-step fixed-effect models. The protocol was registered in PROSPERO ( CRD42019143120 ). The primary outcomes were the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at 1 year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale. Results Bleeding Academic Research Consortium type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively; HR: 0.56; 95% confidence interval [CI]: 0.41 to 0.75; p Conclusions Ticagrelor monotherapy was associated with a lower risk for major bleeding compared with standard DAPT, without a concomitant increase in ischemic events.

Background We evaluated deficit accumulation and how deficits affected cognition and physical activity among breast cancer survivors and non-cancer controls. Methods Newly diagnosed nonmetastatic survivors (n = 353) and matched non-cancer controls (n = 355) ages 60-98 years without neurological impairments were assessed presystemic therapy (or at enrollment for controls) from August 2010 to December 2016 and followed for 36 months. Scores on a 42-item index were analyzed in growth-mixture models to determine deficit accumulation trajectories separately and combined for survivors and controls. Multilevel models tested associations between trajectory and cognition (FACT-Cog and neuropsychological tests) and physical activity (IPAQ-SF) for survivors and controls. Results Deficit accumulation scores were in the robust range, but survivors had higher scores (95% confidence intervals [CI]) than controls at 36 months (0.18, 95% CI = 0.16 to 0.19, vs 0.16, 95% CI = 0.14 to 0.17; P = .001), and averages included diverse deficit trajectories. Survivors who were robust but became frailer (8.8%) had similar baseline characteristics to those remaining robust (76.2%) but experienced a 9.6-point decline self-reported cognition (decline of 9.6 vs 3.2 points; P = .04) and a 769 MET minutes per week decline in physical activity (P < .001). Survivors who started and remained prefrail (15.0%) had self-reported and objective cognitive problems. At baseline, frail controls (9.5%) differed from robust controls (83.7%) on deficits and self-reported cognition (P < .001). Within combined trajectories, frail survivors had more sleep disturbances than frail controls (48.6% [SD = 17.4%] vs 25.0% [SD = 8.2%]; P = .05). Conclusions Most survivors and controls remained robust, and there were similar proportions on a frail trajectory. However, there were differences in deficit patterns between survivors and controls. Survivor deficit accumulation trajectory was associated with patient-reported outcomes. Additional research is needed to understand how breast cancer and its treatments affect deficit accumulation.

Obstructive hypertrophic cardiomyopathy (oHCM) is a disease of the cardiomyocyte in which dynamic left ventricular outflow track obstruction may lead to heart failure, valvular disease, and sudden death. Little is known about healthcare resource utilization (HRU) and costs associated with oHCM. This study investigated the clinical and economic burden of oHCM in patients with or without symptoms associated with oHCM.We used the US IBM MarketScan Commercial and Medicare Supplemental database to identify patients with oHCM (January 2009-March 2019). Control patients without cardiomyopathy were matched to each patient with oHCM based on age, sex, region, and index year (3:1 ratio). One-year HRU and cost data were compared between all oHCM, symptomatic oHCM, and asymptomatic oHCM subgroups, and their respective controls.Among 11,401 eligible patients with oHCM (mean age 57 years, 42% female), 5,667 (50%) were symptomatic (23% chest pain, 57% dyspnea, 29% fatigue, 17% syncope). oHCM was associated with significant increases in all-cause hospitalizations, hospital days, outpatient visits, and total healthcare costs (mean ± standard deviation: $26,929 ± 77,720 vs. $6,808 ± 25,712,The use of claims data relies on International Classification of Diseases (ICD-9 and ICD-10) diagnosis codes, which might be inaccurate. Only commercially insured patients were included.In a real-world population, oHCM was associated with substantial increases in HRU and incremental costs of ∼$20,000/year when compared with matched controls-a difference that increased to ∼$35,000/year among symptomatic patients. Further studies are warranted to understand the potential impact of specific therapies on HRU and the economic burden of oHCM.PLAIN LANGUAGE SUMMARYObstructive hypertrophic cardiomyopathy (oHCM) is a medical condition in which the heart muscle becomes abnormally thick and can cause partial blockage of blood flow out of the heart. Some patients experience symptoms (such as shortness of breath, chest pain, and fatigue) from this condition while others do not. Little is known about the healthcare resource utilization (HRU) and costs associated with oHCM, and if there are any differences between patients with oHCM who experience symptoms versus those who are asymptomatic. Therefore, we performed a study to investigate the clinical and economic burden of oHCM in patients with or without symptoms associated with oHCM. Based on insurance claims data, ∼50% of all patients with diagnosed oHCM are symptomatic. Symptomatic patients experience nearly 8 times as many hospitalizations and cost the healthcare system$35,000 per year more than matched controls. In contrast, asymptomatic patients with oHCM have a much smaller difference in HRU and costs (∼$3,600/year) compared with matched controls. The results of this study suggest that effective therapies for oHCM may provide economic value, even if the impact of therapy is limited solely to the relief of symptoms.

BACKGROUND:The risk factors and adverse outcomes related to maternal depression and child malnutrition are a leading cause of morbidity and mortality in low and middle-income countries (LMIC) including Pakistan. Above 25% of women suffer from maternal depression. Up to 50% children are under-nourished which contributes to 35% of all under-5 deaths in the country. AIM:To determine the efficacy of Learning through Play Plus Thinking Healthy Program (LTP Plus) intervention to reduce maternal depression in mothers with undernourished children. METHODS:In this randomised controlled trial, all eligible mothers presenting to the paediatric departments were invited to participate in the study. Out of the total 256 mothers screened, 107 were included, 54 of those were randomly allocated to LTP Plus group and 53 to treatment as usual (TAU). Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depression. Hamilton Depression Rating Scale (HDRS), Maternal Attachment Inventory (MAI), Social Support Scale (OSLO-3) and the Euro-QoL (EQ-5D) were used to measure the severity of depression, mother-child attachment, level of support and health related quality of life dimensions. Assessments were completed at baseline, end of intervention (3 months from baseline) and at 6 months from baseline. RESULTS:Mothers in the LTP Plus group significantly showed improvements in depression (p

Haemophilia B (HB) is less well studied than haemophilia A (HA); despite similarities between the two inherited bleeding disorders, important differences remain that require further research.B-Natural is a multi-centre, prospective, observational study of HB, designed to increase understanding of clinical manifestations, treatment, quality-of-life (QoL), inhibitor development, immune tolerance induction (ITI) outcome, renal function and create a biorepository for future investigations.Participants include sibling pairs/groups without a current/history of inhibitors and singletons or siblings with a current/history of inhibitors followed for six months. Demographics, medical, social history and treatment were recorded. A physical examination including joint range of motion (ROM) was performed; QoL was assessed. Samples were collected for F9 gene mutation, HLA typing, non-inhibitory antibodies and renal function testing.Twenty-four centres enrolled 224 individuals from 107 families including 29 with current/history of inhibitors. Of these, 68, 30.4%, had severe (1% FIX level of normal); 114, 50.9%, moderate (1%-5%); and 42, 18.8%, mild (5-40%) disease. At enrolment, 53.1% had 50 + exposure days to exogenous FIX. Comparison of joint scores showed significant (P .05) differences between those with severe (with/without inhibitors), and those with moderate/mild disease. The majority with severe disease, 80.0% with current/history of inhibitors and 64.3% of those without, were treated with prophylaxis.B-Natural provides data supporting an increased understanding of HB and its impact throughout life. The need for optimal disease control to normalize physical and psychosocial outcomes is underscored, and further analyses will contribute to an increased understanding of critical issues in HB.

Background Venous thromboembolism (VTE) in patients with major pelvic fractures who undergo preperitoneal pelvic packing (PPP) has not been investigated. We hypothesized that patients who undergo PPP are at high risk for VTE, thus early prophylactic anticoagulation and screening duplex are warranted. Study design All patients requiring PPP from 2015 to 2019 were reviewed. Management and outcomes were analyzed. Results During the study period, 79 patients underwent PPP. Excluding the early deaths, 17 patients had deep venous thrombosis (DVT) and 6 had pulmonary emboli (PE); 4 patients had both DVT/PE. Overall mortality was 15%. Thirty-two patients underwent screening duplex within 72 h of admission and 10 were positive for DVT. Conclusion Patients with complex pelvic trauma undergoing PPP have a 23% incidence of DVT and an additional 8% incidence of PE. 31% of screening ultrasounds are positive. The overall mortality was 15%. With a high incidence of VTE in this patient population, we recommend screening duplex ultrasounds.

Objectives The aim of this study was to examine the relationship between chronic obstructive pulmonary disease (COPD) and outcomes after transcatheter mitral valve repair (TMVr) for severe secondary mitral regurgitation. Background TMVr with the MitraClip improves clinical and health-status outcomes in patients with heart failure and severe (3+ to 4+) secondary mitral regurgitation. Whether these benefits are modified by COPD is unknown. Methods COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) was an open-label, multicenter, randomized trial of TMVr plus guideline-directed medical therapy (GDMT) versus GDMT alone. Patients on corticosteroids or continuous oxygen were excluded. Multivariable models were used to examine the associations of COPD with mortality, heart failure hospitalization (HFH), and health status and to test whether COPD modified the benefit of TMVr compared with GDMT. Results Among 614 patients, 143 (23.2%) had COPD. Among patients treated with TMVr, unadjusted analyses demonstrated increased 2-year mortality in those with COPD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.33 to 3.26), but this association was attenuated after risk adjustment (adjusted HR: 1.48; 95% CI: 0.87 to 2.52). Although TMVr led to reduced 2-year mortality among patients without COPD (adjusted HR: 0.47; 95% CI: 0.33 to 0.67), for patients with COPD, 2-year all-cause mortality was similar after TMVr versus GDMT alone (adjusted HR: 0.94; 95% CI: 0.54 to 1.65; pint = 0.04), findings that reflect offsetting effects on cardiovascular and noncardiovascular mortality. In contrast, TMVr reduced HFH (adjusted HR: 0.48 [95% CI: 0.28 to 0.83] vs. 0.46 [95% CI: 0.34 to 0.63]; pint = 0.89) and improved both generic and disease-specific health status to a similar extent compared with GDMT alone in patients with and without COPD (pint >0.30 for all scales). Conclusions In the COAPT trial, COPD was associated with attenuation of the survival benefit of TMVr versus GDMT compared with patients without COPD. However, the benefits of TMVr on both HFH and health status were similar regardless of COPD. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079 )

Objective To determine the degree of contemporary practice variation for the treatment of urethral stricture disease (USD) given repeated endoscopic management yields poor long-term success. Materials and Methods The AUA Quality (AQUA) Registry collects data from participating urologists across practice settings by direct interface with local electronic health record systems. We identified procedures used for USD using Current Procedural Terminology (CPT) and International Statistical Classification of Diseases (ICD-9/-10) codes. We assessed the association between patient and provider factors and repeated endoscopic treatment using generalized linear models. Provider details were derived from AUA Census. Results We identified 20,640 male patients with USD treated surgically in AQUA from 2014-2018. The patients were cared for by 1343 providers at 171 practices, 95% of these community-based. Among patients with USD who had treatment, 20,101(97.9%) underwent endoscopic management. 6218(31%) underwent repeated endoscopic treatment during the study period. Urethroplasty was performed in 539(2.6%) patients. Median patient age at first procedure for endoscopic surgery vs. urethroplasty was 73 vs. 39 years old, respectively (p Conclusions Repeated endoscopic management for USD is overused. The utilization of endoscopic management is variable across practices and frequently guideline-discordant, presenting an opportunity for quality improvement.

OBJECTIVES: Identify the metabolites that are increased in the plasma of severely injured patients that developed ARDS versus severely injured patients that did not, and assay if these increased metabolites prime PMNs and induce pulmonary sequestration in an animal model of ARDS. We hypothesize that metabolic derangement due to advanced shock in critically injured patients leads to the pulmonary sequestration of neutrophils (PMNs), which serves as the first event in the acute respiratory distress syndrome (ARDS). SUMMARY BACKGROUND DATA: Intracellular metabolites accumulate in the plasma of severely injured patients. METHODS: Untargeted metabolomics profiling of 67 critically injured patients was completed to establish a metabolic signature associated with ARDS development. Metabolites that signficantly increased were assayed for PMN priming activity in vitro. The metabolites that primed PMNs were tested in a two-event animal model of ARDS to identify a molecular link between circulating metabolites and clinical risk for ARDS. RESULTS: After controlling for confounders, four metabolites significantly increased: creatine, dehydroascorbate, fumarate, and succinate in trauma patients who developed ARDS (p

In January 2020, with support from the U.S. Department of Homeland Security (DHS), CDC instituted an enhanced entry risk assessment and management (screening) program for air passengers arriving from certain countries with widespread, sustained transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). The objectives of the screening program were to reduce the importation of COVID-19 cases into the United States and slow subsequent spread within states. Screening aimed to identify travelers with COVID-19-like illness or who had a known exposure to a person with COVID-19 and separate them from others. Screening also aimed to inform all screened travelers about self-monitoring and other recommendations to prevent disease spread and obtain their contact information to share with public health authorities in destination states. CDC delegated postarrival management of crew members to airline occupational health programs by issuing joint guidance with the Federal Aviation Administration.* During January 17-September 13, 2020, a total of 766,044 travelers were screened, 298 (0.04%) of whom met criteria for public health assessment; 35 (0.005%) were tested for SARS-CoV-2, and nine (0.001%) had a positive test result. CDC shared contact information with states for approximately 68% of screened travelers because of data collection challenges and some states' opting out of receiving data. The low case detection rate of this resource-intensive program highlighted the need for fundamental change in the U.S. border health strategy. Because SARS-CoV-2 infection and transmission can occur in the absence of symptoms and because the symptoms of COVID-19 are nonspecific, symptom-based screening programs are ineffective for case detection. Since the screening program ended on September 14, 2020, efforts to reduce COVID-19 importation have focused on enhancing communications with travelers to promote recommended preventive measures, reinforcing mechanisms to refer overtly ill travelers to CDC, and enhancing public health response capacity at ports of entry. More efficient collection of contact information for international air passengers before arrival and real-time transfer of data to U.S. health departments would facilitate timely postarrival public health management, including contact tracing, when indicated. Incorporating health attestations, predeparture and postarrival testing, and a period of limited movement after higher-risk travel, might reduce risk for transmission during travel and translocation of SARS-CoV-2 between geographic areas and help guide more individualized postarrival recommendations.

Tauopathies including Alzheimer’s disease (AD) are marked by the accumulation of aberrantly modified tau proteins. Acetylated tau, in particular, has recently been implicated in neurodegeneration and cognitive decline. HDAC6 reversibly regulates tau acetylation, but its role in tauopathy progression remains unclear. Here, we identified an HDAC6-chaperone complex that targets aberrantly modified tau. HDAC6 not only deacetylates tau but also suppresses tau hyperphosphorylation within the microtubule-binding region. In neurons and human AD brain, HDAC6 becomes co-aggregated within focal tau swellings and human AD neuritic plaques. Using mass spectrometry, we identify a novel HDAC6-regulated tau acetylation site as a disease specific marker for 3R/4R and 3R tauopathies, supporting uniquely modified tau species in different neurodegenerative disorders. Tau transgenic mice lacking HDAC6 show reduced survival characterized by accelerated tau pathology and cognitive decline. We propose that a HDAC6-dependent surveillance mechanism suppresses toxic tau accumulation, which may protect against the progression of AD and related tauopathies., HDAC6 is a tau deacetylase and acetylation of tau inhibits its function and promotes aggregation. Here the authors show that HDAC6 protects against tau accumulation in a mouse model of tauopathy.

The safety and efficacy of tocilizumab for the treatment of severe respiratory symptoms due to COVID-19 remain uncertain, in particular among solid organ transplant (SOT) recipients. Thus, we evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID-19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID-19, 29 (24.8%) received tocilizumab. The 90-day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, P = .03). When compared to control patients matched by age, hypertension, chronic kidney disease, and administration of high dose corticosteroids, there was no significant difference in mortality (41% vs 28%, P = .27), hospital discharge (52% vs 72%, P = .26), or secondary infections (34% vs 24%, P = .55). Among patients who received tocilizumab, there was also no difference in mortality based on the level of oxygen support (intubated vs not intubated) at the time of tocilizumab initiation. In this matched cohort study, tocilizumab appeared to be safe but was not associated with decreased 90-day mortality. Larger randomized studies are needed to identify whether there are subsets of SOT recipients who may benefit from tocilizumab for treatment of COVID-19.