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Background In March 2020, the COVID-19 virus global pandemic forced healthcare systems to institute regulations including the cancellation of elective surgical cases, which likely decreased resident operative experience. The objective of this study was to determine if the COVID-19 pandemic affected operative experiences of U.S. general surgery residents. Methods The operative experience of general surgery residents was examined nationally and locally. Aggregate Accreditation Council for Graduate Medical Education (ACGME) case logs for 2018-2019 (pre-COVID) and 2019-2020 (COVID) graduates were compared using national mean cumulative operative volume for total major and surgeon chief cases. Locally, ACGME case logs were used to analyze the operative experience among residents at a single, academic center. Average operative volumes per month per resident during peak COVID-19 quarantine months were compared with those the previous year. Results Compared with 2019 graduates, 2020 graduates completed 1.5% fewer total major cases (1055 ± 155 vs 1071 ± 150, p=0.011). This was most evident during chief year, with 8.4% fewer surgeon chief cases logged in 2020 compared to 2019 (264 ± 67 vs 289 ± 69, p < 0.001). Institutional data revealed that during the peak of the pandemic, residents across all levels completed 42.5% fewer total major operations (12 ± 11 vs 20 ± 14, p < 0.001). This effect was more pronounced among junior residents compared with senior and chief residents. Conclusions The COVID-19 pandemic was associated with decreased resident case volume. The ramifications of the COVID-19 pandemic for operative competency and autonomy should be carefully examined., Our study examined the operative volume of U.S. general surgery residents during the COVID-19 pandemic by using ACGME case logs and found that reported resident operative volume decreased during the pandemic both nationally and locally. This finding is important as it impacts future resident education and operative competence for those affected by the COVID-19 pandemic and will need to be addressed by educators and learners moving forward.

Cells regulate their cell volume, but cell volumes may change in response to metabolic and other perturbations. Many metabolomics experiments use cultured cells to measure changes in metabolites in response to physiological and other experimental perturbations, but the metabolomics workflow by mass spectrometry only determines total metabolite amounts in cell culture extracts. To convert metabolite amount to metabolite concentration requires knowledge of the number and volume of the cells. Measuring only metabolite amount can lead to incorrect or skewed results in cell culture experiments because cell size may change due to experimental conditions independent of change in metabolite concentration. We have developed a novel method to determine cell volume in cell culture experiments using a pair of stable isotopically labeled phenylalanine internal standards incorporated within the normal liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics workflow. This method relies on the flooding-dose technique where the intracellular concentration of a particular compound (in this case phenylalanine) is forced to equal its extracellular concentration. We illustrate the LC-MS/MS technique for two different mammalian cell lines. Although the method is applicable in general for determining cell volume, the major advantage of the method is its seamless incorporation within the normal metabolomics workflow.

Introduction: Electronic Health Records (EHR) have been implemented by multiple hospitals all around the world. EHR initiatives tend to be driven by the promise of availability of patient data and enhanced system integration by the need to improve efficiency and cost-effectiveness and by a changing doctor-patient relationship towards where care is divided among a multidisciplinary members of health care professionals and/or by the need to deal with a more complex and rapidly changing environment. The aim of this research is to determine the barriers faced by nurses in Qatar in using EHRs in terms of knowledge, skills, and attitude (KSA). Methods: A survey was sent to approximately 12,000 nurses from different hospitals under Hamad Medical Corporation in Qatar through the corporation's official e-mail from January 1, 2021 to May 31, 2021. The questionnaire was developed and validated by the researcher of the study (α=0.877). The Statistical Package for the Social Sciences (SPSS) version 25.0 was used to analyze the data. Results: A total of 262 nurses participated in the study. Majority of the nurses who participated are females (69%) and ages 31-35 years old (50.4%). Among the respondents 98.5% are staff nurses with various educational levels: bachelor’s degree in Nursing (43.5 %), diploma in Nursing (27%), and Master of Arts in nursing (3.8%). Only 23.3% of the respondents have a length of service of less than 4 years; 76.7% have been with their institution more than 4 years. The majority of respondents came from the inpatient areas (37%), followed by the outpatient nurses (15.3%), and operating room nurses (14.1%). Around 91% of the respondents claimed to have a 0-3 number of trainings in the past 3 years. A significant correlation was found between age (r=-0.124, p=0.045), length of service (r=0.193, p=0.002), and area assignment (r=0.129, p=0.037) with the skill on EHR. Conclusion: Results of the study showed that the dimension of knowledge, skills, and attitude towards the use of EHR is a barrier, but only to a moderate extent. The nurses in Qatar are highly educated, well experienced and are mostly millennials. This opens a great opportunity of acceptance and amplification of EHR in Qatar with the proper training and support to nurses.

Background/purpose To report vitreous and epiretinal seeding of choroidal melanoma after transvitreal fine-needle aspiration biopsy (FNAB). Methods A 74-year-old Caucasian man with a medium-sized, dome-shaped choroidal melanoma without Bruch membrane rupture, retinal invasion, or vitreous seeding. Transvitreal FNAB was performed for cytopathologic evaluation using a long 27-gauge needle attached to a 10-mL syringe by connector tubing. After passing through the pars plana, vitreous cavity, neurosensory retina, and Bruch membrane, the needle was inserted into the tumor and aspiration was performed. Results Cytopathologic evaluation revealed spindle B melanoma cells, and the tumor was subsequently treated with an 18-mm round Iodine-125 radioactive plaque delivering a tumor apex radiation dose of 7,000 cGy. Transscleral FNAB for cytogenetic evaluation performed at the time of plaque application disclosed chromosome three monosomy and chromosome six and eight disomy. Vitreous pigmented cells were first noted 14 months after brachytherapy. Funduscopy and optical coherence tomography at 24 months after plaque radiotherapy showed extensive vitreous and preretinal pigmented seeding that completely covered the optic disk. Fine-needle aspiration biopsy of the vitreous confirmed the presence of malignant melanoma cells, and the right eye was enucleated. Histopathologic evaluation showed a totally necrotic choroidal melanoma and an extensive malignant epiretinal membrane that covered and extended into the substance of the optic nerve head and focally invaded the neurosensory retina. The patient developed liver metastasis 3 years after the initial presentation and died 10 months later. Conclusion This case demonstrates the rare development of extensive vitreous and preretinal seeding with retinal and optic nerve invasion after transvitreal FNAB of choroidal melanoma.

Introduction Phenobarbital has been successfully used in the emergency department (ED) to manage symptoms of alcohol withdrawal, but few studies have reported outcomes for ED patients who receive phenobarbital and are discharged. We compared return encounter rates in discharged ED patients with alcohol withdrawal who were treated with benzodiazepines and phenobarbital. Methods This is a retrospective cohort study conducted at a single academic medical center utilizing chart review of discharged ED patients with alcohol withdrawal from July 1, 2016, to June 30, 2019. Patients were stratified according to ED management with benzodiazepines, phenobarbital, or a combination of both agents. The primary outcome was return ED encounter within three days of the index ED encounter. Multivariate logistic regression identified significant covariates of an ED return encounter. Results Of 470 patients who were discharged with the diagnosis of alcohol withdrawal, 235 were treated with benzodiazepines, 133 with phenobarbital, and 102 with a combination of both. Baseline characteristics were similar among the groups. However, patients who received phenobarbital were provided significantly more lorazepam equivalents compared to patients who received benzodiazepines alone. Treatment with phenobarbital, alone or in combination with benzodiazepines, was associated with significantly lower odds of a return ED visit within three days compared with benzodiazepines alone [AOR 0.45 (95% CI 0.23, 0.88) p = 0.02 and AOR 0.33 (95% CI 0.15, 0.74) p = 0.007]. Conclusions Patients who received phenobarbital for alcohol withdrawal were less likely to return to the ED within three days of the index encounter. Despite similar baseline characteristics, patients who received phenobarbital, with or without benzodiazepines, were provided greater lorazepam equivalents the ED.

Aims The aims of this study were to (1) estimate the effect of extended-release naltrexone compared with placebo on alcohol consumption in patients with alcohol use disorder (AUD) and (2) conduct pre-planned subgroup analyses to test whether being abstinent when initiating treatment (lead-in abstinence) or the duration of treatment improves treatment efficacy. Design Systematic review and random-effects meta-analysis of blinded randomized placebo-controlled trials reporting the effect extended-release naltrexone on alcohol consumption. Setting Outpatient clinics. Participants Seven trials evaluating a total of 1500 adults with AUD receiving monthly injections of either placebo or extended-release naltrexone at doses of 150-400 mg for 2-6 months and some form of behavioral therapy. Measurements Pooled weighted mean difference (WMD) in drinking days per month and heavy drinking days per month. Findings The WMD was -2.0 [95% confidence interval (CI) = -3.4, -0.6; P = 0.03] in favor of extended-release naltrexone for drinking days per month and -1.2 (95% CI = -0.2, -2.1; P = 0.02) for heavy drinking days per month, indicating that treatment resulted in two fewer drinking days per month and 1.2 fewer heavy drinking days per month compared with placebo. Trials not requiring lead-in abstinence and those lasting longer than 3 months reported larger reductions in heavy drinking days per month; WMD -2.0 (95% CI = -3.52, -0.48; P = 0.01) and -1.9 (95% CI = -3.2, -0.5; P = 0.01), respectively. In all cases, the I2 statistics (0-7.2%) did not suggest substantial heterogeneity. Conclusions Extended-release naltrexone reduces drinking days and heavy drinking days per month compared with placebo. Reductions are larger with a longer duration of treatment.

We have recently demonstrated that a significant proportion of fatal out-of-hospital cardiac arrests (OHCAs) are precipitated by occult overdose, which could benefit from antidote therapy administered adjunctively with other cardiac resuscitation measures. We sought to develop simple decision instruments that EMS providers and other first responders can use to rapidly identify occult opioid overdose-associated OHCAs.We examined data from February 2011 through December 2017 in the Postmortem Systematic Investigation of Sudden Cardiac Death study, in which San Francisco (California) County EMS-attended OHCA deaths received autopsy and expert panel adjudication of cause of death. Using classification tree analyses, we derived highly sensitive and specific decision instruments that predicted our primary outcome of occult opioid OD-associated OHCA. We then calculated screening performance characteristics of these instruments.Of 767 OHCA deaths, 80 (10.4%) were associated with occult opioid overdose. Of the eight models with 100% sensitivity for opioid overdose-associated cardiac arrest, the highest specificity model (23.4%, 95% confidence interval [CI] 20.3-26.7%) was age60 years OR race = black or non-Latinx white OR arrest in public place. The highest specificity instrument (96.3%, 95% CI 94.6-97.5%) consisting of age60 years AND race = black or non-Latinx white AND unwitnessed arrest AND female sex had 25% (95% CI 16-35.9%) sensitivity.We have derived simple decision instruments that can identify patients whose OHCA precipitant was occult opioid overdose. These instruments may be used to guide selective administration of the antidote naloxone in OHCA resuscitations.

Background Diversity in surgery has been shown to improve mentorship and patient care. Diversity has improved among general surgery (GS) trainees but is not the case for departmental leadership. We analyzed the race and gender distributions across leadership positions at academic GS programs. Methods Academic GS programs (n = 118) listed by the Fellowship and Residency Electronic Interactive Database Access system were included. Leadership positions were ascertained from department websites. Gender and race were determined through publicly provided data. Results Ninety-two (79.3%) department chairs were white and 99 (85.3%) were men. Additionally, 88 (74.6%) program directors and 34 (77.3%) vice-chairs of education were men. A higher proportion of associate program directors were women (38.5%). Of 787 division-chiefs, 73.4% were white. Only trauma had >10% representation from minority surgeons. Women represented >10% of division chiefs in colorectal, thoracic, pediatric, and plastic/burn surgery. Conclusion Diversity among GS trainees is not yet reflected in departmental leadership. Effort is needed to improve disparities in representation across leadership roles.

Purpose To highlight the increasing importance of gene fusions in the diagnosis, prognosis, and therapy of ocular adnexal tumors. Design Perspective. Methods A focused review of gene fusions, their pathogenic mechanism, and gene fusion detection methods in lacrimal gland and primary orbital and ocular adnexal soft tissue tumors; reappraisal of diagnostic, prognostic, and therapeutic approach to ocular adnexal tumors in light of emerging molecular genetic data. Results The widespread implementation of fluorescence in situ hybridization and next-generation sequencing methods in pathology practice has led to identification of recurrent gene rearrangements and fusions in a variety of tumors. As a result, molecular genetic methods have become the gold standard for diagnosis of tumors with overlapping histology and immunophenotype, such as small round blue cell tumors. Identification of canonic gene fusions has led to development of sensitive and specific immunohistochemical markers, such as STAT6 in solitary fibrous tumor. In addition to diagnostic accuracy, gene fusions have prognostic implications, such as unfavorable prognosis of PAX3-FOXO1 fusion in alveolar rhabdomyosarcoma. Finally, recognition of gene fusions as a driving mechanism in neoplasia has led to development of U.S. Food and Drug Administration–approved targeted therapies, such as TRK inhibitors for NTRK fusion-positive cancers. Conclusion The discovery of recurrent gene fusions in various tumors, including those involving ocular adnexa, has led to a deeper insight into the molecular mechanisms of these neoplasms, revolutionizing our approach to their diagnosis, prognostication, and therapy.

Burnout among surgeons has been attributed to increased workload and decreased autonomy. Although prior studies have examined burnout among transplant surgeons, no studies have evaluated burnout in abdominal transplant surgery fellows. The objective of our study was to identify predictors of burnout and understand its impact on personal and patient care during fellowship. A survey was sent to all abdominal transplant surgery fellows in an American Society of Transplant Surgeons-accredited fellowship. The response rate was 59.2% (n = 77) and 22.7% (n = 17) of fellows met criteria for burnout. Fellows with lower grit scores were more likely to exhibit burnout compared with fellows with higher scores (3.6 vs 4.0, P = .026). Those with burnout were more likely to work >100 hours per week (58.8% vs 27.6%, P = .023), have severe work-related stress (58.8% vs 22.4%, P = .010), consider quitting fellowship (94.1% vs 20.7%, P < .001), or make a medical error (35.3% vs 5.2%, P = .003). This national analysis of abdominal transplant fellows found that burnout rates are relatively low, but few fellows engage in self-care. Personal and program-related factors attribute to burnout and it has unacceptable effects on patient care. Transplant societies and fellowship programs should develop interventions to give fellows tools to prevent and combat burnout.

Intimate partner violence (IPV) is among the most common acts of violence against women worldwide, making it a major global threat to women’s health and safety. The assessment and management of IPV offenders are therefore vital tasks in criminal justice systems. The current study examined whether the DRAOR, a general case management tool, was useful for supervising 112 male IPV offenders in Iowa, United States. Several risk factors emerged as potentially important treatment targets for partner-violent men, including poor attachment with others, substance abuse, anger/hostility, opportunity/access to victims, and problematic interpersonal relationships. While further research is needed to improve the utility of the DRAOR for predicting IPV recidivism, it assesses several factors that are relevant for supervising IPV cases (e.g., substance abuse, anger/hostility, victim access). This suggests the DRAOR could potentially be used to guide case management in the presence of a validated IPV tool that focuses on static risk factors, such as the ODARA. The use of the DRAOR with IPV offenders may also be warranted if they are found to be generally violent/antisocial rather than as family only offenders.

Background Coronavirus disease‐19 (COVID‐19) spans a wide spectrum of illness. Severe cases of COVID‐19 can manifest inflammation in organs other than the lung, in tissues not known to support viral replication, and also in a hypercoagulable state. These observations have suggested that SARS‐CoV‐2 can provoke a hyperimmune response in some cases that could lead to secondary organ damage. Methods With evidence of elevated levels of interleuking‐6 (IL‐6) in patients with severe COVID‐19, we conducted a small pilot off‐label compassionate care study of the IL‐6 receptor inhibitor tocilizumab patients with severe COVID‐19. Results Following a single infusion of tocilizumab in patients with severe manifested rapid declines in C‐reactive protein (CRP), D‐Dimer, and gradual rises in lymphocyte and platelet counts. Conclusions These findings suggest both pathophysiological mechanisms as well as clinical benefit that might be seen with IL‐6 inhibition in severe COVID‐19.

SIGNIFICANCE: Numerous abnormalities in T cells have been described in patients with systemic lupus erythematosus (SLE), including lymphopenia, DNA demethylation, expression of endogenous retroviruses (ERVs), increased cell death, enlarged mitochondria, production of reactive oxygen species (ROS), and the appearance of unusual CD4(−)CD8(−) T cells. Our studies propose a model in which accelerated homeostatic proliferation of T cells promotes an epigenetic and metabolic program, leading to this cluster of abnormalities. RECENT ADVANCES: Growing knowledge of the innate immune disorders in SLE has included increased mitochondrial size and ROS production that induces oligomerization of the mitochondrial antiviral signaling (MAVS) protein and type I interferon production, as well as DNA demethylation, upregulation of inflammatory genes, and expression of certain ERVs in SLE peripheral blood mononuclear cells. All these events are part of the cellular program that occurs during homeostatic proliferation of T cells. Evidence from a murine model of SLE as well as in human SLE reveals that increased T cell homeostatic proliferation may be a driving factor in these processes. CRITICAL ISSUES: Despite extensive knowledge of the myriad autoantibodies in SLE and other immune abnormalities, a cogent model has been lacking to link the numerous and seemingly disparate immune aberrations. This may partly explain the general lack of new drugs specifically for SLE in over 50 years. A more coherent model of SLE would not only unify the variety of immune abnormalities is SLE but would also suggest new therapies. FUTURE DIRECTIONS: The model of augmented homeostatic proliferation leading to increased mitochondrial mass, ROS, DNA demethylation, and upregulation of inflammatory genes suggests strategic new targets for SLE, including antioxidants and certain inhibitors of metabolism. Antioxid. Redox Signal. 36, 410–422.

Systemic lupus erythematosus (SLE) is characterized by increased DNA demethylation in T cells, although it is unclear whether this occurs primarily in a subset of SLE T cells. The process driving the DNA demethylation and the consequences on overall gene expression are also poorly understood and whether this represents a secondary consequence of SLE or a primary contributing factor. Lupus-prone lpr mice accumulate large numbers of T cells with age because of a mutation in Fas (CD95). The accumulating T cells include an unusual population of CD4−CD8−TCR-αβ+ (DN) T cells that arise from CD8+ precursors and are also found in human SLE. We have previously observed that T cell accumulation in lpr mice is due to dysregulation of T cell homeostatic proliferation, which parallels an increased expression of numerous genes in the DN subset, including several proinflammatory molecules and checkpoint blockers. We thus determined the DNA methylome in lpr DN T cells compared with their CD8+ precursors. Our findings show that DN T cells manifest discrete sites of extensive demethylation throughout the genome, and these sites correspond to the location of a large proportion of the upregulated genes. Thus, dysregulated homeostatic proliferation in lpr mice and consequent epigenetic alterations may be a contributing factor to lupus pathogenesis.

Patients with more than one chronic condition often receive care from several providers and facilities, which may lead to fragmentation of care. Poor care coordination in dual health care system use has been associated with increased emergency department visits, hospitalizations, and costs.Dual health care system use is increasing among veterans, and we sought to evaluate the effect of dual health care system use on statin treatment in veterans with type 2 diabetes at high risk of cardiovascular events, using varying degrees of Centers for MedicareMedicaid Services (CMS) services.This was a 10-year retrospective longitudinal cohort study of national clinical and administrative data that included 689,138 veterans with type 2 diabetes who were aged 65 years or older on January 1, 2006. Patients were followed from January 1, 2007, until December 31, 2016. Administrative and clinical data from the Veterans Health Administration's (VHA) Corporate Data Warehouse were merged with CMS inpatient, outpatient, and pharmacy data. Statin use was defined as any therapy and subcategorized as high versus low or moderate intensity per the American College of Cardiology/American Heart Association guidelines. Marginal generalized estimating equation-type models for longitudinal data were used to model the association between dual health care utilization status (50%, 50%-80%, and80% VHA utilization, with the first group serving as the reference group) and statin use after adjusting for measured covariates.The mean ages at baseline for each group were similar and ranged between 75.4 and 76.9 years. For the outcome of any statin use, the group with50% VHA utilization was significantly less likely to receive statin therapy compared with the group with80% VHA utilization (OR = 0.26, 95% CI = 0.26-0.26), while the group with 50%-80% VHA utilization was slightly more likely (OR = 1.05, 95% CI = 1.04-1.07). Similarly, for the high-intensity versus low-/moderate-intensity or no statins outcome, the group with50% VHA utilization was significantly less likely to receive a high-intensity statin compared with the group with80% VHA utilization (OR = 0.56, 95% CI = 0.55-0.57), while the group with 50%-80% VHA utilization was only slightly less likely (OR = 0.95, 95% CI =0.94-0.96).Among veterans with diabetes at high risk of cardiovascular events, dual health care system utilization status appeared to affect statin use. We observed lower odds for any statin use and high-intensity statin therapy among the cohort with the lowest degree of VHA utilization (i.e.,50%). Interventions to increase statin use among veterans at high risk of cardiovascular events with lower degrees of VHA utilization should be explored.This study was supported by a grant funded by the Department of Veterans Affairs' Health Services Research and Development Service and was undertaken at the Health Equity and Rural Outreach Center (HEROIC) at Ralph H. Johnson Veteran Affairs Medical Center, Charleston, SC. The authors report no potential conflicts of interest relevant to this article. This article represents the views of the authors and not those of the Medical University of South Carolina or Veteran Health Administration.

Summary The role of p16 in the diagnosis and prognosis of conjunctival melanocytic lesions in the context of other clinical and immunohistochemical parameters has not been systematically explored. This study was conducted to determine whether p16 is a useful parameter in the diagnosis and prognosis of conjunctival melanocytic nevi and melanoma, either independently or as a component of immunohistochemical panels. Sixty-one patients underwent 61 biopsies for conjunctival melanocytic lesions between 2014 and 2018. Pathologic diagnoses were melanoma (n = 25, 41%), nevus (n = 21, 34%), and conjunctival melanocytic lesion of uncertain malignant potential (n = 15, 25%). The biopsies were assessed for expression of p16, SOX10, HMB45, and Ki-67. In a multivariable model, the parameters most predictive of melanoma versus nevus were diffuse HMB45 staining (odds ratio [OR] = 45, confidence interval [CI] = 4.4–457, P = .02] and p16 nuclear H-score≤115 (OR = 9.5, CI = 1.2–77; P = .04). There was no association of p16 expression with melanoma thickness. Next-generation sequencing identified no CDKN2A mutations or copy number alterations in 12 conjunctival melanomas, including the tumors with absent p16 expression. This study demonstrates that p16 immunohistochemical stain is useful in distinguishing conjunctival melanocytic nevi from melanoma, particularly in combination with HMB45. P16 expression does not appear to correlate with CDKN2A status and melanoma thickness.

Purpose Since the original description of “dacryadenoma” by Jakobiec and associates, the data on this unusual epibulbar lacrimal gland lesion remain sparse. The aim of this study was to characterize clinically, morphologically, and immunohistochemically this isolated epibulbar lacrimal gland lesion. Design Retrospective observational case series. Methods Institutional pathology records between 2000 and 2019 were searched for all cases of isolated epibulbar lacrimal gland lesions. Tissue from 3 normal lacrimal glands and 1 complex choristoma were included for comparative analysis. Clinical, histopathologic, and immunohistochemical findings were recorded. Results Four patients with isolated epibulbar lacrimal gland lesions, 2 male and 2 female, with a median age of 18 years (range, 12-57) were identified. All patients presented with recent onset of unilateral pink-to-orange, well-circumscribed subepithelial juxtaforniceal (3/4, 75%), or nasal (1/4, 25%) bulbar conjunctival nodules, which were asymptomatic (3/4, 75%) or associated with foreign body sensation (1/4, 25%). When compared with the normal lacrimal gland and complex choristoma, all isolated epibulbar lacrimal gland lesions were composed predominantly of variably dilated, branching tubular structures with pseudo-apocrine snouts, and either totally absent (2/2, 50%) or rare (2/2, 50%) ducts and rare acinar zymogen granules (3/4, 75%). Conclusion Our study confirms that a subset of isolated epibulbar lacrimal gland lesions differs morphologically and immunohistochemically from normal lacrimal gland tissue and the lacrimal gland in a complex choristoma. These differences range from subtle to overt, suggesting that isolated epibulbar lacrimal gland lesions may have originated from precursor cellular elements indigenous to the conjunctiva (hamartia) and grew into disorganized lacrimal gland tissue.

Purpose To describe the clinical and imaging characteristics, pathologic features, and management options of retinal pigment epithelium (RPE) adenoma/adenocarcinoma. Design Retrospective case series. Participants Fifty-one patients with RPE adenoma/adenocarcinoma. Methods Treatment options for the patients included observation, partial lamellar sclerouvectomy (PLSU), enucleation, and others. Main Outcome Measures Factors related to visual acuity (VA) outcomes (>2 Snellen lines loss, poor final VA [≤20/200], good final vision [≥20/40]), tumor growth, and need for enucleation. Results The mean patient age at diagnosis was 51 years, and the majority of patients were white (40/51, 78%) and female (34/51, 67%). Primary management included observation (29/51, 57%), PLSU (9/51, 18%), enucleation (4/51, 8%), or others (9/51, 18%). Outcomes revealed decreased VA (10/32, 31%), poor final VA (17/32, 53%), good final VA (11/32, 34%), tumor growth (12/25, 48%), and need for enucleation (7/51, 14%). By multivariable analysis, features predictive of decreased VA included increasing baseline tumor thickness (P = 0.01) and presence of vitreous hemorrhage (P = 0.05). Factors predictive of poor final VA included presence of exudative retinal detachment (P = 0.004), baseline VA 20/50 to 20/150 (P = 0.008), and baseline VA ≤20/200 (P = 0.01). Absence of feeding and/or draining vessel was predictive of good VA (P = 0.004). Tumor growth was associated with multiple treatments (P = 0.02). Increased tumor thickness (P = 0.03) and presence of exudative retinal detachment (P = 0.01) were predictive of enucleation. Conclusion RPE adenoma/adenocarcinoma can simulate choroidal melanoma. Greater tumor thickness, vitreous hemorrhage, exudative retinal detachment, and poor baseline VA predict worse visual outcome and greater risk for enucleation.

Purpose To describe a patient with orbital adult T-cell leukemia/lymphoma (ATLL) and to review the literature on presentation, diagnostics, management, and clinical course of this rare disease. Methods A systematic literature review. PubMed/MEDLINE and Google Scholar databases were searched for all well-documented cases of orbital/ocular adnexal ATLL. Results Sixteen patients were included in the final analysis. The median age at diagnosis was 47 years (range, 20-85), 9/16 patients (56%) were male, and patients were of Japanese (10/16, 63%), Caribbean (5/16, 31%), or African (1/16, 6%) origin. Proptosis (6/15, 40%) and visual loss (5/15, 33%) were the most common presenting signs. Involvement of adjacent structures was documented in 8 of 16 (50%) patients. All patients had evidence of systemic ATLL, which was identified concurrently with orbital/ocular adnexal disease in 9 of 15 (60%) patients. Management included multi-agent chemotherapy with steroids (9/13, 69%), antivirals (2/13, 15%), biologic agents (4/13, 31%), and umbilical cord blood transplantation (1/13, 8%). Most patients (8/12, 67%) experienced at least partial remission with disease relapse occurring in 6 of 8 patients (75%). The median survival time was 28 months (95% CI, 5.5-50.5 months). Conclusions Adult T-cell leukemia/lymphoma should be considered in the differential diagnosis of orbital and ocular adnexal space-occupying lesions, particularly in male patients from endemic regions. Orbital disease is frequently locally aggressive and presents concurrently with systemic ATLL, highlighting the importance of comprehensive multimodal work-up and multidisciplinary management. Emerging targeted therapies and hematopoietic stem cell transplant may prolong survival.

Background The NEXUS Chest CT clinical decision rules (CDRs) have been proposed to safely guide selective chest CT use in blunt trauma evaluation. We conducted a cost-effectiveness analysis of the NEXUS Chest CT CDR to determine its impact on missed injuries, cost, and radiation exposure. Methods We constructed a decision model comparing two strategies: implementation of the NEXUS Chest CDR vs. usual care in the evaluation of adults with blunt trauma. We derived probabilities, clinical outcomes, effective radiation dose (ERD) from the NEXUS Chest CT validation cohort and costs from the Charge-master at the primary study site. Our primary outcomes were cost and effective radiation dose (ERD) per missed clinically significant injury (CSI). Results Using a hypothetical cohort of 1000 adults with blunt chest trauma in each arm, the base case model projected that the implementation of the CDR would result in 161 fewer chest CTs, 0.08 additional missed CSIs, a cost savings of $136,432 and a decrease in 1435 mSv, as compared to Usual Care. To detect one additional CSI, the Usual Care strategy would require 2015 more chest CTs with a cost of $1.8 million and 17,934 mSv more radiation. Conclusions Compared to usual care, implementation of the NEXUS Chest CT Major CDR in the evaluation of adults with blunt trauma would greatly reduce CT associated costs and radiation exposure with a slight increased risk of missed CSIs.

Purpose The purpose of this study was to investigate an enlarged dacryoadenotic lacrimal gland and normal lacrimal glands for the presence of goblet cells (mucocytes). Design Retrospective clinicopathologic series. Methods An enlarged lacrimal gland (dacryoadenosis) without obvious histopathologic alterations was extensively evaluated histochemically, immunohistochemically, and ultrastructurally to detect the presence of goblet cells and to compare the findings with those in five normal lacrimal glands. Results Granular, zymogen-rich pyramidal acinar cells in normal glands predominated over a previously not reported subpopulation of nongranular, pale-staining cells in both dacryoadenotic and normal lacrimal glands. These cells histochemically stained positively with mucicarmine and Alcian blue. Immunohistochemical and electron microscopic evaluations established that there was a displacement or replacement of cytoplasmic gross cystic disease fluid protein-15 and CK 7-positive tonofilaments in the pale acinar cells by myriad mucus granules. The goblet cells constituted approximately 2% of the normal acinar cells and 5% of dacryoadenotic acinar cells. A depletion of myoepithelial cells and ectopic intra-acinar ductular cells were also observed in dacryoadenosis. Conclusion Dacryoadenosis is caused by an increase in the number of acini without individual acinar cell hyperplasia. A normal cytologic feature of the lacrimal gland is the presence of acinar goblet cells that had been long overlooked; they are increased in number in dacryoadenosis. Intra-acinar ductular cells and the scattered loss of myoepithelial cells are other abnormalities in dacryoadenosis. The presence of lacrimal gland goblet cells may have physiologic implications for the precorneal tear film and its derangements as well as for the histogenesis of mucus-producing carcinomas.

Because of underutilization of liver allografts, our center previously showed that hepatitis C virus (HCV) antibody-positive/nucleic acid test (NAT)-negative livers when transplanted into HCV nonviremic recipients were safe with a 10% risk of HCV transmission. Herein, we present our single-center prospective experience of using HCV NAT+ liver allografts transplanted into HCV NAT- recipients. An institutional review board-approved matched cohort study was conducted examining post- liver transplantation (LT) outcomes of HCV- patients who received HCV NAT+ organs (treatment group) compared with matched recipients with HCV NAT- organs (matched comparator group) between June 2018 to October 2019. The primary endpoint was success of HCV treatment and elimination of HCV infection. The secondary outcomes included the 30-day and 1-year graft and patient survival as well as perioperative complications. There were 32 recipients enrolled into each group. Because of 1 death in the index admission, 30/31 patients (97%) were given HCV treatment at a median starting time of 47 days (18-140 days) after LT. A total of 19 (63%) patients achieved sustained virological response at week 12 (SVR12). Another 6 patients achieved end-of-treatment response, while 5 remained on therapy and 1 is yet to start treatment. No HCV treatment failure has been noted. There were no differences in 30-day and 1-year graft and patient survival, length of hospital stay, biliary or vascular complications, or cytomegalovirus viremia between the 2 groups. In this interim analysis of a matched cohort study, which is the first and largest study to date, the patients who received the HCV NAT+ organs had similar outcomes regarding graft function, patient survival, and post-LT complications.

Simultaneous liver-kidney transplantation (SLKT) is indicated for patients with end-stage liver disease (ESLD) and concurrent renal insufficiency. En bloc SLKT is an alternative to traditional separate implantations, but studies comparing the two techniques are limited. The en bloc technique maintains renal outflow via donor infrahepatic vena cava and inflow via anastomosis of donor renal artery to donor splenic artery. Comparison of recipients of en bloc (n = 17) vs traditional (n = 17) SLKT between 2013 and 2017 was performed. Recipient demographics and comorbidities were similar. More recipients of traditional SLKT were dialysis dependent (82.4% vs 41.2%, P = .01) with lower baseline pretransplant eGFR (14 vs 18, P = .01). En bloc SLKT was associated with shorter kidney cold ischemia time (341 vs 533 minutes, P < .01) and operative time (374 vs 511 minutes, P < .01). Two en bloc patients underwent reoperation for kidney allograft inflow issues due to kinking and renal steal. Early kidney allograft dysfunction (23.5% in both groups), 1-year kidney graft survival (88.2% vs 82.4%, P = 1.0), and posttransplantation eGFR were similar between groups. In our experience, the en bloc SLKT technique is safe and feasible, with comparable outcomes to the traditional method.

Pediatric-type follicular lymphoma is an uncommon B-cell lymphoma that primarily involves the lymph nodes of the head and neck of children and young adults. Ocular involvement is rare, with only 5 well-documented cases in the literature, all occurring in the conjunctiva. The authors describe a 20-year-old African American man with enlarging bilateral medial conjunctival nodules. Excisional biopsy of the larger left conjunctival lesion, clinically presumed to be pyogenic granuloma, revealed pediatric-type follicular lymphoma composed of expansile follicles with germinal centers containing mitotically active blastoid cells, which coexpressed CD20, CD10, and BCL6 and lacked expression of BCL2. Polymerase chain reaction for immunoglobulin heavy chain rearrangement identified a monoclonal B-cell population. Fluorescence in situ hybridization studies failed to demonstrate BCL2, BCL6, and MALT1 gene rearrangements. Next-generation sequencing revealed a pathogenic MAP2K1 mutation, known to be enriched in pediatric-type follicular lymphoma. This report summarizes the clinical and pathologic diagnostic findings, biologic behavior, and management of conjunctival pediatric-type follicular lymphoma.

Morbid obesity is a barrier to kidney transplant in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (SG) is an increasingly considered intervention, but the safety and long-term outcomes are uncertain. We reviewed prospectively collected data on patients with ESRD and chronic kidney disease (CKD) undergoing SG from 2011 to 2018. There were 198 patients with ESRD and 45 patients with CKD (stages 1-4) who met National Institutes of Health guidelines for bariatric surgery and underwent SG; 72% and 48% achieved a body mass index of ≤ 40 and ≤ 35 kg/m2 , respectively. The mean percentages of total weight loss and excess weight loss were 18.9 ± 10.8% and 38.2 ± 20.3%, respectively. SG reduced hypertension (85.8% vs 52.1%), decreased antihypertensive medication use (1.6 vs 1.0) (P < .01 each), and reduced incidence of diabetes (59.6% vs 32.5%, P < .01). Of the 71 patients with ESRD who achieved a body mass index of ≤ 40 kg/m2 , 45 were waitlisted and received a kidney transplant, whereas 10 remain on the waitlist. Mortality rate after SG was 1.8 per 100 patient-years, compared with 7.3 for non-SG. Patients with stage 3a or 3b CKD exhibited improved glomerular filtration rate (43.5 vs 58.4 mL/min, P = .01). In conclusion, SG safely improves transplant candidacy while providing significant, sustainable effects on weight loss, reducing medical comorbidities, and possibly improving renal function in stage 3 patients.

Purpose To determine if there is a biologic rationale for using checkpoint inhibitor drugs targeting programmed cell death ligand 1 (PD-L1) and PD-L2 in the treatment of adenoid cystic carcinoma of the orbit. Methods Twenty-three cases of adenoid cystic carcinoma involving the orbit (13 primary lacrimal gland, 5 secondarily extending into the orbit, and 5 unspecified) were examined histopathologically. Immunohistochemistry for PD-L1, PD-L2, and CD8 was performed. Charts were reviewed for clinical correlations. Results Expression of PD-L1 and of PD-L2 was overall low in adenoid cystic carcinoma (mean expression 1.4 ± 0.9 of 5 for PD-L1, mean 0.83 ± 1.1 of 5 for PD-L2), and tumor-infiltrating CD8-positive T-lymphocytes were sparse (mean 1.1 ± 0.51 of 3). Only 13 of the 23 (57%) cases expressed PD-L1 as a combined positive score ≥1 of cells. No associations were found between expression levels of these markers and patient sex, tumor site of origin, Tumor, Node, Metastasis stage, or patient outcome. A significant association was observed between stromal PD-L1 expression and tumor histopathologic subtype (p = 0.05), and between tumor PD-L1 expression and prior exposure to radiation (p = 0.03). Conclusions Checkpoint inhibitor drugs may have limited impact in the treatment and clinical course of orbital adenoid cystic carcinoma based on the low frequency of CD8 infiltrate and low expression of PD-L1 and PD-L2. Pretreatment with radiation, however, may improve tumor response to checkpoint inhibitor drugs.

Background: Muir-Torre syndrome (MTS) is defined clinically as the association of cutaneous sebaceous neoplasm and visceral malignancy. Ancillary tests are considered crucial for diagnosis. Although screening guidelines for MTS, including the Mayo MTS scoring system, have been proposed, there are no ophthalmic site-specific guidelines. Summary: A literature review conducted by PubMed search for articles describing patients with periocular sebaceous neoplasm and MTS disclosed 31 publications describing 60 patients, 36 (60%) of whom fulfilled clinical criteria for MTS, 6 (10%) whose diagnosis was based on screening ancillary studies, 14 (23%) who fulfilled clinical criteria and had supporting screening ancillary studies, and 4 (7%) who fulfilled clinical criteria and had supporting diagnostic genetic testing. Most patients were male (34 vs. 15 females), with a median age of 59 years (range 37–79 years). The most common diagnosis was sebaceous carcinoma (40/60, 67%), followed by sebaceous adenoma (16/60, 27%), followed by other tumors with sebaceous differentiation (4/60, 6%). The periocular lesions were identified prior to visceral malignancy in 10 out of 45 (22%) cases, after visceral malignancy in 34 out of 45 (76%) cases, and concurrently with visceral malignancy in 1 out of 45 (2%) cases. Immunohistochemistry for mismatch repair proteins was performed in 41 out of 60 (68%) and 14 out of 38 (37%) of the tumors had lost MSH2. Based on Mayo-MTS scores of 2 or greater, and after removing visceral malignancies not included in their scoring algorithm, 26 out of 30 of patients (87%) with complete data were considered to be appropriate candidates for further work-up. A survey of current practice was conducted by questionnaires, distributed to ophthalmic pathologists, ocular oncologists, and oculoplastic surgeons from national and international professional societies. Of the 103 physicians who participated in the survey, 91 (88%) felt that MTS evaluation guidelines were not sufficiently clear. Key Messages: Our findings suggest that Mayo MTS screening guidelines may be applicable to periocular sebaceous neoplasms. The uncertainty of ophthalmic specialists about optimal screening guidelines for MTS reflects the heterogeneity of defining criteria for MTS and limited molecular genetic data. Larger studies with detailed clinical, histopathologic, and molecular genetic data are required to formally assess screening guidelines for MTS in patients with periocular sebaceous neoplasms.

IMPORTANCE: High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving. OBJECTIVE: To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world. DESIGN, SETTING, AND PARTICIPANTS: An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers. INTERVENTION: Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma. MAIN OUTCOMES AND MEASURES: High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis. RESULTS: Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (=3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (

BACKGROUND: Coronavirus disease-19 (COVID-19), resulting from infection with SARS-CoV-2, spans a wide spectrum of illness. In severely ill patients, highly elevated serum levels of certain cytokines and considerable cytolytic T cell infiltrates in the lungs have been observed. These same patients may bear low to negligible viral burdens suggesting that an overactive immune response, often termed cytokine storm, contributes to the severity of COVID-19. We report the safety and efficacy of baricitinib combined with remdesivir and dexamethasone in 45 hospitalized patients with COVID-19 pneumonia at a tertiary academic medical center. METHODS: Retrospective review of 45 patients hospitalized with COVID-19 pneumonia. Patients received 7-day course of baricitinib, 5-day course of remdesivir and 10-day course of dexamethasone. Clinical status and biomarkers were obtained daily. Outcomes assessed include mortality, duration of hospitalization, presence of shock, need for supplemental oxygen, need for non-invasive ventilation, need for mechanical ventilation and development of thrombosis. RESULTS: Obesity and multiple medical comorbidities were associated with hospitalization in the setting of COVID-19. Treated patients demonstrated rapid declines of C-reactive protein (CRP), ferritin and D-dimer with gradual improvement in hemoglobin, platelet counts and clinical status. Only 2 of 45 (4.4%) treated patients required mechanical ventilation after initiating treatment and there were six deaths (13.3%).Only 2 of 45 (4.4%) treated patients required mechanical ventilation after initiating treatment. There were six deaths (13.3%) and these were associated with lower BMI. CONCLUSIONS: These findings support the utility of immunosuppression via JAK inhibition in moderate to severe COVID-19 pneumonia.

Objective Specific responsivity features are not directly targeted in offender rehabilitation programs but may impact a client's receptivity. We investigated if two features may explain why high-quality correctional programs do not uniformly impact all high-risk, high-needs clients. Hypotheses The current study was exploratory. We hypothesized a relationship between higher static risk and poorer program outcomes and then explored if this relationship was attenuated by age and motivation. Method Program providers rated the performance of incarcerated males (n = 2,417, Mean age = 33.6, SD = 9.9, Range = 18-81) who attended one of six types of programs during incarceration (for general, violent, and sexual offenders). Using risk scores calculated at prison entry, we predicted performance and official record recidivism. Preprogram motivation and age were moderators. Results Five of 24 exploratory multilevel models revealed an attenuated relationship between risk and program outcome among older offenders (percent variance explained = 17.9% within violence groups; 11.5% within living skills groups; and a 9% difference in predicted recidivism rates among high-risk attendees of family violence groups) and offenders with higher preprogram motivation (percent variance explained = 43.6% within violence groups, and a 7% difference in predicted recidivism rates among high risk attendees in living skills groups). Conclusions Age and motivation can be specific responsivity features that may deserve attention in rehabilitation practice. However, observed effects may have been weakened by underdeveloped, single-indicator measurement strategies. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Aim: Physical therapy and exercise are considered essential components in the management of Parkinson's disease (PD). Using our retrospective data and years of experience in assigning persons with PD to multilevel group classes we propose a two-part physical therapy decision-making tool consisting of participant and exercise program considerations. Methods: Retrospective medical record review and therapist consensus identified evaluation considerations determined to aide clinical decision making. The ability of these variables (i.e., demographics, clinical characteristics, clinical measures cut-offs) to predict the class assignment decision of PD-specialized physical therapists was evaluated using discriminant function analysis. Results: Therapist-assigned groups differed significantly on all clinical measures (p

The operative experience of today's general surgery resident has changed, but little is known about the modern experience as nonprimary surgeon. We set out to explore changes in the operative experience of general surgery residents as first assistant (FA) and teaching assistant (TA).This is a review of ACGME national operative log reports from 1990 to 2018. TA and FA cases were analyzed. Statistical analysis was performed using polynomial regression analysis and Kruskal-Wallis test. Statistical significance was set at p0.05.30,260 individuals completed general surgery residency during the study period with medians of 951 (interquartile range: 929-974) total major, 63 (31-184) FA, and 32 (25-48) TA cases. As a proportion of total cases completed, FA cases decreased from 21.8% of the total operative experience in 1990 to 2.5% in 2018, and TA cases declined from 7.4% of the total operative experience in 1990 to 3.5% in 2018. Regression modeling demonstrated that both operative roles decreased over time, but at a progressively decreasing rate, with FA cases reaching a "floor" around 2010 and TA cases reaching a "breakpoint" in 2008 at which time operative volume rebounded and began to increase. Among the core general surgery domains of abdomen and alimentary tract, compositional analysis revealed a decrease across each of the 11 operative subcategories (all p0.05) for FA, and for TA, a decrease in 6 of the 11 operative subcategories (stomach, small intestine, large intestine, anorectal, hernia, and biliary, all p0.05).Over the past 3 decades, the resident operative experience as nonprimary surgeon has decreased dramatically, with today's residents graduating with fewer FA and TA cases. As surgical training has traditionally relied heavily on an apprenticeship model for learning technical skills, it is essential that surgical educators recognize and rectify these trends.

Objectives The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. Summary background data Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. Methods From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. Results With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P Conclusions This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.