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Dengue virus infection in humans ranges from asymptomatic infection to severe infection, with ∼2.5 % overall disease fatality rate. Evidence of neurological manifestations is seen in the severe form of the disease, which might be due to the direct invasion of the viruses into the CNS system but is poorly understood. In this study, we demonstrated that the aged AG129 mice are highly susceptible to dengue serotypes 1–4, and following the adaptation, this resulted in the generation of neurovirulent strains that showed enhanced replication, aggravated disease severity, increased neuropathogenesis, and high lethality in both adult and aged AG129 mice. The infected mice had endothelial dysfunction, elicited pro-inflammatory cytokine responses, and exhibited 100 % mortality. Further analysis revealed that aged-adapted DENV strains induced measurable alterations in TLR expression in the aged mice as compared to the adult mice. In addition, metabolomics analysis of the serum samples from the infected adult mice revealed dysregulation of 18 metabolites and upregulation of 6-keto-prostaglandin F1 alpha, phosphocreatine, and taurocholic acid. These metabolites may serve as key biomarkers to decipher and comprehend the severity of dengue-associated severe neuro-pathogenesis.

Background: This study aims to examine and determine the role of race/ethnicity in chronic conditions in women diagnosed with gestational diabetes mellitus (GDM) during any of their previous pregnancies. Methods: We used the National Health and Nutrition Examination Survey (NHANES) from2007–2016 to identify women who self-reported prior GDM and chronic disease diagnoses such as cardiovascular disease, hypertension, depression, and type 2 diabetes mellitus (T2DM).We used bivariate analysis using the chi-square test (χ²) and multiple logistic regressions to perform statistical test for associations, taking into consideration design and sample weight. Results: Among participants with prior GDM diagnoses, black women had a 74.4% prevalence of chronic disease, followed by Whites, 58.5% Hispanics, 58.0%, and Asians, 51.9% (P=0.009).Black women with prior GDM diagnoses had 2.4 odds of having chronic conditions compared to Whites (adjusted odds ratio [AOR]=2.40, 95% confidence interval [CI] = 1.28-4.50). In addition, they had higher odds of being former smokers (AOR=1.73, 95% CI=1.01-2.96),current smokers (AOR=1.96, 95% CI=1.06-3.61), having a body mass index (BMI) of 25-29.9(AOR=2.55, 95% CI=1.10-5.87), or a BMI ≥30 (AOR=4.09, 95% CI = 2.05-8.17) compared to their White counterparts. Hispanic women had lower odds of being diagnosed with GDM and associated chronic diseases. Conclusion: Black women with GDM were disproportionally affected and at higher risk to be diagnosed with chronic conditions. Smoking and obesity were strongly associated with chronic disease diagnoses. Our findings also suggest a ‘Hispanic Paradox’, requiring further study. These findings inform primary care clinicians and Obstetricians, and Gynecologists of at-risk patients who could benefit from lifestyle modification recommendations and counseling.

Objective: The purpose of this study was to evaluate the diagnostic utility of SATB2 in detecting CRC origin for patients presenting with metastatic carcinomas. Study Design: Cross sectional, comparative study. Place and Duration of Study: Study was conducted at department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from January 2019 to June 2019. Materials and Methods: Already diagnosed 68 cases of metastatic carcinoma of various origins with unknown primary were retrieved from tumour registry. Paraffin embedded blocks were taken and a panel of Immunohistochemistry was applied which includes CK7, CK20,CDX2 and SATB2. Positivity of SATB2 alone, and combination of SATB2 with CK 7,CK20 and CDX2 was evaluated. Results: Out of 68 metastatic adenocarcinoma cases 28(41%) had positive SATB2 expression and 38 (56%) were negative. All the positive SATB2 cases had 100 % (28/28) expression with CDX2, 93% (26/28) of the cases had expression with CK20 and 21% (6/28) of the cases showed expression of CK7. The sensitivity of SATB2 alone was 100% in metastatic colorectal carcinoma as compared to CK20 and CDX2. The sensitivity of SATB2 in combination with CDX2 (100%) and CK20 (93%)in comparison to the double combination of CK20 and CDX2(93 %). The sensitivity of SATB2 and CK20 combination was 93%, which was equal to CK20 and CDX2 combination. Conclusions: Our results show that SATB2 is a sensitive marker in the IHC panel for cases with suspected metastasis from colorectal region.

Gas gangrene is a life threatening infection of muscles and soft tissues which is associated with very high mortality rate. Non clostridial gas gangrene is a rare phenomenon that mostly occurs in diabetic patients. Gas gangrene leads to various systemic manifestations. A 66-year-old female patient, diabetic with chronic kidney disease, on haemodialysis was presented as a rare case of non clostridial right great toe gas gangrene, which progressed to systemic toxicity and stroke within a period of 72 hours in postoperative period. The source of infection in this case may have been Acinetobacter which is a gram-negative bacterium. Despite prompt diagnosis and intensive therapy, the patient died 15 days after the operation. After going through literature, no case was found to be reported of stroke in postoperative period due to non clostridial gas gangrene thus making it a unique case to report. Also, only few cases of life threatening non clostridial gas gangrene are reported in literature.

The current Coronavirus Disease 2019 (COVID-19) has had an immense adverse effect on provision of routine healthcare services including maternity care. Prenatal invasive procedures are amongst the most affected due to their availability at limited centres, reallocation of health resources, restricted mobility of individuals and the perceived ‘semi-elective’ nature of these procedures. However, these are essential procedures, even life-saving in cases of fetal anaemia, and time-sensitive especially considering the upper limit of legal age of medical termination of pregnancy in India. Data on COVID-19 is currently limited and the risk of vertical transmission is unknown. We present our experience of prenatal invasive procedure during April 2020 and May 2021, the peak months of COVID-19 and stringent lockdown.

We retrospectively reviewed the records of 273 renal transplant recipients who received allograft transplants between 1994 and 2004 and recorded the incidence and types of de novo malignancies that developed in these patients. The study was carried out at the Al-karama and Al-rasheed kidney transplant centers in Baghdad, Iraq. A total of 16 patients developed malignancies. The tumors included Kaposi′s sarcoma (KS) in eight patients, squamous cell carcinoma (SCC) in four, basal cell carcinoma (BCC) in two and both renal cell carcinoma of the allograft and brain tumor in one patient. Thus, KS was the most common malignancy encountered in our series, with a prevalence of 2.9%, followed by SCC observed in 1.5% and BCC found in 0.7 % of the patients. The average latency period between transplantation and development of malignancy was 6.5 months for KS, 3.0 months for SCC and 8.5 months for BCC. To our knowledge, this is the first long-term follow-up study for malignant complications identified in kidney recipients in Iraq.

Background: The demand for liver transplantation has led to the utilization of marginal grafts including moderately macrosteatotic livers (macrosteatosis ≥30% [Mas30]), which are associated with an elevated risk of graft failure. Machine perfusion (MP) has emerged as a technique for organ preservation and viability testing; however, little is known about MP in Mas30 livers. This study evaluates the utilization and outcomes of Mas30 livers in the era of MP., Methods: The Organ Procurement and Transplantation Network database was queried to identify biopsy-proven Mas30 deceased donor liver grafts between June 1, 2016, and June 23, 2023. Univariable and multivariable models were constructed to study the association between MP and graft utilization and survival., Results: The final cohort with 3317 Mas30 livers was identified, of which 72 underwent MP and were compared with 3245 non-MP livers. Among Mas30 livers, 62 (MP) and 1832 (non-MP) were transplanted (utilization of 86.1% versus 56.4%, P  < 0.001). Donor and recipient characteristics were comparable between MP and non-MP groups. In adjusted analyses, MP was associated with significantly increased Mas30 graft utilization (odds ratio, 7.89; 95% confidence interval [CI], 3.76-16.58; P  < 0.001). In log-rank tests, MP was not associated with 1- and 3-y graft failure (hazard ratio, 0.49; 95% CI, 0.12-1.99; P  = 0.319 and hazard ratio 0.43; 95% CI, 0.11-1.73; P  = 0.235, respectively)., Conclusions: The utilization rate of Mas30 grafts increases with MP without detriment to graft survival. This early experience may have implications for increasing the available donor pool of Mas30 livers., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: P.L.A. has received grant support from the Gift of Life Foundation and the American Society of Transplant Surgeons related to ex vivo machine perfusion and normothermic regional perfusion research. The other authors declare no conflicts of interest.

Given liver transplantation organ scarcity, selection of recipients and donors to maximize post-transplant benefit is paramount. Several scores predict post-transplant outcomes by isolating elements of donor and recipient risk, including the donor risk index, Balance of Risk, pre-allocation score to predict survival outcomes following liver transplantation/survival outcomes following liver transplantation (SOFT), improved donor-to-recipient allocation score for deceased donors only/improved donor-to-recipient allocation score for both deceased and living donors (ID2EAL-D/-DR), and survival benefit (SB) models. No studies have examined the performance of these models over time, which is critical in an ever-evolving transplant landscape. This was a retrospective cohort study of liver transplantation events in the UNOS database from 2002 to 2021. We used Cox regression to evaluate model discrimination (Harrell's C) and calibration (testing of calibration curves) for post-transplant patient and graft survival at specified post-transplant timepoints. Sub-analyses were performed in the modern transplant era (post-2014) and for key donor-recipient characteristics. A total of 112,357 transplants were included. The SB and SOFT scores had the highest discrimination for short-term patient and graft survival, including in the modern transplant era, where only the SB model had good discrimination (C ≥ 0.60) for all patient and graft outcome timepoints. However, these models had evidence of poor calibration at 3- and 5-year patient survival timepoints. The ID2EAL-DR score had lower discrimination but adequate calibration at all patient survival timepoints. In stratified analyses, SB and SOFT scores performed better in younger (< 40 y) and higher Model for End-Stage Liver Disease (≥ 25) patients. All prediction scores had declining discrimination over time, and scores relying on donor factors alone had poor performance. Although the SB and SOFT scores had the best overall performance, all models demonstrated declining performance over time. This underscores the importance of periodically updating and/or developing new prediction models to reflect the evolving transplant field. Scores relying on donor factors alone do not meaningfully inform post-transplant risk., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The prevalence of obesity is rising in the general population. Donor obesity (body mass index ≥30 kg/m 2 ) may potentially reduce the donor pool and impact outcomes in living donor liver transplantation (LDLT)., Methods: We utilized the national transplant database to investigate the impact of donor obesity on donor and recipient outcomes. This was a retrospective cohort study of all LDLTs performed in the United States between January 2010 and June 2023. Outcomes of interest were analyzed by univariable and multivariable logistic regression. Patient and graft survival was evaluated using Kaplan-Meier and Cox proportional analysis., Results: Six hundred seventy-four donors with obesity and 3498 donors without obesity were analyzed. Donors with obesity had higher rates of readmission within 1 y of donation (15.9% versus 11.6%; P = 0.003). The risk of readmission was significantly different between 6 wk and 6 mo of donation (8.8% versus 5.9%; P = 0.036). Donor body mass index (odds ratio [OR], 1.460; 95% confidence interval [CI], 1.129-1.999; P = 0.004) and preoperative alkaline phosphatase levels (OR, 1.005; 95% CI, 1.000-1.011; P = 0.038) were independent predictors of donor readmission. High LDLT center volume was associated with reduced odds of donor readmission (OR, 0.509; 95% CI, 0.373-0.694; P  < 0.001). Graft and recipient survival was comparable., Conclusions: Selection of living donors with obesity may be a potential avenue to increase the available donor pool without compromising recipient outcomes; however, they are at an increased risk for readmission between 6 wk and 6 mo of donation. The reason for readmission requires further study., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: In 2015, the United Network for Organ Sharing implemented a policy introducing a 6-mo waiting period before granting model for end-stage liver disease exception points to liver transplant (LT) candidates with hepatocellular carcinoma (HCC). This study analyzes the policy impact on post-LT HCC recurrence., Methods: This was a United Network for Organ Sharing retrospective cohort study of patients with HCC who underwent LT from January 1, 2010, to May 31, 2019. HCC-specific data included alpha-fetoprotein, tumor characteristics, locoregional therapy (LRT), and explant data used to calculate the Risk Estimation of Tumor Recurrence After Transplant score. The primary exposure was pre-/post-policy era, divided on October 8, 2015. Survival analysis techniques were used to evaluate the unadjusted and sequentially adjusted association between policy era and HCC recurrence, accounting for competing risks., Results: A total of 7940 patients were included, 5879 (74.0%) pre-policy era and 2061 (26.0%) post-policy era. Post-policy patients were older, received more LRT, and had lower alpha-fetoprotein levels and smaller tumor sizes at transplant. Incidence rates of HCC recurrence were 19.8 and 13.7 events per 1000 person-years for pre- and post-policy eras, respectively. Post-policy era was associated with an unadjusted 35% reduction in the risk of HCC recurrence ( P  < 0.001). After adjusting for recipient, donor, and tumor characteristics at listing this association remained (subhazard ratio 0.69; 95% confidence interval, 0.55-0.86; P  = 0.001); however, after additionally adjusting for LRT episodes and Risk Estimation of Tumor Recurrence After Transplant score, there was no longer a statistically significant association (subhazard ratio 0.77; 95% confidence interval, 0.59-1.00; P  = 0.054)., Conclusions: We observed a significant reduction in post-LT HCC recurrence after policy implementation. This may be due to waitlist selection of healthier patients, increased LRT utilization, and potential selection of favorable tumor biology., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In liver transplantation, advances in ex situ normothermic machine perfusion (NMP) have improved outcomes compared with traditional static cold storage (SCS) in donation after circulatory death (DCD) organs. We aimed to characterize trends in the utilization of NMP versus SCS in DCD liver transplantation in the United States., Methods: This retrospective cohort study used data from the United Network for Organ Sharing database to identify recipient-donor adult liver transplant pairs from DCD donors from January 2016 to June 2022. Utilization of NMP and changes in donor risk index (DRI) and components between NMP and SCS were assessed across transplant year eras (2016-2018, 2019-2020, and 2021-2022). Statistical comparisons were made using the Kruskal-Wallis test or the chi-square test., Results: A total of 3937 SCS and 127 NMP DCD donor transplants were included. Utilization of NMP ranged from ~0.4% to 3.5% from 2016 to 2021 and rose significantly to 11.2% in early 2022. Across transplant eras, median DRI increased significantly for SCS and NMP, but the magnitude of the increase was larger for NMP. With NMP DCDs, there were significant increases in median donor age, national share proportion, and "cold ischemic time" over time. Finally, there was a shift toward including higher DRI donors and higher model for end-stage liver disease score transplant recipients with NMP in later transplant eras., Conclusions: In recent years, NMP utilization has increased and expanded to donors with higher DRI and recipients with higher model for end-stage liver disease score at transplant, suggesting increasing familiarity and risk tolerance with NMP technology. As NMP remains a relatively new technique, ongoing study of patient outcomes, organ allocation practices, and utilization patterns is critical., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Small-for-size syndrome (SFSS) is a well-recognized complication following liver transplantation (LT), with up to 20% developing this following living donor LT (LDLT). Preventing SFSS involves consideration of factors before the surgical procedure, including donor and recipient selection, and factors during the surgical procedure, including adequate outflow reconstruction, graft portal inflow modulation, and management of portosystemic shunts. International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplant Society of India Consensus Conference was convened in January 2023 to develop recommendations for the prediction and management of SFSS in LDLT. The format of the conference was based on the Grading of Recommendations, Assessment, Development, and Evaluation system. International experts in this field were allocated to 4 working groups (diagnosis, prevention, anesthesia, and critical care considerations, and management of established SFSS). The working groups prepared evidence-based recommendations to answer-specific questions considering the currently available literature. The working group members, independent panel, and conference attendees served as jury to edit and confirm the final recommendations presented at the end of the conference by each working group separately. This report presents the final statements and evidence-based recommendations provided by working group 2 that can be implemented to prevent SFSS in LDLT patients., Competing Interests: The authors declare no funding or conflicts of interest, (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Bariatric surgery procedures, in particular Roux-en-Y gastric bypass (RYGB), have been associated with subsequent alcohol-related complications. However, previous studies lack data to account for changes in body mass index (BMI) or alcohol use over time, which are key potential confounders., Objective: To evaluate the association between RYGB, sleeve gastrectomy, or gastric banding on subsequent alcohol use disorder (AUD)-related hospitalization and all-cause mortality as compared with referral to a weight management program alone., Design, Setting, and Participants: This cohort study included 127 Veterans Health Administration health centers in the US. Patients who underwent RYGB, sleeve gastrectomy, or gastric banding or who were referred to MOVE!, a weight management program, and had a BMI (calculated as weight in kilograms divided by height in meters squared) of 30 or greater between January 1, 2008, and December 31, 2021, were included in the study., Exposures: RYGB, sleeve gastrectomy, or gastric banding or referral to the MOVE! program., Main Outcomes and Measures: The primary outcome was time to AUD-related hospitalization from the time of bariatric surgery or MOVE! referral. The secondary outcome was time to all-cause mortality. Separate propensity scores were created for each pairwise comparison (RYGB vs MOVE! program, RYGB vs sleeve gastrectomy, sleeve gastrectomy vs MOVE!). Sequential Cox regression approaches were used for each pairwise comparison to estimate the relative hazard of the primary outcome in unadjusted, inverse probability treatment weighting (IPTW)-adjusted (generated from the pairwise logistic regression models), and IPTW-adjusted approaches with additional adjustment for time-updating BMI and categorical Alcohol Use Disorders Identification Test-Concise scores., Results: A total of 1854 patients received RYGB (median [IQR] age, 53 [45-60] years; 1294 men [69.8%]), 4211 received sleeve gastrectomy (median [IQR] age, 52 [44-59] years; 2817 men [66.9%]), 265 received gastric banding (median [IQR] age, 55 [46-61] years; 199 men [75.1%]), and 1364 were referred to MOVE! (median [IQR] age, 59 [49-66] years; 1175 men [86.1%]). In IPTW Cox regression analyses accounting for time-updating alcohol use and BMI, RYGB was associated with an increased hazard of AUD-related hospitalization vs MOVE! (hazard ratio [HR], 1.70; 95% CI, 1.20-2.41; P = .003) and vs sleeve gastrectomy (HR, 1.98; 95% CI, 1.55-2.53; P < .001). There was no significant difference between sleeve gastrectomy and MOVE! (HR, 0.76; 95% CI, 0.56-1.03; P = .08). While RYGB was associated with a reduced mortality risk vs MOVE! (HR, 0.63; 95% CI, 0.49-0.81; P < .001), this association was mitigated by increasing alcohol use over time., Conclusions and Relevance: This cohort study found that RYGB was associated with an increased risk of AUD-related hospitalizations vs both sleeve gastrectomy and the MOVE! program. The mortality benefit associated with RYGB was diminished by increased alcohol use, highlighting the importance of careful patient selection and alcohol-related counseling for patients undergoing this procedure.

Objective: To define benchmark cutoffs for redo liver transplantation (redo-LT)., Background: In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, there is a lack of benchmark data to reliably evaluate outcomes after redo-LT., Methods: We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers., Results: Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks., Conclusion: This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Patients with cirrhosis have increased risk of postoperative mortality. Several models have been developed to estimate this risk; however, current risk estimation scores cannot compare surgical risk with the risk of not operating., Objective: To identify clinical optimal thresholds to favor operative or nonoperative management for a common cirrhosis surgical scenario, the symptomatic abdominal hernia., Design, Setting, and Participants: This was a Markov cohort decision analytical modeling study evaluating elective surgery vs nonoperative management for a symptomatic abdominal hernia in a patient with cirrhosis. Transition probabilities and utilities were derived from the literature and from data using an established cirrhosis cohort in the Veterans Health Administration. Participants included patients who were referred to a surgery clinic for a symptomatic abdominal hernia. Data were obtained from patients diagnosed with cirrhosis between January 1, 2008 and December 31, 2018. Data were analyzed from January 1 to May 1, 2022., Main Outcomes and Measures: Expected quality-adjusted life-years (QALYs) were estimated for each pathway and iterated over baseline model for end-stage liver disease-sodium (MELD-Na) scores ranging from 6 to 25. Markov models were cycled over a 5-year time horizon., Results: A total 2740 patients with cirrhosis (median [IQR] age, 62 [56-66] years; 2699 [98.5%] men) were referred to a surgery clinic for a symptomatic abdominal hernia; 1752 patients (63.9%) did not receive surgery. The median (IQR) follow-up was 42.1 (25.3-70.0) months. Using this cohort to estimate the mortality risk of operative and nonoperative pathways, an initial MELD-Na threshold of 21.3 points, below which surgery was associated with maximized QALYs was identified. Nonoperative management was associated with increased QALYs above this MELD-Na threshold. Although more patients experienced death with a surgical treatment decision across all initial MELD-Na values, this was counterbalanced by increased time spent in a resolved hernia state associated with increased utility. Model results were sensitive to the probability of hernia recurrence and hernia incarceration and utility decrement in the symptomatic hernia state., Conclusions and Relevance: This decision analytical model study found that elective surgical treatment for a symptomatic abdominal hernia was favored even in the setting of relatively high MELD-Na scores. Patient symptoms, hernia-specific characteristics, and surgeon and center expertise may potentially impact the optimal strategy, emphasizing the importance of shared decision-making.

Background: Given the national opioid crisis, postoperative analgesia at discharge must be thoughtfully prescribed. Data specifically related to thoracic procedures remain scarce. This study assessed adequacy of pain control with standardized and limited opioids after thoracic procedures., Methods: A standardized prescription comprised 15 hydromorphone tabs, 7 days of acetaminophen, and 3 days of ibuprofen was provided on discharge to elective thoracic surgery patients. On the first postoperative visit, patients completed a questionnaire regarding the number of hydromorphones used, use of additional opioids, pain-related limitation to function, and adequacy of pain control., Results: A total of 122 patients undergoing thoracic surgery procedures were surveyed. Twelve underwent open procedures and were excluded. An additional 6 patients who used opioids chronically preoperatively were also excluded. The remaining 104 patients were included in the study. Median age was 66 years (age range, 17-90 years) and median length of stay was 2 days (range, 1-15 days). Seventeen (16%) patients used all prescribed hydromorphone and 56 (54%) used none, 18 (17%) asked for additional or other opioid, and 14 (13%) felt that their pain significantly limited their function. Nine (9%) felt that that their pain was inadequately controlled., Conclusions: Pain after thoracic procedures, especially video-assisted thoracoscopic surgery, is adequately controlled with minimal opioid doses (combined with adjuncts), with less than 1 in 5 patients requiring additional prescriptions and very few patients complaining of pain that significantly limited their function. This study shows that a standardized limited opioid prescription is safe, is adequate, and can easily be implemented for the majority of thoracic surgery patients., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

One anastomosis gastric bypass (OAGB) surgery became a common bariatric procedure in recent years. In this surgery, the distal stomach, duodenum, and proximal jejunum are bypassed, leading to weight loss, improvement in metabolic parameters, and a change in hormonal secretion. We sought to generate and characterize a mouse model for OAGB. Mice fed for 26 wk on a high-fat diet were assigned to OAGB, sham surgery, or caloric restriction and were followed for 50 more days on a high-fat diet. Physiological and histological parameters of the mice were compared during and at the end of the experiment. OAGB-operated mice lost weight and displayed low levels of plasma lipids, high insulin sensitivity, and rapid glucose metabolism compared with sham-operated mice. OAGB-operated mice had higher energy expenditure, higher levels of glucagon-like peptide (GLP-1), and lower albumin than weight-matched calorie-restricted mice. There was no difference in the histology of the endocrine pancreas. The livers of OAGB mice had little hepatic steatosis yet presented with a large number of phagocytic cells. The OAGB mouse model recapitulates many of the phenotypes described in patients that underwent OAGB and enables molecular and physiological studies on the outcome of this surgery. NEW & NOTEWORTHY A mouse model for one anastomosis gastric bypass (OAGB) surgery displays similar outcomes to clinical reports and enables to study the weight loss-dependent and -independent effects of this bariatric surgery.

Introduction and Importance: Intrathoracic schwannomas are rare and difficult to diagnose. However, they are the most common type of neurogenic tumor in the chest. Most patients are incidentally diagnosed or develop symptoms from mass effect, such as chest pain, dysphagia or dyspnea. Larger tumors have been resected using open approaches, while smaller ones are often excised with minimally invasive approaches., Case Presentation: A 60-year-old woman with a prior Roux-en-Y gastric bypass and a history of dysphagia, decreased appetite, and weight loss was referred for evaluation. CT chest revealed an 8 cm soft tissue mass centered in the distal esophagus. Gastroscopy showed the tumor to be 8 cm as well, with 2 cm of normal esophagus prior to the gastric pouch. A right-sided video-assisted thoracoscopic (VATS) approach for enucleation was successfully completed with primary esophageal repair for an 8.0 × 5.5 × 6.5 cm schwannoma., Clinical Discussion: Surgical resection for schwannomas is often indicated due to symptoms from mass effect (Moro et al., 2017). There are reports of VATS and robotic-assisted thoracic surgery approaches for small tumors. These techniques are appealing due to shorter length of stays and less post-operative pain. None have been described for lesions larger than 6 cm., Conclusion: Minimally invasive approaches such as VATS for large schwannomas are technically feasible and safe to perform without the need for a thoracotomy., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we showed that we can identify pathology-related changes in hepatocyte transcriptional programs. In patients with metastatic colorectal carcinoma, we detected clinically relevant and patient-specific information, including transcriptionally active human epidermal growth factor receptor 2 (HER2) amplifications. Altogether, cfChIP-seq, using low sequencing depth, provides systemic and genome-wide information and can inform diagnosis and facilitate interrogation of physiological and pathological processes using blood samples.

Malignant cell growth is fueled by interactions between tumor cells and the stromal cells composing the tumor microenvironment. The human liver is a major site of tumors and metastases, but molecular identities and intercellular interactions of different cell types have not been resolved in these pathologies. Here, we apply single cell RNA-sequencing and spatial analysis of malignant and adjacent non-malignant liver tissues from five patients with cholangiocarcinoma or liver metastases. We find that stromal cells exhibit recurring, patient-independent expression programs, and reconstruct a ligand-receptor map that highlights recurring tumor-stroma interactions. By combining transcriptomics of laser-capture microdissected regions, we reconstruct a zonation atlas of hepatocytes in the non-malignant sites and characterize the spatial distribution of each cell type across the tumor microenvironment. Our analysis provides a resource for understanding human liver malignancies and may expose potential points of interventions., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Liver transplantation during the COVID-19 pandemic is challenging. Both donor and recipient issues can be influenced by the risks attributed to the pandemic. Allocation policy may need to be modified and criteria may be influenced by local infection rates and availability of medical facilities. Modifying immunosuppression (IS) protocols is controversial and is not evidence-based. In this study, we review the published literature on liver transplant recipients who were infected with COVID-19. A literature review was performed using PubMed, ScienceDirect, and WHO databases to identify relevant English-language articles published up to May 20, 2020. Fifteen articles reported 120 liver transplant recipients who were infected with COVID-19. Only 10 papers with 22 patients reported full encounter characteristics. Four papers reported 23, 17, 13, and 6 patients, respectively, but with minimal data. One paper reported the authors' own 39 patients' characteristics and demographics. The mean age was 58.2 years with 66% males. The most commonly reported presentations in descending order were fever (91%), cough (36.7%), shortness of breath (SOB) (31.8%), and diarrhea (31.8%). Liver transplant patients infected with COVID-19 were maintained on Tac (79%), mycophenolate (MMF) (48.4%), and Prednisone (29.6%) and were managed by reducing MMF in 14.3% of patients and reducing Tac in 14.3% of patients; 28.6% of patients needed ICU admission, 13.6% of patients had died, and the reported general population COVID-19 mortality rate was 3.4%. The clinical presentation of COVID-19 in liver transplant recipients may be different from the general population, with higher rates of severe disease, complications, and mortality.

Kidney transplantation at the time of a global viral pandemic has become challenging in many aspects. Firstly, we must reassess deceased donor safety (for the recipient) especially in communities with a relatively high incidence of coronavirus disease 19 (COVID-19). With respect to elective live donors, if one decides to do them at all, similar considerations must be made that may impose undue hardship on the donor. Recipient selection is also problematic since there is clear evidence of a much higher morbidity and mortality from COVID-19 for patients older than 60 and those with comorbidities such as hypertension, diabetes, obesity and lung disease. Unfortunately, many, if not most of dialysis patients fit that mold. We may and indeed must reassess our allocation policies, but this must be done based on data rather than conjecture. Follow-up routines must be re-engineered to minimize patient travel and exposure. Reliance on technology and telemedicine is paramount. Making this technology available to patients is extremely important. Modifying or changing immunosuppression protocols is controversial and not based on clinical studies. Nevertheless, we should reassess the need for induction therapy across the board for ordinary patients and the more liberal use of mammalian target of rapamycin inhibitors in transplant patients with proven infection., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)