Expression, purification and preliminary crystallographic analysis of bacterial transmembrane protein EfeU for iron import.

The bacterial Efe system functions as an importer of free Fe2+ into cells independently of iron-chelating compounds such as siderophores and consisted of iron-binding protein EfeO, peroxidase EfeB, and transmembrane permease EfeU. While we and other researchers reported crystal structures of EfeO and EfeB, that of EfeU remains undetermined. In this study, we constructed expression system of EfeU derived from Escherichia coli, selected E. coli Rosetta-gami 2 (DE3) as an expression host, and succeeded in purification of the proteins which were indicated to form an oligomer by blue native PAGE. We obtained preliminary data of the X-ray crystallography, suggesting that expression and purification methods we established in this study enable structural analysis of the bacterial Efe system.

Coronavirus Disease 2019 (COVID-19) in Heart Transplant Recipients and Anti-SARS-CoV-2 Monoclonal Antibodies: Experience, Lessons Learnt, and Future Challenges.

Solid organ transplant recipients (SOTRs), including heart transplant (HT) recipients, infected with Coronavirus disease 2019 (COVID-19) are at higher risk of hospitalization, mechanical ventilation, or death when compared with general population. Advances in diagnosis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have reduced COVID-19-related mortality rates from ~30% in the early pandemic to <3% in 2022 among HT recipients. We performed a retrospective chart review including adult HT recipients at Westchester Medical Center from January 1, 2020 to December 10, 2022, who received anti-SARS-CoV-2 monoclonal antibodies (mAbs) for treatment of mild-to-moderate COVID-19, and those who received tixagevimab/cilgavimab for preexposure prophylaxis. Additionally, a comprehensive review of the literature involving SOTRs who received mAbs for COVID-19 was conducted. In this largest single-center study in this population, 42 adult HT recipients received casirivimab/imdevimab (36%), sotrovimab (31%), or bebtelovimab (29%) for treatment of mild-to-moderate COVID-19. Among these recipients, no infusion-associated adverse effects, progression of disease, COVID-19-associated hospitalizations, or death were noted. Preexposure prophylaxis with tixagevimab/cilgavimab was given to 63 HT recipients in a dedicated infusion center (40%), inpatient setting (33%), or at time of annual heart biopsy (27%). No immediate adverse events were noted. There were 11 breakthrough infections, all mild. Overall, the data suggests that HT recipients receiving mAbs have reduced rates of hospitalization, need for intensive care unit care, or death. Use of anti-SARS-CoV-2 mAbs in SOTRs is resource intensive and requires a programmatic team approach for optimal administration and to minimize any risk of disparities in their use.

Radiation Therapy for Sister Mary Joseph's Nodule: A Review.

Purpose: Umbilical metastasis, known as Sister Mary Joseph's nodule (SMJN), is a manifestation of advanced malignant disease. Patients with SMJN usually require supportive care or palliative systemic chemotherapy. However, with the increasing number of older and infirm patients, radiation therapy for SMJN is needed more frequently. Therefore, we conducted this review to provide insights into radiation treatment for this rare condition. Methods and Materials: We searched PubMed on October 16, 2022, and obtained 275 articles that described SMJN or metastatic tumors within or near the umbilicus, as well as 255 case reports or case series (298 patients) and 20 reviews, original articles, or other study types, 1 of which also described a case. Results: The prognosis of patients with SMJN is extremely poor. However, some patients can survive for more than 2 years. The primary organs of the umbilical metastasis are mainly in the gastrointestinal tract, including the stomach, colon, and pancreas. In addition to these organs, the ovaries, uterine corpus, and breasts are the major organs affected in women. Metastasis may be divided into 4 types according to the tumor location and mechanism of the extension: within the umbilicus, not within although existing near or adjacent to the umbilicus, in the umbilical or paraumbilical hernia sac, and iatrogenic disease. Only 7 reports described patients who received radiation therapy in detail. The patients were divided into 2 groups: a relatively long course and high total dose (approximately 45 Gy) group, and a short course and low total dose group. Conclusions: Umbilical metastasis, known as SMJN, is a rare disease and is divided into 4 types based on the location of the disease and extent mechanism. Although the prognosis of the disease is poor, some patients survive for more than 2 years. Only 7 case reports precisely described radiation therapy. Half of the patients were treated with a short course, whereas the other half were treated with relatively high doses of up to 45 Gy.

The effects of acuity circle policy on racial disparity in liver transplantation.

BACKGROUND: A new deceased donor liver allocation policy using an acuity circle-based model was implemented with the goal of providing equitable access to liver transplantation. We assessed the effect of the acuity circle policy on racial disparities in liver transplantation by analyzing waitlist mortality, transplant probability, and post-transplant outcomes. METHODS: We conducted a retrospective analysis of 23,717 adult liver transplantation candidates listed during the pre-acuity circle period and 21,051 during the post-acuity circle period (N = 44,768) in the United Network for Organ Sharing database from February 2020 to December 2021. RESULTS: Acuity circle-policy implementation was not associated with any significant difference in 90-day waitlist mortality but increased the 90-day probability of all candidates. Implementation did not decrease 90-day waitlist mortality but increased the 90-day transplant probability for all patients. One-year patient and liver graft survival were comparable between the study periods for all recipients, but Black recipients had higher rates of 1-year post-liver transplantation mortality and liver graft failure in both periods. CONCLUSION: Although the implementation of the acuity circle policy is associated with an increase in transplant probability in White, Black, and Hispanic liver transplantation candidates, it did not change their waitlist mortality, nor did it lead to any improvement in the preexistent worse post-transplant outcomes in Black liver transplantation recipients.

Non-operative management of cirrhotic patients with acute calculous cholecystitis: How effective is it?

INTRODUCTION: Nonoperative management (NOM) of acute calculous cholecystitis (ACC) in patients with cirrhosis was proposed. We examined the outcomes of cirrhotic patients with ACC treated with cholecystectomy compared to NOM. METHODS: We analyzed the 2017-Nationwide Readmissions Database including cirrhotic patients with ACC. Patients were stratified: cholecystectomy, percutaneous cholecystostomy (PCT), and antibiotics only. PRIMARY OUTCOMES: complications, failure of NOM. SECONDARY OUTCOMES: mortality, length of stay (LOS), and charges. RESULTS: 3454 patients were identified. 1832 underwent cholecystectomy, 360 PCT, and 1262 were treated with antibiotics. PCT patients had higher mortality 16.9% vs. the antibiotics group 10.9% vs. cholecystectomy group 4.2%. PCT patients had longer LOS, but lower charges compared to the operative group. Failure of NOM was 28.2%. On regression, PCT was associated with mortality. CONCLUSION: ACC remains a morbid disease in cirrhosis patients. One in three failed NOM, had longer LOS, and higher mortality. Further studies are warranted to identify predictors of NOM failure. LEVEL OF EVIDENCE: Level III, prognostic.

Complex Abdominal Wall Reconstruction with Biologic Mesh for Ventral/Umbilical Hernias in Patients with Cirrhosis: Technique and Outcomes.

INTRODUCTION: Patients with cirrhosis undergoing non-liver transplant surgery have a higher risk or adverse events than those without cirrhosis. The main objectives of this study were to describe characteristics, outcomes, and outcome predictors of cirrhotic patients undergoing complex abdominal wall reconstruction (CAWR) with biologic mesh. MATERIALS AND METHODS: This study had retrospective and prospective components, including all cirrhotic patients at our center with CAWR for ventral/umbilical hernia repair with biologic mesh between December 2016 and November 2021. RESULTS: We studied 37 patients with cirrhosis. Their mean age was 57.2 years, and 64.9% were male. The median body mass index (BMI) was 28.1kg/m2. Ascites was present in 83.3% of patients. The other most common comorbidities were alcohol abuse (67.6%), hypertension (37.8%), and diabetes (24.3%). All complications in aggregate occurred in 11 patients (29.7%). Six patients (16.2%) underwent reoperation. Surgical site infections (SSIs) occurred in five patients (13.5%). Four deaths occurred within 90 days (11.2% cumulative mortality). By 120 days, there were five deaths (14.2% mortality, but none due to the operation). Seven predictor variables achieved an area under the receiver operating characteristic curve (AUROC) for SSI of 0.963, and two predictors yielded an AUROC of 0.825 for 120-day mortality. CONCLUSIONS: Our results suggest that CAWR for ventral/umbilical hernias among cirrhotic patients is feasible given a dedicated CAWR team in collaboration with transplant surgeons and a transplant hepatologist. The rates of adverse outcomes were low or at the midpoint of the range of the study-specific estimates.

Inferior outcomes of liver transplantation for hepatocellular carcinoma during early-COVID-19 pandemic in the United States.

BACKGROUND: Early in the coronavirus disease 2019 (COVID-19) pandemic, there was a significant impact on routine medical care in the United States, including in fields of transplantation and oncology. AIM: To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation (LT) for hepatocellular carcinoma (HCC) in the United States. METHODS: WHO declared COVID-19 as a pandemic on March 11, 2020. We retrospectively analyzed data from the United Network for Organ Sharing (UNOS) database regarding adult LT with confirmed HCC on explant in 2019 and 2020. We defined pre-COVID period from March 11 to September 11, 2019, and early-COVID period as from March 11 to September 11, 2020. RESULTS: Overall, 23.5% fewer LT for HCC were performed during the COVID period (518 vs 675, P < 0.05). This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July 2020. Among LT recipients for HCC, concurrent diagnosis of non-alcoholic steatohepatitis significantly increased (23 vs 16%) and alcoholic liver disease (ALD) significantly decreased (18 vs 22%) during the COVID period. Recipient age, gender, BMI, and MELD score were statistically similar between two groups, while waiting list time decreased during the COVID period (279 days vs 300 days, P = 0.041). Among pathological characteristics of HCC, vascular invasion was more prominent during COVID period (P < 0.01), while other features were the same. While the donor age and other characteristics remained same, the distance between donor and recipient hospitals was significantly increased (P < 0.01) and donor risk index was significantly higher (1.68 vs 1.59, P < 0.01) during COVID period. Among outcomes, 90-day overall and graft survival were the same, but 180-day overall and graft were significantly inferior during COVID period (94.7 vs 97.0%, P = 0.048). On multivariable Cox-hazard regression analysis, COVID period emerged as a significant risk factor of post-transplant mortality (Hazard ratio 1.85; 95%CI: 1.28-2.68, P = 0.001). CONCLUSION: During COVID period, there was a significant decrease in LTs performed for HCC. While early postoperative outcomes of LT for HCC were same, the overall and graft survival of LTs for HCC after 180 days were significantly inferior.

Use of Donor Hearts ≥50 Years Old for Septuagenarians in Heart Transplantation.

BACKGROUND: The impact of using donors ≥50 years old on heart transplantation outcomes of septuagenarians is unknown, which may have a potential to expand the donor pool. METHODS: From January 2011 to December 2021, 817 septuagenarians received donor hearts <50 years old (DON<50) and 172 septuagenarians received donor hearts ≥50 years old (DON≥50) in the United Network for Organ Sharing database. Propensity score matching was performed using recipient characteristics (167 pairs). The Kaplan-Meier method and Cox proportional hazards model were used to analyze death and graft failure. RESULTS: The number of heart transplants in septuagenarians has been increasing (54 per year in 2011 to 137 per year in 2021). In a matched cohort, the donor age was 30 years in DON<50 and 54 years in DON≥50. In DON≥50, cerebrovascular disease was the main cause of death (43%), whereas head trauma (38%) and anoxia (37%) were the causes in DON<50 (P < .001). The median heart ischemia time was comparable (DON<50, 3.3 hours; DON≥50, 3.2 hours; P = .54). In matched patients, 1- and 5-year survival rates were 88.0% (DON<50) vs 87.2% (DON≥50) and 79.2% (DON<50) vs 72.3% (DON≥50), respectively (log-rank, P = .41). In the multivariable Cox proportional hazards models, donors ≥50 years old were not associated with death in matched (hazard ratio, 1.05; 95% CI, 0.67-1.65; P = .83) and nonmatched groups (hazard ratio, 1.11; 95% CI, 0.82-1.50; P = .49). CONCLUSIONS: The use of donor hearts older than 50 years can be an effective option for septuagenarians, thereby potentially increasing organ availability without compromising outcomes.

Outcomes of Liver Transplantation Using Machine Perfusion in Donation after Cardiac Death vs Brain Death in the US.

BACKGROUND: Liver transplant (LT) outcomes using machine perfusion (MP) in donation after brain death (DBD) is promising, but the LT outcomes of MP in donation after cardiac death (DCD) is limited in the US. The aim of this study was to compare LT outcomes of MP between DCD and DBD. STUDY DESIGN: We analyzed data from the United Network for Organ Sharing between 2016 and 2021 among adult LT recipients. Propensity score matching was performed to assess the outcomes between DCD and DBD. RESULTS: A total of 380 LTs (295 from DBD and 85 from DCD) were performed using MP. When compared with DBD, DCD group had older median recipient age (61 vs 58 years, p = 0.03), higher prevalence of diabetes (41% vs 28%, p = 0.02), lower model for end-stage liver disease score (17 vs 22, p < 0.01), longer wait time (276 vs 143 days, p < 0.01) and younger median donor age (40 vs 51 years, p < 0.01). The most common primary diagnosis was alcohol-related liver disease, and hepatocellular carcinoma was more common in the DCD group (22% vs 13%). On survival analysis, 1-year overall/graft survivals (DCD 95.4% vs DBD 92.1%, p = 0.54; DCD 91.7% vs DBD 89.8%, p = 0.86) were the same. After propensity score matching, overall/graft survivals were the same. In Cox regression analysis, DCD was not an independent risk factor of mortality (hazard ratio 0.80; 95% CI 0.25 to 2.52; p = 0.70) and graft failure (hazard ratio 0.58; 95% CI 0.17 to 1.97; p = 0.38). CONCLUSIONS: In transplant recipients who underwent LT using MP, posttransplant outcomes of overall and graft survival were similar among DCD and DBD cohorts.

Improving blunt cerebrovascular injury screening in motor vehicle collision patients: Does airbag deployment matter?

BACKGROUND: Motor vehicle collisions (MVCs) can cause blunt cerebrovascular injury (BCVI). Exploring MVC characteristics that increase BCVI may reduce missed injuries. This study aims to evaluate the association between airbag deployment and BCVI. METHODS: We analyzed the 2016-Trauma Quality Improvement Database including adult MVC drivers. Patients were stratified: airbag deployment(A+) and no-airbag deployment(A-). Outcomes were BCVI, and cervical spine injuries (CSI). RESULTS: A total of 122,973 patients were identified: A+: 106,492, and A-: 16,481. The incidence of BCVI was 1907 (1.6%): and CSI was 20,711 (16.8%). A+ patients had a higher rate of BCVI (1.6% vs. 1.1%; p < 0.001), but a lower rate of CSI (16.2% vs. 21.4%; p < 0.001). On regression analysis, A+ was associated with BCVI (1.419[1.184-1.701]; p < 0.001) but was protective for CSI (0.767[0.672-0.878]; p < 0.001). CONCLUSION: A+ may be an unrecognized risk factor for BCVI even for patients without a CSI. Expanding BCVI screening criteria to include A+ may reduce missed injuries. LEVEL OF EVIDENCE: Level III, prognostic.

Trends and outcomes of liver transplantation among older recipients in the United States.

BACKGROUND: The average age of recipients and donors of liver transplantation (LT) is increasing. Although there has been a change in the indications for LT over the years, data regarding the trends and outcomes of LT in the older population is limited. AIM: To assess the clinical characteristics, age-related trends, and outcomes of LT among the older population in the United States. METHODS: We analyzed data from the United Network for Organ Sharing database between 1987-2019. The sample was split into younger group (18-64 years old) and older group (≥ 65 years old). RESULTS: Between 1987-2019, 155758 LT were performed in the United States. During this period there was a rise in median age of the recipients and percentage of LT recipients who were older than 65 years increased (P < 0.05) with the highest incidence of LT among older population seen in 2019 (1920, 23%). Common primary etiologies of liver disease leading to LT in older patients when compared to the younger group, were non-alcoholic steatohepatitis (16.4% vs 5.9%), hepatocellular carcinoma (14.9% vs 6.9%), acute liver failure (2.5% vs 5.2%), hepatitis C cirrhosis (HCV) (19.2 % vs 25.6%) and acute alcoholic hepatitis (0.13% vs 0.35%). In older recipient group female sex and Asian race were higher, while model for end-stage liver disease (MELD) score and rates of preoperative mechanical ventilation were lower (P < 0.01). Median age of donor, female sex, body mass index (BMI), donor HCV positive status, and donor risk index (DRI) were significantly higher in older group (P < 0.01). In univariable analysis, there was no difference in post-transplant length of hospitalization, one-year, three-year and five-year graft survivals between the two groups. In multivariable Cox-Hazard regression analysis, older group had an increased risk of graft failure during the five-year post-transplant period (hazard ratio: 1.27, P < 0.001). Other risk factors for graft failure among recipients were male sex, African American race, re-transplantation, presence of diabetes, mechanical ventilation at the time of LT, higher MELD score, presence of portal vein thrombosis, HCV positive status, and higher DRI. CONCLUSION: While there is a higher risk of graft failure in older recipient population, age alone should not be a contraindication for LT. Careful selection of donors and recipients along with optimal management of risk factors during the postoperative period are necessary to maximize the transplant outcomes in this population.

Direct Peritoneal Resuscitation (DPR) Improves Acute Physiology and Chronic Health Evaluation (APACHE) IV and Acute Physiology Score When Used in Damage Control Laparotomies: Prospective Cohort Study on 37 Patients.

INTRODUCTION: Using direct peritoneal resuscitation (DPR) as an adjunct when managing patients undergoing damage control laparotomy (DCL) shows promising results. We report our initial experience in utilizing DPR when managing patients who underwent DCL for emergent surgery at the index operation. MATERIALS AND METHODS: We prospectively collected data on 37 patients between August 2020 to October 2021 who underwent DCL with open abdomens after the index operation and utilized DPR. DPR was performed using peritoneal lavage with DIANEAL PD-2-D 2.5% Ca 3.5 mEq/L at a rate of 400ml/hour. Patients' physiological scores and clinical outcomes were evaluated. RESULTS: 86% required DCL and DPR due to septic abdomen/bowel ischemia. The median (interquartile range [IQR]) age was 62 years (53-70); 62% were male, and median (IQR) body mass index was 30.0kg/m2 (25.5-38.4). On DPR initiation, median (IQR) APACHE-IV score was 48 (33-64) and median (IQR) Acute Physiology Score (APS) was 31 (18-54). After initiation, median (IQR) APACHE-IV score and median (IQR) APS were 39 (21-62) and 19 (11-56), respectively, and both showed significant improvement in survivors (p<0.05). Median (IQR) DPR duration was four days (2-8) and primary abdominal closure was achieved in 30 patients (81%). There were eight mortalities (21.6%) within 30 days postoperatively, of which seven were within 3-24 days due to uncontrolled sepsis/multiple organ failure. The most frequent complication was surgical-site infection recorded in 12 patients (32%). Twenty-four patients (67%) were discharged home/transferred to a rehab center/nursing home. CONCLUSION: DPR application showed significant improvement of APACHE-IV score and APS in patients with peritonitis/septic abdomen.

Improving Liver Transplant Outcomes for Hepatitis C Virus Hepatocellular Carcinoma in the Direct-Acting Antiviral Therapy Era.

BACKGROUND: Direct-acting antiviral (DAA) therapy has transformed the outcomes of liver transplant (LT) with hepatitis C virus (HCV). This study aimed to analyze the effects of DAA treatment for HCV-associated hepatocellular carcinoma (HCC) in LT. METHODS: We included patients confirmed with HCC on explant, analyzed data from United Network for Organ Sharing, and defined the pre-DAA era (2012-2013) and DAA era (2014-2016). RESULTS: HCV-associated HCC cases totaled 4778 (62%) during the study period. In the DAA era, the median recipient age was older and the median days on the waiting list were longer. For the donor, median age, body mass index, and the rate of HCV significantly increased in the DAA era. In pathology, the median largest tumor size was significantly higher; however, the rate of completed tumor necrosis was significant higher in the DAA era. The 3-year graft/patient survival had significantly improved in the DAA era. In multivariable analysis, the DAA era (hazard ratio, 0.79; 95% confidence interval, 0.68-0.91) had significantly affected the 3-year graft survival. CONCLUSIONS: DAA has a significant beneficial effect on LT. In the DAA era, graft survival for HCV-associated HCC has been significantly improving.

Liver transplantation does not increase morbidity or mortality in women undergoing surgery for breast cancer.

PURPOSE: The incidence of breast cancer following solid organ transplantation is comparable to the age-matched general population. The rate of de novo breast cancer following liver transplantation varies. Furthermore, there is limited information on the management and outcomes of breast cancer in liver transplant recipients. We aim to evaluate the impact of liver transplantation on breast cancer surgery outcomes and compare the outcomes after breast cancer surgery in liver transplant recipient in transplant versus non-transplant centers. METHODS: National Inpatient Sample database was accessed to identify liver transplant recipient with breast cancer. Mortality, complications, hospital charges, and total length of stay were evaluated with multivariate logistic regression testing. Weighted multivariate regression models were employed to compare outcomes at transplant and non-transplant centers. RESULTS: Ninety-nine women met inclusion criteria for liver transplantation + breast cancer and were compared against women with breast cancer without liver transplantation (n = 736,527). Liver transplantation + breast cancer had lower performance status as confirmed via higher Elixhauser Comorbidity Index (20.5% vs 10.2%, p < 0001). There were significantly more complications in the liver transplantation cohort when compared to the non-liver transplant recipient (15.0% vs 8.2%, p = 0.012). However, on multivariate analysis, liver transplantation was not an independent risk factor for post-operative complications following breast cancer surgery (odd ratio, 1.223, p = 0.480). Cost associated with breast cancer care was significantly higher in those with liver transplantation (2.621, p < 0.001). Breast conservation surgery in liver transplantation had shorter length of stay as compared to breast cancer alone (odds ratio, 0.568, p = 0.027) in all hospitals. CONCLUSION: Liver transplantation does not increase short-term mortality when undergoing breast cancer surgery. Although there were significantly more complications in the liver transplantation cohort when compared to the non-liver transplant recipient (15.0% vs 8.2%, p = 0.012), on multivariate analysis, liver transplantation was not an independent risk factor for postoperative complications following breast cancer surgery. Breast cancer management in liver transplant recipient at non-transplant centers incurred higher charges but no difference in complication rate or length of stay when compared to transplant centers.

Re: Association between intestinal neoplasms and celiac disease - beyond celiac disease and more.

The association between celiac disease and enteropathy-associated T cell lymphoma has been known. The pathogenesis of the development of malignant neoplasms remains limited. In addition to celiac disease, we believe that other underlying mechanisms contribute to the developing malignant neoplasms.

Crystal structures of EfeB and EfeO in a bacterial siderophore-independent iron transport system.

EfeUOB is a siderophore-independent iron uptake mechanism in bacteria. EfeU, EfeO, and EfeB are a permease, an iron-binding or electron-transfer protein, and a peroxidase, respectively. A Gram-negative bacterium, Sphingomonas sp. strain A1, encodes EfeU, EfeO, EfeB together with alginate-binding protein Algp7, a truncated EfeO-like protein (EfeOII), in the genome. The typical EfeO (EfeOI) consists of N-terminal cupredoxin and C-terminal M75 peptidase domains. Here, we detail the structure and function of bacterial EfeB and EfeO. Crystal structures of strain A1 EfeB and Escherichia coli EfeOI were determined at 2.30 Å and 1.85 Å resolutions, respectively. A molecule of heme involved in oxidase activity was bound to the C-terminal Dyp peroxidase domain of EfeB. Two domains of EfeOI were connected by a short loop, and a zinc ion was bound to four residues, Glu156, Glu159, Asp173, and Glu255, in the C-terminal M75 peptidase domain. These residues formed tetrahedron geometry suitable for metal binding and are well conserved among various EfeO proteins including Algp7 (EfeOII), although the metal-binding site (HxxE) is proposed in the C-terminal M75 peptidase domain. This is the first report on structure of a typical EfeO with two domains, postulating a novel metal-binding motif "ExxE-//-D-//-E" in the EfeO C-terminal M75 peptidase domain.

Cirrhosis and COVID-19: Diffuse venous thrombosis and its clinical implication.

A 60-year-old woman with Hepatitis C infection, cirrhosis, recurrent hepatic hydrothorax, and hepatocellular carcinoma was hospitalized with Coronavirus disease-2019 (COVID-19). After her initial discharge, she was re-admitted three weeks later with decompensated liver disease. Imaging revealed extensive thrombosis in the portal vein, superior mesenteric vein, splenic vein and bilateral brachial veins. Given the acute onset and extent of the thrombosis, the patient received therapeutic anticoagulation despite elevated prothrombin time/ international normalized ratio, thrombocytopenia and low fibrinogen. Cirrhotic patients with COVID-19 maybe at high risk of thrombosis, which can present with significant hepatic decompensation.

Inferior Liver Transplant Outcomes during early COVID-19 pandemic in United States.

Background: : Since its declaration as a global pandemic on March11th 2020, COVID-19 has had a significant effect on solid-organ transplantation. The aim of this study was to analyze the impact of COVID-19 on Liver transplantation (LT) in United States. Methods: : We retrospectively analyzed the United Network for Organ Sharing database regarding characteristics of donors, adult-LT recipients, and transplant outcomes during early-COVID period (March 11- September 11, 2020) and compared them to pre-COVID period (March 11 - September 11, 2019). Results: : Overall, 4% fewer LTs were performed during early-COVID period (4107 vs 4277). Compared to pre-COVID period, transplants performed in early-COVID period were associated with: increase in alcoholic liver disease as most common primary diagnosis (1315 vs 1187, P< 0.01), higher MELD score in the recipients (25 vs 23, P<0.01), lower time on wait-list (52 vs 84 days, P<0.01), higher need for hemodialysis at transplant (9.4 vs 11.1%, P=0.012), longer distance from recipient hospital (131 vs 64 miles, P<0.01) and higher donor risk index (1.65 vs 1.55, P<0.01). Early-COVID period saw increase in rejection episodes before discharge (4.6 vs 3.4%, P=0.023) and lower 90-day graft/patient survival (90.2 vs 95.1 %, P<0.01; 92.2 vs 96.5 %, P<0.01). In multivariable cox-regression analysis, early-COVID period was the independent risk factor for graft failure at 90-days post-transplant (Hazard Ratio 1.77, P<0.01). Conclusions: : During early-COVID period in United States, overall LT decreased, alcoholic liver disease was primary diagnosis for LT, rate of rejection episodes before discharge was higher and 90-days post-transplant graft survival was lower.

Gallbladder cancer: Historical treatment and new management options.

Gallbladder cancer is a rare, aggressive malignancy that has a poor overall prognosis. Effective treatment consists of early detection and surgical treatment. With the wide spread treatment of gallbladder disease with minimally invasive techniques, the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease. Although the treatment remains mostly surgical, newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease. We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.