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Liver diseases epidemiology has changed with advances in perioperative care. Transplantation at large centers is favorable among older and younger recipients. Local limitations on transplantation for recipients older than 65 years were cancelled in 2014. This study evaluates the effects of age on the transplantation outcome of Israeli patients in the era after removal of the limitations on recipient age.This retrospective analysis examined prospective data on patients older than 18 years who underwent liver or liver-kidney transplantation between 2014 and 2019 at 2 transplantation centers. Patients were divided into 4 age groups (group 1: ≤59 years; group 2: 60-64 years; group 3: 65-69 years; and group 4: ≥70 years). Each group's associations of pretransplantation factors with outcome and survival were examined.Two hundred sixty-one recipients underwent 269 transplantations (mean age: 53 ± 12.61 y). There were 181 male (67.8%) and 88 female recipients (67.28%). Overall, 207 patients (79.6%) survived ≥12 months. One-year survival rates were 82.9%, 73.2%, 71.4%, and 93.8% for groups 1 to 4, respectively (not statistically significant; P = .11). One-year graft survival was similar between groups. More patients with chronic obstructive pulmonary disease, diabetes mellitus, or ischemic heart disease tended to survive12 months. Cardiovascular complication was more common in older groups and affected survival.Patient age alone should not be used to deny access to transplantation, which could benefit older nonfrail individuals. However, risk factors such as male sex, chronic obstructive pulmonary disease, ischemic heart disease, diabetes mellitus, and concomitant kidney-liver transplantation should be carefully considered.

The soft texture of the pancreas parenchyma may influence the incidence of pancreatic leakage after pancreaticoduodenectomy (PD). One possible method to assess pancreatic texture and atrophy, is via computed tomography (CT) scan of the abdomen. The purpose of our study was to evaluate the relation between the preoperative CT scan and the incidence of pancreatic fistula after PD.A retrospective single-center study including patients who underwent PD for a benign and malignant tumor of the periampullary region between the years 2000 and 2016. Demographic and imaging data were analysed and a correlation with the post-operative leak was evaluated.Pancreatic leak was documented in 34 out of 154 (22.1%) patients. All the leakage cases occurred in the preserved pancreas group (33.1% of the total preserved pancreas group alone). No leak was documented in the atrophic pancreas group. This difference between the two groups was found to be statistically significant (Atrophic pancreas in the preoperative CT scan may be protective against leakage after PD. These findings may help the surgeon to risk stratify patients accordingly. In addition, the findings suggest that patients with a preserved pancreas may require more protective methods to prevent leakage.

Traumatic pancreatic injury (TPI) is rare as an isolated injury. There is a trend to perform conservative treatment even in patients with complete duct dissection and successful treatment. This study reviewed our 20 years of experience in the management of TPI and assessed patient outcomes according to age group and treatment strategy.A retrospective analysis of patients diagnosed and treated with TPI at a level-I trauma center from 2000-2019. Patients were divided into two groups: adults and pediatrics. Conservative treatment cases were subjected to subgroup analysis. Level of evidence: IV.Of a total of 77 patients, the mean age was 24.89 ± 15.88 years. Fifty-six (72.7%) patients had blunt trauma with motor vehicle accident. Blunt trauma was the predominant mechanism in 42 (54.5%) patients. Overall, 38 (49.4%) cases had grade I or II injury, 24 (31.2%) had grade III injury, and 15 (19.5%) had grade IV injury. A total of 30 cases had non-operative management (NOM). Successful NOM was observed in 16 (20.8%) cases, including eight (32.0%) pediatric cases and eight (15.4%) adult cases. Higher American association for the surgery of trauma (AAST) grade of injury was associated with NOM failure (16.7% for grade I/II, 100% for grade III, and 66.7% for grade IV injury;High AAST grade TPI is associated with a high rate of NOM failure in both pediatric and adults.

PDF file - 3639K, Representative images of pancreatic lesions in wild type mice implanted with DMBA, or in Pdx1-Cre; LSL-Kras G12D mice.

PDF file - 56K, Proliferation rate analysis.

PDF file - 39K, Pathologic score of PanIN lesions in Pdx1-Cre; LSL-KRAS G12D mice, wild type (n=4 mice) or heterozygous (n=7) for the phospho-rpS6 mutant.

PDF file - 66K

PDF file - 44K, Staining for γH2AX (brown) in sections of the intestine from a CK1α-deficient mouse

PDF file - 47K, Mosaic phosphorylation of rpS6 in wild type islets.

BackgroundDetermining the humoral immunogenicity of tozinameran (BNT162b2) vaccine in patients requiring chronic renal replacement therapy, and its impact on COVID-19 morbidity several months after vaccination, will guide risk assessment and subsequent changes in vaccination policy.MethodsIn a prospective post-vaccination cohort study with up to 5 months follow-up we studied outpatient dialysis and kidney transplant patients and respective healthcare teams. Outcomes were anti S1/S2 antibody response to vaccine or infection and infection rate during followup.Results175 dialysis patients (40% women, 65±15 years), 252 kidney transplant patients (33% women, 54±14 years) and 71 controls (65% women, 44±14 years) were followed. Three months or longer after vaccination we detected anti S1/S2 IgG antibodies in 80% of dialysis patients, 44% of transplant recipients and 100% of controls, whereas respective rates after infection were 94%, 75% and 100%. Predictors of non-response were older age, diabetes, history of cancer, lower lymphocyte count and lower vitamin-D levels. Factors associated with lower titers in dialysis patients were modality (hemodialysis vs peritoneal) and high serum ferritin levels. In transplant patients, hypertension and higher calcineurin or mTOR inhibitor drug levels were linked with diminished antibody response. Vaccination associated with fewer subsequent infections (HR=0.23, p10titer (pConclusionsDialysis patients, and more so kidney transplant recipients, mounted reduced antibody response to COVID-19 mRNA vaccination, and lesser humoral response associated with more infections. Measures to identify and protect non-responsive patients are urgently required.SignificanceReports on the humoral immunogenicity of SARS-CoV-2 mRNA vaccines in patients with end stage renal disease are scarce, and association with subsequent COVID-19 morbidity is unknown. In this cohort study that included 175 patients treated with dialysis, 252 kidney transplant recipients and 71 control volunteers, the proportion achieving an antibody response was time- and group-dependent, reaching 80%, 44% and 100% at 3 months post prime inoculation. Personal history of vaccination, positive antibody responses and antibody titers associated with significantly lower risk of COVID-19 infection. Thus, in patients with end stage renal disease, SARS-CoV-2 antibody testing may be warranted after vaccination, to identify non-responders at higher risk for disease.

Background Living kidney donation is widely practiced, and short- and long-term outcomes are acceptable. Within the living kidney donor population there are unique ethnic groups who practice customs that affect kidney function. In Judaism, Yom Kippur (Day of Atonement) is a 25- to 26-hour fast practiced yearly. There are no studies describing the effect of this fast on LKDs. Methods Living kidney donors were approached via e-mail. Exclusion criteria were conditions considered prohibitive of fasting. Control participants were potential living kidney donors approved by the standard medical evaluation but that had not yet donated. Blood and urine samples were obtained at 3 time points: baseline: 3 months before fast; fasting: 1 hour after fast; and follow-up: 14 days after fast. Results In total, 85 living kidney donors and 27 control participants were included. Donors were older (42.8 vs 38.8 years) and had a higher baseline creatinine (103 vs 72 umol/L). All other parameters were the same. The percent change between fasting and nonfasting creatinine was smaller in living kidney donors than in control participants (0.12% vs 0.21% change, P = .04). Values of sodium, albumin, and osmolarity were not different between groups. Time from donation did not influence results. Conclusions Living kidney donors practicing a day fast showed a different pattern regarding the change in creatinine levels. This pattern cannot be considered hazardous for living kidney donors. The emotional wellbeing of living kidney donors is of utmost importance, and this first report of the safety of a 24-hour fast is reassuring. These findings may be of interest to other religious groups, for example, the Muslim community which observes Ramadan.

Sleeve gastrectomy (SG) is an effective treatment for extreme obesity; however, long-term weight loss outcomes remain largely understudied. We aimed to examine the long-term weight changes following SG and patient characteristics and lifestyle patterns related to weight loss outcomes. Data from medical records of patients operated in a tertiary university medical center between 2008 and 2014 were reviewed, along with information derived from a telephone questionnaire. Information included the following: current medical status, medications, side effects, behavior, lifestyle habits, and weight changes. A total of 212 patients (69.3% females) were included, with a median follow-up duration of 8 years post-SG. Mean age and baseline body mass index (BMI) of participants were 39.7 ± 12.0 years and 42.2 ± 4.9 kg/m2, respectively. Mean BMI, percentage excess weight loss, and percentage total body weight loss were 33.1 ± 6.1, 55.5 ± 27.5%, and 21.7 ± 10.7%, respectively. Higher baseline BMI was found to be the strongest independent predictor for insufficient weight loss (OR = 0.90, P = 0.001, 95% CI 0.85, 0.96). Sweetened beverage intake, usage of psychiatric medications, higher initial BMI, and lower age were significant predictors for increased weight gain from nadir weight (P

The appropriate strategies to minimize skeletal deterioration following bariatric surgeries are inconclusive. This randomized controlled trial evaluated the effect of preoperative vitamin supplementation on bone mineral density (BMD) and biochemical parameters in females post-sleeve gastrectomy (SG). Participants were randomized to a 2-month preoperative treatment with a multivitamin and vitamin D 4000 IU/d (intervention arm) or 1200 IU/d (control arm). Preoperative and 12-month postoperative follow-up evaluations included anthropometrics, biochemical parameters, and dual energy X-ray absorptiometry (DEXA). Sixty-two females (median age 29.7 years and median BMI 43.4 kg/m2) were recruited, 87% completed the 12-month follow-up. For the intervention and control arms, significant and similar reductions at 12-months post-surgery were observed in BMD of the hip (−6.8 ± 3.7% vs. −6.0 ± 3.6%; P = 0.646) and of the femoral neck (−7.1 ± 5.8% vs. −7.2 ± 5.5%; P = 0.973). For the intervention compared to the control arm, the 25 hydroxyvitamin D (25(OH)D) increment was greater after 2 months treatment, and vitamin D deficiency rates were lower at 3 and 6-months follow-up (P 0.339). Predictors for BMD decline in the total hip were the percentage of excess weight-loss, age>50 years, and lower initial BMI (P ≤ 0.003). SG was associated with a significant decline in BMD of the hip and femoral neck in young and middle-aged women, and was unaffected by preoperative vitamin D supplementation. Females who are peri-menopausal or with greater postoperative weight-loss should be particularly followed for BMD decline.

The role of angioembolization in managing hemodynamically stable patients with liver injury has obviated the need for surgery. Although mortality and morbidity rates after the adoption of this technique have decreased, this procedure is not devoid of complications. This study assesses the impact of this procedure and its associated complications. We performed a case series analysis of patients with hepatic trauma in a level one trauma center over 10 years (2008–2017). Data were collected from hospital records of patients with liver injury and analyzed according to demographics, injury type, management strategy, procedure time, efficacy, complications of embolization, and outcome. We included all patients who underwent angioembolization. Patients who underwent surgery only or had incomplete records were excluded. Of 366 patients with liver trauma, eighteen were managed with angioembolization. Of which, thirteen had grade IV injury or higher, while five had grade II or III. Twelve patients had blunt liver trauma. Six patients were initially managed by laparotomy followed by angioembolization. The most common embolized artery was the right hepatic artery (eleven patients). Nine patients had at least one complication after the procedure. The liver collection was the most common complication (seven patients). There was one hepatic complication-related death. Morbidity was more common in patients who underwent exploratory laparotomy before angioembolization compared to angioembolization alone. Those who had a laparotomy before the angioembolization may have a higher complication rate.

Objective Von Hippel-Lindau (VHL) syndrome is a rare and complex disease. We described in 1996 a three generation VHL 2A kindred with 11 mutation carriers. We aim to share our experience regarding the long-term follow-up of this family and the management of all our other VHL patients focusing on frequently encountered neuroendocrine tumors: pheochromocytoma/paraganglioma and pancreatic neuroendocrine neoplasms (PNEN). Methods All VHL patients in follow-up at our tertiary center from 1980 to 2019 were identified. Clinical, laboratory, imaging and therapeutic characteristics were retrospectively analyzed. Results We identified 32 VHL patients in 16 different families, 7/16 were classified as VHL 2 subtype. In the previously described family, the 4 initially asymptomatic carriers developed a neuroendocrine tumor; 7 new children were born, 3 of them being mutation carriers; 2 patients died, one due to metastatic PNEN-related liver failure. Pheochromocytoma was frequent (22/32), bilateral (13/22;59%), often diagnosed in early childhood when active screening was timely performed, associated with paraganglioma in 5/22, rarely malignant (1/22) and recurred after surgery in some cases after more than 20 years. PNEN occurred in 8/32 patients (25%), and was metastatic in three. Surgery and palliative therapy allowed relatively satisfactory outcomes. Severe disabling morbidities due to central-nervous system and ophthalmologic hemangiomas, and other rare tumors as chondrosarcoma in 2 patients and polycythemia in 1 patient were observed. Conclusions Multidisciplinary approach and long-term follow-up is mandatory in VHL patients to manage the multiple debilitating morbidities and delay mortality in these complex patients.

DNA methylation is a fundamental epigenetic mark that governs chromatin organization, cell identity, and gene expression. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 207 healthy tissue samples.Replicates of the same cell-type are >99.5% identical, demonstrating robustness of cell identity programs to genetic variation and environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny, and identifies methylation patterns retained since gastrulation. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hyper-methylated loci are rare and are enriched for CpG islands, polycomb targets, and CTCF binding sites, suggesting a novel role in shaping cell type-specific chromatin looping. The atlas provides an essential resource for interpretation of disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.Summary paragraphDNA methylation, a fundamental epigenetic mark, governs chromatin organization and gene expression1, thus defining the molecular identity of cells and providing a window into developmental processes with wide-ranging physiologic and clinical ramifications. Current DNA methylation datasets have limitations, typically including only a fraction of methylation sites, many from cell lines that underwent massive changes in culture or from tissues containing unspecified mixtures of cells2–6.We present a human methylome atlas based on deep whole-genome bisulfite sequencing of 39 sorted, primary cell types and use this dataset to address fundamental questions in developmental biology, physiology and pathology. Biological replicates are >99.5% identical, demonstrating unappreciated robustness to genetic variation and environmental perturbations. Clustering recapitulates key elements of tissue ontogeny, identifying methylation patterns retained since gastrulation. Loci uniquely unmethylated in individual cell types identify novel transcriptional enhancers and are enriched for tissue-specific transcription factors binding motifs. In contrast, loci uniquely hyper-methylated in specific cell types are rare, enriched for CpG islands and polycomb targets, and overlap CTCF binding sites, suggesting a novel role in shaping cell-type-specific chromatin looping. Finally, the atlas facilitates fragment-level deconvolution of tissue and plasma methylomes across thousands of cell-type specific regions to quantify their individual components at unprecedented resolution.The human cell-type-specific methylation atlas provides an essential resource for studying gene regulation by defining cell-type-specific distal enhancers and regulators of 3D organization, for identifying pathological changes in DNA methylation, and for the interpretation of methylation-based liquid biopsies.A deep methylation atlas of 39 human cell types, sorted from healthy samplesMethylomes record developmental history of cellsThousands of novel cell type-specific methylation markersHypo-methylation uncovers cell type-specific regulatory map of distal enhancersHyper-methylation across CTCF sitesCell type-specific biomarkers facilitate fragment-level deconvolution of tissues and cfDNA

Food addiction and binge eating are common among individuals with obesity. However, a paucity of studies prospectively examined the prevalence and implications of food addiction before and post-bariatric surgery. We aimed to examine the prevalence of food addiction and binge eating before and after sleeve gastrectomy (SG) and to assess their associations with behavioral and weight loss outcomes. We followed at 3 (M3), 6 (M6), and 12 (M12) months postoperative, 54 women who underwent SG. Data collected including anthropometrics, nutritional intake, food tolerance, and physical activity measures. The Yale Food Addiction Scale and the Binge Eating Scale were used to characterize food addiction and binge eating, respectively. The mean baseline age and BMI were 32.1 ± 11.1 years and 44.9 ± 4.9 kg/m2, respectively. Pre-surgery, food addiction, and binge eating were identified in 40.7% and 48.1% of patients, respectively. The prevalence of food addiction decreased significantly up to M6, but increased to 29.3% at M12. The prevalence of binge eating decreased significantly through the follow-up up to 17.4% at M12. Those who met criteria for food addiction at M12 achieved significantly lower excess weight loss at M12 compared with those not meeting this criterion (P = 0.005). Food addiction scores at M12 negatively correlated with weekly physical activity (r = − 0.559; P

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.

Nutritional deficiencies are a well-recognized long-term complication following bariatric surgery. The presence of preoperative deficiencies has been shown to be predictive of postoperative deficiencies.The aim of the study was to investigate the prevalence of micronutrient deficiency in a large sample of patients with severe obesity preoperatively, and to determine whether such deficiencies may be related to patient's sex, body mass index, or ethnic subgroup.A cross-sectional study of data collected at the time of the preoperative evaluation.Data were collected during the preoperative evaluation of 872 bariatric surgery candidates in a university hospital in Israel between 2011 and 2018. The patients were 72.9% women, with a mean age of 37.9±12.1 years and mean body mass index of 42.4±4.7 MAIN OUTCOME MEASURES: Nutritional deficiencies according to blood assays. Data on anthropometrics, comorbidities, and demographic characteristics was also collected.Baseline differences between patient subgroups were analyzed using independent-samples t test, analysis of variance, or χDeficiencies of vitamin D, iron, folate, vitamin B-12, elevated parathyroid hormone and low transferrin saturation were present in 75.2%, 42.6%, 28.5%, 8.5%, 35.5%, and 70% of patients, respectively. Nutritional deficiencies were significantly more common among women compared with men for iron (45.9% vs 33.5%; P=0.002), low transferrin saturation (77.7% vs 44.6%; P0.001), vitamin D (77.5% vs 69.2%; P=0.019) and elevated parathyroid hormone level (39.5% vs 22.9%; P=0.002). Iron, transferrin saturation, and vitamin D deficiencies were more prevalent in Arab patients compared with Jewish patients: 59.6% vs 36%; P0.001, 80.2% vs 62.8%; P=0.003, and 85.1% vs 71.6%; P0.001, respectively. Vitamin D and iron deficiency were more common among higher body mass index subgroups (P=0.004 and P=0.040, respectively).The results indicate a high prevalence of nutritional deficiencies, mainly of iron and vitamin D in bariatric surgery candidates. Patients at higher risk for nutritional deficiencies include those with higher body mass index, women, and Arabs.

DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2–5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

The Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine has been offered to nonallergic ≥16-year-old Israeli adults since December 19, 2020. Data regarding factors associated with vaccine ineffectiveness are limited. The aim of this study is to assess the impact of hepatic fibrosis on the efficacy of the BioNTech vaccine. Serum severe acute respiratory syndrome coronavirus 2 spike immunoglobulins (S IgG) obtained at least 7 days following vaccination completion was correlated with the prevaccine calculated Fibrosis-4 (FIB-4) score among 719 employees in the Hadassah Medical Center, Jerusalem. Positive vaccine response (S IgG levels ≥ 19 AU/mL) was found in 708 of 719 individuals (98.5%). Vaccine failure (S IgG levels 19) was found in 11 (1.5%); of these, 7 were immunosuppressed. Mean FIB-4 available in 501 of 708 vaccine responders was 1.13 ± 0.66, mean age 51.4 ± 12.4 years (29.3% males), and mean S IgG titers 239.7 ± 86.1 AU/mL. Similar to the general population, 70.5% had normal FIB-4 (1.3), 26.8% undetermined FIB-4 (1.3-2.67), and 2.7% advanced FIB-4 (2.67). When divided into response subgroups, 158 of 501 individuals (30.1%) with IgG titers 19-100 AU/mL had a mean FIB-4 of 1.48 ± 0.82; 198 (39.5%) with IgG titers 101-200 AU/mL had mean FIB-4 of 1.22 ± 0.76; 83 (16.6%) with titers 201-300 AU/mL had mean FIB-4 of 1.04 ± 0.48; 38 (7.6%) individuals with IgG titers 301-400 AU/ml had a mean FIB-4 of 1.08 ± 0.63; and 121 (24.2%) with IgG titers400 AU/mL had mean FIB-4 of 1.18 ± 0.87. Increased FIB-4, age, and male gender significantly correlated with lower postvaccine IgG titers (P 0.001). FIB-4 results were confirmed using FibroScan data displaying advanced fibrosis impact on weakened COVID-19 vaccine response. Conclusion: Immune suppression, older age, male gender, and advanced chronic liver disease are risk factors for lower vaccine response. The FIB-4 provides a simple tool to prioritize candidates for third-dose vaccine booster.

Sleeve gastrectomy (SG) is an effective treatment for extreme obesity; however, long-term weight loss outcomes remain largely understudied. We aimed to examine the long-term weight changes following SG and patient characteristics and lifestyle patterns related to weight loss outcomes.Data from medical records of patients operated in a tertiary university medical center between 2008 and 2014 were reviewed, along with information derived from a telephone questionnaire. Information included the following: current medical status, medications, side effects, behavior, lifestyle habits, and weight changes.A total of 212 patients (69.3% females) were included, with a median follow-up duration of 8 years post-SG. Mean age and baseline body mass index (BMI) of participants were 39.7 ± 12.0 years and 42.2 ± 4.9 kg/mSG patients were found to maintain a notable long-term weight loss. Nevertheless, weight regain and insufficient weight loss were prevalent in the long-term post-operative period, and were related to certain lifestyle patterns. Clinical practice should emphasize the relationship between post-operative weight loss outcomes and specific behaviors. Efforts should be made to educate patients on the need for lifelong follow-up and support.

Many obstacles may complicate renal transplant, the preferred treatment for end-stage renal disease. Anatomic anomalies are of special importance during surgery. Double inferior vena cava is a rare anomaly reported in 0.2% to 3% of the population and may complicate renal transplant in certain cases. We present a case of a 29-year-old man with end-stage renal disease who was scheduled for repeat kidney renal transplant from a living related donor. His transplant posed many challenges to the transplant team. These included (1) difficult access for dialysis, which required transhepatic insertion of a dialysis catheter, (2) anomalous inferior vena cava anatomy with a double inferior vena cava, (3) a blocked right inferior vena cava, and (4) a small blocked bridging vein connecting the right inferior vena cava to an additional left inferior vena cava. A stent was inserted into the bridging vein to allow venous drainage from the graft. During the transplant procedure, the donated kidney was transplanted into the left iliac fossa and anastomosed to the left external iliac vein. The surgery was successful, without major operative or postoperative complications. The patient was discharged with normal renal function and enjoys normal renal function 6 months after surgery. This case emphasizes the importance of pretransplant evaluation and preparation and the need for high index of suspicion for anatomic variants in donors and recipients.

Small bowel obstruction is an uncommon disease in pregnant women and rare when it is caused by intussusception. Intussusception is a rare cause of intestinal obstruction in adult. When it occurs, it is almost always secondary to an underlying pathology acting as a lead point for invagination, such as polyps, hemartomas, lipomas, leiomyomas, Meckel's diverticulum, adenomas, strictures, and malignancies. Ectopic pancreatic tissue is a very rare pathology acting as the lead point. In this case, we present a very rare case of intussusception in a young pregnant woman, caused by an intramural ectopic pancreatic tissue in the ileum.

Summary: Background: Hydatid cyst is a zoonotic disease caused by Echinococcus genera. Surgery is needed in most cases. We aimed to describe our center's experience in the surgical management of hepatic hydated cysts (HHC). Methods: Data was retrospectively collected for patients who underwent operative management for HHC between the years 1994–2014. Results: Sixty-nine underwent surgical treatment for HHC. Group A included 34 treated with an unroofing procedure, group B included 24 patients who underwent hepatectomy and group C included 11 patients who underwent peri-cystectomy. The median ± (range) age for groups A, B and C were 39.5 (6.5–69), 40 (17–74) and 32 (20–62), respectively (P > 0.1). Post-operative complications occurred in 16, 11 and 5 patients in group A, B and C, respectively, as assessed by clavien-dindo classification (CDC). The average CDC was significantly higher in the hepatectomy group as compared to the unroofing group (2.3 vs.1.5, P = 0.04). Recurrence was significantly higher after the unroofing procedure as compared to the hepatectomy group (P = 0.05). Conclusion: Surgery remains the mainstay of treatment for HHC, once surgery is pursued, the results are satisfactory. Keywords: Echinococcus, Hydated cyst, Liver surgery, Morbidity, Mortality

The appropriate strategies to minimize skeletal deterioration following bariatric surgeries are inconclusive. This randomized controlled trial evaluated the effect of preoperative vitamin supplementation on bone mineral density (BMD) and biochemical parameters in females post-sleeve gastrectomy (SG).Participants were randomized to a 2-month preoperative treatment with a multivitamin and vitamin D 4000 IU/d (intervention arm) or 1200 IU/d (control arm). Preoperative and 12-month postoperative follow-up evaluations included anthropometrics, biochemical parameters, and dual energy X-ray absorptiometry (DEXA).Sixty-two females (median age 29.7 years and median BMI 43.4 kg/mSG was associated with a significant decline in BMD of the hip and femoral neck in young and middle-aged women, and was unaffected by preoperative vitamin D supplementation. Females who are peri-menopausal or with greater postoperative weight-loss should be particularly followed for BMD decline.

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.

Food addiction and binge eating are common among individuals with obesity. However, a paucity of studies prospectively examined the prevalence and implications of food addiction before and post-bariatric surgery. We aimed to examine the prevalence of food addiction and binge eating before and after sleeve gastrectomy (SG) and to assess their associations with behavioral and weight loss outcomes.We followed at 3 (M3), 6 (M6), and 12 (M12) months postoperative, 54 women who underwent SG. Data collected including anthropometrics, nutritional intake, food tolerance, and physical activity measures. The Yale Food Addiction Scale and the Binge Eating Scale were used to characterize food addiction and binge eating, respectively.The mean baseline age and BMI were 32.1 ± 11.1 years and 44.9 ± 4.9 kg/mThe reduction in food addiction observed at M6 was not maintained at M12. Food addiction at M12 was associated with poorer weight loss, eating, and lifestyle behaviors. Clinical practice should focus on the psychological aspects associated with obesity.

Background Traumatic superior mesenteric artery (SMA) and vein (SMV) injuries are rare but often lethal. The ideal management options of traumatic SMV injury are still controversial. Management options include venous repair and ligation. Splenic vein turndown procedure (SVTP) is a rare procedure that has been described in only 6 cases in the literature. Here, we reviewed the literature on the usage of the splenic vein turndown procedure (SVTP) as an alternative option in patients with traumatic SMV injury. Methods We performed a narrative review for the available literature on the usage of the splenic vein as an autologous graft in the management of the SMV injury. We included all studies of SVTP in traumatic SMV injuries only. Results We included only 5 studies. In total, 7 patients underwent SVTP. Five patients presented with a penetrating abdominal vascular trauma (AVT) and 2 patients with a blunt AVT. The advantages of the SVTP include no need for additional incisions to harvest potential autologous grafts, minimally increased operative time, and 1 less anastomotic site compared to other conduit options. Conclusions In cases of traumatic SMV injuries with associated splenic or pancreatic injuries that need distal pancreatosplenectomy, surgeons may consider SVTP as an ideal management option rather than primary repair or ligation.

Goblet cell carcinoma, a tumor that is assumed to originate from crypt base stem cells, is a distinct type of tumor, that occurs typically in the appendix, however, extra-appendiceal locations were also described in few cases. We herein present a unique case of a 48-year-old male with a diagnosis of primary gastric Goblet cell carcinoma that was initially discovered at the time of an endoscopy performed to evaluate an unremitting abdominal pain that was accompanied by remarkable weight loss; four polypoid fragments of the gastric mucosa were sent for histopathologic examination which showed a moderately differentiated goblet cell carcinoma in addition to classical neuroendocrine tumor. Later, laparoscopic D2 total gastrectomy with appendectomy were performed and confirmed the previously mentioned findings along with a normal histopathology of the appendix.

Tumor progression and metastasis are the major causes of death among cancer associated mortality. Metastatic cells acquire features of migration and invasion and usually undergo epithelia-mesenchymal transition (EMT). Acquirement of these various hallmarks rely on different cellular pathways, including TGF-β and Wnt signaling. Recently, we reported that WW domain-containing oxidoreductase (WWOX) acts as a tumor suppressor and has anti-metastatic activities involving regulation of several key microRNAs (miRNAs) in triple-negative breast cancer (TNBC). Here, we report that WWOX restoration in highly metastatic MDA-MB435S cancer cells alters mRNA expression profiles; further, WWOX interacts with various proteins to exert its tumor suppressor function. Careful alignment and analysis of gene and miRNA expression in these cells revealed profound changes in cellular pathways mediating adhesion, invasion and motility. We further demonstrate that WWOX, through regulation of miR-146a levels, regulates SMAD3, which is a member of the TGF-β signaling pathway. Moreover, proteomic analysis of WWOX partners revealed regulation of the Wnt-signaling activation through physical interaction with Disheveled. Altogether, these findings underscore a significant role for WWOX in antagonizing metastasis, further highlighting its role and therapeutic potential in suppressing tumor progression.

Liver cancer is one of the most lethal malignancies with very poor prognosis once diagnosed. The most common form of liver cancer is hepatocellular carcinoma (HCC). The WW domain-containing oxidoreductase (WWOX) is a large gene that is often perturbed in a wide variety of tumors, including HCC. WWOX has been shown to act as a tumor suppressor modulating cellular metabolism via regulating hypoxia-inducible factor 1α (HIF-1α) levels and function. Given that WWOX is commonly inactivated in HCC, we set to determine whether specific targeted deletion of murine Wwox affects liver biology and HCC development. WWOX liver-specific knockout mice (WwoxΔHep) showed more potent liver regeneration potential and enhanced proliferation as compared with their control littermates. Moreover, WWOX deficiency in hepatocytes combined with diethylnitrosamine treatment increased the tumor burden, which was associated with increased HIF1α levels and target gene transactivation. Inhibition of HIF1α by systemic treatment with digoxin significantly delayed HCC formation. Our work suggests that WWOX inactivation has a central role in promoting HCC through rewiring of cellular metabolism and modulating proliferation.

To evaluate the outcomes, weight loss predictors, and gastrointestinal symptoms of patients after laparoscopic sleeve gastrectomy (LSG). The postoperative medical status of the patients was obtained retrospectively using a questionnaire and was compared to existing medical data before the surgery. We included 201 candidates, 178 patients completed mean of 3 years of follow-up. Mean excess body weight loss (%EWL) was 65.14% ± 15.74 at 6 months, 78.53% ± 20.28 at 12 months, and 74.32% ± 23.92 at 3 years after LSG. Older age (P = 0.018), higher baseline BMI (P = 0.003), and higher number of medications (P

BACKGROUND Liver transplantation (LT) is the treatment of choice for most end-stage liver diseases. This treatment increases survival rates and improves quality of life. Because of the shortage of organ donors, as opposed to waiting patients, the need to optimize the matching of donors to recipients for maximum utility is crucial. AIM The aim of this study was to examine a predictive model based on the combination of donor and recipient risk factors using the liver Donor Risk Index (DRI) and recipient Model of End-stage Liver Disease (MELD) to predict patients' survival following LT. PATIENTS AND METHODS The charts of 289 adult primary LT patients, who had undergone transplantation in Israel between 2010 and 2015, were studied retrospectively using prospectively gathered data. RESULTS Two variables, DRI and MELD, were found to significantly affect post-transplant patient survival. DRI negatively affected survival in a continuous fashion, whereas MELD had a significantly negative effect only at MELD more than 30. Both female sex and the presence of hepatocellular carcinoma were associated with increased patient survival. CONCLUSION According to our findings, the model described here is a novel prediction tool for the success of orthotopic LT and can thus be considered in liver allocation.

γδT cells are a major component of epithelial tissues and play a role in tissue homeostasis and host defense. γδT cells also reside in the gingiva, an oral tissue covered with specialized epithelium that continuously monitors the challenging dental biofilm. Whereas most research on intraepithelial γδT cells focuses on the skin and intestine epithelia, our knowledge on these cells in the gingiva is still incomplete. In this study, we demonstrate that even though the gingiva develops after birth, the majority of gingival γδT cells are fetal thymus-derived Vγ6(+) cells, and to a lesser extent Vγ1(+) and Vγ4(+) cells. Furthermore, we show that γδT cells are motile and locate preferentially in the epithelium adjacent to the biofilm. Vγ6(+) cells represent the major source of IL-17–producing cells in the gingiva. Chimeric mice and parabiosis experiments indicated that the main fraction of gingival γδT cells is radioresistant and tissue-resident, persisting locally independent of circulating γδT cells. Notably, gingival γδT cell homeostasis is regulated by the microbiota as the ratio of Vγ6(+) and Vγ4(+) cells was reversed in germ-free mice, and their activation state was decreased. As a consequence, conditional ablation of γδT cells results in elevated gingival inflammation and subsequent alterations of oral microbial diversity. Taken together, these findings suggest that oral mucosal homeostasis is shaped by reciprocal interplays between γδT cells and local microbiota.

Liver cancer is one of the most lethal malignancies with very poor prognosis once diagnosed. The most common form of liver cancer is hepatocellular carcinoma (HCC). The WW domain-containing oxidoreductase (WWOX) is a large gene that is often perturbed in a wide variety of tumors, including HCC. WWOX has been shown to act as a tumor suppressor modulating cellular metabolism via regulating hypoxia-inducible factor 1α (HIF-1α) levels and function. Given that WWOX is commonly inactivated in HCC, we set to determine whether specific targeted deletion of murine Wwox affects liver biology and HCC development. WWOX liver-specific knockout mice (Wwox

The beneficial effect of bariatric surgery (BS) in type 2 diabetes mellitus patients is well established. Conversely, little is known about the efficacy of BS in type 1 diabetes mellitus (T1DM) patients, despite the increasing prevalence of obesity in this population. A retrospective review was carried out on a prospectively collected bariatric surgery registry of all patients undergoing BS at two university hospitals between 2010 and 2015. Patients with T1DM were identified, and detailed chart reviews were obtained. In this time period, we operated on thirteen patients with T1DM. Eight were female (61.5 %). Median age at time of surgery was 38 ± 8.3 (range 28–53) years. The procedures performed were laparoscopic sleeve gastrectomy (n = 10) and laparoscopic Roux-en-Y gastric bypass (n = 3). On median postoperative follow-up of 24 (range 2.5–51) months, mean body mass index significantly decreased from 39.9 ± 4.1 to 30.1 ± 3.9 kg/m2 (P

Hepatic hydatid cysts (HHCs) are common in endemic areas. Mostly they are asymptomatic, but some cause serious complications. We report 2 cases of HHC complicated arterial bleeding. Owing to signs of active bleeding, the patients were treated with selective embolization of the hepatic artery to stop the bleeding and stabilize the patients' condition. Subsequently, partial hepatectomy of the involved liver lobe was performed in an elective setting and without postoperative complications. We recommend bridging therapy by selective angiography and embolization for hemorrhagic hepatic hydatid cyst before definitive surgical treatment.

Psychosocial factors greatly impact the course of patients throughout the liver transplantation process. A retrospective chart review was performed of patients who underwent liver transplantation at Hadassah-Hebrew University Medical Center between 2002 and 2012. A composite psychosocial score was computed based on the patient's pre-transplant evaluation. Patients were divided into two groups based on compliance, support and insight: Optimal psychosocial score and Non-optimal psychosocial score. Post-liver transplantation survival and complication rates were evaluated. Out of 100 patients who underwent liver transplantation at the Hadassah-Hebrew University Medical Center between 2002 and 2012, 93% had a complete pre-liver transplant psychosocial evaluation in the medical record performed by professional psychologists and social workers. Post-liver transplantation survival was significantly higher in the Optimal group (85%) as compared to the Non-optimal group (56%, p = .002). Post-liver transplantation rate of renal failure was significantly lower in the Optimal group. No significant differences were observed between the groups in other post-transplant complications. A patient's psychosocial status may impact outcomes following transplantation as inferior psychosocial grades were associated with lower overall survival and increased rates of complications. Pre-liver transplant psychosocial evaluations are an important tool to help predict survival following transplantation.

Background: Achieving complete cytoreduction of peritoneal surface malignancies (PSM) can be challenging. In most cases, delivery of heated intra-peritoneal chemotherapy (HIPEC) is straightforward. However, using the closed technique in some cases may be technically challenging; for example, in patients requiring abdominal closure using a large synthetic mesh. In cases where groin hernias are present, it is imperative to resect the hernia sac, since it may contain tumor deposits. In cases with major inguinal involvement where disease may spread out of the hernia sac or in cases where a hernia repair was performed while disease is present, inguinal perfusion should be considered. Aim: To describe our experience with combined intra-peritoneal and inguinal perfusion of HIPEC following cytoreductive surgery. Patients and Methods: This is a retrospective review of all patients who underwent cytoreductive surgery (CRS) and HIPEC at our institution. A prospectively maintained database containing data of patients treated by CRS and HIPEC (n=122) was reviewed. All patients with macroscopic inguinal involvement by PSM with complete cytoreduction perfused by HIPEC were included. Results: We identified five cases who underwent CRS and combined intraperitoneal and inguinal perfusion after resection of large inguinal tumor deposits (n=4) or after a recent hernia repair with hernial sac involvement by mucinous adenocarcinoma (n=1). All five patients were successfully perfused using an additional outflow catheter placed in the groin. Discussion: In cases of inguinal involvement by PSM, complete cytoreduction should be achieved and perfusion of the involved groin considered as it is feasible and safe.