Gut microbiome predicts cognitive function and depressive symptoms in late life.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

Health care access, psychosocial outcomes and mental health in adults living with epilepsy during the COVID-19 pandemic.

PURPOSE: People living with epilepsy (PLWE) have a higher prevalence of mental health comorbidities and poorer psychosocial outcomes compared to the general population. The aim of this study was to examine psychosocial outcomes, mental health, healthcare accessibility, and seizure burden in PLWE during the COVID-19 pandemic. METHODS: We conducted a cross-sectional study of adults with epilepsy treated in an urban multicenter health system from 2021 to 2022. A standardized questionnaire assessed for COVID-19 history, comorbidities, access to antiseizure medications (ASMs) and neurological care, seizure burden, and psychosocial outcomes (e.g., employment, social and financial support). The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were administered to evaluate for depression and anxiety. Frequency and proportions for categorical variables and median and interquartile ranges for continuous variables were calculated. RESULTS: Fifty-five PLWE participated (95 % response rate). Median age was 40 years (IQR 31.5-66.5), 61.8 % were women, 47.3 % had a bachelor's degree or higher and 29.1 % each had Medicaid and Medicare insurance. Race (from highest to lowest %) was: 32.7 % White, 20 % Black, 20 % Latinx, 14.5 % Asian, and 12.7 % selected "other" or "prefer not to say." COVID-19 had been diagnosed in 21.8 % of participants. Symptoms of anxiety and depression were self-reported by 43.6 % and 34.5 % of patients, respectively, with many describing this symptom as new post-pandemic (37.5 % and 31.6 %, respectively). Using validated scales, 52.7 % had depression (PHQ-9 score ≥ 5) with 30.9 % having moderate/severe depression (PHQ-9 score ≥ 10), while 29.1 % had probable generalized anxiety disorder (GAD-7 score ≥ 8). Seizure burden increased in 21.8 % of participants, while 20 % reported fewer seizures and 29.1 % were seizure free since the COVID-19 pandemic. Economic impacts of the pandemic included job loss (25 % amongst those employed at onset of pandemic), new or worsened financial difficulties (40 %), and new or worsened social support issues (30.9 %). Of all participants, 18.2 % reported difficulties accessing ASMs and 25.5 % cancelled visits, but of those with cancelled visits, 78.6 % had their appointments rescheduled as a telehealth visit. CONCLUSION: Our cohort of PLWE experienced some challenges during the COVID-19 pandemic including poorer mental health and financial and employment-related stressors. Encouragingly, healthcare access was relatively spared during the COVID-19 crisis, with some patients even reporting a reduction in seizure burden. However, PLWE require ongoing psychosocial support with particular attention to decompensation of mental health and social stressors that may be exacerbated by the COVID-19 pandemic.

Learning curve of laparoscopic living donor right hepatectomy.

BACKGROUND: The feasibility and learning curve of laparoscopic living donor right hepatectomy was assessed. METHODS: Donors who underwent right hepatectomy performed by a single surgeon were reviewed. Comparisons between open and laparoscopy regarding operative outcomes, including number of bile duct openings in the graft, were performed using propensity score matching. RESULTS: From 2014 to 2018, 103 and 96 donors underwent laparoscopic and open living donor right hepatectomy respectively, of whom 64 donors from each group were matched. Mean(s.d.) duration of operation (252·2(41·9) versus 304·4(66·5) min; P < 0·001) and median duration of hospital stay (8 versus 10 days; P = 0·002) were shorter in the laparoscopy group. There was no difference in complication rates of donors (P = 0·298) or recipients (P = 0·394) between the two groups. Total time for laparoscopy decreased linearly (R2 = 0·407, ß = -0·914, P = 0·001), with the decrease starting after approximately 50 procedures when cases were divided into four quartiles (2nd versus 3rd quartile, P = 0·001; 3rd versus 4th quartile, P = 0·023). Although grafts with bile duct openings were more abundant in the laparoscopy group (P = 0·022), no difference was found in the last two quartiles (P = 0·207). CONCLUSION: Laparoscopic living donor right hepatectomy is feasible and an experience of approximately 50 cases may surpass the learning curve.

ANTECEDENTES: Se evaluó la viabilidad y la curva de aprendizaje de la hepatectomía derecha de donante vivo MÉTODOS: Se llevó a cabo una revisión de los donantes sometidos a hepatectomía derecha por un único cirujano. Las comparaciones entre el abordaje abierto y laparoscópico con respecto a los resultados operatorios, incluyendo el número of aberturas de los conductos biliares en el injerto se realizó utilizando un análisis de emparejamiento por puntaje de propensión. RESULTADOS: Desde 2014 a 2018, 96 y 103 donantes fueron sometidos a hepatectomía derecho de donante vivo por cirugía abierta y laparoscópica, respectivamente, de los cuales 64 donantes fueron emparejados para ambos grupos. La media del tiempo operatorio (304,3 ± 66,5 versus 252,2 ± 41,9 minutos, P < 0,001) y la mediana de la estancia hospitalaria fueron más cortas en el grupo de cirugía laparoscópica (10 versus 8 días, P = 0,002). No hubo diferencias entre ambos grupos en las tasas de complicaciones de los donantes (P = 0,298) o receptores (P = 0,394). El tiempo total de la laparoscopia disminuyó linealmente (R2= 0,407, ß = -0,914, P = 0,001) y esta disminución comenzó a partir aproximadamente de los 50 casos realizados cuando los casos fueron divididos en cuatro cuartiles (segundo a tercero y tercero a cuarto, P = 0,001 y P = 0,023, respectivamente). Aunque los injertos con aperturas de los conductos biliares fueron más numerosos en el grupo laparoscópico (P = 0,022), no se hallaron diferencias en los dos últimos cuartiles (P = 0,207). CONCLUSIÓN: La hepatectomía derecha de donante vivo por vía laparoscópica es viable, y una experiencia de aproximadamente 50 casos, puede superar la curva de aprendizaje.

Case-matched comparison of ABO-incompatible and ABO-compatible living donor liver transplantation.

BACKGROUND: ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has a high success rate. There are few detailed comparisons regarding biliary complications, infective complications and patient survival between ABO-compatible (ABO-C) and ABO-I LDLT. The aim was to compare the outcomes of ABO-I LDLT with those of ABO-C LDLT using the matched-pairs method. METHODS: Patients who underwent ABO-I LDLT procedures between 2010 and 2013 were studied. They were matched for significant variables with patients who had ABO-C LDLT (1:2 matching). RESULTS: Forty-seven ABO-I LDLT procedures were included. Ninety-four patients who had ABO-C LDLT were selected as a comparator group. The incidence of cytomegalovirus, bacterial and fungal infections during the first 3 months was similar after ABO-I LDLT and ABO-C LDLT (85 versus 76 per cent, 28 versus 37 per cent, and 13 versus 20 per cent, respectively). Antibody-mediated rejection occurred after two procedures within 2 weeks of transplantation, but liver function improved with plasma exchange in both patients. There were no differences in the rate of acute rejection and biliary complications between ABO-I and ABO-C groups (P = 0.478 and P = 0.511 respectively). Three patients who had ABO-I LDLT developed diffuse intrahepatic biliary complications and progressed to graft failure. The 1-, 2- and 3-year patient survival rates after ABO-I LDLT and ABO-C LDLT were 89 versus 87 per cent, 85 versus 83 per cent, and 85 versus 79 per cent, respectively. CONCLUSION: The short-term outcomes of ABO-I LDLT were comparable to those of ABO-C LDLT in this study. ABO-I LDLT is an effective and safe transplant option with the potential to expand the pool of live donors.

Influence of hepatitis B virus reactivation on the recurrence of HBV-related hepatocellular carcinoma after curative resection in patients with low viral load.

It is unclear whether the reactivation of hepatitis B virus (HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resection in patients with chronic hepatitis B. The aim of this study was to identify the influence of HBV reactivation on the recurrence of hepatitis B-related HCC after curative resection in patients with low viral load (HBV DNA <2000 IU/mL). We retrospectively analysed a total of 130 patients who underwent curative resection for HBV-related early stage HCC (single nodule; <5 cm/two or three nodules; <3 cm) with pre-operative HBV DNA levels <2000 IU/mL with serial HBV DNA tests. The predictive factors including HBV reactivation for the recurrence of HBV-related HCC after curative resection were investigated. Fifty-three patients (41%) had HBV reactivation after resection among 130 patients. HBV reactivation was observed in 22 of 53 patients with undetectable baseline HBV DNA and in 31 of 77 patients with detectable baseline HBV DNA. Cumulative recurrence rates after resection at 1, 2 and 3 years were 17.0%, 23.3% and 31.4%, respectively. The multivariable analysis demonstrated that the risk factors for the recurrence were the presence of microvascular invasion (hazard ratio (HR) 2.62, P = 0.003), multinodularity (HR 4.61, P = 0.005), HBV reactivation after resection (HR 2.03, P = 0.032) and HBeAg positivity (HR 2.06, P = 0.044). HBV reactivation after curative resection is associated with the recurrence of HBV-related HCC in patients with low viral load.

Simulated pressure changes in multilayer, multicomponent wrap systems when transitioning from rest to standing.

OBJECTIVE: The objective of this paper was to investigate the pressure applied to the lower leg by multilayer, multicomponent wrap systems, in different positions Method: The stretch profiles of five multilayer, multicomponent wrap systems were tested, three 2-layer and two 4-layer systems. These were quantified in the laboratory using a tensile testing device. The circumference of the lower leg was measured on healthy participants in three locations (ankle, B1 level, and calf) in three different postures (rest, dorsiflexion, and standing). RESULTS: The largest changes in circumference were used to simulate the pressure changes under the multilayer, multicomponent products using Laplace's Law. While the pressure differences were large for the zinc plaster product, pressure changes ranged from 5-10mmHg for the other, more elastic products. Additionally, it was noted that the leg decreased in circumference at the B1 level and calf for the majority of participants when transitioning from sitting to standing. This decrease in size results in a decrease in bandage tension and applied pressure. CONCLUSION: These results show that the sub-bandage pressure is not significantly affected by changes in posture when used as intended, within the therapeutic range. DECLARATION OF INTEREST: This study was sponsored by Carolon. L. Reid, and S. Kravitz are employees of Carolon and E. Grant is a Member of the Board. M. Hegarty-Craver and C. Kwon have received monetary compensation as researchers for Carolon.

Serpin peptidase inhibitor clade A member 1 is a biomarker of poor prognosis in gastric cancer.

BACKGROUND: In a previous study, we reported that serpin peptidase inhibitor clade A member 1 (serpinA1) is upregulated in Snail-overexpressing gastric cancer. Although serpinA1 has been studied in several types of cancer, little is known about its roles and mechanisms of action. In this study, we examined the role of serpinA1 in the migration and invasion of gastric cancers and determined its underlying mechanism. METHODS: Expression levels were assessed by western blot analyses and real-time PCR. Snail binding to serpinA1 promoter was analysed by chromatin immunoprecipitation (ChIP) assays. The roles of serpinA1 were studied using cell invasion and migration assays. In addition, the clinicopathologic and prognostic significance of serpinA1 expression were validated in 400 gastric cancer patients using immunohistochemical analysis. RESULTS: Overexpression of Snail resulted in upregulation of serpinA1 in gastric cancer cell lines, AGS and MKN45, whereas knockdown of Snail inhibited serpinA1 expression. Chromatin immunoprecipitation analysis showed that overexpression of Snail increased Snail recruitment to the serpinA1 promoter. Overexpression of serpinA1 increased the migration and invasion of gastric cancer cells, whereas knockdown of serpinA1 decreased invasion and migration. Moreover, serpinA1 increased mRNA levels and release of metalloproteinase-8 in gastric cancer cells. Serpin peptidase inhibitor clade A member 1 was observed in the cytoplasm of tumour cells and the stroma by immunohistochemistry. Enhanced serpinA1 expression was significantly associated with increased tumour size, advanced T stage, perineural invasion, lymphovascular invasion, lymph node metastases, and shorter overall survival. CONCLUSIONS: Serpin peptidase inhibitor clade A member 1 induces the invasion and migration of gastric cancer cells and its expression is associated with the progression of gastric cancer. These results may provide a potential target to prevent invasion and metastasis in gastric cancer.

Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease.

Somatic inactivation of PTEN occurs in different human tumors including glioblastoma, endometrial carcinoma and prostate carcinoma. Germline mutations in PTEN result in a range of phenotypic abnormalities that occur with variable penetrance, including neurological features such as macrocephaly, seizures, ataxia and Lhermitte-Duclos disease (also described as dysplastic gangliocytoma of the cerebellum). Homozygous deletion of Pten causes embryonic lethality in mice. To investigate function in the brain, we used Cre-loxP technology to selectively inactivate Pten in specific mouse neuronal populations. Loss of Pten resulted in progressive macrocephaly and seizures. Neurons lacking Pten expressed high levels of phosphorylated Akt and showed a progressive increase in soma size without evidence of abnormal proliferation. Cerebellar abnormalities closely resembled the histopathology of human Lhermitte-Duclos disease. These results indicate that Pten regulates neuronal size in vivo in a cell-autonomous manner and provide new insights into the etiology of Lhermitte-Duclos disease.

Emergency Department and Urgent Care Medical Malpractice Claims 2001-15.

INTRODUCTION: This study reviews malpractice, also called medical professional liability (MPL), claims involving adult patients cared for in emergency departments (ED) and urgent care settings. METHODS: We conducted a retrospective review of closed MPL claims of adults over 18 years, from the Medical Professional Liability Association's Data Sharing Project database from 2001-2015, identifying 6,779 closed claims. Data included the total amount, origin, top medical specialties named, chief medical factors, top medical conditions, severity of injury, resolution, average indemnity, and defense costs of closed claims. RESULTS: Of 6,779 closed claims, 65.9% were dropped, withdrawn, or dismissed. Another 22.8% of claims settled for an average indemnity of $297,709. Of the 515 (7.6%) cases that went to trial, juries returned verdicts for the defendant in 92.6% of cases (477/515). The remaining 7.4% of cases (38/515) were jury verdicts for the plaintiff, with an average indemnity of $816,909. The most common resulting medical condition cited in paid claims was cardiac or cardiorespiratory arrest (10.4%). Error in diagnosis was the most common chief medical error cited in closed claims. Death was the most common level of severity listed in closed (38.5%) and paid (42.8%) claims. Claims reporting major permanent injury had the highest paid-to-closed ratio, and those reporting grave injury had the highest average indemnity of $686,239. CONCLUSION: This retrospective review updates the body of knowledge surrounding medical professional liability and represents the most recent analysis of claims in emergency medicine. As the majority of emergency providers will be named in a MPL claim during their career, it is essential to have a better understanding of the most common factors resulting in MPL claims.

Laparoscopic right posterior sectionectomy versus laparoscopic right hemihepatectomy for hepatocellular carcinoma in posterior segments: Propensity Score Matching Analysis.

BACKGROUND AND AIMS:: This study was designed to analyze the feasibility of laparoscopic right posterior sectionectomy compared to laparoscopic right hemihepatectomy in patients with hepatocellular carcinoma located in the posterior segments. MATERIAL AND METHODS:: The study included patients who underwent either laparoscopic right posterior sectionectomy or laparoscopic right hemihepatectomy for hepatocellular carcinoma located in segment 6 or 7 from January 2009 to December 2016 at Samsung Medical Center. After 1:1 propensity score matching, patient baseline characteristics and operative and postoperative outcomes were compared between the two groups. Disease-free survival and overall survival were compared using Kaplan-Meier log-rank test. RESULTS:: Among 61 patients with laparoscopic right posterior sectionectomy and 37 patients with laparoscopic right hemihepatectomy, 30 patients from each group were analyzed after propensity score matching. After matching, baseline characteristics of the two groups were similar including tumor size (3.4 ± 1.2 cm in laparoscopic right posterior sectionectomy vs 3.7 ± 2.1 cm in laparoscopic right hemihepatectomy, P = 0.483); differences were significant before matching (3.1 ± 1.3 cm in laparoscopic right posterior sectionectomy vs 4.3 ± 2.7 cm in laparoscopic right hemihepatectomy, P = 0.035). No significant differences were observed in operative and postoperative data except for free margin size (1.04 ± 0.71 cm in laparoscopic right posterior sectionectomy vs 2.95 ± 1.75 cm in laparoscopic right hemihepatectomy, P < 0.001). Disease-free survival (5-year survival: 38.0% in laparoscopic right posterior sectionectomy vs 47.0% in laparoscopic right hemihepatectomy, P = 0.510) and overall survival (5-year survival: 92.7% in laparoscopic right posterior sectionectomy vs 89.6% in laparoscopic right hemihepatectomy, P = 0.593) did not differ between the groups based on Kaplan-Meier log-rank test. CONCLUSION:: For hepatocellular carcinoma in the posterior segments, laparoscopic right posterior sectionectomy was feasible compared to laparoscopic right hemihepatectomy when performed by experienced laparoscopic surgeons.

Clinical significance of posttransplantation vesicoureteral reflux during short-term period after kidney transplantation.

BACKGROUND: Urinary tract infection (UTI) may occur in the form of asymptomatic bacteruria but severe cases may cause life-threatening pyelonephritis or sepsis in immunosuppressed kidney transplant recipients. Vesicoureteral reflux (VUR) is one risk factor in the transplanted kidney. But controversy exists regarding the effect of VUR in terms of graft outcomes. The objective of this study was to analyze the clinical outcomes among patients with posttransplantation VUR. PATIENTS AND METHODS: Between April 2005 and June 2006, we examined 75 patients with functioning grafts for more than 1 year by voiding cystourethrography at 1 year for the grade of posttransplantation VUR: group A, absent (n = 28) including grade I (n = 6) and II (n = 22); group B, including grade III (n = 17) and IV (n = 2). Patient characteristics included etiology of end-stage renal disease, duration of dialysis before transplantation, serum creatinine, creatinine clearance at 1 and 12 months after transplantation, and postoperative complications. The presence/absence of UTI, acute rejection, and graft loss were compared for significance. RESULT: Posttransplantation VUR present in 47/75 patients (61.3%) was over grade III in 19 patients. There was no difference in significant risk factors between the groups as well as between the reflux subgroups. VUR did not influence graft function with the only significant factor being acute cellular rejection. CONCLUSION: We failed to confirm a risk of developing posttransplantation VUR. Posttransplantation VUR did not negatively affect graft function; acute cellular rejection was the only factor that influenced it. Longer follow-up needs to be performed to clarify the long-term effects of posttransplantation VUR on graft function.

Renal transplantation in patients with a small bladder.

BACKGROUND: In patients undergoing kidney transplantation with a small bladder, many surgeons are faced with technical difficulties about the implantation as well as about satisfactory bladder rehabilitation. The objective of this study was to clarify the clinical outcomes of patients with end-stage renal disease who had a bladder capacity of less than 100 mL on preoperative voiding cystourethrogram after renal transplantation using extravesical ureteroneocystostomy. PATIENTS AND METHODS: We retrospectively studied 345 patients with end-stage renal disease who underwent renal transplantation between April 2002 and June 2006. These patients were classified into two groups according to their preoperatively estimated bladder capacity using a voiding cystourethrogram. Group A had a bladder capacity of less than 100 mL (n = 23; 6.7%) and group B had a capacity of 100 mL or more (n = 322; 93.3%). For each group, the clinical outcome, including serum creatinine level at 1 month and 1 year after transplantation, bladder capacity, surgical complications, and prevalence of urinary tract infection (UTI) requiring hospital admission were recorded and the graft survival rate calculated. RESULTS: Compared with group B, group A had undergone a longer duration of dialysis and required cadaveric kidney transplantation more frequently (P < .05). Postoperative surgical complications occurred in nine cases. There was no difference in the frequency of surgical complications and UTI requiring hospital admission between group A and group B. At 1 year posttransplant, bladder capacity was 342.0 +/- 43.8 mL (range, 300-400 mL) and 429.1 +/- 75.9 mL (range, 200-500 mL), respectively (P = .015). There was no statistical difference between the groups in the serum creatinine level and the graft survival rate at 5 years after transplantation (100% vs 92.4%). CONCLUSIONS: Similar to patients with a normal bladder size, renal transplantation can be successfully achieved in patients with a small bladder. Attempts to increase the bladder capacity by programmed training of the bladder and bladder expansion by surgical intervention seem unnecessary.

Peroneal neuropathy after liver transplantation.

INTRODUCTION: The incidence of peroneal neuropathy (PN), occurring predominantly in the left leg, increases after the incorporation of intermittent pneumatic compression (IPC) devices among adult liver transplantation (OLT) recipients in our hospital. The aim of this study was to investigate the possible risk factors for PN and the reason for the left-leg predominance. METHODS: We retrospectively reviewed the medical records of 501 OLT recipients. The patients were first divided into 2 groups, PN (n = 33) and non-PN (n = 468), to assess possible risk factors. The patients were then categorized into IPC (n = 262) and non-IPC (n = 239) groups according to the use of IPC devices. In a subsequent prospective study, we measured the degree and duration of the tilt of the operating table during OLT to investigate their relationship to the predominant left-leg PN. RESULTS: The rate of IPC device use was significantly greater among the PN than non-PN group (78.8% vs 50.4%, P < .01). The incidence of PN was significantly higher among the IPC than non-IPC group (9.9% vs 2.9%, P < .01). The degree and duration of left tilt of the operating table were greater and longer than the right tilt. CONCLUSIONS: The use of IPC devices during OLT increased the occurrence of PN and the left tilt of the operating table was strongly related to the predominant left-leg PN. Careful protection of the vulnerable point and minimization of the tilting of the operating table is advised during OLT, especially when IPC devices are used.

Isolation and characterization of mouse mesenchymal stem cells.

OBJECTIVE: Mesenchymal stem cells (MSCs) have been studied in regenerative medicine because of their unique immunologic characteristics. However, before clinical application in humans, animal models are needed to confirm their safety and efficacy. To date, appropriate methods and sources to obtain mouse MSCs have not been identified. Therefore, we investigated MSCs isolated from 3 strains of mice and 3 sources for the development of MSCs in a mouse model. MATERIALS AND METHODS: Male BALB/c, C3H and C57BL/6 mice were used to isolate MSCs from various tissues including bone marrow (BM), compact bone, and adipose tissue. The MSCs were maintained in StemXVivo medium. Immunophenotypes of the MSCs were analyzed by FACS and their growth potential estimated by the number of colony-forming unit fibroblasts. RESULTS: All MSCs that were isolated from BM, compact bone, and adipose tissue showed plastic-adherent, fibroblastic-like morphologic characteristics regardless of the mouse strain or cell source. However, culture of BM MSCs was less successful than the other tissue types. The FACS phenotype analysis revealed that the MSCs were positive for CD29, CD44, CD105, and Sca-1, but negative for CD34, TER-119, CD45, and CD11b. According to the results of the characterization, the adipose tissue MSCs showed higher growth potential than did other MSCs. CONCLUSION: The results of this study showed that culture of adipose tissue and compact bone-MSCs was easier than BM MSCs. Based on the results of immunophenotype and growth potential, C57BL/6 AT-MSCs might be a suitable source to establish a mouse model of MSCs.

Reconstitution of human lymphocytes following ex vivo expansion of human umbilical cord blood CD34+ cells and transplantation in Rag2-/- gamma c-/- mice model.

BACKGROUND: Due to ethical issues, in vivo studies of the human immune system have been difficult. Thus, small-animal xenotransplantation models have been employed, although they scarcely sustain a human immune response. In this study, we compared human cell repopulation tendencies and functionality in Rag2-/- gamma c-/- mice following various ex vivo expanded human hematopoietic stem cells (HSCs). METHODS: Human umbilical cord blood (UCB) CD34+ cells were cultured for 7 days with a cytokine combination of stem cell factor, Flk2/Flt3 ligand, and thrombopoietin, with absence or presence of rhIL-3, then transplanted into Rag2-/- gamma c-/- mice. Reconstituted human lymphocytes were analyzed based on the expression of CD45 as well as CD3, CD19, and CD56 in peripheral blood (PB) until 16 weeks after transplantation. BrdU assay and functional analysis of reconstituted human lymphocytes used PHA- or rhIL-2-stimulated splenocytes and bone marrow cells from recipient mice. RESULTS: The percentage of human CD45dim cells, not CD45bright cells, in PB of mice transplanted with cultured HSCs with rhIL-3 was much higher than in the group without rhIL-3 (approximately 2.5-fold at week 10 posttransplantation). The humanized mice showed systemic repopulation with a comprehensive array of human lymphohematopoietic cells, including T, B, natural killer (NK) cells, and even dendritic cells. However, the expression level was also dim. The number of CD3+ T cells and CD56+ NK cells was especially increased in the presence of rhIL-3. In addition, after in vitro restimulation proliferation assays and NK activity of interferon-gamma secretion showed greater effects in the presence of rhIL-3. CONCLUSION: These data suggested that the development of a diverse repopulation of human lymphocytes was possible in Rag2-/- gamma c-/- mice after transplantation of cultured UCB CD34+ HSCs with interleukin-3.

Comparison of Posttransplant Outcomes in Living Donor Liver Transplantation for Obese and Nonobese Recipients.

BACKGROUND: Although living donor liver transplantation for obese recipients has increased, it has not been determined that posttransplant outcomes in obese recipients are inferior compared with nonobese recipients. METHODS: From January 2001 to December 2016, there was a total of 58 (6%) obese patients (body mass index ≥30) in a cohort of 973 adult patients that underwent living donor liver transplantation. Propensity score matching and classification were performed based on the type of obesity, and there were 58 patients in the obese group and 141 patients in the nonobese group. We performed comparative analysis of posttransplant outcomes including Model for Early Allograft Function (MEAF) scoring and early allograft dysfunction (EAD). RESULTS: EAD was found in 11 (19%) and 31 (22%) patients in the obese and nonobese groups, respectively (P = .71). The obese group had a higher MEAF score than the nonobese group (5.2 vs 4.5, P = .007). The mean hospitalization of the obese group was shorter than in the nonobese group (32 vs 42 days, P = .003). Other posttransplant outcomes were similar between the obese and nonobese groups, including acute cellular rejection (8 vs 10 cases, P = .17), early graft failure (8 vs 12 cases, P = .30), index hospital mortality (6 vs 11 cases, P = .58), and comprehensive complication index (26.0 vs 24.6, P = .76). CONCLUSION: Posttransplant outcomes of the obese group were not inferior to the nonobese group. However, obesity can impact the severity of EAD and the incidence of early graft failure, based on significantly higher MEAF scores.

Early Vs Late Liver Retransplantation: Different Characteristics and Prognostic Factors.

BACKGROUND: East Asia is a known endemic area for hepatitis B, and living donor liver transplantation is mainly performed. Liver retransplantation (ReLT) is expected to become an increasing problem because of a shortage of organs. This study aimed to compare early and late ReLT with consideration of specific circumstances and disease background of East Asians. METHODS: Between October 1996 and January 2015, 51 patients underwent ReLT; we performed a retrospective analysis of data obtained from medical records of the patients. Clinical characteristics, indication, causes of death, survival rate, and prognostic factors were investigated. RESULT: The survival rate for early ReLT (n = 18) was 51.5% and that for late ReLT (n = 33) was 50.1% at 1 year postoperatively. Continuous venovenous hemodialysis and the use of mechanical ventilators were more frequent, and pre-retransplant intensive care unit stay and prothrombin time was longer in early ReLT than in late ReLT. Operation time was longer and the amount of intraoperative blood loss was greater in late ReLT than in early ReLT. Multivariate analysis showed that a higher C-reactive protein level increased mortality in early ReLT (P = .045), whereas a higher total bilirubin level increased the risk of death in late ReLT (P = .03). CONCLUSION: Patients with early ReLT are likely to be sicker pre-retransplantation and require adequate treatment of the pretransplant infectious disease. On the other hand, late ReLT is likely to be technically more difficult and should be decided before the total bilirubin level increases substantially.