Hyldgaardharding8767

diagnosis must be kept in mind when patients treated with adalimumab present with sudden-onset convulsions. Careful dental examination should be performed before administration of adalimumab.There is little consensus on the optimal timing of anti-tumor necrosis factor (anti-TNF) therapy to decrease the rates of hospitalization and surgery in Crohn disease (CD). We aimed to assess the real-world outcomes of anti-TNF therapy and estimate the optimal timing of anti-TNF therapy in Korean patients with CD.Claims data were extracted from the Korean Health Insurance Review and Assessment Service database. Incident patients diagnosed with CD between 2009 and 2016, with at least 1 anti-TNF drug prescription, and with follow-up duration > 6 months were stratified according to the number of relapses prior to initiation of anti-TNF therapy groups A (≤1 relapse), B (2 relapses), C (3 relapses), and D (≥4 relapses). The cumulative survival curves free from emergency hospitalization (EH) and surgery were compared across groups.Among the 2173 patients analyzed, the best and worst prognoses were noted in groups A and D, respectively. The incidences of EH and surgery decreased significantly as the use of anti-TNF agents increased. The 5-year rate of hospitalization was significantly lower in group A than in groups C and D (P = .004 and .020, respectively), but similar between groups A and B. The 5-year rate of surgery was lower in group A than in group C (P = .024), but similar among groups A, B, and D.In Asian patients with CD, anti-TNF therapy reduces the risk of EH and surgery and should be considered before three relapses, regardless of disease duration.BACKGROUND MicroRNAs (miRNA) are short noncoding RNAs which each cause repression of many target genes. Previous work has demonstrated that therapeutic blockade of single microRNAs is possible. miR-24-3p and miR-145-5p are reported to have a detrimental role in ischaemia reperfusion injury (IRI). As the action of miRNAs is inhibitory, we hypothesised that dual blockade of both miRNAs could synergistically upregulate shared target genes. METHODS Quantification of miRNA expression in donated kidneys was performed using PCR panels. IRI was modelled in vitro by placing Human Umbilical Vein Endothelial Cells (HUVECs) into a hypoxic incubator (1% O2) for 24hrs, with reoxygenation for 6hrs. RNA expression was quantified with RT-qPCR and protein expression assessed with Western blot. Antisense oligonucleotides (ASOs) were used to inhibit miRNAs. RESULTS miR-24-3p and miR-145-5p were highly expressed in human kidneys following extended cold ischemia. In vitro, hypoxia caused significant upregulation of miR-24-3p (p≤0.001) and miR-145-5p (p≤0.001), and significant downregulation in mRNA of shared targets SOD2 (p≤0.001) and HMOX1 (p≤0.001). These changes were mirrored at the protein level. Dual inhibition of both miR-24-3p and miR-145-5p prior to hypoxia-reoxygenation caused significant upregulation of SOD2 and HMOX1 protein; fold-change of 3.17 (p≤0.05) and 6.97 (p≤0.05) respectively. Dual inhibition resulted in reduced cellular ROS production compared to negative control (p≤0.05) and single blockade of miR-24-3p (p≤0.01) or miR-145-5p (p≤0.05). CONCLUSION Dual blockade of 2 miRNAs can act synergistically to increase the expression of shared gene targets. Dual blockade of miR-24-3p and miR-145-5p represents a novel therapeutic option worthy of further research.BACKGROUND Preconditioning of donor livers prior to organ retrieval may improve organ quality after transplantation. We investigated whether preconditioning with metformin reduces preservation injury and improves hepatobiliary function in rat donor livers during ex situ normothermic machine perfusion (NMP) and after orthotopic liver transplantation. check details METHODS Lewis rats were administered metformin via oral gavage, after which a donor hepatectomy was performed followed by a standardized cold storage period of 4 hours. Graft assessment was carried out using NMP via double perfusion of the hepatic artery and portal vein. In an additional experiment, rat donor livers preconditioned with metformin were stored on ice for 4 hours and transplanted to confirm postoperative liver function and survival. Data was analyzed and compared with sham-fed controls. RESULTS Graft assessment using NMP confirmed that preconditioning significantly improved ATP production, markers for hepatobiliary function (total bile production, biliary bilirubin and bicarbonate), and significantly lowered levels of lactate, glucose and apoptosis. After orthotopic liver transplantation, metformin preconditioning significantly reduced transaminase levels. CONCLUSION Preconditioning with metformin lowers hepatobiliary injury and improves hepatobiliary function in an in situ and ex situ model of rat donor liver transplantation.BACKGROUND Living kidney donors are carefully screened, but despite overall good health, long-term donor outcomes have been shown to vary by predonation demographics. Since 2013 the United Network for Organ Sharing has mandated 2 year postdonation follow-up with measurements of kidney function and proteinuria. METHODS Using data from the Scientific Registry of Transplant Recipients, we sought to analyze donor factors associated with the percent change of kidney function from baseline (predonation) to 2 years postdonation, along with incidence of proteinuria reported within the same follow up period. RESULTS Older donor age, male gender, black race, and body mass index (BMI) greater than 25 kg/m were independently associated with a greater percent decline in estimated glomerular filtration rate (eGFR). Male gender, black race, and higher BMI were also independently associated with incident proteinuria. In contrast, younger donor age was associated with proteinuria, but proteinuria did not correlate with greater decline in eGFR in the overall cohort. CONCLUSION Donor factors associated with lower eGFR at 2 years postdonation were similar to those previously found to be associated with long-term risk for End Stage Renal Disease (ESRD). Early postdonation assessment of kidney function and proteinuria may help to identify donors who are at greater risk of ESRD and who may benefit from more intense long-term monitoring.BACKGROUND Immunosuppressive nonadherence is a risk factor for worse outcomes after kidney transplantation (KT). Brazil, having the world's largest public, fully covered transplantation system and the second highest KT volume worldwide, provides a unique setting for studying multilevel correlates of nonadherence (patient, healthcare provider, transplant center, and healthcare system levels) independent of patients' financial burden. METHODS By applying a multistage sampling approach, we included 1105 patients from 20 KT centers. Nonadherence to immunosuppressives (implementation phase) was defined as any deviation in taking or timing adherence and/or dose reduction assessed by the BAASIS. Based on Bronfenbrenner's ecological model, we assessed multilevel factors using established instruments and measures specifically developed for this study and analyzed their independent contribution to nonadherence by performing sequential logistic regression analysis. RESULTS The nonadherence prevalence rate was 39.7%. The following factors were independently associated with nonadherence Patient level- having a stable partner (OR0.75; CI0.58-0.97), nonadherence to appointments (OR2.98; IC2.03-4.39), and nonadherence to physical activity recommendations (OR1.84; CI1.38-2.46); and Transplant center level - satisfaction with the waiting room structure (OR0.54;CI0.42-0.71), consultation >30 minutes (OR1.60; CI1.19-2.14), adequacy of the consultation frequency (OR0.62; CI0.43-0.90), and centers with >500 beds (OR0.58; CI0.46-0.73). CONCLUSIONS As the first multicenter study assessing multilevel correlates of nonadherence in KT, our findings point to the need for multilevel interventions beyond the patient level, targeting transplant center practice patterns as an approach to tackle nonadherence.BACKGROUND Uterus transplantation is a treatment for absolute uterine infertility and can be performed with living and deceased donors. Given the safety and increased utilization of robotic assistance with other gynecologic and transplant donor operations, we adopted a robot-assisted approach to donor hysterectomy. This study compared early outcomes and morbidity of the robot-assisted approach to donor hysterectomy with the traditionally performed open approach and addressed whether the robot-assisted approach is safe and offers advantages for the donor. METHODS Our institution has performed 18 living donor hysterectomies for uterus transplantation. This retrospective review compared the last 5 cases utilizing a robot-assisted technique and vaginal extraction of the uterus graft with the first 13 cases performed with an open laparotomy technique. Demographic, intraoperative, and postoperative data were examined. RESULTS There were no differences between the robot-assisted and the open living donor group with respect to age, body mass index, or gynecological history. Although the median operative time was shorter for the open approach (6.27 vs 10.46 h), the donors' median estimated blood loss, length of hospital stay, and length of sick leave were less with the robot-assisted approach. There was no conversion to open hysterectomy in the robot-assisted cases, and the incidence of complications was similar between the 2 groups. There was no difference in early graft function. CONCLUSION These preliminary results show that robot-assisted living donor hysterectomy is feasible and safe for the donors; it allows a faster postoperative recovery and the same early graft function.BACKGROUND Procuring a good quality transbronchial-biopsy (TBB) sample is essential for diagnosing acute cellular rejection (ACR) after lung transplantation (LT). Insufficient TBB samples are graded 'AX.' We hypothesized that AX samples may be associated with a higher risk for chronic lung allograft dysfunction (CLAD) or death/retransplant, through a potential anatomic or physiologic underlying pulmonary process or due to undiagnosed ACR episodes. METHODS We conducted a single-center, retrospective, cohort study drawn from all consecutive adult, first, bilateral LT between 1999-2015. We reviewed all biopsies obtained within the first year posttransplant and compared outcomes of patients with ≥1 AX to patients with no AX. Association of any AX or percent AX with time to CLAD or death/retransplant was assessed using Cox Proportional Hazards models. RESULTS The cohort consisted of 809 patients with a median of 6 (IQR 5, 6) biopsies and 16.7% (IQR 0, 25) AX samples within the first-year posttransplant. 439 (54.3%) subjects had ≥1AX sample obtained within the time period. Median time to CLAD or death/retransplant, from 1-year posttransplant, was 761 (320, 1587) and 1200 (662, 2308) days, respectively. In the multivariable analysis, there was no difference in risk for CLAD (HR=1.05, 95% CI 0.87-1.28, P=0.60), or death/retransplant (HR=1.14, 95% CI 0.92-1.42, P=0.24) between patients with ≥1AX biopsy versus none. Among subjects with ≥1 AX, having more than 50% AX biopsies was not associated with outcome. CONCLUSION This is the first study to demonstrate that AX biopsies are not associated with an increased risk of CLAD or death/retransplant after LT and may not require to repeat the biopsy.