Thiesengrantham9487

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. 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. LXH254 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.