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The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal vein thrombosis (PVT) remains controversial. This study aimed to conduct a systematic review and meta-analysis to evaluate the role of TIPS for the management of PVT in adult patients with liver disease.Multiple databases were searched through April 2017. Data were gathered to estimate the rates of technical success, portal vein recanalization, portal patency, hepatic encephalopathy, and mean change in portal pressure gradient in patients with PVT who underwent TIPS. Estimates were pooled across studies using the random effects model.Eighteen studies were included in the analysis. The pooled technical success rate was 86.7% [95% confidence interval (CI)=78.6-92.1%]. Rate of portal vein recanalization was 84.4% (95% CI=78.4-89.0%). The rate of complete recanalization was 73.7% (95% CI=64.3-81.3%). Portal patency was 86.9% (95% CI=79.7-91.8%). Mean change in portal pressure gradient was 14.5 mmHg (95% CI=11.3-17.7 mmHg). Hepatic encephalopathy was 25.3% (95% CI=19.2-32.6%). The number of major adverse events reported across studies was low. The majority of the analyses were not associated with substantial heterogeneity.The use of TIPS in the management of PVT is feasible and effective in achieving a significant and sustainable reduction in clot burden with a low risk of major complications. TIPS should be considered as a viable treatment option in patients with PVT. Given the limited amount of randomized comparative studies reported, additional trials are warranted to assess the safety and efficacy of TIPS as a treatment modality in PVT, in comparison to other treatment options, such as anticoagulation.

Introduction Liver transplantation (LT) remains the gold standard for treatment of end-stage liver disease. Given the increasing number of liver transplantation in females of reproductive age, our aim was to conduct a systematic review and meta-analysis evaluating pregnancy outcomes after LT. Methods MEDLINE, Embase, and Scopus databases were searched for relevant studies. Study selection, quality assessment, and data extraction were conducted independently by 2 reviewers. Estimates of pregnancy-related outcomes in LT recipients were generated and pooled across studies using the random-effects model. Results A comprehensive search identified 1,430 potential studies. Thirty-eight studies with 1,131 pregnancies among 838 LT recipients were included in the analysis. Mean maternal age at pregnancy was 27.8 years, with a mean interval from LT to pregnancy of 59.7 months. The live birth rate was 80.4%, with a mean gestational age of 36.5 weeks. The rate of miscarriages (16.7%) was similar to the general population (10%-20%). The rates of preterm birth, preeclampsia, and cesarean delivery (32.1%, 12.5%, and 42.2%, respectively) among LT recipients were all higher than the rates for the general US population (9.9%, 4%, and 32%, respectively). Most analyses were associated with substantial heterogeneity. Discussion Pregnancy outcomes after LT are favorable, but the risk of maternal and fetal complications is increased. Large studies along with consistent reporting to national registries are necessary for appropriate patient counseling and to guide clinical management of LT recipients during pregnancy.

OBJECTIVES We aimed to investigate the efficacy and safety of different antithrombotic strategies in patients undergoing transcatheter aortic valve implantation (TAVI) using network meta-analyses. BACKGROUND Meta-analyses comparing single antiplatelet therapy (SAPT) vs. dual antiplatelet therapy (DAPT), ± oral anticoagulant (OAC) was conducted to determine the appropriate post TAVI antithrombotic regimen. However, there was limited direct comparisons across the different therapeutic strategies. METHODS MEDLINE and EMBASE were searched through December 2018 to investigate the efficacy and safety of different antithrombotic strategies (SAPT, DAPT, OAC, OAC + SAPT, and OAC + DAPT) in patients undergoing TAVI. The main outcome were all-cause mortality, major or life-threatening bleeding events, and stroke. RESULTS Our search identified 3 randomized controlled trials and 10 nonrandomized studies, a total of 20,548 patients who underwent TAVI. All OACs were vitamin K antagonists. There was no significant difference on mortality except that OAC + DAPT had significantly higher rates of mortality compared with others (p < .05, I2 = 0%). SAPT had significantly lower rates of bleeding compared with DAPT, OAC+SAPT, and OAC+DAPT (hazard ratio [HR]: 0.59 [0.46-0.77], p < .001, HR: 0.58 [0.34-0.99], p = .045, HR: 0.41 [0.18-0.93], p = .033, respectively, I2 = 0%). There was no significant difference on stroke among all antithrombotic strategies. CONCLUSION Patients who underwent TAVI had similar all-cause mortality rates among different antithrombotic strategies except OAC+DAPT. Patients on SAPT had significantly lower bleeding risk than those on DAPT, OAC + SAPT, and OAC + DAPT. Our results suggest SAPT is the preferred regimen when there is no indication for DAPT or OAC. When DAPT or OAC is indicated, DAPT + OAC should be avoided.

Amputation has been known to be a rare adverse event of sodium glucose co-transporter-2 (SGLT2) inhibitors. It remains unclear whether the SGLT2 inhibitor as a class or specific categories of the SGLT2 inhibitors are linked with an increased risk of amputation. The objective of this meta-analysis was to investigate the association between the amputation risk and the use of SGLT2 inhibitors. The main outcome measure was the risk of amputation. Multiple databases were searched up to February 2020 and data extraction was performed. Inclusion criteria were randomized controlled trials (RCTs) which reported risk of amputation with SGLT2 inhibitors over non-SGLT2 inhibitors or placebo. The risk of bias was assessed by Cochrane bias tool. The initial search yielded 1,873 citations and a total of five RCTs were included in the meta-analysis. The five included studies evaluated a total of 39,067 patients with diabetes mellitus, including 21,395 patients on SGLT2 inhibitors. The incidence rate of amputation ranged from 0.36 to 3.18% in the SGLT2 inhibitor group and from 0% to 2.87% in the control group. Follow up duration ranged from 24 weeks to 4.2 years. Use of SGLT2 inhibitors was not associated with significant increase in the risk of amputation as compared with controls (OR: 1.31, 95% CI: 0.92–1.87, I2 = 75%). Subgroup analysis showed that neither canagliflozin, empagliflozin, nor dapagliflozin was associated with increased risk of amputation. In conclusion, our meta-analysis showed that neither canagliflozin nor other SGLT2 inhibitors increase the risk of amputation.

There is no universally available laboratory test to diagnose bile acid diarrhoea (BAD). Objective To conduct a systematic review and meta-analysis to identify a biomarker for idiopathic BAD in patients with functional bowel disorder (FBD) with diarrhoea. Design We searched multiple databases through 15 May 2015. Data were only available to estimate the diagnostic yield of each test (the prevalence of a positive test). Estimates were pooled across studies using the random effects model. Results We included 36 studies, enrolling 5028 patients (24 using 75 selenium homotaurocholic acid test ( 75 SeHCAT) retention of 75 SeHCAT retention ( Conclusions Overall, the test with the highest diagnostic yield conducted in the largest number of studies was 75 SeHCAT retention, which is not widely available in many countries outside Europe and Canada. Using different diagnostic tests, 25% (average) of patients with lower FBD with diarrhoea has evidence of idiopathic BAD. These tests serve to identify idiopathic BAD among patients with FBD with diarrhoea. Further studies are required to appraise the performance characteristics of tests for idiopathic BAD.

The most common gastrointestinal disorders that include evidence of dysmotility include: gastroparesis, the lower functional gastrointestinal disorders associated with altered bowel function (such as chronic [functional] diarrhea, chronic idiopathic constipation) and opioid-induced constipation. These conditions, which are grouped as gastrointestinal motility and functional disorders, are characterized by abnormal motor, sensory or secretory functions that alter bowel function and result in a significant disease burden, since currently available treatments do not completely alleviate symptoms. New drugs are being developed for these disorders, targeting mechanisms involved in the pathophysiology of these diseases, specifically, motor function, intestinal secretion and bile acid modulation.The article provides a brief overview of motility disorders and the drugs approved and currently available for these indications. It also provides an evaluation of the efficacy, safety and possible mechanisms of the drugs currently under investigation for the treatment of gastroparesis, chronic diarrhea, chronic idiopathic constipation and opioid-induced constipation, based on animal to Phase II studies. Medications with complete Phase III trials are excluded from this discussion.Treatment of gastrointestinal motility disorders requires the understanding of the pathophysiological mechanisms, biomarkers to identify subgroups of these disorders and robust pharmacological studies from animal to Phase II studies. These are prerequisites for the development of efficacious medications and individualizing therapy in order to enhance the treatment of these patients.

Serum‐derived bovine immunoglobulin/protein isolate (SBI), an oral nutritional therapy, is efficacious in diverse diarrheal diseases. In an open‐label study in 15 patients with irritable bowel syndrome‐diarrhea (IBS‐D), we evaluated effects of SBI (5.0 g, twice a day) for 8 weeks on safety, on bowel function and abdominal pain, tryptophan metabolism (K:T ratio), intestinal permeability (13C‐mannitol and lactulose excretion), bile acid synthesis (fasting serum FGF‐19 and C4), duodenal and stool microbiome, and the expression of 90 genes related to inflammation, immune function, and tight junctions in duodenal mucosa. Statistical analysis (paired tests, baseline vs. treatment) was based on intention to treat (ITT) principles. One of 15 Caucasian patients (13F, 2M, age 40.3 ± 2.3y, BMI 34.3 ± 3.0 kg/m2) withdrew without completing studies. There were improvements in stools/day (decrease, P

Purpose The purpose of this study was to determine the radiologic tolerance of the lateral center edge angle (LCEA) and anterior center edge angle (ACEA) to pelvic rotation. Methods Eleven dry cadaveric pelvises from an osteological collection were reconstructed and placed in anatomic position with corresponding bilateral proximal femurs. Conventional anteroposterior (AP) and false-profile (FP) pelvic radiographs were taken at 5° increments with fluoroscopy from 0° to 25° of rotation. LCEA and ACEA were measured for conventional and rotated AP and FP fluoroscopic views, respectively. Statistical analysis was conducted to determine the error in ACEA and LCEA with pelvic rotation. Results The mean LCEA was 29.1° (95% confidence interval [CI], 25.5°-32.7°). Mean ACEA was 38.9° (95% CI, 34.1°-43.8°). There was significant change in the LCEA past 10° of rotation (P = .041). There was significant change in the ACEA with 5o or more of rotation (P Conclusions Rotation of AP and FP radiographs significantly affects the measured values of the LCEA and ACEA, respectively. The ACEA experiences more dramatic changes with rotation of the FP view compared with the LCEA with the same amount of rotation of an AP view. This study illustrates the importance of verifying the quality of the FP radiograph when using ACEA to guide therapy for hip pathology. Clinical Relevance This study emphasizes the importance of evaluating pelvic rotation when using the center edge angle to assess femoral head coverage.

Objective To compare efficacy of pharmacotherapies for chronic idiopathic constipation (CIC) based on comparisons to placebo using Bayesian network meta-analysis. Data sources We conducted searches (inception to May 2015) of MEDLINE, EMBASE, Scopus and Cochrane Central, as well as original data from authors or drug companies for the medications used for CIC. Study selection Phase IIB and phase III randomised, placebo-controlled trials (RCT) of ≥4 weeks9 treatment for CIC in adults with Rome II or III criteria for functional constipation; trials included at least one of four end points. Data extraction and synthesis Two investigators independently evaluated all full-text articles that met inclusion criteria and extracted data for primary and secondary end points, risk of bias and quality of evidence. Outcomes Primary end points were ≥3 complete spontaneous bowel movements (CSBM)/week and increase over baseline by ≥1 CSBM/week. Secondary end points were change from baseline (Δ b ) in the number of SBM/week and Δ b CSBM/week. Results Twenty-one RCTs (9189 patients) met inclusion and end point criteria: 9 prucalopride, 3 lubiprostone, 3 linaclotide, 2 tegaserod, 1 each velusetrag, elobixibat, bisacodyl and sodium picosulphate (NaP). All prespecified end points were unavailable in four polyethylene glycol studies. Bisacodyl, NaP, prucalopride and velusetrag were superior to placebo for the ≥3 CSBM/week end point. No drug was superior at improving the primary end points on network meta-analysis. Bisacodyl appeared superior to the other drugs for the secondary end point, Δ b in number of SBM/week. Conclusions Current drugs for CIC show similar efficacy. Bisacodyl may be superior to prescription medications for Δ b in the number of SBM/week in CIC.

Prior studies in with irritable bowel syndrome with diarrhea (IBS-D) patients showed immune activation, secretion, and barrier dysfunction in jejunal or colorectal mucosa. We measured mRNA expression by RT-PCR of 91 genes reflecting tight junction proteins, chemokines, innate immunity, ion channels, transmitters, housekeeping genes, and controls for DNA contamination and PCR efficiency in small intestinal mucosa from 15 IBS-D and 7 controls (biopsies negative for celiac disease). Fold change was calculated using 2(−ΔΔCT) formula. Nominal P values ( P < 0.05) were interpreted with false detection rate (FDR) correction ( q value). Cluster analysis with Lens for Enrichment and Network Studies (LENS) explored connectivity of mechanisms. Upregulated genes (uncorrected P < 0.05) were related to ion transport (INADL, MAGI1, and SONS1), barrier (TJP1, 2, and 3 and CLDN) or immune functions (TLR3, IL15, and MAPKAPK5), or histamine metabolism (HNMT); downregulated genes were related to immune function (IL-1β, TGF-β1, and CCL20) or antigen detection (TLR1 and 8). The following genes were significantly upregulated ( q < 0.05) in IBS-D: INADL, MAGI1, PPP2R5C, MAPKAPK5, TLR3, and IL-15. Among the 14 nominally upregulated genes, there was clustering of barrier and PDZ domains (TJP1, TJP2, TJP3, CLDN4, INADL, and MAGI1) and clustering of downregulated genes (CCL20, TLR1, IL1B, and TLR8). Protein expression of PPP2R5C in nuclear lysates was greater in patients with IBS-D and controls. There was increase in INADL protein (median 9.4 ng/ml) in patients with IBS-D relative to controls (median 5.8 ng/ml, P > 0.05). In conclusion, altered transcriptome (and to lesser extent protein) expression of ion transport, barrier, immune, and mast cell mechanisms in small bowel may reflect different alterations in function and deserves further study in IBS-D.

Background & Aims Nonselective β-blockers (NSBBs), given to reduce the risk of variceal bleeding, have been associated with increased mortality in patients with cirrhosis and refractory ascites in some, but not all, studies. We performed a systematic review and meta-analysis to evaluate the effect of NSBBs on all-cause mortality in patients with cirrhosis and refractory ascites. Methods We performed a comprehensive search of MEDLINE, Embase, Web of Science, and Scopus databases through January 2015, supplemented with a manual search. Trial-specific risk ratios (RRs) were pooled using the random-effects model. Results Our analysis included 3 randomized control trials and 8 observational studies of propranolol, carvedilol, nadolol, and metoprolol, reporting 1206 deaths among 3145 patients with ascites. The control groups received other interventions to prevent variceal bleeding. NSBB use was not associated with increased all-cause mortality in all patients with ascites (RR, 0.95; 95% confidence interval [CI], 0.67–1.35); nonrefractory ascites alone (RR, 0.96; 95% CI, 0.50–1.82), or refractory ascites alone (RR, 0.95; 95% CI, 0.57–1.61). Results were similar in randomized controlled trials and observational studies. Use of NSBBs was not associated with increased mortality at 6, 12, 18, and 24 months. Overall, the included studies had a medium to high risk of bias, except for 3 clinical trials in which the risk of biased was determined to be low. Conclusions The use of NSBBs was not associated with a significant increase in all-cause mortality in patients with cirrhosis and ascites or refractory ascites. Certainty in the available estimates is low; a randomized trial of only patients with ascites is needed to answer this question. This meta-analysis does not support the position that NSBBs routinely be withheld from patients with ascites.