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With the expanding use of cardiac implantable electronic device (CIED) therapy, intravascular device infections are becoming more common. In the case of transvenous implantable cardioverter-defibrillator (ICD) infections requiring extraction for bacterial clearance, there remains no standard method to deliver temporary ICD therapy following device removal. We present a case of persistent bacteremia complicated by monomorphic ventricular tachycardia (VT) electrical storm where biventricular ICD system extraction was performed and a temporary transvenous dual-coil lead with an externalized ICD generator was used to treat VT episodes prior to the re-implantation of a new permanent system. This case demonstrates the utility of a temporary externalized transvenous ICD system in the successful detection and pace-termination of VT, thereby reducing episodes of painful and potentially harmful external defibrillator shocks during the treatment of CIED infection., Competing Interests: Dr. Maher has received grant funding from LuxMed Systems and Circa Scientific and consulting/speaking honoraria from Biosense Webster, Inc. Dr. Kreidieh has received educational grant funding from Medtronic, Inc., unrelated to this work. The remaining authors report no conflicts of interest for the published content. No funding information was provided., (Copyright: © 2024 Innovations in Cardiac Rhythm Management.)

Background: Use of an antibiotic-eluting envelope (AEE) during cardiac implantable electronic device procedures reduces infection risk but increases procedural costs. We aim to estimate the cost-effectiveness of AEE use during cardiac implantable electronic device procedures among patients with heart failure., Methods: A state-transition cohort model of heart failure patients undergoing cardiac implantable electronic device implantation or generator replacement was developed with input parameters estimated from randomized trials, registries, surveys, and claims data. Effectiveness was estimated from the World-Wide Randomized Antibiotic Envelope Infection Prevention Trial. AEE was assumed to cost $953 per unit. The model projected mortality, quality-adjusted life-years, costs, and the incremental cost-effectiveness ratio of AEE use compared with usual care from a US healthcare sector perspective over a lifetime horizon. We assumed a cost-effectiveness threshold of $100 000 per quality-adjusted life-year gained., Results: Compared with usual care, AEE use in initial implantations produced an incremental cost-effectiveness ratio of $112 000 per quality-adjusted life-year gained (39% probability of being cost-effective). In generator replacement procedures, AEE use produced an incremental cost-effectiveness ratio of $54 000 per quality-adjusted life-year gained (84% probability of being cost-effective). Results were sensitive to the underlying rate of infection, cost of the AEE, and durability of AEE effectiveness., Conclusions: Universal AEE use for cardiac implantable electronic device procedures in patients with heart failure with reduced ejection fraction is unlikely to be cost-effective, reinforcing the need for individualized risk assessment to guide uptake of the AEE in clinical practice. Selective use in patients at increased risk of infection, such as those undergoing generator replacement procedures, is more likely to meet health system value benchmarks.

Background and Aims: In addition to managing malignant obstruction, esophageal stents (ESs) have evolved to address various benign etiologies of dysphagia. We sought to evaluate national trends and changes in practice of ES placement for both benign and malignant etiologies in hospitalized patients with dysphagia., Methods: The National Inpatient Sample (2003-2013) was used to include all adult inpatients (≥18 years of age) with endoscopy-guided ES placement for a symptom of dysphagia. Multivariable analyses for indications that impact temporal trends (3 time periods: 2003-2005, 2006-2009, and 2010-2013) and for hospital outcomes were performed., Results: A total of 7198 ESs were deployed endoscopically in hospitalized patients with dysphagia. Compared with malignant etiologies, there was a significant increase in ES placement for benign conditions (2013 vs 2003: 32.7% vs 14.5%, respectively; P < .001). Multivariable analysis using 2003 to 2005 as a reference showed that patients with benign etiologies for dysphagia predominantly contributed to the increase of ES placement during the most recent time period (2010-2013: odds ratio, 2.09; 95% confidence interval, 1.40-3.13). Multivariable analysis of hospital outcomes revealed no differences in inpatient mortality, duration of hospital stay, and hospital costs between malignant and benign indications., Conclusions: In the preceding decade, ES placement for hospitalized patients with dysphagia has increased, driven largely by an over 8-fold rise in stent placement for benign indications. These findings warrant continued efforts to improve stent technology to decrease the risk of migration and review practice guidelines involving ES placement for benign etiologies., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Goals: The goal of this study was to evaluate the influence of defecation postural modification devices (DPMDs) on normal bowel patterns., Background: The introduction of DPMDs has brought increased awareness to bowel habits in western populations., Materials and Methods: A prospective crossover study of volunteers was performed that included real-time collection of data regarding bowel movements (BMs) for 4 weeks (first 2 wk without DPMD and subsequent 2 wk with DPMD). Primary outcomes of interest included BM duration, straining, and bowel emptiness with and without DPMD use., Results: In total, 52 participants (mean age, 29 y and 40.1% female) were recruited for this study. At baseline 15 subjects (28.8%) reported incomplete emptying, 23 subjects (44.2%) had increased straining, and 29 subjects (55.8%) noticed blood on their toilet paper in the past year. A total of 1119 BMs were recorded (735 without DPMD and 384 with DPMD). Utilizing the DPMD resulted in increased bowel emptiness (odds ratio, 3.64; 95% confidence interval (CI), 2.78-4.77) and reduced straining patterns (odds ratio, 0.23; 95% CI, 0.18-0.30). Moreover, without the DPMD, participants had an increase in BM duration (fold increase, 1.25; 95% CI, 1.17-1.33)., Conclusions: DPMDs positively influenced BM duration, straining patterns, and complete evacuation of bowels in this study.

Goals: The goal of this study was to evaluate outcomes of colonoscopy in the setting of post myocardial infarction (MI) gastrointestinal bleeding (GIB) in a large population-based data set., Background: The literature to substantiate the proposed safety of colonoscopy following an acute MI is limited., Study: The Nationwide Inpatient Sample (2007 to 2013) was utilized to identify all adult patients (age, 18 y or above) hospitalized with a primary diagnosis of ST-elevation MI and receiving left heart catheterization (STEMI-C). The outcomes of patients with concomitant diagnosis of GIB receiving endoscopic intervention with esophagogastroduodenoscopy (EGD) or colonoscopy postcatheterization were compared with those who did not. Primary outcomes including mortality, length of stay, and hospital costs were evaluated with univariate and multivariate analysis., Results: There were 131,752 patients with post-STEMI-C GIB (5.35% of all STEMI-C patients) and same admission colonoscopy was performed in 1599 patients (1.21%). Although the prevalence of post-STEMI-C GIB increased from 4.27% in 2007 to 5.87% in 2013 (P<0.001), patients receiving colonoscopy decreased from 1.42% to 1.09% (P<0.001) over the course of the study period. Multivariate analysis revealed that patients receiving no endoscopic intervention [odds ratio, 3.61; 95% confidence interval: 1.57, 8.31] or EGD alone (OR, 2.70; 95% confidence interval: 1.12, 6.49) have higher mortality compared with those receiving colonoscopy., Conclusions: Same admission colonoscopy performed for post-STEMI-C GIB was associated with lower mortality. However, despite increased incidence of GIB in these patients during the study period, a lower percentage of patients received colonoscopy. These results suggest that colonoscopy is safe but underutilized in this setting.

Aims: There is a lack of population studies evaluating the impact of bariatric surgery (BRS) on all-cause inpatient mortality. We sought to determine the impact of prior BRS on all-cause mortality and healthcare utilization in hospitalized patients., Methods: We analyzed the National Inpatient Sample database from 2007 to 2013. Participants were adult (≥ 18 years) inpatients admitted with a diagnosis of morbid obesity or a history of BRS. Propensity score-matched analyses were performed to compare mortality and healthcare resource utilization (hospital length of stay and cost)., Results: There were 9,044,103 patient admissions with morbid obesity and 1,066,779 with prior BRS. A propensity score-matched cohort analysis demonstrated that prior BRS was associated with decreased mortality (OR = 0.58; 95% CI [0.54, 0.63]), shorter length of stay (0.59 days; P < 0.001), and lower hospital costs ($2152; P < 0.001) compared to morbid obesity. A subgroup of propensity score-matched analysis among patients with high-risk of mortality (leading ten causes of mortality in morbid obesity) revealed a consistently significant reduction in odds of mortality for patients with prior BRS (OR = 0.82; 95% CI [0.72, 0.92])., Conclusion and Relevance: Hospitalized patients with a history of BRS have lower all-cause mortality and healthcare resource utilization compared to those who are morbidly obese. These observations support the continued application of BRS as an effective and resource-conscious treatment for morbid obesity.

Aim: To determine the readmission rate, its reasons, predictors, and cost of 30-d readmission in patients with cirrhosis and ascites., Methods: A retrospective analysis of the nationwide readmission database (NRD) was performed during the calendar year 2013. All adults cirrhotics with a diagnosis of ascites, spontaneous bacterial peritonitis, or hepatic encephalopathy were identified by ICD-9 codes. Multivariate analysis was performed to assess predictors of 30-d readmission and cost of readmission., Results: Of the 59597 patients included in this study, 18319 (31%) were readmitted within 30 d. Majority (58%) of readmissions were for liver related reasons. Paracentesis was performed in 29832 (50%) patients on index admission. Independent predictors of 30-d readmission included age < 40 (OR: 1.39; CI: 1.19-1.64), age 40-64 (OR: 1.19; CI: 1.09-1.30), Medicaid (OR: 1.21; CI: 1.04-1.41) and Medicare coverage (OR: 1.13; CI: 1.02-1.26), > 3 Elixhauser comorbidity (OR: 1.13; CI: 1.05-1.22), nonalcoholic cirrhosis (OR: 1.16; CI: 1.10-1.23), paracentesis on index admission (OR: 1.28; CI: 1.21-1.36) and having hepatocellular carcinoma (OR: 1.21; CI: 1.05; 1.39). Cost of index admission was similar in patients readmitted and not readmitted ( P -value: 0.34); however cost of care was significantly more on 30 d readmission ($30959 ± 762) as compared to index admission ($12403 ± 378), P -value: < 0.001., Conclusion: Cirrhotic patients with ascites have a 33% chance of readmission within 30-d. Younger patients, with public insurance, nonalcoholic cirrhosis and increased comorbidity who underwent paracentesis are at increased risk of readmission. Risk factors for unplanned readmission should be targeted given these patients have higher healthcare utilization., Competing Interests: Conflict-of-interest statement: None of the authors have conflicts of interest.

Aim: To examine the effect of center size on survival differences between simultaneous liver kidney transplantation (SLKT) and liver transplantation alone (LTA) in SLKT-listed patients., Methods: The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Post-transplant survival was evaluated using stratified Cox regression with interaction between transplant type (LTA vs SLKT) and center volume., Results: During the study period, 393 of 4580 patients (9%) listed for SLKT underwent a LTA. Overall mortality was higher among LTA recipients (180/393, 46%) than SLKT recipients (1107/4187, 26%). The Cox model predicted a significant survival disadvantage for patients receiving LTA vs SLKT [hazard ratio, hazard ratio (HR) = 2.85; 95%CI: 2.21, 3.66; P < 0.001] in centers performing 30 SLKT over the study period. This disadvantage was modestly attenuated as center SLKT volume increased, with a 3% reduction (HR = 0.97; 95%CI: 0.95, 0.99; P = 0.010) for every 10 SLKs performed., Conclusion: In conclusion, LTA is associated with increased mortality among patients listed for SLKT. This difference is modestly attenuated at more experienced centers and may explain inconsistencies between smaller-center and larger registry-wide studies comparing SLKT and LTA outcomes., Competing Interests: Conflict-of-interest statement: None of the above listed authors have any reported conflicts of interest to disclose.

Background: Transarterial chemoembolization (TACE) is a palliative procedure frequently used in patients with advanced hepatocellular carcinoma (HCC). We examined the national inpatient trends of TACE and related outcomes in the United States over the last decade., Methods: We utilized the National Inpatient Sample (2002 to 2012) and performed trend analyses of TACE for HCC in all adult patients (age >18 years). Multivariate analyses for the outcomes of in-hospital "procedure-related complications" (PRCs) and "post-procedure complications" (PPCs) were performed. We also compared early (2002 to 2006) and late (2007 to 2012) eras by multivariate analyses to identify predictors of complications, healthcare resource utilization and mortality., Results: Overall, 19058 patients underwent TACE for HCC where PRCs and PPCs were seen in 24.2% and 17.6% of patients, respectively. The overall trends in the use of TACE (P<0.001) and associated PRCs (P=0.006) were observed to be increasing. There was less mortality [adjusted Odds ratio (aOR): 0.58; 95% CI: 0.41, 0.82], reduced length of hospital stay (-1.87 days; 95% CI: -2.77, -0.97) and increased hospital charges ($19232; 95% CI: 11013, 27451) in the late era. Additionally, there was increased mortality (aOR: 4.07; 95% CI: 2.96, 5.59), PRCs (aOR: 3.21; 95% CI: 2.56, 4.02), and PPCs (aOR: 2.70; 95% CI: 2.11, 3.46) among patients with coagulopathy., Conclusions: There is an increasing trend of TACE utilization in HCC. However, the outcomes are worse in patients with coagulopathy. Although PRCs have increased, mortality has decreased in recent years. These findings should be considered during TACE evaluation in patients with HCC., (Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.)

Esophageal cancer (EC) is increasing in prevalence due to rising incidence and improved treatment strategies. Dysphagia is a significant morbidity in patients with EC requiring nutritional intervention. We sought to evaluate outcomes of nutritional interventions for EC patients hospitalized with dysphagia at a population level. The National Inpatient Sample (2002-2012) was utilized to include all adult inpatients (≥18 years of age) with EC and presence of dysphagia and stricture that underwent nutritional interventions including feeding tube (FT) placement, esophageal stenting, or parenteral nutrition (PN). Temporal trends were examined with multivariate analysis performed for mortality, length of stay (LOS), and cost of hospitalization. A total of 509,593 EC patients had 12,205 hospitalizations related to dysphagia. The hospitalization rates doubled over the study period (1.52% vs. 3.28%, p < 0.001). The most common nutritional intervention was FT (27%), followed by esophageal stenting (13%), and PN (11%). PN was more frequently associated with a diagnosis of sepsis (6.1%, p = 0.023) compared to FT (2.5%) or esophageal stenting (1.8%). Multivariate analysis demonstrated FT and esophageal stenting had comparable mortality (OR 1.06, 95% CI: 0.49, 2.32); however, PN was associated with higher mortality (OR 2.37, 95% CI: 1.22, 4.63), cost of hospitalization ($5,510, 95% CI: 2,262, 8,759), and LOS (2.13 days, 95% CI: 0.72, 3.54). This study shows that hospitalizations for EC with dysphagia and related nutritional interventions are increasing. As a single modality, parenteral nutrition should be avoided. Among our esophageal stent and FT population, further studies are necessary to determine adequate interventions based on disease stage., (© The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Diverticulitis in patients with cirrhosis has been associated with higher surgical mortality, but no prior studies evaluate non-surgical treatment results., Aims: Our aim was to compare the outcomes of hospitalization for diverticulitis in patients with and without cirrhosis., Methods: We utilized the Nationwide Inpatient Sample (2007-2013) for patients with and without cirrhosis hospitalized for diverticulitis. Patients were further stratified by the presence of compensated versus decompensated cirrhosis. Validated ICD-9 codes captured patients and surgical procedures. Multivariate logistic regression models were fit. The primary outcomes of interest were mortality and surgical intervention rates., Results: There were 1,555,469 patients hospitalized for diverticulitis without cirrhosis, and 7523 patients hospitalized for diverticulitis with cirrhosis. On multivariate analysis, patients with cirrhosis had an increased mortality rate (OR 2.28; 95% CI 1.48-3.5). There were no significant differences in surgical interventions. Subgroup multivariate analyses of compensated cirrhosis (n = 6170) and decompensated cirrhosis (n = 1353) revealed that decompensated cirrhosis had an increased mortality rate (OR 4.99; 95% CI 2.48-10.03) when compared to patients without cirrhosis, whereas those with compensated cirrhosis did not (OR 1.67; 95% CI 0.96-2.91). Those with compensated cirrhosis underwent less surgical interventions (OR 0.82; 95% CI 0.67-0.99) compared to those without cirrhosis. Patients with diverticulitis and cirrhosis had increased costs and lengths of hospitalization., Conclusion: Presence of cirrhosis in patients hospitalized for diverticulitis is associated with an increased mortality rate. These are novel findings, and future clinical studies should focus on improving diverticulitis outcomes in this group.

Background: Total hip arthroplasty (THA) is a common procedure used to treat bony hip deformities and skeletal dysplasia in dwarfism. These surgeries are often more difficult than conventional THA as they may involve malformed joints and poor bone quality, and may require smaller prostheses. This study aims to investigate whether implant survivorship and revision rates vary among patients with and without dwarfism undergoing THA., Methods: A retrospective case-control study was performed for 102 THAs completed between 1997 and 2014 in patients under the height threshold of 147.32 cm. This cohort was matched 1:1.5 with patients of normal height with respect to age, gender, year of surgery, and Charlson comorbidities. All cases had a minimum follow-up of 1 year. A chart review was performed to identify patient and surgical characteristics, including outcomes. Radiographs were assessed for deformity, loosening, and periprosthetic fractures among other factors., Results: The 2-, 5-, and 10-year survivorship of THA in patients with dwarfism was 92.9%, 92.9%, and 80.7%, respectively; and 94.4%, 86.4%, and 86.4% for controls, respectively (p = 0.95). The dwarfism cohort demonstrated an OR of 3.81 and 3.02 for revision for periprosthetic fractures (p = 0.11) and mechanical wear (p = 0.21), respectively., Conclusions: THA in patients with dwarfism achieves comparable results to a non-dwarfism population with regards to implant survivorship; however, there is a trend toward increased periprosthetic fractures and wear-related failures. Surgeons should be aware of this potentially higher risk in this population and take morphological differences into account during surgical planning and technique.

Aim: To investigate the reproducibility of the in vivo endoscopic ultrasound (EUS) - guided needle based confocal endomicroscopy (nCLE) image patterns in an ex vivo setting and compare these to surgical histopathology for characterizing pancreatic cystic lesions (PCLs)., Methods: In a prospective study evaluating EUS-nCLE for evaluation of PCLs, 10 subjects underwent an in vivo nCLE (AQ-Flex nCLE miniprobe; Cellvizio, MaunaKea, Paris, France) during EUS and ex vivo probe based CLE (pCLE) of the PCL (Gastroflex ultrahigh definition probe, Cellvizio) after surgical resection. Biopsies were obtained from ex vivo CLE-imaged areas for comparative histopathology. All subjects received intravenous fluorescein prior to EUS and pancreatic surgery for in vivo and ex vivo CLE imaging respectively., Results: A total of 10 subjects (mean age 53 ± 12 years; 5 female) with a mean PCL size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms (IPMNs), 3 mucinous cystic neoplasms (MCNs), 2 cystic neuroendocrine tumors (cystic-NETs), 1 serous cystadenoma (SCA), and 2 squamous lined PCLs. Characteristic in vivo nCLE image patterns included papillary projections for IPMNs, horizon-type epithelial bands for MCNs, nests and trabeculae of cells for cystic-NETs, and a "fern pattern" of vascularity for SCA. Identical image patterns were observed during ex vivo pCLE imaging of the surgically resected PCLs. Both in vivo and ex vivo CLE imaging findings correlated with surgical histopathology., Conclusion: In vivo nCLE patterns are reproducible in ex vivo pCLE for all major neoplastic PCLs. These findings add further support the application of EUS-nCLE as an imaging biomarker in the diagnosis of PCLs., Competing Interests: Conflict-of-interest statement: None of the authors have any conflicts of interest or financial ties to disclose.

Intraductal papillary mucinous neoplasms are classified into gastric, intestinal, pancreatobiliary, and oncocytic subtypes where morphology portends disease prognosis. The study aim was to demonstrate EUS-guided needle-based confocal laser endomicroscopy imaging features of intraductal papillary mucinous neoplasm subtypes. Four subjects, each with a specific intraductal papillary mucinous neoplasm subtype were enrolled. An EUS-guided needle-based confocal laser endomicroscopy miniprobe was utilized for image acquisition. The mean cyst size from the 4 subjects (2 females; mean age = 65.3±12 years) was 36.8±12 mm. All lesions demonstrated mural nodules and focal dilation of the main pancreatic duct. EUS-nCLE demonstrated characteristic finger-like papillae with inner vascular core for all subtypes. The image patterns of the papillae for the gastric, intestinal, and pancreatobiliary subtypes were similar. However, the papillae in the oncocytic subtype were thick and demonstrated a fine scale-like or honeycomb pattern with intraepithelial lumina correlating with histopathology. There was significant overlap in the needle-based confocal laser endomicroscopy findings for the different intraductal papillary mucinous neoplasm subtypes; however, the oncocytic subtype demonstrated distinct patterns. These findings need to be replicated in larger multicenter studies., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to report.

Aim: To determine the impact of transjugular intrahepatic porto-systemic shunt (TIPS) on post liver transplantation (LT) outcomes., Methods: Utilizing the United Network for Organ Sharing (UNOS) database, we compared patients who underwent LT from 2002 to 2013 who had underwent TIPS to those without TIPS for the management of ascites while on the LT waitlist. The impact of TIPS on 30-d mortality, length of stay (LOS), and need for re-LT were studied. For evaluation of mean differences between baseline characteristics for patients with and without TIPS, we used unpaired t -tests for continuous measures and χ 2 tests for categorical measures. We estimated the impact of TIPS on each of the outcome measures. Multivariate analyses were conducted on the study population to explore the effect of TIPS on 30-d mortality post-LT, need for re-LT and LOS. All covariates were included in logistic regression analysis., Results: We included adult patients (age ≥ 18 years) who underwent LT from May 2002 to September 2013. Only those undergoing TIPS after listing and before liver transplant were included in the TIPS group. We excluded patients with variceal bleeding within two weeks of listing for LT and those listed for acute liver failure or hepatocellular carcinoma. Of 114770 LT in the UNOS database, 32783 (28.5%) met inclusion criteria. Of these 1366 (4.2%) had TIPS between the time of listing and LT. We found that TIPS increased the days on waitlist (408 ± 553 d) as compared to those without TIPS (183 ± 330 d), P < 0.001. Multivariate analysis showed that TIPS had no effect on 30-d post LT mortality (OR = 1.26; 95%CI: 0.91-1.76) and re-LT (OR = 0.61; 95%CI: 0.36-1.05). Pre-transplant hepatic encephalopathy added 3.46 d (95%CI: 2.37-4.55, P < 0.001), followed by 2.16 d (95%CI: 0.92-3.38, P = 0.001) by TIPS to LOS., Conclusion: TIPS did increase time on waitlist for LT. More importantly, TIPS was not associated with 30-d mortality and re-LT, but it did lengthen hospital LOS after transplantation., Competing Interests: Conflict-of-interest statement: None of the authors have any conflicts of interest.

Hepatorenal syndrome (HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation (LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant (SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include: (1) estimation of glomerular filtration rate of 30 mL/min or less for 4-8 wk; (2) proteinuria > 2 g/d; or (3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding long-term benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL/min per 1.73 m(2) may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community.

Stem cell-based therapy is a promising intervention for ischemic heart diseases. However, the functional integrity of stem cells is impaired in an ischemic environment. Here, we report a novel finding that heat shock significantly improves Sca-1(+) stem cell survival in an ischemic environment by the regulation of the triangle: heat shock factor 1 (HSF1), HSF1/miR-34a, and heat shock protein 70 (HSP70). Initially we prove that HSP70 is the key chaperone-mediating cytoprotective effect of heat shock in Sca-1(+) cells and then we establish miR-34a as a direct repressor of HSP70. We found that miR-34a was downregulated in heat shocked Sca-11 stem cells (HSSca-11 cells) [corrected]. Intriguingly, we demonstrate that the downregulation of miR-34a is attributed to HSF1-mediated epigenetic repression through histone H3 Lys27 trimethylation (H3K27me3) on miR-34a promoter. Moreover, we show that heat shock induces exosomal transfer of HSF1 from Sca-1(+) cells, which directs ischemic cardiomyocytes toward a prosurvival phenotype by epigenetic repression of miR-34a. In addition, our in vivo study demonstrates that transplantation of (HS) Sca-1(+) cells significantly reduces apoptosis, attenuates fibrosis, and improves global heart functions in ischemic myocardium. Hence, our study provides not only novel insights into the effects of heat shock on stem cell survival and paracrine behavior but also may have therapeutic values for stem cell therapy in ischemic heart diseases., (© AlphaMed Press.)

Desmosomes and gap junctions are situated in the intercalated disks of cardiac muscle and maintain the integrity of mechanical coupling and electrical impulse conduction between cells. The desmosomal plakin protein, desmoplakin (DSP), also plays a crucial role in the stability of these interconnected components as well as gap junction connexin proteins. In addition to cell‑to‑cell junctions, other molecules, including voltage‑gated sodium channels (Nav1.5) are present in the intercalated disk and support the contraction of cardiac muscle. Mutations in genes encoding desmosome proteins may result in fatal arrhythmias, including arrhythmogenic right ventricular cardiomyopathy (ARVC). Therefore, the aim of the present study was to determine whether the presence of DSP is necessary for the normal function and localization of gap junction protein connexin43 (Cx43) and Nav1.5. To examine this hypothesis, RNA interference was utilized to knock down the expression of DSP in HL‑1 cells and the content, distribution and function of Cx43 and Nav1.5 was assessed. Western blotting and flow cytometry experiments revealed that Cx43 and Nav1.5 expression decreased following DSP silencing. In addition, immunofluorescence studies demonstrated that a loss of DSP expression led to an abnormal distribution of Cx43 and Nav1.5, while scrape‑loading dye/transfer revealed a decrease in dye transfer in DSP siRNA‑treated cells. The sodium current was also recorded by the whole‑cell patch clamp technique. The results indicated that DSP suppression decreased sodium current and slowed conduction velocity in cultured cells. The present study indicates that impaired mechanical coupling largely affects electrical synchrony, further uncovering the pathogenesis of ARVC.

Background: Alzheimer's disease (AD) is an age related progressive neurodegenerative disorder. One of the reasons for Alzheimer's neuropathology is the generation of large aggregates of Aß42 that are toxic in nature and induce oxidative stress, aberrant signaling and many other cellular alterations that trigger neuronal cell death. However, the exact mechanisms leading to cell death are not clearly understood., Methodology/principal Findings: We employed a Drosophila eye model of AD to study how Aß42 causes cell death. Misexpression of higher levels of Aß42 in the differentiating photoreceptors of fly retina rapidly induced aberrant cellular phenotypes and cell death. We found that blocking caspase-dependent cell death initially blocked cell death but did not lead to a significant rescue in the adult eye. However, blocking the levels of c-Jun NH(2)-terminal kinase (JNK) signaling pathway significantly rescued the neurodegeneration phenotype of Aß42 misexpression both in eye imaginal disc as well as the adult eye. Misexpression of Aß42 induced transcriptional upregulation of puckered (puc), a downstream target and functional read out of JNK signaling. Moreover, a three-fold increase in phospho-Jun (activated Jun) protein levels was seen in Aß42 retina as compared to the wild-type retina. When we blocked both caspases and JNK signaling simultaneously in the fly retina, the rescue of the neurodegenerative phenotype is comparable to that caused by blocking JNK signaling pathway alone., Conclusions/significance: Our data suggests that (i) accumulation of Aß42 plaques induces JNK signaling in neurons and (ii) induction of JNK contributes to Aß42 mediated cell death. Therefore, inappropriate JNK activation may indeed be relevant to the AD neuropathology, thus making JNK a key target for AD therapies.