Miracle-dz/UniFAR-FTUs huggingface dataset:
Liver transplantation for subacute hepatocellular failure due to massive steatohepatitis after bariatric surgery

New therapeutic options for obesity include restrictive bowel surgery and surgery that promotes malabsorption, such as the Fobi‐Capella (gastric bypass) and Scopinaro (biliopancreatic diversion) techniques. Complications associated with these procedures, such as hepatocellular failure, have been observed with increasing frequency. Reported here are 3 patients who, 7 to 24 months after bariatric surgery, developed hepatocellular failure, for which liver transplantation was considered to be indicated. Liver transplantation was undertaken in 2 of the patients; the third patient died while waiting for this procedure. We discuss the possible causes of this uncommon and poorly understood complication of surgery for obesity. One possibility is that it might arise as a result of progression of steatohepatitis. An alternative concept is that this complication may be secondary to rapid, massive loss of body weight. Liver Transpl 14:881–885, 2008. © 2008.
Variable length tandem repeat polyglutamine sequences in the flexible tether region of the Tsr chemotaxis receptor of Escherichia coli.

Methyl-accepting chemotaxis proteins (MCPs) are receptors that play an important role in bacterial chemotaxis. Methylation of Tsr, the MCP that mediates chemotaxis towards serine in Escherichia coli, is thought to be facilitated by binding of the methyltransferase to a flexible tether region at the C-terminal end of Tsr. This study analysed natural length variants of the tether that occur in E. coli due to genetic instability in tandem repeat DNA sequences that code for glutaminyl (Q) residues, creating polyQ sequences of variable lengths in the tether region. The tsr gene of E. coli K-12 (strain MG1655) codes for 4Q at the beginning of its 35 aa tether region. The tether varies in length from 35 to 47 residues among pathogenic and non-pathogenic strains of Escherichia, Shigella spp. , Salmonella, Yersinia and Photorhabdus. Among previous sequences, Escherichia and Shigella mostly have 4Q and 7Q variants, and one strain (E. coli HS) has 10Q. In E. coli isolated from 50 humans and 75 animals (dogs, cats, horses, birds, etc.), polyQ up to 13Q (44 aa tether) were identified (6 strains); relative frequencies were 7Q ( approximately 77 % of the total) >4Q (14 %) >13Q (5 %) >10Q (4 %). Phylogenetic analysis revealed that E. coli strains with 10Q or 13Q largely fell within two clusters. Serine chemotaxis was not significantly different among 7Q, 10Q and 13Q strains, and was comparable to chemotaxis in the frequently studied K-12 strain. These results are consistent with models indicating that polyQ sequences from 7Q to 13Q are flexible, and that longer tethers, within this range, would not change the precision of adaptation mediated by methylation. Studies of this naturally variable polyQ region in E. coli may also have relevance to mechanisms that mediate polyQ instability in human genetic diseases.
Left-Sided Endocarditis Caused by Staphylococcus aureus: A Comparison of Clinical and Prognostic Factors of Patients With Native and Prosthetic Valve Endocarditis

Background: Staphylococcus aureus is the leading cause of mortality in patients with infectious endocarditis. Despite intensive research, some debate still exists on risk factors for mortality and the role of valve replacement on outcome. Methods: We conducted a retrospective review of cases of S. aureus endocarditis diagnosed with strict case definitions in a single institution and compared infection in patients with native and prosthetic valves. Results: Eighty-four patients with definitive left-sided endocarditis were analyzed. The incidence of left-sided endocarditis caused by S. aureus ranged from 2 to 4 cases per 10,000 admissions per year. The mitral valve was more commonly involved than the aortic valve (58% vs 34%). Prosthetic valve endocarditis (PVE) was hospital acquired more frequently than native valve endocarditis (NVE) (21% vs 54%; odds ratio [OR], 0.24; 95% confidence interval [CI], 0.09-0.63). Bacteremia during effective antimicrobial therapy (25% vs 57%; OR, 0.25; 95% CI, 0.10-0.65), cardiac failure (43% vs 68%; OR, 0.36; 95% CI, 0.14-0.92), and central nervous system complications (28% vs 36%; OR, 0.72; 95% CI, 0.27-1.89) were more frequently observed in patients with PVE. The overall mortality was 33%, and it was lower in cases of NVE (28% vs 43%; OR, 0.52; 95% CI, 0.21-1.37). Patients without complications survived the infection, but a trend toward a higher mortality in patients who developed 1 (19%), 2 (40%), or 3 (83%) complications was observed (Spearman &rgr; = 0.568; P < 0.001). Valve replacement was more frequently performed in patients with PVE (37% vs 71%; OR, 0.24; 95% CI, 0.09-0.64). Among patients with NVE, no single complication was significantly associated with mortality, and we did not find survival advantage of surgical treatment. In cases of PVE, surgical treatment determined a survival benefit (OR, 0.02; 95% CI, 0.00-0.33). Conclusions: Clinical and prognostic differences do exist between NVE and PVE due to S. aureus. The sum of cardiac, renal, and central nervous system complications was the main determinant of mortality. Although cardiac surgery did not determine a survival benefit in patients with NVE, valve replacement seemed to improve the survival rate in patients with PVE.
Effectiveness of a Behavioral Approach to Improve Healthcare Worker Compliance With Hospital Dress Code

BACKGROUND The VU University Medical Center, a tertiary-care hospital in the Netherlands, has adopted a dress code based on national guidelines. It includes uniforms provided by the hospital and a ‘bare-below-the-elbow’ policy for all healthcare workers (HCWs) in direct patient care. Because compliance was poor, we sought to improve adherence by interventions targeted at the main causes of noncompliance. OBJECTIVE To measure compliance with the dress code, to assess causes of noncompliance and to assess whether a behavioral approach (combing a nominal group technique with participatory action) is effective in improving compliance METHODS Between March 2014 and June 2016, a total of 1,920 HCWs were observed in hospital hallways for adherence to the policy, at baseline, and at follow-up measurements. Based on the outcome of the baseline measurement, a nominal group technique was applied to assess causes of noncompliance. The causes revealed served as input for interventions that were developed, prioritized, and tailored to specific groups of HCWs and specific departments through participatory action. RESULTS We identified lack of knowledge, lack of facilities, and negative attitudes as the main causes of noncompliance. The importance of each cause varied for different groups of HCWs. Tailored interventions targeted at these causes increased overall compliance by 39.6% (95% CI, 31.7–47.5). CONCLUSION The combination of a nominal group technique and participatory action approach is an effective method to increase and sustain compliance with hospital dress code. This combined approach may also be useful to improve adherence to other guidelines. Infect Control Hosp Epidemiol 2017;38:1435–1440
Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms.

BACKGROUND & AIMS The Helicobacter pylori gene cagA and s1 or m1 forms of vacA are more common in disease-associated strains. Recently, forms of cagA encoding multiple type C EPIYA segments (which increase phosphorylation-dependent CagA activity) and a new type i1 "intermediate region" polymorphism in vacA (which confers toxicity) have been described. We assessed the association of new and established cagA and vacA polymorphisms with disease. METHODS We studied 203 H pylori-infected subjects (53 gastric cancer [GC], 52 peptic ulcer [PU], and 98 gastritis). vacA signal, mid and intermediate region polymorphisms, cagA presence, and EPIYA-C segment number were analyzed by polymerase chain reaction. RESULTS cagA-positive strains were significantly associated with GC and PU (P < .001 and P < .05). GC risk was further associated with the number of cagA EPIYA-C segments (odds ratio [OR] = 7.37, 95% confidence interval [CI] = 1.98-27.48 for 1 EPIYA-C segment; OR = 32.5, 95% CI = 8.41-125.58 for 2 or more EPIYA-C segments). Increasing number of EPIYA-C segments also increased the risk of intestinal metaplasia. Type s1 and i1 vacA alleles were also associated with GC and type i1 vacA with PU (OR = 2.58, 95% CI = 1.19-5.61), including a significant association with duodenal ulcer. In multivariate analysis, the associations of cagA EPIYA-C segment number with GC and intestinal metaplasia as well as vacA i1 type association with PU remained. CONCLUSIONS We confirmed the associations of cagA and vacA polymorphisms with disease but now define their most important features. For cancer risk, among Western strains, the most important factor is the number of cagA EPIYA-C segment. For PU risk, it is the intermediate region type of vacA.
Biliary reconstruction for infantile living donor liver transplantation: Roux‐en‐Y hepaticojejunostomy or duct‐to‐duct choledochocholedochostomy?

Hepaticojejunostomy is a standard biliary reconstruction method for infantile living donor liver transplantation (LDLT), but choledochocholedochostomy for infants is not generally accepted yet. Ten pediatric recipients weighing no more than 10 kg underwent duct‐to‐duct choledochocholedochostomy (DD) for biliary reconstruction for LDLT. Patients were followed up for a median period of 26.8 months (range: 4.0–79.0 months). The incidence of posttransplant biliary complications for DD was compared with that for Roux‐en‐Y hepaticojejunostomy (RY). No DD patients and 1 RY patient (5%) developed biliary leakage (P > 0.05), and biliary stricture occurred in 1 DD patient (10%) and none of the RY patients (P > 0.05); none of the DD patients and 5 RY patients (25%) suffered from uncomplicated cholangitis after LDLT (P > 0.05), and 1 DD patient (10%) and 2 RY patients (10%) died of causes unrelated to biliary complications. In conclusion, both hepaticojejunostomy and choledochocholedochostomy resulted in satisfactory outcome in terms of biliary complications, including leakage and stricture, for recipients weighing no more than 10 kg. Liver Transpl 14:1761–1765, 2008. © 2008 AASLD.
What practicing pharmacists think about their role in healthcare: Preliminary findings from Karachi, Pakistan

Objective: This study is aimed to explore the understanding of pharmacists about their perceived role in the health care system of Pakistan. Methods: A 15-item questionnaire, which was devised on the basis of literature survey, was self-administered to a convenience sample of practicing pharmacists in Karachi, Pakistan. The questionnaire constituted components regarding their desired practice setting, expectations concerning their professional function and the opinion on the future of profession. Results: The demographic characteristics highlighted male (47.1%) and female (52.9%) to be in equal proportion with more than 65% of the respondents ≤30 years of age (n = 67; 65.7%). Majority of the respondents hold bachelor degree in pharmacy (n = 82; 80.4%). Majority of the respondents had <5 years experience (n = 70; 68.6%). More than 75% of the respondents worked in hospital settings (n = 80; 78.4%). Majority of the respondents (n = 78; 76.5%) expressed their dissatisfaction towards their role as a pharmacist. Nearly half of the respondents (n = 47; 46.1%) visualized themselves as mere dispensers, while around one-fourth of the respondents (n = 24; 23.5%) perceived themselves as drug information pharmacist. In the context to their education and training as pharmacists, the opinion seems to be divided as half of the respondents expressed satisfaction (n = 46; 45.1%), while the other half showed dissatisfaction (n = 49; 48.0%). More than 90% of the respondents agreed to learn new skills a key to achieve career satisfaction. Conclusion: The pharmacists expressed dissatisfaction about their perceived status in the healthcare system of Pakistan. In order to intensify the feel of professionalism, reconceptualization of education and training system is advocated.
The Kruppel-like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease.

BACKGROUND & AIMS Although nonalcoholic fatty liver disease (NAFLD) is increasingly common, only a minority of affected individuals develop fibrotic liver disease. Based on its role in liver growth and repair, we explored whether Kruppel-like factor 6 (KLF6) plays a role in NAFLD progression. METHODS KLF6 expression in 31 fibrosis scored NAFLD liver biopsy specimens was assessed by real-time polymerase chain reaction. Transfected minigene constructs were used to study the effect of a polymorphism, KLF6-IVS1-27G>A, that promotes KLF6 alternative splicing in vitro. We genotyped KLF6-IVS1-27G>A in 3 groups of patients (UK group 1, n = 306; Italian group 2, n = 109; trio group 3, n = 61 children and parents). RESULTS KLF6 expression was increased in association with increased steatosis, inflammation, and fibrosis in NAFLD livers. KLF6-IVS1-27G>A promoted alternative splicing of KLF6 and abrogated the up-regulation of both alpha-smooth muscle actin and collagen 1 in LX-2 cells. Group 1 genotyping identified KLF6-IVS1-27G>A in 44 of 306 (14.4%) patients. Notably, KLF6-IVS1-27G>A was associated significantly with milder NAFLD, with only 25% having more advanced fibrosis compared with 45% of wild-type (wt) individuals. This trend was confirmed in group 2. A linear regression analysis including all 415 patients, adjusted for age, sex, body mass index, and blood glucose level, confirmed that presence of the wt KLF6 allele was an independent predictor of fibrotic NAFLD. Furthermore, we have shown preferential transmission of the wt allele to children with fibrotic NAFLD. CONCLUSIONS We report a functional polymorphism in the KLF6 gene associated with advanced NAFLD and believe further study of KLF6 may enhance our understanding of this disease process.
Ulcerative colitis is a disease of accelerated colon aging: evidence from telomere attrition and DNA damage.

BACKGROUND & AIMS Telomere shortening is implicated in cancer and aging and might link these 2 biologic events. We explored this hypothesis in ulcerative colitis (UC), a chronic inflammatory disease that predisposes to colorectal cancer and in which shorter telomeres have been associated with chromosomal instability and tumor progression. METHODS Telomere length was measured by quantitative polymerase chain reaction in colonocytes and leukocytes of 2 different sets of UC patients and compared with normal controls across a wide range of ages. For a subset of patients, telomere length was measured in epithelium and stroma of right and left colon biopsy specimens. A third set of biopsy specimens was analyzed for phosphorylation of histone H2AX (gammaH2AX), a DNA damage signal, by immunofluorescence and for telomere length by quantitative fluorescence in situ hybridization. Relationships between telomere length, gammaH2AX intensity, age, disease duration, and age of disease onset were explored. RESULTS Colonocyte telomeres shorten with age almost twice as rapidly in UC patients as in normal controls. This extensive shortening occurs within approximately 8 years of disease duration. Leukocyte telomeres are slightly shorter in UC patients than in controls, but telomeres of colon stromal cells are unaffected. gammaH2AX intensity is higher in colonocytes of UC patients than in controls and is not dependent on age or telomere length. CONCLUSIONS Colonocytes of UC patients show premature shortening of telomeres, which might explain the increased and earlier risk of cancer in this disease. Shorter leukocyte telomeres and increased gammaH2AX in colonocytes might reflect oxidative damage secondary to inflammation.
The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.

BACKGROUND & AIMS Although the clinical phenotype of Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer) has been well described, little is known about disease in PMS2 mutation carriers. Now that mutation detection methods can discern mutations in PMS2 from mutations in its pseudogenes, more mutation carriers have been identified. Information about the clinical significance of PMS2 mutations is crucial for appropriate counseling. Here, we report the clinical characteristics of a large series of PMS2 mutation carriers. METHODS We performed PMS2 mutation analysis using long-range polymerase chain reaction and multiplex ligation-dependent probe amplification for 99 probands diagnosed with Lynch syndrome-associated tumors showing isolated loss of PMS2 by immunohistochemistry. Penetrance was calculated using a modified segregation analysis adjusting for ascertainment. RESULTS Germ-line PMS2 mutations were detected in 62% of probands (n = 55 monoallelic; 6 biallelic). Among families with monoallelic PMS2 mutations, 65.5% met revised Bethesda guidelines. Compared with the general population, in mutation carriers, the incidence of colorectal cancer was 5.2-fold higher, and the incidence of endometrial cancer was 7.5-fold higher. In North America, this translates to a cumulative cancer risk to age 70 years of 15%-20% for colorectal cancer, 15% for endometrial cancer, and 25%-32% for any Lynch syndrome-associated cancer. No elevated risk for non-Lynch syndrome-associated cancers was observed. CONCLUSIONS PMS2 mutations contribute significantly to Lynch syndrome, but the penetrance for monoallelic mutation carriers appears to be lower than that for the other mismatch repair genes. Modified counseling and cancer surveillance guidelines for PMS2 mutation carriers are proposed.
Centers for medicare and medicaid services hospital-acquired conditions policy for central line-associated bloodstream infection (CLABSI) and cather-associated urinary tract infection (CAUTI) shows minimal impact on hospital reimbursement

Objective In 2008, the Centers for Medicare and Medicaid Services (CMS) stopped reimbursing for hospital-acquired conditions (HACs) not present on admission (POA). We sought to understand why this policy did not impact central line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) trends. Design Retrospective cohort study. Setting Acute-care hospitals in the United States. Participants Fee-for-service Medicare patients discharged January 1, 2007, through December 31, 2011. Methods Using inpatient Medicare claims data, we analyzed billing practices before and after the HAC policy was implemented, including the use and POA designation of codes for CLABSI or CAUTI. For the 3-year period following policy implementation, we determined the impact on diagnosis-related groups (DRG) determining reimbursement as well as hospital characteristics associated with the reimbursement impact. Results During the study period, 65,205,607 Medicare fee-for-service hospitalizations occurred at 3,291 acute-care, nonfederal US hospitals. Based on coding, CLABSI and CAUTI affected 0.23% and 0.06% of these hospitalizations, respectively. In addition, following the HAC policy, 82% of the CLABSI codes and 91% of the CAUTI codes were marked POA, which represented a large increase in the use of this designation. Finally, for the small numbers of CLABSI and CAUTI coded as not POA, financial impacts were detected on only 0.4% of the hospitalizations with a CLABSI code and 5.7% with a CAUTI code. Conclusions Part of the reason the HAC policy did not have its intended impact is that billing codes for CLABSI and CAUTI were rarely used, were commonly listed as POA in the postpolicy period, and infrequently impacted hospital reimbursement.
Treatment of hepatitis C in liver transplant recipients

Recurrent hepatitis C after liver transplantation is a universal phenomenon. Graft reinfection occurs rapidly; once it is established, allograft cirrhosis and decompensation rapidly ensue in many patients. Treatment with pegylated interferon plus ribavirin is the standard of care among nontransplant patients with hepatitis C; however, the applicability of these therapies in liver transplant patients is severely limited. Before transplantation, many patients are simply too ill to endure the long treatment duration necessary to achieve viral eradication; thus, treatment‐related toxicity is a frequent barrier to success. Clinical trials in the pretransplantation population have yielded poor outcomes, with sustained virologic response rates only as high as 25%. Early after transplantation, treatment may be initiated prophylactically, or it may be initiated therapeutically in patients with evidence of recurrent disease. In small studies, prophylactic therapy has been associated with sustained virologic response rates lower than 20%, whereas in therapeutic intervention studies, sustained virologic response rates have ranged from 20% to 37%. In the setting of therapeutic intervention, preliminary indications suggest that rapid and early virologic response may become important clinical tools enabling the early identification of patients likely to respond to treatment. Two important clinical trials, PHOENIX (Pegasys and Copegus Administered After Liver Transplantation for Hepatitis C) in the prophylactic setting and PROTECT (Pegylated Interferon Alfa‐2b and Ribavirin After Orthotopic Liver Transplantation: Efficacy and Safety in Hepatitis C Recurrence Therapy) in the therapeutic setting, are under way and should further advance our understanding of the management of hepatitis C in patients undergoing liver transplantation. Liver Transpl 15:126–135, 2009. © 2009 AASLD.
Menstrual phase effects on smoking cessation: a pilot feasibility study.

BACKGROUND AND OBJECTIVES A growing body of research suggests that nicotine withdrawal and cigarette craving may vary across the menstrual cycle and that the luteal phase of the cycle may be associated with increases in each. This potential relationship suggests that careful timing of quit attempts during the menstrual cycle may improve initial success at abstinence, although there are no direct tests of this approach yet published. Our objectives were to preliminarily test the effect of timing of quit attempts for smoking cessation relative to menstrual cycle and to identify methodological procedures that could guide subsequent, larger clinical trials. METHODS In this pilot study, we randomized female smokers aged 18-40 who were not currently using hormonal contraception to quit smoking during either the follicular (n = 25) or luteal phase (n = 19) of their menstrual cycle. Participants were provided with two sessions of smoking cessation counseling (90 minutes total). All participants were provided with a transdermal nicotine patch contingent on maintenance of abstinence throughout the course of the 6-week study. RESULTS Among participants who initiated treatment, received the patch, and made a quit attempt (n = 35), carbon monoxide-verified repeated point prevalence abstinence 2 weeks after the target quit date was higher in the follicular than the luteal group (32% vs. 19%, respectively; OR = 2.0, 95% CI = 0.4-9.8). Within the overall study population, this difference was slightly lower (24% vs. 16%; OR = 1.7, 95% CI = 0.4-7.8). CONCLUSIONS Timing quit attempts based on menstrual phase is feasible. Insights gained from this study and the recommendations made herein may inform future research on this important clinical question.