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Background: Hepatic encephalopathy (HE) is highly prevalent in patients with liver diseases. The pathophysiology of HE is centered on the synergic role of hyperammonemia and systemic inflammation. However, some data suggest altered functioning of the blood–brain barrier (BBB). Assessing BBB function is challenging in clinical practice and at the bedside. Protein-S-100 Beta (PS100-Beta) could be a useful peripheral marker of BBB permeability in HE. This study aimed to assess plasmatic PS100-Beta levels in a prospective cohort of patients admitted to the intensive care unit (ICU) with decompensated cirrhosis with and without overt HE. Methods: We retrospectively evaluated a prospective cohort of cirrhotic patients admitted to the ICU from October 2013 to September 2015 that had an available plasmatic PS100-Beta measurement. Patients with previous neurological impairment or limitation of intensive or resuscitative measures were excluded. Overt HE was defined as West-Haven grades 2 to 4. The patients were compared to a control cohort of outpatient clinic cirrhotic and non-cirrhotic patients explored for isolated elevation of liver enzymes. After ICU discharge, the patients were followed for at least 3 months for the occurrence of overt HE. Adverse outcomes (liver transplantation or death) were collected. The ability of PS100-Beta – in combination with other factors – to predict overt HE was evaluated in a multivariate analysis using logistic regression. Likelihood ratios were used to determine the effects and calculate odds ratios (OR). Survival analysis was performed by using the Kaplan–Meier method and survival between groups was compared using a Log-rank test. Results: A total of 194 ICU patients and 207 outpatients were included in the study. Increased levels of plasmatic PS100-Beta were detected in the ICU decompensated cirrhotic patients compared with the outpatients ([0.15±0.01] mg/L vs. [0.08±0] mg/L, P

Background & Aims: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting, and data from multicentre studies are scarce. The aim of this study was to dissect the potential association between PPI use and minimal (MHE) and overt HE (OHE). Methods: Data from patients with cirrhosis recruited at seven centres across Europe and the US were analysed. MHE was defined by the psychometric hepatic encephalopathy score (PHES). PPI use was recorded on the day of testing with PHES. Patients were followed for OHE development and death/liver transplantation. Results: A total of 1,160 patients with a median MELD of 11 were included (Child-Pugh stages: A 49%/B 39%/C 11%). PPI use was noted in 58% of patients. Median follow-up time was 18.1 months, during which 230 (20%) developed an OHE episode, and 224 (19%) reached the composite endpoint of death/liver transplantation. In multivariable analyses, PPI use was neither associated with the presence of MHE at baseline nor OHE development during follow-up. These findings were consistent in subgroup analyses of patients with Child-Pugh A or B cirrhosis and after excluding patients with a history of OHE. PPI use was also not associated with a higher risk of OHE, neither in patients with an indication for treatment nor in patients without an indication. Conclusions: PPI use is not associated with a higher risk of HE in patients with cirrhosis. Based on these findings, at present, a prescription should not be prohibited in case of a generally accepted indication. Impact and implications: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting. In this study, PPI use was not associated with a higher risk of minimal HE at baseline or overt HE during follow-up in patients with cirrhosis. Based on these findings, prescription of a PPI for a generally accepted indication should not be prohibited in patients with cirrhosis.

Genrefying a library's fiction collection is a common practice in school libraries. However, there is little research to explain the benefits or drawbacks of this practice. Using a within-subjects/time-series action research design, this study was conducted to understand more about the impact of genrefying the fiction collection in a single library. This study found that elementary students could locate fiction books faster and to greater satisfaction with a genrefied collection than in a collection in which fiction was arranged in a FIC label format, which is typically seen in standard Dewey Decimal classification.

BackgroundAs much as 80% of children on the autism spectrum exhibit challenging behaviors (ie, behaviors dangerous to the self or others, behaviors that interfere with learning and development, and behaviors that interfere with socialization) that can have a devastating impact on personal and family well-being, contribute to teacher burnout, and even require hospitalization. Evidence-based practices to reduce these behaviors emphasize identifying triggers (events or antecedents that lead to challenging behaviors); however, parents and teachers often report that challenging behaviors surface with little warning. Exciting recent advances in biometric sensing and mobile computing technology allow the measurement of momentary emotion dysregulation using physiological indexes. ObjectiveWe present the framework and protocol for a pilot trial that will test a mobile digital mental health app, the KeepCalm app. School-based approaches to managing challenging behaviors in children on the autism spectrum are limited by 3 key factors: children on the autism spectrum often have difficulties in communicating their emotions; it is challenging to implement evidence-based, personalized strategies for individual children in group settings; and it is difficult for teachers to track which strategies are successful for each child. KeepCalm aims to address those barriers by communicating children’s stress to their teachers using physiological signaling (emotion dysregulation detection), supporting the implementation of emotion regulation strategies via smartphone pop-up notifications of top strategies for each child according to their behavior (emotion regulation strategy implementation), and easing the task of tracking outcomes by providing the child’s educational team with a tool to track the most effective emotion regulation strategies for that child based on physiological stress reduction data (emotion regulation strategy evaluation). MethodsWe will test KeepCalm with 20 educational teams of students on the autism spectrum with challenging behaviors (no exclusion based on IQ or speaking ability) in a pilot randomized waitlist-controlled field trial over a 3-month period. We will examine the usability, acceptability, feasibility, and appropriateness of KeepCalm as primary outcomes. Secondary preliminary efficacy outcomes include clinical decision support success, false positives or false negatives of stress alerts, and the reduction of challenging behaviors and emotion dysregulation. We will also examine technical outcomes, including the number of artifacts and the proportion of time children are engaged in high physical movement based on accelerometry data; test the feasibility of our recruitment strategies; and test the response rate and sensitivity to change of our measures, in preparation for a future fully powered large-scale randomized controlled trial. ResultsThe pilot trial will begin by September 2023. ConclusionsResults will provide key data about important aspects of implementing KeepCalm in preschools and elementary schools and will provide preliminary data about its efficacy to reduce challenging behaviors and support emotion regulation in children on the autism spectrum. Trial RegistrationClinicalTrials.gov NCT05277194; https://www.clinicaltrials.gov/ct2/show/NCT05277194 International Registered Report Identifier (IRRID)PRR1-10.2196/45852

Portal hypertension (PHT) often complicates hepatocellular carcinoma (HCC) treatment and prognosis. We aimed to assess PHT's impact on AtezoBev outcomes and identify predictors of acute variceal bleeding (AVB) and clinical ascites occurrence. A prospective cohort of 200 HCC patients treated with AtezoBev was studied alongside a retrospective cohort of 123 patients treated with Sorafenib. We assessed factors influencing progression-free survival (PFS), overall survival (OS), AVB and clinical ascites development, focusing on PHT parameters, and comparing outcomes within and between the two cohorts (time-dependent Cox model and adjusted survival curves). Among the AtezoBev cohort, 10% experienced AVB, 24% had high-risk esophageal varices (EV) and 46% vascular invasion. Median PFS and OS in the AtezoBev cohort was 5.13 and 12.2 months. AVB (HR=1.81;[95%CI:1.03–3.17]) and clinical ascites occurrence (HR=2.29;[95%CI:1.52–3.45]) were independently associated with mortality. AVB incidence was 12% at 12 months in AtezoBev patients and EV, history of AVB<6months and vascular invasion were independently associated with AVB. The Sorafenib cohort had shorter median PFS and OS, with similar AVB incidence and only EV were associated with AVB. PHT-related events significantly affect not only liver decompensation but also OS in AtezoBev-treated patients. We suggest a more widespread use of NSBB to prevent liver decompensation, with intensified prophylaxis for high-risk patients. [ABSTRACT FROM AUTHOR]

Despite the astonishing progress in treating chronic hepatitis C virus (HCV) infection with direct-acting antiviral agents, liver fibrosis remains a major health concern in HCV infected patients, in particular due to the treatment cost and insufficient HCV screening in many countries. Only a fraction of patients with chronic HCV infection develop liver fibrosis. While there is evidence that host genetic factors are involved in the development of liver fibrosis, the common variants identified so far, in particular by genome-wide association studies, were found to have limited effects. Here, we conducted an exome association study in 88 highly selected HCV-infected patients with and without fibrosis. A strategy focusing on TGF-β pathway genes revealed an enrichment in rare variants of the endoglin gene (ENG) in fibrosis patients. Replication studies in additional cohorts (617 patients) identified one specific ENG variant, Thr5Met, with an overall odds ratio for fibrosis development in carriers of 3.04 (1.39–6.69). Our results suggest that endoglin, a key player in TGF-β signaling, is involved in HCV-related liver fibrogenesis.

We present a case of root abscess with aorta to right atrium fistula due to vancomycin-intermediate Staphylococcus aureus (VISA) after limb amputation and cardiac surgery. Patient underwent redo aortic valve replacement, patch repair of aorta to right atrial fistula, and tricuspid valve repair with a ring. Fistula formation is a rare complication of prosthetic valve endocarditis (PVE). This is the first case to discuss aortocavitary fistula (ACF) formation due to VISA. Transesophageal echocardiogram (TEE) is the preferred imaging modality to diagnose ACF.

Salvage transjugular intrahepatic portosystemic shunt (TIPSS) has proven its efficacy to treat refractory variceal bleeding for patients with cirrhosis. However, this procedure is associated with very poor outcomes. As it is used as a last resort to treat a severe complication of cirrhosis, it seems essential to improve our practice, with the aim of optimizing management of those patients. Somehow, many questions are still unsolved: which stents should be used? Should a concomitant embolization be systematically considered? Is there any alternative therapeutic in case of recurrent bleeding despite TIPSS? What are the long-term outcomes on survival, liver transplantation, and hepatic encephalopathy after salvage TIPSS? Is this procedure futile in some patients? Is prognosis with salvage TIPSS nowadays as bad as earlier, despite the improvement of prophylaxis for variceal bleeding? The aim of this review is to summarize those data and to identify the lacking ones to guide further research on salvage TIPSS.

Abstract Biochemical experiments, animal models, and observational studies in humans all support a role of dipeptidyl peptidase 4 (DPP4) in the N‐terminal truncation of CXCL10, which results in the generation of an antagonist form of the chemokine that limits T‐cell and NK cell migration. Motivated by the ability to regulate lymphocyte trafficking in vivo, we conducted two prospective clinical trials to test the effects of DPP4 inhibition on CXCL10 processing in healthy donors and in chronic hepatitis C patients, a disease in which DPP4 levels are found to be elevated. Participants were treated daily with 100 mg sitagliptin, a clinically approved DPP4 inhibitor. Plasma samples were analyzed using an ultrasensitive single‐molecule assay (Simoa) to distinguish the full‐length CXCL101–77 from the NH2‐truncated CXCL103–77, as compared to the total CXCL10 levels. Sitagliptin treatment resulted in a significant decrease in CXCL103–77 concentration, a reciprocal increase in CXCL101–77, with only minimal effects on total levels of the chemokine. These data provide the first direct evidence that in vivo DPP4 inhibition in humans can preserve the bioactive form of CXCL10, offering new therapeutic opportunities for DPP4 inhibitors.

Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8+ T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8+ T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8+ T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection.

BACKGROUND:Human genetic factors influence the outcome of pegylated interferon and ribavirin hepatitis C therapy. We explored the role of IL28B, APOH and ITPA SNPs on the outcomes of triple therapy including telaprevir or boceprevir in patients with compensated cirrhosis chronically infected with HCV-1. PATIENTS AND METHODS:A total of 256 HCV-1 Caucasian treatment-experienced patients with compensated cirrhosis from the ANRS CO20-CUPIC cohort were genotyped for a total of 10 candidate SNPs in IL28B (rs12979860 and rs368234815), APOH (rs8178822, rs12944940, rs10048158, rs52797880, rs1801689 and rs1801690) and ITPA (rs1127354 and rs7270101). We tested the association of IL28B and APOH SNPs with sustained virological response and of ITPA SNPs with anemia related phenotypes by means of logistic regression assuming an additive genetic model. RESULTS:None of the six APOH SNPs were associated with sustained virological response. The favorable alleles of the IL28B SNPs rs12979860 and rs368234815 were associated with sustained virological response (rs12979860: OR = 2.35[1.50-3.70], P = 2x10(-4)). Refined analysis showed that the effect of IL28B SNPs on sustained virological response was restricted to prior PegIFN/RBV relapse (OR = 3.80[1.82-8.92], P = 8x10(-4)). We also confirmed the association between ITPA low activity alleles and protection against early hemoglobin decline in triple therapy (P = 2x10(-5)). CONCLUSION:Our results suggest that the screening of rs12979860 may remain interesting for decision making in prior relapse HCV-1 Caucasian patients with compensated cirrhosis eligible for a telaprevir- or boceprevir-based therapy.

E-mail has created friction between school districts' proprietary needs and employees' privacy rights. This article examines e-mail law (constitutional, statutory, and common) and issues (employer monitoring, discover problems, admissibility, and attorney-client privilege) and provides policy guidelines. The 1996 Communications Decency Act, designed to protect children from lewd Internet materials, is being challenged in the U.S. Supreme Court. (20 references) (MLH)

In response to an earlier article by Eugene Lincoln, presents two hypothetical cases that respectively deal with the possible effects of drug use on school premises and with a policy governing mandatory urine testing for student athletes. Cites factors that should be incorporated in any mandatory drug testing policy. (MLF)

In a Philadelphia-area school district, teachers who substantially improve student performance (as individuals or as groups) now receive up to $5,000 more yearly. One of only three performance-pay plans in the country, the plan relies on objective evaluative data, not administrator observations. (MLH)

In 2015, West Coast Baptist College purchased an 80,000 volume library collection from a closing Bible institution. During 2017-2020, both the original 40,000 volume collection and purchased 80,000 volume collection were merged, relocated to a larger facility, thoroughly weeded into a 60,000 volume collection, and converted from Dewey Decimal Classification into the Library of Congress Classification. This article summarizes several factors to consider on switching classifications and our experience from the conversion process [ABSTRACT FROM AUTHOR]

While there are studies and resources about training and retaining student workers in an academic library, there is little research on whether the library's collection classification can have an effect on library student workers' perception on their work and job fulfillment. While employed at the West Coast Baptist College (WCBC) Library, library student workers developed opinions on library work in general as well as their perception on both the Dewey Decimal Classification (DDC) and the Library of Congress Classification (LCC) while the library converted from the former to the latter. The case study found that seventy-five percent of the participating library student workers preferred LCC over DDC which minimally affected their enjoyment of working in the WCBC Library. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is common in patients with chronic diseases. It is evaluated using the International Index of Erectile Function (IIEF5) questionnaire. The relationship between ED and cirrhosis is complex. The aims of our study were (1) to assess the prevalence of ED in cirrhosis and (2) to evaluate factors associated with ED, with a special focus on minimal hepatic encephalopathy (MHE). We performed a prospective, observational study. Patients with cirrhosis were invited to complete the IIEF5 questionnaire. The exclusion criteria were clinical hepatic encephalopathy (HE) and dementia. MHE was evaluated by the psychometric hepatic encephalopathy test score (PHES) and the critical flicker frequency (CFF). Between April 2016 and April 2017, 87 patients were included (age: 55 [51–57] years, Child–Pugh score: 8 [7–9], MELD score: 13 [11–16]. Minimal HE was diagnosed in 33% of the patients according to the PHES and in 44% of the patients according to the CFF. ED was diagnosed in 74/87 patients (85%) when compared to 12.5% in healthy controls (p < 0.001). In a multivariate analysis, the independent factors associated with ED were age, Child–Pugh and MELD scores. Significant correlations were identified between the IIEF5 and each component of the PHES. ED should be systematically screened in cirrhotics, especially in patients with MHE. [ABSTRACT FROM AUTHOR]

The increasing incidence of hepatocellular carcinoma ( HCC) in Western countries requests reliable tumour markers for preclinical diagnosis. We evaluated the diagnostic accuracy of des-gamma-carboxy prothrombin ( DCP), in comparison with alpha-fetoprotein ( AFP) in a French cohort using a new analyser. One hundred and sixty-two patients with virus-related cirrhosis (46 HCC patients and 116 controls) were recruited in this retrospective proof-of-concept study. DCP was measured on new Lumipulse® G600 analyzer and AFP on usual Cobas e602 analyzer in serum samples that were collected at the time of HCC diagnosis for HCC patients or during follow-up for controls. DCP and AFP levels were higher in HCC patients. The area under receiver operating characteristic curve was larger for DCP than for AFP (0.89 vs 0.77, P=.03). At the cut-off value of 128 m AU/mL, sensitivity and specificity for DCP were 74% and 92%. At the cut-off value of 20 μg/L, sensitivity and specificity for AFP were 63% and 82%. NRI>0 for the association of ' AFP+ DCP' were 101%, P<.0001, and 23%, P=.03, compared to ' AFP' or ' DCP' alone, respectively. We conclude that DCP outperformed AFP for the detection of HCC. [ABSTRACT FROM AUTHOR]

The article evaluates several digital educational tools that can be used in teaching and are free to students or educators, including ToDoist at todoist.com, Toggl Tract at toggl.com, and Trello at trello.com.