The high-affinity immunoglobulin receptor FcγRI potentiates HIV-1 neutralization via antibodies against the gp41 N-heptad repeat.

The HIV-1 gp41 N-heptad repeat (NHR) region of the prehairpin intermediate, which is transiently exposed during HIV-1 viral membrane fusion, is a validated clinical target in humans and is inhibited by the Food and Drug Administration (FDA)-approved drug enfuvirtide. However, vaccine candidates targeting the NHR have yielded only modest neutralization activities in animals; this inhibition has been largely restricted to tier-1 viruses, which are most sensitive to neutralization by sera from HIV-1-infected individuals. Here, we show that the neutralization activity of the well-characterized NHR-targeting antibody D5 is potentiated >5,000-fold in TZM-bl cells expressing FcγRI compared with those without, resulting in neutralization of many tier-2 viruses (which are less susceptible to neutralization by sera from HIV-1-infected individuals and are the target of current antibody-based vaccine efforts). Further, antisera from guinea pigs immunized with the NHR-based vaccine candidate (ccIZN36)3 neutralized tier-2 viruses from multiple clades in an FcγRI-dependent manner. As FcγRI is expressed on macrophages and dendritic cells, which are present at mucosal surfaces and are implicated in the early establishment of HIV-1 infection following sexual transmission, these results may be important in the development of a prophylactic HIV-1 vaccine.

Clostridioides difficile infection in patients with and without COVID-19 during the pandemic: A retrospective cohort study from a tertiary referral hospital.

OBJECTIVES: This study aims to detect the prevalence and specific characteristics of Clostridioides difficile infection (CDI) during the COVID-19 pandemic. METHODS: In this retrospective observational study, conducted in a tertiary hospital in Greece between May 2021 and October 2022, patients with CDI from COVID-19 and Internal Medicine wards were enrolled and compared based on epidemiological and disease-associated data. RESULTS: In total, 4322 patients were admitted, and 435 samples for CDI were analyzed, with 104/435 (23.9 %) sample positivity and 2.4 % prevalence. We observed an increased prevalence of CDI compared to the beginning of the COVID-19 pandemic (prevalence = 1.7 %, p = 0.003). 35.6 % of the CDI patients were hospitalized in the COVID-19 ward and 64.4 % in the Internal Medicine ward. COVID-19 patients were younger (p = 0.02) with a lower Charlson Comorbidity Index (CCI) compared to the Internal Medicine ward patients (p < 0.001). With regards to the origin of CDI cases, in the Internal Medicine ward, 68.7 % presented with Hospital-Onset CDI, 17.9 % with Community Onset-Healthcare Associated CDI and 13.4 % with Community Associated CDI, while in the COVID-19 ward, the respective percentages were 86.5 %, 5.4 % and 8.1 %. Finally, there was an increased CDI-related CFR (Case Fatality Ratio) in the Internal Medicine ward compared to the COVID-19 ward (28.4 % vs. 5.4 %, p = 0.001). CONCLUSIONS: Increased CDI prevalence and testing were observed compared to the beginning of the COVID-19 pandemic. Lower CDI-related CFR was observed in patients with COVID-19, which may be credited to the patients' significantly lower median age and CCI, as well as to the majority of deaths being due to respiratory failure.

Anticoagulation in Patients with Liver Cirrhosis: Friend or Foe?

Concepts regarding the status of the coagulation process in cirrhosis are rapidly changing. Instead of a disease defined by excessive bleeding risk, recent studies have shown cirrhosis to be associated with a fragile state of rebalanced hemostasis, easily swayed in either direction, thrombosis, or bleeding. These findings, combined with the ever-growing population of patients with cirrhosis with an indication for anticoagulation (AC) and the emergence of the non-alcoholic fatty liver disease epidemic, have prompted a reexamination of the use of AC in patients with cirrhosis, either as a treatment for a concurrent thrombotic disorder or even as a possible therapeutic option that could influence the natural course of the disease and its complications. In recent years, a significant number of studies have been formulated to evaluate these possibilities. These studies evaluated, among others, the efficacy and safety of AC in thrombotic disorders or thrombotic complications of cirrhosis, its effect on survival, and the class of anticoagulants which is more suitable for patients with cirrhosis, depending on disease severity. This review examines recent studies investigating the use of AC in patients with cirrhosis and attempts to provide a simple guide for clinicians regarding the use of AC in patients with cirrhosis and its potential risks and benefits.

Cardiometabolic effects of direct-acting antivirals in patients with hepatitis C.

Hepatitis C virus (HCV) has long been associated with several extrahepatic manifestations, including increased cardiovascular risk. The emergence of direct-acting antivirals (DAAs) has allowed us to evaluate the potential reversal of these manifestations after successful treatment. Therefore, many studies have provided significant takeaways regarding the positive effect of DAAs therapy on insulin resistance, type 2 diabetes mellitus, cardiovascular disease and atherosclerosis. In contrast, studies have shown detrimental effects on lipid metabolism and indeterminate results regarding renal function and uric acid metabolism. Nevertheless, as more and more patients achieve sustained virological response, the effects of HCV eradication on cardiometabolic processes will be extensively studied, allowing more reliable conclusions on the extent of extrahepatic outcomes.

The Prevalence of Gastrointestinal Bleeding in COVID-19 Patients: A Systematic Review and Meta-Analysis.

Introduction: Severe acute respiratory syndrome coronavirus 2 caused the coronavirus disease of 2019 (COVID-19), which rapidly became a pandemic, claiming millions of lives. Apart from the main manifestations of this infection concerning the respiratory tract, such as pneumonia, there are also many manifestations from the gastrointestinal tract. Of these, bleeding from the gastrointestinal tract is a significant complication quite dangerous for life. This bleeding is divided into upper and lower, and the primary pathophysiological mechanism is the entering of the virus into the host cells through the Angiotensin-converting enzyme 2 receptors. Also, other comorbidities and the medication of corticosteroids and anticoagulants are considered to favor the occurrence of gastrointestinal bleeding (GIB). Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the studies were searched in two different databases (Scopus and PubMed) from November 2019 until February 2023. All studies that reported GIB events among COVID-19 patients were included. Results: 33 studies were selected and reviewed to estimate the prevalence of GIB. A total of 134,905 patients with COVID-19 were included in these studies, and there were 1458 episodes of GIB. The prevalence of GIB, in these 33 studies, ranges from 0.47% to 19%. This range of prevalence is justified by the characteristics of the COVID-19 patients. These characteristics are the severity of COVID-19, anticoagulant and other drug treatments, the selection of only patients with gastrointestinal manifestations, etc. The pooled prevalence of gastrointestinal bleeding was estimated to be 3.05%, rising to 6.2% when only anticoagulant patients were included. Conclusions: GIB in COVID-19 patients is not a rare finding, and its appropriate and immediate treatment is necessary as it can be life-threatening. The most common clinical findings are melena and hematemesis, which characterize upper GIB. Treatment can be conservative; however, endoscopic management of bleeding with embolization is deemed necessary in some cases.

Post-COVID-19 and Irritable Bowel Syndrome: A Literature Review.

The emergence of post-COVID-19 syndrome (PCS), a complex and multifactorial condition that follows the acute COVID-19 infection, has raised serious concerns within the global medical community. Concurrently, Irritable Bowel Syndrome (IBS), a widespread chronic gastrointestinal (GI) dysfunction, is considered to be one of the most common disorders of gut-brain interaction (DGBI) that significantly affects the quality of life and social functioning of patients. PCS presents a wide range of symptoms and GI manifestations, including IBS. This review aims to analyze the GI involvement and the prolonged symptoms of COVID-19 infection as part of PCS, in order to explore the potential development of post-infection IBS (PI-IBS) in COVID-19 patients. Irritating factors such as enteric infection, psychosocial conditions, food antigens, and antibiotics may lead to abnormalities in the physiological function of the GI system and could be involved in the development of PI-IBS. Through the presentation of the pathophysiological mechanisms and epidemiological studies that assessed the prevalence of IBS as part of PCS, we attempted to provide a better understanding of the long-term consequences of COVID-19 and the pathogenesis of PI-IBS. Even though PI-IBS is becoming a global challenge, there are only a few studies about it and therefore limited knowledge. Currently, the majority of the existing treatment options are referred to non-COVID-19-associated DGBIs. Forthcoming studies may shed light on the mechanisms of PI-IBS that could be targeted for treatment development.

A Derivative of the D5 Monoclonal Antibody That Targets the gp41 N-Heptad Repeat of HIV-1 with Broad Tier-2-Neutralizing Activity.

HIV-1 infection is initiated by the viral glycoprotein Env, which, after interaction with cellular coreceptors, adopts a transient conformation known as the prehairpin intermediate (PHI). The N-heptad repeat (NHR) is a highly conserved region of gp41 exposed in the PHI; it is the target of the FDA-approved drug enfuvirtide and of neutralizing monoclonal antibodies (mAbs). However, to date, these mAbs have only been weakly effective against tier-1 HIV-1 strains, which are most sensitive to neutralizing antibodies. Here, we engineered and tested 11 IgG variants of D5, an anti-NHR mAb, by recombining previously described mutations in four of D5's six antibody complementarity-determining regions. One variant, D5_AR, demonstrated 6-fold enhancement in the 50% inhibitory dose (ID50) against lentivirus pseudotyped with HXB2 Env. D5_AR exhibited weak cross-clade neutralizing activity against a diverse set of tier-2 HIV-1 viruses, which are less sensitive to neutralizing antibodies than tier-1 viruses and are the target of current antibody-based vaccine efforts. In addition, the neutralization potency of D5_AR IgG was greatly enhanced in target cells expressing FcγRI, with ID50 values of <0.1 µg/ml; this immunoglobulin receptor is expressed on macrophages and dendritic cells, which are implicated in the early stages of HIV-1 infection of mucosal surfaces. D5 and D5_AR have equivalent neutralization potency in IgG, Fab, and single-chain variable-fragment (scFv) formats, indicating that neutralization is not impacted by steric hindrance. Taken together, these results provide support for vaccine strategies that target the PHI by eliciting antibodies against the gp41 NHR and support investigation of anti-NHR mAbs in nonhuman primate passive immunization studies. IMPORTANCE Despite advances in antiretroviral therapy, HIV remains a global epidemic and has claimed more than 32 million lives. Accordingly, developing an effective HIV vaccine remains an urgent public health need. The gp41 N-heptad repeat (NHR) of the HIV-1 prehairpin intermediate (PHI) is highly conserved (>90%) and is inhibited by the FDA-approved drug enfuvirtide, making it an attractive vaccine target. However, to date, anti-NHR antibodies have not been potent. Here, we engineered D5_AR, a more potent variant of the anti-NHR antibody D5, and established its ability to inhibit HIV-1 strains that are more difficult to neutralize and are more representative of circulating strains (tier-2 strains). The neutralizing activity of D5_AR was greatly potentiated in cells expressing FcγRI; FcγRI is expressed on cells that are implicated at the earliest stages of sexual HIV-1 transmission. Taken together, these results bolster efforts to target the gp41 NHR and the PHI for vaccine development.

Drug-Induced Liver Injury in Hospitalized Patients during SARS-CoV-2 Infection.

In the last few years, the world has had to face the SARS-CoV-2 infection and its multiple effects. Even though COVID-19 was first considered to be a respiratory disease, it has an extended clinical spectrum with symptoms occurring in many tissues, and it is now identified as a systematic disease. Therefore, various drugs are used during the therapy of hospitalized COVID-19 patients. Studies have shown that many of these drugs could have adverse side-effects, including drug-induced liver injury-also known as DILI-which is the focus of our review. Despite the consistent findings, the pathophysiological mechanism behind DILI in COVID-19 disease is still complex, and there are a few risk factors related to it. However, when it comes to the diagnosis, there are specific algorithms (including the RUCAM algorithm) and biomarkers that can assist in identifying DILI and which we will analyze in our review. As indicated by the title, a variety of drugs are associated with this COVID-19-related complication, including systemic corticosteroids, drugs used for the therapy of uncontrolled cytokine storm, as well as antiviral, anti-inflammatory, and anticoagulant drugs. Bearing in mind that hepatotoxicity is very likely to occur during COVID-19, especially in patients treated with multiple medications, we will also refer to the use of other drugs used for DILI therapy in an effort to control and prevent a severe and long-term outcome.

Development of clinical guidelines for service provision of functional electrical stimulation to support walking: mixed method exploration of stakeholder views.

BACKGROUND: Over the past 20 years Functional Electrical Stimulation (FES) has grown in clinical use to support walking in people with lower limb weakness or paralysis due to upper motor neuron lesions. Despite growing consensus regarding its benefits, provision across the UK and internationally is variable. This study aimed to explore stakeholder views relating to the value of a clinical guideline focusing on service provision of FES to support walking, how people might use it and what should be included. METHODS: A mixed methods exploration sought the views of key stakeholders. A pragmatic online survey (n = 223) focusing on the study aim was developed and distributed to the email distribution list of the UK Association for Chartered Physiotherapists Interested in Neurology (ACPIN). In parallel, a qualitative service evaluation and patient public involvement consultation was conducted. Two group, and seven individual interviews were conducted with: FES-users (n = 6), their family and carers (n = 3), physiotherapists (n = 4), service providers/developers (n = 2), researchers (n = 1) and distributors of FES (n = 1). Descriptive analysis of quantitative data and framework analysis of qualitative data were conducted. RESULTS: Support for clinical guideline development was clear in the qualitative interviews and the survey results. Survey respondents most strongly endorsed possible uses of the clinical guideline as ensuring best practice and supporting people seeking access to a FES service. Data analysis and synthesis provided clear areas for inclusion in the clinical guidelines, including current research evidence and consensus relating to who is most likely to benefit and optimal service provision as well as pathways to access this. Specific areas for further investigation were summarised for inclusion in the first stage of a Delphi consensus study. CONCLUSIONS: Key stakeholders believe in the value of a clinical guideline that focuses on the different stages of service provision for FES to support walking. A Delphi consensus study is being planned based on the findings.

Elevated Levels of Alveolar Nitric Oxide May Indicate Presence of Small Airway Inflammation in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Pulmonary manifestations of inflammatory bowel disease (IBD), albeit not rare, are largely overlooked in clinical practice. The role of exhaled nitric oxide (eNO) as an established biological marker of airway inflammation compels us to use it as a tool to investigate the exact nature of these manifestations. METHODS: Fractional eNO (FeNO) was measured in multiple flows, and with the use of a mathematical model, alveolar concentration of NO (CANO) and bronchial flux of NO (JawNO) were assessed in 27 patients with IBD [17 with Crohn's disease (CD) and 10 with ulcerative colitis (UC)] and in 39 healthy controls. Carefully selected criteria were used to exclude patients or healthy controls that presented factors considered to be correlated with eNO measurements. Disease activity was measured in Crohn's patients using the CD activity index (CDAI) score and in UC using the partial Mayo score. RESULTS: CANO was significantly higher in the IBD group, compared to the control group (p < 0.0001). FeNO was significantly increased in patients with IBD (p = 0.023), while there was no statistical significance found regarding levels of JawNO in patients with IBD (p = 0.106), both compared to controls. There was no significant correlation between any eNO component and markers of disease activity. CONCLUSIONS: Alveolar concentration of NO is elevated in patients with IBD, regardless of disease activity. This may suggest that subclinical small airway inflammation is present in patients with IBD, even those with mild or inactive disease.

Helicobacter pylori infection diagnosis and management: current practices of Greek gastroenterologists.

Background: The diagnosis and management of Helicobacter pylori (H. pylori) infection vary significantly, depending on country, area, and specialty. The aim of this study was to record the current practices of Greek gastroenterologists in the screening and treatment of H. pylori infection. Method: An anonymous questionnaire consisting of 19 questions about the management of H. pylori infection was sent with the aid of the Hellenic Society of Gastroenterology to all members of the Society. Results: The questionnaire was completed by 180 gastroenterologists, with a response rate of 31.4%. Diagnostic tests to confirm H. pylori infection are ordered by >90% of the gastroenterologists for patients with current peptic ulcer disease, gastric lymphoma, family history of gastric cancer, and an endoscopic appearance suggestive of gastritis. Most gastroenterologists (55.8%) also tested for H. pylori in patients with gastroesophageal reflux disease (GERD). Histopathology was the most preferred (60.6%) method when testing was decided during endoscopy, while urea breath test was the most preferred method (67.8%) regardless of endoscopy. Most gastroenterologists use quadruple eradication regimens supported by international guidelines (90%), while 65.6% of the physicians answered that they systematically recommend the addition of probiotics to standard therapy. Most physicians (82.8%) answered that they always confirm the eradication of the pathogen. Conclusions: The majority of Greek gastroenterologists conform to the recommendations of international guidelines regarding the diagnosis and management of H. pylori infection, except for the screening of patients with GERD. A considerable number of doctors use probiotics in addition to standard therapy.

Comparative Assessment of Endoscopic Ultrasound-Guided Biopsies vs. Percutaneous Biopsies of Pancreatic Lesions: A Systematic Review and Meta-Analysis of Diagnostic Performance.

Introduction: Pancreatic cancer ranks as the fourth deadliest form of cancer. However, it is essential to note that not all pancreatic masses signal primary malignancy. Therefore, it is imperative to establish the correct differential diagnosis, a process further supported by pre-operative biopsy procedures. This meta-analysis aims to compare the diagnostic performance of two minimally invasive biopsy approaches for pancreatic tissue sampling: percutaneous biopsies guided by computed tomography or ultrasound, and transduodenal biopsies guided by endoscopic ultrasound (EUS). Methods: A systematic literature search was conducted in the MEDLINE and Scopus databases. The included studies analyzed the diagnostic performance of the two biopsy methods, and they were assessed for risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Statistical analysis was carried out using the RevMan and MetaDisc software packages. Results: The statistical analysis of the results demonstrated the superiority of the percutaneous approach. Specifically, the pooled sensitivity, specificity, LR+, LR-and DOR for the percutaneous approach were 0.896 [95% CI: 0.878-0.913], 0.949 [95% CI: 0.892-0.981], 9.70 [95% CI: 5.20-18.09], 0.20 [95% CI: 0.12-0.32] and 68.55 [95% CI: 32.63-143.98], respectively. The corresponding values for EUS-guided biopsies were 0.806 [95% CI: 0.775-0.834], 0.955 [95% CI: 0.926-0.974], 12.04 [95% CI: 2.67-54.17], 0.24 [95% CI: 0.15-0.39] and 52.56 [95% CI: 13.81-200.09], respectively. Nevertheless, it appears that this statistical superiority is also linked to the selection bias favoring larger and hence more readily accessible tumors during percutaneous biopsy procedures. Conclusions: Concisely, our meta-analysis indicates the statistical superiority of the percutaneous approach. However, selecting the optimal biopsy method is complex, influenced by factors like patient and tumor characteristics, clinical resources, and other relevant considerations.

Bispecific antibodies with broad neutralization potency against SARS-CoV-2 variants of concern.

The ongoing emergence of SARS-CoV-2 variants of concern (VOCs) that reduce the effectiveness of antibody therapeutics necessitates development of next-generation antibody modalities that are resilient to viral evolution. Here, we characterized N-terminal domain (NTD) and receptor binding domain (RBD)-specific monoclonal antibodies previously isolated from COVID-19 convalescent donors for their activity against emergent SARS-CoV-2 VOCs. Among these, the NTD-specific antibody C1596 displayed the greatest breadth of binding to VOCs, with cryo-EM structural analysis revealing recognition of a distinct NTD epitope outside of the site i antigenic supersite. Given C1596's favorable binding profile, we designed a series of bispecific antibodies (bsAbs) termed CoV2-biRNs, that featured both NTD and RBD specificities. Notably, two of the C1596-inclusive bsAbs, CoV2-biRN5 and CoV2-biRN7, retained potent in vitro neutralization activity against all Omicron variants tested, including XBB.1.5, EG.5.1, and BA.2.86, contrasting the diminished potency of parental antibodies delivered as monotherapies or as a cocktail. Furthermore, prophylactic delivery of CoV2-biRN5 significantly reduced the viral load within the lungs of K18-hACE2 mice following challenge with SARS-CoV-2 XBB.1.5. In conclusion, our NTD-RBD bsAbs offer promising potential for the design of resilient, next-generation antibody therapeutics against SARS-CoV-2 VOCs.

Estimation of glomerular filtration rate in patients with cirrhosis: evaluation of equations currently used in clinical practice and validation of Royal Free Hospital cirrhosis glomerular filtration rate.

OBJECTIVE: Conventional creatinine-based glomerular filtration rate (GFR) equations have been reported to overestimate renal function in patients with cirrhosis. The Royal Free Hospital (RFH) cirrhosis GFR equation was developed to accurately estimate GFR in this population. The aim of this study was to evaluate the ability of widely available equations [Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), Modification of Diet in Renal Disease equations (MDRD-4, MDRD-6)] and the RFH equation to correctly estimate the GFR of patients with cirrhosis. METHODS: We retrospectively analyzed data from patients with cirrhosis who underwent measurement of GFR with the use of 51Cr-EDTA (GFR-M). The CKD-EPI, MDRD-4, MDRD-6 and RFH equations were calculated, while bias, precision and accuracy were estimated for each one of them and then compared with paired t-tests. Bias was defined as the mean difference between the GFR-M and the result of each equation; precision was defined as the SD of the differences and accuracy was defined as the square root of the mean squared error (mean of the squared differences). Higher values are associated with worse bias and better precision/accuracy. RESULTS: One-hundred and thirty-four cirrhotic patients were included. Bias was estimated for CKD-EPI, MDRD-4, MDRD-6 and RFH at -5.91, -3.13, 0.92 and 18.24, respectively. Significant differences were observed between all equations (P < 0.001). Regarding precision, only the comparison between MDRD-4 (20.81) and RFH (16.6) yielded a statistically significant result (P = 0.037). Finally, CKD-EPI (19.32) and MDRD-6 (18.81) exhibited better accuracy than GFR-RFH (24.61) (P = 0.006 and 0.001). CONCLUSION: RFH demonstrates inferior accuracy in predicting renal function in patients with cirrhosis, in comparison to conventional equations.

Ampullary Large-Cell Neuroendocrine Carcinoma, a Diagnostic Challenge of a Rare Aggressive Neoplasm: A Case Report and Literature Review.

Ampullary large-cell neuroendocrine carcinomas (LCNECs) are extremely rare, and available data are limited on case reports. They present with jaundice, non-specific abdominal pain, or weight loss, imitating adenocarcinoma. Their incidence increases due to the improved diagnostic techniques. However, preoperative diagnosis remains challenging. We report the case of a 70-year-old man with a history of metabolic syndrome, cholecystectomy, and right hemicolectomy, presenting with jaundice. Laboratory results showed increased liver biochemistry indicators and elevated CA 19-9. Esophagogastroduodenoscopy revealed an ulcerative tumor on the ampulla of Vater, and the biopsy revealed neuroendocrine carcinoma. Although computed tomography (CT) detected enlarged regional lymph nodes, the positron emission tomography (PET) showed a hyperactive lesion only in this area. Pylorus-preserving pancreatoduodenectomy with R0 resection was performed. Pathologic evaluation of the 3.1 × 1.9 cm tumor revealed an LCNEC with immunohistochemical positivity at Synaptophysin, EMA, CD56, and cytokeratin CK8/18. The Ki-67 index was 45%. Two out of the nine dissected lymph nodes were occupied by the neoplasm. The patient was discharged home free of symptoms, and adjuvant chemotherapy with carboplatin + etoposide was initiated. A comprehensive review of the reported cases showed that the preoperative biopsy result was different from the final diagnosis in few cases, regarding the subtypes. Conventional radiology cannot identify small masses, and other methods, such as endoscopy, magnetic resonance cholangiopancreatography (MRCP), and FDG-PET scan, might aid the diagnosis. Diagnosis is based on histology and immunohistochemical markers of the surgical specimens. The treatment of choice is pancreatoduodenectomy, followed by adjuvant chemotherapy. However, recurrence is frequent, and the prognosis remains poor.

Alcohol consumption in patients with nonalcoholic fatty liver disease: yes, or no?

Excessive alcohol intake is an established risk factor for chronic liver disease. At the same time, moderate alcohol intake appears to reduce cardiovascular morbidity. Accordingly, recommendations for alcohol intake in patients with nonalcoholic fatty liver disease (NAFLD), who are at increased risk for liver-related and cardiovascular events, are a point of debate. Some studies have shown beneficial effects of alcohol on cardiovascular and overall mortality in this specific subset of patients. Nonetheless, even light alcohol intake appears to aggravate liver disease and increase the risk of hepatocellular cancer. Therefore, patients with nonalcoholic steatohepatitis or advanced fibrosis should be advised against consuming alcohol. On the other hand, only light alcohol consumption (<10 g/day) might be permitted in patients without significant hepatic fibrosis, provided that they are carefully followed-up. As the research field focusing on NAFLD keeps widening, more prospective studies regarding this specific subject are expected, and may provide a basis for less ambiguous recommendations.

Endoscopic sedation practices of Greek gastroenterologists: a nationwide survey.

BACKGROUND: Sedation in gastrointestinal endoscopy is rapidly evolving worldwide. However, this has led to significant disagreements, especially regarding the use of propofol by non-anesthesiologists. The aim of this study was to document the practices of Greek gastroenterologists regarding sedation and compare them to previous surveys. METHODS: The study was conducted in 2 periods, December 2015 and June 2018. In each period, the same online questionnaire regarding endoscopic sedation practices was sent to all registered Greek gastroenterologists (509 and 547 gastroenterologists, respectively). RESULTS: The response rates were 38.3% and 47.1%, respectively. In each period, 25.1% and 16.7% of physicians did not use sedation. Most gastroenterologists (approx. 70% in both instances) answered that they "almost never" collaborate with an anesthesiologist during endoscopy. Midazolam was by far the most popular sedation agent, used by almost 90% of physicians in both periods. Propofol was used by 30.8% and 27% of physicians, respectively. Physicians using propofol were significantly more satisfied with the sedation than other physicians, while propofol was the agent selected by most physicians if they were to undergo endoscopy themselves. Most physicians cited medicolegal reasons and inadequate training as chief reasons for not using propofol. CONCLUSIONS: Sedation use is widespread among Greek gastroenterologists. Although midazolam is the most commonly used agent, propofol is preferred (theoretically) by most physicians and achieves the best satisfaction. The introduction of a strict training curriculum for endoscopic sedation can effectively eliminate the barriers preventing gastroenterologists from administering propofol, while at the same time ensuring optimal patient safety during endoscopy.

Validating and expanding the Baveno VI criteria for esophageal varices in patients with advanced liver disease: a multicenter study.

INTRODUCTION: According to the Baveno VI workshop, patients with compensated advanced liver disease, platelet count (PLT) >150,000/µL and liver stiffness measurement (LSM) <20 kPa can avoid screening endoscopy for high-risk varices (HRVs). The purpose of this study was to validate these criteria in a multicenter Greek cohort and consider other approaches that may further decrease the number of endoscopies. METHODS: We prospectively enrolled patients with advanced liver disease (defined as LSM >12 kPa) and evaluated them according to the Baveno VI criteria. Exclusion criteria were splanchnic vein thrombosis, use of ß-blockers, and esophageal varices. Screening endoscopy was conducted within 6 months of liver stiffness and laboratory measurements. RESULTS: One-hundred seven consecutive patients were enrolled in the study to undergo LSM and screening endoscopy. Of these, 13 met the Baveno VI criteria (12.1%); none of the latter had HRVs. Additional parameters were examined, among which the quotient PLT/log10LSM exhibited the largest area under the curve; concerning the latter, values ≤122,000 µL-1 x kPa-1 predicted high-risk varices with 100% sensitivity and negative predictive value (NPV), preventing 20.6% of patients from unneeded screening endoscopy (P=0.003). Moreover, values ≤92,000 µL-1 x kPa-1 exhibited 86% sensitivity and 94% NPV, preventing 44.9% of patients from unneeded screening endoscopy (P=0.001), while maintaining a tolerable percentage of overlooked patients with HRVs (6.3%). CONCLUSIONS: The Baveno VI criteria were successfully validated in our study. The quotient PLT/log10LSM can be used to further decrease the number of screening endoscopies in patients with advanced liver disease.