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Clinical Journal of Gastroenterology May 2024This report describes the clinical course of a 41 year-old African woman who presented with an episode of acute alcoholic pancreatitis followed next by severe alcoholic...
This report describes the clinical course of a 41 year-old African woman who presented with an episode of acute alcoholic pancreatitis followed next by severe alcoholic hepatitis (SAH). Initially admitted for pancreatitis, the patient responded promptly to comprehensive treatment with strict abstinence from alcohol. However, remarkable elevations in white blood cell count to 44,000/µL and total bilirubin level to 12.4 mg/dL were observed 5-7 weeks later. Contrast-enhanced computed tomography revealed rapidly progressing hepatosplenomegaly. Histological analysis of a liver biopsy detected ballooned hepatocytes with Mallory-Denk bodies and significant neutrophilic infiltration in the hepatic parenchyma, which confirmed the diagnosis of SAH. The patient's hepatosplenomegaly and overall condition improved with supportive care alone. The reported case reveals the unexpected fact that SAH can develop after alcoholic acute pancreatitis.
PubMed: 38809500
DOI: 10.1007/s12328-024-01988-x -
Science Translational Medicine May 2024Despite the wide availability of several safe and effective vaccines that prevent severe COVID-19, the persistent emergence of severe acute respiratory syndrome...
Despite the wide availability of several safe and effective vaccines that prevent severe COVID-19, the persistent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that can evade vaccine-elicited immunity remains a global health concern. In addition, the emergence of SARS-CoV-2 VOCs that can evade therapeutic monoclonal antibodies underscores the need for additional, variant-resistant treatment strategies. Here, we characterize the antiviral activity of GS-5245, obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved viral RNA-dependent RNA polymerase (RdRp). We show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, SARS-CoV, SARS-CoV-related bat-CoV RsSHC014, Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant. Moreover, in mouse models of SARS-CoV, SARS-CoV-2 (WA/1 and Omicron B1.1.529), MERS-CoV, and bat-CoV RsSHC014 pathogenesis, we observed a dose-dependent reduction in viral replication, body weight loss, acute lung injury, and pulmonary function with GS-5245 therapy. Last, we demonstrate that a combination of GS-5245 and main protease (M) inhibitor nirmatrelvir improved outcomes in vivo against SARS-CoV-2 compared with the single agents. Together, our data support the clinical evaluation of GS-5245 against coronaviruses that cause or have the potential to cause human disease.
Topics: Animals; SARS-CoV-2; Prodrugs; Antiviral Agents; Humans; Mice; Administration, Oral; Chlorocebus aethiops; Vero Cells; COVID-19 Drug Treatment; COVID-19; Virus Replication; Nucleosides; Coronavirus Infections; Female; Disease Models, Animal
PubMed: 38776389
DOI: 10.1126/scitranslmed.adj4504 -
Lancet (London, England) May 2024Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Extended optical treatment versus early patching with an intensive patching regimen in children with amblyopia in Europe (EuPatch): a multicentre, randomised controlled trial.
BACKGROUND
Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the clinical guidelines of several countries. The aim of this study was to compare an intensive patching regimen, with and without extended optical treatment (EOT), in a randomised controlled trial.
METHODS
EuPatch was a randomised controlled trial conducted in 30 hospitals in the UK, Greece, Austria, Germany, and Switzerland. Children aged 3-8 years with newly detected, untreated amblyopia (defined as an interocular difference ≥0·30 logarithm of the minimum angle of resolution [logMAR] best corrected visual acuity [BCVA]) due to anisometropia, strabismus, or both were eligible. Participants were randomly assigned (1:1) via a computer-generated sequence to either the EOT group (18 weeks of glasses use before patching) or to the early patching group (3 weeks of glasses use before patching), stratified for type and severity of amblyopia. All participants were initially prescribed an intensive patching regimen (10 h/day, 6 days per week), supplemented with motivational materials. The patching period was up to 24 weeks. Participants, parents or guardians, assessors, and the trial statistician were not masked to treatment allocation. The primary outcome was successful treatment (ie, ≤0·20 logMAR interocular difference in BCVA) after 12 weeks of patching. Two primary analyses were conducted: the main analysis included all participants, including those who dropped out, but excluded those who did not provide outcome data at week 12 and remained on the study; the other analysis imputed this missing data. All eligible and randomly assigned participants were assessed for adverse events. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN51712593) and is no longer recruiting.
FINDINGS
Between June 20, 2013, and March 12, 2020, after exclusion of eight participants found ineligible after detailed screening, we randomly assigned 334 participants (170 to the EOT group and 164 to the early patching group), including 188 (56%) boys, 146 (44%) girls, and two (1%) participants whose sex was not recorded. 317 participants (158 in the EOT group and 159 in the early patching group) were analysed for the primary outcome without imputation of missing data (median follow-up time 42 weeks [IQR 42] in the EOT group vs 27 weeks [27] in the early patching group). 24 (14%) of 170 participants in the EOT group and ten (6%) of 164 in the early patching group were excluded or dropped out of the study, mostly due to loss to follow-up and withdrawal of consent; ten (6%) in the EOT group and three (2%) in the early patching group missed the 12 week visit but remained on the study. A higher proportion of participants in the early patching group had successful treatment (107 [67%] of 159) than those in the EOT group (86 [54%] of 158; 13% difference; p=0·019) after 12 weeks of patching. No serious adverse events related to the interventions occurred.
INTERPRETATION
The results from this trial indicate that early patching is more effective than EOT for the treatment of most children with amblyopia. Our findings also provide data for the personalisation of amblyopia treatments.
FUNDING
Action Medical Research, NIHR Clinical Research Network, and Ulverscroft Foundation.
Topics: Humans; Amblyopia; Child, Preschool; Female; Male; Child; Eyeglasses; Visual Acuity; Sensory Deprivation; Treatment Outcome; Europe
PubMed: 38704172
DOI: 10.1016/S0140-6736(23)02893-3 -
Journal of Cellular and Molecular... Apr 2024Liver cirrhosis is a silent disease in humans and is experimentally induced by many drugs and toxins as thioacetamide (TAA) in particular, which is the typical model for...
Liver cirrhosis is a silent disease in humans and is experimentally induced by many drugs and toxins as thioacetamide (TAA) in particular, which is the typical model for experimental induction of hepatic fibrosis. Thus, the objective of the present study was to elucidate the possible protective effects of lactéol® forte (LF) and quercetin dihydrate (QD) against TAA-induced hepatic damage in male albino rats. Induction of hepatotoxicity was performed by TAA injection (200 mg/kg I/P, twice/ week) in rats. LF (1 × 10 CFU/rat 5 times/week) and QD (50 mg/kg 5 times/week) treated groups were administered concurrently with TAA injection (200 mg/kg I/P, twice/ week). The experimental treatments were conducted for 12 weeks. Hepatotoxicity was evaluated biochemically by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) in the serum and histopathologically with the scoring of histopathological changes besides histochemical assessment of collagen by Masson's trichrome and immunohistochemical analysis for α-smooth muscle actin (α-SMA), Ki67 and caspase-3 expression in liver sections. Our results indicated that LF and QD attenuated some biochemical changes and histochemical markers in TAA-mediated hepatotoxicity in rats by amelioration of biochemical markers and collagen, α-SMA, Ki67 and caspase3 Immunoexpression. Additionally, LF and QD supplementation downregulated the proliferative, necrotic, fibroblastic changes, eosinophilic intranuclear inclusions, hyaline globules and Mallory-like bodies that were detected histopathologically in the TAA group. In conclusion, LF showed better hepatic protection than QD against TAA-induced hepatotoxicity in rats by inhibiting inflammatory reactions with the improvement of some serum hepatic transaminases, histopathological picture and immunohistochemical markers.
Topics: Humans; Rats; Male; Animals; Quercetin; Thioacetamide; Ki-67 Antigen; Liver Cirrhosis; Liver; Flavonoids; Chemical and Drug Induced Liver Injury; Collagen; Oxidative Stress; Calcium Carbonate; Drug Combinations; Lactose
PubMed: 38534093
DOI: 10.1111/jcmm.18196 -
Hepatology Communications Apr 2024The precision of clinical criteria and the utility of liver biopsy for diagnosis or prognosis remain unclear in patients with alcohol-associated hepatitis (AH). We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The precision of clinical criteria and the utility of liver biopsy for diagnosis or prognosis remain unclear in patients with alcohol-associated hepatitis (AH). We systematically reviewed the literature to answer these questions.
METHODS
Four databases were searched for studies describing the precision of clinical criteria (National Institute on Alcohol Abuse and Alcoholism, European Association for Study of Liver, or classical) and the role of histology in AH. The precision(positive predictive value) of criteria was pooled through random-effects meta-analysis, and its variation was investigated through subgroups and meta-regression of study-level factors with their percent contribution to variation (R2). The risk of bias among studies was evaluated through the QUADAS2 tool (PROSPERO-ID-CRD4203457250).
RESULTS
Of 4320 studies, 18 in the systematic review and 15 (10/5: low/high risk of bias, N=1639) were included in the meta-analysis. The pooled precision of clinical criteria was 80.2% (95% CI: 69.7-89.7, I2:93%, p < 0.01), higher in studies with severe AH (mean-Model for End-Stage Liver Disease > 20) versus moderate AH (mean-Model for End-Stage Liver Disease < 20): 92% versus 67.1%, p < 0.01, and in studies with serum bilirubin cutoff 5 versus 3 mg/dL (88.5% vs.78.8%, p = 0.01). The factors contributing to variation in precision were Model for End-Stage Liver Disease (R2:72.7%), upper gastrointestinal bleed (R2:56.3%), aspartate aminotransferase:aspartate aminotransferase ratio (R2:100%), clinical criteria (R2:40.9%), bilirubin (R2:22.5%), and Mallory body on histology (R2:19.1%).The net inter-pathologist agreement for histologic findings of AH was variable (0.33-0.97), best among 2 studies describing AH through simple and uniform criteria, including steatosis, ballooning, and neutrophilic inflammation. Few studies reported the utility of histology in estimating steroid responsiveness (N = 1) and patient prognosis (N = 4); however, very broad septa, pericellular fibrosis, and cholestasis were associated with mortality. Bilirubinostasis was associated with infection in 1 study.
CONCLUSIONS
Clinical criteria are reasonably precise for diagnosing severe AH, while there is an unmet need for better criteria for diagnosing moderate AH. Histologic diagnosis of AH should be simple and uniform.
Topics: Humans; End Stage Liver Disease; Severity of Illness Index; Hepatitis, Alcoholic; Aspartate Aminotransferases; Bilirubin
PubMed: 38497934
DOI: 10.1097/HC9.0000000000000404 -
Kyobu Geka. the Japanese Journal of... Mar 2024A 51-year-old man visited to our hospital because of chest discomfort and hematemesis. He was diagnosed with Mallory-Weiss syndrome and followed in outpatient clinic....
A 51-year-old man visited to our hospital because of chest discomfort and hematemesis. He was diagnosed with Mallory-Weiss syndrome and followed in outpatient clinic. One week later, he visited our hospital again for fever and discomfort. Chest computed tomography (CT) showed a foreign body perforated in the mediastinum in the upper esophagus, and he was urgently hospitalized for surgical removal of esophageal foreign body. Before surgery he vomited the esophageal foreign body with a lot of blood. Hematemesis was stopped spontaneously and contrast-enhanced CT revealed a pseudoaneurysm in the distal aortic arch, so thoracic endovascular aortic repair (TEVAR) was performed to prevent rupture. Esophageal endoscopy found that the site of esophageal injury healed spontaneously, so the patient was followed conservatively with antibiotics. He was discharged on postoperative day 18 uneventfully. TEVAR was an effective treatment for aortic injury caused by esophageal foreign body in our case.
Topics: Male; Humans; Middle Aged; Hematemesis; Esophagus; Aortic Diseases; Foreign Bodies; Endovascular Procedures
PubMed: 38465495
DOI: No ID Found -
Digestive Diseases and Sciences Apr 2024To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database.
OBJECTIVE
To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database.
METHODS
Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020.
RESULTS
Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes.
CONCLUSION
Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity.
Topics: Humans; Dronedarone; Amiodarone; Anti-Arrhythmia Agents; Dyphylline; Chemical and Drug Induced Liver Injury
PubMed: 38416280
DOI: 10.1007/s10620-023-08251-2 -
Clinical Neurology and Neurosurgery Mar 2024Retrospective chart review of patients receiving long-segment fusion during a five-year period.
STUDY DESIGN
Retrospective chart review of patients receiving long-segment fusion during a five-year period.
OBJECTIVE
To determine whether obese patients receive comparable benefits when receiving long-segment fusion compared to non-obese patients and to identify factors that may predict hardware failure and post-surgical complications among obese patients.
METHODS
Demographic, spinopelvic radiographic, patient-reported outcome measures (PROMs), and complications data was retrospectively collected from 120 patients who underwent long-segment fusion during a five-year period at one tertiary care medical center. Radiographic measurements were pelvic incidence, pelvic tilt (PT), lumbar lordosis, L4-S1 lordosis, thoracic kyphosis, sagittal vertical axis, PI-LL mismatch, and proximal junction cobb angle at upper instrumented vertebrae + 2 (UIV+2). PROMs were Oswestry disability index, numeric rating scale (NRS) Back Pain, NRS Leg Pain, RAND SF-36 pain, and RAND SF-36 physical functioning. Included patients were adults and had at least 2-years of postoperative follow-up. Descriptive and multivariate statistical analysis was performed with α = 0.05.
RESULTS
Patients with a BMI ≥ 30 (n=63) and patients with a BMI < 30 (n=57) demonstrated comparable improvements (P>0.05) for all spinopelvic radiographic measurements and PROMs. Each cohort demonstrated significant improvements from pre-assessment to post-assessment on nearly all spinopelvic radiographic measurements and PROMs (P<0.05), except PT and L4-S1 lordosis where neither group improved (p=0.95 and 0.58 for PT and P=0.23 and 0.11 for L4-S1 lordosis fornon-obese and obese cohorts respectively) and SF-36 physical functioning where the non-obese cohort not statistically improve (P=0.08). Patients with a BMI ≥ 30 demonstrated an increased incidence of cardiovascular complications (P=0.0293), acute kidney injury (P=0.0241), rod fractures (P=0.0293), and reoperations (P=0.0241) when compared to patients with a BMI < 30.
CONCLUSION
This study adds to a growing body of evidence linking demographic factors with risks of hardware failure. Further, this data challenges the assumption that obese patients may not receive sufficient benefit to be long-segment surgical candidates. However, given their elevated risk for post-operative and delayed hardware complications, obese patients should be appropriately counseling before undergoing surgery.
Topics: Adult; Humans; Lordosis; Retrospective Studies; Spinal Fusion; Lumbar Vertebrae; Thoracic Vertebrae; Postoperative Complications; Back Pain; Obesity; Treatment Outcome
PubMed: 38402706
DOI: 10.1016/j.clineuro.2024.108187 -
Trends in Cognitive Sciences Feb 2024Scholars have argued for centuries that affective states involve interoception, or representations of the state of the body. Yet, we lack a mechanistic understanding of... (Review)
Review
Scholars have argued for centuries that affective states involve interoception, or representations of the state of the body. Yet, we lack a mechanistic understanding of how signals from the body are transduced, transmitted, compressed, and integrated by the brains of humans to produce affective states. We suggest that to understand how the body contributes to affect, we first need to understand information flow through the nervous system's interoceptive pathways. We outline such a model and discuss how unique anatomical and physiological aspects of interoceptive pathways may give rise to the qualities of affective experiences in general and valence and arousal in particular. We conclude by considering implications and future directions for research on interoception, affect, emotions, and human mental experiences.
PubMed: 38395706
DOI: 10.1016/j.tics.2024.01.009