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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 -
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 -
Indian Journal of Pathology &... 2024Autoimmune liver diseases (AILD) represent a spectrum of related yet distinct immune-mediated disorders. The literature on the prevalence of these AILDs in Indian... (Observational Study)
Observational Study
AIMS
Autoimmune liver diseases (AILD) represent a spectrum of related yet distinct immune-mediated disorders. The literature on the prevalence of these AILDs in Indian population is scarce. This study aims to assess the prevalence and clinicopathological spectrum of various AILDs especially the overlap syndrome.
MATERIALS AND METHODS
A 10-year (2011-2020) cross-sectional, retrospective observational study of histological proven cases of AILD was conducted. Clinical, demographic, and laboratory parameters were retrieved. Two pathologists independently reviewed the liver biopsies and reassessed 18 histopathological parameters.
RESULTS
During the study period, 17664 liver biopsies were received, out of which 1060 (6%) biopsies of AILD were identified. After exclusion, we had 721 cases which revealed a distribution of autoimmune hepatitis (AIH)-64.7%, primary biliary cholangitis (PBC)-14.8%, primary sclerosing cholangitis (PSC)-7.6%, overlap AIH-PBC 11%, and overlap AIH-PSC 1.7%. AIH patients had significantly higher prevalence for severe lobular inflammation (27%, P ≤ 0.001), several lobular plasma cells (37%, P ≤ 0.001), central perivenulitis (30%, P ≤ 0.001), hepatic rosettes (51%, P ≤ 0.001), and necrosis (35.5%, P ≤ 0.001), while PBC patients had significantly higher frequency of florid duct lesions (11.2%, P ≤ 0.001), duct loss (83.17%, P ≤ 0.001), bile duct damage (76.6%, P ≤ 0.001), and periportal copper deposits (19.6%, P ≤ 0.001). Overlap AIH-PBC group had the highest proportion of severe portal inflammation (27.5%, P ≤ 0.001), prominent portal plasma cells (75%, P ≤ 0.001), moderate interface activity (53.7%, P ≤ 0.001), Mallory-Denk bodies (27.5%, P ≤ 0.001), and periportal cholate stasis (25%, P ≤ 0.001).
CONCLUSION
Prevalence of biopsy-proven AILDs in our study cohort is 6%. AIH (64.7%) is the most common AILD followed by PBC (14.8%). Overlap syndrome (AIH-PBC) showed prevalence of 11%.
Topics: Humans; Liver Cirrhosis, Biliary; Prevalence; Cross-Sectional Studies; Liver Diseases; Autoimmune Diseases; Hepatitis, Autoimmune; Syndrome; Inflammation
PubMed: 38358198
DOI: 10.4103/ijpm.ijpm_72_22 -
Virchows Archiv : An International... Apr 2024Mallory-Denk bodies (MDBs) are hepatocellular cytoplasmic inclusions, which occur in certain chronic liver diseases, such as alcohol-related (ASH) and metabolic...
Mallory-Denk bodies (MDBs) are hepatocellular cytoplasmic inclusions, which occur in certain chronic liver diseases, such as alcohol-related (ASH) and metabolic dysfunction-associated (MASH) steatohepatitis, copper toxicosis, some drug-induced liver disorders, chronic cholangiopathies, and liver tumors. Our study focused on the expression of the senescence markers p21 and p16 in hepatocytes containing MDBs in steatohepatitis, chronic cholangiopathies with fibrosis or cirrhosis, Wilson's disease, and hepatocellular carcinomas. Cytoplasm and nuclei of MDB-containing hepatocytes as well as MDB inclusions, except those associated with carcinoma cells, were strongly p16-positive, p21-positive, as well as p21-negative nuclei in MDB-containing hepatocytes which were observed whereas MDBs were p21-negative. Expression of the senescence marker p16 suggests that MDB formation reflects an adaptive response to chronic stress resembling senescence with its consequences, i.e., expression of inflammation- and fibrosis-prone secretome. Thus, senescence can be regarded as "double-edged sword" since, on the one hand, it may be an attempt of cellular defense, but, on the other, also causes further and sustained damage by inducing inflammation and fibrosis related to the senescence-associated secretory phenotype and thus progression of chronic liver disease.
Topics: Humans; Cellular Senescence; Hepatocytes; Cyclin-Dependent Kinase Inhibitor p16; Mallory Bodies; Cyclin-Dependent Kinase Inhibitor p21; Carcinoma, Hepatocellular; Liver Neoplasms; Liver; Biomarkers; Liver Diseases
PubMed: 38289501
DOI: 10.1007/s00428-024-03748-1 -
Journal of Clinical and Translational... Jan 2024Hepatocellular ballooning is a common finding in chronic liver disease, mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies (MDB)....
BACKGROUND AND AIMS
Hepatocellular ballooning is a common finding in chronic liver disease, mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies (MDB). Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes (BH) are damaged cells on the path to death or rather viable cells, possibly involved in neoplastic development.
METHODS
Using specimens from 96 cirrhotic human livers, BH characteristics were assessed for their glycogen/lipid stores, enzyme activities, and proto-oncogenic signaling cascades by enzyme- and immunohistochemical approaches with serial paraffin and cryostat sections.
RESULTS
BH were present in 43.8% of cirrhotic livers. Particularly pronounced excess glycogen storage of (glycogenosis) and/or lipids (steatosis) were characteristic, ground glass features and MDB were often observed. Decreased glucose-6-phosphatase, increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis, lipid metabolism, and cholesterol biosynthesis were discovered. Furthermore, components of the insulin signaling cascade were upregulated along with insulin dependent glucose transporter glucose transporter 4 and the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin signaling pathway associated with lipogenesis.
CONCLUSIONS
BH are hallmarked by particularly pronounced glycogenosis with facultative steatosis, many of their features being reminiscent of metabolic aberrations documented in preneoplastic hepatocellular lesions in experimental animals and chronic human liver diseases. Hence, BH are not damaged entities facing death but rather viable cells featuring metabolic reprogramming, indicative of a preneoplastic nature.
PubMed: 38250461
DOI: 10.14218/JCTH.2023.00242 -
Innovative Surgical Sciences Jun 2023The Kasabach-Merritt syndrome (KMS) is characterized by the occurrence of hemangioendothelioma (giant hemangioma with thrombosis leading to thrombocytopenia), which can...
Laparoscopic cholecystectomy for symptomatic cholecystolithiasis (CCL) in "Kasabach-Merritt syndrome" (KMS) (Kaposi-tumor like hemangioendothelioma with case-specific perioperative management).
OBJECTIVES
The Kasabach-Merritt syndrome (KMS) is characterized by the occurrence of hemangioendothelioma (giant hemangioma with thrombosis leading to thrombocytopenia), which can be associated with disseminated intravasal coagulation. Specific aim: Based on (i) selective references from the current scientific literature and derived recommendations as well as (ii) own experiences obtained in the diagnostic and perioperative management of a representative case from daily practice in abdominal surgery, the specific case undergoing elective cholecystectomy (CCE) in KMS is to be described by means of scientific case report.
CASE PRESENTATION
(Patient-, finding- and treatment-specific characteristics): - Medical history: 72-years old female patient with a known KMS of the left arm and upper thorax, recurrent thrombophlebitis of the left arm and thoracic veins, previous upper GI bleeding (Mallory-Weiss syndrome in 2006, chronic anemia in lack of vitamin B12, type-A gastritis, former bleeding complications after teeth extraction/open appendectomy 1962/Caesarean section 1968 with need of transfusion [60 red blood cell packages]), intraabdominal adhesions, hypothyreosis, initial liver cirrhosis. - Symptomatology: Characteristic for cholecystolithiasis (CCL). - Diagnostic: Abdominal ultrasound shows CCL, fibroscan does not confirm suspicious cirrhosis. Laboratory parameters showed: Activation of intravasal coagulation with elevated prothrombin fragments, D-dimers and reduced antiplasmin concentration. Accelerated fibrinolysis capacity; currently, no secondary thrombocytopenia or factor-13 decrease. In addition, fibrinogen concentration within normal range, no hint onto the manifestation of an aquired von-Willebrand's syndrome. - Diagnosis: Chronic fibrosing cholecystitis in CCL after former acute cholecystitis (3 months ago) with indication for surgical intervention. - Therapy: Laparoscopic CCE including careful exploration of upper abdominal cavity for KMS manifestation (with no revision of bile duct) and peritoneal adhesiolysis (histological finding, chronic fibrosing cholecystitis with thickening of the wall of the gall bladder but no hint of malignancy) under perioperative prophylaxis with antibiotics and temporary cessation of platelet medication for 7 d preoperatively, "bridging" with low molecular weight heparin (Clexane, 1 × 40 mg s.c.; Sanofi-Aventis, Frankfurt/Main, Germany); 1 h preoperatively, 15-20 mg/kg body weight Cyclocapron i.v. (once again 6-8 h postoperatively; thereafter, 500 mg of Cyclocapron 4×/d until the 3rd postoperative day). - Intraoperatively: Congestion of veins but not at the immediate surgical field (gall bladder, hepatic bed of the gall bladder, Calot's triangle). - Outcome: Uneventful, in particular, no (bleeding) complications.
CONCLUSIONS
If surgical approach is indicated, the intervention should be thoroughly planned (in particular, under elective circumstances) with regard to hemangioma site and extension as well as distance to the surgical field and possible surgical alternative options (surgical access site, open/laparoscopic approach etc.) to prevent - at the best possible rate - bleeding complications intra-/postoperatively and, thus, to provide adequate patient safety.
PubMed: 38058777
DOI: 10.1515/iss-2022-0017 -
PeerJ. Computer Science 2023Figures and captions in medical documentation contain important information. As a result, researchers are becoming more interested in obtaining published medical figures...
BACKGROUND
Figures and captions in medical documentation contain important information. As a result, researchers are becoming more interested in obtaining published medical figures from medical papers and utilizing the captions as a knowledge source.
METHODS
This work introduces a unique and successful six-fold methodology for extracting figure-caption pairs. The A-torus wavelet transform is used to retrieve the first edge from the scanned page. Then, using the maximally stable extremal regions connected component feature, text and graphical contents are isolated from the edge document, and multi-layer perceptron is used to successfully detect and retrieve figures and captions from medical records. The figure-caption pair is then extracted using the bounding box approach. The files that contain the figures and captions are saved separately and supplied to the end useras theoutput of any investigation. The proposed approach is evaluated using a self-created database based on the pages collected from five open access books: Sergey Makarov, Gregory Noetscher and Aapo Nummenmaa's book "Brain and Human Body Modelling 2021", "Healthcare and Disease Burden in Africa" by Ilha Niohuru, "All-Optical Methods to Study Neuronal Function" by Eirini Papagiakoumou, "RNA, the Epicenter of Genetic Information" by John Mattick and Paulo Amaral and "Illustrated Manual of Pediatric Dermatology" by Susan Bayliss Mallory, Alanna Bree and Peggy Chern.
RESULTS
Experiments and findings comparing the new method to earlier systems reveal a significant increase in efficiency, demonstrating the suggested technique's robustness and efficiency.
PubMed: 37547417
DOI: 10.7717/peerj-cs.1452