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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 -
Traffic Injury Prevention 2024Between 2010 and 2020, an annual average of more than 70,000 pedestrians were injured in U.S. motor vehicle crashes. Pedestrian fatalities increased steadily over that...
OBJECTIVE
Between 2010 and 2020, an annual average of more than 70,000 pedestrians were injured in U.S. motor vehicle crashes. Pedestrian fatalities increased steadily over that period, outpacing increases in vehicle occupant fatalities. Strategies for reducing pedestrian injuries include pedestrian crash prevention and improved vehicle design for protection of pedestrians in the crashes that cannot be prevented. This study focuses on understanding trends in injuries sustained in U.S. pedestrian crashes to inform continuing efforts to improve pedestrian crash protection in passenger vehicles.
METHODS
More than 160,000 adult pedestrians injured in motor vehicle crashes who were admitted to U.S. trauma centers between 2007 and 2016 were drawn from the National Trauma Data Bank (NTDB) Research Data Sets. The injuries in those cases were used to explore the shifting patterns of pedestrian injuries.
RESULTS
The proportion of pedestrians with thorax injuries increased 3.0 percentage points to 30.7% of trauma center-admitted NTDB pedestrian cases over the 10 years studied, and the proportion with pelvis/hip injuries increased to 21.2%. The proportion of cases with head injuries fell to 48.6%, and the percentage of pedestrians with lower extremity injury (44%) did not change significantly over the 10 year period. Assessment of possible reasons for the shifts suggested that increasing numbers of sport utility vehicles, population increases among the oldest age groups, and improvements in pedestrian protection in U.S. passenger vehicles likely contributed to, but did not completely account for, the relative changes in injury frequency in each body region.
CONCLUSIONS
More important than the reasons for the shifts in the relative frequency of injury to each body region are the conclusions that can be drawn regarding priorities for pedestrian protection research. Though head/face and lower extremity injuries remained the most frequently injured body regions in adult pedestrians admitted to NTDB trauma centers, the relative frequency of thorax and pelvis/hip injuries increased steadily, underlining the increasing importance of pedestrian protection research on these body regions.
Topics: Adult; Humans; United States; Accidents, Traffic; Pedestrians; Walking; Motor Vehicles; Leg Injuries; Hip Injuries; Wounds and Injuries
PubMed: 38175182
DOI: 10.1080/15389588.2023.2281271 -
Chemosphere Feb 2024This research investigated the ecological impact of exposing Eisenia fetida, an essential component of soil ecosystems, to the organophosphate pesticide ethoprophos,...
This research investigated the ecological impact of exposing Eisenia fetida, an essential component of soil ecosystems, to the organophosphate pesticide ethoprophos, widely used in agriculture. With a focus on understanding the specific effects on earthworms, we employed three concentrations (7.5, 15, and 30 mg/kg) over 28 days, considering the pesticide's short half-life and existing data on environmental concentrations. We aimed to contribute to a broader understanding of how these pesticides affect soil health. Histological analysis, including staining with Hematoxylin-eosin, Mallory Trichrome, Periodic acid-Schiff, and Alcian blue methods, was conducted on control and treatment groups. The histological and histopathological results were evaluated using the light microscopy, revealing various degenerations in the epithelial and muscle layers. Scanning electron microscopy analysis detected concentration-related notable compaction of the body surface, asymmetry, and distortion in the body segments. In the exposed groups, especially those subjected to higher ethoprophos concentrations, the grid-like appearance of the clitellum was visibly disturbed. This disturbance in the grid-like pattern is indicative of structural changes and disruptions at the microscopic level. Furthermore, total protein, carbohydrate, lipid analyses, as well as acid phosphatase and alkaline phosphatase enzyme activities, were also evaluated for earthworms from each experimental group. The analyses showed a concentration-related decrease in all biochemical measurements, except acid phosphatase enzyme activity. In conclusion, our study reveals that the environmentally realistic concentrations of ethoprophos, an effective and widely used pesticide in pest control, have detrimental effects on the health and physiology of E. fetida. These effects are manifested through histological deformities, altered biochemical profiles, and observable physiological disturbances. These results shed light on the harmful effects of ethoprophos on earthworms, underlining the necessity to restrict its usage in agricultural practices and thereby support environmental sustainability.
Topics: Animals; Oligochaeta; Microscopy, Electron, Scanning; Ecosystem; Pesticides; Soil; Acid Phosphatase; Soil Pollutants; Organothiophosphates
PubMed: 38141679
DOI: 10.1016/j.chemosphere.2023.141019 -
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 -
Ultrastructural Pathology Jan 2024Diabetes mellitus (DM) is one of the most common metabolic diseases causing damage in many organs in the body including the testes. Royal Jelly (RJ) is one of the honey...
Diabetes mellitus (DM) is one of the most common metabolic diseases causing damage in many organs in the body including the testes. Royal Jelly (RJ) is one of the honey bee products that has antioxidant, anti-inflammatory and antidiabetic properties. This study was performed to evaluate the changes in the microscopic structure of the testes in Streptozotocin (STZ)-induced diabetic rats, and the possible protective role of RJ. 60 adult male albino rats were divided into three groups. Group I Control group, Group II STZ group, and Group III STZ+RJ group. Group II received a single dose of STZ (50 mg/kg) by intraperitoneal injection. Group III received a single dose of STZ as in the second group then received RJ orally by intragastric tube in dose of (100 mg/kg/day) for 4 weeks after confirmation of diabetes. Light and electron microscopic studies were performed. Group II revealed marked structural changes affecting seminiferous tubules with sever reduction in germinal epithelium and loss of mature spermatozoa in their lumina. The interstitial tissue revealed degenerated Leydig cells and congested blood vessels. Mallory trichrome stained section of group II revealed marked increase in the amount of collagen fibers. Group III revealed highly preserved testicular architecture almost near to that appeared in the control group except few tubules that were damaged. In conclusion, RJ protected the testicular structure from the damaging effect of diabetic oxidative stress through its antioxidant effect thus preserving male fertility.
Topics: Rats; Male; Animals; Testis; Streptozocin; Diabetes Mellitus, Experimental; Electrons; Antioxidants
PubMed: 37927047
DOI: 10.1080/01913123.2023.2277170 -
Pediatric Critical Care Medicine : a... Feb 2024Extremes of patient body mass index are associated with difficult intubation and increased morbidity in adults. We aimed to determine the association between being...
Adverse Tracheal Intubation Events in Critically Ill Underweight and Obese Children: Retrospective Study of the National Emergency Airway for Children Registry (2013-2020).
OBJECTIVES
Extremes of patient body mass index are associated with difficult intubation and increased morbidity in adults. We aimed to determine the association between being underweight or obese with adverse airway outcomes, including adverse tracheal intubation (TI)-associated events (TIAEs) and/or severe peri-intubation hypoxemia (pulse oximetry oxygen saturation < 80%) in critically ill children.
DESIGN/SETTING
Retrospective cohort using the National Emergency Airway for Children registry dataset of 2013-2020.
PATIENTS
Critically ill children, 0 to 17 years old, undergoing TI in PICUs.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Registry data from 24,342 patients who underwent TI between 2013 and 2020 were analyzed. Patients were categorized using the Centers for Disease Control and Prevention weight-for-age chart: normal weight (5th-84th percentile) 57.1%, underweight (< 5th percentile) 27.5%, overweight (85th to < 95th percentile) 7.2%, and obese (≥ 95th percentile) 8.2%. Underweight was most common in infants (34%); obesity was most common in children older than 8 years old (15.1%). Underweight patients more often had oxygenation and ventilation failure (34.0%, 36.2%, respectively) as the indication for TI and a history of difficult airway (16.7%). Apneic oxygenation was used more often in overweight and obese patients (19.1%, 19.6%) than in underweight or normal weight patients (14.1%, 17.1%; p < 0.001). TIAEs and/or hypoxemia occurred more often in underweight (27.1%) and obese (24.3%) patients ( p < 0.001). TI in underweight children was associated with greater odds of adverse airway outcome compared with normal weight children after adjusting for potential confounders (underweight: adjusted odds ratio [aOR], 1.09; 95% CI, 1.01-1.18; p = 0.016). Both underweight and obesity were associated with hypoxemia after adjusting for covariates and site clustering (underweight: aOR, 1.11; 95% CI, 1.02-1.21; p = 0.01 and obesity: aOR, 1.22; 95% CI, 1.07-1.39; p = 0.002).
CONCLUSIONS
In underweight and obese children compared with normal weight children, procedures around the timing of TI are associated with greater odds of adverse airway events.
Topics: Infant; Child; Humans; Infant, Newborn; Child, Preschool; Adolescent; Retrospective Studies; Critical Illness; Overweight; Pediatric Obesity; Thinness; Intubation, Intratracheal; Hypoxia; Registries
PubMed: 37909825
DOI: 10.1097/PCC.0000000000003387 -
Chemosphere Jan 2024Quantifying mercury (Hg) concentrations in invertebrates is fundamental to determining risk for bioaccumulation in higher trophic level organisms in coastal food webs....
Quantifying mercury (Hg) concentrations in invertebrates is fundamental to determining risk for bioaccumulation in higher trophic level organisms in coastal food webs. Bioaccumulation is influenced by local mercury concentrations, site geochemistry, individual feeding ecologies, and trophic position. We sampled seven species of invertebrates from five coastal sites in the Minas Basin, Bay of Fundy, and determined body concentrations of methylmercury (MeHg), total mercury (THg), and stable isotopes of nitrogen (δN) and carbon (δC). To evaluate the effects of environmental chemistry on Hg production and bioaccumulation, bulk sediments from all sites were analysed for THg, %Loss on ignition (LOI) (carbon), and sulfur isotopes (δS), and concentrations of MeHg, Total Organic Carbon (TOC), sulfate, and sulfide were measured in porewaters. The mean concentration of MeHg in tissues for all invertebrates sampled was 10.03 ± 7.04 ng g). MeHg in porewater (mean = 0.22-1.59 ng L) was the strongest predictor of invertebrate MeHg, but sediment δS (-0.80-14.1‰) was also a relatively strong predictor. δS in tissues (measured in three species; Corophium volutator, Ilyanassa obsoleta, and Littorina littorea) were positively related to MeHg in invertebrates (r = 0.55, 0.22, and 0.71 respectively), and when used in combination with δN and δC values improved predictions of Hg concentrations in biota. Hg concentrations in the amphipod Corophium volutator (mean MeHg = 10.60 ± 1.90 ng g) were particularly well predicted using porewater and sediment chemistry, highlighting this species as a useful bioindicator of Hg contamination in sediments of the Bay of Fundy.
Topics: Animals; Methylmercury Compounds; Bioaccumulation; Fishes; Invertebrates; Mercury; Food Chain; Carbon; Water Pollutants, Chemical; Environmental Monitoring
PubMed: 37866498
DOI: 10.1016/j.chemosphere.2023.140502 -
Autophagy Feb 2024SQSTM1/p62 bodies are phase-separated condensates that play a fundamental role in intracellular quality control and stress responses. Despite extensive studies...
SQSTM1/p62 bodies are phase-separated condensates that play a fundamental role in intracellular quality control and stress responses. Despite extensive studies investigating the mechanism of formation and degradation of SQSTM1/p62 bodies, the constituents of SQSTM1/p62 bodies remain elusive. We recently developed a purification method for intracellular SQSTM1/p62 bodies using a cell sorter and identified their constituents by mass spectrometry. Combined with mass spectrometry of tissues from selective autophagy-deficient mice, we identified vault, a ubiquitous non-membranous organelle composed of proteins and non-coding RNA, as a novel substrate for selective autophagy. Vault directly binds to NBR1, an SQSTM1/p62 binding partner recruited to SQSTM1/p62 bodies, and is subsequently degraded by selective autophagy dependent on the phase separation of SQSTM1/p62. We named this process "vault-phagy" and found that defects in vault-phagy are related to nonalcoholic steatohepatitis (NASH)-derived hepatocellular carcinoma. Our method for purifying SQSTM1/p62 bodies will contribute to elucidating the mechanisms of several stress responses and diseases mediated by SQSTM1/p62 bodies.
Topics: Animals; Mice; Adaptor Proteins, Signal Transducing; Sequestosome-1 Protein; Autophagy; Liver Neoplasms; Organelles
PubMed: 37815214
DOI: 10.1080/15548627.2023.2266996