Cross-species transmission and histopathological variation in specific-pathogen-free minipigs infected with different hepatitis E virus strains.

Hepatitis E virus (HEV) is a major cause of viral hepatitis worldwide. Pigs are the natural host of HEV genotype 3 and the main reservoir of HEV. As the host range of HEV genotype 3 expands, the possibility that HEV from various species can be transmitted to humans via pigs is increasing. We investigated the potential cross-species transmission of HEV by infecting minipigs with swine HEV (swHEV), rabbit HEV (rbHEV), and human HEV (huHEV) and examining their histopathological characteristics and distribution in various organs. Fifteen specific-pathogen-free Yucatan minipigs were infected with swHEV, rbHEV, huHEV, or a mock control. In the present study, we analysed faecal shedding, viremia, and serological parameters over a seven-week period. Our results indicated that swHEV exhibited more robust shedding and viremia than non-swHEVs. Only swHEV affected the serological parameters, suggesting strain-specific differences. Histopathological examination revealed distinct patterns in the liver, pancreas, intestine, and lymphoid tissues after infection with each HEV strain. Notably, all three HEVs induced histopathological changes in the pancreas, supporting the association of HEVs with acute pancreatitis. Our results also identified skeletal muscle as a site of HEV antigen presence, suggesting a potential link to myositis. In conclusion, this study provides valuable insights into the infection dynamics of different HEV strains in minipigs, emphasizing the strain-specific variations in virological, serological, and histological parameters. The observed differences in infection kinetics and tissue tropism will contribute to our understanding of HEV pathogenesis and the potential for cross-species transmission.

Comparing customized ChatGPT and pathology residents in histopathologic description and diagnosis of common diseases.

This study aimed to evaluate and analyze the performance of a customized Chat Generative Pre-Trained Transformer (ChatGPT), known as GPT, against pathology residents in providing microscopic descriptions and diagnosing diseases from histopathological images. A dataset of representative photomicrographs from 70 diseases across 14 organ systems was analyzed by a customized version of ChatGPT-4 (GPT-4) and pathology residents. Two pathologists independently evaluated the microscopic descriptions and diagnoses using a predefined scoring system (0-4 for microscopic descriptions and 0-2 for pathological diagnoses), with higher scores indicating greater accuracy. Microscopic descriptions that received perfect scores, which included all relevant keywords and findings, were then presented to the standard version of ChatGPT to assess its diagnostic capabilities based on these descriptions. GPT-4 showed consistency in microscopic description and diagnosis scores across five rounds, accomplishing median scores of 50 % and 48.6 %, respectively. However, its performance was still inferior to junior and senior pathology residents (73.9 % and 93.9 % description scores and 63.9 % and 87.9 % diagnosis scores, respectively). When analyzing classic ChatGPT's understanding of microscopic descriptions provided by residents, it correctly diagnosed 35 (87.5 %) of cases from junior residents and 44 (68.8 %) from senior residents, given that the initial descriptions consisted of keywords and relevant findings. While GPT-4 can accurately interpret some histopathological images, its overall performance is currently inferior to that of pathology residents. However, ChatGPT's ability to accurately interpret and diagnose diseases from the descriptions provided by residents suggests that this technology could serve as a valuable support tool in pathology diagnostics.

Immunotoxicity and oxidative damage in Litopenaeus vannamei induced by polyethylene microplastics and copper co-exposure.

This study examines the combined effects of polyethylene microplastics (PE-MP) and copper (Cu2+) on the immune and oxidative response of Litopenaeus vannamei. PE-MP adsorbed with Cu2+ at 2.3, 6.8, and 16.8 ng (g shrimp)-1) were injected into L. vannamei. Over 14 days, survival rates were monitored, and immune and oxidative stress parameters were assessed. The results showed that combined exposure to PE-MP and Cu2+ significantly reduced the survival rate and decreased total haemocyte count. Immune-related parameters (phagocytic rate, phenoloxidase and superoxide dismutase (SOD)) and antioxidant-related parameters (SOD, catalase and glutathione peroxidase mRNA and enzyme) also decreased, while respiratory burst activity significantly increased, indicating immune and antioxidant system disruption. Additionally, there was a significant increase in oxidative stress, as measured by malondialdehyde levels. Histopathological analysis revealed severe muscle, hepatopancreas, and gill damage. These results suggest that simultaneous exposure to PE-MP and Cu2+ poses greater health risks to white shrimp.

Evidence for enduring cardiac and multiorgan toxicity after repeated exposure to the synthetic cannabinoid JWH-018 in male rats.

The use of synthetic cannabinoid receptor agonists (SCRAs) represents a public health concern. Besides abuse liability and cognitive impairments, SCRA consumption is associated with serious medical consequences in humans, including cardiotoxicity. The precise mechanisms underlying cardiac or other toxicities induced by SCRAs are not well understood. Here, we used in silico, in vivo, and ex vivo approaches to investigate the toxicological consequences induced by exposure to the SCRA JWH-018. Along with in silico predictive toxicological screening of 36 SCRAs by MC4PC software, adult male Sprague-Dawley rats were repeatedly exposed to JWH-018 (0.25mg/kg ip) for 14 consecutive days, with body temperature and cardiovascular parameters measured over the course of treatment. At 1 and 7 days after JWH-018 discontinuation, multiorgan tissue pathologies and heart mitochondria bioenergetics were assessed. The in silico findings predicted risk of cardiac adverse effects specifically for JWH-018 and other aminoalkylindole SCRAs (i.e., electrocardiogram abnormality and QT prolongation). The results from rats revealed that repeated, but not single, JWH-018 exposure induced hypothermia and cardiovascular stimulation (e.g., increased blood pressure and heart rate) which persisted throughout treatment. Post-mortem findings demonstrated cardiac lesions (i.e., vacuolization, waving, edema) 1 day after JWH-018 discontinuation, which may contribute to lungs, kidneys, and liver tissue degeneration observed 7 days later. Importantly, repeated JWH-018 exposure induced mitochondrial dysfunction in cardiomyocytes, i.e., defective lipid OXPHOS, which may represent one mechanism of JWH-018-induced toxicity. Our results demonstrate that repeated administration of even a relatively low dose of JWH-018 is sufficient to affect cardiovascular function and induce enduring toxicological consequences, pointing to risks associated with SCRA consumption.

TPPP-BRD9 Fusion-Related Gallbladder Carcinomas are Frequently Associated with Intracholecystic Neoplasia, Neuroendocrine Carcinoma, and a Distinctive Small Tubular-Type Adenocarcinoma Commonly Accompanied with a Syringomatous Pattern.

A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors' database. Among the 16 TPPP-BRD9 fusion-positive GBC cases, most were females (F:M=7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p<0.001), all with gastro-pancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC): 3 cases (27% vs. 4.6% in the reference database, p=0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a "syringoid" appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubular-spindle cell pattern accompanied by hemorrhage. In conclusion, TPPP-BRD9 fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the TPPP-BRD9 fusion-positive pattern of GBC.

Bridging Histopathology and Radiomics Toward Prognosis of Metastasis in Early Breast Cancer.

Tumor histomorphology is crucial for the prognostication of breast cancer outcomes because it contains histological, cellular, and molecular tumor heterogeneity related to metastatic potential. To enhance breast cancer prognosis, we aimed to apply radiomics analysis-traditionally used in 3D scans-to 2D histopathology slides. This study tested radiomics analysis in a cohort of 92 breast tumor specimens for outcome prognosis, addressing -omics dimensionality by comparing models with moderate and high feature counts, using least absolute shrinkage and selection operator for feature selection and machine learning for prognostic modeling. In the test folds, models with radiomics features [area under the curves (AUCs) range 0.799-0.823] significantly outperformed the benchmark model, which only included clinicopathological (CP) parameters (AUC = 0.584). The moderate-dimensionality model with 11 CP + 93 radiomics features matched the performance of the highly dimensional models with 1,208 radiomics or 11 CP + 1,208 radiomics features, showing average AUCs of 0.823, 0.799, and 0.807 and accuracies of 79.8, 79.3, and 76.6%, respectively. In conclusion, our application of deep texture radiomics analysis to 2D histopathology showed strong prognostic performance with a moderate-dimensionality model, surpassing a benchmark based on standard CP parameters, indicating that this deep texture histomics approach could potentially become a valuable prognostic tool.

The Protective Effect of Gallic Acid Against Bisphenol A-Induced Ovarian Toxicity and Endocrine Disruption in Female Rats.

Purpose: This study aimed to investigate the protective effects of gallic acid (GA) against ovarian damage induced by bisphenol A (BPA) exposure in female rats. We evaluated whether GA can mitigate the adverse effects of BPA on ovarian structure, inflammatory markers, oxidative stress, apoptosis, and reproductive hormone levels. Methods: Thirty-two female rats were categorized into four groups: control, GA, BPA, and GA+BPA. Histopathological evaluations of ovarian tissue were performed using hematoxylin-eosin staining. The immunohistochemical analysis was conducted for inflammatory, oxidative DNA damage, and apoptotic markers (Tumor necrosis factor alpha [TNFα], cyclooxygenase-2 [COX2], interleukin-1 beta [IL-1ß], 8-hydroxydeoxyguanosine [8-OHdG], and caspase 3). Oxidative stress was assessed by measuring malondialdehyde and superoxide dismutase levels. Furthermore, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone levels were quantified using enzyme-linked immunosorbent assay. Results: Histopathological outcomes revealed that BPA significantly induced follicular degeneration, which was effectively mitigated by GA treatment (P < 0.05). Immunohistochemical analysis highlighted the exacerbation of inflammatory responses and oxidative DNA damage and apoptosis (TNFα, COX-2, IL-1ß, 8-OHdG, and caspase 3) in BPA-exposed tissues, which were reduced in the presence of GA (P < 0.05). The assessment of oxidative stress demonstrated that GA could significantly decrease lipid peroxidation and partially restore antioxidant defense mechanisms disrupted by BPA (P < 0.05). Hormonal profiling indicated that BPA exposure altered the levels of FSH, LH, estrogen, and progesterone, with GA treatment showing a capacity to modulate these changes, especially in progesterone levels (P < 0.05). Conclusions: The findings suggest that GA exhibits protective properties against BPA-induced ovarian damage through its antioxidative and anti-inflammatory activities, alongside its ability to modulate hormonal imbalances. This research underscores the therapeutic potential of GA in safeguarding reproductive health against environmental toxicants.

A rare case of acantholytic squamous cell carcinoma presenting on non-sun exposed palpebral conjunctiva.

Purpose: This report describes the clinical and histological characteristics and management of a keratinized lesion of the palpebral conjunctiva in a 59-year-old male. The lesion was identified as a rare acantholytic variant of squamous cell carcinoma that atypically arose from a non-sun exposed region of palpebral conjunctiva. Management was complete excision via Mohs surgery. Observations: A 59-year-old male presented with ocular irritation and chronic foreign body sensation in the right eye. Exam revealed a keratinized lesion in the right lower tarsal conjunctiva, and an initial shave biopsy was non-diagnostic. 12 months later, the patient presented with similar symptoms and a larger, more irregular lesion for which histopathology of a tarsal-involving excisional biopsy was consistent with acantholytic squamous cell carcinoma with involved margins. The patient subsequently underwent complete excision via Mohs surgery and a secondary reconstruction. Conclusions and importance: Acantholytic variants of squamous cell carcinoma are rare and are described as arising from areas with routine sun exposure. This case reports such a lesion arising from non-sun exposed tarsal conjunctiva, as identified by histopathology of a full-thickness excisional biopsy. The lesion was successfully managed with complete excision via Mohs surgery and secondary reconstruction. Given that this histologic variant may be more aggressive and have higher rates of recurrence than other forms of squamous cell carcinoma, this case highlights the importance of complete excisional biopsy and accurate histopathology of concerning periocular lesions and offers a template for management of similar lesions. The unique presenting location should bring awareness to consideration of this type of malignancy developing on palpebral conjunctiva.

Building living systematic reviews and reporting standards for comparative microscopic analysis of white diseases in hard corals.

Over the last 4 decades, coral disease research has continued to provide reports of diseases, the occurrence and severity of disease outbreaks and associated disease signs. Histology using systematic protocols is a gold standard for the microscopic assessment of diseases in veterinary and medical research, while also providing valuable information on host condition. However, uptake of histological analysis for coral disease remains limited. Increasing disease outbreaks on coral reefs as human impacts intensify highlights a need to understand the use of histology to date in coral disease research. Here, we apply a systematic approach to collating, mapping and reviewing histological methods used to study coral diseases with 'white' signs (i.e., white diseases) in hard coral taxa and map research effort in this field spanning study design, sample processing and analysis in the 33 publications identified between 1984 and 2022. We find that studies to date have not uniformly detailed methodologies, and terminology associated with reporting and disease description is inconsistent between studies. Combined these limitations reduce study repeatability, limiting the capacity for researchers to compare disease reports. A primary outcome of this study is the provision of transparent and repeatable protocols for systematically reviewing literature associated with white diseases of hard coral taxa, and development of recommendations for standardised reporting procedures with the aim of increasing uptake of histology in addition to allowing for ongoing comparative analysis through living systematic reviews for the coral disease field.

Fetal rhabdomyoma in a Thoroughbred filly.

A newborn Thoroughbred filly presented with a large mass located on the ventro-rostral aspect of the mandible. The mass was surgically removed under general anaesthesia. Upon gross examination, the mass was well circumscribed with a heterogeneous lobulated appearance. The results of histopathology and immunohistochemistry were consistent with a diagnosis of congenital fetal rhabdomyoma. On follow-up at six months post-surgical excision, no abnormalities were noted on clinical examination.

Malaria Tropica: An Autopsy Case Report With a Discussion on the Presence of Malaria in Bulgaria.

Malaria is an infectious disease caused by several types of parasitic plasmodia and transmitted to humans through Anopheles mosquitoes. The disease has long been widespread and has caused a significant number of deaths and decreased life quality from sequelae worldwide. As understanding of the disease increased immensely at the beginning of the 20th century, eradication plans were implemented to decrease disease transmission. This led to the successful eradication of malaria across predominantly industrialized countries, with multiple geographic areas remaining malaria endemic zones to this day. With climate changes and migration, the risk of reintroduction of malaria to malaria-free zones has risen due to relatively easy travel to endemic zones and importation of cases. On the one hand, this is a significant public health risk and, on the other, a challenge to the medical system, as healthcare workers in malaria-free zones are often ill-prepared to recognize, diagnose, and treat malaria cases. Herein, we present an autopsy and histopathology case report of tropical (falciparum) malaria, complicated with blackwater fever (malignant malaria) with prevalent gross and histopathological changes, including hemomelanin deposition in the spline, liver, and bone marrow; visible parasitic forms in the remaining red blood cells; Durk's granulomas, sludge, and petechial hemorrhages in the central nervous system; and hemoglobin casts within the renal tubular structures. We also discuss the history and risk of reintroducing malaria into a malaria-free zone - Bulgaria.

Giant conjunctival melanoma with rich vascularization causing persistent bleeding.

The present study reported a rare case of persistent bleeding caused by conjunctival melanoma containing abundant vascular channels. A 44-year-old Japanese woman presented with a left upper eyelid nodule in February 2023. A pigmented conjunctival mass was present in the upper palpebral conjunctiva. Enhanced computed tomography demonstrated marked enhancement in the left eyelid in the artery phase, indicating hemangioma. The patient suffered blunt trauma to the face in May 2023 and continuous bleeding occurred. Doctors in the emergency room attempted hemostasis by diathermy and suture, but the bleeding could not be stopped. The patient eventually underwent emergent orbital exenteration of the left eye. At high magnification of the histology sample of the bleeding site, small-to-large vascular channels with various vascular lumens made up of endothelial cells within the conjunctival melanoma tissue could be observed. The tumor cells were positive for SOX10, Melan A, S100 and HMB45. We herein propose a novel variant of conjunctival melanoma with rich vascularization, clinically causing persistent bleeding.

Effects of chronic oral exposure to insecticide teflubenzuron on the midgut of the honey bee Apis mellifera workers: histopathological insights into pesticide toxicity.

The honey bee Apis mellifera plays a significant role as a pollinator of native and cultivated plants, by increasing the productivity of several cultures, preserving the flora, and producing forest seeds. However, bee populations are declining worldwide, including A. mellifera, due to Colony Collapse Disorder, mainly resulting from the constant use of pesticides in the crops. Teflubenzuron is a physiological insecticide that belongs to the benzoylurea group, which inhibits chitin synthesis, the main component of the insect integument classified as safe for non-target insects, including bees. However, its effect on non-target organs of insects remains unknown. The midgut is the main organ of the digestive tract, which works in digestion and absorption and may be exposed to pesticides that contaminate food resources. The present work aimed to verify if the insecticide teflubenzuron is toxic and has histopathological effects on the midgut of A. mellifera adult workers. Workers exposed orally and chronically to the field-realistic concentration of teflubenzuron present 81.54% mortality. The epithelium of the midgut of these bees presents high vacuolization, spherocrystals, cell fragments released to the organ lumen, apocrine secretion, nuclear pyknosis, loss of cell-cell contact, and damage to regenerative cell nests and to the peritrophic matrix. These results indicate that the chitin synthesis-inhibiting insecticide teflubenzuron is toxic to A. mellifera after chronic oral exposure, at realistic field concentration, although it is classified as non-toxic to adult and non-target insects.

Effect of co-administration of gallic acid and quercetin or gallic acid and rutin on impaired spermatogenesis and oxidative damage in a busulfan-treated rat model.

Gallic acid (GAL), rutin (RUT), and quercetin (QUE) are common antioxidant agents in fruits and vegetables with intriguing pharmacological effects. In the present study, we compared the therapeutic outcomes of GAL + QUE in comparison with GAL + RUT co-treatment in a busulfan (BUS) model of testicular injury in Wistar rats. BUS (4 mg kg-1 body weight (b.w) was injected intraperitoneally daily for 4 days. GAL + RUT or GAL + QUE (20 mg kg-1 b. w) was delivered by oral gavage for 52 days. Examination of the testes of BUS-treated rats both biochemically and under light microscopy revealed an increased level of lipid peroxidation, DNA fragmentation, glutathione-S-transferase, lactate dehydrogenase, gamma-glutamyl transpeptidase, alkaline phosphatase and acid phosphatase with a concomitant decrease in the level of antioxidants: glutathione, ascorbic acid, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, suggesting testicular injury. Tissue sections confirmed the testicular injury-induced by BUS, including diminished spermatogenesis score index, tubular diameter, gonado-somatic index, testis weight, epithelia thickness and higher percentage of aberrant tubules. GAL + QUE co-administration had better recovery effects than GAL + RUT on the biochemical markers and protected against BUS-induced testicular damage. GAL + QUE treatment regimen has better capacity to maintain the antioxidant capacity of the testes and is more potent at reducing BUS-induced oxidative damage compared to GAL + RUT.

Bridging the gap: understanding contemporary autopsies in acute leukemia by comparing ante-mortem and post-mortem profiles.

This study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009-2022) of 46 autopsied cases (age >12 years). B-ALL was the dominant subtype (34.8%). Liver and spleen were the common sites of active leukemia (63% cases). Symptoms like dyspnea and altered sensorium associated significantly with heart (p = .031) and brain leukostasis (p = .006). Measurable residual disease (MRD) negativity correlated with disease-free status outside the bone marrow, while MRD-positive cases displayed leukemic infiltrates. Infections were identified in 23 autopsied cases, notably linked to post-induction and post-transplant fatalities. Surprisingly, 18 of these 23 cases had unexpected infections mainly fungal (13 cases) with Aspergillus species as the most common. Diagnostic discrepancies were identified in 48% of cases. Malignant infiltration (46%) and infections (25%) were the leading causes of death. This research sheds light on leukemia in extra-medullary tissues, uncovers novel clinical-pathological associations, and highlights overlooked therapy side effects, offering insights for future case management.

Widespread correction of brain pathology in feline alpha-mannosidosis by dose escalation of intracisternal AAV vector injection.

Alpha-mannosidosis is caused by a genetic deficiency of lysosomal alpha-mannosidase, leading to the widespread presence of storage lesions in the brain and other tissues. Enzyme replacement therapy is available but is not approved for treating the CNS, since the enzyme does not penetrate the blood-brain barrier. However, intellectual disability is a major manifestation of the disease; thus, a complimentary treatment is needed. While enzyme replacement therapy into the brain is technically feasible, it requires ports and frequent administration over time that are difficult to manage medically. Infusion of adeno-associated viral vectors into the cerebrospinal fluid is an attractive route for broadly targeting brain cells. We demonstrate here the widespread post-symptomatic correction of the globally distributed storage lesions by infusion of a high dose of AAV1-feline alpha-mannosidase (fMANB) into the CSF via the cisterna magna in the gyrencephalic alpha-mannosidosis cat brain. Significant improvements in clinical parameters occurred, and widespread global correction was documented pre-mortem by non-invasive magnetic resonance imaging. Postmortem analysis demonstrated high levels of MANB activity and reversal of lysosomal storage lesions throughout the brain. Thus, CSF treatment by adeno-associated viral vector gene therapy appears to be a suitable complement to systemic enzyme replacement therapy to potentially treat the whole patient.

Clinical analysis of lupus miliaris disseminatus faciei: a cross-sectional study and literature review.

Background: The clinical similarity of lupus miliaris disseminatus faciei (LMDF) and other papular granulomatous facial disorders often makes its correct diagnosis challenging. Diagnosis often requires the assistance of pathological examination, and dermoscopy can be used as an auxiliary and non-invasive examination method, however, the current findings remain incomplete. Objectives: This study aimed to summarize the clinical, histopathological and dermoscopic features of LMDF in the Chinese Han population and aiming to provide practical significance to correct diagnosis. Methods: 109 patients of LMDF were collected in the Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University from August 2015 to August 2023. The clinical and histopathological manifestations of all patients, as well as the dermoscopic image features of 44 cases, including background, follicular findings, vessels, and other structures, were summarized and evaluated. Results: The most significant histopathological features of LMDF in 109 cases is epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. The most significant dermoscopic features of LMDF in all 44 cases were orange structureless background (30/44), follicular plug (32/44), follicular white scar-like area (32/44), unspecific linear vessels (24/44), linear vessels with branch (24/44) and white streaks (18/44). Conclusion: Histopathologically, LMDF is characterized by the presence of epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. Dermoscopically, it exhibits a distinctive orange structureless background, follicular plug, follicular white scar-like area, nonspecific linear vessels, linear vessels with branches, and white streaks.

Histopathological impact of SARS-CoV-2 on the liver: Cellular damage and long-term complications.

Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

Gastroesophageal reflux following per-oral endoscopic myotomy: Can we improve outcomes?

This editorial is an analysis the review article by Nabi et al recently published in this journal. Achalasia Cardia is a disease whose pathophysiology is still unclear. It is known that there is inflammation of unknown aetiology leading to loss of ganglion cells in the muscularis propria. The end result is lower oesophageal sphincter spasm, loss of receptive relaxation, decreased oesophageal peristalsis, all leading on to varying degrees of dysphagia. The treatment of this condition is palliative in nature, performed by myotomy of the lower oesophagus either surgically or endoscopically. Gastroesophageal reflux disease (GERD) has been associated with the myotomy performed, particularly with the Peroral Endoscopic Myotomy (POEM) procedure. Nabi et al have provided an excellent overview of the latest developments in predicting, preventing, evaluating, and managing GERD subsequent to POEM. Based on this theme, this review article explores the concept of using histology of the oesophageal muscle layer, to grade the disease and thereby help tailoring the length/type of myotomy performed during the POEM procedure. In the future, will a histology based algorithm available preoperatively, help modify the POEM procedure, thereby decreasing the incidence of GERD associated with POEM?

Vaginal leiomyoma in a perimenopausal woman: A rare case report and review of the literature.

Vaginal leiomyomas, originating from the anterior vaginal wall, are exceedingly uncommon, with only around 300 reported cases documented in the literature to date. We present a rare case of a 50-year-old female who visited the outpatient department with complaints of abnormal uterine bleeding, and heaviness in abdomen with mass protrusion outside introitus since one year. Ultrasonography indicated adenomyosis of the uterus, with a suspected mass protruding through the posterior bladder or anterior vaginal wall. MRI imaging was conducted large polypoidal mass lesion is seen within the vaginal cavity two assymetrical round ends with close proximity to bladder and urethra with pedunculated submucosal uterine fibroid with adenomyotic changes . The provisional diagnosis of? vaginal leiomyoma along with pedunculated submucosal uterine fibroid with Adenomyosis made. Patient planned for Hysterectomy for submucosal leiomyoma with Adenomyosis and excision of vaginal mass via vaginal route. The size of vaginal mass was around size 5 * 6cm size enucleated, redundant vaginal wall excised and same sent for histopathology examination. The cut section of the vaginal mass showed whorled appearance .The Histopathology of vaginal mass showed Vaginal leiomyoma. Postoperative period was uneventful. The patient anatomy was restored and had no complaint of difficulty in urination and symptomatically improved.