Histological Markers Research Articles

Induction of plasmalemmal vesicle-associated protein exacerbates glomerular endothelial injury in thrombotic microangiopathy.

Glomerular endothelial cell (GEnC) injury is a common feature across the wide spectrum of glomerular diseases. We recently reported that the endothelial-specific knockout of Krüppel-like factor 4 (Klf4) increases the susceptibility to GEnC injury and subsequent development of subacute thrombotic microangiopathy (TMA). However, the mechanism(s) mediating GEnCs response to injury in TMA are poorly understood. Single-nucleus RNA-sequencing demonstrated enrichment in pathways involved in angiogenesis, permeability, focal adhesion, dedifferentiation, and cytoskeletal organization in the endothelial cluster in mice with TMA. Plasmalemmal vesicle-associated protein (Plvap), a structural component of fenestral diaphragms, was highly enriched specifically in injured GEnCs. Induction of Plvap in cultured GEnCs increased proliferation, migration, and cell permeability with an accompanying loss of mature GEnC markers. Immunostaining for PLVAP in human kidney biopsies confirmed the increase in glomerular PLVAP in TMA, which correlated with a higher grade of glomerular injury. To date, this is the first study to show that the induction of Plvap in GEnCs shifts the cells to an immature state, which might exacerbate glomerular injury in TMA.NEW & NOTEWORTHY This study investigated the mechanism(s) underlying glomerular endothelial cell (GEnC) injury in thrombotic microangiopathy (TMA). We identified plasmalemmal vesicle-associated protein (PLVAP) as specifically upregulated in injured GEnCs in TMA, which was accompanied by pathways involved in angiogenesis and loss of differentiation. Induction of Plvap increased proliferation and migration of GEnCs. Human kidney biopsies with TMA demonstrated an increase in glomerular PLVAP, which correlated with histological markers of GEnC injury, confirming its pathologic role in TMA.

Lesion Formation in Cardiac Pulsed-Field Ablation: Acute to Chronic Cellular Level Changes.

As pulsed-field ablation (PFA) emerges as a promising therapy for atrial arrhythmias, an understanding of the cellular injury to cardiac tissue is critical to evaluating and interpreting results for each PFA system. This review aims to detail the mechanism of cell death for PFA, compare the cell death mechanism to thermal ablation modalities, clarify common histology markers, detail the progression of PFA lesions from the acute, to subacute, to chronic maturation states, and discuss clinical indicators of PFA lesions.

Beyond Metaplasia: Unraveling the Complex Pathogenesis of Autoimmune Atrophic Gastritis and Its Implications for Gastric Cancer Risk.

Autoimmune gastritis (AIG) is a chronic inflammatory condition characterized by immune-mediated destruction of gastric parietal cells, leading to oxyntic atrophy, achlorhydria, and hypergastrinemia. While AIG was historically linked to gastric adenocarcinoma and type I neuroendocrine tumors (NETs), recent evidence suggests the risk of adenocarcinoma in AIG is lower than previously believed, particularly in Helicobacter pylori (H. pylori)-negative patients. The increased cancer risk in AIG is mainly attributed to concurrent or past H. pylori infection. The incidence of gastric adenocarcinoma in AIG ranges from 0.12% to 0.5% per year, with cumulative risks over 10 years reported at 1%-3%. In contrast, type I NETs are more commonly associated with AIG, with an annual incidence of 0.68%-2.8% and cumulative rates as high as 15.3% over five years. Adenomatous polyps, which can progress to malignancy, have been reported in 4.6%-13.6% of AIG patients. This review examines the immune and molecular mechanisms underlying AIG's pathogenesis, positioning it as a model of immune-mediated epithelial injury with limited carcinogenic potential. AIG is associated with reparative metaplastic phenotypes, such as pseudopyloric and complete intestinal metaplasia, which contrast with the more aggressive incomplete intestinal metaplasia observed in H. pylori-induced gastritis. The reduced risk of adenocarcinoma in AIG is attributed to the absence of H. pylori, a T cell-dominated microenvironment, minimal macrophage infiltration, and protective factors such as altered gastric microbiota, epigenetic modifications, increased CD3+ intraepithelial cytotoxic T lymphocytes, and reduced interleukin-33/interleukin-13 signaling. Although AIG is linked to preneoplastic changes, its primary neoplastic risks include the development of type I NETs and adenomatous polyps, which carry a potential for malignant transformation, necessitating long-term surveillance in patients with hypergastrinemia, extensive atrophy, and associated gastric lesions. Challenges persist in distinguishing AIG from other atrophic gastritis types due to limitations in serological and histological markers, but emerging diagnostic tools, such as lymphocyte profiling and molecular assays, promise improved accuracy. This review underscores the importance of tailored surveillance and management strategies to address the distinct neoplastic risks associated with AIG, while advocating for further research into its immune landscape and molecular pathways.

P1083 Biological therapy and histological tumor necrosis factor - alpha expression in Inflammatory Bowel Disease patients

Abstract Background Tumor necrosis factor alpha (TNF-alpha) is crucial in IBD pathogenesis: previous studies showed that its expression correlates to the degree of colonic inflammation and that its issue levels may predict response to biologic agents. This project addresses immunohistochemical (IHC) TNF-alpha expression profiles and patterns in ileal, colonic, and rectal biopsies before and after biologic therapy, matched with endoscopic and clinical severity indexes. Thus, this study aims to identiy possible histological and IHC markers predictive of drug response. Methods A cohort of ten patients with Inflammatory Bowel Disease (7 Crohn’s Disease and 3 Ulcerative Colitis) treated with biologic agents were phenotypically defined according to the Montreal classification and retrospectively characterized as responders or non- responders. These features were pioneeringly integrated with IHC quantiying TNF-alpha positivity and endoscopic severity scores (SES-CD, Mayo endoscopic subscore) aHer the collection of colonoscopy biopsy specimens. IHC TNF-alpha assessment evidenced pronounced cytoplasmic staining of inflammatory cells in the lamina propria amidst crypts and occasionally with a transmural distribution. Elevated TNF-alpha positive cells (arbitrary cut-off of ≥ 20) were chiefly observed at diagnosis or relapse in the intestinal segments affected by the disease. Results For each colonoscopy, endoscopic activity (SES-CD/Mayoendoscopic score) significantly correlated with the dichotomic number of TNF-alpha+ cells measured in the biopsies at the endoscopic (ESOD) and histologic (HSOD) site of disease (p=0,039; p=0,046). Furthermore, the number of TNF-alpha positive cells in the HSOD segment at the first check-up available during treatment was significantly associated with response to first-line biologics (p= 0,023), thus suggest whether treatment continuation was appropriate or not. Conclusion This study thoroughly examines the link between IHC investigation of TNF-alpha positivity, Montreal classification at diagnosis, and endoscopic activity indexes. TNF-alpha IHC analysis could further stratify IBD patients and increase diagnostic accuracy, securing a patent- and disease-tailored therapy and avoiding unnecessary and ineffective treatments. As an outcome, it could reduce fruitless health expenditures resulting from failed therapeutic attempts. Lastly, this evaluation could spark new possibilities for molecular biology research regarding TNF-alpha functionality on the ileocolon and further elucidate the mechanisms underlying IBD. References Villanacci V et al "Histopathology of inlammatory bowel disease- Position statement of the Pathologists of the Italian Group of the Study of the Inflammatory Bowel Disease (IG- IBD) and Italian Group of Gastrointestinal Pathologists (GIPAD-SIAPEC) " Digestive ad Liver Disease 2020 Daperno et al . "Development and validation of a new, simplified endoscopic activity score of Crohn’s Disease: the SES - CD" GIE 2002

P0828 The impact of etrasimod on neutrophils in the ELEVATE UC clinical programme

Abstract Background Neutrophils are thought to play a role in the pathogenesis of ulcerative colitis (UC); they are believed to be the principal source of faecal calprotectin and are a histological marker of disease activity in mucosal biopsies. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active UC. This post hoc analysis evaluated neutrophils in patients (pts) receiving etrasimod or placebo (PBO) in the ELEVATE UC clinical programme. Methods We assessed percentage changes from baseline (BL) in absolute neutrophil counts (ANC) throughout ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369)1 for all pts and those who did or did not achieve clinical remission (clinical remitters) or endoscopic improvement-histologic remission (EIH remitters) at Week (Wk) 12. Transcriptional characterisation followed by cell type deconvolution analysis from bulk RNA-seq was performed on colonic biopsies to assess for neutrophils in clinical remitters vs nonremitters (at Wk 12). Incidence of neutropenia and potential associated infections were assessed. Results BL blood and colonic biopsy samples, respectively, were available for 432 and 340 pts (ELEVATE UC 52) and 353 and 249 pts (ELEVATE UC 12). Pts receiving etrasimod vs PBO had significant percent decreases from BL in ANC from Wk 4 (-14.9% vs -4.9%, p<0.05; ELEVATE UC 52) and Wk 2 (-12.0% vs 0.3%, p<0.05; ELEVATE UC 12); the greatest decrease was seen for pts receiving etrasimod at Wk 12 in ELEVATE UC 12 (-16.8%) and nadir was reached at Wk 20 in ELEVATE UC 52 (-24.5%) and maintained through Wk 52. Wk 12 clinical remitters vs nonremitters receiving etrasimod had significantly greater percent decrease in ANC from BL at most time points (p<0.05; Figure); a similar trend was seen for EIH remitters vs nonremitters. Colonic neutrophils were also significantly decreased at Wk 12 vs BL for pts receiving etrasimod (false discovery rate [FDR] <0.05) but not PBO, and for clinical remitters vs nonremitters receiving etrasimod (FDR <0.05). Across both trials, nine (etrasimod) and four (PBO) pts had neutrophil counts <1 × 109/L at any post-BL assessment. Of these pts, none reported subsequent serious, severe or opportunistic infections; one pt receiving etrasimod experienced a nonserious infection ≤60 days after reported neutropenia. Conclusion Our data support a relationship between decreased circulating and mucosal neutrophil levels and clinical and endoscopic improvement with etrasimod treatment in pts with UC, while showing a low likelihood of neutropenia.

P0184 Molecular signature of bowel urgency in Ulcerative Colitis

Abstract Background Bowel urgency is a ‘top three’ symptom of concern to patients with ulcerative colitis (UC), but the mechanisms are unclear [1]. Determining the molecular signatures of bowel urgency would reveal targetable mechanisms and generate measurable endpoints for future use. Methods Clinical data from the Oxford University Hospitals real world cohort were analysed. Oxford patient-reported Simple Clinical Colitis Activity Index (SCCAI) scores (including bowel urgency scale 0-3) were extracted from the TrueColours-IBD remote monitoring platform [2], which includes 2,186 patients with UC. Contemporaneous routinely scored endoscopic (UCEIS) and histological (Nancy index) activity were extracted from medical records. Molecular RNA-sequencing (RNAseq) signatures were generated from diagnostic biopsies. Results Overall, bowel urgency showed weak-to-moderate correlations (Spearman correlation coefficient <0.4) with clinical laboratory (CRP, albumin and haemoglobin), endoscopic (UCEIS) and histological (Nancy histologic index) measures of disease activity. By contrast, bowel urgency correlated moderately-to-strongly (Spearman correlation coefficient >0.6) with most other patient-reported symptom measures (bowel frequency, general wellbeing and total SCCAI). Based on bulk RNAseq profiling from biopsies of patients with UC obtained within two weeks of a reported SCCAI, we defined molecular signatures of cellular contractility, lymphocyte activation, B cell immunity and chemotaxis. Molecular signatures that most strongly correlated with objective markers of inflammation (such as endoscopic and histological measures) were also correlated with reported bowel urgency [FIGURE 1]. However, there were notable cases of discordance between urgency and objective measures of inflammation [FIGURE 2]. Conclusion At a cohort level, bowel urgency correlates with laboratory, endoscopic and histological measures of UC, but most strongly correlates with other patient reported symptoms indicative of disease activity. In corroboration, at a molecular RNA-level, bowel urgency similarly correlates with endoscopic and histologic markers of disease severity. However, on a patient-level there is a notable subset of patients with UC who demonstrate discordance between patient-reported urgency and objective markers of inflammation. Together, this suggests the presence of both overlapping and non-overlapping mechanisms of the symptomatic experience of urgency and bowel inflammation, which we are dissecting at a cellular level.

Therapeutic Potential of Rosmarinic Acid in Tramadol-Induced Hepatorenal Toxicity: Modulation of Oxidative Stress, Inflammation, RAGE/NLRP3, ER Stress, Apoptosis, and Tissue Functions Parameters.

Tramadol (TRM), a widely used opioid analgesic for moderate to severe pain, is associated with liver and kidney toxicity at high doses or prolonged use. This study investigates the protective role of rosmarinic acid (RA), a natural phenolic compound known for its antioxidant, anti-inflammatory, and cell-protective properties, against TRM-induced hepatorenal toxicity. Thirty-five male Wistar rats were divided into five groups: Control, TRM, RA, TRM+RA25, and TRM+RA50. Rats received TRM (50 mg/kg) and RA (25 or 50 mg/kg), with liver and kidney function tests, oxidative stress, inflammation, ER stress, apoptosis, and tissue damage indicators assessed through qRT-PCR, ELISA, Western blotting, H&E, and immunohistochemical analysis. TRM induced liver and kidney dysfunctions, evident from increased ALT, AST, ALP, urea, creatinine, nephrin, TIM-1 and 8-OHdG levels, along with activated oxidative stress, inflammation, ER stress, and apoptosis pathways. RA significantly reduced these effects, ameliorating histologic and immunohistochemical markers of tissue damage and inflammation. RA demonstrates therapeutic potential by mitigating TRM-induced hepatorenal toxicity and preserving tissue integrity.

The Effect of Systemic Inflammation and Clinicopathologic Features on Survival in Malignant Pleural Mesothelioma: A Multicenter Analysis.

Background and Objectives: Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with a poor prognosis. Identifying reliable prognostic factors is crucial for risk stratification and optimizing treatment strategies. This study aimed to evaluate the impact of clinicopathologic factors and systemic inflammatory markers on survival outcomes in patients with MPM. Materials and Methods: This retrospective, multicenter study included 217 patients diagnosed with MPM between January 2009 and March 2024. Data on age, gender, histology, disease stage, treatment modalities, and inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein/albumin ratio (CAR) were collected. Survival outcomes were analyzed using Kaplan-Meier methods, and prognostic factors were evaluated using Cox regression analysis. Results: CAR was identified as an independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Patients with CAR < 0.98 had significantly longer OS (87.0 months vs. 14.0 months, p < 0.001) and PFS (17.61 months vs. 8.96 months, p = 0.010). While NLR was significant in univariate analysis (OS: 25.0 months for NLR < 2.58 vs. 21.0 months for NLR ≥ 2.58, p = 0.040), it did not retain significance in the multivariate model (p = 0.180). Epithelioid histology and early-stage disease were strongly associated with improved survival outcomes (OS: 32.0 vs. 11.0 months for epithelioid vs. non-epithelioid histology, p < 0.001; 32.0 vs. 12.0 months for early-stage vs. metastatic disease, p < 0.001). Conclusions: CAR is a strong independent prognostic factor in MPM, reflecting systemic inflammation and nutritional status. Epithelioid histology and early-stage disease are associated with significantly longer survival, underscoring the critical role of early detection in improving patient outcomes.

Quantifying Tumor Budding: Implications for Prognosis in Gastric Adenocarcinoma.

The mechanism of tumor budding (TB) in gastric adenocarcinoma (GAC) and its relationship with biological indicators and prognostic significance, remains unclear. In this study, we conducted a comprehensive analysis using whole-slide imaging to evaluate TB in 75 cases of GAC. Our findings revealed the risk factors associated with TB in GAC and their impact on patient prognosis. The results indicate that the majority of cases exhibited a TB grade exceeding 10 (n=41), followed by 6-10 (n=15). Histologic grade (R=0.26, P=0.06), pT stage (R=0.56, P=0.00), neural invasion (R=0.29, P=0.01), marginal zone growth pattern (R=0.25, P=0.02), and basal zone growth pattern (R=0.38, P=0.001) are associated with TB in GAC. Logistic regression analysis revealed that the infiltrative growth pattern in both the marginal zone (odds ratio=5.90, 95% CI: 1.04-33.44, P=0.05) and basal zone (odds ratio=12.80, 95% CI: 2.03-80.68, P=0.01) were identified as risk factors for TB in GAC. Univariate analysis demonstrated a negative correlation between TB and TB grade with overall survival and progression-free survival in GAC patients. Furthermore, the multivariate COX analysis revealed that TB and TB grade, along with American Joint Committee on Cancer stage, lymph node metastasis, and pT stage, independently influenced the prognosis of GAC patients. In conclusion, a comprehensive evaluation of TB could serve as a significant histologic marker for risk stratification in GAC.

DNA Methylation in Prostate Cancer: Clinical Implications and Potential Applications.

Prostate cancer is a common cancer with a variable prognosis. Its management is currently guided by histological and biological markers such as the Gleason score and PSA. Developments in molecular biology are now making it possible to identify new targets for better classification of prostate cancer. Among emerging biomarker, DNA methylation, an epigenetic process, is increasingly being studied in carcinogenesis. Techniques for analyzing DNA methylation are constantly improving, and digital PCR now allows absolute methylation quantification with high sensitivity. These techniques can be performed on circulating tumor DNA. We conducted a literature review of scientific articles addressing the topic of DNA methylation in prostate cancer. This review summarizes the different genes whose methylation is involved in carcinogenesis and their clinical implications, both diagnostic and prognostic. Methylation monitoring could also be useful for the prediction of treatment response. However, most studies are retrospective, and prospective studies are needed to validate these data.

Deep learning uncovers histological patterns of YAP1/TEAD activity related to disease aggressiveness in cancer patients.

Over the last decade, Hippo signaling has emerged as a major tumor-suppressing pathway. Its dysregulation is associated with abnormal expression of YAP1 and TEAD-family genes. Recent works have highlighted the role of YAP1/TEAD activity in several cancers and its potential therapeutic implications. Therefore, identifying patients with a dysregulated Hippo pathway is key to enhancing treatment impact. Although recent studies have derived RNA-seq-based signatures, there remains a need for a reproducible and cost-effective method to measure the pathway activation. In recent years, deep learning applied to histology slides have emerged as an effective way to predict molecular information from a data modality available in clinical routine. Here, we trained models to predict YAP1/TEAD activity from H&E-stained histology slides in multiple cancers. The robustness of our approach was assessed in seven independent validation cohorts. Finally, we showed that histological markers of disease aggressiveness were associated with dysfunctional Hippo signaling.

Differentiated thyroid cancer in adolescents – does extent of disease at presentation differ with age?

Abstract Objectives The authors sought to assess whether the age of 18 reflects a true pathological inflection point that justifies transitioning between pediatric and adult paradigms of care with differentiated thyroid cancer (DTC). Methods A retrospective chart review was conducted for patients aged 12–24 undergoing hemithyroidectomy or total thyroidectomy for papillary or follicular thyroid carcinoma from 2010 to 2020. Results A total of 153 patients receiving surgery for DTC were assessed for pathological stage, nodal metastasis, and thyroid neoplasm characteristics. When comparing pathologic tumor staging of patients &lt;18 vs. ≥18 years old, there was a significant relationship between age and pT stage (p=0.009), but not between age and pN stage (p=0.319). However, when comparing patients ≤15 vs. &gt;15 years, there was a significant relationship between age and pT stage (p=0.015) and age and pN stage (p=0.016). Patients ≤15 years of age most commonly had stage pT2 tumors (48.9 %, n=22), whereas most &gt;15 years had stage pT1 tumors (37.9 %, n=41). Of patients whose lymph nodes were analyzed, patients ≤15 years were most likely to have pN1b disease (31.1 %, n=14), while patients &gt;15 years were most likely to have pN0 disease (33.3 %, n=36). Conclusions In this sample, separating children and adults at an age of 15, rather than 18, yielded more significant differences in risk of nodal involvement. Markers of invasive histology were more common in patients older than 15, while nodal involvement was more common in patients 15 and under.

Antituberculosis drug-induced hepatotoxicity: Preclinical benefit of glutamine

Background: Rifampicin/isoniazid/pyrazinamide/ethambutol (RIPE) which is the corner stone for the treatment of tuberculosis may cause hepatotoxicity. Glutamine (Gtn) is an important amino acid with potential cell-regulative and cytoprotective capabilities. Objective: This study assessed the ability of Gtn to prevent RIPE-induced hepatotoxicity in rats. Materials and Methods: Thirty adult Wistar rats (both sexes) weighing 180-220 were used. The rats were randomized into 6 groups of n=5/group and orally administered with the experimental agents daily for 30 days as follows: Groups 1-3 were administered with ([Control] normal saline, 0.2mL), Gtn (80mg/kg) and RIPE (Rifampicin 150, isoniazid/75, pyrazinamide 400 and ethambutol 275 mg/kg), respectively. Groups 4-6 were supplemented with Gtn (20mg/kg, 40mg/kg, 80mg/kg) prior to the administration of RIPE, respectively. On day 31, the rats were weighed, anesthetized and blood samples were collected and assessed for serum biochemical markers. Liver samples were weighed and examined for histology and oxidative stress markers. Results: Body weight, liver superoxide dismutase, glutathione peroxidase, catalase and glutathione levels decreased significantly (p

Analysis of Clinically Symptomatic Patients to Differentiate Inflammatory Breast Cancer from Mastitis in Asian Women.

To differentiate inflammatory breast cancer (IBC) from mastitis in Asian women presenting with symptoms of inflammation. Between January 2012 and June 2024, 101 Asian women with symptoms of inflammation underwent breast ultrasound (US). Clinical and demographic data were extracted from patients' medical records. US analysis assessed lesion bilaterality, location, type, size, internal changes, and lymph node status. Patients with suspicious findings had US-guided biopsies, and pathology reports were reviewed for tumor histology and immunohistochemical markers. Logistic regression was used to determine odds ratios. Of the 101 participants, 14 (13.9%) were diagnosed with IBC and 87 (86.1%) were diagnosed with mastitis. Patients with IBC were significantly older (46.4 vs. 38.4 years, p = 0.020) and showed a higher prevalence of postmenopausal status (57.1% vs. 12.6%, p < 0.0001). These patients experienced a longer symptom onset duration (37.7 vs. 12.7 days, p = 0.002) and more frequent localized symptoms like swelling (50.0% vs. 13.8%, p = 0.004). US findings showed that 21.4% of IBC lesions involved the entire breast, compared to only 1.1% in patients with mastitis (p = 0.001). Biopsy results revealed that invasive ductal carcinoma was the most common malignancy (78.6%). Logistic regression identified symptom onset duration (adjusted odds ratio (OR) 1.07, p = 0.014) and swelling (adjusted OR 15.24, p = 0.016) as significant predictors of IBC. In Asian women, age, menopausal status, symptom onset duration, and swelling are effective in differentiating IBC from mastitis. Logistic regression confirmed that symptom onset duration and swelling are significant predictors of IBC, with US findings indicating larger lesion sizes and more frequent whole-breast involvement.

Exploration of plasma tryptophan levels along with Ki-67 expression binomial investigation for forecasting tumor aggressiveness within invasive ductal breast cancer.

Ki-67 is a histological marker indicating cancer aggressiveness, while tryptophan (TRP) depletion modulates immune responses, including tumor aggressiveness. The study evaluates Ki-67's predictive value in relation to plasma TRP levels in invasive ductal carcinoma of breast cancer, aiming to improve understanding of tumor characteristics and clinical behavior. A study involving 165 women, measured plasma TRP levels and Ki-67 and analyzed their relationship with tumor aggressiveness markers using statistical analyses and predictive models. Our study highlighted a significant correlation between decreased plasma levels of TRP and a high mitotic index, measured by the Ki-67 marker (Pearson correlation coefficient r = -0.402; p = 0.011). Tryptophan levels below 40 µmol/L were associated with a Ki-67 level above 15%, suggesting more active tumor growth in patients. Additionally, several risk factors for BC were identified within the studied population. The demographic and clinical characteristics of the participants include an average age of 63 years, plasma glucose levels above 1.2 g/L, and plasma TRP levels below 40 µmol/L, which are associated with an increased risk of BC. Furthermore, various polynomial logistic regression models indicate that TRP levels may be predicted based on Ki-67 expression, providing a promising approach to refine prognostic assessments. The study showed a correlation between low levels of tryptophan (TRP) and a high Ki-67 mitotic index in breast cancer patients, particularly in invasive ductal carcinoma, which is strongly linked to the aggressiveness of the disease. The integration of these markers into routine practice remains a technical and economic challenge.

Challenging Diagnosis of Intestinal Tuberculosis: A Review

Intestinal tuberculosis (ITB), a subset of extrapulmonary tuberculosis (EPTB), arises from Mycobacterium tuberculosis infection, primarily affecting the ileocecal region due to its lymphatic tissue richness. Representing approximately 10% of global EPTB cases, ITB is most prevalent in regions with high tuberculosis (TB) incidence. Its nonspecific symptoms—abdominal pain, diarrhea, fever, and weight loss—pose significant diagnostic challenges and frequently overlap with conditions like Crohn’s disease (CD). This diagnostic complexity is compounded by shared clinical, endoscopic, and histological features, with misdiagnosis risking inappropriate immunosuppressive therapy that exacerbates TB progression. Diagnostic tools include endoscopy with biopsy, imaging modalities (CT, MRI, ultrasound), and molecular assays like GeneXpert for rapid detection and drug resistance assessment. While histological markers such as caseating granulomas aid differentiation, advanced molecular methods enhance diagnostic precision. Emerging technologies, including next-generation sequencing, CRISPR-based diagnostics, and artificial intelligence in imaging, show promise in addressing diagnostic gaps. However, resource-limited settings face significant barriers, relying on less sensitive conventional methods. Integrated approaches combining clinical, histopathological, and molecular evaluations are essential for accurate diagnosis and effective management. Strengthening healthcare infrastructure, expanding access to advanced diagnostics, and leveraging innovative technologies are critical for reducing ITB-related morbidity and mortality. Keywords: Intestinal tuberculosis, Diagnostic challenges, Molecular diagnostics, Artificial intelligence, GeneXpert.

Multi-center real-world data-driven web calculator for predicting outcomes in IDH-mutant gliomas: Integrating molecular subtypes and treatment modalities.

Isocitrate dehydrogenase (IDH)-mutant gliomas generally have a better prognosis than IDH-wild-type glioblastomas, and the extent of resection significantly impacts prognosis. However, there is a lack of integrated tools for predicting outcomes based on molecular subtypes and treatment modalities. This study aimed to identify factors influencing gross total resection (GTR) rates and to develop a clinical prognostic tool for IDH-mutant gliomas. We analyzed 650 patients with IDH-mutant gliomas from 3 Chinese medical centers (Shanghai, Hong Kong, and Zhengzhou). Data included age, sex, extent of resection, radiotherapy status, tumor grade, histology, and molecular markers (1p19q, TERT promoter, BRAF, EGFR, 10q). Patients were categorized based on GTR status, and a nomogram predicting 3-, 5-, and 10-year overall survival (OS) was developed using Cox proportional hazards regression and validated with time-dependent ROC and calibration plot analyses. Non-GTR was associated with diffuse astrocytoma (73.0% vs. 53.5%), 1p19q non-codeletion (67.9% vs. 48.7%), and wildtype TERT promoter (63.6% vs. 52.4%). The nomogram, incorporating age, TERT promoter status, extent of resection, grade, and radiotherapy status, demonstrated strong discriminatory ability (AUC > 0.75) and good calibration. Decision curve analysis indicated that it outperformed WHO grade-based classification in identifying high-risk patients. An online calculator was developed for clinical use (http://www.szflab.site/nomogram/). We developed and validated a nomogram and online tool that integrates molecular and clinical factors for predicting outcomes in IDH-mutant gliomas, enhancing clinical decision-making.

Chenodeoxycholic acid alleviated the cyclosporine-induced nephrotoxicity by decreasing oxidative stress and suppressing renin-angiotensin system through AT2R and ACE2 mRNA upregulation in rats.

Oxidative stress, inflammation and renin-angiotensin system (RAS) activation play an important role in the nephrotoxicity which is caused by the long-term use of the immunosuppressive drug cyclosporine (CsA). This study investigates whether chenodeoxycholic acid (CDCA), an endogenous farnesoid X receptor (FXR) agonist with antioxidant and anti-inflammatory effects, modulates CsA nephrotoxicity. CsA (25mg/kg/day; s.c.) was administered to rats for 12 days. CDCA (20mg/kg/day; i.p.) injection was started 3 days before CsA and continued for 15 days. CDCA improved renal damage and function in CsA-administered rats. Renal function markers in serum, renal histology, oxidative stress, inflammation and RAS components were determined in kidney. CDCA reduced CsA-induced renal increases in NADPH oxidase 4 and NADPH oxidase 2 mRNA expressions, oxidative stress and inflammation. CDCA elevated renal FXR, small heterodimer partner-1, hypoxia-inducible factor and vascular endothelial growth factor and nuclear factor erythroid 2-related factor mRNA expressions in CsA rats. It prevents renin angiotensin system activation by reducing angiotensin II (Ang-II) levels in serum and upregulating renal mRNA expressions of Ang II type-II receptor (AT2R) and angiotensin converting enzyme 2 (ACE2), but not AT1R and ACE in CsA rats. Our results indicate that CDCA may be a protective agent against CsA-nephrotoxicity by decreasing inflammation, oxidative stress and RAS activation via AT2R and ACE2 upregulations.

Determination of individual age and ontogenetic stages of fossil tetrapods using paleohistological methods

The determination of individual age and ontogenetic stage (juvenile, subadult, adult) of fossil vertebrates is important for the initial determination of taxonomic affiliation, as well as for further evolutionary and paleobiological interpretations. Determination of individual age and ontogenetic stage (= relative age) is carried out by various methods, including paleohistological analysis. The study of thin sections of tetrapod bones allows us to assume how many years the animal lived (skeletochronological method) and to determine the ontogenetic stage according to a set of age-related histological markers: change in the type of bone matrix and vascularization, change in the distance between growth marks, formation of the external fundamental system (EFS), formation of the inner (endosteal) and outer (periosteal) circumferential layers (OCL, ICL), occurrences of secondary remodeling – Haversian substitution and formation of trabeculae. Depending on the phylogenetic position and biological peculiarities of the study group of tetrapods, the set of age “histologic markers” may be different.

Vitamin E improves serum markers and histology in adults with metabolic dysfunction-associated steatotic liver disease: Systematic review and meta-analysis.

Multiple clinical trials have been conducted to study the potential benefits of vitamin E for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Despite available evidence, vitamin E is not widely used. This study aimed to assess the effect of vitamin E on serum markers of liver inflammation, specifically serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and histology, including resolution of metabolic dysfunction-associated steatohepatitis (MASH), in adult patients with MASLD. A systematic literature search on randomized controlled trials published in English was conducted using electronic databases. Standardized mean difference (SMD) and mean difference (MD)were used for continuous outcomes, while risk ratio (RR) was used for dichotomous outcomes, with corresponding 95% confidence interval (CI). A total of eight studies were included in the qualitative synthesis while seven studies were included in the meta-analysis. Vitamin E significantly reduced serum ALT and AST levels with SMD of -0.82 (95% CI, -1.13 to -0.51) and -0.68 (95% CI, -0.94 to -0.41), respectively. Vitamin E significantly reduced steatosis, lobular inflammation, and hepatocyte ballooning with a MD of -0.60 (95% CI, -0.83 to -0.37), -0.34 (95% CI, -0.53 to -0.16), -0.32 (95% CI, -0.53 to -0.12), and increased MASH resolution with a RR of 1.9 (95%CI, 1.20 to 3.02). However, vitamin E did not reduce fibrosis, with a MD of -0.23 (95% CI, -0.51 to 0.05). Vitamin E resulted in significant improvement in serum markers of liver inflammation and histology in patients with MASLD.