BACKGROUND AND STUDY AIMS:Celiac Disease (CD) is a systemic, immune-mediated disease triggered by dietary gluten in genetically predisposed individuals. It primarily affects the proximal small intestine and is accompanied by severe gastrointestinal and/or extra-intestinal manifestations. This study aimed to examine the frequency of clinical manifestations associated with CD, assess adherence rates to GFD and its effects on symptoms' resolution and overall improvement, and finally, to determine factors associated with disease symptom severity. PATIENTS AND METHODS:We conducted a 10-year retrospective analysis (2015-2024) of 1779 patients who presented to SRHUH with celiac disease symptoms, among whom 51 were biopsy-confirmed celiac disease cases. Data were collected from a comprehensive patient-completed questionnaire. Symptom severity was classified as Mild, Moderate, or Severe. RESULTS:Among the biopsy-confirmed CD patients, 27.5% showed severe symptoms, and 82.4% were classified as Marsh 3C. While gastrointestinal manifestations were the most prevalent, CD patients also reported dental, neurological, musculoskeletal, cardiac, and psychiatric manifestations. Female patients showed significantly higher rates of nutritional supplement use, persistent symptoms after diagnosis, complications, anemia, and deficiencies in iron and vitamin D compared to males. In contrast, growth problems were significantly more common in males. In CD women, symptom severity was associated with medication use, headaches, peripheral neuropathy, bone/joint pain, muscle cramps, quality of life, and psychological state. Histologic severity (partial vs total villous atrophy) and anemia were not associated with symptom severity. CONCLUSION:In this Lebanese tertiary-care cohort, CD predominantly affected adult females, with high rates of malabsorption-related complications and extra-intestinal complaints. Early diagnosis and dietary management may help mitigate disease progression and improve clinical outcomes.
BACKGROUND AND STUDY AIMS:Circular RNAs (circRNAs) are characterized by their covalently closed-loop configuration. They are increasingly being recognized as key modulators of tumorigenesis and cancer progression. Studies have revealed aberrant hsa_circ_0001839 expression in various cancer types. However, its effect and underlying mechanisms in gastric cancer (GC) remain unknown. Therefore, we systematically investigated the clinical importance of hsa_circ_0001839 in gastric cancer and its molecular mechanisms in disease progression. PATIENTS AND METHODS:Paired tumor specimens and histologically normal adjacent tissues were collected from 117 patients with GC who underwent curative surgery. RT-qPCR was performed to measure hsa_circ_0001839 expression in clinical samples and cell lines. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate the prognostic relevance of this circRNA. Lastly, cell transfection, CCK-8, Transwell invasion, and dual-luciferase reporter assays were performed to validate the functional effects on GC cells and regulatory interactions with target genes. RESULTS:Compared with matched non-tumor tissues, hsa_circ_0001839 expression was markedly increased in gastric cancer tissues. High hsa_circ_0001839 expression significantly correlated with larger tumor dimensions, deeper invasion depth, advanced TNM stage, and the presence of lymph node metastasis. Multivariate Cox analysis revealed that high hsa_circ_0001839 expression is an independent predictor of poor prognosis. Functionally, hsa_circ_0001839 knockdown effectively suppressed the malignant phenotypes of GC cells, significantly decreasing their proliferative, migratory, and invasive abilities. Mechanistically, hsa_circ_0001839 directly binds to the 3'-untranslated region of miR-634, thereby repressing its function. CONCLUSION:As an oncogenic circRNA, hsa_circ_0001839 is critically implicated in gastric cancer progression and unfavorable patient outcomes, underscoring its dual application as a promising prognostic biomarker and a potential therapeutic intervention target.
BACKGROUND:Children with type 1 diabetes (T1D) have an elevated risk of celiac disease (CD), but region-specific prevalence estimates for the Eastern Mediterranean Region (EMR) are inconsistent and methodologically heterogeneous. So, we conducted a systematic review and meta-analysis to obtain a pooled estimate of CD in T1D children in EMR. METHODS:A comprehensive search was conducted across three databases. Observational studies that assessed the prevalence of CD in children with diabetes (<18 years) in EMR were included. We assessed the quality of included studies with the JBI critical appraisal tool. Data extraction and assessment were guided by the PRISMA checklist. The primary outcome was pooled CD prevalence (seropositive and biopsy-confirmed). Publication bias and heterogeneity were assessed. The certainty of evidence was reported using the GRADE framework. Subgroup analysis of seropositive CD across countries in EMR and mean T1D duration. FINDINGS:We identified 15 studies (N = 4740 type 1 diabetes children) from 8 countries -namely Saudi Arabia, Jordan, Iran, Iraq, Morocco, Egypt, Turkey, Oman. Of these, 7 were cross-sectional studies, 7 were cohort studies, and only one was a case-control study. No study from the remaining countries met our inclusion criteria. Among 4740 participants, the pooled seroprevalence of CD was 13% (95% CI: 0.10-0.15, I2 = 84%) and the biopsy-confirmed pooled prevalence was 7% (95% CI: 0.05-0.09, I2 = 42%). Pooled prevalence was higher for those with longer mean duration of T1D. Higher prevalence was observed in Saudi T1DM children. Study quality was generally low to moderate, and there was no publication bias in estimates. Overall certainty of evidence was graded as moderate for CD biopsy and low for seroprevalence. CONCLUSIONS:CD prevalence in pediatric T1D in the EMR is substantially higher than population baselines, as 1 in 8 in T1DM seropositive children compared to 1 in 14 in biopsy-confirmed T1DM children. The prevalence varied across countries, supporting routine, repeated region-adapted screening.
BACKGROUND AND STUDY AIMS:Helicobacter pylori is a widespread pathogen linked to gastritis, peptic ulcers, and gastric cancer. Increasing antimicrobial resistance is making eradication more difficult. The aim is tostudy how clinical symptoms, endoscopic and histopathological findings, bacterial density, and antimicrobial resistance patterns of H. pylori are related in Egyptian patients. PATIENTS AND METHODS:In our study, 100 treatment-naïve patients with gastrointestinal symptoms suggestive of H. pylori infection and positive stool antigen tests underwent endoscopy, gastric biopsy, histopathology, and culture with antimicrobial susceptibility testing. All patients received 14-day levofloxacin-based triple therapy. Treatment response was assessed clinically and by stool antigen testing.. RESULTS:Epigastric pain was the most common symptom, reported by 83% of patients, followed by nausea and vomiting in 58%. Weight loss and pallor were less frequent, at 24% and 18%, respectively. Abnormal upper gastrointestinal endoscopy findings were present in 97% of patients, with 53% showing erosive or ulcerative lesions, indicating significant mucosal involvement. Higher H. pylori bacterial density was associated with gastric ulcers, erosions, mucosal atrophy, and duodenal lesions (p < 0.001). Higher bacterial density was significantly associated with severe mucosal lesions and increased the risk of ulcerative disease, resulting in more severe epigastric pain and gastrointestinal bleeding. Histopathology revealed chronic inflammation in 95% of patients and active inflammation in 80%, indicating ongoing mucosal activity. Treatment failed in 43% of cases and was closely associated with higher bacterial density, confirming the impact of bacterial load on treatment outcomes. Antimicrobial testing showed high resistance to common first-line drugs, including amoxicillin (53.5%), clarithromycin (46.5%), and amoxicillin-clavulanic acid (50.7%). In contrast, meropenem, doxycycline, and rifampicin showed no detected resistance, indicating potential utility against infections with resistance. CONCLUSION:Bacterial density is an important predictor of mucosal damage and treatment failure. The high rate of resistance to standard first-line antibiotics highlights the need for new treatment strategies and region-specific guidelines.
BACKGROUND AND STUDY AIMS:To establish a quantitative and viable-nonviable differentiation system for Helicobacter pylori (Hp) in gastric mucosal biopsy specimens using fluorescence rapid on-site evaluation (F-ROSE), to determine the minimum bacterial count threshold for histopathological positivity, to reveal the bacterial load mechanism underlying the high specificity, low sensitivity, and high false-negative rate of traditional histopathology, and to provide an objective basis for real-time quantitative diagnosis and precise stratification of Hp infection under endoscopy. PATIENTS AND METHODS:A total of 160 gastroscopic biopsy specimens were enrolled and simultaneously examined by F-ROSE quantitative assay and traditional histopathological staining. F-ROSE used acridine orange-ethidium bromide (AO-EB) dual staining to count total, viable, and nonviable bacteria under ×400 high-power field (HPF). Histopathological results were interpreted in a double-blind manner. No traditional gold standard was set; the latent true infection status was inferred by latent class analysis (LCA) combined with Bayesian model, based on which diagnostic efficacy was calculated and the critical bacterial count for histopathological positivity was determined. RESULTS:A total of 102 true positive and 58 true negative cases were inferred. The positive rate of F-ROSE (61.25%) was significantly higher than that of histopathology (41.88%, P < 0.001). Using true infection status as the reference, F-ROSE showed a sensitivity of 94.1%, specificity of 93.1%, and AUC of 0.943; histopathology showed a sensitivity of 65.7%, specificity of 89.7%, and AUC of 0.782. The mean total bacterial count in F-ROSE was (42.6 ± 9.3)/HPF in histopathologically positive specimens, significantly higher than that in true-positive but histopathologically negative specimens (P < 0.001). A total bacterial count ≥22/HPF was the critical value for histopathological positivity, below which the histopathological positive rate was only 9.3%. Traditional histopathology could not distinguish viable from nonviable bacteria and its positivity was related only to total bacterial count, not to bacterial viability. Patients with a viable bacterial ratio > 60% had significantly more severe dyspeptic symptoms. CONCLUSION:Traditional histopathology has high specificity but low sensitivity; it reliably detects Hp only at a bacterial load ≥22/HPF and misses most low-level infections, while being unable to differentiate viable and nonviable bacteria. F-ROSE enables real-time quantification, viability differentiation, and detection of low-level infection, showing promising preliminary diagnostic performance in this single-center Phase I study. These findings require validation in larger multicenter trials with independent reference standards before clinical implementation.
BACKGROUND AND STUDY AIMS:This work was designed to assess the impact of modified WuMei decoction (MWMD) combined with Bifidobacterium triple viable (BTV) enteric-coated capsules on patients following endoscopic resection of colonic polyps. PATIENTS AND METHODS:This study enrolled 80 patients with colonic polyps and divided them into a control group and an observation group. Both groups underwent endoscopic polypectomy. The control group received BTV enteric-coated capsules, while the observation group received both BTV enteric-coated capsules and MWMD. Baseline characteristics, postoperative recurrence rates, clinical efficacy, traditional Chinese medicine (TCM) syndrome scores, intestinal microbiota, serum inflammatory cytokines, gastrointestinal quality of life index (GLQI), intestinal mucosa repair, and postoperative complications were compared. RESULTS:Baseline characteristics were similar between the two groups (P > 0.05). At 12 months postoperatively, the observation group demonstrated a lower recurrence rate (P < 0.01) and superior clinical outcomes (P < 0.01). After treatment, TCM symptom scores in this group showed significant improvement (P < 0.05), with a notable reduction in Escherichia coli levels (P < 0.01) and a substantial increase in Bifidobacterium and Lactobacillus counts (P < 0.01). The observation group also exhibited higher GLQI scores (P < 0.01), substantially reduced serum inflammatory markers (P < 0.05, P < 0.01), better intestinal mucosal healing (P < 0.01), and a lower incidence of postoperative complications (P < 0.05). CONCLUSION:The combination of MWMD and BTV demonstrated good clinical efficacy in patients undergoing endoscopic resection of colonic polyps, promoting intestinal mucosal repair and reducing postoperative complications.
BACKGROUND AND STUDY AIMS:Discrepancies between endoscopic and histological diagnoses occasionally occur after colorectal polypectomy. This study aimed to evaluate the diagnostic impact of additional histological sections on serrated polyps. PATIENTS AND METHODS:We conducted a retrospective cross-sectional study of resected colorectal polyps between June 2023 and August 2023. Polyps that were endoscopically suspected to be sessile serrated lesions (SSLs) or hyperplastic polyps and resected en bloc were included. Lesions initially diagnosed as normal mucosa were subjected to deeper sectioning and histopathological re-evaluation. Clinicopathological and endoscopic features, including endoscopic SSL diagnosis score, were analysed. RESULTS:Among the 276 eligible lesions, 117 were initially diagnosed as normal mucosa. Deeper sectioning corrected the histopathological diagnosis in 50% of these cases, identifying 5 SSLs and 53 hyperplastic polyps. The lesions reclassified in deeper sections were significantly smaller than those diagnosed in the first sections (P < 0.001). Compared with the "normal mucosa by first and deeper sections" group, the "SSL by deeper section" group showed significantly higher SSL diagnosis scores, including features such as larger size, mucus cap, and indistinct borders (P < 0.01). CONCLUSIONS:Additional histological sectioning significantly improved the diagnostic yield for serrated polyps initially diagnosed as normal mucosa, particularly in small lesions. This effect was most evident in lesions that were ultimately classified as hyperplastic polyps. Endoscopic features suggestive of SSLs were also associated with upgraded diagnoses, although the number of SSL cases was limited.
BACKGROUND AND STUDY AIMS:Non-invasive scores such as APRI, FIB-4, GPR and ALBI are commonly used to evaluate liver fibrosis and functional reserve in patients with chronic hepatitis B (CHB). However, interpretation has predominantly focused on single-time measurements, and the prognostic value of short-term changes (delta scores) remains uncertain. This study evaluated whether one-year changes in these scores are associated with laboratory-based composite deterioration during routine follow-up of CHB patients. PATIENTS AND METHODS:This retrospective cohort included adult CHB patients with two laboratory assessments approximately 12 months apart. APRI, FIB-4, GPR and ALBI were calculated at baseline (T₀) and follow-up (T₁); delta values were defined as ΔScore = T₁ - T₀. Laboratory-based composite deterioration was defined as meeting ≥1 criterion based on albumin, total bilirubin, INR, or platelet count. Logistic regression models, adjusted for age, gender, HBV-DNA level, HBeAg status, and antiviral therapy assessed associations between delta scores and deterioration. ROC analysis evaluated discriminative performance. RESULTS:A total of 297 patients were included (56.9% male; median age 45 years). Laboratory-based composite deterioration occurred in 23.6%. Baseline non-invasive scores were not associated with deterioration, while ΔAPRI, ΔFIB-4 and ΔGPR were significant predictors. In multivariable analyses, each 0.1-unit increase corresponded to higher risk: ΔAPRI (aOR 1.55; p = 0.004), ΔFIB-4 (aOR 1.29; p < 0.001) and ΔGPR (aOR 1.86; p = 0.001). When standardized, ΔFIB-4 demonstrated the strongest association (aOR 7.32 per 1-SD increase). ΔFIB-4 also showed the best discrimination (AUC 0.730). CONCLUSION:One-year dynamic changes in non-invasive scores, particularly ΔFIB-4, provide additional and clinically relevant prognostic information for identifying early deterioration during routine follow-up. Incorporating delta score monitoring into clinical practice may help to detect laboratory-based deterioration at an earlier stage.
Liver disease is among the most common medical conditions in the world, leading to high rates of morbidity and death. Early identification of liver diseases enables prompt care, which may prevent many conditions from progressing to more serious stages, like cirrhosis or liver cancer. Traditionally, models often overlook the predictive importance of nutritional status and focus primarily on liver-specific measures. This research aims to propose a machine learning (ML) approach to predict surgical complications in patients with liver cirrhosis by integrating existing liver function metrics with a comprehensive nutritional risk assessment. In this study, we used the MIMIC-IV dataset, which consists of patient medical records. We utilized a 504-patient cohort with features such as age, gender, bilirubin, albumin, INR (International Normalized Ratio), Child-Pugh score, MELD score (Model for End-Stage Liver Disease), NRS (Nutritional Risk Screening), complication, and composite risk. Mortality was used as the primary outcome variable for prediction. ML models were utilized for training, along with correlation analysis and Explainable Artificial Intelligence (XAI) approaches like SHAP and LIME to interpret the model. The stackable ensemble model was employed to enhance the model's performance and robustness. The proposed model achieved an accuracy of 94% and an AUC of 0.97. This methodology emphasizes the critical importance of nutritional assessment in surgical risk classification. It offers a clinically relevant framework to guide preparatory strategies, promote collaborative decision-making, and improve perioperative care pathways for this vulnerable population.
BACKGROUND AND STUDY AIMS:An integrated screening program with fast-track access to care for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), and Syphilis were implemented in substance use treatment clinic at Cairo University hospitals, Egypt. This study aimed to assess seroprevalence rates of HIV, HBV, HCV, and Syphilis among drug users and evaluate their awareness and uptake of prevention and testing services. PATIENTS AND METHODS:A total of 2545 drug users were screened for HIV, HCV, Treponema pallidum (TP) antibodies, and surface antigen of HBV (HBsAg) between September 2022 and January 2024. Additionally, data on knowledge related to testing and prevention services were collected from 1066 drug users. RESULTS:Seroprevalence rates of HIV, HCV, HBsAg, and Syphilis were 4.4%, 8%, 1.34% and 0.1%, respectively. Among the 1066 drug users interviewed regarding their awareness and uptake of prevention and testing services, only 10 (1%) participants were tested for HCV during the previous nationwide screening campaign; three of them tested positive and two received treatment. Five (0.5%) participants were previously tested for HIV and were negative. Only 3 (0.3%) participants had heard of Pre-exposure prophylaxis (PrEP), while 5 (0.5%) received an HBV vaccination. No participants have ever received free condoms, clean needles or methadone maintenance therapy. CONCLUSIONS:Our findings indicate the need for improved testing, treatment, and prevention services directed to drug users, coupled with focused awareness efforts to increase access to these services.
Ectopic splenic autotransplantation (ESAT) refers to the presence of splenic parenchyma outside its normal anatomical location, most commonly resulting from autotransplantation following splenic trauma or splenectomy. Although often asymptomatic and discovered incidentally, it can clinically mimic gastrointestinal stromal tumors or other submucosal lesions, posing diagnostic challenges and potentially leading to unnecessary surgical resection.This article presents a case of a submucosal mass in the gastric fundus discovered via gastroscopy. The patient underwent endoscopic full-thickness resection (EFTR) and was ultimately diagnosed with ectopic splenic tissue in the gastric fundus. To our knowledge, this represents only the second reported case of gastric splenosis treated with EFTR. And then we conduct a literature review of PubMed-indexed MEDLINE articles published between May 1969 and January 2025 on gastric ESAT, and summarize its clinical characteristics to facilitate preoperative diagnosis and prevent unnecessary surgical interventions.
Gastrointestinal (GI) neoplasms are among the most common and lethal tumors around the world. In spite of the introduction of multiple conventional therapeutics for GI tumors, the treatment of these cancers is challenging. Moreover, they are able to mediate resistance to therapeutics. Therefore, the novel therapeutics should be developed for the treatment of GI tumors based on the underlying mechanisms. Autophagy is a programmed cell death mechanism dysregulated in human cancers and it is a potential therapeutic target. In the current review, a special focus is placed on the role of autophagy in GI neoplasms. The current studies have highlighted the fact that genomic and epigenetic factors can participate in the regulation of autophagy in GI tumors. Autophagy can exert protective function to enhance survival of cancer cells, while it decreases apoptosis, ferroptosis and other cell death mechanisms. On the other hand, the pro-death autophagy impairs the progression of GI tumors. In order to regulate autophagy in GI tumor therapy, the studies have focused on the development of drugs (synthetic drugs and natural compounds) along with nanoparticles for the autophagy modulation in GI cancer therapy. The autophagy-related factors can be considered as prognostic and diagnostic factors in GI tumors.
BACKGROUND AND STUDY AIMS:Technical challenges posed by endoscopic retrograde cholangiopancreatography (ERCP) in obese patients are often reflected in longer fluoroscopy and procedure times, which could impact the outcomes of ERCP. This study aims to explore how obesity influences the outcomes of ERCP. PATIENTS AND METHODS:Medical records of patients with a naïve papilla who underwent ERCP between 2021 and 2024 were retrospectively reviewed. Patients were classified into two groups based on body mass index (BMI): non-obese (BMI < 30) and obese (BMI ≥ 30). A 1:1 propensity score matching was performed regarding age, sex, comorbidities, indication, papilla morphology, and cannulation technique. Adverse events, cannulation time and success, and stone clearance were compared between the groups. RESULTS:Of the total 1351 patients, 294 patients were finally included (147 in each group). In the full cohort, procedure stop due to sedation-related adverse events occurred more frequently in the obese group (6.9% vs. 3.3%, p-value = 0.028). In the matched cohort, there was no significant difference in the rate of post-ERCP pancreatitis in obese and non-obese groups (10.2% vs. 17.7%, p-value = 0.06). Stone clearance was achieved in 82.8% and 73.3% of obese and non-obese groups, respectively (p-value = 0.12). There was no significant difference between the groups regarding cannulation time and success (p-value>0.05). Multivariate analysis revealed that BMI was not associated with either PEP (odds ratio = 0.94, 95% confidence interval: 0.87-1.01) or stone clearance success (odds ratio = 0.95, 95% confidence interval: 0.91-1.03). CONCLUSIONS:Obesity does not appear to be associated with cannulation challenges, procedure success, and post-ERCP adverse events, although sedation-related adverse events occur more frequently in these patients. However, given the limited sample size, the study may be underpowered to detect modest effects, particularly in patients with BMI ≥35 kg/m2.
BACKGROUND AND STUDY AIMS:Although benzodiazepines and opioids are commonly used during endoscopy, there is no consensus on an optimal sedation method. However, more physicians prefer propofol for its favored anesthetic properties. This study aimed to compare the sedation regimens used during endoscopy among gastroenterologists in the private and public sectors in Jordan. PATIENTS AND METHODS:A seven-section survey comprising 47 questions was designed to assess sedation practices during esophago-gastro-duodenoscopy (EGD), colonoscopy, and endoscopic retrograde cholangiopancreatography (ERCP) and was distributed among Jordanian gastroenterologists. RESULTS:Of 125 gastroenterologists, 113 (90%) participated in this study. Sedation was used less frequently in the public vs. private sector for EGD (47.4% vs. 94.6%, respectively) and colonoscopy (76.3% vs. 97.3%, respectively). However, all patients who underwent ERCP received sedation in both health sectors. Propofol was used at a lower rate in the public sector than in the private sector (44.7% vs. 77.3%, respectively, P < 0.001). Although 31% of gastroenterologists lacked formal sedation training, 93% supported national sedation guidelines. CONCLUSIONS:In Jordan, sedation methods used during gastrointestinal endoscopy differ between the public and private sector. Private sector gastroenterologists are more likely to collaborate with anesthesiologists to administer deep sedation and are more satisfied with their sedation regimens than those in the public sector. Standardized protocols and international guidelines are necessary to enhance patient safety and procedural quality.
Objective To identify the key genes differentially expressed across the gastritis-GC spectrum based on multi-stage gastric mucosal samples. Method Five datasets associated with gastric mucosal carcinogenesis were obtained from the GEO database. DEGs between gastritis and GC were first determined. Four ML models, including LASSO, random Forest, SVM-RFE, and Boruta, were used to screen out DEGs. DCA and ROC analyses were performed to identify the highest discriminative potential model, followed by the identification of hub genes within the highest discriminative potential model. The expression pattern across the gastritis-GC spectrum and the potential pathways of hub genes were then explored. Their expression and prognosis differences in GC were then validated using TCGA data, followed by drug sensitivity assessment. RT-PCR, CCK-8, and transwell assays were used to detect the gene expression, cell viability, invasion, and migration. Result Among 4 ML models, LASSO with 20 genes was the highest discriminative potential model to distinguish the gastritis from GC. After importance ranking on 20 genes, LILRA4 and IGF2BP3 were identified as the most important DEGs. Their expressions exhibited an upward trend within the gastritis-GC spectrum. A series of regression analyses, such as ordinal regression, trend regression, and GAM, all confirmed that their expression was significantly higher in GC compared to gastritis. Pathway analysis revealed that they were involved in metabolism and autophagy. LILRA4 was associated with GC status and negatively correlated with drug sensitivity. LILRA4 or IGF2BP3 overexpression promoted GC cell viability, invasion, and migration. Conclusion LILRA4 and IGF2BP3 may be associated genes differentially expressed across the gastritis-GC spectrum. They may have the potential to screen high-risk groups for GC in patients with gastritis.
Vibration-controlled transient elastography (VCTE)-based liver stiffness measurement (LSM) is widely used for non-invasive assessment of liver fibrosis and portal hypertension in chronic liver disease. In daily practice, LSM values are often interpreted using etiology-specific fibrosis cut-offs embedded in device software. However, an increasing proportion of patients now present with mixed liver disease etiologies, particularly combinations of metabolic-associated steatotic liver disease (MASLD) with viral or alcohol-related liver disease. In such patients, applying singleetiology cut-offs may lead to misclassification of fibrosis stage and portal hypertension risk. We highlight the limitations of this approach and argue that LSM should be interpreted within a broader clinical context, integrating platelet count, biochemical markers, and validated risk-stratification algorithms rather than relying solely on fibrosis staging tables.
BACKGROUND:Hepatocellular carcinoma (HCC) incidence continues to rise globally, with treatment efficacy constrained by the tumor microenvironment's high heterogeneity and challenges in early diagnosis. Heme metabolism plays a crucial role in tumor progression, yet its specific function in the development of early-stage HCC remains poorly understood. METHODS:This study comprehensively employed univariate and multivariate Cox regression and least absolute shrinkage and selection operator regression models to systematically identify heme metabolism-related genes (HMRGs) significantly associated with early HCC prognosis. Key diagnostic biomarkers were further identified through Support Vector Machine Recursive Feature Elimination and Extreme Gradient Boosting algorithms. Immune microenvironment characteristics were comprehensively analyzed across different prognostic subgroups based on immune infiltration assessment. Additionally, consensus clustering methods revealed molecular subtyping with distinct prognostic features in early-stage HCC. RESULTS:This study identified four key HMRGs as diagnostic genes for early-stage HCC and constructed a robust diagnostic model based on these findings. Additionally, six HMRGs significantly associated with prognosis were screened. Immune infiltration analysis revealed higher Tregs infiltration and lower NK cells infiltration in the high-risk group. Furthermore, consensus clustering analysis divided early-stage HCC into two molecularly heterogeneous subtypes. CONCLUSION:By systematically analyzing the molecular functions and immune profiles of HMRGs in early-stage HCC, this study contributes to a deeper understanding of its underlying pathology and lays the groundwork for more tailored treatment strategies.
Background and study aims Cystic fibrosis-associated liver disease (CFLD) is a leading cause of mortality. There is no specific test for CFLD diagnosis. Elastography is a noninvasive imaging method for assessing chronic liver disease. We aim in this work to assess the degree of liver stiffness in children with CF using transient elastography (TE). Patients and Methods This cross-sectional study involved 50 children with CF during their outpatient care and 25 healthy children as a control group. Recruitment started in December 2020 until January 2021 because of the COVID-19 pandemic, then resumed from June 2021 till June 2022. The study included a clinical picture, biochemical analysis, and liver stiffness measurement (LSM) using TE (FibroScan). Results Abnormal elastography was reported in 8% of CF children. Mean liver stiffness (LS) byTE was non significantly higher among CF cases when compared with controls (Mean ± SD: 4.9 ± 3.86 Kpa vs 3.85 ± 0.64 Kpa) (P = 0.326). LSM significantly positively correlated with age (r = 0.409; p = 0.003). AST to platelet ratio index (APRI) was significantly higher among patients with CF than control (P < 0.001). Cystic fibrosis liver disease (CFLD) was diagnosed in 8/50 patients (4%). Conclusion Transient elastography can be used to assess liver diseases in patients with CF. AST and ALT do not correlate with LSM.
Helicobacter pylori is a gram-negative bacterium infecting >50% of the world's population and is endemic in Pakistan, however reports on asymptomatic individuals are limited. The present study investigated the prevalence and associated risk factors of H. pylori infection in asymptomatic humans of Khyber Pakhtunkhwa Province in Pakistan, and an overview of previous records in Pakistan. Asymptomatic individuals (n = 600) of age ranges 12-75 years were interviewed using a structured questionnaire, and blood samples were taken for serological assay. The overall prevalence of H. pylori infection was 45% (270/600), significantly higher in males (157, 58%) than females (113, 42%) (P = 0.0003), and peaked in the 31-50 year's (145, 54%), with lowest prevalence in 11-30 year's age group (43, 16%) (P = 0.0001). Marital status was significantly correlated with the infection (P = 0.0001). Higher prevalence was observed in the lower socioeconomic class (170, 63%) compared to middle (90, 33%) and upperclass (10, 4%) (P = 0.0112). Risk was high in tap water (120, 44%) and well water drinkers (105, 39%) (P < 0.0001). A non-significant association of infection was observed among the smokers (75, 28%) and non-smokers (195, 72%) (P = 0.7608). Awareness level and education showed strong association, with infection higher in illiterates (143, 53%) and the lowest prevalence was found in individuals with higher education (23, 9%) (P < 0.0001). Spatially, the infection was high in Swat (55, 20%), followed by Upper Dir, Lower Dir, and Buner (each 34, 13%), Malakand and Shangla (26, 10%), and Chitral (21, 8%) (P < 0.05). Nationally, reported prevalence varies widely from <10% in selected groups to >80% in high-risk cohorts, with high infection rates in Karachi, Quetta, Peshawar, Islamabad, and Abbottabad. Serological assays are frequently used; however, histopathology, stool antigen test, and^13C-urea breath tests are sensitive and accurate for confirming active infection across Pakistan. Preventive measures on an urgent basis should be taken by the health authorities to diagnose and treat the infection at a very early stage.
Hepatocellular carcinoma (HCC), a leading cause of death worldwide, is primarily caused by uncontrolled cellular proliferation, invasion and metastasis leading to tumor development in the liver. miR-195 regulates G1 to S phase transition in the cell cycle by targeting CDK6. In the current study, expression of miR-195 was significantly reduced while that of CDK6 was upregulated in HCC patients. The results of expression analysis were supported by the Pearson correlation coefficient indicating a moderate negative (r = -0.459, p = 0.02) relation between miR-195 and CDK6. However, the association of miR-195 and CDK6 with age and sex was not statistically significant. The predicted secondary and tertiary structures of miR-195 showed the presence of loops, stems, and flanking regions. Further, in silico analysis identified potential amino acid residues in CDK6, CDK4 and Cyclin D1 proteins interacting with the miR-195. We designed a mimic RNA of miR-195 by mutagenesis at 4 points. The mimic RNA_3 of miR-195 presented a well-defined stable structure showing strong binding interactions with CDK4 and Cyclin D1 and comparable interactions with CDK6. In conclusion, our study has demonstrated the potential of using miR-195 mimic RNA as a therapeutic strategy to target the CDK6 gene in HCC with reduced miR-195 expression.
