Medicine and Pharmacology

Abstract: Background/Objectives: Hepatocellular carcinoma ³10 cm has a poor prognosis after surgical resection, largely because of extrahepatic recurrence. Neoadjuvant systemic therapy may improve long-term outcomes. We evaluated neoadjuvant systemic therapy followed by hepatectomy versus upfront surgery for large hepatocellular carcinoma. Methods: We retrospectively analyzed the data of 38 consecutive patients with hepatocellular carcinoma ³10 cm who underwent hepatectomy between April 2011 and October 2025. The patients were divided into neoadjuvant systemic therapy (n = 17; atezolizumab plus bevacizumab, n = 8; lenvatinib, n = 9) and upfront surgery (n = 21) groups. Clinicopathological features, perioperative outcomes, recurrence-free survival, and overall survival were compared. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and modified RECIST. Results: Baseline characteristics were summarized. Perioperative outcomes, including blood loss, operative time, and morbidity, were similar. The systemic therapy group showed higher 5-year recurrence-free survival (45.2% vs. 16.1%, p = 0.016) and overall survival (75.8% vs. 30.6%, p = 0.037) rates than the upfront surgery group. Overall recurrence was lower in the systemic therapy group (35.3% vs. 90.5%, p < 0.001). Extrahepatic recurrence alone occurred in 42.9% of upfront surgery patients versus none in the systemic therapy group. Descriptive analyses suggested differences in tumor marker and radiological responses between the Atezolizumab plus bevacizumab and lenvatinib subgroups, while overall oncological outcomes were comparable. Liver function remained within acceptable ranges during systemic therapy. Conclusions: Neoadjuvant systemic therapy followed by hepatectomy for hepatocellular carcinoma ≥10 cm was associated with favorable recurrence and survival outcomes compared with historical upfront surgery cases, without an apparent increase in perioperative risk.

Abstract: Background: Exposure to damp and water-damaged buildings is associated with well-established respiratory and allergic health effects, and exposed individuals frequently report symptoms across multiple additional systems. Illness persisting after such exposure is widely attributed to retained mycotoxins and treated with oral binders. Urine mycotoxin panels, routinely ordered in functional and integrative practice to support that attribution, cannot distinguish building exposure from ordinary dietary intake. The clinical response to binders, meanwhile, has never been controlled for the bile acid-modulating properties those agents share. Hypothesis: Bile acid malabsorption (BAM) — identified in 28.1% of patients meeting criteria for diarrhea-predominant irritable bowel syndrome (IBS-D) at a seven-day SeHCAT retention threshold below 10%, independently corroborated at 30% by a second meta-analysis at the same threshold, and substantially underdiagnosed in the United States — may explain a clinically important subset of binder responses in this population, particularly among patients with chronic diarrhea following damp-building exposure. The argument advanced here does not require that damp-building exposure cause BAM. It requires only that BAM be present in this population at the base rate observed in any group selected for chronic diarrhea, that it go unscreened, and that agents which treat it be prescribed under a different rationale. Multiple binder types used in this population — including bile acid sequestrants, activated charcoal, and probiotics — share documented bile acid-modulating properties. What has been interpreted as “biotoxin binding” may be substantially or entirely explained by bile acid sequestration and modulation of the bile acid pool. Implications: If confirmed, this hypothesis would redirect clinical attention from unvalidated mycotoxin testing toward a diagnosable, treatable gastrointestinal condition. It would also offer a parsimonious explanation for treatment response patterns — including rapid onset and variable efficacy — that the mycotoxin-binding model does not adequately explain; the discontinuation-relapse pattern sometimes cited for this population is more equivocal, for reasons discussed in Section 7.

Abstract: Background/Objectives: Gastric cancer (GC) is one of the most prevalent malignancies worldwide, highlighting the need for minimally invasive and highly accurate screening methods for its early detection. We evaluated the utility of salivary polyamine-based metabolomic analysis for distinguishing individuals with GC from those without GC. Methods: A total of 53 patients with GC and 37 non-GC controls were included. Participants were recruited from individuals who underwent upper gastrointestinal endoscopy at Tokyo Medical University Hospital between March 2020 and May 2025 and provided saliva samples on the same day. Participants with factors known to affect polyamine levels were excluded. Salivary metabolites quantified by liquid chromatography–mass spectrometry were statistically compared between groups. Acetylated-to-non-acetylated polyamine ratios were used as features to construct a logistic regression-based machine learning model, and discriminative performance was evaluated using receiver operating characteristic analysis. Results: The GC group showed significantly higher concentrations of salivary metabolites. Among individual polyamines, N¹-acetylspermine demonstrated the highest discriminative ability (AUC = 0.845). When acetylated-to-non-acetylated polyamine ratios were analyzed, significant differences between groups were observed for N¹,N⁸-diacetylspermidine/spermidine and N¹-acetylspermine/spermine. A logistic regression model constructed using six such ratios achieved strong predictive performance in the test dataset (AUC = 0.807), with a sensitivity of 81.3% and a specificity of 72.7%. Notably, these ratios outperformed conventional tumor markers such as carcinoembryonic antigen and carbohydrate antigen 19-9, in sensitivity. Conclusions: Our results demonstrate that salivary polyamine analysis, particularly using acetylation ratios, enables accurate and minimally invasive detection of GC and represents a promising adjunctive tool for GC screening.

Abstract: This paper examines the inferential framework used to attribute the positive association between acid-suppressive therapy (AS) and esophageal adenocarcinoma (EAC) to confounding by gastroesophageal reflux disease (GERD), a common indication for AS. The experimental literature has proposed several hypotheses by which AS may increase EAC risk, and reviews of the in vivo literature have suggested that the AS--EAC association may be causal. At the same time, clinical guidelines maintain that the AS--EAC association likely reflects confounding by GERD and cite the findings of decades-old observational studies that either estimate the AS--EAC association among those without reflux-related indications or estimate a common treatment OR after adjusting for the presence of GERD as a main-effect covariate. This paper first examines the causal hypotheses described in the in vivo literature and establishes that the patient's underlying reflux burden is a presupposed effect modifier under each of these hypotheses. It then argues that the epidemiologic findings presented to clinicians as reassuring evidence against causality do not distinguish confounding by GERD from any of these hypotheses.

Abstract: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare and highly aggressive primary liver cancer. It is distinguished by the unequivocal coexistence of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) components within a single tumor. cHCC-CCA accounts for between 0.4% and 14.2% of primary liver cancers, presenting a complex clinical and pathological challenge because of its dual histological morphology and phenotypic diversity. In the past, its classification faced significant diagnostic challenges. However, these issues have been largely addressed by the 2019 World Health Organization 5th Edition reclassification, which requires clear differentiation of hepatocytic and cholangiocytic features using hematoxylin and eosin (H&E) staining. Recent genomic profiling has shown that cHCC-CCA exists on a molecular spectrum, with about 75% of individual tumors being HCC-like or CCA-like. Biliary-dominant subtypes, similar to CCA, often contain actionable alterations like FGFR2 fusions, IDH1 mutations, and HER2 amplification, providing significant opportunities for precision oncology. In contrast, subtypes resembling HCC are commonly driven by mutations in TP53 and the TERT promoter. Major hepatectomy combined with regional lymphadenectomy continues to be a fundamental curative treatment. However, liver transplantation is increasingly being recognized as a viable option for carefully selected patients with early-stage cirrhosis. In the advanced or recurrent stage, the traditional first-line treatment continues to be cytotoxic gemcitabine combined with platinum-based therapies. Meanwhile, combinations involving immune checkpoint inhibitors, like atezolizumab and bevacizumab, or more complex regimens that integrate locoregional therapy, TKIs, and PD-(L)1 inhibitors, offer hopeful prospects for improving survival rates. This optimism is supported by research indicating that 57% of tumors exhibit a high immune microenvironment. This review provided an overview of the current knowledge of the clinical classification, risk stratification, histogenesis, molecular biology and clinical management of cHCC-CCA to inform current multidisciplinary management approaches and outline future paths in precision oncology.

Abstract: Background/Objectives: Contemporary data on active Helicobacter pylori infection among young adults in Albania are limited. This study estimated Urea Breath Test (UBT)-detected prevalence among university students and described awareness, self-reported knowledge, gastrointestinal symptoms, and previous healthcare engagement. Methods: A cross-sectional study during 2023–2025 combined questionnaire data and interpretable UBT results from 390 consenting students aged ≥18 years in academic years I–IV in Korçë, Albania. The questionnaire underwent cultural adaptation, expert assessment, and pilot testing. Prevalence was reported with a Wilson 95% confidence interval (CI); questionnaire percentages used item-specific valid-response denominators. Results: UBT was positive in 107/390 students, giving a prevalence of 27.4% (95% CI 23.2–32.1%). Women comprised 321/390 (82.3%) participants. Overall, 209/385 (54.3%) had heard of H. pylori, 155/353 (43.9%) reported knowing associated diseases, and 152/363 (41.9%) reported knowing a transmission mode. School and health professionals were the leading reported information sources. Previous testing was reported by 21/388 (5.4%), stomach problems by 77/377 (20.4%), and gastric ulcer by 6/369 (1.6%). The highest proportions of moderate-or-greater symptoms involved bloating sensation (54/378, 14.3%), abdominal distension (54/380, 14.2%), and general abdominal complaints (49/382, 12.8%). Among six previously treated respondents with complete follow-up information, none reported post-treatment retesting. Extreme-case sensitivity estimates among 420 consenting students ranged from 25.5% to 32.6%. Conclusions: Approximately one in four tested students had evidence of current H. pylori infection, while self-reported knowledge and previous testing were limited. The findings support targeted university health education, access to clinically appropriate testing, and continuity through treatment and confirmation of eradication. Representative studies are needed before extrapolating to the broader population or adopting universal student screening.

Abstract: Introduction Aspirin initially recognized for its anti-inflammatory, antipyretic and analgesic properties hold a prominent role in the treatment of cardiovascular disease. Cyclooxygenase, COX, 1 and 2 activity in cirrhotic liver disease has been studied by several groups and stratified into COX dependent and independent mechanisms. COX2 gene expression has been identified to be significantly increased in cirrhotic liver disease and various other states of chronic hepatic inflammation. Our study investigates the relationship of aspirin use, an established COX inhibitor, and outcomes in patients hospitalized with ascitic cirrhosis. Methodology The National Inpatient Sample, NIS, database from 2017 to 2022 was analyzed for patients age >18 who were hospitalized for ascitic cirrhosis and its decompensations using ICD-10 diagnostic codes. These patients were further partitioned based on their use of aspirin. The principal outcome of this investigation is in-hospital mortality, with secondary outcomes including odds of portal vein thrombosis, septic shock, ICU admission and acute kidney injury. Secondary outcomes also included the odds of developing hepatic decompensations including need for EGD, hepatorenal syndrome, spontaneous bacterial peritonitis, SBP, developing HCC with and without pulmonary metastasis and of undergoing a transjugular intrahepatic portosystemic shunt, TIPS, procedure. Multivariate logistic regression was applied to the outcomes, and the Charlson Comorbidity Index was used to adjust for confounders. A p-value (pv) of <0.05 was considered statistically significant. Results In our analysis of the NIS, 568,990 patients were identified with ascitic cirrhosis and 11.7% (66,572) of this population were identified to use aspirin. Aspirin use was identified to have a significantly reduced odds of in-patient mortality (adjusted odds ratio) [aOR] 0.540, p value <0.001 95% CI (confidence interval): 0.461 – 0.631. Patients with aspirin use demonstrated significantly reduced odds of portal vein thrombosis, septic shock, ICU admission, and acute kidney injury. Those with ascitic cirrhosis and aspirin use also conveyed reduced odds of developing hepatocellular carcinoma, pulmonary metastasis and hepatic decompensations including hepatorenal syndrome and of undergoing TIPS. Discussion Cirrhotic liver disease remains a global health burden with increasing prevalence and mortality in recent years. This mortality increase remains a critical driver for treatment innovation with continual examination of our repertoire of medications for possible repurposed applications. Elevated COX2 expression has been identified to mediate and accelerate acute and chronic inflammatory states therefore driving the onset of cirrhotic liver disease and hepatic decompensation. Aspirin use and its inhibitory action on COX2 demonstrated a significantly reduced risk of in-hospital mortality. These findings reveal that aspirin use is also linked to a significant reduction in odds of in-hospital mortality, of developing major secondary complications and of developing hepatic decompensation known to increase mortality and morbidity in those with cirrhosis as compared to those who do not use aspirin.

Abstract: Gastric cancer incidence is markedly higher among Korean-born and first-generation Korean migrants than among non-Hispanic white populations in the United States, even after relocation to a lower-incidence Westernized environment. This persistent disparity, sometimes termed the “migrant paradox,” raises the question of why elevated risk does not fully resolve despite changes in geography and lifestyle. Helicobacter pylori infection is the dominant etiologic factor in noncardia gastric carcinogenesis and remains central to most prevention strategies, but infection status alone cannot account for the wide variation in cancer risk observed among populations with comparable H. pylori prevalence. This literature review examines factors beyond H. pylori infection that may help explain why elevated gastric cancer risk persists in Korean diaspora populations after migration. Key factors considered include bacterial virulence factors (cagA and vacA genotypes), host inflammatory-response polymorphisms (including interleukin-1 beta and related cytokine pathways), behavioral exposures (high salt intake, preserved and fermented foods, smoking, and incomplete acculturation), and emerging evidence on gastric microbiome shifts beyond H. pylori alone. Across these domains, the literature suggests that no single factor fully accounts for population-level disparities; rather, gastric cancer risk in Korean migrants reflects the interaction of pre-migration exposures, host susceptibility, and post-migration environmental change. These findings have direct implications for prevention: H. pylori eradication, while effective, works best as the anchor of a risk-stratified approach that also incorporates dietary counseling, smoking cessation, and endoscopic surveillance for premalignant gastric lesions.

Abstract: Liver regeneration is critical determinant of survival following acetaminophen (APAP) overdose, is driven primarily by proliferation of surviving hepatocytes. Hepatic progenitor cells (HPCs) are bipotential cells activated when hepatocyte proliferation is impaired. Contribution of HPCs to liver regeneration after APAP overdose remains unclear. This study investigated the contribution of HPCs to hepatocyte repopulation after severe APAP overdose using lineage tracing mouse models. Two-month-old male C57BL/6J mice were fasted overnight and then administered a 600 mg/kg overdose of APAP (600APAP). For lineage tracing, male ROSA^mT-mG mice were injected with AAV8-TBG-Cre to label hepatocytes. Two weeks after AAV administration, mice were fasted overnight and then administered a 600 mg/kg overdose of APAP. Liver and blood samples were collected multiple times. C57BL/6J mice treated with severe acetaminophen overdose (600APAP) show substantial liver injury, with peak serum ALT and hepatic necrosis at 72 h, followed by progressive recovery. HPC activation was evidenced by increased expression of EpCAM, A6, and CK19 during recovery phase. APAP administration to ROSA^mT-mG mice induced liver injury and subsequent regeneration and recovery comparable to wild type mice. Detection of HNF4α/tdTomato double-positive cells, hepatocytes originating from HPCs, were detected after injury but represented only 0.3–0.6% of total hepatocytes. Taken together, this study indicates that despite an increase of HPCs markers, lineage tracing model demonstrate that HPCs transdifferentiation contribute minimally to hepatocyte replenishment following severe APAP-induced liver injury.

Abstract: Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent, is closely linked to obesity, and carries significant hepatic and cardiometabolic risk. Current first-line lifestyle interventions often yield suboptimal results. Endoscopic sleeve gastroplasty (ESG), a minimally invasive endobariatric procedure, has shown safety and efficacy for weight loss, but evidence, particularly regarding liver-specific outcomes in Asian populations, is limited. We evaluated the effectiveness and safety of ESG on hepatic steatosis, liver function, and weight in unselected Asian patients with MASLD and obesity. Methods: This case series reports six patients with MASLD who underwent ESG for obesity management after failing dietary and weight-loss programs. Patients were followed at 3 and 6 months. Primary outcomes were changes in steatosis (ultrasound attenuation parameter, UAP), liver function (alanine aminotransferase, ALT), and procedure-related adverse events; secondary outcomes were total body weight loss (%TBWL), change in body mass index (ΔBMI), and technical success. Results: The cohort comprised three men and three women with a mean age of 47.8 ± 7.52 years and a median baseline body mass index of 32.37 (interquartile range 29.24–38.00) kg/m². All patients with available follow-up achieved normalization of UAP and ALT after the procedure, and no major complications occurred. A weight loss of −9.33 ± 6.80 kg with a %TBWL of −9.97 ± 5.29% was observed (p = 0.02), and all procedures were technically successful. Conclusions: ESG appears to be a promising treatment for hepatic steatosis in patients with obesity and MASLD, but these findings should be validated through larger, controlled studies.

Abstract: Background: Acute phosphate nephropathy (APhN) is a potentially severe and irreversible form of tubulointerstitial kidney injury associated with oral sodium phosphate (OSP) bowel preparation. Because the clinical presentation may be nonspecific and routine imaging can be unrevealing, the diagnosis may remain unrecognized until kidney biopsy is performed. Methods: We retrospectively analyzed three patients with biopsy-proven APhN after documented OSP exposure between 2020 and 2025. Clinical course, kidney function, urinary findings, imaging, and histopathology were reviewed. Results: All three patients showed a substantial decline in kidney function after OSP exposure, but the causal association was recognized only retrospectively after kidney biopsy demonstrated calcium phosphate crystal deposition and tubulointerstitial injury. In one patient, severe kidney injury progressed to dialysis-dependent end-stage kidney disease. Two patients had pre-existing chronic kidney disease, whereas one had only mildly impaired baseline kidney function. Renal ultrasonography did not reliably identify nephrocalcinosis. Urinary α1-microglobulin was elevated in all three patients, consistent with tubular injury. Conclusions: APhN may be clinically underrecognized because kidney injury can be detected late and routine imaging may be normal despite histological nephrocalcinosis. A history of bowel preparation should therefore be actively sought in patients with otherwise unexplained kidney dysfunction. Avoidance of OSP in patients at increased renal risk and timely monitoring of kidney function after exposure may facilitate prevention and earlier recognition.

Abstract: Background: Metabolic dysfunction-associated fatty liver disease (MASLD) is the most common chronic liver disease in children and adolescents. While magnetic resonance imaging–proton density fat fraction (MRI-PDFF) provides quantification of hepatic fat, its cost and accessibility restrict its use for screening and monitoring. Emerging quantitative ultrasound techniques offer non-invasive alternatives for pediatric hepatic steatosis assessment. This scoping review synthesized evidence on emerging quantitative ultrasound techniques in children. Methods: A scoping review was conducted in accordance with PRISMA-ScR guidelines. MEDLINE (PubMed), Embase, and Scopus were searched for studies published between January 2019 and October 2025. Studies evaluating quantitative ultrasound techniques for children were included. Controlled attenuation parameter (CAP) studies were identified but excluded to focus on emerging non-CAP modalities. Data extraction included study characteristics, reference standards, and findings. Results: Fifty-five studies met the eligibility criteria for quantitative ultrasound. After excluding 40 CAP only studies, fifteen evaluating non-CAP quantitative ultrasound modalities were included in the final synthesis. The most studied techniques included ultrasound-derived fat fraction (UDFF), attenuation-based techniques, and backscatter-based analysis. Several studies reported correlations with MRI-PDFF and good to excellent diagnostic performance, with proposed attenuation cutoffs ranging from 0.54 to 0.73 dB/cm/MHz. However, heterogeneity was observed in study design, populations, acquisition protocols, and reference standards. Conclusion: Emerging quantitative ultrasound techniques show promising diagnostic accuracy for pediatric hepatic steatosis and may represent accessible alternatives for noninvasive liver fat quantification. Their implementation could facilitate earlier identification of pediatric MASLD. However, methodological heterogeneity and lack of standardization, require prospective multicenter validation and pediatric-specific thresholds.

Abstract: Background: Pancreatic cancer is a leading cause of cancer-related mortality. Locally advanced pancreatic cancer (LAPC) remains associated with low resection rates and poor survival despite advances in systemic therapy. Intratumoral Phosphorus-32 (P-32) microparticle implantation is an emerging locoregional brachytherapy approach for unresectable LAPC. Methods: This prospective single-center observational cohort study included patients with unresectable LAPC treated with gemcitabine plus nab-paclitaxel and EUS-guided intratumoral P-32 microparticle implantation. Intratumoral distribution was assessed by SPECT/CT. Tumour response was evaluated according to RECIST 1.1, with local disease control rate (LDCR) assessed at approximately 16 weeks. Adverse events were graded according to CTCAE version 4.0. Results: Seventeen patients underwent P-32 implantation (median age, 70 years; ECOG PS 0–1). SPECT/CT confirmed appropriate intratumoral distribution in all patients, with no implantation-related procedural complications. At 16 weeks, 7/16 evaluable patients (43.8%) achieved partial response and 9/16 (56.2%) had stable disease, resulting in an LDCR of 100% among evaluable patients and 94.1% in the all-treated analysis. Mean target-lesion diameter decreased from 3.4 to 2.8 cm, with a median reduction of 21.4%. CA19-9 decreased by ≥50% in 13/16 evaluable patients (81.2%). Four patients (23.5%) underwent surgical resection, all achieving R0 resection. Adverse events were predominantly grade 1–2; one grade 3 event and no grade 4–5 events occurred. Conclusions: P-32 microparticle implantation combined with systemic chemotherapy was feasible and demonstrated encouraging early local activity with an acceptable safety profile. These findings support further prospective evaluation in larger cohorts.

Abstract: Background: The clinical overlap between gastrointestinal (GI) conditions and psychiatric disorders represents a challenge in clinical practice. Eating disorders (EDs)-including anorexia nervosa, bulimia nervosa, binge eating disorder (BED), as well as newly classified entities such as Avoidant/Restrictive Food Intake Disorder (ARFID) and orthorexia nervosa-frequently co-occur with GI diseases, complicating their management. Objective: This narrative review aims to summarize current knowledge regarding the prevalence, pathophysiological mechanisms, and diagnostic challenges associated with the coexistence of various EDs in patients with inflammatory bowel disease (IBD), disorders of gut-brain interaction (DGBIs), celiac disease, and gut microbiota alterations. Methods: The review was structured in accordance with the SANRA guidelines. A comprehensive literature search of PubMed and Scopus as primary databases, supplemented by Google Scholar was conducted for articles published from 2011 through early 2026. Results: The analyzed literature indicates a complex, bidirectional relationship driven by the gut-brain axis. Chronic GI symptoms often necessitate dietary modifications, which can inadvertently trigger or mask pathological restrictive eating behaviors. Diagnosing ARFID and orthorexia in these cohorts is particularly challenging due to overlapping somatic symptoms. Primary EDs can lead to significant GI distress and severe microbiome dysbiosis, perpetuating a vicious cycle of inflammation and malnutrition. Conclusions: The convergence of EDs and GI conditions requires heightened clinical vigilance. Distinguishing between necessary, symptom-driven dietary restrictions and pathological eating behaviors is crucial. Implementing an integrated, multidisciplinary care model-involving gastroenterologists, psychiatrists, and dietitians-is essential to improve diagnostic accuracy and patient outcomes.

Abstract: Background/Objectives: Superficially serrated adenoma is a recently recognized subtype of colorectal serrated lesions. Case Reports: We report a case of a rectal superficially serrated adenoma in a 57-year-old Japanese woman with ulcerative colitis and a history of follicular lymphoma. Endoscopically, the lesion presented as a superficial sessile lesion without a nodule component and was completely removed by cold snare polypectomy. Histopathological examination revealed a characteristic combination of superficially serrated epithelium and vertically oriented adenoma-like glands. Immunohistochemistry confirmed serrated differentiation of the superficial epithelial component. Molecular analyses identified a KRAS Q61H mutation and a novel PTPRK::RSPO3 fusion that retained the entire RSPO3 coding region. Conclusions: To our knowledge, this represents the first reported case of RSPO3 fusion in a superficially serrated adenoma associated with ulcerative colitis in Japan. Although some aspects of the molecular pathogenesis of superficially serrated adenoma have been increasingly investigated, its clinicopathological features, particularly in the setting of ulcerative colitis, remain poorly characterized. Additional clinicopathological and molecular studies are required to determine whether superficially serrated adenomas arising in patients with ulcerative colitis represent incidental sporadic lesions or a distinct subset associated with the inflammatory bowel disease setting.

Abstract: Liver fibrosis is a serious complication of non-alcoholic fatty liver disease (NAFLD) and the metabolic syndrome (MetS), conditions closely linked to obesity. We investigated the levels and dynamics of liver fibrosis biomarkers and liver fat content during personalized weight loss intervention in individuals with obesity, NAFLD, and concomitant MetS (n=30), with assessments at baseline, 1, and 5 months. Liver fat content decreased significantly (p < 0.0001), corresponding with complete resolution of steatosis in 36.7% of the participants, after 1 month of weight loss. Similarily, the fibrosis markers: T1 (p < 0.01), CK18 (p < 0.01), PIIINP (p < 0.0001), TIMP1 (p < 0.001), and MACK3 (p < 0.001) dropped after 1 month. CK18 (p < 0.01) and MACK3 (p < 0.001) further changed from 1 to 5 months, while FNI decreased after 5 months (p < 0.01). Except for CK18, the dynamics of these changes were more pronounced from baseline to 1 month compared with 1 to 5 months. Finally, MACK3 showed promise for explaining T1.Our study underlines the importance of weight loss in swiftly mitigating liver steatosis and supports the integration of non-invasive biomarkers to monitor fibrosis risk in individuals with obesity, NAFLD, and MetS.

Abstract: Background: COVID-19 infection has been a major cause of hospitalization and mortality in the United States. Patients with liver cirrhosis may be especially vulnerable to severe outcomes of COVID-19 infection because of immune dysfunction, systemic inflammation, portal hypertension, and reduced physiologic reserve. These factors can increase the risk of severe infection, multiorgan complications, and poor inpatient outcomes. Using the 2020-2022 United States National Inpatient Sample, this study evaluates the effect of cirrhosis among adults hospitalized with COVID-19. Methods: We performed a retrospective cohort study using the National Inpatient Sample (NIS) database. Adult hospitalizations with COVID-19 from 2020 to 2022 were included and stratified according to the presence or absence of cirrhosis. Using multivariable logistic regression analyses, we evaluated in-hospital mortality as the primary outcome. Secondary outcomes included need for mechanical ventilation, septic shock, ARDS, ECMO utilization, acute kidney injury, renal replacement therapy, length of stay, and hospital charges. Results: A total of 5,934,565 hospitalized COVID-19 patients were included, of which 115,170 had concomitant cirrhosis. COVID-19 patients with cirrhosis had a higher in-hospital mortality than those without cirrhosis (16.8% vs. 11.3%; aOR 1.28; 95% CI 1.22-1.32). Patients with liver cirrhosis were also associated with higher odds of invasive mechanical ventilation, vasopressor use and septic shock. Conclusions: Cirrhosis was independently associated with increased in-hospital mortality and complications including need for invasive mechanical ventilation and septic shock in adults hospitalized with COVID-19. Although mortality associated with these patients have declined over time, they represent a high risk group that requires close monitoring.

Abstract: Background: Bicarbonate mineral waters have been reported to modulate biliary dynamics. Prior symptom based data with Aqua 3 suggested digestive benefits, but objective confirmation is still lacking. Aims: To evaluate, the effect of Aqua 3 on gallbladder motility in fasting healthy adults, compared with an oligomineral water. Methods: In this randomized, crossover study, twenty healthy volunteers underwent two ultrasound sessions after an overnight fast and the ingestion of 500 mL of either Aqua 3 (bicarbonate mineral water) or oligomineral water. Gallbladder volume was measured at baseline and after 10, 20, 30, and 60 minutes. Primary endpoint was the maximum ejection fraction. Results: Bicarbonate mineral water induced a rapid increase in ejection fraction: peaking at 10 minutes, persisting at 20 minutes and attenuating by 30 minutes. At 60 minutes, gallbladder refilling exceeded baseline. Oligomineral water produced only modest early emptying at 10 minutes, no significant change at 20 minutes, and progressive refilling thereafter. Throughout the observation period, ejection fraction was significantly higher after bicarbonate than oligomineral water. Maximum ejection fraction was significantly greater with bicarbonate than oligomineral water, occurring most frequently at 10 minutes for both waters. Conclusions: A single 500 mL dose of bicarbonate mineral water elicits a rapid and pronounced cholagogue response, with ejection fraction increases evident within 10 minutes that significantly exceed those observed after oligomineral water, providing a mechanistic rationale for the previously reported digestive benefits of bicarbonate mineral water. These findings may be clinically relevant for optimizing early postprandial digestion and mitigating biliary stasis in hypomotile gallbladders.

Abstract: Metabolic dysfunction – Associated Steatotic Liver Disease (MASLD) represents the emerging leading cause of Chronic Liver Disease (CLD) worldwide, with a global prevalence of approx. 30% in the general population that parallels global rates of obesity and Type 2 Diabetes (T2D). At present no validated therapy is available to block or slow down disease progression to Metabolic dysfunction – Associated SteatoHepatitis (MASH), liver fibrosis and cirrhosis and hepatocellular carcinoma (HCC). At present there is a lack of reliable biomarkers able to identify MASH patients at risk of disease progression and/or HCC development. According to the knowledge that pro-inflammatory cytokines play a key role in MASLD/MASH progression and HCC development, in this review we will discuss the role in this disease and other CLD of Oncostatin M (OSM), a cytokine belonging to the IL-6 family, and of pathways involving OSM and its receptor β (OSM/OSMRβ axis). OSM and related pathways are emerging as selective in sustaining disease progression by promoting chronic inflammation and fibrogenesis. Moreover, OSM/OSMRβ axis is critically involved in MASH-related HCC development by affecting proliferation, angiogenesis, invasiveness and metastasis as well as by reshaping MASH-related tumour immune microenvironment. OSM/OSMRβ axis is then emerging as a selective MASH-related putative therapeutic target.

Abstract: Gastroesophageal reflux disease (GERD) is one of the most commonly diagnosed gastrointestinal disorders. Moreover, symptoms of GERD may be confused with symptoms of some cardiovascular diseases. This paper presents an analysis of cough sounds recorded from a volunteer who suffers from GERD. The samples were collected at five different occasions, during which the proband showed different severity of GERD symptoms. The samples are analysed using the following popular signal analysis methods: short-time Fourier transform, total harmonic distortion, Hilbert transform, power spectrum and continuous wavelet transform. The results show that differentiation between different symptom loads of GERD by the sound of cough alone is possible after an appropriate cough waveform transformation.