Socioeconomic disadvantage may influence the chronic hepatitis B (CHB) care continuum and the stage at which clinically relevant liver disease is recognised. However, evidence linking both individual- and area-level socioeconomic disadvantage to histologically assessed liver fibrosis in CHB remains limited. We examined whether socioeconomic disadvantage at the individual and area levels was associated with liver fibrosis severity in adults with CHB in Türkiye. In this nationwide multicentre observational study, adults with CHB who underwent liver biopsy in routine care between 1 January 2019 and 31 December 2024 across 24 centres in Türkiye were screened. Clinical and histopathological data were obtained retrospectively from medical records, while socioeconomic data were collected after biopsy through structured face-to-face interviews. Fibrosis was staged using the Ishak system. Individual socioeconomic indicators and province-level categories of the socioeconomic development index (SEDI) were examined. The primary analysis used ordinal logistic regression. Supportive analyses included multivariable logistic regression, 1:1 propensity score matching with conditional logistic regression, overlap weighting, likelihood-ratio tests for interaction, chi-square or Fisher’s exact tests, Kruskal–Wallis tests, and Wilcoxon rank-sum tests, with Benjamini–Hochberg adjustment for post-hoc comparisons. The analytic cohort included 956 adults, of whom 53.7
Claudin 18 isoform 2 (CLDN18.2) has emerged as a clinically validated therapeutic target in gastric and gastroesophageal junction (GEJ) adenocarcinoma following the regulatory approval of zolbetuximab in combination with first-line chemotherapy. Accurate prevalence data at the clinically validated immunohistochemical threshold are essential for patient selection, healthcare resource planning, and treatment strategy. Reported prevalence estimates vary widely across studies due to differences in populations, methodologies, and immunohistochemical protocols. This systematic review and meta-analysis aimed to generate a robust pooled prevalence estimate of CLDN18.2 expression at the threshold used in pivotal phase III trials. PubMed, Embase, and the Cochrane Library were searched from database inception through March 12th, 2026. Studies reporting CLDN18.2 expression in gastric or gastroesophageal junction adenocarcinoma using the ≥ 75
Immunotherapy has changed the therapeutic approach to advanced gastric cancer (AGC) and has shown survival benefits compared with standard chemotherapy. However, in clinical practice, its use remains heterogeneous. Differences in diagnostic pathways, organisational aspects, and regional settings may lead to delays in treatment access. This study aimed to analyse these issues and to describe possible shared strategies to improve the use of immunotherapy in AGC in Italy. The analysis was performed in two steps. First, a focus group comprising 13 oncologists and pathologists from 5 national reference centres was organised to collect information on the use of immunotherapy biomarker tests and the main barriers encountered in daily practice. Based on the topics emerging from this discussion, a second step was conducted using a consensus questionnaire. The questionnaire was sent to a multidisciplinary group composed of 19 oncologists, pathologists, surgeons, pharmacists, and endoscopists. Several common problems were reported during the focus group discussion. These included delays in biomarker testing, differences in pre-analytical procedures among centres, the absence of shared quality indicators, and difficulties in tracking tissue samples, especially when samples were sent from outside hospitals. In addition, limited interaction among different specialists was frequently mentioned. The results of the questionnaire indicated a high level of agreement on several proposed actions, such as the evaluation of regional differences, the use of organisational models already adopted in some Italian oncology networks, the introduction of new biomarkers together with dedicated training activities, and the use of digital tools to support the discussion of complex cases. All survey items reached the predefined consensus threshold. This study identified several organizational and diagnostic challenges affecting the implementation of immunotherapy in AGC. Participants highlighted a number of potential priorities for improvement, including optimization of diagnostic workflows, stronger multidisciplinary collaboration, and greater coordination across centres. These findings may inform future initiatives aimed at reducing variability in clinical practice and supporting equitable access to innovative treatments.
Appendiceal adenocarcinoma is a rare malignancy with a high risk of peritoneal recurrence, especially in locally advanced stages. While intraoperative systemic chemotherapy (ISC) is standard for metastatic disease, its role in non-metastatic Stage II–III patients remains controversial. This study aimed to evaluate the survival benefit of ISC in this population. We conducted a retrospective cohort study using the National Cancer Database (2006–2022). Patients with clinical Stage II–III (T4, N0–2) appendiceal adenocarcinoma who underwent surgical resection were included. Overall survival (OS) was compared between patients who received ISC and controls using Kaplan-Meier statistics and multivariable Cox proportional hazard models. A total of 616 patients were identified, 130 (21.1
Tumor-agnostic targeted therapy has expanded precision oncology by allowing selected molecular alterations to guide treatment across conventional organ boundaries. In gastrointestinal (GI) cancers, however, actionability is not uniformly independent of histology. This narrative review examines NTRK and RET fusions as paradigmatic tumor-agnostic targets and contrasts them with histology-tuned or GI-specific fusion-directed strategies, particularly NRG1 fusion-positive pancreatic adenocarcinoma and cholangiocarcinoma. Targeted PubMed/MEDLINE and regulatory-agency searches were updated through August 3, 2026. In the initial 55-patient larotrectinib analysis, ORR was 75
Tuberculosis (TB) and HIV co-infection remains a major public health challenge in resource-limited settings. Liangshan Yi Autonomous Prefecture in Southwest China bears a dual high burden of HIV and TB. This study aimed to analyze the epidemiological trends of HIV-TB co-infection in Liangshan from 2019 to 2024 and to inform integrated prevention strategies. A retrospective analysis was conducted on 3367 HIV-TB co-infected cases extracted from the National HIV/AIDS and TB surveillance systems. Records were linked via unique identifiers. Descriptive statistics and chi-square tests for trend assessed incidence trends, demographics, transmission routes, treatment outcomes, and drug resistance. From 2019 to 2024, HIV-TB incidence declined from 12.26 to 8.76 per 100,000 (χ2trend = 40.459, P < 0.001), driven by high-burden counties and populations under 45 years (all P < 0.001). Patients were predominantly young males (61.10
Abstract Background Echinococcosis, a severe zoonotic parasitic disease, imposes a significant health burden in western China, primarily as alveolar (AE) and cystic (CE) forms caused by Echinococcus multilocularis ( Em ) and E. granulosus sensu lato ( Egsl ), respectively. Its transmission, tied to a complex host cycle, is strongly influenced by climatic factors. This study aimed to model the ecological niches of these parasites, validate predictions with epidemiological data, and project the impact of climate change on future transmission risk geography. Methods Utilizing location data of 1247 human cases diagnosed in western China from 1981 to 2016, obtained from the National Echinococcosis Control Program, and contemporary climate data, we developed optimized Maximum Entropy (MaxEnt) models. This involved defining an appropriate spatial resolution, screening 19 bioclimatic variables to select key predictors (7 for Em , 6 for Egsl ), and identifying optimal model parameters. Model performance was evaluated using the Area Under the Curve (AUC) and AUC of 10% Receiver Operating Characteristic (AUCpROC) curve, and validity was assessed via correlation with county-level incidence. Future habitat suitability was projected for multiple periods (2011–2100) under three climate scenarios (SSP-126, SSP-370, SSP-585) generated by 5 global climate models. Results The models demonstrated high predictive accuracy (AUC > 0.92; AUCpROC: 0.084 for Em , 0.070 for Egsl ) and a significant positive correlation with incidence ( ρ > 0.6, P < 0.0001). Em and Egsl exhibited distinct climatic niches: Em prefers cool, stable climates with moderate summer moisture, while Egsl spreads in areas with dry-cold winters, warm-humid summers, and moderate seasonality. Future projections reveal a spatially heterogeneous reshaping of risk. While overall suitability increases, Em 's suitable area is projected to shift toward higher altitudes (e.g., expanding in Qinghai and Xizang but contracting in Ningxia and Gansu). In contrast, Egsl shows widespread outward expansion from current endemic margins, particularly across the Tibetan Plateau. Qinghai and Xizang are identified as key expansion hotspots for both Em and Egsl . Conclusion The findings confirm distinct ecological drivers for the suitability of Em and Egsl , and indicate that climate change will potentially shift the endemic areas of AE and expand those of CE in western China. This underscores the necessity for forward-looking, spatially targeted surveillance and control strategies, informed by a One Health approach, to mitigate the evolving burden of echinococcosis.
CLDN18.2 is specifically overexpressed in gastric cancer tissues and represents an important emerging therapeutic target in gastriccancer treatment. Bispecific antibodies (BsAbs), a class of antibody-based therapeutics capable of simultaneously targeting two antigensites, have recently entered clinical development for the treatment of CLDN18.2-positive gastric cancer. This review systematicallysummarizes the molecular designs, functional subtypes, and clinical development of CLDN18.2-related BsAbs, while analyzing currentchallenges and potential optimization strategies. Currently, CLDN18.2-related BsAbs that have entered clinical development mainlycomprise three categories: T-cell engagers, T-cell costimulators, and immune checkpoint-blocking BsAbs. These agents havedemonstrated preliminary antitumor activity in later-line monotherapy and first-line combination therapy settings, with generallymanageable safety profiles. Optimization of target combinations, precise patient selection, strategies to overcome efficacy limitations, and improved safety management represent important directions for enhancing the therapeutic value of BsAb-based approaches.
The incorporation of immune checkpoint inhibitors (ICIs) into first-line therapy has changed the treatment landscape of advanced gastric and gastroesophageal junction cancer. This review summarizes the clinical evidence for chemotherapy after prior ICI exposure, discusses potential biological mechanisms, and considers practical treatment sequencing in the ICI era. We conducted a targeted narrative review of PubMed/MEDLINE and major oncology congress proceedings through July 19, 2026. Original clinical studies reporting outcomes of systemic chemotherapy after prior ICI exposure in advanced gastric or gastroesophageal junction cancer were prioritized, with selected evidence from other tumor types and mechanistic studies included for context. Retrospective and observational studies suggest that chemotherapy after anti-PD-1 therapy can retain clinically meaningful activity, although the evidence is heterogeneous and largely non-randomized. Taxane plus ramucirumab is the most extensively studied post-ICI regimen, but available data in the contemporary first-line-ICI setting do not establish superiority over other guideline-supported second-line options. Whether favorable outcomes reflect true immunologic chemosensitization, residual immune activation interacting with subsequent cytotoxic or anti-angiogenic therapy, or patient selection remains unresolved. Current evidence supports individualized selection among guideline-recommended second-line regimens, including taxane plus ramucirumab, single-agent taxane, and irinotecan, after first-line fluoropyrimidine/platinum plus ICI. Prospective post-ICI validation and biomarker-integrated studies are needed.
Much work remains to achieve the sustainable development goals for improved sanitation access for all. Subsidised sanitation interventions are often criticised due to the possibility of the infrastructure being neglected or culturally inappropriate for target communities. The BALatrine intervention is a novel approach consisting of a community-wide subsidised recipient-aided installation of an improved latrine with septic tank (‘BALatrine’) and education package. This study aimed to investigate the long-term usage and cultural acceptability of the BALatrine project four to six years following its implementation in a main trial. We conducted a cross-sectional follow-up study in September 2022 of 88 households who received BALatrines in two villages between 2016 and 2017. Quantitative and qualitative interviews with the household head and members were conducted to understand BALatrine usage and perceptions. Descriptive statistics were used to tabulate interview responses. The BALatrines were still in excellent condition with 89
Claudin 18 isoform 2 (CLDN18.2) has emerged as a clinically actionable target in gastric and gastroesophageal junction adenocarcinoma. Zolbetuximab plus chemotherapy established the first validated CLDN18.2-directed strategy, but also highlighted clinically important limitations: incomplete primary sensitivity, spatial and temporal heterogeneity of antigen expression, gastrointestinal toxicity, uncertain biomarker persistence after treatment, and the absence of an evidence-based sequence after progression. These limitations have accelerated development of antibody-drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies, T-cell engagers, and rational combinations with chemotherapy or immune checkpoint blockade. This review summarizes current evidence through July 2026, examines plausible mechanisms of resistance and biomarker evolution, and proposes a cautious, modality-specific framework for future clinical development. Updated clinical data support proof of concept across multiple modalities. IBI343, an exatecan-based ADC, has shown antitumor activity with predominantly hematologic toxicity; vedotin-based ADCs demonstrate a different linker-payload profile with additional concern for microtubule-related cumulative toxicity. Randomized phase II data with satricabtagene autoleucel have established progression-free survival benefit over treatment of physician's choice in previously treated disease, although lymphodepletion-related cytopenias and cytokine-release syndrome require specialized infrastructure. Early studies of givastomig and IBI389 further support immune-engaging approaches. Tissue immunohistochemistry remains the reference method for treatment selection; circulating tumor DNA cannot currently reproduce membranous protein intensity or spatial distribution, and liquid-biopsy approaches for CLDN18.2 reassessment remain investigational.
The Advanced Lung Cancer Inflammation Index (ALI) combines body mass index, serum albumin, and the neutrophil-to-lymphocyte ratio, but overlaps with many other prognostic scores in pancreatic ductal adenocarcinoma (PDAC). We evaluated whether ALI is independently prognostic in de novo metastatic PDAC and whether it adds information beyond performance status and established scores. In this single-centre retrospective cohort of patients with de novo metastatic PDAC diagnosed between 2019 and 2023, ALI was calculated at diagnosis. It was compared head-to-head with NLR, PNI, mGPS, CONUT, SII, PLR, LMR, and HALP using Harrell’s concordance index (C-index), and its incremental value over a clinical model (ECOG performance status, CA 19 − 9, liver metastasis, age) was quantified with bootstrap internal validation. Of 102 patients, 101 were analysable (47 deaths; median follow-up 14.3 months). Low ALI (≤ 26.4) was associated with shorter median overall survival than high ALI (10.6 vs. 21.8 months; hazard ratio 1.97; p = 0.025), but this was not independent after multivariable adjustment for performance status (adjusted hazard ratio 1.62, 95
BRAF V600E-mutated metastatic colorectal cancer (mCRC) is a biologically distinct subtype characterized by right-sided predominance, frequent overlap with serrated-pathway biology, and historically poor outcomes with conventional chemotherapy. Therapeutic progress has been driven by the recognition that BRAF inhibition alone is inadequate in colorectal cancer because adaptive epidermal growth factor receptor (EGFR)-mediated feedback rapidly restores MAPK signaling. This narrative review evaluates the clinical development and practical integration of BRAF-targeted therapy in BRAF V600E-mutated mCRC, with particular emphasis on first-line treatment, MMR/MSI status, patient fitness, and treatment sequencing in the post-BREAKWATER era. Combined BRAF and EGFR inhibition established encorafenib plus cetuximab as a standard option after prior therapy. The phase 3 BREAKWATER program has now moved BRAF-targeted treatment into first-line practice by demonstrating improved outcomes with encorafenib plus cetuximab combined with fluoropyrimidine-basedchemotherapy, including mFOLFOX6 and FOLFIRI backbones. These data define a chemo-targeted approach for fit patients with non-MSI-H/dMMR disease. For MSI-H/dMMR tumors, first-line immune checkpoint blockade should be prioritized irrespective of BRAF V600E status unless immunotherapy is absolutely contraindicated. Important uncertainties remain regarding whether BRAF/EGFR targeting should be added to immunotherapy in MSI-H/dMMR disease, as well as the management of frail or oxaliplatin-ineligible patients, maintenance therapy, local treatment integration, and sequencing after frontline encorafenib exposure. Treatment selection in the post- BREAKWATER era should therefore integrate molecular context, patient fitness, and remaining evidence gaps.
Colorectal mucinous adenocarcinoma (CMA) is a unique subtype of adenocarcinoma. This study aimed to compare characteristics, treatments, and survival outcomes of early-onset and later-onset CMA. This investigation was a retrospective cohort study from the National Cancer Institute’s SEER Research Data database from 2000 to 2022 on patients with CMA. Patients aged < 50 years (early-onset) and patients aged ≥ 50 years (later-onset) were compared regarding disease characteristics, treatments, and survival. The main outcome measures were 5-year overall survival (OS) and cancer-specific survival (CSS). The study included 55,853 patients; 10.4
HER2 has emerged as an actionable molecular alteration in metastatic colorectal cancer (mCRC), particularly in patients with RAS wild-type disease and tumors with strong HER2 overexpression or ERBB2 amplification. Once recognized mainly as a mechanism of resistance to anti-EGFR therapy, HER2 now defines a therapeutically relevant subgroup. Dual HER2 blockade with trastuzumab-based combinations and antibody-drug conjugates, particularly trastuzumab deruxtecan, have demonstrated clinically meaningful activity in treatment-refractory disease. Emerging phase III data with trastuzumab rezetecan further support HER2-directed therapy, although peer-reviewed publication, regulatory status, and regional availability remain important considerations. This narrative review focuses on the practical integration of HER2 testing and HER2-directed treatment into mCRC care. We summarize colorectal cancer-specific diagnostic approaches, evidence for established and emerging regimens, and treatment-selection considerations according to RAS/BRAF status, HER2 expression level, prior anti-EGFR exposure, comorbidities, toxicity risk, and local access. We also discuss the complementary roles of tissue testing and circulating tumor DNA, including repeat molecular assessment at progression. Finally, we propose a clinician-oriented framework for early patient identification, treatment sequencing, and resistance assessment. Optimal sequencing between dual HER2 blockade and antibody-drug conjugates remains uncertain and requires prospective evaluation.
Abstract Background Mosquitoes transmit diverse pathogens, some of which cause mosquito-borne diseases (MBDs). Climate and socioeconomic changes, such as temperature fluctuations, altered rainfall patterns, and urbanization, may affect the distributions of key vectors, particularly Aedes and Anopheles , and increase the health burden of MBDs. West Africa is a historically high-endemic region for MBDs, including malaria and dengue. However, existing studies in this region remain limited in scope, making comprehensive, high-resolution spatial mapping of vectors and pathogens inadequate. This study aimed to map the distributions of mosquitoes and mosquito-associated pathogens and identify potentially suitable areas for key mosquito species in West Africa, thereby supporting regional surveillance and control efforts. Methods We conducted a scoping review of English-language studies in PubMed, Web of Science, Embase, and Scopus through 7 March 2023. From eligible studies, relevant online databases, and GenBank, we extracted records of mosquito species, mosquito-associated pathogens, and human infections documented by outbreaks, pathogen isolation, molecular detection, or serology. Geographic records were standardized to WGS84 and mapped in ArcGIS 10.7. Potential distributions of key mosquito species were modeled in Maxent 3.4.1 using 24 climatic, topographic, population, land-cover, and related variables. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results We compiled 19,578 occurrence records for 302 mosquito species in 16 genera and 598 records for 124 mosquito-associated pathogens from 22 families; 20 pathogens were reported to infect humans. Aedes , Anopheles and Culex occurred in all 16 countries, and Anopheles harbored the most pathogen species ( n = 55). DENV was detected in mosquitoes in five countries but human infections were reported in 13. Models for nine key mosquito species yielded AUC values of 0.763–0.912. Land cover contributed more than 10% to six models, and suitable habitats were predicted in Cape Verde for five species without occurrence records in the country. Conclusions We established a geospatial database of mosquitoes and their associated pathogens in West Africa. Current records remain incomplete and unevenly distributed, with gaps in key vector occurrence and limited mosquito-based detection of viral and parasitic pathogens relative to human infection evidence. Ecological niche modeling suggests that suitable habitats of some important mosquito species may extend beyond their reported ranges. These findings can guide targeted field surveys and coordinated mosquito–pathogen surveillance in under-sampled areas of West Africa.
Abstract Background Liver fibrosis caused by Schistosoma japonicum may continue to progress even following successful praziquantel chemotherapy. Although liver biopsy remains the gold standard for diagnosis of liver fibrosis, its invasiveness limits clinical applications. Conventional non-invasive indices, such as aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index, often show suboptimal performance in schistosomiasis-related cases. This study aimed to develop and validate a machine learning (ML)-based model using epidemiological and laboratory data to identify liver fibrosis in individuals with prior S. japonicum infection, as a step toward precision management. Methods Data were obtained from the Jiangsu S. japonicum Infection Cohort (Jiangsu Province, China), involving 6158 participants with a documented history of infection who completed follow-up assessments during 2021–2022. Modeling variables were selected using LASSO regression and variance inflation factor analysis. Five ML models (k-nearest neighbor, logistic regression, support vector machine, decision tree, and extreme gradient boosting (XGBoost)) were evaluated. Model performance was compared against APRI and FIB-4 using the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and shapley additive explanations (SHAP) for interpretability. Results In the validation set, the XGBoost model demonstrated the highest diagnostic performance with an AUC of 0.854 (95% confidence interval ( CI): 0.826–0.881), outperforming other ML models (AUC range: 0.609–0.776). This was significantly superior to FIB-4 (AUC = 0.514) and APRI (AUC = 0.516) ( P < 0.001). DCA confirmed that the XGBoost model provided a substantial clinical net benefit across a broad range of threshold probabilities. According to Shapley additive explanations analysis, variables such as alcohol intake (mean SHAP value = 0.401), gamma-glutamyl transferase (0.295), and triglycerides (0.292) were the most influential predictors of liver fibrosis risk. Conclusions The XGBoost-based model offers a robust, non-invasive tool for identifying liver fibrosis in individuals with prior S. japonicum infection, with alcohol intake, gamma-glutamyl transferase, and triglycerides identified as the critical predictors. By outperforming traditional indices and leveraging routinely available data, this model represents a promising advancement toward precision management of individuals with prior S. japonicum infection, offering a scalable approach for early intervention, risk‑stratified assessment, and monitoring of hepatic morbidity in post‑transmission settings.
Microsatellite instability (MSI) is a key biomarker for immunotherapy in gastric cancer (GC), but preoperative non-invasive prediction remains challenging. Radiomics is promising; however, a systematic evaluation of its diagnostic performance with explicit consideration of overfitting and model comparison is lacking. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to March 25, 2026, for studies on radiomics for preoperative MSI prediction in GC. A bivariate random-effects model pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Subgroup analyses were performed by model type, data source, validation type, and algorithm. Thirteen studies (2,447 patients) were included. In validation sets (17 data points), the pooled AUC was 0.82 (95 https://www.crd.york.ac.uk/PROSPERO/view/CRD420251148467 .
Peritoneal metastases remain a major therapeutic challenge in gastric cancer. PERISCOPE II provided the first direct randomised comparison of an integrated operative strategy with continued systemic therapy in patients selected for limited peritoneal disease. Gastrectomy, cytoreductive surgery (CRS) and sequential heated oxaliplatin–normothermic docetaxel did not improve survival and caused substantial morbidity. The trial result should thus exclude routine adoption of that pathway, but it should not be interpreted as proof that every form of peritoneal-directed treatment is futile. Its multicomponent intervention was undertaken after brief systemic treatment, without mandatory laparoscopic confirmation of peritoneal response before randomisation, and frequently disrupted further systemic therapy. Meanwhile, DRAGON-01 has shown that repeated normothermic intraperitoneal paclitaxel can improve survival when added to systemic treatment, and STOPGAP has demonstrated the feasibility of serial laparoscopic reassessment and response-directed surgery in a Western pathway. Future trials should therefore separate two questions: whether intraperitoneal therapy adds benefit to contemporary biomarker-directed systemic treatment, and whether operative consolidation benefits the exceptional responders thereby identified. Surgery should become the consequence of demonstrated systemic and peritoneal response, not the intervention used to discover it.
