Wang X, Dong W, Shen R
… +17 more, Yu X, Zhang Y, Wang W, Yin X, Hu Y, Peng X, Yang G, Rao Q, Deng X, Wang R, Tang F, Huang Y, Jin Z, Cai Q, Xu H, Tang Y, Du D
INTRODUCTION: The recent global outbreaks of monkeypox virus (MPXV) and chikungunya virus (CHIKV) underscore the urgent need for rapid, accessible, and cost-effective diagnostic methods. Conventional CRISPR/Cas fluoresce...INTRODUCTION: The recent global outbreaks of monkeypox virus (MPXV) and chikungunya virus (CHIKV) underscore the urgent need for rapid, accessible, and cost-effective diagnostic methods. Conventional CRISPR/Cas fluorescence assays rely on trans-cleavage of ssDNA/RNA reporters labeled with expensive fluorophores and quenchers, which limits widespread application. OBJECTIVES: This study aims to develop and optimize a label-free, fluorogenic DNA aptamer-based reporter for a portable, one-pot Cas12a detection system capable of highly sensitive detection of MPXV and CHIKV directly from clinical specimens. METHODS: We evaluated commonly used ssDNA aptamers for their fluorescence emission upon Thioflavin T (ThT) binding and their cleavage efficiency by Cas12a. Through systematic mutagenesis targeting G-rich regions, we enhanced fluorescence emission. Additionally, poly-A linkers were introduced between G-rich motifs to promote Cas12a cleavage efficiency. Circular dichroism (CD) spectroscopy confirmed G-quadruplex (G4) formation in the aptamers. The assay's sensitivity and specificity were assessed using simulated clinical samples, followed by validation with actual clinical specimens. The performance of direct detection from simulated clinical samples was compared to qRT-PCR. A battery-powered heating-pad, a mini-centrifuge, and a flashlight were used to validate its POCT applicability. RESULTS: We designed and optimized a cost-effective, stable fluorogenic ssDNA aptamer that specifically binds to ThT. The aptamer ThT-3-5.1 exhibited the highest fluorescence enhancement and cleavage efficiency by Cas12a. Leveraging this aptamer, we developed a rapid, portable, one-pot detection platform (ROD-ThT) capable of detecting as few as 1 copy/reaction of MPXV and CHIKV nucleic acids within 35 min. Validation with clinical samples confirmed the assay's reliability without the need for nucleic acid purification. CONCLUSION: Our simple, efficient, portable, and affordable ROD-ThT platform holds great promise for disease diagnostics and management, particularly in resource-limited settings.
BACKGROUND AND AIMS: Biomarkers of protein nutritional status are essential for understanding the relationship between diet and frailty. The fraction of mercaptoalbumin in total serum albumin (f(HMA)) is associated with...BACKGROUND AND AIMS: Biomarkers of protein nutritional status are essential for understanding the relationship between diet and frailty. The fraction of mercaptoalbumin in total serum albumin (f(HMA)) is associated with protein deficiency and physical function in older adults. However, whether f(HMA) explains the relationship between protein intake and frailty remains unclear. We aimed to determine whether f(HMA) reflects frailty severity and clarify the relationship between protein intake and nutritional biomarkers in older adults. METHODS: This cross-sectional study analyzed data from 377 adults aged ≥65 years. Participants were classified as robust, prefrailty, or frailty based on the revised Japanese version of the Cardiovascular Health Study criteria. Dietary protein intake was assessed using a brief-type self-administered diet history questionnaire. Protein nutritional status was evaluated using serum albumin, f(HMA), transthyretin, total protein, and branched-chain amino acids levels. Relationships between protein intake and biomarkers were analyzed using multivariate linear regression while associations with frailty severity were examined using ordinal logistic regression. Mediation analysis assessed whether f(HMA) mediated the effect of protein intake on frailty status (prefrailty-or-worse vs robust). In an exploratory analysis, machine learning models were developed to discriminate frailty using a random forest classifier. RESULTS: The prevalence of prefrailty and frailty was 52.5% and 14.7%, respectively. Protein intake was negatively associated with frailty severity (P = 0.041). Only f(HMA) was positively associated with protein intake (P = 0.005) and negatively associated with frailty or prefrailty (P < 0.001 and P = 0.008). f(HMA) was independently associated with protein intake and frailty status and partially statistically mediated their relationship (P = 0.009). The classification model incorporating f(HMA) outperformed traditional biomarker-based models, achieving an area under the receiver operating characteristic curve of 0.80. CONCLUSIONS: f(HMA) may serve as a useful biomarker linking protein nutrition to frailty in older adults. Further studies are required to confirm the predictive role of f(HMA) in frailty progression.
Bowel involvement is a severe manifestation of deep endometriosis that affects approximately 8-12% of women with endometriosis. Bowel endometriosis is most commonly localised in the rectosigmoid colon and frequently coex...Bowel involvement is a severe manifestation of deep endometriosis that affects approximately 8-12% of women with endometriosis. Bowel endometriosis is most commonly localised in the rectosigmoid colon and frequently coexists with other pelvic lesions. The pathogenesis of bowel endometriosis is multifactorial, involving hormonal, inflammatory, immune, genetic, and anatomical factors. Clinical presentation ranges from asymptomatic disease to severe gastrointestinal and pelvic symptoms, which can mimic other digestive disorders such as irritable bowel syndrome and inflammatory bowel disease. Diagnostic delays frequently exceed 7-10 years. Transvaginal ultrasound and MRI are the main non-invasive tools for the diagnosis and preoperative assessment of rectosigmoid endometriosis. First-line medical therapy with combined oral contraceptives or progestogens might provide symptom control but is not curative, whereas surgery is reserved for bowel obstruction or severe or refractory symptoms, with surgical approach tailored to disease characteristics and patient needs. Fertility outcomes remain uncertain, and the complexity of long-term management, including the rare risk of malignant transformation, supports the need for multidisciplinary follow-up.
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) in patients with diabetes mellitus (DM) represents a clinically heterogeneous subgroup, yet biomarkers that reflect diabetes-associated tumor biology and chemotherapy r...BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) in patients with diabetes mellitus (DM) represents a clinically heterogeneous subgroup, yet biomarkers that reflect diabetes-associated tumor biology and chemotherapy response remain limited. In particular, the influence of diabetes duration on treatment resistance in PDAC is poorly understood. METHODS: We performed an integrated translational analysis combining reanalysis of public single-cell RNA sequencing (scRNA-seq) datasets, clinical serum biomarker profiling, and functional validation using pancreatic cancer cell lines and patient-derived organoids. Circulating REG4 concentrations were measured in independent PDAC cohorts and correlated with diabetes duration, overall survival, and response to FOLFIRINOX. Functional relevance was assessed under diabetes-mimicking hyperglycemic conditions. RESULTS: Single-cell transcriptomic analysis demonstrated enrichment of REG4-expressing tumor cells within the classical PDAC subtype specifically in diabetic patients. Clinically, circulating REG4 concentrations were significantly elevated in PDAC patients with long-standing diabetes, and high REG4 levels were associated with poor overall survival and resistance to FOLFIRINOX exclusively in this subgroup. In contrast, no prognostic association was observed in non-diabetic or new-onset diabetic patients. In patient-derived organoids and pancreatic cancer cell lines, chronic glucose exposure induced REG4 expression, activation of WNT/β-catenin signaling, suppression of apoptotic pathways, and increased resistance to FOLFIRINOX, recapitulating key clinical features of long-standing diabetes-associated PDAC. CONCLUSIONS: These findings suggest REG4 as a candidate diabetes duration-dependent prognostic and predictive biomarker in pancreatic cancer, warranting validation in larger prospective cohorts. By linking metabolic context to chemotherapy resistance through REG4-associated signaling, this study provides a translational framework for patient stratification and treatment optimization in diabetes-associated PDAC.
Denz R, van de Sand H, Basten J
… +23 more, Meiszl K, Tokic M, Oganowski T, Grüter T, Stock S, Simic D, Shukri A, Kiltz U, Zacharopoulou M, Vollmar HC, Otte IC, Giehl C, Lauer R, Stallmach A, Franz A, Marschall U, Saam J, Tiemann C, Reeb K, Meyer I, Hellwig K, Timmesfeld N, VAC-MAC Consortium
J Infect Public Health
· 2026 Jul · PMID 42398453
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BACKGROUND: Individuals with autoimmune or immune mediated diseases (AID) are more susceptible to infections and often experience worse outcomes if infected, underscoring the importance of vaccination. However, it remain...BACKGROUND: Individuals with autoimmune or immune mediated diseases (AID) are more susceptible to infections and often experience worse outcomes if infected, underscoring the importance of vaccination. However, it remains unclear whether vaccine effectiveness (VE) differs between persons with and without AID. Our aim was to compare the effectiveness of influenza and herpes zoster vaccines in both groups, where the AID group consists of individuals with either multiple sclerosis (MS), chronic inflammatory bowel disease (IBD) or chronic inflammatory rheumatic disorders (CIRD). METHODS: We emulated five target trials using claims data from a large German health insurance provider: one for herpes zoster and four for influenza across different seasons. We used 1:1 balanced risk set matching and Cox proportional hazards models with interaction terms between vaccination status and AID status to estimate VE and differences in VE across groups. RESULTS: For the herpes zoster trial, 169,054 vaccinated individuals were matched to the same number of controls, including 10,994 AID individuals per group. Herpes zoster VE was 68.73 (95% CI 55.75-77.91) in the AID group and 60.30 (55.59-64.52) in the non-AID group (VE ratio: 1.14, 95% CI 0.93-1.30). Across four influenza seasons (2015/2016-2018/2019) between 1403,342 and 1713,064 individuals were included, including between 56,662 and 78,320 AID individuals. Influenza VE varied by outcome, season, and assumptions, but VE ratios remained near one in most analyses (VE ratios: -0.92-3.77), with all CIs including one. CONCLUSIONS: There was no evidence that VE differs meaningfully between individuals with and without AID, conditional on the included confounders. Both vaccines were similarly effective across groups, suggesting that VE is not reduced in MS, IBD, or CIRD patients. Further research is necessary to validate these findings for other AID and infections.
Cai S, Dharmayani PNA, Lewandowska M
… +10 more, Wijekulasuriya S, Varghese G, Carrigan A, Vizheh M, Boutros R, Goodall S, George J, Zekry A, Zurynski Y, Accelerated translational research in PRImary Liver Cancer Program Group
Public Health
· 2026 Jul · PMID 42398368
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OBJECTIVES: To synthesise evidence on hepatitis B/C (HBV/HCV) prevention programmes that reduce long-term liver disease and hepatocellular carcinoma (HCC) in high-income countries with opioid misuse, high immigration fro...OBJECTIVES: To synthesise evidence on hepatitis B/C (HBV/HCV) prevention programmes that reduce long-term liver disease and hepatocellular carcinoma (HCC) in high-income countries with opioid misuse, high immigration from endemic regions, and risk-based prevention strategies. STUDY DESIGN: Mixed-methods systematic review. METHODS: MEDLINE, Embase, CINAHL, and Scopus were searched for peer-reviewed English-language studies (January 2013-November 2025). Eligible studies evaluated tailored or enhanced HBV/HCV prevention programmes in high-income countries and reported improvements in liver-related outcomes. Evidence on disease burden, risk factors, programme effectiveness, cost-effectiveness, and facilitators and barriers was synthesised. Study quality was assessed using ROBINS-I and CHEERS. RESULTS: Twenty-three studies assessed prevention strategies including screening, vaccination, early treatment, ongoing liver disease monitoring, and HCC surveillance. Locally targeted community screening identified 15.3%-34.3% of undiagnosed HBV/HCV infections. Integrated care pathways and monitoring programmes enabled detection of advanced fibrosis (5.3%-46.2%) and HCC (3.5%-39.2%). Early treatment reduced long-term disease burden and economic costs. Cross-sector collaboration, community engagement, and integrated care models were notable enablers. CONCLUSIONS: Prevention strategies were shown to improve case finding, early detection of chronic infection and liver damage, linkage to care, treatment uptake, and surveillance adherence. Population-level modelling also demonstrated reductions in long-term disease burden and costs. However, direct evidence that implemented programmes reduce HCC incidence and mortality remains limited, and methodological heterogeneity constrains synthesis. Strengthening evidence on programme effectiveness in preventing advanced liver disease and HCC is needed. Co-designed, patient-centred, integrated programmes spanning the hepatitis-HCC care continuum may enhance equity and maximise prevention benefits when implemented at scale.
Diagnosis and management of porphyrias require appropriate biochemical testing. Tests available to practicing physicians in the US are not consistent and depend greatly on what is offered by individual laboratories. In a...Diagnosis and management of porphyrias require appropriate biochemical testing. Tests available to practicing physicians in the US are not consistent and depend greatly on what is offered by individual laboratories. In addition, harmonization, whereby results and interpretations from different laboratories are comparable, is not assured. Members of American Porphyrias Expert Collaborative (APEX) recommend that specific tests should be available to all physicians in the US for diagnosis and monitoring of porphyrias, and that harmonization of laboratory practices and results reporting across laboratories should be achieved. These efforts will lead to the development and more effective implementation of guidelines for the diagnosis and monitoring of porphyrias by both community providers and porphyria expert centers.
Kim YK, Cha YJ, Park SE
… +26 more, Kim HK, Kwon C, Kim G, Oh YR, Vázquez-Rosa E, Dahiya U, Moinova H, Koh Y, Gao F, Tripathi SJ, Chakraborty S, Jo DG, Woo M, Park H, Myung SJ, Cheon J, Lee Y, Qi X, Paul BD, Fink S, Kasturi L, Lutterbaugh J, Markowitz SD, Pieper AA, Kang YP, Shin MK
The prostaglandin- and autocoid-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is shown here to be pathologically elevated in Parkinson's disease (PD) patients and mouse models of PD in the substantia n...The prostaglandin- and autocoid-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is shown here to be pathologically elevated in Parkinson's disease (PD) patients and mouse models of PD in the substantia nigra, the region of the brain where dopaminergic neurons are lost in PD. Inhibiting 15-PGDH by pharmacologic blockade or partial genetic reduction restores redox homeostasis and mitigates microglial and astrocyte activation, dopaminergic neuron loss, and motor impairment across three mouse models of PD. These models included systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), intranigral lipopolysaccharide (LPS), and intrastriatal AAV-α-synuclein with intra-ventral tegmental area α-synuclein preformed fibrils (PFFs). The neuroprotective efficacy of 15-PGDH inhibition in PD is shown to be mediated by downregulation of the dopaminergic neuronal cell death mediator lipocalin-2 (Lcn2), the pro-inflammatory cytokine interleukin-1β, the reactive oxygen generator Cybb/Nox2, and oxidative tissue damage. Mechanistically, in vitro exposure of BV2 microglia to LPS recapitulates induction of Lcn2, Cybb/N OX2 and superoxide, and all three of these effects are reversed by co-treating with prostaglandin E2 (PGE2), the prototypical degradation substrate of 15-PGDH. With a 15-PGDH inhibitor (MF-300) currently in human clinical trials for peripheral indications, these findings have translational relevance for PD.
INTRODUCTION: Pediatric cholelithiasis incidence is increasing. Adult guidelines and the recently developed pediatric DUCT criteria aim to identify patients at risk for choledocholithiasis, but pediatric validation is la...INTRODUCTION: Pediatric cholelithiasis incidence is increasing. Adult guidelines and the recently developed pediatric DUCT criteria aim to identify patients at risk for choledocholithiasis, but pediatric validation is lacking. This study aimed to identify predictive factors for pediatric choledocholithiasis. METHODS: We conducted a retrospective cohort study of children ≤18 y undergoing cholecystectomy from January 1, 2018 to May 31, 2023 at an academic medical center. Patients with cancer, chronic pancreatitis, or acalculous cholecystitis were excluded. Demographic and clinical data were abstracted from electronic records. Choledocholithiasis was defined by positive intraoperative cholangiogram or endoscopic retrograde cholangiopancreatography detection of stones/sludge. Univariate analyses identified potential predictors, and multivariable logistic regression assessed independent associations controlling for age and sex. Receiver operating characteristic curves determined optimal cutoff values for total bilirubin and common bile duct (CBD) size. RESULTS: Among 283 patients (median age 15 y, 74.7% female, 82.1% public insurance, 74.2% minority race/ethnicity), total bilirubin, alanine aminotransferase, aspartate aminotransferase, and sonographic CBD size were associated with choledocholithiasis on univariate analysis (P < 0.01). Multivariable analysis showed CBD size independently increased odds of choledocholithiasis by 57% per 1 mm (P < 0.001) and total bilirubin increased odds of choledocholithiasis by 21% per 0.1 mg/dL increase in bilirubin (P = 0.012). Optimal cutoffs were 6 mm CBD (area under curve: 0.87) and bilirubin of 1.4 mg/dL (area under curve: 0.79). CONCLUSIONS: CBD dilation ≥6 mm predicted choledocholithiasis, consistent with DUCT criteria, but a lower total bilirubin (≥1.4 mg/dL) was also associated with increased risk. These findings support the need for a validated pediatric-specific predictive tool to guide timely intervention and optimize resource use.
Harden D, Rodriguez N, Roybal K
… +18 more, Coffin T, Johnson G, Le Beaux K, Connolly M, Rountree J, Ukaegbu C, Revette AC, Nava-Coulter B, Caruso A, Roberts J, Brodney S, Schoolcraft K, Syngal S, Drew DA, May FP, Haas JS, Wendt SJ, Warner ET
J Med Internet Res
· 2026 Jul · PMID 42398058
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BACKGROUND: The use of web-based approaches to identify, recruit, enroll, survey, and interview health-related research participants has increased over time, with rapid acceleration since the COVID-19 pandemic. These app...BACKGROUND: The use of web-based approaches to identify, recruit, enroll, survey, and interview health-related research participants has increased over time, with rapid acceleration since the COVID-19 pandemic. These approaches can make research more accessible to a broader population, but also increase the risk of fraudulent or imposter participants infiltrating research studies. While this threat has been discussed extensively in quantitative survey research, less has been reported in qualitative and mixed methods studies. OBJECTIVE: This study aims to identify recurring patterns of fraudulent study participation and to offer strategies for identification, remediation, and reporting. METHODS: Encounters with fraudulent or imposter individuals during recruitment, enrollment, survey distribution, data collection, and focus group sessions in 2 multisite qualitative and mixed methods research studies are presented. Content from both studies was analyzed to identify common themes and develop strategies for prevention and remediation. RESULTS: Investigators across 2 multisite studies observed several indicators of suspected fraudulent activity, including large response volumes over a short period, highly repetitive email addresses, higher-than-expected proportions of phone numbers with area codes outside the study area, and unusual email/phone responses using atypical language and phrasing. Several imposter or fraudulent individuals disrupted online focus group sessions. To mitigate these issues, both studies implemented remediation strategies, including enhanced screening procedures at baseline, cross-checking of survey responses, and additional identity verification methods prior to participation. Studies took various actions to address these experiences, including notifying the institutional review board, recruitment platforms, and funders. CONCLUSIONS: This multisite study identified multiple ways that imposter or fraudulent participants can pose a significant and evolving threat to the integrity of qualitative and mixed methods. These types of fraudulent actors can distort data and undermine research credibility. Lessons learned highlight the importance of real-time recruitment and enrollment analysis and the need for transparent reporting. Addressing this issue will require a comprehensive approach to prevent and address fraudulent study participation that includes collaboration with multiple stakeholders and the broader research community to effectively address this issue.
Romandini E, Perri G, Maekawa A
… +14 more, Bannone E, Sahakyan MA, Kleive DB, Ghorbani P, Marchegiani G, Montorsi R, Cattelani A, Gilg S, Fretland ÅA, Holmberg M, Sparrelid E, Labori KJ, Edwin B, Salvia R
BACKGROUND: The International Study Group for Pancreatic Surgery (ISGPS) recently introduced a standardized definition and grading system for postpancreatectomy acute pancreatitis (PPAP), which was validated for pancreat...BACKGROUND: The International Study Group for Pancreatic Surgery (ISGPS) recently introduced a standardized definition and grading system for postpancreatectomy acute pancreatitis (PPAP), which was validated for pancreatoduodenectomy but not for distal pancreatectomy (DP). This study investigated the incidence and predictors of PPAP following DP and its associated postoperative complications. METHODS: Patients who underwent DP for all indications between 2015 and 2022 at three European centres were retrospectively analysed. PPAP was defined according to the ISGPS criteria (postoperative serum hyperamylasaemia (POH), radiological findings) and patient clinical deterioration. Standard univariable and multivariable and receiver operating characteristic (ROC) curve analyses were conducted. RESULTS: Among 1192 patients, PPAP occurred in 45 (3.8%): 35 grade B (2.9%) and 10 grade C (0.8%). POH without PPAP occurred in 165 patients (13.8%). Clinical outcomes worsened progressively across patients without POH/PPAP, with POH only, and with PPAP (Clavien-Dindo ≥ IIIa: 17.8%, 21.2%, and 53.3%, respectively; overall P < 0.001). PPAP was associated with higher rates of postoperative complications, including pancreatic fistula (68.9%), delayed gastric emptying (17.8%), and unplanned intensive care unit admission (17.8%). Compared with POH only, PPAP was associated with higher C-reactive protein (CRP) levels on postoperative day (POD) 2 and POD3. Among patients with POH, higher CRP levels on POD3 remained independently associated with PPAP in multivariable analysis (adjusted odds ratio 1.01; P < 0.001), together with multiorgan resection and smoking status. ROC curve analyses supported the discriminatory performance of CRP, particularly on POD3. CONCLUSION: PPAP is a rare but potentially severe complication after DP. Among patients with POH, elevated early postoperative CRP, particularly on POD3, may allow early risk stratification, identifying those at high risk of PPAP who may benefit from targeted mitigation strategies.
BACKGROUND: Crohn's disease (CD) is characterized by transmural inflammation, and achieving transmural healing (TH), may lead to improved long-term outcomes. However, evidence supporting this hypothesis is limited. METHO...BACKGROUND: Crohn's disease (CD) is characterized by transmural inflammation, and achieving transmural healing (TH), may lead to improved long-term outcomes. However, evidence supporting this hypothesis is limited. METHODS: Adult patients diagnosed with CD who underwent ileocolonoscopy and cross-sectional imaging within 6 months were included. Long-term outcomes of CD-related surgery and hospitalization in patients with TH, endoscopic healing (EH) alone, radiologic healing (RH) alone, and no healing (NH) were assessed. We used Cox proportional hazards models and modified Poisson regression. RESULTS: Among 180 included patients, 26.7% achieved TH, 21.1% achieved EH, 12.8% achieved RH, and 39.4% were classified as NH. At baseline, 54.4% were on biologics which increased to 81.7% at last follow-up (76-78 months across groups). Cumulative probabilities of surgery were lowest in patients with TH (0%, 2.3%, 7.0% at 1, 3, and 5 years) and highest in patients with NH (13%, 20.5%, and 26.9%, respectively) (P = .03). On Cox proportional hazard regression analysis, TH was associated with a significantly reduced risk of CD-related surgery (hazard ratio, 0.01; 95% confidence interval, 0.00-0.35; P = .009) compared with NH. The probabilities of surgery were lower for patients with RH compared with EH (10% vs 13.2%, 10% vs 18.4%, and 21.2% vs 26.9% at 1, 3, and 5 years) but were not statistically significant (P = .41). Probabilities of CD-related hospitalization were lowest with TH (4.3%, 8.8%, and 13.6% at 1, 3 and 5 years) but were not statistically different than other healing categories (P = .67). CONCLUSIONS: TH was associated with superior long-term outcomes compared with EH or RH alone. Future studies should focus on standardizing its definition and evaluate treat-to-target strategies.
Schoeneich R, Patel RR, Lee BR
… +11 more, Disano P, Gao MT, VanDerGraaf M, Gosse M, El Abiad R, Levin A, Chandrasekharan C, Hoshi H, Bellizzi AM, Fei NH, Grewal US
Am J Clin Oncol
· 2026 Jun · PMID 42397948
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OBJECTIVES: Hereditary diffuse gastric cancer (HDGC) due to germline CDH1 pathogenic or likely pathogenic (P/LP) variants has traditionally been managed with prophylactic total gastrectomy (PTG), although contemporary da...OBJECTIVES: Hereditary diffuse gastric cancer (HDGC) due to germline CDH1 pathogenic or likely pathogenic (P/LP) variants has traditionally been managed with prophylactic total gastrectomy (PTG), although contemporary data suggest a lower and more heterogeneous cancer risk. Real-world management patterns remain incompletely defined. METHODS: We conducted a retrospective, single-center cohort study of adult patients with germline CDH1 P/LP variants managed between 2011 and 2024. Patients were categorized as undergoing PTG within 1 year of diagnosis or deferring surgery with endoscopic surveillance (ES). Primary outcomes included the detection of signet ring cell carcinoma (SRCC) and invasive gastric cancer. RESULTS: A total of 27 patients were identified (median age: 48 y; 81.5% female). Eight (29.6%) underwent early PTG, while 18 (66.7%) initially deferred surgery; 1 presented with de novo metastatic gastric cancer. Among PTG patients, 7 of 8 (87.5%) had Tis/T1a SRCC, and none had nodal involvement. Among those deferring PTG, surveillance was heterogeneous: 8 (44.4%) underwent structured ES, 6 (33.3%) had a single endoscopy, and 4 (22.2%) had no surveillance. Within structured ES, 1 patient (12.5%) developed invasive T2 disease, while the others had Tis/T1a SRCC or normal histology. Delayed gastrectomy (27.8%) revealed predominantly T1a SRCC without nodal involvement. CONCLUSIONS: Most detected lesions were early-stage and node-negative, and delayed gastrectomy did not appear to compromise pathologic outcomes in selected patients. However, invasive progression during surveillance underscores that ES is not without risk. These findings support a risk-adapted, patient-centered approach to CDH1 management with emphasis on structured surveillance and shared decision-making.
Enteral feeding is an essential intervention for patients unable to meet their nutritional needs orally, but it carries risks that require skilled nursing recognition and management. This article provides a practical ove...Enteral feeding is an essential intervention for patients unable to meet their nutritional needs orally, but it carries risks that require skilled nursing recognition and management. This article provides a practical overview of the most common complications encountered across the range of enteral tube types - including refeeding syndrome, nausea and vomiting, aspiration, diarrhoea and constipation, tube blockage, and tract infection - and outlines the nursing management strategies supported by current evidence and guidance. Prompt identification of complications, accurate documentation, early escalation and effective multidisciplinary working are central to safe enteral feeding practice.
OBJECTIVES: Individuals at high-risk (HRI) of developing pancreatic adenocarcinoma (PDAC) are offered intensive screening to detect PDAC at an early, curable stage. There is scant data on how HRI PDAC screening programs...OBJECTIVES: Individuals at high-risk (HRI) of developing pancreatic adenocarcinoma (PDAC) are offered intensive screening to detect PDAC at an early, curable stage. There is scant data on how HRI PDAC screening programs perform in clinical practice outside of large, prospective cohort studies. This study assessed the screening patterns, outcomes, and adherence of HRIs participating in a structured PDAC screening program. METHODS: We conducted a retrospective cohort study of HRIs at a single, quaternary care referral center between 2009-2025. Based on risk factors, patients were offered structured testing with non-invasive imaging (most commonly magnetic resonance imaging, MRI) and/or endoscopic ultrasound (EUS). Demographic and clinical information was obtained through chart review. Adherence rates were calculated, and a multivariable analysis was conducted to identify factors associated with adherence. RESULTS: 316 patients met high-risk criteria and underwent screening. Seven PDACs were detected during a mean cohort follow up of 2.5 years; six early-stage PDACs (four stage I, two stage II) were detected during surveillance, and one stage III PDAC was diagnosed due to symptoms in a patient non-adherent to screening. Seven patients underwent surgical resection, including four with PDAC and three with worrisome lesions on imaging or endoscopic ultrasound (two high-risk cystic lesions and one PanIN-IB). There was one death from PDAC in a patient with stage IA disease who didn't undergo resection. The mean adherence rate for the cohort was 76.5% over 3.8 years. Individuals with pathogenic germline variants demonstrated higher adherence (P=0.02). CONCLUSION: A PDAC screening program for HRIs identified early stage PDAC in an important proportion of patients. While overall adherence rates are high, additional research is needed to identify barriers affecting patient adherence.
Stefan-van Staden RI, Georgescu-State R, Comnea-Stancu IR
… +7 more, Cioates Negut C, Tuchiu-Stanca BM, Gheorghe DC, Ilie-Mihai RM, Stefan AI, Brisc C, Orăşeanu A
A novel stochastic electrochemical sensing platform based on a β-cyclodextrin/silver oxide nanoparticle-decorated multiwalled carbon nanotube composite (β-CD/AgONPs@MWCNT/CPE) was developed for the molecular enantiorecog...A novel stochastic electrochemical sensing platform based on a β-cyclodextrin/silver oxide nanoparticle-decorated multiwalled carbon nanotube composite (β-CD/AgONPs@MWCNT/CPE) was developed for the molecular enantiorecognition and enantioanalysis of 12 amino acids (l/d-glutamine, l/d-tryptophan, l/d-cysteine, l/d-methionine, l/d-lysine, l/d-phenylalanine, l/d-valine, l/d-serine, l/d-leucine, l/d-ornithine, l/d-pipecolic acid, and l/d-alanine) in biological samples. The AgONPs were synthesized via an environmentally friendly approach using green tea extract as a reducing and stabilizing agent, enabling a sustainable fabrication process with good experimental reproducibility under controlled conditions. Structural and morphological analyses, along with electrochemical characterization, confirmed the uniform incorporation of β-CD and AgONPs onto MWCNTs, thereby enhancing both electron-transfer kinetics and molecular recognition efficiency. The sensing interface exhibited low limits of quantification, a wide linear concentration range, and high sensitivity, enabling simultaneous enantioselective detection of amino acids in complex biological matrices, including whole blood, tumor tissue, saliva, and urine. Biological samples were collected from patients confirmed with gastric cancer as well as from healthy volunteers. Recovery values exceeded 97.0% ( = 10), with standard deviations (SDs) from the mean value of less than 0.10 (the recovery value represents the average of 10 determinations performed for the same sample) when a refreshed surface of the sensor was used for a new determination; without refreshing, the surface the mean value was the same but the deviations from the mean varied from 1.7 to 3.4. The platform has demonstrated good potential as a screening tool for clinical diagnostics and metabolic studies.
Peutz-Jeghers Syndrome (PJS) is caused by germline pathogenic variants in the STK11 gene and is associated with elevated lifetime risks for several cancers, including lung cancer. Currently, no formal recommendations exi...Peutz-Jeghers Syndrome (PJS) is caused by germline pathogenic variants in the STK11 gene and is associated with elevated lifetime risks for several cancers, including lung cancer. Currently, no formal recommendations exist for lung cancer screening in PJS. This structured narrative review compares lung cancer risk in PJS with lung cancer risk in individuals currently eligible for screening based on age and smoking history. PubMed and Web of Science were searched from 1/1/1980 to 9/11/2023 using the terms "Peutz-Jeghers Syndrome" AND "Cancer." Studies reporting lung cancer risk in PJS were included. Reported lung cancer risks were compared to 5-year, 10-year, and lifetime lung cancer risks in the general population based on age and pack-years of smoking. Seventeen studies were included. Across the studies, the incidence of lung cancer ranged from 0.8 to 13.3%. Studies that included lung cancer risk relative to the general population reported a relative risk range of 2.9-22.9. Cumulative risk was reported in 5 studies and surpassed 5% by age 60 (range 7 to 17%). Guidelines for low-dose CT (LDCT) lung cancer screening for individuals aged 50-80 with a smoking history of at least 20 pack-years are associated with a similar or higher threshold for lung cancer risk. The lifetime lung cancer risk for individuals with PJS is similar to current guideline-based risk thresholds for screening based on age and smoking status. Given their elevated lifetime risk, individuals with PJS may be candidates for LDCT for lung cancer screening and should be formally studied to elucidate the risks, benefits, and optimal implementation in this patient population.