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11 pages, 229 KB  
Article
Bronchoalveolar Results in Young Children with Chronic Lung Symptoms: Lessons Learned from an Allergy–Pulmonology Project Guided by an Updated Mini Review of the Current Literature of Bronchoalveolar Lavage Eosinophilia and Neutrophilia in Normal Children
by Russell J. Hopp, Elizabeth A. Eischeid, Steven Rose and Heather Thomas
Children 2026, 13(2), 231; https://doi.org/10.3390/children13020231 (registering DOI) - 6 Feb 2026
Abstract
Background: Pediatric bronchoscopy and bronchoalveolar lavage (BAL) are valuable procedures, used by pediatric pulmonologists in a wide variety of clinical scenarios. Reports of indications for BAL include investigations of infectious processes, for unusual or poorly responsive pneumonia, and non-infections reasons, including interstitial lung [...] Read more.
Background: Pediatric bronchoscopy and bronchoalveolar lavage (BAL) are valuable procedures, used by pediatric pulmonologists in a wide variety of clinical scenarios. Reports of indications for BAL include investigations of infectious processes, for unusual or poorly responsive pneumonia, and non-infections reasons, including interstitial lung disease and aspiration syndromes. BAL in pediatric asthma is occasionally done in severe and uncontrolled asthma, to rule out co-morbid conditions or to investigate asthma phenotypes. We report here the results of BAL in young children with global pre-BAL diagnoses, with comprehensive analysis of the BAL cellularity and culture results, and with a post hoc review by an allergist. The results of BAL in children with enigmatic pulmonary processes were compared to the expected BAL cellularity in normal children, obtained by an expanded historical mini review. Methods: The initial objective was to perform a mini review of the collective published data for normal/control children with BAL differential cell counts with the purpose of using the results to compare normals to the information obtained on the symptomatic children with BAL results from pulmonologists in our combined allergy–pulmonary division. The exploratory study group was children 0–6 years of age who underwent a BAL from 2000 to 2024 at an academic pulmonary-allergy division. The children had presumptive diagnoses requiring investigation, including the most common diagnoses of asthma, chronic cough, aspiration, or refractory bronchitis, and in this post hoc protocol only the diagnoses provided on the pre- and/or post-operative summary by the divisional pulmonologist(s) performing the BAL were used in the post hoc analysis. Secondarily, the operative day pre- and/or post-lavage diagnoses were used to divide the children into groups (based on operative day diagnoses) to stratify their lavage results, based on eosinophils, neutrophils, culture positivity and lipid-laden macrophages. Normative data collected from the literature was used as the historically expected results for the BAL group(s) analysis. Results: A mini review of BAL cellularity across 25+ years of literature was performed to establish normative data for our subsequent analysis. Both eosinophils and neutrophils are low or absent in normal children based on the comprehensive literature review. As a part of a larger cohort of 500 children ages 0–20 years, 317 children ages 0–6 were selected for review. The protocol was approved by the University Institutional Review Board. Using the mini review as reference, we found that eosinophil counts of one or more were recovered in over 20% of all children, regardless of bronchoscopy indication. Neutrophilia > 50% of cells and/or bacteria colony counts > 100,000 organisms were also frequent findings (>50 percent of the children). As a separate observation, lipid-laden macrophages did not isolate to aspiration indications for the bronchoscopy and lavage. Conclusions: An updated mini review of the cellularity expected in control children provided a context to the findings in our studied exploratory sample population. There was a high recovery of neutrophils coupled with culture positivity found across all children undergoing BAL. Eosinophils > 1 were present in up to 25% with a pre-lavage asthmatic symptom indication, but almost an equal percentage in other children with non-asthma-like conditions was surprising. Lipid-laden macrophage data was unhelpful. Full article
(This article belongs to the Section Pediatric Allergy and Immunology)
13 pages, 1348 KB  
Article
Deciphering the Genomic Landscape of Oropharyngeal Squamous Cell Carcinoma: Distinct Mutation Patterns in Disease
by Beau Hsia, Gabriel Bitar, Pedro S. Bonilla, Vinay D. Veluvolu, Nathan Tran, Saif Alshaka, Eli Oved, Bhavish Aubeelauck, Hassan Nur, Abubakar Tauseef, Vijay A. Patel and Aliasgher Khaku
Life 2026, 16(2), 282; https://doi.org/10.3390/life16020282 (registering DOI) - 6 Feb 2026
Abstract
Objective: We aimed to characterize the somatic mutational landscape of oropharyngeal squamous cell carcinoma (OPSCC) and identify potential genomic drivers of tumor progression and therapeutic resistance using the AACR GENIE database. Study Design: Retrospective genomic analysis was employed. Setting: We used publicly available [...] Read more.
Objective: We aimed to characterize the somatic mutational landscape of oropharyngeal squamous cell carcinoma (OPSCC) and identify potential genomic drivers of tumor progression and therapeutic resistance using the AACR GENIE database. Study Design: Retrospective genomic analysis was employed. Setting: We used publicly available data from the American Association for Cancer Research (AACR) Project GENIE database accessed via cBioPortal. Methods: We analyzed 412 tumor samples from 401 patients diagnosed with OPSCC. Somatic mutations, clinical variables and tumor characteristics were extracted and analyzed. Statistical comparisons of mutation frequencies across gender and tumor stage (primary vs. metastatic) were conducted. Co-occurrence and mutual exclusivity analyses were performed to identify significant genomic patterns. Results: The most frequently mutated genes included TP53 (30.1%), PIK3CA (26.0%), and KMT2D (21.6%). Gender-specific analyses suggested potential enrichment of TP53 and MET mutations in females and of ZNF750 in males. Distinct mutation patterns were observed between primary and metastatic tumors; primary tumors were enriched for mutations in TP53 and CDKN2A, while metastatic lesions harbored unique alterations in genes like CBLB and BUB1B, suggesting pathways involved in immune evasion and chromosomal instability may drive disease progression. Co-occurrence was noted between PIK3CA and FBXW7, and mutual exclusivity between TP53 and CYLD. Conclusions: This study identifies distinct genomic signatures in OPSCC subgroups, highlighting candidate biomarkers in pathways like PI3K/AKT signaling that warrant further investigation. Validating these markers in prospective trials is a critical next step to translate these findings into personalized therapeutic strategies for OPSCC patients. Full article
(This article belongs to the Special Issue New Trends in Otorhinolaryngology)
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15 pages, 1261 KB  
Systematic Review
Efficacy and Safety of Minocycline-Containing Bismuth Quadruple Therapies Versus Standard First-Line Bismuth Quadruple Therapies for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis
by Hakim Ullah Wazir, Abdul Muqeet Khuram, I M Khalid Reza, Hafsa Ajmal, Hafsa Parveen, Zeeshan Ahmed, Yousra Iftequar, Noora Inam, Ilyas Muhammad Sulaiman, Nayanika Tummala, Hafiz Muhammad Moaaz Sajid, Anum Zia Khan and Ussama Shafaqat
Infect. Dis. Rep. 2026, 18(1), 16; https://doi.org/10.3390/idr18010016 (registering DOI) - 6 Feb 2026
Abstract
Background: Growing antibiotic resistance and the limited availability of key components in standard Helicobacter pylori treatments have driven the search for effective alternatives. Minocycline, with its broad-spectrum activity and favorable pharmacokinetics, has emerged as a promising substitute. This meta-analysis compares the safety and [...] Read more.
Background: Growing antibiotic resistance and the limited availability of key components in standard Helicobacter pylori treatments have driven the search for effective alternatives. Minocycline, with its broad-spectrum activity and favorable pharmacokinetics, has emerged as a promising substitute. This meta-analysis compares the safety and efficacy of minocycline-containing bismuth quadruple therapy (MBQT) to conventional first-line BQT regimens, incorporating data from the recent study by Lin et al. Methods: The inclusion criteria were randomized controlled trials (RCTs) with a target population of both treatment-naïve and previously treated patients diagnosed with Helicobacter pylori (H. pylori) infection. The intervention received by eligible patients was a minocycline–bismuth quadruple therapy (MBQT) regimen containing bismuth, minocycline, proton pump inhibitors (PPI), and any additional antibiotic with a minimum period of 2 weeks of administration. We excluded study designs other than RCT and clinical trials that include patients without confirmed H. pylori infection, animal populations, in vitro experiments, and reports of other outcomes that did not include a minimum intervention duration of 2 weeks. A comprehensive literature search was conducted on PubMed, EMBASE, Cochrane Library, and ScienceDirect from inception to 20 May 2025. After screening via Rayyan, data were extracted on an Excel spreadsheet. Quality was assessed using the Cochrane RoB 2.0 tool. Eligible randomized controlled trials (RCTs) were included and analyzed using RevMan 5.4. Outcomes assessed were intention-to-treat and per-protocol eradication rates. Adverse effects were compared among therapies. A random-effects model was used; an I2 < 50% and p-value < 0.05 indicated homogeneity and significant results respectively. Results: Five RCTs with 7 interventions involving 2812 patients were included. The pooled odds ratio (OR) for MBQT in intention-to-treat (ITT) analysis was 1.25 (95% CI: 0.96–1.61), showing a non-significant trend. No heterogeneity was detected (I2 = 0.0%). In the modified ITT (mITT) analysis (2 studies), MBQT showed higher eradication (OR: 1.70, 95% CI: 0.00–1042.90), but wide CI and high heterogeneity (I2 = 70.7%) limited interpretation. All studies were included in the per-protocol (PP) analysis, which showed a statistically significant improvement with MBQT (OR: 1.67, 95% CI: 1.14–2.45) and low heterogeneity (I2 = 5.2%), suggesting consistent results. Although not statistically significant, MBQT was associated with a slightly lower rate of adverse events compared to standard therapy (OR: 0.81, 95% CI: 0.59–1.12). I2 = 50.6% showed moderate heterogeneity in safety outcomes. Discussion: the number of included RCTs was modest, with only five studies meeting eligibility criteria, and only two contributing to the modified intention-to-treat analysis. The risk-of-bias assessment showed variation in methodological quality across the included studies. Several studies exhibited high risk judgments in critical domains. particularly randomization, deviations from intervention, and selective reporting. Patients who completed the treatment benefited more from MBQT, which also had a comparable safety profile to conventional BQT regimens. In the treatment of H. pylori infection, MBQT may be considered a safe alternative for first-line treatment. Full article
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17 pages, 51927 KB  
Article
Identifying Inefficient Urban Land Stock in High-Density Cities: A Multi-Source Geospatial Framework
by Zhigang Zhao, Minmin Li, Shilong Wei, Ding Ma, Wei Zhu, Xiaoming Li, Yebin Chen and Yafei Wang
Sustainability 2026, 18(3), 1662; https://doi.org/10.3390/su18031662 (registering DOI) - 6 Feb 2026
Abstract
China’s urban development is shifting from extensive expansion to stock-oriented renewal, making the precise identification of inefficient land stock essential for sustainable spatial governance. To overcome the limitations of single-source data and coarse delineation, we propose a multi-source geospatial framework integrating land-use surveys, [...] Read more.
China’s urban development is shifting from extensive expansion to stock-oriented renewal, making the precise identification of inefficient land stock essential for sustainable spatial governance. To overcome the limitations of single-source data and coarse delineation, we propose a multi-source geospatial framework integrating land-use surveys, socioeconomic statistics, spatiotemporal mobility trajectories, and ecological indicators. Using Shenzhen as a case study, we construct an eight-indicator system across social, economic, and ecological dimensions and apply entropy-based objective weighting to support GIS-based weighted overlay evaluation. The results identify 65.37 km2 of inefficient land in 2019, accounting for approximately 7% of Shenzhen’s construction land, with a distinctive “edge aggregation and corridor extension” pattern concentrated along urban–rural fringes and administrative boundaries. Inefficient land is highly uneven across districts, with Longgang (21.11 km2) and Bao’an (12.57 km2) contributing 51.5% of the total and exhibiting statistically spatial clustering (p < 0.01). The observed configuration reflects path-dependent historical development and policy–ecology constraints, including the interaction between ecological control boundaries and peripheral expansion. Overall, by integrating multi-source spatiotemporal big data within a multi-dimensional evaluation framework, the framework offers an objective and transferable approach for diagnosing inefficient land stock and informing targeted urban renewal strategies in high-density cities worldwide. Full article
(This article belongs to the Section Sustainable Urban and Rural Development)
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9 pages, 228 KB  
Article
Beyond Foodborne HAV: Sexual Transmission Drives a New Wave of Cases in Romania
by Adrian Paun, Irina Ianache, Ruxandra Moroti, Georgiana Pomohaci, Gratiela Tardei, Mike Youle, Simona Ruta and Cristiana Oprea
Viruses 2026, 18(2), 215; https://doi.org/10.3390/v18020215 (registering DOI) - 6 Feb 2026
Abstract
Background: In 2022, Romania experienced a sharp increase in hepatitis A virus (HAV) infections, with evidence of predominant fecal–oral transmission through sexual contact, raising concern for an outbreak among men who have sex with men (MSM). Methods: We conducted a prospective [...] Read more.
Background: In 2022, Romania experienced a sharp increase in hepatitis A virus (HAV) infections, with evidence of predominant fecal–oral transmission through sexual contact, raising concern for an outbreak among men who have sex with men (MSM). Methods: We conducted a prospective multicenter study between 1 March 2022 and 1 March 2023 in two tertiary hospitals in Bucharest. HAV infection was defined by a compatible clinical presentation, elevated liver enzymes, and positive anti-HAV IgM serology. Clinical and laboratory characteristics were compared by transmission route and HIV status. Results: A total of 191 patients were diagnosed with HAV, including 105 MSM and 86 with foodborne transmission. All were unvaccinated. Most patients were male (82.2%), with a median age of 30 years (IQR 24–38). MSM were significantly younger and reported higher-risk sexual behaviors, including chemsex and multiple or occasional partners (p < 0.0001). Among MSM, 48 (25.1%) were living with HIV, most with preserved immune status and undetectable viral loads. Clinical manifestations were similar across groups, with jaundice being most frequent (89.5%). However, MSM exhibited more severe hepatocellular injury, reflected by higher ASAT and ALAT levels and lower prothrombin concentration, independent of HIV status. MSM were also more likely to have concomitant sexually transmitted infections, including syphilis and mpox (p < 0.001). Disease was predominantly mild, although MSM had longer hospital stays. Conclusions: The 2022 HAV surge in Romania was driven by both sexual and foodborne transmission. Targeted HAV vaccination, along with integrated sexual health services and harm-reduction strategies, is essential to prevent future outbreaks. Full article
(This article belongs to the Special Issue HIV and Viral Hepatitis Co-Infection)
12 pages, 1158 KB  
Article
Symptomatic Pheochromocytoma: A Risk Model
by María Consuelo Muñoz, Beatriz Febrero, Miriam Abellán and José Manuel Rodríguez
Cancers 2026, 18(3), 528; https://doi.org/10.3390/cancers18030528 (registering DOI) - 6 Feb 2026
Abstract
Background/Objectives: Pheochromocytoma (PHEO) is increasingly detected incidentally or through genetic screening; however, predictors of symptomatic presentation and its perioperative impact remain unclear. We aimed to quantify the prevalence of symptomatic PHEO, identify associated factors, compare perioperative outcomes, and develop a predictive nomogram. [...] Read more.
Background/Objectives: Pheochromocytoma (PHEO) is increasingly detected incidentally or through genetic screening; however, predictors of symptomatic presentation and its perioperative impact remain unclear. We aimed to quantify the prevalence of symptomatic PHEO, identify associated factors, compare perioperative outcomes, and develop a predictive nomogram. Methods: We retrospectively analyzed patients diagnosed and/or operated on for PHEO at a tertiary referral center between 1984 and 2021. Associations with symptomatic presentation were assessed using univariate and multivariable logistic regression analyses. A nomogram was constructed based on independent predictors and evaluated using receiver operating characteristic (ROC) analysis and the area under the curve (AUC). Results: Among 173 patients (mean age 44.4 ± 15.8 years; 53.2% women), 67.1% were symptomatic. In multivariable analysis, male sex (odds ratio [OR] 0.33; p = 0.023) and the presence of a germline mutation (OR 0.15; p = 0.004) were associated with a lower likelihood of symptoms, whereas a noradrenergic secretion profile was associated with a higher likelihood (OR 12.73; p = 0.02). Symptomatic patients had higher rates of intraoperative (OR 2.60; p = 0.032) and postoperative complications (OR 3.09; p = 0.04). The nomogram incorporating sex, genetic status, and noradrenergic profile demonstrated moderate discrimination (AUC 0.799; 95% confidence interval 0.722–0.877; p < 0.001). Conclusions: Symptomatic PHEO is associated with sex, genetic status, and noradrenergic secretion profile and is linked to increased perioperative morbidity. A simple nomogram based on readily available variables may help estimate individual risk and support perioperative management. Full article
(This article belongs to the Special Issue New Insights into Pheochromocytoma and Paraganglioma)
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15 pages, 246 KB  
Article
Genetic Syndromes and Multimorbidity in Adults with Congenital Heart Disease and Heart Failure: Insights from the PATHFINDER-CHD Registry
by Ann-Sophie Kaemmerer-Suleiman, Fritz Mellert, Stephan Achenbach, Pinar Bambul-Heck, Robert Cesnjevar, Oliver Dewald, Helena Dreher, Andreas Eicken, Anna Engel, Peter Ewert, Annika Freiberger, Jürgen Hörer, Christopher Hohmann, Stefan Holdenrieder, Michael Huntgeburth, Harald Kaemmerer, Renate Kaulitz, Frank Klawonn, Christian Meierhofer, Steffen Montenbruck, Nicole Nagdyman, Rhoia C. Neidenbach, Robert D. Pittrow, Christoph R. Sinning, Fabian von Scheidt, Pelagija Zlatic, Frank Harig and Mathieu N. Suleimanadd Show full author list remove Hide full author list
J. Clin. Med. 2026, 15(3), 1290; https://doi.org/10.3390/jcm15031290 (registering DOI) - 6 Feb 2026
Abstract
Background/Objectives: Progress in diagnostic and therapeutic strategies has resulted in an increasing prevalence of adults with congenital heart disease (ACHD), including those involving genetically determined syndromes. This study aimed to characterize prevalence, congenital phenotypes, heart failure (HF) stages, comorbidity burden, and current medical [...] Read more.
Background/Objectives: Progress in diagnostic and therapeutic strategies has resulted in an increasing prevalence of adults with congenital heart disease (ACHD), including those involving genetically determined syndromes. This study aimed to characterize prevalence, congenital phenotypes, heart failure (HF) stages, comorbidity burden, and current medical management of ACHD and concomitant genetically determined syndromes enrolled in a prospective HF-focused registry. Methods: The PATHFINDER-CHD Registry is a German-based (est. 2022) multicenter observational registry. This web-based platform consecutively tracks ACHD patients across the heart failure spectrum, including those with current or prior HF, as well as those at high structural or functional risk. HF stage was classified using a modified ACC/AHA scheme adapted for CHD; functional capacity was graded according to the Perloff classification. Baseline demographics, CHD anatomy, prior surgical/interventional treatment, cardiac and extracardiac comorbidities, and medication were collected from medical records. Results: Among 1987 enrolled ACHD, 107 (5.4%) had a genetic syndrome (n = 65, 60.7% women; mean age 33.5 ± 9.4 years; range 18–68). Most common syndromes were trisomy 21 (n = 49; 45.8%) and 22q11.2 deletion (n = 27; 25.2%); 31 patients (30.0) had rarer syndromes. Predominant CHD diagnoses were atrioventricular septal defect (n = 42, 39.3%), tetralogy of Fallot (n = 19, 17.8%), and pulmonary atresia with ventricular septal defect (n = 7, 6.5%). A systemic left ventricle was present in 102 (95.3%); 40 (37.4%) had primarily cyanotic CHD, and 7 (6.5%) an Eisenmenger physiology. Most patients (n = 71; 66.4%) had undergone definite surgical repair; 25 patients (23.3%) had at least one catheter intervention, including transcatheter valve implantation in 17 cases (15.9%). HF stage was mainly B (n = 30, 28.0%) or C (n = 75, 70.1%). Perloff functional class I/II was present in 97 (90.7%). Leading cardiac comorbidities included intrinsic aortopathy (n = 49, 45.8%), pulmonary arterial hypertension (n = 12, 11.2%), and arrhythmias (n = 10, 9.3%). Frequent extracardiac comorbidities were thyroid dysfunction (n = 34, 31.8%), kidney disease (n = 16, 15.0%), hyperuricemia (n = 13, 12.1%), and depression (n = 15, 14.0%). Pharmacotherapy was used in 66 patients (61.7%). Beta-blockers (n = 25, 23.4%) were common, while ACEi/ARB (n = 9, 8.4%), diuretics (n = 10, 9.3%), MRAs (n = 8, 7.5%), and SGLT2 inhibitors (n = 3; 2.8%) were infrequently prescribed; no patient received ARNI or digitalis. For targeted treatment of pulmonary arterial hypertension, phosphodiesterase-5 inhibitors (n = 7, 6.5%), endothelin receptor antagonists (n = 6, 5.6%), or prostacyclin analogues (n = 1, 0.9%) were used. As oral anticoagulants, vitamin K antagonists or direct oral anticoagulants (DOACs) were prescribed in 17 cases (15.9%). Forty-one patients (38.3%) received thyroid hormone replacement. Conclusions: Syndromic ACHD constitute a small but clinically high-risk subgroup within an HF-oriented registry, marked by complex CHD, substantial cardio–extracardiac multimorbidity (notably aortopathy, PAH, thyroid disease, renal dysfunction, depression), and low utilization of contemporary HF therapies. These data support specialized, interdisciplinary, longitudinal care pathways and prospective studies addressing outcomes and evidence-based HF management in syndromic ACHD. Full article
(This article belongs to the Section Cardiology)
8 pages, 1284 KB  
Brief Report
Individualized Evaluation on Suspicion of Fibrotic Metabolic-Dysfunction-Associated Steatohepatitis: Real-World Experience from a Referral Center in Denmark
by Eva Efsen Dahl, Gro Linno Willemoe, Mark Berner-Hansen and Frank Vinholt Schiødt
J. Pers. Med. 2026, 16(2), 95; https://doi.org/10.3390/jpm16020095 (registering DOI) - 6 Feb 2026
Abstract
Background/Objectives: New guidelines for management of metabolic-dysfunction-associated steatotic liver disease (MASLD) patients recommend an individualized medicine approach mainly targeting patients with fibrotic metabolic-dysfunction-associated steatohepatitis (MASH) and metabolic risk factors for progression of disease. This cohort study reports real-world experience for the individual evaluation [...] Read more.
Background/Objectives: New guidelines for management of metabolic-dysfunction-associated steatotic liver disease (MASLD) patients recommend an individualized medicine approach mainly targeting patients with fibrotic metabolic-dysfunction-associated steatohepatitis (MASH) and metabolic risk factors for progression of disease. This cohort study reports real-world experience for the individual evaluation and final diagnosis of patients on suspicion of fibrotic MASH according to standardized international criteria. We aimed to identify patients with significant fibrosis (F2–F4). Methods: Adult patients with metabolic syndrome and/or elevated alanine aminotransferases (ALT > 50) referred in a 5-year period (2018–2022) on suspicion of fibrotic MASH were included. Medical history, anthropometric measurements, and routine (blood tests, ultrasound) and specific examinations were applied. Liver biopsy was offered for definite diagnosis and to evaluate MASLD characteristics. Patient demographics and characteristics as well as the absolute number and proportion of patients with definite MASLD and fibrotic MASH are reported. Results: A total of 137 adult patients were included. Ten percent of patients were evaluated without liver biopsy and diagnosed with chronic liver diseases other than MASLD. Liver-biopsied patients (n = 123) had a mean age (SD) of 49 (14) years, and 50% were males. Overweight or obesity was present in 94%, dyslipidemia in 74%, hypertension in 40%, and type 2 diabetes mellitus in 34%. Of all 137 patients, 104 (76%) were diagnosed with definite MASLD and 80 (58%) with definite MASH. A total of 74 (54%) patients had definite fibrotic MASH, while 41 (30%) had significant (F2–4) fibrotic MASH. Eight patients (6%) had cirrhotic (F4) MASH. A multivariate logistic regression analysis indicated that patients with type 2 diabetes, older age, and higher BMI were associated with an apparent increased risk of F2–F4 fibrosis. Conclusions: The majority of referred patients had cardiometabolic–hepatic metabolic risk factors and were diagnosed with definite MASLD. More than half of these were diagnosed with fibrotic MASH. Older age, type 2 diabetes, and higher BMI were apparent risk factors for MASH F2–F4 fibrosis. We conclude that the individual cardiovascular–hepatic risk profile applied supports the new guidelines and may be useful for referral and further evaluation at expert care centers in a real-world setting. Full article
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11 pages, 1475 KB  
Opinion
Disruption of Islet β-Cells Integrity via TNF-α Activated Apoptotic Signalling in Acute Pancreatitis
by Mudassir Alam and Kashif Abbas
Rom. J. Prev. Med. 2026, 4(1), 1; https://doi.org/10.3390/rjpm4010001 - 5 Feb 2026
Abstract
Tumor necrosis factor alpha (TNF-α) serves as a major regulator of inflammatory responses. The initial, critical release and activation of TNF-α in acute pancreatitis (AP) is primarily triggered within the pancreatic acinar cells through intracellular mechanisms in response to initial injury. This local, [...] Read more.
Tumor necrosis factor alpha (TNF-α) serves as a major regulator of inflammatory responses. The initial, critical release and activation of TNF-α in acute pancreatitis (AP) is primarily triggered within the pancreatic acinar cells through intracellular mechanisms in response to initial injury. This local, acinar cell-derived TNF-α recruits immune cells into the pancreas, which then produce more TNF-α, leading to the amplification of the inflammatory cascade. This opinion emphasises the role of TNF-α-mediated dysfunction of pancreatic β-cells and apoptosis induction through the Bax/Bcl-2/caspase-3 pathway. AP is often diagnosed by autodigestive pancreatic damage and systemic inflammatory response with transient or persistent hyperglycaemia. TNF-α signalling takes place through TNFR1, which initiates apoptotic events that weaken mitochondrial integrity leading to β-cell disruption and diminished insulin secretion. Studies reported TNF-α-mediated increases in Bax expression, anti-apoptotic Bcl-2 suppression and activation of caspase-3. Therapeutic strategies such as TNFR1 inhibitors, Bax/Bcl-2 modulators and BH3 mimetics possess great potential to preserve β-cell integrity. However, TNF-α inhibition requires a careful approach in order to avoid compromising immune defence in AP patients. TNF-α-driven β-cell apoptosis represents a strong link between inflammation and metabolic dysfunction that makes it a suitable target for AP. Future directions should prioritise translational research in human cohorts and developing receptor-specific interventions to balance immune modulation with β-cell preservation. Full article
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16 pages, 1188 KB  
Article
From Annotation to Prediction: Hospital-Grade Early Seizure Risk Prediction from Adult EEG
by Norah Alharbi, Mashael Aldayel, Shrooq Alsenan, Raneem Alyami, Enas Almowalad and Eman Alkethiry
Diagnostics 2026, 16(3), 492; https://doi.org/10.3390/diagnostics16030492 - 5 Feb 2026
Abstract
Background: Manual review of EEG recordings in clinical settings is inherently time-consuming and labor-intensive. These challenges highlight a pressing need for automated EEG analysis tools capable of supporting clinicians by improving efficiency and diagnostic accuracy. Objectives: This study aims to develop [...] Read more.
Background: Manual review of EEG recordings in clinical settings is inherently time-consuming and labor-intensive. These challenges highlight a pressing need for automated EEG analysis tools capable of supporting clinicians by improving efficiency and diagnostic accuracy. Objectives: This study aims to develop and validate an AI-based model for the automated interpretation of adult EEG recordings. Unlike previous approaches that emphasize seizure detection during ictal states, our model targets the early prediction of seizure risk through systematic annotation and recognition of interictal patterns. Methods: The model is designed to accurately distinguish between normal and abnormal EEGs, encompassing both interictal and ictal activity. Abnormal EEGs will be further classified into three clinically relevant categories: (1) non-epileptiform abnormalities such as focal or diffuse slowing, (2) epileptiform discharges, and (3) electrographic seizures. Three AI-based classification algorithms were implemented: Support Vector Machine (SVM), Random Forest (RF), and K-Nearest Neighbors (KNN). Results: RF demonstrated optimal performance across most tasks, achieving 96.50% accuracy for normal activity identification. This AI-driven system enhances the efficiency, consistency, and accessibility of EEG interpretation. It is particularly valuable in settings with limited access to neurophysiologists and offers an innovative approach to improving diagnostic timelines and clinical decision-making. Conclusions: Ultimately, this tool will support physicians in diagnosing neurological conditions and monitoring patient progress over time. Full article
(This article belongs to the Special Issue A New Era in Diagnosis: From Biomarkers to Artificial Intelligence)
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32 pages, 2425 KB  
Review
MASH in Type 2 Diabetes: Pathophysiology, Diagnosis, and Therapeutic Management—A Narrative Review
by Adela Gabriela Ştefan, Adina Mitrea, Diana Clenciu, Ionela Mihaela Vladu, Maria Magdalena Roşu, Diana Cristina Protasiewicz-Timofticiuc, Theodora Claudia Radu-Gheonea, Ion-Cristian Efrem, Anca Maria Amzolini, Beatrice Elena Vladu, Ana-Maria Efrem, Delia-Viola Reurean Pintilei, Eugen Moţa and Maria Moţa
Medicina 2026, 62(2), 325; https://doi.org/10.3390/medicina62020325 - 5 Feb 2026
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as one of the greatest challenges for the modern public health system and serves as the foundation for the development of advanced stages, such as metabolic dysfunction-associated steatohepatitis (MASH), which may progress to fibrosis, cirrhosis, [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as one of the greatest challenges for the modern public health system and serves as the foundation for the development of advanced stages, such as metabolic dysfunction-associated steatohepatitis (MASH), which may progress to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). MASLD and type 2 diabetes mellitus (T2DM) mutually exacerbate one another. MASLD increases the incidence of T2DM and the risk of complications in patients already affected. T2DM accelerates progression to MASH, which has become the second leading cause of liver transplantation and end-stage liver disease, and is associated with hepatic decompensation, cirrhosis, HCC, chronic kidney disease, and cardiovascular disease. MASLD and MASH are strongly linked to T2DM and obesity, pathogenesis including genetic polymorphisms, environmental factors, and multiple metabolic disturbances: insulin resistance (IR), gut dysbiosis, altered adipokine signaling, such as reduced adiponectin alongside increased pro-inflammatory cytokines. Inflammation plays a central role in the development of HCC in MASH, even in the absence of significant fibrosis. The Fibrosis-4 index (FIB-4) should be used as a first-line noninvasive tool to assess fibrosis risk. Additionally, ultrasound-based transient elastography (FibroScan) supports clinicians in assessing steatosis and fibrosis severity. Histologically, MASH is characterized by steatosis, lobular inflammatory changes, and ballooning degeneration of hepatocytes, with or without associated fibrosis. Accurately diagnosing and stratifying MASLD based on fibrosis risk is crucial to identify patients who may benefit from pharmacological treatment or can be managed only with lifestyle interventions. Patients should attain above 10% weight loss through lifestyle modifications. Resmetirom is recommended in F2/F3 fibrosis stages. For treating T2DM, glucagon-like peptide-1 receptor agonists and coagonists, sodium–glucose cotransporter-2 inhibitors, metformin (if glomerular filtration rate exceeds 30 ml/min), and insulin (in decompensated cirrhosis) are preferred. Clinical insights derived from trials are expected to optimize quality of life and long-term outcomes in patients with MASH. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Type 2 Diabetes Mellitus)
21 pages, 5045 KB  
Article
Neurophysiological Profiles in a Family with Multiple SHANK3-Related Phelan–McDermid Syndrome Cases
by Anastasia Neklyudova, Katerina Lind, Galina Portnova, Ksenia Golovina, Maria I. Mitina, Andrey D. Manakhov and Olga Sysoeva
Int. J. Mol. Sci. 2026, 27(3), 1567; https://doi.org/10.3390/ijms27031567 - 5 Feb 2026
Abstract
We present a family case study of Phelan–McDermid syndrome (PMS), a neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene, in which two of three siblings were clinically diagnosed with PMS. Sanger sequencing identified a novel heterozygous deletion in exon 20 of SHANK3 [...] Read more.
We present a family case study of Phelan–McDermid syndrome (PMS), a neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene, in which two of three siblings were clinically diagnosed with PMS. Sanger sequencing identified a novel heterozygous deletion in exon 20 of SHANK3 (c.3679del, p.Ala1227Profs*168), predicted to introduce a premature stop codon and truncate the protein; this variant was absent in the unaffected sibling. Auditory steady-state responses (ASSRs) were recorded at 16, 27, and 40 Hz. The 40 Hz ASSR was markedly reduced in both affected siblings, reaching statistical significance in the younger child and remaining non-significant in the older sibling, while it was preserved in the unaffected sibling. These findings suggest that the 40 Hz ASSR is particularly sensitive to SHANK3-related cortical inhibitory dysfunction during childhood and adolescence, with reduced sensitivity in early adulthood. The results highlight the potential of the 40 Hz ASSR as an electrophysiological biomarker in PMS and underscore the need for age-stratified normative control datasets to enable robust individual-level interpretation and support its use in biomarker development, clinical trial stratification, and monitoring of treatment response. Full article
(This article belongs to the Special Issue Molecular Investigations in Neurodevelopmental Disorders)
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3 pages, 144 KB  
Editorial
How to Properly Diagnose and Treat Immune-Related Adverse Events During Immunotherapy in Patients with Cancer: Discussion Between Specialists
by Angioletta Lasagna and Paolo Sacchi
Cancers 2026, 18(3), 523; https://doi.org/10.3390/cancers18030523 - 5 Feb 2026
Abstract
Immune checkpoint inhibitors and other immune-based cancer therapies have profoundly transformed the treatment of solid and hematological malignancies, leading to durable responses and significant survival benefits in a growing number of patients [...] Full article
27 pages, 10049 KB  
Review
Cardiovascular CT in Bicuspid Aortic Valve Disease: A State-of-the-Art Narrative Review of Advances, Clinical Integration, and Future Directions
by Muhammad Ali Jawed, Cagri Ayhan, Robert Byrne, Sandeep Singh Hothi, Sherif Sultan, Mark Spence and Osama Soliman
J. Clin. Med. 2026, 15(3), 1268; https://doi.org/10.3390/jcm15031268 - 5 Feb 2026
Abstract
Bicuspid Aortic Valve (BAV) disease is recognized as the most common congenital heart condition and is frequently associated with complex valvular and aortic disorders. Cardiovascular computed tomography (CT) has become essential for diagnosing BAV, planning procedures, and evaluating patients after treatment. This is [...] Read more.
Bicuspid Aortic Valve (BAV) disease is recognized as the most common congenital heart condition and is frequently associated with complex valvular and aortic disorders. Cardiovascular computed tomography (CT) has become essential for diagnosing BAV, planning procedures, and evaluating patients after treatment. This is largely due to CT’s high spatial resolution and its ability to perform volume imaging effectively. This review provides an up-to-date overview of the increasing role of cardiovascular CT in the management of bicuspid aortic valve (BAV). It covers various aspects, including BAV morphology, optimal sizing for transcatheter aortic valve replacement (TAVR), and post-procedural monitoring. We highlight significant innovations, such as supra-annular sizing techniques and artificial intelligence (AI)-guided analysis, that position CT at the nexus of anatomy, function, and targeted treatment. Additionally, we address controversies concerning inconsistencies in sizing algorithms, recent classification challenges, and radiation exposure. Future development areas include AI predictive tools, radiomic phenotyping, and CT-guided precision medicine. This synthesis aims to provide clinicians and researchers with a high-level guide to the clinical integration of cardiovascular CT and its future in the BAV population. This review provides the most current, comprehensive synthesis on the pivotal role of cardiovascular CT in BAV management, offering a roadmap for integrating advanced imaging into clinical practice and guiding future research priorities. Full article
(This article belongs to the Special Issue Advances in Cardiovascular Computed Tomography (CT))
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12 pages, 258 KB  
Article
Clinical Significance of Cytokeratin 19-Fragments (CYFRA 21-1), Osteopontin (OPN) and Human Epididymis Protein 4 (HE4) in Pancreatic Adenocarcinoma
by Augustin Catalin Dima, Daniel Vasile Balaban, Iulia-Ioana Stanescu-Spinu, Ana Teodorescu, George Manucu, Laura Ioana Coman, Alina Dima, Cezar Betianu, Mihai Tanase, Daniela Miricescu, Mariana Jinga and Catalin Carstoiu
Int. J. Mol. Sci. 2026, 27(3), 1562; https://doi.org/10.3390/ijms27031562 - 5 Feb 2026
Abstract
Pancreatic cancer remains one of the most aggressive digestive neoplasms, especially due to late diagnosis. The aim of our study was to investigate cytokeratin-19 fragments (CYFRA 21-1), osteopontin (OPN), and human epididymis protein 4 (HE4) clinical significance in pancreatic adenocarcinoma. Our research is [...] Read more.
Pancreatic cancer remains one of the most aggressive digestive neoplasms, especially due to late diagnosis. The aim of our study was to investigate cytokeratin-19 fragments (CYFRA 21-1), osteopontin (OPN), and human epididymis protein 4 (HE4) clinical significance in pancreatic adenocarcinoma. Our research is a single-center cross-sectional prospective study that included sixty hospitalized patients diagnosed with pancreatic adenocarcinoma and fourteen controls. CYFRA 21-1, OPN, and HE4 were tested in all participants using Luminex x MAP technology. Serum CYFRA 21-1 levels were weakly correlated with those of OPN (r = 0.302; p = 0.009), HE4 (r = 0.485; p < 0.001), and carbohydrate antigen (CA) 125 (r = 0.376; p = 0.037). Similarly to CA 19-9 and CA 125, the serum OPN levels were higher in patients with pancreatic cancer when compared to controls, 3.37 (1.84; 9.12) ng/mL versus 1.59 (1.09; 2.51) ng/mL; p = 0.003. However, in multivariate analysis, the OPN was not an independent predictor for pancreatic cancer. Further, the receiver operating characteristic (ROC) curve analysis identified CA 19-9 as the biomarker with the highest diagnostic accuracy, while CYFRA 21-1, OPN, and HE4 did not reach clinically meaningful results. Further, the CYFRA 21-1 levels were significantly higher in cases subjected to significant weight loss before admission. Full article
(This article belongs to the Section Biochemistry)
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