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26 pages, 2810 KB  
Article
Age-, Sex- and Region-Specific Patterns in Sensitization Rates to Food Allergens and Food Allergy Prevalence in Croatian Children: The H2020 IMPTOX and ERDF P4 Study Findings
by Jan Pantlik, Marcel Lipej, Ivana Banić, Maja Šutić, Sandra Mijač, Petra Anić, Ana-Marija Genc, Ana Vukić, Antonija Piškor, Adrijana Miletić Gospić, Željka Vlašić Lončarić, Milan Jurić, Vlatka Drinković, Ivana Marić, Tin Kušan and Mirjana Turkalj
Children 2026, 13(2), 234; https://doi.org/10.3390/children13020234 - 6 Feb 2026
Abstract
Background/Objectives: Food allergy (FA) is a substantial health burden in children. FA is often associated with malnutrition and malabsorption, due to restrictive food avoidance diets, which can significantly impair the patient’s and their family’s quality of life. To this date, population-based data combining [...] Read more.
Background/Objectives: Food allergy (FA) is a substantial health burden in children. FA is often associated with malnutrition and malabsorption, due to restrictive food avoidance diets, which can significantly impair the patient’s and their family’s quality of life. To this date, population-based data combining sensitization and clinical allergy remain limited. This study aimed to assess the patterns of sensitization rates to food and food allergy prevalence rates in Croatian children and to evaluate differences according to age, sex, and region of origin. Materials and Methods: In this cross-sectional study, 1948 preschool and school-aged children from three Croatian regions (Zagreb, Dalmatia, and Slavonia) were included. Participants underwent skin prick testing to common food and inhalant allergens. Data on personal and family medical history were collected using questionnaires and medical records. FA prevalence was evaluated using self-reported data in school-aged children and physician-diagnosed FA data in preschool children. Results: Overall, 41% of participants were sensitized to at least one allergen, while 13% were sensitized to at least one food allergen. Tree nuts—particularly hazelnut—were the most common food-derived sensitizers, followed by hen’s egg, cow’s milk, and fish. Boys exhibited higher total sensitization rates than girls (44.2% vs. 37.5%; p = 0.001), higher food allergen sensitization rates (14.7% vs. 11.4%; p = 0.037), and higher total polysensitization rates (30.7% vs. 22.6%; p < 0.001). School-aged children showed higher total sensitization (44.8% vs. 33.4%; p < 0.001) and polysensitization rates (29.8% vs. 20.5%; p < 0.001) than preschool children, while sensitization to food allergens did not differ between age groups. Food allergen sensitization rates differed by region, with higher prevalence in Zagreb compared with Dalmatia and Slavonia (p = 0.0055), whereas total sensitization rates did not differ regionally. The agreement between sensitization and self-reported FA among school-aged children was low (κ = 0.22; p < 0.001), as was the agreement between sensitization and physician-diagnosed FA in preschool children (κ = 0.13; p < 0.001), despite high specificity in both analyses (95% and 99%%, respectively). Conclusions: Allergic sensitization is common among Croatian children, but it poorly predicts clinically relevant food allergy. These findings highlight the multifactorial nature of allergen sensitization in children and emphasize the need for improvements in diagnostic pathways, targeted prevention strategies, and continued surveillance to optimize allergy prevention and management in children. Full article
(This article belongs to the Special Issue Diagnosis, Treatment and Care of Pediatric Allergy)
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11 pages, 2539 KB  
Article
Computerized Tomography Morphometric Assessment of the Internal Acoustic Meatus: Sex Differences, Orientation Angles, and Surgical Implications
by Emine Deniz Gözen, Fırat Tevetoğlu, Ahmet Ertaş, Haydar Murat Yener, Osman Kızılkılıç and Ali İhsan Soyluoğlu
J. Clin. Med. 2026, 15(3), 1312; https://doi.org/10.3390/jcm15031312 - 6 Feb 2026
Abstract
Objective: We aimed to evaluate the morphometric characteristics of the internal acoustic meatus (IAM) using high-resolution computed tomography (CT), with emphasis on sex- and age-related differences, with particular emphasis on the IAM orientation angle as a less-studied spatial parameter and its potential [...] Read more.
Objective: We aimed to evaluate the morphometric characteristics of the internal acoustic meatus (IAM) using high-resolution computed tomography (CT), with emphasis on sex- and age-related differences, with particular emphasis on the IAM orientation angle as a less-studied spatial parameter and its potential clinical and forensic relevance. Methods: Temporal bone CT scans of 162 patients (94 females, 68 males; age 1–77 years) were retrospectively analyzed. Measurements included the IAM inlet diameter, length, mid-diameter, lateral angle (LA), and orientation angle. Inter-observer agreement was assessed in 30 randomly selected cases. Morphometric parameters were compared by sex and age using t-tests and Mann–Whitney U tests. Results: Mean IAM lengths were 11.0 mm (right) and 11.1 mm (left), and the mean mid-diameter was 4.2 mm bilaterally. IAM lengths and diameters showed no significant sex- or age-related differences (p > 0.05). In contrast, LA and orientation angle differed significantly by sex (p < 0.05), with females showing higher LA values, which may influence posterior fossa surgical exposure. Conclusions: IAM size parameters are largely independent of sex and age, whereas lateral and orientation angles exhibit sex-related variation. Preoperative evaluation of IAM orientation on CT can support skull base surgical planning, and LA may provide supportive morphometric information in forensic contexts, although it should not be considered a standalone sex classification parameter. Full article
(This article belongs to the Section Otolaryngology)
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30 pages, 14017 KB  
Article
Beat-to-Beat QT Variability: A Population Study of the QT Variability Index Composition
by Jan Řehoř, Kateřina Helánová, Martina Šišáková, Tomáš Novotný, Irena Andršová and Marek Malik
Diagnostics 2026, 16(3), 502; https://doi.org/10.3390/diagnostics16030502 - 6 Feb 2026
Abstract
Background/Objectives: One of the topics of electrocardiographic risk factor studies is investigations of beat-to-beat QT interval variability. The seminal study that reported QT variability as a prognostic risk factor introduced the so-called QT variability index (QTVi). QTVi quantification relies not only on [...] Read more.
Background/Objectives: One of the topics of electrocardiographic risk factor studies is investigations of beat-to-beat QT interval variability. The seminal study that reported QT variability as a prognostic risk factor introduced the so-called QT variability index (QTVi). QTVi quantification relies not only on the variance of QT intervals but also on correction factors, including RR interval variance, heart rate, and overall QT interval duration. This study investigated the influence of all the measured factors on QTVi values. Methods: Long-term electrocardiograms (ECGs) were obtained from 251 healthy subjects (mean age 33.6 ± 9.1 years, 108 females) during repeated postural tests that involved supine, sitting, and standing positions maintained for 10 or 15 min. During each position, a 5-min ECG segment with a stable heart rate and without any ectopic disturbances was found. In these segments, standard deviations of normal-to-normal RR (NN) interval durations (SDNN) and of beat-to-beat QT interval durations (SDQT) were measured together with the means of NN and QT intervals. QTVi was subsequently calculated. For each subject, results obtained during each postural position were averaged. Results: In multivariable regression models, evaluated separately in female and male sex-subgroups of the population, QTVi values were significantly dependent on SDQT, SDNN, and mean NN intervals (all p < 0.001) but practically independent of mean QT interval durations. Conclusions: QTVi is significantly influenced by factors that are unrelated to the beat-to-beat changes in QT interval durations. This needs to be considered when interpreting QTVi values. In future studies, multivariable statistical models are needed to ensure that QTVi findings are independent of associated heart rate variability indices. Full article
13 pages, 559 KB  
Article
Contrast Sensitivity and Colour Vision Tests for Early Detection and Monitoring of Hydroxychloroquine Retinal Toxicity: A Preliminary Study
by Amal Aldarwesh, Latifah Alwadman, Ali Almustanyir, Mosaad Alhassan, Muhammed S. Alluwimi, Ansam Alateeq and Ibrahim Almaghlouth
J. Clin. Med. 2026, 15(3), 1309; https://doi.org/10.3390/jcm15031309 - 6 Feb 2026
Abstract
Background/Objectives: Hydroxychloroquine (HCQ) is used to manage various autoimmune diseases, including systemic lupus erythematosus. The prolonged use of HCQ is associated with retinopathy and irreversible visual loss due to retinal toxicity. Despite adherence to dosage regimens, patients may develop functional rather than [...] Read more.
Background/Objectives: Hydroxychloroquine (HCQ) is used to manage various autoimmune diseases, including systemic lupus erythematosus. The prolonged use of HCQ is associated with retinopathy and irreversible visual loss due to retinal toxicity. Despite adherence to dosage regimens, patients may develop functional rather than structural changes, without detectable abnormalities on routine examination using visual acuity and optical coherence tomography (OCT). The study aimed to detect early signs of retinopathy in patients with autoimmune diseases treated with HCQ. Methods: This cross-sectional study included patients (n = 36) with autoimmune diseases who were treated with HCQ. The control group (n = 35) comprised healthy volunteers matched for age and sex. All participants were screened using colour vision tests (Ishihara, Konan ColourDX high definition [HD]), and retinal thickness was evaluated using OCT. Results: Our findings suggest a significant reduction in the contrast threshold of the L and M-cone photoreceptors compared with that of the control using Konan ColourDX HD. The OCT measurements revealed no statistically significant difference in retinal thickness between patients and controls; however, the contrast sensitivity test showed a significant reduction at all spatial frequencies (p < 0.0001). Conclusions: The current study suggests that the Konan ColourDX cone contrast test HD and contrast sensitivity testing may be valuable for periodic monitoring of patients receiving HCQ, potentially enabling earlier detection of toxicity. However, longitudinal studies with larger cohorts are needed to confirm these findings and to further establish the clinical value of these functional visual tests. Full article
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16 pages, 609 KB  
Article
Melanoma Presentations Before, During, and After the COVID-19 Pandemic: A Multicenter Cohort Study from North Rhine-Westphalia, Germany
by Thilo Gambichler, Carmen Colo, Sera Selina Weyer-Fahlbusch, Laura Susok, Stefanie Boms and Nessr Abu Rached
Cancers 2026, 18(3), 539; https://doi.org/10.3390/cancers18030539 - 6 Feb 2026
Abstract
Background: The COVID-19 pandemic disrupted access to routine dermatologic care and may have delayed melanoma diagnosis and management. Evidence on the post-pandemic period and on hospital-based referral cohorts remains limited. We assessed melanoma presentations before, during and after the pandemic in three skin [...] Read more.
Background: The COVID-19 pandemic disrupted access to routine dermatologic care and may have delayed melanoma diagnosis and management. Evidence on the post-pandemic period and on hospital-based referral cohorts remains limited. We assessed melanoma presentations before, during and after the pandemic in three skin cancer centers in North Rhine-Westphalia, Germany. Methods: We conducted a multicenter retrospective cohort study of inpatients with cutaneous melanoma grouped into Phase 1 (February 2017–February 2020), Phase 2 (March 2020–March 2023), and Phase 3 (April 2023–May 2024). The primary endpoint was Breslow tumor thickness (TT) among invasive melanomas, analyzed using multivariable log-linear regression adjusted for center, age, sex, anatomic site, and histologic subtype. Secondary endpoints included T category and AJCC stage distributions (including stage 0/Tis), macroscopic primary tumor specimen dimensions (area and volume; available cases), staging work-up and sentinel lymph node biopsy (SLNB) indicators, and exploratory laboratory parameters (LDH, S100, CRP) and dermal mitotic rate. Results: We included 2960 patients (Phase 1: 1162; Phase 2: 1251; Phase 3: 547). Median TT among invasive melanomas was 1.1 mm (IQR 0.6–2.3), 1.1 mm (0.5–2.4), and 1.0 mm (0.5–2.3) across phases (p = 0.037). In adjusted models among invasive tumors, TT did not increase (Phase 2 vs. Phase 1: 0.97, 95% CI 0.90–1.04; Phase 3 vs. Phase 1: 0.94, 0.86–1.03). AJCC stage 0 decreased from 7.7% and 6.1% to 2.0%; adjusted OR Phase 3 vs. Phase 1: 0.24 (95% CI 0.13–0.46). Within invasive tumors, the distribution of T categories (T1a–T4) and AJCC stages I–IV was similar across periods. Among cases with available macroscopic primary tumor specimen dimensions, median area and volume were higher during and after the pandemic (area p = 0.030; volume p = 0.042), but period effects attenuated in models adjusted for TT. Exploratory analyses suggested a higher proportion of elevated LDH and a lower proportion of elevated S100 across periods, while CRP and dermal mitotic rate showed no clear period shift. Conclusions: In this large melanoma inpatient cohort, the pandemic period was not associated with thicker invasive melanomas after covariate adjustment. However, a persistent reduction in stage 0/Tis presentations in the post-pandemic period suggests ongoing disruption or shifting of early detection and referral pathways. Exploratory increases in macroscopic tumor dimensions may point to changes not captured by thickness alone, but require cautious interpretation given missingness and potential documentation effects. Full article
(This article belongs to the Special Issue Advances in Cancer Data and Statistics: 2nd Edition)
19 pages, 645 KB  
Article
Comprehensive Morphometric MRI Assessment in Children with Breath-Holding Spells: Integration of Automated (Vol2Brain) and Semi-Automated (3D Slicer) Segmentation Methods
by Adil Aytaç and Hilal Aydın
Tomography 2026, 12(2), 21; https://doi.org/10.3390/tomography12020021 - 6 Feb 2026
Abstract
Objectives: To evaluate regional anatomical differences in brain volume, surface area, and cortical thickness between children with breath-holding spells (BHSs) and a control group using morphometric MRI analyses. Methods: Three-dimensional T1-weighted cranial MRI data from 48 children with BHSs and 50 [...] Read more.
Objectives: To evaluate regional anatomical differences in brain volume, surface area, and cortical thickness between children with breath-holding spells (BHSs) and a control group using morphometric MRI analyses. Methods: Three-dimensional T1-weighted cranial MRI data from 48 children with BHSs and 50 control children were retrospectively analyzed, yielding volumetric, surface area, and cortical thickness measures for 135 brain regions. All measurements were assessed relative to total intracranial volume (ICV). Group comparisons were performed using analysis of covariance with age, sex, and ICV as covariates, followed by Benjamini–Hochberg false discovery rate correction (q < 0.05). Results: The BHS group exhibited reduced bilateral amygdala volumes (left: q = 0.042; right: q = 0.038). Both cortical thickness and volume were reduced in the right anterior insula (thickness: q = 0.046; volume: q = 0.049). In addition, cortical thickness was reduced in the bilateral anterior cingulate cortices (left: p = 0.019, q = 0.045; right: p = 0.017, q = 0.043) as well as in the right medial frontal cortex (p = 0.009, q = 0.036). Subregional cerebellar analysis demonstrated volume reductions in the right lobule VI (q = 0.031), left lobule VIIA (Crus I) (q = 0.043), and vermis IX–X (q = 0.039). Conclusions: Detecting measurable morphometric changes in brain regions involved in autonomic and emotional regulation in children with BHSs will contribute to understanding the neurobiological characteristics associated with BHSs. Full article
(This article belongs to the Section Neuroimaging)
17 pages, 528 KB  
Article
Self-Perceived Hearing Handicap and Audiometric Severity in Age-Related Hearing Loss: Associations with Age and Sex
by Luka Bonetti
Audiol. Res. 2026, 16(1), 24; https://doi.org/10.3390/audiolres16010024 - 6 Feb 2026
Abstract
Background/Objective: Self-perceived hearing handicap (SPHH) reflects functional consequences of hearing loss beyond audiometric measures. Clarifying its relationship with audiometric severity and demographic factors is important for understanding age-related hearing loss (ARHL). This study examined associations between SPHH, audiometric measures, age, and sex [...] Read more.
Background/Objective: Self-perceived hearing handicap (SPHH) reflects functional consequences of hearing loss beyond audiometric measures. Clarifying its relationship with audiometric severity and demographic factors is important for understanding age-related hearing loss (ARHL). This study examined associations between SPHH, audiometric measures, age, and sex in individuals with ARHL. Methods: A total of 145 adults (50 men, 95 women) aged 60–89 years (mean 71.65 ± 7.19 years) participated. Hearing status was defined using better-ear pure-tone average thresholds at 0.5, 1, 2, and 4 kHz (BE PTA-4), with ≥20 dB HL as the cutoff and World Health Organization (WHO)-defined severity categories. SPHH was assessed using the Croatian Hearing Handicap Inventory for the Elderly–Screening version (HHIE-S-CRO). HHIE-S-CRO total and subscale scores were examined across BE PTA-4 values and hearing loss categories. Associations were analyzed using correlation and linear regression adjusted for age and sex; group differences were tested using the Kruskal–Wallis test, and ordinal logistic regression assessed monotonic trends across ordered severity categories. Results: HHIE-S-CRO total and subscale scores increased with worsening BE PTA-4 and across hearing loss categories, with substantial overlap. Strong correlations were observed between HHIE-S-CRO scores and audiometric measures. In linear regression, BE PTA-4 was independently associated with HHIE-S-CRO total, emotional, and social/situational scores, whereas age and sex were not. Kruskal–Wallis tests showed significant differences across hearing loss categories. Ordinal logistic regression anchored to WHO severity categories demonstrated graded associations for HHIE-S-CRO total and emotional scores, while the social/situational subscale showed greater dispersion and overlap despite a statistically significant association. Conclusions: SPHH in ARHL shows a strong association with audiometric severity, with particularly robust correspondence for overall and emotional domains, underscoring the complementary role of patient-reported outcome measures alongside audiometric assessment. Full article
(This article belongs to the Special Issue Hearing Loss: Causes, Symptoms, Diagnosis, and Treatment—Volume II)
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10 pages, 366 KB  
Article
Association Between MGMT Promoter Methylation and Clinical and Lifestyle Factors in Glioblastoma: A Single-Center Study in Korea
by Mee-Seon Kim, Yu-Mi Lee, Shin-Ah Son, DongJa Kim, Chaejin Lee and Jeong-Hyun Hwang
J. Clin. Med. 2026, 15(3), 1305; https://doi.org/10.3390/jcm15031305 - 6 Feb 2026
Abstract
Background/Objectives: Although O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a key predictive biomarker in glioblastoma, its association with clinical and lifestyle characteristics remains poorly understood. Methods: We retrospectively analyzed 105 patients who underwent surgical treatment for glioblastoma at Kyungpook National University Hospital between August [...] Read more.
Background/Objectives: Although O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a key predictive biomarker in glioblastoma, its association with clinical and lifestyle characteristics remains poorly understood. Methods: We retrospectively analyzed 105 patients who underwent surgical treatment for glioblastoma at Kyungpook National University Hospital between August 2012 and April 2022 to evaluate the relationship between MGMT promoter methylation status and clinical and lifestyle factors. Collected variables included age, sex, body weight, body height, smoking history, and comorbidities such as hypertension, diabetes mellitus, and hyperlipidemia. Results: Current smoking was significantly associated with MGMT promoter methylation in both univariate and multivariate analyses (adjusted odds ratio [OR], 4.6; p = 0.03). Additionally, a history of hypertension was associated with MGMT promoter methylation after multivariate adjustment (adjusted OR, 3.6; p = 0.03). Conclusions: MGMT promoter methylation in glioblastoma was associated with current smoking and a history of hypertension, suggesting lifestyle-related factors may influence epigenetic mechanisms underlying MGMT promoter methylation in glioblastoma. Full article
(This article belongs to the Section Clinical Neurology)
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21 pages, 737 KB  
Article
Antibody Avidity Profiles as Diagnostic Biomarkers in Differentiating Acute and Chronic Anisakis simplex—Related Allergic Diseases
by Juan González-Fernández, Laura Ullate, Marta Rodero, Alvaro Daschner and Carmen Cuéllar
Antibodies 2026, 15(1), 13; https://doi.org/10.3390/antib15010013 - 6 Feb 2026
Abstract
Background/Objectives: Allergic features of anisakiasis, caused by ingestion of third-stage larvae of Anisakis simplex via raw or undercooked fish, manifest clinically as acute gastroallergic anisakiasis (GAA) or chronic urticaria with Anisakis sensitization (CU+). Differentiating these clinical phenotypes remains challenging. This study aimed to [...] Read more.
Background/Objectives: Allergic features of anisakiasis, caused by ingestion of third-stage larvae of Anisakis simplex via raw or undercooked fish, manifest clinically as acute gastroallergic anisakiasis (GAA) or chronic urticaria with Anisakis sensitization (CU+). Differentiating these clinical phenotypes remains challenging. This study aimed to evaluate the maturation and avidity of specific antibodies (IgE, IgG4, IgG, and IgA) as biomarkers for discriminating between acute and chronic forms of anisakiasis. Methods: A prospective cohort of 65 patients from Madrid, Spain, was classified into three groups: GAA (n = 22), CU+ (n = 22), and chronic urticaria without sensitization (CU−, n = 21). Serum samples were analyzed for antigen-specific immunoglobulins using ELISA and Western blot. Avidity indices (AIs) were quantified through urea dissociation assays. Statistical comparisons and correlation analyses were performed to associate antibody avidity with clinical phenotype and demographic variables. Results: GAA patients exhibited significantly lower IgE avidity indices compared to CU+ individuals (mean AI: 79.9% vs. 88.5%), indicating a less mature IgE response during acute infection. Conversely, IgG4 and IgG avidity were elevated in GAA relative to CU+, reflecting an active but transient immune response. IgA antibodies were detected in both groups, although avidity differences lacked discriminatory capacity. No sex- or age-related differences in antibody avidity were observed. Longitudinal follow-up of GAA patients demonstrated an increase in IgE avidity over time. Conclusions: Quantitative assessment of antibody avidity, particularly for IgE and IgG4, enhances understanding of A. simplex immunopathogenesis and serves as a valuable biomarker for distinguishing acute from chronic clinical presentations. These findings support the use of avidity indices in the diagnosis, staging, and clinical management of anisakiasis. Full article
(This article belongs to the Section Antibody-Based Diagnostics)
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16 pages, 1155 KB  
Article
Hemoglobin–Albumin–Lymphocyte–Platelet (HALP) Score as a Novel Biomarker for Predicting Coronary Slow Flow in Patients with Angina and/or Ischemia and Nonobstructive Coronary Arteries
by Çağatay Tunca, Reha Yasin Şengül, Mehmet Taha Özkan, Alperen Taş, Yusuf Bozkurt Şahin, Saadet Demirtaş İnci, Veysel Ozan Tanık and Bülent Özlek
J. Clin. Med. 2026, 15(3), 1302; https://doi.org/10.3390/jcm15031302 - 6 Feb 2026
Abstract
Background: The coronary slow flow phenomenon (CSFP) is an angiographic entity increasingly recognized in patients with angina and/or ischemia but non-obstructive coronary arteries (ANOCA/INOCA), associated with systemic inflammation, endothelial dysfunction, and microvascular abnormalities. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a [...] Read more.
Background: The coronary slow flow phenomenon (CSFP) is an angiographic entity increasingly recognized in patients with angina and/or ischemia but non-obstructive coronary arteries (ANOCA/INOCA), associated with systemic inflammation, endothelial dysfunction, and microvascular abnormalities. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a novel immunonutritional index that may reflect this multifactorial risk profile. Methods: This retrospective single-center case–control study included 122 patients with CSFP and 126 age- and sex-matched controls with normal coronary flow, all presenting with symptoms of chronic coronary syndrome. CSFP was diagnosed via corrected TIMI frame count. HALP and other inflammatory indices (NLR, PLR, SII, SIRI) were calculated from baseline laboratory values. Associations were evaluated using multivariable logistic regression, ROC analysis, and restricted cubic spline (RCS) modeling. Results: The HALP score was significantly lower in CSFP patients (mean 56.2 vs. 65.9, p < 0.001). In multivariable analysis, HALP was independently associated with CSFP (adjusted OR: 0.951; 95% CI: 0.930–0.972; p < 0.001), whereas NLR lost significance. PLR, SII, and SIRI remained independently associated. HALP showed the highest diagnostic performance (AUC: 0.698), significantly outperforming all other indices (DeLong p < 0.001). A HALP cutoff ≤ 56.4 provided 58.2% sensitivity and 77.0% specificity. RCS analysis demonstrated a significant non-linear inverse relationship (p for non-linearity = 0.034). Subgroup analyses confirmed consistent associations across age, sex, hypertension, and diabetes strata. Conclusions: The HALP score is independently associated with CSFP and outperforms traditional inflammatory indices. Its low cost and accessibility make it a promising tool for clinical risk stratification in ANOCA/INOCA patients, pending validation in multicenter prospective studies. Full article
(This article belongs to the Special Issue Acute Coronary Syndromes | Circulation Research)
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14 pages, 985 KB  
Article
The Role of Sex Hormone-Binding Globulin (SHBG) as a Marker of Metabolic Dysfunction-Associated Steatotic Liver Disease, with an Extended Analysis in Both Men and Women
by Ljiljana Fodor Duric, Zrinka Čolak Romić, Dino Pavičić, Josip Čurić, Velimir Belčić, Ivija Rajković, Irijana Rajković, Jelena Muslim, Nikolina Basic Jukic, Bozidar Vujicic, Tonko Gulin, Matko Gulin, Mladen Grgurević and Anja Oberiter Korbar
J. Clin. Med. 2026, 15(3), 1301; https://doi.org/10.3390/jcm15031301 - 6 Feb 2026
Abstract
Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with insulin resistance and metabolic disturbances. Sex hormone-binding globulin (SHBG) is closely linked to metabolic regulation and has been shown to differ between individuals with and without MASLD. Objective: This study aimed [...] Read more.
Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with insulin resistance and metabolic disturbances. Sex hormone-binding globulin (SHBG) is closely linked to metabolic regulation and has been shown to differ between individuals with and without MASLD. Objective: This study aimed to investigate the associations between SHBG and MASLD and their relationships with insulin resistance, body mass index (BMI), age, and sex in a combined male–female cohort. Patients and Methods: We studied 98 men and 54 women with MASLD and 74 men and 55 women without MASLD (aged 25–64 years). Participants underwent abdominal ultrasonography and fasting blood sampling, including measurements of glucose, liver enzymes, lipids, insulin, SHBG, estradiol, and testosterone. Results: SHBG levels were lower in individuals with MASLD than in controls, with a more pronounced reduction in women. MASLD status was associated with an approximately 10 nmol/L lower SHBG concentration (p < 0.0001; gender × MASLD interaction p = 0.0462). Higher estradiol levels were associated with higher SHBG concentrations (p = 0.0009), although this association differed by sex (gender × log-estradiol interaction p = 0.0147). Older age and higher total cholesterol levels were associated with higher SHBG levels, whereas higher triglyceride levels were associated with lower SHBG levels. Conclusions: SHBG showed significant associations with MASLD and with key metabolic and hormonal factors, including BMI, age, and sex. Inclusion of both men and women extends prior male-only research and provides a broader characterisation of sex-specific associations in MASLD. Full article
(This article belongs to the Section Clinical Research Methods)
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8 pages, 207 KB  
Article
Patent Foramen Ovale Does Not Affect Left Atrial Pressure in Atrial Fibrillation Ablation Patients
by Marek Kiliszek, Marcin Wańczuk, Beata Uziębło-Życzkowska, Krystian Krzyżanowski and Paweł Krzesiński
J. Clin. Med. 2026, 15(3), 1299; https://doi.org/10.3390/jcm15031299 - 6 Feb 2026
Abstract
Background: Elevated left atrial pressure is often a consequence of left ventricular diastolic dysfunction. Patent foramen ovale (PFO) with left-to-right shunt could serve as a left atrium unloading factor. The aim of the study was to test whether PFO in patients with atrial [...] Read more.
Background: Elevated left atrial pressure is often a consequence of left ventricular diastolic dysfunction. Patent foramen ovale (PFO) with left-to-right shunt could serve as a left atrium unloading factor. The aim of the study was to test whether PFO in patients with atrial fibrillation (AF) is linked to lower left atrial pressure (LAP). Methods: A retrospective analysis was performed on consecutive patients undergoing AF ablation from 2019 to 2023. The presence of PFO was assessed with standard transesophageal echocardiography, performed in all patients before ablation. LAP was measured directly in the left atrium just after transseptal puncture. Mean LAP was analyzed. Results: A total of 409 patients were included in the analysis, 85 of whom had PFO (20.8%). There were no significant differences between the groups in baseline characteristics such as age, sex, and comorbidities. Overall, 34.4% of patients had a history of heart failure, independent of the presence of a patent foramen ovale (PFO). Mean LAP was not significantly different between patients with and without PFO (p = 0.36). Conclusions: In patients undergoing AF ablation, more than 20% of patients have PFO. The presence of PFO does not significantly influence LAP, measured directly in the left atrium. The presence of PFO is not linked to a lower prevalence of heart failure. Full article
(This article belongs to the Special Issue Clinical Aspects of Cardiac Arrhythmias and Arrhythmogenic Disorders)
13 pages, 744 KB  
Article
Proton Pump Inhibitors and Disproportionate Reporting of Acute Kidney Injury and Tubulointerstitial Nephritis: A FAERS Pharmacovigilance Study, 2020–2025
by Thamir M. Alshammari, Mohammad Kanan Alshammari, Hind M. Alosaimi, Ayesha Yasmeen and Mamoon H. Syed
J. Clin. Med. 2026, 15(3), 1298; https://doi.org/10.3390/jcm15031298 - 6 Feb 2026
Abstract
Background/Objectives: Proton pump inhibitors (PPIs) are widely used, yet questions persist about kidney-related adverse events. We evaluated disproportional reporting of acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) with PPIs in the FDA Adverse Event Reporting System (FAERS) from 2020 to 2025. Methods: [...] Read more.
Background/Objectives: Proton pump inhibitors (PPIs) are widely used, yet questions persist about kidney-related adverse events. We evaluated disproportional reporting of acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) with PPIs in the FDA Adverse Event Reporting System (FAERS) from 2020 to 2025. Methods: FAERS reports were screened using MedDRA Preferred Terms. Report characteristics and annual counts of AKI and TIN reports were summarized. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Information Content (IC) were used to assess disproportionality. Results: We identified 13,654 PPI-associated AKI reports and 2409 TIN reports in FAERS (2020–2025). Reports were predominantly from the United States, and missing age/sex information was common. Hospitalization was reported in 12.3% of AKI and 22.7% of TIN reports, and death in 9.1% and 5.0%, respectively. Across all years, disproportionality analyses using ROR, PRR, EBGM, and IC consistently met signal thresholds for both outcomes, with stronger signals in 2020–2022 and attenuation thereafter alongside declining report counts. Conclusions: FAERS data show persistent disproportional reporting of AKI and TIN with PPI use. Causality cannot be inferred, but the findings support cautious, indication-based PPI prescribing and highlight the need for robust studies to clarify renal safety. Full article
(This article belongs to the Special Issue Clinical Pharmacology: Adverse Drug Reactions)
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11 pages, 1328 KB  
Article
Non-Exudative Macular Neovascularization in Various Acquired Macular Degenerations with Double- and Triple-Layer Sign on OCT
by Joanna Gołębiewska, Ilona Katarzyna Jędrzejewska, Justyna Mędrzycka, Mariusz Przybyś and Radosław Różycki
Diagnostics 2026, 16(3), 497; https://doi.org/10.3390/diagnostics16030497 - 6 Feb 2026
Abstract
Background/Objectives: To investigate the rate of exudative progression over time in patients with non-exudative macular neovascularization (NE-MNV) associated with various acquired macular degenerations presenting with a double-layer sign (DLS) or triple-layer sign (TLS) on optical coherence tomography (OCT), and to identify potential [...] Read more.
Background/Objectives: To investigate the rate of exudative progression over time in patients with non-exudative macular neovascularization (NE-MNV) associated with various acquired macular degenerations presenting with a double-layer sign (DLS) or triple-layer sign (TLS) on optical coherence tomography (OCT), and to identify potential predictors of this progression. Methods: Fifty-one eyes of fourty-nine patients with a DLS or TLS on OCT images were identified. OCT angiography (OCTA) was performed to detect NE-MNV, and only eyes with confirmed NE-MNV were included in the final analysis. Central macular thickness (CMT), choroidal thickness (CT), morphology of the abnormal vessels, the duration of follow-up, progression to active exudative MNV, and the status of the contralateral eye were assessed. Results: The final analysis included 32 eyes of 30 participants with NE-MNV. The median observation period was 46 months. The causes of NE-MNV were age- related macular degeneration (AMD) in 59.38% of eyes, pachychoroid epitheliopathy (PPE) in 37.50%, and other causes in 3.12%. Exudation developed in 15.62% of eyes (median time to onset: 24 months), predominantly in the AMD subgroup. Abnormalities in the fellow eye were present in 59.38% of cases. Neither age nor other factors, including sex, cause of MNV, CMT, CT, MNV morphology, or fellow eye status, were statistically significant predictors of progression to active MNV (p = 0.67, p > 0.99, p = 0.62, p = 0.09, p = 0.09, p = 0.2, p = 0.62, resp.). Conclusions: NE-MNV is an asymptomatic condition that may occur in the course of various retinal diseases. While DLS and TLS demonstrate high sensitivity and specificity for the diagnosis of NE-MNV, their presence does not always indicate concurrent MNV. Multimodal imaging is essential for accurate monitoring of these patients and detection of potential disease progression. Full article
(This article belongs to the Special Issue Diagnosis and Management of Retinopathy—2nd Edition)
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12 pages, 317 KB  
Article
Impaired Bone Density and Quality in Type 1 Diabetes Mellitus: Prevalence and Key Clinical Correlations
by Simona Zaccaria, Isabella Nardone, Sium Wolde Sellasie, Laura Giurato, Chiara Pecchioli, Pasquale Di Perna and Luigi Uccioli
J. Clin. Med. 2026, 15(3), 1292; https://doi.org/10.3390/jcm15031292 - 6 Feb 2026
Abstract
Background: Type 1 diabetes mellitus (T1DM) is associated with an increased risk of fragility fractures that cannot be fully explained by reduced bone mineral density (BMD), highlighting a potential role for bone quality impairment. The purpose of this study was to evaluate the [...] Read more.
Background: Type 1 diabetes mellitus (T1DM) is associated with an increased risk of fragility fractures that cannot be fully explained by reduced bone mineral density (BMD), highlighting a potential role for bone quality impairment. The purpose of this study was to evaluate the prevalence of altered bone density and microarchitecture and to identify their main clinical correlates in adults with T1DM and seemingly adequate glycemic control at the time of assessment. Methods: Sixty-eight adults aged 18–69 years with T1DM attending a diabetes technology outpatient clinic were enrolled in this single-center, cross-sectional study. BMD at the lumbar spine, femoral neck, and total hip was assessed by dual-energy X-ray absorptiometry (DXA) and classified as reduced based on age and sex: Z-score < −2.0 SD for premenopausal women and men < 50 years, and T-score ≤ −2.5 SD for postmenopausal women and men ≥ 50 years. Bone microarchitecture was evaluated using trabecular bone score (TBS). Clinical, metabolic, and lifestyle variables were collected, including glycated hemoglobin (HbA1c; good control ≈ 7.0%/53 mmol/mol), diabetes duration, microvascular complications, and physical activity (PA) assessed by the International PA Questionnaire (IPAQ; moderate–high PA defined according to combined high and moderate IPAQ categories). Results: Reduced BMD was observed in 35.3% of patients and was associated with older age (p < 0.001), longer disease duration (p = 0.044), lower body mass index (p = 0.031), poorer glycemic control (p = 0.03), microvascular complications such as diabetic peripheral neuropathy (p = 0.028) and retinopathy (p = 0.045), and low PA (p = 0.012). Altered TBS was present in 45.6% of patients and was associated with older age (p < 0.001), longer diabetes duration (p = 0.011), higher HbA1c levels (p < 0.001), diabetic peripheral neuropathy (p = 0.002), retinopathy (p = 0.007), cardiovascular risk factors (dyslipidemia p = 0.002, hypertension p = 0.002), and low PA (p < 0.001). In multivariable analyses, older age and higher HbA1c were independently associated with reduced TBS, whereas moderate–high PA was associated with a lower likelihood of impaired bone microarchitecture. Conclusions: Impaired bone density and bone quality are highly prevalent in adults with T1DM and are frequently associated with longer disease duration, poorer metabolic control, and chronic complications. Our findings support the potential value of a combined assessment of BMD and TBS in fracture risk evaluation, together with strategies aimed at preventing diabetes-related complications and promoting healthy lifestyle behaviors. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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