Journal of Clinical Medicine

24 pages, 1947 KB

Open AccessSystematic Review

Clinical Outcomes of Platelet-Rich Fibrin in Endodontic Microsurgery: A Systematic Review and Meta-Analysis

by Carlos Valdivieso del Pueblo, Paloma Montero-Miralles, María León-López, Juan J. Segura-Sampedro, Daniel Cabanillas-Balsera, Jenifer Martín-González and Juan J. Segura-Egea

J. Clin. Med. 2026, 15(16), 6392; https://doi.org/10.3390/jcm15166392 - 18 Aug 2026

Abstract

Background/Objectives: Platelet-rich fibrin (PRF) and its derivatives have been proposed as biological adjuncts to enhance tissue healing following endodontic microsurgery (EMS). However, current evidence regarding their effects on postoperative recovery and long-term bone regeneration remains inconsistent. This study aimed to evaluate the efficacy [...] Read more.

Background/Objectives: Platelet-rich fibrin (PRF) and its derivatives have been proposed as biological adjuncts to enhance tissue healing following endodontic microsurgery (EMS). However, current evidence regarding their effects on postoperative recovery and long-term bone regeneration remains inconsistent. This study aimed to evaluate the efficacy of PRF and its derivatives as adjuncts in endodontic microsurgery by separately assessing patient-centered postoperative outcomes and radiographic and volumetric bone-healing outcomes through a systematic review and meta-analysis. Methods: This systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261400163). Randomized controlled trials and comparative clinical studies evaluating PRF or its derivatives as adjuncts to EMS were eligible. MEDLINE/PubMed, Embase, Scopus, Web of Science, Cochrane CENTRAL, and reference lists were searched from inception to April 2026. Outcomes included postoperative pain, edema, quality of life, clinical–radiographic healing, CBCT volumetric bone regeneration, bone density, and outcomes in complex defects. Risk of bias was assessed using RoB 2 and ROBINS-I. Random-effects meta-analyses were performed where appropriate, and certainty of evidence was evaluated using the GRADE approach. Results: Seventeen clinical reports corresponding to sixteen independent datasets were included. PRF and its derivatives improved early postoperative recovery, particularly postoperative pain during the first postoperative week. Meta-analysis demonstrated a significant reduction in early postoperative pain favoring PRF-based interventions (SMD/Hedges g = −0.62; 95% CI, −1.03 to −0.21; p = 0.003). Evidence regarding long-term bone regeneration and clinical–radiographic healing remained heterogeneous and inconclusive. CBCT-based studies suggested accelerated early bone healing, although no consistent superiority was demonstrated at 6–12 months. The certainty of evidence ranged from moderate for postoperative pain to very low for volumetric bone regeneration. Interpretation of the findings is limited by clinical and methodological heterogeneity and the small number of studies available for several outcomes. Conclusions: The available evidence suggests that PRF may improve early postoperative recovery and soft-tissue healing after endodontic microsurgery. However, current evidence does not support PRF as a predictable substitute for bone grafts or regenerative biomaterials in large or non-contained defects. Well-designed CBCT-based randomized clinical trials with standardized outcome measures are needed. Full article

(This article belongs to the Special Issue Root Canal Treatment and Healing Outcomes: Clinical Application of Endodontic Biomaterials and Postoperative Management)

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21 pages, 599 KB

Open AccessArticle

Preconception Learned Helplessness as a Cognitive Vulnerability to Lower Maternal Bonding Across the Perinatal Period

by Moriah Azoulay, Sharon Florentin, Adi Klein, Amit Klein, Neta Elbaz Hemo, Tamuz Weinberger, Noa Yakirevich Amir, Keren Avirame, Tal Sido, Atira Bick, Netta Levin, Inbal Reuveni and Shiri Ben-David

J. Clin. Med. 2026, 15(16), 6391; https://doi.org/10.3390/jcm15166391 - 18 Aug 2026

Abstract

Background: Maternal bonding is a key determinant of maternal and infant well-being, yet little is known about preconception factors that shape its development. Learned helplessness (LH), a stable cognitive vulnerability characterized by perceived uncontrollability and diminished efficacy, may predispose women to poorer [...] Read more.

Background: Maternal bonding is a key determinant of maternal and infant well-being, yet little is known about preconception factors that shape its development. Learned helplessness (LH), a stable cognitive vulnerability characterized by perceived uncontrollability and diminished efficacy, may predispose women to poorer maternal bonding. This study examined whether preconception LH predicts antenatal and postpartum bonding and whether this association is mediated by antenatal bonding and prenatal affective symptoms. Methods: A sample of 151 euthymic, nulliparous women was followed prospectively from preconception through pregnancy and postpartum, completing questionnaires assessing LH, depressive and anxiety symptoms, and antenatal and postpartum bonding. Analyses used structural equation modeling, linear mixed-effects models, hierarchical regression, and parallel mediation. Results: LH showed high stability from preconception to postpartum (r = 0.71), with no mean-level change, whereas affective symptoms increased. Antenatal bonding predicted postpartum bonding (β = 0.52, p < 0.001). Higher preconception LH predicted lower antenatal bonding (b = −0.20, p = 0.002) and lower postpartum bonding (b = −0.29, p < 0.001), beyond affective symptoms in the corresponding period. The LH–postpartum bonding association was partially mediated by antenatal bonding (β = −0.10, p = 0.005), but not by prenatal depression or anxiety symptoms. Conclusions: Preconception LH reflects a stable cognitive vulnerability linked to poorer maternal bonding. Its association with postpartum bonding was partly mediated by antenatal bonding, but not by prenatal affective symptoms, suggesting that LH’s relevance to postpartum bonding begins when the maternal bond develops during pregnancy. Assessing LH before conception or early in pregnancy may help identify vulnerability to lower bonding, beyond current affective symptoms. Full article

(This article belongs to the Special Issue Advances in Perinatal Mental Health: Prevention, Screening, Treatment, and Support Across Pregnancy and Postpartum)

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44 pages, 1171 KB

Open AccessReview

The Gut–Brain Axis in Fetal Alcohol Spectrum Disorder (FASD): Why the Gut Shapes Behavior, Depression, and Self-Injurious Behavior in Children with Prenatal Alcohol Exposure—A Narrative Review with a Proposal for Staged Nutritional and Microbiological Intervention

by Katarzyna Zych-Krekora, Oskar Sylwestrzak and Michał Krekora

J. Clin. Med. 2026, 15(16), 6390; https://doi.org/10.3390/jcm15166390 - 18 Aug 2026

Abstract

Prenatal alcohol exposure (PAE) leads to fetal alcohol spectrum disorder (FASD), the most common preventable cause of neurodevelopmental impairment. The classical narrative attributes the clinical picture of FASD exclusively to direct ethanol-induced brain injury. In the present review, we argue that this perspective [...] Read more.

Prenatal alcohol exposure (PAE) leads to fetal alcohol spectrum disorder (FASD), the most common preventable cause of neurodevelopmental impairment. The classical narrative attributes the clinical picture of FASD exclusively to direct ethanol-induced brain injury. In the present review, we argue that this perspective is incomplete and leads to diagnostic errors, most often to the misdiagnosis of ADHD in children who in fact have FASD. We propose that, alongside the direct neurotoxicity of ethanol, an important and clinically under-recognized complementary mechanism is gut–brain axis dysfunction: alcohol damages the enteric nervous system and enteric glial cells, induces dysbiosis with deep deficits of butyrate and other short-chain fatty acids (SCFAs), damages the enterochromaffin cells responsible for 90% of peripheral serotonin production, and—through translocation of lipopolysaccharide (LPS) and activation of the Toll-like receptor 4 (TLR4)—sustains a neuroinflammatory brain signature. This cascade—superimposed on direct ethanol neurotoxicity—may account for the high rates of depression, anxiety, self-injurious behavior, and suicide attempts observed in individuals with FASD and for the limited efficacy of traditional interventions focused solely on the central nervous system. The 2024 Polish Institute of Mother and Child (Okulicz-Kozaryn et al.) study showed that 50.3% of pregnant women consumed alcohol, and 11% did so regularly, against only 7% who admitted so in questionnaires. The real clinical picture of children with FASD is further complicated by three factors to which we devote separate sections in this paper: prenatal co-exposure to nicotine, cannabinoids, and opioids; the loss of vertical microbiota transmission and breastfeeding in children transferred to foster care (where the prevalence of FASD is 18.8% and in children’s homes in some regions reaches up to 80%); and the substantial over-representation of preterm and small-for-gestational-age (SGA) infants (in the Hasken et al. cohort, 18.4% of children with FASD were born preterm and 51.4% were born SGA). In the final section, we present a structured, staged protocol for nutritional and microbiological intervention grounded in a hierarchy of evidence: from interventions supported by randomized controlled trials (RCT-level; choline) through interventions supported by strong mechanistic rationale and RCTs in related populations (sodium butyrate, Lactobacillus rhamnosus GG, GOS/FOS prebiotics—galacto-oligosaccharides and fructo-oligosaccharides, and omega-3 fatty acids) to experimental interventions. The protocol also covers the window before 2 years of age: we argue that, given the over-representation of preterm and SGA infants among children with FASD, the analogy to preterm infants on parenteral nutrition and to post-institutional infants applies in substantial part to the same patients, which justifies extending the indications for choline and other nutritional interventions. The paper includes a compact table of dosing proposals for each age window (from pregnancy to school-age child) and provides clinicians with concrete answers: where to start, what to avoid, and what to monitor, with explicit signposting of regulatory limitations for individual substances in Poland and the European Union. Full article

(This article belongs to the Section Obstetrics & Gynecology)

13 pages, 659 KB

Open AccessArticle

Study Clinical Characteristics and Outcomes of Candida auris Candidemia in Adult Intensive Care Unit Patients: A 30-Month Retrospective Study

by Murat Unsel, Güldem Turan, Neval Elgormus and Hafize Uzun

J. Clin. Med. 2026, 15(16), 6389; https://doi.org/10.3390/jcm15166389 - 18 Aug 2026

Abstract

Background: Candida auris (C. auris) has emerged as a multidrug-resistant fungal pathogen causing healthcare-associated outbreaks worldwide, particularly in intensive care units (ICUs). Its environmental persistence, multidrug resistance, and high mortality make it a major challenge for infection prevention and clinical [...] Read more.

Background: Candida auris (C. auris) has emerged as a multidrug-resistant fungal pathogen causing healthcare-associated outbreaks worldwide, particularly in intensive care units (ICUs). Its environmental persistence, multidrug resistance, and high mortality make it a major challenge for infection prevention and clinical management. This study aimed to investigate the clinical characteristics, clinical exposures, treatment outcomes, and mortality of adult ICU patients with C. auris candidemia during the first 30 months after the opening of a tertiary care hospital. Methods: This retrospective observational study included all adult patients (≥18 years) admitted to five ICUs between 1 July 2020 and 31 December 2022 who developed culture-confirmed C. auris candidemia. Isolates were identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) with the Microflex LT/SH Smart MS system (Bruker Daltonics, Bremen, Germany) according to routine microbiological laboratory procedures. Demographic characteristics, underlying diseases, invasive procedures, clinical exposures, microbiological findings, treatment, APACHE II scores, and clinical outcomes were retrospectively analyzed. Results: During the 30-month study period, 3716 adult patients were admitted to the ICUs, and candidemia developed in 432 (11.6%). Of these episodes, 22 (5.1%) were caused by C. auris. The first C. auris candidemia case occurred 184 days after hospital opening. The mean age was 55 ± 17 years, and overall ICU mortality was 77.3%. Sepsis (36.4%), malignancy (22.7%), and cerebrovascular disease (18.2%) were the most common reasons for ICU admission. All patients had received broad-spectrum antibiotics, whereas central venous catheterization and invasive mechanical ventilation were present in 77.3% of cases. The mean interval from ICU admission to candidemia was 49 ± 15 days. Caspofungin was used as first-line antifungal therapy in all patients. Non-survivors had significantly higher APACHE II scores (32.8 ± 4.9 vs. 26.4 ± 6.6, p = 0.029) and predicted mortality rates (80.1% vs. 53.3%, p = 0.012). Antifungal treatment duration was significantly shorter among non-survivors (p < 0.001), whereas no significant differences were observed in age, ICU length of stay, or time to blood culture clearance. Conclusions: C. auris candidemia was observed in critically ill patients with prolonged ICU stays and frequent invasive interventions and was associated with high all-cause ICU mortality. Higher APACHE II scores were associated with mortality in this cohort, reflecting greater baseline severity of illness. Given the small sample size and descriptive, exploratory nature of the study, these findings should be interpreted with caution. The effectiveness of specific infection-control, diagnostic, or therapeutic interventions was not evaluated. Larger multicenter prospective studies are needed to better characterize the epidemiology, clinical outcomes, and factors associated with mortality in C. auris candidemia. Full article

(This article belongs to the Section Intensive Care)

15 pages, 1728 KB

Open AccessArticle

AI-Derived Pericardial Effusion Volume and Long-Term Mortality After Transcatheter Aortic Valve Implantation

by Gretha Hecke, Nikolaus Clodi, Bernhard Scharinger, Matthias Hammerer, Laura Preuss, Uta C. Hoppe, Klaus Hergan, Elke Boxhammer, Christoph Knapitsch and Nikolaos Schörghofer

J. Clin. Med. 2026, 15(16), 6388; https://doi.org/10.3390/jcm15166388 - 18 Aug 2026

Abstract

Background: Pericardial effusion is a common finding on pre-procedural computed tomography (CT) in patients undergoing transcatheter aortic valve implantation (TAVI). However, its clinical significance remains uncertain. Using artificial intelligence (AI)-based image analysis, we sought to determine whether pericardial effusion represents an incidental imaging [...] Read more.

Background: Pericardial effusion is a common finding on pre-procedural computed tomography (CT) in patients undergoing transcatheter aortic valve implantation (TAVI). However, its clinical significance remains uncertain. Using artificial intelligence (AI)-based image analysis, we sought to determine whether pericardial effusion represents an incidental imaging finding, a marker of hemodynamic burden, or a prognostically relevant phenotype. Methods: This retrospective single-center study included 470 consecutive patients undergoing TAVI for severe aortic stenosis. Pericardial effusion volume was quantified using an AI-based CT segmentation workflow and categorized as no effusion (0 mL), trace effusion (>0–<5 mL), small effusion (5–<30 mL), or larger effusion (≥30 mL). Associations with baseline clinical and echocardiographic characteristics were assessed. Long-term mortality was evaluated using Kaplan–Meier analysis, Cox regression models, and restricted cubic spline analyses. Results: Detectable pericardial effusion was present in 276 patients (58.7%), although larger effusions were uncommon (5.1%). Increasing pericardial effusion volume was associated with a higher prevalence of atrial fibrillation (p = 0.001), higher systolic pulmonary artery pressure (p = 0.004), and lower TAPSE/sPAP ratios (p = 0.007). In contrast, left ventricular ejection fraction and transvalvular gradients did not differ across effusion categories. During long-term follow-up, no significant differences in mortality were observed between pericardial effusion groups (log-rank p = 0.46). Pericardial effusion volume was not associated with mortality when analyzed as a continuous variable (HR 1.00, 95% CI 0.996–1.01; p = 0.842), after logarithmic transformation (adjusted HR 0.91, 95% CI 0.76–1.08; p = 0.293), or in restricted cubic spline analyses. Conclusions: AI-derived pericardial effusion volume identifies a hemodynamic phenotype characterized by atrial fibrillation, pulmonary hypertension, and impaired right ventricular–pulmonary arterial coupling. Despite these associations, pericardial effusion volume does not independently predict long-term mortality after TAVI, suggesting that it reflects cardiovascular congestion and remodeling rather than a prognostically relevant phenotype. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Computed Tomography (CT))

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18 pages, 530 KB

Open AccessReview

IDH-Mutant Diffuse Glioma: From Metabolic Origins to Targeted Therapy

by Tadeja Urbanic-Purkart

J. Clin. Med. 2026, 15(16), 6387; https://doi.org/10.3390/jcm15166387 - 18 Aug 2026

Abstract

Background/Objectives: Isocitrate Dehydrogenase (IDH)1/2-mutant diffuse gliomas represent a biologically distinct subgroup of adult brain tumors in which eary metabolic reprogramming and accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) drive epigenetic, immunologic, and clinical characteristics, including a high burden of glioma-associated epilepsy. This review [...] Read more.

Background/Objectives: Isocitrate Dehydrogenase (IDH)1/2-mutant diffuse gliomas represent a biologically distinct subgroup of adult brain tumors in which eary metabolic reprogramming and accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) drive epigenetic, immunologic, and clinical characteristics, including a high burden of glioma-associated epilepsy. This review summarizes the molecular and metabolic consequences of IDH mutations, their role in glioma-associated epilepsy, and the evolving impact of mutant IDH-targeted therapies in contemporary neuro-oncology. Methods: We conducted a narrative review of key molecular, translational, imaging, and clinical studies on IDH-mutant diffuse gliomas. The literature included the 2021 (World Health Organization) WHO Classification of Tumours of the Central Nervous System, studies investigating D-2HG biology and glioma-associated epilepsy, and prospective clinical trials and real-world evidence evaluating IDH-targeted therapies and contemporary antiseizure management. Particular emphasis was placed on vorasidenib, advanced metabolic imaging, and emerging liquid biopsy approaches. Results: IDH mutations are early driver events that promote D-2HG accumulation, resulting in widespread epigenetic reprogramming, metabolic dysregulation, and an immunosuppressive tumor microenvironment. D-2HG has also been implicated in the development of glioma-associated epilepsy, although the underlying mechanisms remain incompletely understood. Advances in integrated histomolecular diagnostics, magnetic resonance spectroscopy, amino acid positron emission tomography, and cerebrospinal fluid liquid biopsy have improved disease classification and treatment monitoring. Mutant IDH inhibitors, particularly vorasidenib, prolong progression-free survival, delay the need for subsequent treatment, and reduce intratumoral D-2HG concentrations, and have shown encouraging early signals of improved seizure control and preserved health-related quality of life in patients with grade 2 IDH-mutant gliomas, although this evidence remains preliminary and requires confirmation in larger prospective studies. Conclusions: IDH-mutant diffuse gliomas exemplify precision neuro-oncology, in which a single metabolic alteration informs diagnosis, disease monitoring, and targeted therapeutic approach. Additionally, ongoing studies are expected to further define the role of IDH inhibition across different disease stages and in combination with immunotherapy and standard treatments. Lastly, future clinical trials should systematically incorporate seizure outcomes, neurocognitive function, patient-reported outcomes, and immunologic endpoints to optimize both tumor control and quality of life. Full article

(This article belongs to the Special Issue Clinical and Diagnostic Strategies for Glioma Treatment)

14 pages, 605 KB

Open AccessArticle

Cilostazol and Functional Outcomes in Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Analysis

by Jin Kikuchi, Yusuke Otsu, Sosho Kajiwara, Kimihiko Orito, Masaru Hirohata, Kiyohiko Sakata, Katsumi Takizawa, Yoji Tanaka, Masaki Chin, Hiroki Kurita, Akihiro Hirayama, Koreaki Irie, Kenichiro Suyama, Ichiro Nakahara, Nobutaka Horie, Motohiro Morioka and Fusao Ikawa

J. Clin. Med. 2026, 15(16), 6386; https://doi.org/10.3390/jcm15166386 - 18 Aug 2026

Abstract

Background/Objectives: Poor-grade aneurysmal subarachnoid hemorrhage (SAH; WFNS grades 4–5) carries a historically dismal prognosis, driven by early brain injury and delayed cerebral ischemia (DCI). Despite advances in neurocritical care, effective pharmacological strategies for this vulnerable population remain limited. This multicenter study investigated [...] Read more.

Background/Objectives: Poor-grade aneurysmal subarachnoid hemorrhage (SAH; WFNS grades 4–5) carries a historically dismal prognosis, driven by early brain injury and delayed cerebral ischemia (DCI). Despite advances in neurocritical care, effective pharmacological strategies for this vulnerable population remain limited. This multicenter study investigated prognostic factors for functional recovery, with particular emphasis on the potential benefit of adjunctive cilostazol, a phosphodiesterase-3 inhibitor with vasodilatory and antiplatelet properties. Methods: This multicenter retrospective cohort study analyzed 394 patients with WFNS grade 4–5 aneurysmal SAH treated at 10 institutions between 2018 and 2024. The primary outcome was favorable functional status (modified Rankin Scale 0–2) at 6 months. Multivariable logistic regression was performed to identify independent predictors of outcome. Sensitivity analyses were also performed to assess the potential influence of missing 6-month outcome data. Results: Six-month outcomes were available for 318 patients (80.7%), of whom 107 (33.6%) achieved favorable recovery. Patients with favorable outcomes were significantly more likely to have received cilostazol than those with unfavorable outcomes (70.1% vs. 55.5%; p = 0.016). In multivariable logistic regression, cilostazol use remained associated with a favorable outcome (odds ratio [OR] 2.29; 95% confidence interval [CI] 1.01–5.22; p = 0.048) after adjustment for age (OR 0.95; p < 0.001), WFNS grade 5 (OR 0.46; p = 0.012), ventricular drainage, and cerebral infarction. Sensitivity analyses, including propensity score–weighted and missing-outcome analyses, yielded directionally favorable estimates but were not statistically significant. Conclusions: Despite the severity of the initial insult, one-third of patients with available 6-month follow-up achieved functional independence. Cilostazol use was associated with favorable functional outcome in the primary analysis, although statistical significance was not retained in sensitivity analyses addressing missing outcomes. These findings suggest a potential therapeutic signal of cilostazol in poor-grade aneurysmal SAH, warranting prospective validation. Full article

(This article belongs to the Special Issue Recent Advances and Future Perspectives of Subarachnoid Hemorrhage)

13 pages, 408 KB

Open AccessArticle

All-Cause Hospitalisation After Endoscopic Diagnosis of Diverticular Disease: A Prospective Real-World Cohort Study

by Anna Maria Pietrzak, Agnieszka Chreptowicz, Marcin Stanisław Pietrzak and Andrzej Mróz

J. Clin. Med. 2026, 15(16), 6385; https://doi.org/10.3390/jcm15166385 - 18 Aug 2026

Abstract

Background: Diverticular disease (DD) represents an important clinical and healthcare burden, particularly in ageing populations. The relationship between the Diverticular Inflammation and Complication Assessment (DICA) classification and overall healthcare utilisation remains insufficiently defined. The aim of our study was to assess predictors [...] Read more.

Background: Diverticular disease (DD) represents an important clinical and healthcare burden, particularly in ageing populations. The relationship between the Diverticular Inflammation and Complication Assessment (DICA) classification and overall healthcare utilisation remains insufficiently defined. The aim of our study was to assess predictors and causes of all-cause hospitalisation during follow-up in patients with DD evaluated using the DICA classification. Methods: This prospective observational study included consecutive ambulatory patients with DD evaluated endoscopically in a tertiary gastroenterology centre during a 6-month period. Patients were prospectively followed for 3 years. Demographic and clinical characteristics, DICA classification, treatment, diverticulitis episodes and hospital admissions were recorded. The primary endpoint was any all-cause hospitalisation during follow-up. Results: Among 243 patients, all-cause hospitalisation occurred in 101 patients (41.6%), while recurrent hospitalisation occurred in 37 (15.2%). The cumulative hospitalisation burden reached 1607 hospital days. Acute diverticulitis occurred in 15 patients (6.2%), with only one diverticulitis-related hospitalisation, and no diverticular disease-related surgery was recorded. In multivariable analysis, age (OR 1.49; 95% CI 1.06–2.11; p = 0.023) and respiratory comorbidity (OR 5.31; 95% CI 1.49–18.88; p = 0.010) were independently associated with hospitalisation, whereas DICA ≥ 2 was not. However, the estimate for respiratory comorbidity should be interpreted cautiously because it was based on only 14 affected patients and had a wide confidence interval. Conclusions: Although all-cause hospitalisation was common and driven predominantly by age and comorbidity rather than diverticular disease severity, diverticular disease-specific outcomes were generally favourable in this stable ambulatory cohort. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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10 pages, 2830 KB

Open AccessPerspective

Surgery 4.0: From the Smart Operating Room to the Learning Operating Room

by Andrew A. Gumbs, Roland Croner and Jean-Claude Couffinhal

J. Clin. Med. 2026, 15(16), 6384; https://doi.org/10.3390/jcm15166384 - 18 Aug 2026

Abstract

The connected operating room captures, transmits, and displays data, but it does not learn. This perspective presents Chirurgie 4.0 (C40), a French-led initiative born within the Commission Innovation of the Académie nationale de chirurgie, which proposes not only a concept but a method [...] Read more.

The connected operating room captures, transmits, and displays data, but it does not learn. This perspective presents Chirurgie 4.0 (C40), a French-led initiative born within the Commission Innovation of the Académie nationale de chirurgie, which proposes not only a concept but a method for the safe adoption of artificial intelligence (AI) in surgery. At its core is the C40 Maturity Model of the Operating Room, a human-governed “surgical world model” describing the transition from the Smart OR to the Learning OR across six levels, from the conventional operating room to a sovereign, federated network of surgical world models. We situate surgical autonomy on an explicit six-level scale, show that autonomous devices are already an accepted clinical reality in fields such as interventional cardiology, ophthalmology, neuro- and orthopedic surgery, and argue that governance must be native rather than retrofitted, through a Cognitive Governance Layer resting on human oversight, explainability, auditability and agent governance. We describe the economic and sovereignty stakes specific to intelligent surgical technologies and set out the design of the 2026 C40 field survey, whose results will feed a Livre Blanc for public decision-makers. C40 offers five steps that can genuinely be climbed, and a method for climbing them safely, with the surgeon retaining final clinical authority at every step. Full article

(This article belongs to the Section General Surgery)

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12 pages, 1452 KB

Open AccessArticle

Real-World Effectiveness of Polymerized House-Dust-Mite Subcutaneous Immunotherapy up to 24 Months: Why Baseline Symptom Severity Shapes Measurement of the Combined Symptom–Medication Response

by Margarita Rosa Acevedo Matos, Omar Francisco Sierra Salgado, Yenny Alexandra Mendez, Sandra del Pozo and Miguel Casanovas

J. Clin. Med. 2026, 15(16), 6383; https://doi.org/10.3390/jcm15166383 - 18 Aug 2026

Abstract

Background/Objectives: Allergic rhinoconjunctivitis (AR) induced by house dust mites (HDMs) is a common condition that impairs quality of life, and allergen immunotherapy is the only treatment accepted to modify its natural course. However, real-world evidence on polymerized HDM subcutaneous immunotherapy (SCIT) remains [...] Read more.

Background/Objectives: Allergic rhinoconjunctivitis (AR) induced by house dust mites (HDMs) is a common condition that impairs quality of life, and allergen immunotherapy is the only treatment accepted to modify its natural course. However, real-world evidence on polymerized HDM subcutaneous immunotherapy (SCIT) remains limited. We evaluated the up to 24-month effectiveness of polymerized HDM SCIT and examined how baseline symptom burden affects the measured response. Methods: In a retrospective, single-arm, real-world cohort, 353 patients (mean age 15.9 (12.3) years) with HDM-induced AR with/without asthma (asthma subpopulation, n = 112) initiated polymerized SCIT (ALXOID^®, Inmunotek S.L., Spain) with an extract of house dust mites (Dermatophagoides pteronyssinus, D. farinae, Blomia tropicalis). Patients were followed for up to 24 months; 139 contributed an observation at month 12 and 67 at month 24. The primary outcome was the Rhinoconjunctivitis Combined Symptom–Medication Score (RCSMS); secondary outcomes were a visual analog scale (VAS) and the ESPRINT-15 quality-of-life questionnaire. Effectiveness was estimated using mixed models for repeated measures. The pre-specified primary-analysis population was restricted to a baseline RCSMS ≥ 2 to avoid floor effects and regression to the mean at low baseline scores. Results: At month 24, the RCSMS decreased by 0.938 points (−35.3%) in the full cohort and by 48.3% in the baseline RCSMS ≥ 2 population; in the full cohort, the VAS and ESPRINT-15 improved by 50.6% and 69.7%, respectively (all p < 0.001; within-subject effect sizes were small for the full-cohort RCSMS and medium for all other outcomes). The shape of the improvement trajectory did not differ by age group, and all age groups exceeded the minimal clinically important difference; the age analysis was exploratory. Patients with baseline RCSMS < 2 showed continued improvement in VAS and ESPRINT-15 scores. In contrast, the RCSMS increased, a pattern consistent with a statistical floor effect, suggesting limited responsiveness of the score at low baseline values. Conclusions: Up to 24 months, polymerized HDM SCIT was associated with clinically meaningful improvements in symptoms, medication use, and quality of life, most clearly in patients with a baseline RCSMS ≥ 2. Baseline symptom severity should be considered when interpreting combined symptom–medication outcomes in allergen immunotherapy. The single-arm design precludes causal inference. Full article

(This article belongs to the Section Immunology & Rheumatology)

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14 pages, 522 KB

Open AccessArticle

The Relationships Among Tinnitus Intensity, Complexity, Sound Intolerance, and Psychiatric Symptoms

by Stefani Maihoub, Panayiota Mavrogeni, Aphrodite Mavrogenis and András Molnár

J. Clin. Med. 2026, 15(16), 6382; https://doi.org/10.3390/jcm15166382 - 18 Aug 2026

Abstract

Objective: This study investigated the associations between tinnitus-related features, psychological symptoms, and everyday functioning. Material and Methods: In this study, 293 patients with primary subjective tinnitus participated. Participants received otorhinolaryngological and audiological evaluations and completed the Tinnitus Handicap Inventory (THI), Beck [...] Read more.

Objective: This study investigated the associations between tinnitus-related features, psychological symptoms, and everyday functioning. Material and Methods: In this study, 293 patients with primary subjective tinnitus participated. Participants received otorhinolaryngological and audiological evaluations and completed the Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), and Generalised Anxiety Disorder-7 (GAD-7) questionnaires. Results: Significant positive correlations were observed between total THI scores and several tinnitus characteristics, including subjective loudness, pitch, complexity, and sound intolerance. Higher THI scores were also associated with higher depression and anxiety scores. Psychoacoustically matched tinnitus intensity was positively correlated with perceived tinnitus loudness; however, no significant association was found between overall THI scores and psychoacoustic tinnitus intensity. Longer tinnitus duration was positively correlated with both tinnitus loudness and participant age, while age was also positively associated with tinnitus loudness. Subjective tinnitus loudness, pitch, complexity, and sound intolerance were positively correlated with both BDI and GAD-7 scores. After applying the Bonferroni correction for multiple comparisons, the following correlations were no longer statistically significant: psychoacoustic tinnitus intensity with subjective tinnitus loudness and the THI Functional (F) subscale; tinnitus duration with subjective tinnitus loudness; subjective tinnitus loudness with BDI and GAD-7 scores; and age with subjective tinnitus loudness and tinnitus pitch. However, all remaining significant correlations were retained. In linear regression analyses, THI scores were independently associated with sound intolerance, tinnitus pitch, and BDI scores, while THI scores were also independently associated with BDI scores and sound intolerance in reciprocal models. Conclusions: In this single-centre, cross-sectional study of patients with tinnitus and without a control group, greater tinnitus handicap was associated with subjective tinnitus pitch, sound intolerance, and depressive symptoms. Subjective tinnitus loudness was positively associated with psychoacoustically matched tinnitus intensity before correction for multiple testing but was not retained after Bonferroni adjustment. Several subjective tinnitus characteristics remained associated with symptoms of depression and anxiety after adjustment for multiple comparisons. These findings describe associations within the studied population and should not be interpreted as evidence of causal relationships or generalised beyond similar clinical populations without further multicentre, longitudinal, controlled studies. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Surgical Strategies Update on Ear Disorders: 2nd Edition)

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17 pages, 1407 KB

Open AccessReview

Present-Day State of Percutaneous Endovascular Aortic Aneurysm Repair

by Paweł Grzyb, Bartosz Rodziewicz, Joanna Halman, Łukasz Znaniecki and Jacek Wojciechowski

J. Clin. Med. 2026, 15(16), 6381; https://doi.org/10.3390/jcm15166381 - 18 Aug 2026

Abstract

Abdominal aortic aneurysm (AAA) carries a rupture-related mortality exceeding 80% when untreated. Percutaneous endovascular aortic aneurysm repair (pEVAR) represents the current technical frontier, although evidence regarding its clinical and economic benefits remains heterogeneous. This narrative review of PubMed, Scopus, and Web of Science [...] Read more.

Abdominal aortic aneurysm (AAA) carries a rupture-related mortality exceeding 80% when untreated. Percutaneous endovascular aortic aneurysm repair (pEVAR) represents the current technical frontier, although evidence regarding its clinical and economic benefits remains heterogeneous. This narrative review of PubMed, Scopus, and Web of Science from inception to 1 August 2026 synthesises comparative data from 67 publications and four manufacturer websites to evaluate the clinical, quality-of-life, and economic outcomes of pEVAR against open femoral exposure. Current evidence suggests that pEVAR may serve as a feasible alternative to open femoral exposure, offering potential benefits regarding access-site morbidity, hospital length of stay, and early postoperative pain. While RCTs report pEVAR’s early perioperative advantages, evidence regarding long-term safety, anatomy, and costs remains predominantly observational. Additionally, pEVAR allows for locoregional anaesthesia, a strategy hypothesized to positively influence short-term outcomes in ruptured aneurysm emergencies, although prospective validation is required. However, maintaining these benefits relies heavily on overcoming the procedural learning curve and ensuring rigorous pre-procedural patient selection via computed tomography angiography to avoid severe vessel calcification and excessive depth. Available evidence suggests that in carefully selected patients, pEVAR yields an overall safety profile comparable to surgical cutdown, while potentially mitigating the risk of access-site complications. Full article

(This article belongs to the Section Cardiovascular Medicine)

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20 pages, 1515 KB

Open AccessArticle

Dural Puncture Epidural, Standard Epidural, and No Epidural: Comparative Effects on Labor Progression and Neonatal Outcomes

by Kubra C. Yilmaz, Humeyra E. Ates Eminoglu, Mariah Arif, Tugba Aksungur, Gul C. Colak, Seyhmus Tunc, Mehmet B. Tozoglu, Ahmet S. Saracoglu, Fatma Acil, Mustafa Bicak and Kevser Arkan

J. Clin. Med. 2026, 15(16), 6380; https://doi.org/10.3390/jcm15166380 - 18 Aug 2026

Abstract

Objective: To compare non-epidural labor, standard epidural analgesia, and dural puncture epidural analgesia with respect to labor progression, obstetric outcomes, analgesia-related outcomes, and neonatal results. Methods: This single-center retrospective observational cohort study included 168 term singleton parturients: 58 without epidural analgesia, 56 with [...] Read more.

Objective: To compare non-epidural labor, standard epidural analgesia, and dural puncture epidural analgesia with respect to labor progression, obstetric outcomes, analgesia-related outcomes, and neonatal results. Methods: This single-center retrospective observational cohort study included 168 term singleton parturients: 58 without epidural analgesia, 56 with standard epidural analgesia, and 54 with dural puncture epidural analgesia. The primary outcome was the duration of the second stage of labor. Secondary outcomes included first-stage duration, mode of delivery, blood loss, transfusion, analgesia quality, maternal side effects, umbilical venous pH, biochemical acidosis, Apgar scores, neonatal intensive care unit admission, and neonatal resuscitation. Analyses included group comparisons, adjusted models, quantile regression, Firth penalized logistic regression, propensity-score inverse probability weighting, and a nulliparous sensitivity analysis. Results: Second-stage duration was comparable across groups (median 40.0, 45.0, and 48.5 min in the no-epidural, standard epidural, and dural puncture epidural groups, respectively; p = 0.118). Active pushing time was likewise comparable (8.0, 8.5, and 12.0 min, respectively; p = 0.292), and quantile regression, together with a nulliparous sensitivity analysis—in which the second stage was longest in the no-epidural group—did not indicate epidural-related labor prolongation. Compared with standard epidural analgesia, dural puncture epidural analgesia showed numerically lower pain scores and a numerically lower rescue bolus requirement (30/54 [55.6%] vs. 39/56 [69.6%]; p = 0.183), although neither difference reached statistical significance. Umbilical cord venous pH and biochemical acidosis (cord venous pH < 7.20) did not differ significantly among groups (p = 0.266 and p = 0.335, respectively). The only neonatal endpoint that differed between groups was a recorded fetal acidosis flag, which was more frequent in the epidural groups (0%, 7.1%, and 16.7%; p = 0.004) but was not corroborated by objective cord pH, Apgar scores, neonatal resuscitation, or a significant increase in neonatal intensive care unit admission (5.2%, 10.7%, and 16.7%; p = 0.145). Conclusions: Contemporary low-dose standard epidural and dural puncture epidural analgesia were not associated with clinically meaningful prolongation of labor, active pushing time, or major obstetric intervention. Dural puncture epidural analgesia showed a non-significant trend toward more favorable analgesic performance compared with standard epidural analgesia. Objective neonatal acid–base measures (cord venous pH and biochemical acidosis) did not differ significantly between groups; only a recorded fetal acidosis flag was more frequent in the epidural groups, without correlation to objective cord pH or to adverse clinical neonatal outcomes. These results support the obstetric and neonatal safety of contemporary low-dose epidural techniques; the isolated recorded acidosis signal warrants confirmation in prospective studies with standardized cord blood gas sampling. Full article

(This article belongs to the Special Issue Clinical Updates and Current Challenges in Obstetrical Anesthesia)

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25 pages, 2084 KB

Open AccessSystematic Review

Clinical and Radiographic Outcomes of Calcium-Silicate-Based Materials in Primary-Tooth Pulpotomy: An Umbrella Review

by Carlos M. Ardila, Anny M. Vivares-Builes and Eliana Pineda-Vélez

J. Clin. Med. 2026, 15(16), 6379; https://doi.org/10.3390/jcm15166379 - 18 Aug 2026

Abstract

Background/Objectives: Calcium-silicate-based materials, many of which are commonly classified as bioceramics, are increasingly used for pulpotomy in vital primary teeth. This umbrella review synthesized systematic reviews and meta-analyses evaluating their clinical and radiographic outcomes. Methods: Eligible reports were systematic reviews of human primary-tooth [...] Read more.

Background/Objectives: Calcium-silicate-based materials, many of which are commonly classified as bioceramics, are increasingly used for pulpotomy in vital primary teeth. This umbrella review synthesized systematic reviews and meta-analyses evaluating their clinical and radiographic outcomes. Methods: Eligible reports were systematic reviews of human primary-tooth pulpotomy involving calcium-silicate-based materials and reporting clinical and/or radiographic outcomes. MEDLINE/PubMed, Embase, and Scopus were searched from inception through June 2026. Methodological quality was appraised using AMSTAR-2, overlap was quantified using the Corrected Covered Area (CCA), and certainty was assessed using a GRADE-informed approach. Findings were integrated through structured narrative synthesis and review-level functional meta-synthesis. The protocol was registered in PROSPERO (CRD420261338396). Results: Eleven systematic reviews were included, comprising 78 unique primary-study reports and 180 study occurrences; aggregate participant totals were not calculated because of primary-study overlap. AMSTAR-2 confidence ranged from critically low to moderate, and overlap was high (CCA 13.1%). MTA and Biodentine showed broadly comparable clinical and radiographic outcomes through 24 months. Evidence for Biodentine versus formocresol was less consistent: one meta-analysis reported more favorable radiographic outcomes with Biodentine; whereas, another found no substantial difference; clinical superiority was not consistently demonstrated. Comparisons with ferric sulfate were generally inconclusive, and evidence for newer calcium-silicate-based formulations remained limited. No material demonstrated sustained long-term superiority. Certainty was predominantly low, with very low certainty for several sparsely studied comparisons. Conclusions: Contemporary calcium-silicate-based materials show high clinical and radiographic success in vital primary-tooth pulpotomy, but comparative conclusions remain constrained by methodological limitations, high overlap, and limited certainty. Full article

(This article belongs to the Special Issue Pediatric Dentistry: Recent Advances, Current Issues and Future Challenges)

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16 pages, 1211 KB

Open AccessArticle

Comparison of Cardiometabolic Profiles in Patients with Nonfunctioning Adrenal Incidentalomas and Mild Autonomous Cortisol Secretion

by Rabia Eker Akilli, Ulcaz Perihan Aksoydan, Omer Tepe, Gamze Akkus, Onur Sinan Deveci, Anil Akray and Imam Gunay

J. Clin. Med. 2026, 15(16), 6378; https://doi.org/10.3390/jcm15166378 - 18 Aug 2026

Abstract

Objective: To compare the cardiometabolic characteristics of patients with mild autonomous cortisol secretion (MACS) and nonfunctioning adrenal incidentalomas (NFAI), with particular emphasis on their biochemical and echocardiographic profiles. Methods: This retrospective study included 67 patients with adrenal incidentalomas, classified as NFAI [...] Read more.

Objective: To compare the cardiometabolic characteristics of patients with mild autonomous cortisol secretion (MACS) and nonfunctioning adrenal incidentalomas (NFAI), with particular emphasis on their biochemical and echocardiographic profiles. Methods: This retrospective study included 67 patients with adrenal incidentalomas, classified as NFAI (n = 32) or MACS (n = 35) according to the post-1-mg dexamethasone suppression test (DST) cortisol concentration. Clinical characteristics, hormonal profiles, metabolic parameters, conventional echocardiographic measurements, and global longitudinal strain (GLS) were compared between the groups. Associations between GLS and biochemical parameters were evaluated using correlation analyses, with Benjamini–Hochberg false discovery rate correction applied for multiple testing. Results: Compared with the NFAI group, patients with MACS had lower adrenocorticotropic hormone (ACTH) (13.0 ± 7.1 vs. 18.6 ± 9.7 pg/mL, p = 0.008) and dehydroepiandrosterone sulfate (DHEA-S) concentrations (46.4 ± 31.6 vs. 82.8 ± 48.0 µg/dL, p < 0.001), as well as higher post-1-mg DST cortisol concentrations (3.4 ± 1.3 vs. 1.2 ± 0.5 µg/dL, p < 0.001). Triglyceride concentrations were also higher in the MACS group (165.3 ± 70 vs. 129.4 ± 90.2 m g/dL, p = 0.004). Most conventional echocardiographic parameters were comparable between the groups. GLS did not differ significantly between NFAI and MACS patients (21.92 ± 2.2 vs. 21.94 ± 1.9, respectively; mean difference: 0.0, 95% CI: −1.0 to 1.0, p = 0.846). Nominal correlations between GLS and selected biochemical parameters did not remain statistically significant after false discovery rate correction. Conclusions: MACS was associated with distinct endocrine and metabolic characteristics compared with NFAI; however, no significant between-group difference in GLS was observed. These cross-sectional findings do not establish myocardial dysfunction or a temporal relationship between cortisol autonomy and cardiovascular alterations. Larger prospective longitudinal studies are required to clarify the cardiovascular implications of MACS. Full article

(This article belongs to the Section Cardiovascular Medicine)

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18 pages, 12893 KB

Open AccessReview

Usefulness of Strain Echocardiography in Heart Failure with Preserved Ejection Fraction

by Maria Concetta Pastore, Clarissa Carmona De Azevedo Bellagamba, Andrea Stefanini, Alessia Pinelli, Giulia Elena Mandoli, Luna Cavigli, Flavio D’Ascenzi, Marta Focardi and Matteo Cameli

J. Clin. Med. 2026, 15(16), 6377; https://doi.org/10.3390/jcm15166377 - 18 Aug 2026

Abstract

Heart failure with preserved ejection fraction (HFpEF) represents an increasingly prevalent clinical syndrome, driven by population ageing and the growing burden of cardiometabolic comorbidities, and is associated with significant morbidity and mortality. Due to its heterogeneous pathophysiology and the frequent absence of overt [...] Read more.

Heart failure with preserved ejection fraction (HFpEF) represents an increasingly prevalent clinical syndrome, driven by population ageing and the growing burden of cardiometabolic comorbidities, and is associated with significant morbidity and mortality. Due to its heterogeneous pathophysiology and the frequent absence of overt structural abnormalities, early diagnosis and accurate risk stratification remain challenging. In the current era of emerging disease-modifying therapies, the identification of sensitive imaging markers able to detect early myocardial dysfunction and refine patient characterization has become increasingly important. Speckle-tracking echocardiography has emerged as a valuable tool for the comprehensive evaluation of HFpEF, allowing the assessment of subclinical myocardial impairment beyond conventional parameters. Left ventricular global longitudinal strain (LV-GLS) identifies subtle systolic dysfunction despite preserved left ventricular ejection fraction (LVEF) and provides incremental diagnostic and prognostic information. Accordingly, LV-GLS has been incorporated into contemporary diagnostic algorithms and may represent a promising marker for monitoring disease progression and therapeutic response. Beyond the left ventricle (LV), left atrial (LA) strain has gained increasing relevance as a marker of atrial myopathy and elevated filling pressures. Left atrial reservoir strain (LARS) detects early atrial dysfunction before overt structural remodelling, improves the identification of HFpEF in patients with unexplained dyspnoea, and provides additional prognostic information, including prediction of atrial fibrillation and thromboembolic risk. Moreover, right ventricular free-wall longitudinal strain (RV-FWLS) allows early recognition of right ventricular involvement and has shown important prognostic implications, particularly in relation to pulmonary vascular dysfunction and exercise intolerance. Overall, a multi-chamber strain-based approach may improve HFpEF diagnosis, phenotyping, and risk stratification, supporting a transition toward a more personalized management strategy. Further prospective studies are needed to define the role of strain imaging in guiding therapeutic decisions and monitoring treatment response. Full article

(This article belongs to the Special Issue Current Concepts and Clinical Application of Echocardiography)

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13 pages, 2132 KB

Open AccessArticle

Hyperacute Cytokine Kinetics and Early Interleukin-10 Elevation as Predictors of Neurological Outcome in Post-Cardiac Arrest Syndrome

by Jea Hun Oh, Hyo Joon Kim, Kyung Man Cha, Daehee Kim, Kiwook Kim, In Soo Kim, Ji Hoon Kim, Chun Song Youn, Sang Hoon Oh, Hyo Jin Bang, Ae Kyung Gong and Ji Sook Lee

J. Clin. Med. 2026, 15(16), 6376; https://doi.org/10.3390/jcm15166376 - 18 Aug 2026

Abstract

Background: Post-cardiac arrest syndrome (PCAS) involves a complex interplay between systemic inflammatory and compensatory anti-inflammatory responses. The hyperacute kinetics of these cytokines and their incremental prognostic value beyond established brain injury biomarkers remain inadequately characterized. We aimed to evaluate whether the 6 h [...] Read more.

Background: Post-cardiac arrest syndrome (PCAS) involves a complex interplay between systemic inflammatory and compensatory anti-inflammatory responses. The hyperacute kinetics of these cytokines and their incremental prognostic value beyond established brain injury biomarkers remain inadequately characterized. We aimed to evaluate whether the 6 h post–return-of-spontaneous-circulation (ROSC) cytokine profile predicts neurological outcome, with the Th1/Th2 ratio largely reflecting the IL-10 signal. Methods: This retrospective analysis of prospectively collected data from a single-center cardiac arrest registry included 56 cardiac arrest survivors (40 out-of-hospital, 16 in-hospital) treated with targeted temperature management (TTM) at 33 °C or 36 °C between January 2024 and December 2025. Serum IL-6, IL-10, IFN-γ (interferon-γ), and TNF-α (tumor necrosis factor-α) were measured at five time points (initial presentation (INIT), and 6, 24, 48, and 72 h post-ROSC). Neurological outcome was assessed using the Cerebral Performance Category (CPC) scale at 6 months after cardiac arrest, with poor outcome defined as CPC 3–5. Results: Eighteen patients (32.1%) had a good outcome (CPC 1–2) and 38 (67.9%) had a poor outcome at 6 months after cardiac arrest. Among the 38 poor-outcome patients, 2 were classified as CPC 3, 8 as CPC 4, and 28 as CPC 5 (death) at 6 months; the 6-month outcome was available for all 56 patients, with no loss to follow-up. Patients with poor outcomes exhibited a synchronized surge of IL-6 and IL-10 peaking at 6 h post-ROSC. IL-10 at 6 h showed the highest discriminative power among cytokines (area under the curve (AUC) 0.844) compared with IL-6 (AUC 0.761). Multivariable analysis using Youden-derived cut-offs revealed that IL-10 ≥ 154.32 pg/mL (adjusted odds ratio (aOR) 15.28, 95% CI 2.02–115.38, p = 0.008) and a Th1/Th2 ratio ≥ 0.0314 (aOR 0.09, 95% CI 0.01–0.61, p = 0.013) were independently associated with neurological outcome after adjustment for age and initial shockable rhythm. Conclusions: The 6 h post-ROSC window is a critical inflection point for immune dysregulation in PCAS. Early IL-10 elevation and collapse of the Th1/Th2 balance are independently associated with poor neurological recovery and add incremental prognostic information to established brain injury biomarkers. External validation in larger prospective cohorts is required. Full article

(This article belongs to the Special Issue Cardiac Arrest and Postcardiac Arrest Care: State of the Art and Future Directions)

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13 pages, 1314 KB

Open AccessArticle

Integrated Ultrasound Features, Cytologic Subclassification, and Systemic Inflammatory Markers for Predicting Malignancy in Bethesda III Thyroid Nodules

by Emine Yildirim, Pelin Cobanoglu Akbas, Sibel Bektas, Adem Senturk, Pelin Basım, Umut Fırat Turan, Nesimi Mecit, Hanifi Onalan, Hafize Uzun and Mustafa Uygar Kalaycı

J. Clin. Med. 2026, 15(16), 6375; https://doi.org/10.3390/jcm15166375 - 18 Aug 2026

Abstract

Background/Objectives: Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance; AUS/FLUS) thyroid nodules represent a heterogeneous group with variable malignancy risk, creating challenges in clinical management. This study aimed to evaluate the associations of preoperative ultrasonographic findings, inflammation-based hematological markers, and [...] Read more.

Background/Objectives: Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance; AUS/FLUS) thyroid nodules represent a heterogeneous group with variable malignancy risk, creating challenges in clinical management. This study aimed to evaluate the associations of preoperative ultrasonographic findings, inflammation-based hematological markers, and cytological atypia subtypes with final histopathological outcomes in surgically treated Bethesda III thyroid nodules. Methods: This retrospective study included 72 adult patients with Bethesda III thyroid nodules who underwent thyroid surgery between January 2020 and December 2025. Demographic characteristics, ultrasonographic findings, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), cytological atypia subtypes, and final histopathological diagnoses were analyzed. Univariate and multivariable logistic regression analyses were performed to identify predictors of malignancy. Results: Final histopathological examination revealed benign lesions in 49 patients (68.1%) and malignant lesions in 23 patients (31.9%). Age, sex, nodule size, multinodular goiter, Hashimoto thyroiditis, microcalcifications, hypoechogenicity, suspicious margins, and TI-RADS category were not significantly associated with malignancy (all p > 0.05). Similarly, NLR and PLR did not differ significantly between benign and malignant nodules (NLR: 1.80 vs. 1.98, p = 0.319; PLR: 117.9 vs. 135.0, p = 0.398). Among cytological atypia subtypes, nuclear atypia demonstrated the highest malignancy rate (50.0%) and was significantly associated with malignant histopathological outcomes (OR = 3.364, 95% CI: 1.182–9.570, p = 0.023). After adjustment for age and biopsied nodule size, nuclear atypia remained an independent predictor of malignancy (adjusted OR = 3.963, 95% CI: 1.298–12.094, p = 0.016). Conclusions: In surgically treated Bethesda III thyroid nodules, nuclear atypia was the only independent predictor of malignancy, whereas ultrasonographic characteristics, NLR, and PLR showed limited predictive value. Subclassification of Bethesda III nodules according to cytological atypia may improve preoperative risk stratification and support clinical decision-making. Because the study included only surgically treated patients, the findings should be interpreted in the context of a surgically selected cohort and may not be generalizable to the overall Bethesda III population. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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11 pages, 241 KB

Open AccessArticle

Prevalence, Severity, and Neuropsychiatric Correlates of Internet Gaming Disorder Among Saudi University Student Gamers: An Epidemiological Cross-Sectional Study

by Abdullah Alharbi, Faihan F. Alshaibany, Majed M. Aljabri, Bandar S. Alharbi, Alya Alghamdi, Bader M. Almutairy, Waleed M. Alshehri, Norah M. Alyahya and Abdulaziz M. Alodhailah

J. Clin. Med. 2026, 15(16), 6374; https://doi.org/10.3390/jcm15166374 - 18 Aug 2026

Abstract

Background: Despite the WHO’s recognition of Gaming Disorder in the ICD-11, epidemiological data on its prevalence and neuropsychiatric correlates among Saudi Arabian university students remain limited. Such data are critical for calibrating campus mental health resources and developing evidence-based screening protocols. This [...] Read more.

Background: Despite the WHO’s recognition of Gaming Disorder in the ICD-11, epidemiological data on its prevalence and neuropsychiatric correlates among Saudi Arabian university students remain limited. Such data are critical for calibrating campus mental health resources and developing evidence-based screening protocols. This study aimed to estimate the prevalence of Internet Gaming Disorder (IGD) in a sample of Saudi university student gamers and evaluate the clinical utility of impulsivity and resilience as case-detection tools. Methods: In a cross-sectional survey of students who engaged in electronic gaming for at least one hour per week (N = 207; 58.9% male), participants completed the IGDS9-SF, CD-RISC-10, and S-UPPS-P scales. Data were analyzed using binary logistic regression and Receiver Operating Characteristic (ROC) curves to identify predictors and compare the discriminative validity of the constructs. Results: Among these student gamers, the overall IGD prevalence was 18.4%, with significantly higher rates in males (24.6%) than females (9.4%; χ²(1) = 7.71, p = 0.006). Significant predictors of IGD included sex, daily gaming hours, higher impulsivity, and lower resilience. ROC analysis revealed that a composite impulsivity-resilience index (AUC = 0.80) outperformed single-construct screening using only impulsivity (AUC = 0.71) or resilience (AUC = 0.68). Cases exhibited markedly higher impulsivity and lower resilience than non-cases. Conclusions: Among Saudi university student gamers, IGD prevalence is clinically significant, particularly among heavier and male gamers. A composite impulsivity-resilience screening index showed superior detection accuracy in this sample and warrants further validation for integration into university mental health assessment protocols. Full article

(This article belongs to the Section Epidemiology & Public Health)

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