Medical Sciences

34 pages, 4656 KB

Open AccessArticle

The Therapeutic Landscape of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum: Five Decades of Evolving Treatment and Supportive Care

by Flavia Gabriela Ban, Andrei-Flavius Radu, Ada Radu, Delia Mirela Tit and Gabriela S. Bungau

Med. Sci. 2026, 14(3), 419; https://doi.org/10.3390/medsci14030419 - 22 Jul 2026

Viewed by 351

Abstract

Background/Objectives: Among the most common medical conditions of pregnancy, nausea and vomiting of pregnancy (NVP) and its severe form hyperemesis gravidarum (HG) represent a clinically significant and increasingly researched area of maternal health. However, the global evolution, structural organization, and thematic development [...] Read more.

Background/Objectives: Among the most common medical conditions of pregnancy, nausea and vomiting of pregnancy (NVP) and its severe form hyperemesis gravidarum (HG) represent a clinically significant and increasingly researched area of maternal health. However, the global evolution, structural organization, and thematic development of this literature remain insufficiently characterized. This bibliometric study maps five decades of global research on therapeutic and supportive interventions for NVP and HG. Methods: Web of Science Core Collection records were searched on 10 May 2026, restricted to English-language articles and reviews published up to 2025, and deduplicated to 1182 unique documents. A secondary thematic filter was subsequently applied to generate a refined obstetric subset for the country collaboration, keyword co-occurrence, and thematic evolution analyses. Bibliometric performance, collaboration networks, source impact, institutional output, PELT-based changepoint detection, metadata completeness, keyword co-occurrence, and thematic evolution were analyzed using VOSviewer, Bibliometrix/Biblioshiny, and custom Python scripts. Results: Publication output increased markedly after 2010 and reached its maximum in 2025. PELT sensitivity analysis localized the principal transitions to the mid-1990s and early 2010s, informing three broad analytical macroperiods: 1975–1994, 1995–2009, and 2010–2025. The United States dominated cumulative output and collaboration intensity, while Canada, England, Australia, Italy, Germany, and China showed substantial scientific influence. Core publication venues were concentrated in obstetrics, gynecology, reproductive safety, and pregnancy-focused clinical medicine. Keyword and thematic analyses showed a transition from early vomiting, Bendectin, exposure, and pregnancy-safety concerns toward pharmacological treatment, complementary interventions, controlled clinical evaluation, maternal–fetal outcomes, and supportive management. Metadata-completeness analysis identified a major pre-1991 indexing discontinuity, requiring caution when interpreting long-range keyword-based trends. Conclusions: These findings outline the trajectory of the field and highlight priorities for future research, including stronger comparative evidence for pharmacological, complementary, and supportive-care strategies, broader international collaboration, and prospective studies to strengthen the evidence base for managing NVP and HG. Full article

(This article belongs to the Section Gynecology)

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15 pages, 746 KB

Open AccessSystematic Review

Metabolic Effects of Testosterone Replacement Therapy in Men with Functional Secondary Hypogonadism, Obesity and Type 2 Diabetes or Metabolic Syndrome: A Systematic Review

by Christos Ntais, Apostolos Vantarakis and Ioanna P. Chatziprodromidou

Med. Sci. 2026, 14(3), 418; https://doi.org/10.3390/medsci14030418 - 22 Jul 2026

Viewed by 7034

Abstract

Background/Objectives: Functional secondary hypogonadism is frequent in men with obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), but whether testosterone replacement therapy (TRT) produces clinically relevant metabolic benefits remains uncertain. This systematic review evaluated double-blind randomized placebo-controlled trials of TRT in obese [...] Read more.

Background/Objectives: Functional secondary hypogonadism is frequent in men with obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), but whether testosterone replacement therapy (TRT) produces clinically relevant metabolic benefits remains uncertain. This systematic review evaluated double-blind randomized placebo-controlled trials of TRT in obese men with functional secondary hypogonadism and either T2DM or metabolic syndrome. Methods: PubMed and Scopus were searched up to May 2026. Eligible studies enrolled adult men with biochemical hypogonadism and T2DM or metabolic syndrome, compared TRT with placebo, and reported metabolic outcomes. Open-label, single-blind, and non-randomized studies were excluded. Risk of bias was assessed with the Cochrane RoB 2 framework and certainty of evidence with GRADE. Results: Eight trials were included. The most consistent signal was improvement in body composition, mainly increased lean mass and reduced fat mass. Effects on insulin resistance were favorable in several trials but heterogeneous. GRADE certainty was low for fat mass, lean mass, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and it was very low for clamp-derived insulin sensitivity, HbA1c, fasting glucose, lipid outcomes, inflammatory and vascular surrogate markers, and long-term safety. Conclusions: Low-certainty evidence suggests that TRT may improve body composition and HOMA-IR in carefully selected men with functional secondary hypogonadism and metabolic disease, whereas effects on glycemic and lipid outcomes remain very uncertain. TRT should not be regarded as an antidiabetic or lipid-lowering intervention. Larger phenotype-specific trials with longer follow-up are needed. Full article

(This article belongs to the Section Endocrinology and Metabolic Diseases)

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11 pages, 316 KB

Open AccessArticle

Serum Catestatin Level as a Novel Biomarker of Oral Lichen Planus

by Mia Roglic Karan, Dinko Martinovic, Ema Puizina, Lovre Martinovic, Jasna Puizina, Daniela Supe-Domic, Roko Santic, Josko Bozic and Livia Sukanec

Med. Sci. 2026, 14(3), 417; https://doi.org/10.3390/medsci14030417 - 22 Jul 2026

Viewed by 337

Abstract

Background/Objectives: Oral lichen planus (OLP) is a chronic immune-mediated disease of the oral mucosa in which T-cell infiltration, epithelial injury, and stress-related neuroendocrine signaling appear to intersect. Catestatin (CST), a peptide generated from chromogranin A (CgA), modulates catecholamine release and inflammatory cell responses; [...] Read more.

Background/Objectives: Oral lichen planus (OLP) is a chronic immune-mediated disease of the oral mucosa in which T-cell infiltration, epithelial injury, and stress-related neuroendocrine signaling appear to intersect. Catestatin (CST), a peptide generated from chromogranin A (CgA), modulates catecholamine release and inflammatory cell responses; however, its association with localized mucosal inflammation in OLP has not been clarified. This study aimed to compare serum CST levels between OLP patients and healthy controls and to examine their association with clinical subtype, disease severity, and vitamin D status. Methods: In this cross-sectional study, 51 patients with clinically and histopathologically confirmed OLP and 60 healthy controls were enrolled at the University Hospital of Split. Serum CST was quantified using ELISA. OLP severity was assessed with the REU score by a single experienced oral medicine examiner who was blinded to laboratory results, and pain and burning were recorded separately using 0–10 VASs. Results: Serum CST levels were significantly higher in OLP patients compared to healthy controls (p < 0.001). CST levels showed a strong positive correlation with the REU total score (r = 0.781, p < 0.001), as well as with VAS pain (r = 0.708, p < 0.001) and VAS burning (r = 0.729, p < 0.001). Erosive OLP exhibited significantly higher CST levels compared to the non-erosive subtype (p < 0.001). Furthermore, serum vitamin D levels were significantly lower in OLP patients (p < 0.001), with no significant correlation observed between CST and vitamin D levels. Conclusions: Serum CST levels were higher in OLP patients and showed close associations with REU scores and symptoms, with the strongest signal observed in erosive disease. CST may therefore contribute to the neuroendocrine-immune profile of OLP and may be useful as an adjunctive marker of clinically active or erosive disease. Larger prospective studies including salivary and tissue-based CST measurements are needed before CST can be used for routine monitoring. Full article

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14 pages, 2398 KB

Open AccessArticle

The Impact of Bilateral Salpingectomy on Ovarian Reserve: A Prospective Analysis of Hormonal, Ultrasound and Clinical Correlations

by Teodora Radu, Matyas Mar, Marius Gliga and Claudiu Marginean

Med. Sci. 2026, 14(3), 416; https://doi.org/10.3390/medsci14030416 - 22 Jul 2026

Viewed by 545

Abstract

Background: Opportunistic salpingectomy is widely used in gynecological surgery as a preventive measure against ovarian carcinoma. Questions have been raised about the potential impact of salpingectomy on ovarian function, given the possibility of ovarian vascularity disruption through the utero-ovarian arch located in [...] Read more.

Background: Opportunistic salpingectomy is widely used in gynecological surgery as a preventive measure against ovarian carcinoma. Questions have been raised about the potential impact of salpingectomy on ovarian function, given the possibility of ovarian vascularity disruption through the utero-ovarian arch located in the mesosalpinx. The aim of this study was to evaluate the short-term effects of bilateral salpingectomy on ovarian reserve. Methods: This prospective cohort study included forty premenopausal women, aged 34–50 years, who underwent hysterectomy with bilateral salpingectomy and ovarian preservation for benign uterine conditions. Ovarian reserve was evaluated before surgery and three months postoperatively, using serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH) and antral follicle count (AFC). Health-related quality of life was assessed using the Women’s Health Questionnaire (WHQ). Results: Serum FSH levels increased significantly after surgery, while AMH levels decreased significantly (both p < 0.05). No significant postoperative changes were observed in AFC. The overall WHQ score increased significantly, indicating a mild deterioration in health-related quality of life. The greatest postoperative changes were observed in the depressive, somatic and sexual domains, where menstrual symptoms improved following surgery. No significant correlation was found between WHQ scores and hormonal or ultrasonographic markers of ovarian reserve. Conclusions: Bilateral salpingectomy performed during hysterectomy was associated with significant short-term hormonal changes, while AFC remained stable. Although patient-reported quality of life slightly worsened after surgery, these changes were not correlated with hormonal or ultrasonographic markers of ovarian reserve. Larger controlled studies with longer follow-up are required to determine the long-term clinical significance of these findings. Full article

(This article belongs to the Section Gynecology)

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13 pages, 1085 KB

Open AccessArticle

Factors Associated with Clinically Meaningful Pain Reduction Following Phase-I Complex Decongestive Therapy in Breast Cancer-Related Lymphedema

by Lucia Demjanovič Kendrová, Wioletta Mikuľáková, Jakub Čuj, Pavol Nechvátal, Katarína Hnatová, Miloslav Gajdoš, Štefánia Andraščíková and Peter Takáč

Med. Sci. 2026, 14(3), 415; https://doi.org/10.3390/medsci14030415 - 22 Jul 2026

Viewed by 372

Abstract

Background: Upper-limb lymphedema after breast cancer treatment is associated with pain, functional limitations, and impaired quality of life. Although complex decongestive therapy (CDT) is standard conservative care, prospective evidence regarding factors associated with clinically meaningful response remains limited. We evaluated the short-term [...] Read more.

Background: Upper-limb lymphedema after breast cancer treatment is associated with pain, functional limitations, and impaired quality of life. Although complex decongestive therapy (CDT) is standard conservative care, prospective evidence regarding factors associated with clinically meaningful response remains limited. We evaluated the short-term outcomes following Phase-I CDT and identified factors associated with clinically meaningful pain reduction. Methods: A prospective observational study was conducted in 94 women with breast cancer-related lymphedema undergoing a standardized 14-day Phase-I CDT program. Outcomes included limb circumference, pain intensity measured using the Visual Analogue Scale (VAS), and quality of life assessed with LYMQOL-Arm. Clinically meaningful improvement was defined a priori as a reduction of at least 2 points on the VAS (ΔVAS ≥ 2). Analyses included paired t-tests, Cohen’s d, multivariable logistic regression, analysis of covariance (ANCOVA), and receiver operating characteristic (ROC) analysis. Results: Significant reductions in limb circumference were observed across all measurement levels (3.08–5.83%; all p < 0.001). Pain intensity decreased from 5.53 ± 2.15 to 2.82 ± 1.41, with a mean reduction of 2.71 points (95% CI 2.32–3.11; p < 0.001) and a very large effect size (Cohen’s d = 1.40). All LYMQOL domains improved significantly. Higher baseline pain intensity was associated with a greater likelihood of achieving the predefined criterion for clinically meaningful improvement (OR 3.03; 95% CI 1.91–4.80), while older age was associated with reduced odds of response (OR 0.90; 95% CI 0.85–0.96). Baseline pain intensity demonstrated good discriminative performance (AUC 0.85). Circumference changes were not correlated with subjective improvement. Conclusions: Following the 14-day Phase-I CDT program, statistically significant reductions in total limb circumference, clinically meaningful pain reduction, and significant improvements in quality of life were observed. Exploratory analyses demonstrated an association between baseline pain intensity and the predefined responder outcome; however, this association is structurally influenced by the mathematical relationship between baseline VAS and the responder definition, baseline-dependent opportunity for improvement, and regression to the mean. Therefore, it should not be interpreted as evidence of an independent predictive effect and requires external validation before being considered for patient stratification or clinical decision-making. Because of the observational pre–post design without a control group, the observed changes cannot be attributed specifically to Phase-I CDT. Full article

(This article belongs to the Section Gynecology)

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Graphical abstract

15 pages, 1250 KB

Open AccessArticle

Improved Prognostic Staging in Endometrial Cancer: Clinical Impact of Aggressive Subtypes in a Multicenter Cohort

by Tatiana Cuesta-Guardiola, Alicia Quirós, Pluvio Jesús Coronado Martín and Augusto Pereira Sánchez

Med. Sci. 2026, 14(3), 414; https://doi.org/10.3390/medsci14030414 - 22 Jul 2026

Viewed by 335

Abstract

Objectives: Assessment of the impact on survival of endometrial carcinoma according to the 2009 FIGO (International Federation of Gynecology and Obstetrics) classification and the new FIGO 2023 classification highlighting the worse prognosis of the aggressive subtypes. Methods: This multicenter retrospective study [...] Read more.

Objectives: Assessment of the impact on survival of endometrial carcinoma according to the 2009 FIGO (International Federation of Gynecology and Obstetrics) classification and the new FIGO 2023 classification highlighting the worse prognosis of the aggressive subtypes. Methods: This multicenter retrospective study included 1181 patients with endometrial cancer. Comprehensive clinical, pathological and treatment-related variables were collected. Primary outcomes included overall survival assessed through five-year follow-ups. Statistical analysis included comparative tests, Kaplan–Meier survival estimation, Cox proportional hazards models and ROC curves analysis to review prognostic accuracy. Results: Aggressive endometrial carcinoma (n = 353) showed significant worse overall survival compared with non-aggressive cases (35.7 versus 60 months). A novel classification based on FIGO 2023 was developed, integrating histological aggressiveness into a different stage and combining early non-aggressive stages in only one stage. While FIGO 2009 and 2023 classifications showed prognostic value, the new model improved risk stratification, clearly distinguishing high-risk groups. Multivariate analysis identified aggressive subtype, stage, age, diabetes, myometrial invasion and lymphovascular invasion as independent predictors. Conclusions: Aggressive histological subtype in endometrial cancer should carry greater prognostic weight in terms of survival and clinical management. Our findings support a potential shift in the current paradigm for these relatively rare but high-risk cases. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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20 pages, 3448 KB

Open AccessArticle

Beneficial Effect of COVID-19 Vaccination on Decreased Pulmonary Vascular and Airway Volumes of Patients with Long-COVID Syndrome

by Eslam Samaha, Emilie Han, Dominika Lukovic, Kevin Hamzaraj, Jutta Bergler-Klein, Ena Hasimbegovic and Mariann Gyöngyösi

Med. Sci. 2026, 14(3), 413; https://doi.org/10.3390/medsci14030413 - 22 Jul 2026

Viewed by 1641

Abstract

Background: Despite normal lung imaging and preserved pulmonary and cardiac function, many patients with long COVID continue to experience persistent respiratory symptoms. This study aimed to quantify the pulmonary blood and airway volumes in patients with long COVID compared with healthy controls and [...] Read more.

Background: Despite normal lung imaging and preserved pulmonary and cardiac function, many patients with long COVID continue to experience persistent respiratory symptoms. This study aimed to quantify the pulmonary blood and airway volumes in patients with long COVID compared with healthy controls and to evaluate the associations of COVID-19 vaccination with these imaging parameters. Methods: Patients with long COVID presenting with persistent respiratory symptoms despite normal laboratory findings, pulmonary function tests, chest radiography, and chest computed tomography (CT) were prospectively enrolled. CT datasets were analyzed using functional respiratory imaging (FRI), incorporating the three-dimensional reconstruction and automated segmentation of the lungs, airways, and pulmonary vasculature. Quantitative imaging parameters were compared with those of historical healthy controls from the COPDGene study, matched for age, sex, body mass index, comorbidities, and pulmonary function test parameters. Results: Thirty patients with long COVID (mean 221 ± 128 days after confirmed SARS-CoV-2 infection) and 30 matched healthy controls were included. Compared with controls, patients with long COVID demonstrated significantly lower pulmonary blood volumes in small and large pulmonary vessels, together with significantly reduced intrapulmonary airway volumes. Within the long COVID cohort, full COVID-19 vaccination was associated with a significantly greater small-vessel pulmonary blood volume and lobar airway volume compared with non-vaccinated individuals. Conclusions: These findings indicate that patients with long COVID exhibit persistent reductions in pulmonary blood and airway volumes despite normal conventional imaging and pulmonary function tests, suggesting the presence of subtle microvascular and small-airway abnormalities that may contribute to ongoing respiratory symptoms. The association between full COVID-19 vaccination and higher small-vessel pulmonary blood and lobar airway volumes suggests a potential protective effect on pulmonary structure and function; however, these findings require confirmation in larger, prospective controlled studies. Full article

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13 pages, 9415 KB

Open AccessSystematic Review

The Impact of Time-to-Intervention on Mortality and Functional Outcome in Acute Subdural Hematoma: A Systematic Review and Meta-Analysis

by Bogdan Jabłoński, Wojciech Górecki, Justyna Fercho, Jacek Szypenbejl, Maksymilian Niemczyk, Oskar Chasles, Zuzanna Krasula, Zuzanna Wites and Mariusz Siemiński

Med. Sci. 2026, 14(3), 412; https://doi.org/10.3390/medsci14030412 - 21 Jul 2026

Viewed by 484

Abstract

Introduction: Acute subdural hematoma (aSDH) represents one of the most lethal and debilitating forms of traumatic brain injury (TBI) encountered in neurosurgical emergency settings, carrying high mortality rates and severe long-term functional deficits. Historically, the timing of surgical decompression has been considered a [...] Read more.

Introduction: Acute subdural hematoma (aSDH) represents one of the most lethal and debilitating forms of traumatic brain injury (TBI) encountered in neurosurgical emergency settings, carrying high mortality rates and severe long-term functional deficits. Historically, the timing of surgical decompression has been considered a critical modifiable prognostic factor. However, contemporary evidence regarding the relationship between time to surgery and clinical outcomes remains inconsistent. This systematic review and meta-analysis evaluates the impact of surgical timing on mortality and functional status in adult patients undergoing evacuation for acute subdural hematoma. Methods: A systematic review was conducted according to the PRISMA 2020 guidelines and registered in PROSPERO. A database search was performed across PubMed, Scopus, Embase and Web of Science for relevant studies published between 2009 and 2026. Peer-reviewed cohort studies and clinical trials including adults (>18 years) with CT- or MRI-confirmed aSDH were included. Data extraction focused on baseline characteristics, surgical timing thresholds, and primary outcomes of mortality and functional status assessed using the Glasgow Outcome Scale (GOS). Methodological quality was assessed using the Newcastle-Ottawa Scale. Relative risks (RR) and risk differences (RD) with 95% confidence intervals (CI) were calculated using a random-effects model. Results: The search identified 1815 records, of which six studies, including 926 patients, met the inclusion criteria. Meta-analysis found no statistically significant association between time to surgery and mortality (RR 1.01, 95% CI [0.69, 1.48], p = 0.96; RD −0.02, 95% CI [−0.19, 0.15]). High statistical heterogeneity was observed (I² = 80%) across the included cohorts. Most studies indicated that patients who underwent rapid neurosurgical intervention frequently presented with significantly worse baseline neurological status, which acts as a primary confounding factor and drives poorer prognostic trends. Conclusions: While historical paradigms emphasize a 4h period for subdural hematoma evacuation, our meta-analysis indicates that a straightforward linear relationship between time to intervention and improved survival or functional outcome is absent in contemporary clinical studies. Surgical timing thresholds must be interpreted cautiously, as the decision-making process is heavily guided by clinical triage bias, where rapidly deteriorating patients are prioritized for urgent decompression. Crude timing thresholds do not reflect a lack of causal benefit of early intervention but rather highlight the profound confounding by indication embedded in contemporary neurotrauma literature. Future multicenter investigations adjusting for admission severity, pupillary reactivity, associated intracranial pathology and other confounding factors are crucial to isolate the true prognostic value of surgical timing in aSDH. Full article

(This article belongs to the Section Critical Care Medicine)

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14 pages, 1594 KB

Open AccessArticle

by Alessandra Francica, Fabiola Perrone, Irene Maffei, Maria Teresa Denora and Giovanni Battista Luciani

Med. Sci. 2026, 14(3), 411; https://doi.org/10.3390/medsci14030411 - 21 Jul 2026

Viewed by 334

Abstract

Background: Current ESC/EACTS guidelines recommend bioprosthetic valves for aortic valve replacement (AVR) in patients > 65 years, yet their use is increasing among younger individuals. The INSPIRIS Resilia (IR) valve, a next-generation bioprosthesis, was designed to improve durability and reduce structural valve degeneration [...] Read more.

Background: Current ESC/EACTS guidelines recommend bioprosthetic valves for aortic valve replacement (AVR) in patients > 65 years, yet their use is increasing among younger individuals. The INSPIRIS Resilia (IR) valve, a next-generation bioprosthesis, was designed to improve durability and reduce structural valve degeneration (SVD). This study compares clinical and valve-related outcomes up to six years in patients undergoing AVR with either the IR or its predecessor, the Perimount Magna Ease (PME) valve. Methods: Between January 2017 and December 2023, 2053 patients underwent isolated or combined AVR at a single institution (1602 PME; 451 IR). Propensity-score matching identified 224 patient pairs with comparable baseline characteristics. Outcomes were assessed over follow-up extending up to six years, focusing on cardiovascular and valve-related adverse events. Transvalvular gradients were also assessed at follow-up. Results: After matching, mean age was 64.2 ± 7.7 years in both groups. Freedom from cardiovascular mortality at six years was similar between PME and IR (96.6% vs. 98.2%; p = 0.34), as were rates of stroke, rehospitalization, prosthetic valve endocarditis, and reintervention. A total of 12 PME (5.4%) and six IR valves (2.5%) were explanted during follow-up (p = 0.15), with prosthetic endocarditis representing the leading cause of reintervention. Only one case of severe SVD was observed in both groups. Conclusions: In patients undergoing AVR with comparable baseline risk profiles, IR and PME valves demonstrated similar clinical, valve-related, and hemodynamic outcomes up to six years of follow-up. Prosthetic valve endocarditis represented the leading cause of valve failure, whereas structural valve deterioration remained rare. Longer follow-up and a greater number of valve-related events will be necessary to determine whether differences in bioprosthetic valve degeneration emerge over time. Full article

(This article belongs to the Section Cardiovascular Disease)

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15 pages, 1345 KB

Open AccessArticle

Characteristics of Inpatient Falls and Factors Associated with Fall-Related Fractures and Recurrent Falls in a Japanese University Hospital

by Norio Imai, Yoji Horigome, Daisuke Homma and Hiroyuki Kawashima

Med. Sci. 2026, 14(3), 410; https://doi.org/10.3390/medsci14030410 - 21 Jul 2026

Viewed by 329

Abstract

Background: Inpatient falls are among the most common adverse events in acute-care hospitals and may result in functional decline, prolonged hospitalization, and increased healthcare costs. However, the characteristics of fall-related fractures and recurrent falls in university hospitals have not been fully investigated. Methods: [...] Read more.

Background: Inpatient falls are among the most common adverse events in acute-care hospitals and may result in functional decline, prolonged hospitalization, and increased healthcare costs. However, the characteristics of fall-related fractures and recurrent falls in university hospitals have not been fully investigated. Methods: We retrospectively reviewed all inpatient fall events reported to the Department of Patient Safety at Niigata University Medical and Dental Hospital between January 2021 and December 2025. Patients younger than 20 years were excluded. Data regarding patient characteristics, mobility status, fracture occurrence, recurrent falls, medication use, and clinical departments were collected from medical records. Univariate and multivariable logistic regression analyses were performed to identify factors associated with fall-related fractures and recurrent falls. Results: A total of 2571 fall events were identified, yielding an incidence of 2.306 falls per 1000 inpatient-days. Malignant neoplasms were the most common primary diagnosis (36.9%). The incidence of falls was highest in the Departments of Neurology and Neurosurgery. Fall-related fractures occurred in 54 cases (2.1%), most commonly involving the lower extremities, including 17 proximal femoral fractures. Multivariable analysis identified mobility status as the only independent factor associated with fractures (odds ratio [OR], 1.821; 95% confidence interval [CI], 1.263–2.627; p = 0.001). Receiver operating characteristic analysis demonstrated a mobility cutoff value of 2.5, indicating an increased fracture risk among patients who were ambulatory with assistive devices or had higher mobility levels. Recurrent falls were observed in 439 patients (24.2%). Reduced mobility (OR, 0.837; 95% CI, 0.713–0.981; p = 0.028), polypharmacy (≥5 medications) (OR, 1.634; 95% CI, 1.254–2.016; p < 0.001), and use of central nervous system depressants (OR, 1.363; 95% CI, 1.124–1.653; p = 0.002) were independently associated with recurrent falls. Conclusions: Patients with fall-related fractures tended to have relatively high mobility, whereas recurrent falls were associated with reduced mobility, polypharmacy, and central nervous system depressant use. Different characteristics of falls were observed across clinical departments. These findings may help identify patients at high risk for adverse fall-related outcomes and support the development of targeted fall-prevention strategies in university hospitals. Full article

(This article belongs to the Section Nursing Research)

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20 pages, 725 KB

Open AccessReview

Primary Lymphomas of the Female Genital Tract: Recognizing the Rare Mimicker of Gynecologic Malignancy

by Sofoklis Stavros, Maria-Anastasia Daskalaki, Stefanos Dafopoulos, Efthalia Moustakli, Ismini Anagnostaki, Anastasios Potiris, Theodoros Karampitsakos, Konstantinos Dafopoulos, Georgios Daskalakis and Peter Drakakis

Med. Sci. 2026, 14(3), 409; https://doi.org/10.3390/medsci14030409 - 21 Jul 2026

Viewed by 447

Abstract

Primary lymphomas of the female genital tract (PLFGT) are extremely rare neoplasms, representing a minor fraction of both extranodal lymphomas and gynecologic malignancies. Due to their nonspecific clinical presentation and overlapping imaging features with more common gynecologic tumors, diagnosis is often delayed or [...] Read more.

Primary lymphomas of the female genital tract (PLFGT) are extremely rare neoplasms, representing a minor fraction of both extranodal lymphomas and gynecologic malignancies. Due to their nonspecific clinical presentation and overlapping imaging features with more common gynecologic tumors, diagnosis is often delayed or missed. This narrative review aims to synthesize current evidence on the clinical characteristics, histologic subtypes, diagnostic approaches, treatment strategies, and prognostic factors of PLFGT, emphasizing recent developments that may influence clinical practice. A comprehensive literature review was conducted, incorporating data from institutional case series, population-based studies, and recent genomic investigations focusing on PLFGT across various anatomical sites: ovary, uterus, cervix, and vagina. PLFGT typically affects women aged 44–68 years, with the ovary being the most frequently involved organ. The most common subtype is diffuse large B-cell lymphoma (DLBCL), followed by Burkitt lymphoma and marginal zone lymphoma. Patients usually present with pelvic pain, mass, or abnormal bleeding, while B symptoms are infrequent. Image-guided core needle biopsy has emerged as a valuable diagnostic approach that may reduce unnecessary surgery. Characteristic sonographic findings, such as hypoechoic, well-defined lesions and homogeneous uterine echo reduction, should raise clinical suspicion, though primary and metastatic disease cannot be distinguished solely by imaging. Rituximab-containing regimens (R-CHOP) are the mainstay of treatment and have improved outcomes. Despite treatment, central nervous system (CNS) recurrence remains a concern, particularly in ovarian involvement. Additionally, mutations in MYD88 and CD79B, although not prognostic, offer potential for personalized therapy. Timely diagnosis and appropriate systemic therapy are critical for improving survival in PLFGT. Advances in imaging, biopsy techniques, and molecular profiling are reshaping the diagnostic and therapeutic landscape of this rare but clinically significant disease. Full article

(This article belongs to the Section Gynecology)

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13 pages, 962 KB

Open AccessArticle

Surgical Timing, Preoperative Oxygenation, and Sex Are Associated with Oxidative Stress and α₁-Microglobulin Response in Neonatal Open-Heart Surgery

by Amanda Kristiansson, Alma M. Borgarsdóttir, Magnus Gram, David Ley and Åsa Jungner

Med. Sci. 2026, 14(3), 408; https://doi.org/10.3390/medsci14030408 - 21 Jul 2026

Viewed by 408

Abstract

Background: Neonatal open-heart surgery induces profound oxidative stress, yet its perioperative dynamics remain incompletely characterized. This study quantified urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostane as markers of oxidative damage, and plasma α₁-microglobulin (A1M) as an endogenous antioxidant, while exploring the influence [...] Read more.

Background: Neonatal open-heart surgery induces profound oxidative stress, yet its perioperative dynamics remain incompletely characterized. This study quantified urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostane as markers of oxidative damage, and plasma α₁-microglobulin (A1M) as an endogenous antioxidant, while exploring the influence of pre- and intraoperative factors. Methods: In a prospective cohort of 40 term neonates with critical congenital heart defects undergoing open-heart surgery, serial urinary and plasma samples were collected perioperatively. Biomarker concentrations were analyzed using mixed-effects regression models to assess associations with postnatal age, sex, preoperative oxygenation, oxygen surge at bypass initiation, and cell-free hemoglobin in the prime solution. Results: Urinary 8-OHdG and 8-isoprostane increased following bypass separation; 8-OHdG remained elevated through postoperative days 0–2, while 8-isoprostane returned toward baseline by day 1. Plasma A1M declined at bypass initiation, recovered to preoperative levels at separation, and rose thereafter. Females exhibited higher A1M concentrations throughout. Longer time to surgery was associated with greater preoperative oxidative stress, and lower preoperative arterial pO₂ correlated with increased 8-isoprostane at bypass separation. No statistically significant associations were identified between intraoperative variables and biomarker levels, although the study was designed to be a hypothesis generating study and not powered to detect modest intraoperative effects. Conclusions: This exploratory study delineates distinct perioperative trajectories of oxidative stress and antioxidant response in neonates undergoing open-heart surgery, with surgical timing, preoperative hypoxemia, and sex emerging as relevant associations. No statistically significant associations were identified between intraoperative variables and biomarker levels; however, the study was hypothesis-generating in design and not powered to detect modest intraoperative effects. Full article

(This article belongs to the Section Cardiovascular Disease)

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14 pages, 703 KB

Open AccessArticle

Impact of the COVID-19 Pandemic on Primary Care Referral Patterns and Resource Utilization in a Hospital Emergency Department: A Comparative Pre- and Later-Pandemic Study

by Angel Iván Díaz-Salado, Francisco Javier García-Sánchez, Alicia Fuente-Gaforio, Andrés Estropá-Zapater, Irene Pérez-Arévalo, Sandra Moreno-Ruiz, María Teresa Sánchez-Álvarez and Natalia Mudarra-García

Med. Sci. 2026, 14(3), 407; https://doi.org/10.3390/medsci14030407 - 21 Jul 2026

Viewed by 423

Abstract

Background: The COVID-19 pandemic profoundly disrupted healthcare utilization patterns at both primary care (PC) and hospital emergency department (ED) levels. This study aimed to assess the impact of the pandemic on referral patterns from PC to a hospital ED and on the resource [...] Read more.

Background: The COVID-19 pandemic profoundly disrupted healthcare utilization patterns at both primary care (PC) and hospital emergency department (ED) levels. This study aimed to assess the impact of the pandemic on referral patterns from PC to a hospital ED and on the resource consumption associated with those referrals. Methods: A descriptive, retrospective, longitudinal comparative study with multivariable sensitivity analyses was conducted at a first-level hospital of Madrid (Spain). All consecutive PC-to-ED referrals received during two observation windows were included: a pre-pandemic period (1 June–31 December 2019;

n = 946

) and a Later-Pandemic period (1 January–30 June 2022;

n = 1797

). Sociodemographic characteristics, referral form quality, diagnostic specialty, and in-ED resource utilization variables were collected and compared using

χ^{2}

, Student’s t-test, and Mann–Whitney U tests as appropriate. To assess seasonal confounding, multivariable logistic and ordinal regression models adjusting for calendar season, age, and sex were performed for the primary resource-utilization outcomes. Results: A total of 2743 referrals were analyzed. The monthly referral rate increased by approximately 122% between periods (135/month vs. 300/month). A statistically significant but clinically negligible difference in mean age was observed (

53.1 \pm 18.3

vs.

54.9 \pm 19.0

years;

p = 0.015

); no significant sex differences were found. Referral form completion improved significantly for clinical history (94.5% vs. 98.2%;

p < 0.001

). Orthopedics referrals nearly tripled (5.8% vs. 18.4%), while respiratory/COVID-19-related referrals represented 22.0% of the 2022 caseload. ED length of stay between 3 and 6 h increased from 13.0% to 42.8% (

p < 0.001

), while the need for urgent blood tests fell from 68.9% to 56.0% (

p < 0.001

), hospital admission from 68.4% to 10.9% (

p < 0.001

), and referral to another center from 12.3% to 0.9% (

p < 0.001

). In multivariable sensitivity analyses, the period effect remained statistically significant after adjustment for calendar season, age, and sex for hospital admission (adjusted OR

= 0.062

; 95% CI: 0.037–0.106;

p < 0.001

) and urgent blood test utilization (adjusted OR

= 0.470

; 95% CI: 0.326–0.678;

p < 0.001

), although study period and season remain partly confounded by the non-overlapping design. Conclusions: During the later-pandemic period, PC-to-ED referrals increased substantially while being associated with fewer complementary investigations and fewer hospital admissions. This study documents between-period differences in referral patterns and ED resource utilization rather than causal effects; the differences persisted after adjustment for seasonality but cannot be definitively attributed to the pandemic. Future multi-center longitudinal studies are needed to confirm these trends and clarify their underlying mechanisms. Full article

(This article belongs to the Section Critical Care Medicine)

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13 pages, 1363 KB

Open AccessReview

Faecal Calprotectin: A Non-Invasive Marker for Diagnosing and Monitoring Acute Diverticulitis

by Aamer Mohammed, Yahiya Baig and Alexandra E. Butler

Med. Sci. 2026, 14(3), 406; https://doi.org/10.3390/medsci14030406 - 19 Jul 2026

Viewed by 467

Abstract

Background: Acute diverticulitis (AD) is a prevalent gastrointestinal disorder with a significant recurrence rate. Faecal calprotectin (FC) is a non-invasive biomarker of intestinal inflammation, but its role in diagnosing and monitoring diverticulitis remains to be fully established. Objective: This narrative review aims to [...] Read more.

Background: Acute diverticulitis (AD) is a prevalent gastrointestinal disorder with a significant recurrence rate. Faecal calprotectin (FC) is a non-invasive biomarker of intestinal inflammation, but its role in diagnosing and monitoring diverticulitis remains to be fully established. Objective: This narrative review aims to evaluate the current evidence on the utility of FC in the diagnosis, severity assessment, prediction of recurrence, and monitoring of therapeutic response in patients with diverticular disease (DD) and AD. Methods: A structured literature search was conducted using PubMed, Scopus, and ScienceDirect for peer-reviewed original studies published in English between 2004 and April 2025. The search strategy combined terms related to diverticular disease and faecal calprotectin. Studies reporting original data on FC in DD were synthesised narratively. Results: FC demonstrates significant utility across multiple clinical applications in DD. For diagnosis, FC is markedly elevated in AD (mean 556–695 μg/g) and symptomatic uncomplicated diverticular disease (SUDD) (median 181 μg/g), while remaining normal in irritable bowel syndrome (mean 50 μg/g), enabling differentiation between organic and functional disorders. FC correlates strongly with endoscopic disease severity, with positivity rates increasing from 48.6% in DICA 1 to 93.2% in DICA 3 (p < 0.0001). For predicting recurrence, elevated FC identifies patients at high risk, with one study reporting 87.5% of recurrent cases showing prior FC elevation and a negative predictive value of 96.8%. FC also exhibits excellent short-term prognostic capacity (AUC 0.976 at 3 months) and responds to therapeutic intervention, with significant reductions following successful treatment with probiotics, nutraceuticals, budesonide, and other agents. Conclusions: FC is a promising non-invasive biomarker for diagnosing diverticulitis, assessing disease severity, predicting recurrence, and monitoring treatment response. Its ability to detect subclinical inflammation makes it particularly useful for risk stratification. However, the current evidence base consists predominantly of retrospective and observational studies, and standardised thresholds require further validation through prospective trials before routine clinical implementation can be recommended. Full article

(This article belongs to the Section Hepatic and Gastroenterology Diseases)

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29 pages, 5615 KB

Open AccessReview

Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas: History, Myths, and Realities Between Past and Future

by Riccardo Urgesi, Cristiano Pagnini, Maria Carla Di Paolo, Lorella Pallotta, Gianfranco Fanello, Pavlos Antypas, Elio Pietro Perrone, Giuseppe Villotti, Andrea D’Amico, Fernando De Angelis and Maria Giovanna Graziani

Med. Sci. 2026, 14(3), 405; https://doi.org/10.3390/medsci14030405 - 19 Jul 2026

Viewed by 689

Abstract

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is among the most clinically relevant and conceptually intricate precancerous lesions encountered in modern gastroenterology. First identified in the early 1980s as a “mucin-producing tumor,” IPMN has since undergone a profound redefinition: from an obscure [...] Read more.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is among the most clinically relevant and conceptually intricate precancerous lesions encountered in modern gastroenterology. First identified in the early 1980s as a “mucin-producing tumor,” IPMN has since undergone a profound redefinition: from an obscure and poorly classified entity to a well-established precursor of pancreatic ductal adenocarcinoma (PDAC), shaped by characteristic molecular alterations such as KRAS, GNAS, and RNF43 mutations. Over the past two decades, the reported incidence of IPMN has risen sharply, a trend largely attributable to the widespread use of high-resolution cross-sectional imaging rather than a genuine increase in disease prevalence. IPMNs are categorized anatomically into main-duct (MD-IPMN), branch-duct (BD-IPMN), and mixed-type forms and histologically into gastric, intestinal, pancreatobiliary, and oncocytic subtypes, each associated with distinct malignant potential and prognostic implications. International consensus guidelines (Sendai 2006; Fukuoka 2012; Fukuoka revision 2017; Kyoto 2024) have progressively refined strategies for risk stratification and surgical decision-making. Nevertheless, significant debate persists regarding optimal surveillance intervals, thresholds for resection, and the management of low-risk branch-duct lesions. This review offers a comprehensive and critically evaluated synthesis about IPMN, spanning its historical recognition, molecular pathogenesis, epidemiology, clinical manifestations, diagnostic evaluation, pathological features, differential diagnosis, surveillance paradigms, long-term complications, associated conditions, therapeutic options, and future directions. Particular attention is given to longstanding “myths” that have influenced clinical practice and to emerging “realities” grounded in contemporary molecular and clinical evidence. Our aim is to provide physicians with a clear and updated framework for navigating the complexities of IPMN management in current practice. Full article

(This article belongs to the Section Hepatic and Gastroenterology Diseases)

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13 pages, 904 KB

Open AccessPerspective

When Surgical Innovation Outpaces Evidence: Does Modern Maximal Resection Require Re-Evaluation of Postoperative Radiotherapy in Glioblastoma?

by Tomasz Tykocki

Med. Sci. 2026, 14(3), 404; https://doi.org/10.3390/medsci14030404 - 18 Jul 2026

Viewed by 261

Abstract

Postoperative radiotherapy (RT) improves survival in glioblastoma, and its role in standard management is not disputed. The randomized trials establishing this benefit, however, were conducted before computed tomography, magnetic resonance imaging (MRI), molecular classification, and temozolomide (TMZ), in heterogeneous populations of “operated malignant [...] Read more.

Postoperative radiotherapy (RT) improves survival in glioblastoma, and its role in standard management is not disputed. The randomized trials establishing this benefit, however, were conducted before computed tomography, magnetic resonance imaging (MRI), molecular classification, and temozolomide (TMZ), in heterogeneous populations of “operated malignant glioma” treated with whole-brain or large-field RT versus best supportive care. Their pooled survival benefit (risk ratio 0.81; 95% CI 0.74–0.88) robustly answers the historical question they were designed to address. Since then, advances in surgery, imaging, molecular diagnostics, and systemic therapy have created a modern best-prognosis subgroup—young patients with excellent performance status, MRI-confirmed complete or supramaximal resection of an IDH-wildtype glioblastoma, and median survival approaching or exceeding three years—for whom no clearly defined historical counterpart exists. This perspective provides a structured appraisal of the directness of the landmark randomized evidence using GRADE concepts and translates that appraisal into a graded roadmap for future de-escalation trial designs. Across population, intervention, comparator, and outcomes, the historical trials exhibit substantial indirectness, while the only randomized RT-versus-no-RT evidence from the modern era derives from elderly patients representing the opposite prognostic extreme. This is not an argument against RT. The infiltrative biology of glioblastoma, predominantly in-field recurrence, and radioresistant stem-cell populations strongly support continued benefit. Rather, the unresolved question concerns the magnitude of benefit after maximal contemporary therapy and whether selected de-escalation strategies merit prospective evaluation. Our thesis is one of collective scientific equipoise regarding an unresolved evidence question rather than individual clinician equipoise or refutation of current standard care. Full article

(This article belongs to the Section Neurosciences)

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26 pages, 3426 KB

Open AccessArticle

An Exploratory Study on the Interrelation of Breast Cancer Molecular Phenotypes with Breast Cancer-Associated Adipose Tissues (BCAATs), Neoadjuvant, and Adjuvant Therapies: A Focus on Prognosis and Survival

by Mihaela Maria Pasca Fenesan, Razvan George Bogdan, Andrei Alexandru Cosma, Vlad Vornicu, Eugen Melnic, Diana Veronica Radu, Patricia Baran, Zorin Crainiceanu, Rodica Elena Heredea, Olga Cernetchi and Anca Maria Cimpean

Med. Sci. 2026, 14(3), 403; https://doi.org/10.3390/medsci14030403 - 18 Jul 2026

Viewed by 328

Abstract

Background/Aim. We previously described four distinct breast cancer (BC)-associated adipose tissue (BCAAT) subtypes that have a significant impact on survival. In this exploratory study, we aimed to determine whether these BCAAT subtypes exhibit significant correlations with neoadjuvant and adjuvant therapies and BC molecular [...] Read more.

Background/Aim. We previously described four distinct breast cancer (BC)-associated adipose tissue (BCAAT) subtypes that have a significant impact on survival. In this exploratory study, we aimed to determine whether these BCAAT subtypes exhibit significant correlations with neoadjuvant and adjuvant therapies and BC molecular subtypes. Methods. Four BCAAT subtypes previously identified as fibroblast-rich (F^Rich_BCAAT), myofibroblast-rich (MyoF^Rich_BCAAT), vascular-rich (V^Rich_BCAAT), and mixed vascular- and inflammation-rich (VI^Rich_BCAAT) were analyzed according to their distribution in BC molecular subtypes, as well as in relation to neoadjuvant therapy and survival. Results. Triple-negative BC and Luminal B (LB) BC are related to V^Rich and VI^Rich BCAAT subtypes and were affected by Epirubicin/Cyclophosphamide (EC)+ paclitaxel (PTX) therapy, which significantly enhanced overall survival (OS) and disease-free survival (DFS). For the Luminal A (LA) BC subtype, EC + docetaxel (DTX) had significant impact on survival independent of BCAAT subtype. Conclusions. BCAAT subtypes strongly influenced neoadjuvant therapy response and survival depending on BC molecular subtype. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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15 pages, 1051 KB

Open AccessArticle

Prognostic Impact of Baseline Potassium Abnormalities in Patients with Heart Failure with Reduced Ejection Fraction: A Real-World Cohort Study

by Alvaro Roldan-Guerra, Jorge Perea-Armijo, Rafael González-Manzanares, Juan Carlos Castillo-Domínguez, Manuel Crespin-Crespin, Manuel Pan-Álvarez Ossorio, Manuel Anguita-Sánchez and José López-Aguilera

Med. Sci. 2026, 14(3), 402; https://doi.org/10.3390/medsci14030402 - 18 Jul 2026

Viewed by 300

Abstract

Introduction: Abnormal serum potassium levels are a common issue in patients with heart failure with reduced ejection fraction (HFrEF), limiting the use of prognostically beneficial therapies. The primary aim of this study was to characterise the HFrEF population according to baseline potassium levels [...] Read more.

Introduction: Abnormal serum potassium levels are a common issue in patients with heart failure with reduced ejection fraction (HFrEF), limiting the use of prognostically beneficial therapies. The primary aim of this study was to characterise the HFrEF population according to baseline potassium levels and to assess their impact on medium- to long-term prognosis. Methods: A retrospective study was conducted on a cohort of consecutive patients with HFrEF recruited at our centre. Patients were classified according to baseline serum potassium levels into: Group 1 (<3.5 mEq/L), Group 2 (3.5–5.0 mEq/L), and Group 3 (>5.0 mEq/L). Prognostic impact was assessed in terms of HF readmissions, HF mortality and all-cause mortality. Results: A total of 409 patients were analysed. The median age was 69 years [IQR 59–77], with a predominance of male patients (74.1%). There were 26 patients (6.36%) with hypokalaemia, 365 (89.24%) with normokalaemia, and 18 (4.4%) with hyperkalaemia. Group 1 showed a higher prevalence of diabetes mellitus (69.2% vs. 47.4% vs. 33.4%; p = 0.043) and a greater proportion of patients with ≥2 previous admissions for HF (25% vs. 10.5% vs. 0%; p = 0.008). No differences were observed regarding echocardiographic parameters, markers of congestion, or HFrEF treatment. After a median follow-up of 60 months, no significant differences were found between groups in rates of HF readmissions, HF mortality and all-cause mortality. Conclusions: Patients with hypokalaemia exhibited a higher prevalence of diabetes mellitus and previous HF admissions. In our population, no differences were observed between groups in the use of prognostically beneficial therapies or in outcomes in terms of HF rehospitalisations and mortality. Full article

(This article belongs to the Section Cardiovascular Disease)

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13 pages, 1659 KB

Open AccessArticle

Asymptomatic Atrial Fibrillation in Contemporary Clinical Practice: Insights from the REGUEIFA Registry

by Carlos Minguito-Carazo, Laila González Melchor, María Vázquez Caamaño, Emilio Fernández-Obanza Windcheid, Raquel Marzoa, Miriam Piñeiro Portela, Eva González Babarro, Pilar Cabanas Grandío, Olga Durán Bobín, Óscar Prada Delgado, Juliana Elices Tejada, Evaristo Freire, Mario Gutiérrez Feijoo, Javier Muñiz, Francisco Gude, Eduardo Barge Caballero, Carlos González-Juanatey and Javier García Seara

Med. Sci. 2026, 14(3), 401; https://doi.org/10.3390/medsci14030401 - 18 Jul 2026

Viewed by 297

Abstract

Background: Asymptomatic atrial fibrillation (AF) represents a substantial proportion of diagnosed AF cases; however, its prognostic implications remain controversial. This study aimed to compare clinical characteristics, treatment strategies, and outcomes between asymptomatic and symptomatic AF patients in a contemporary real-world registry. Methods [...] Read more.

Background: Asymptomatic atrial fibrillation (AF) represents a substantial proportion of diagnosed AF cases; however, its prognostic implications remain controversial. This study aimed to compare clinical characteristics, treatment strategies, and outcomes between asymptomatic and symptomatic AF patients in a contemporary real-world registry. Methods: This observational subanalysis included 997 patients from the prospective multicenter REGUEIFA registry with 2-year follow-up. Patients were classified as asymptomatic if they had a baseline European Heart Rhythm Association (EHRA) score of I. Clinical characteristics, therapeutic strategies, and the incidence of a composite endpoint including cardiovascular death, stroke, major bleeding, or worsening heart failure were analyzed. Results: Overall, 33.7% of patients were asymptomatic. Compared with symptomatic patients, asymptomatic patients had a lower prevalence of heart failure, hypertension, and cardiomyopathy, lower CHA₂DS₂-VASc scores, and a higher prevalence of preserved left ventricular ejection fraction. Rhythm control strategies were less frequently used in asymptomatic patients (58.33% vs. 65.96%; p = 0.018), despite similar arrhythmia recurrence rates after treatment (p = 0.490). The incidence of the composite endpoint was lower in asymptomatic patients (8.39 [6.53–10.78] vs. 12.12 [10.43–14.09] per 100 person-years; p = 0.013), mainly driven by lower cardiovascular mortality. No significant differences were observed in stroke, major bleeding, worsening heart failure, or all-cause mortality. In multivariable analysis adjusted for clinically relevant covariates, symptomatic patients exhibited a higher incidence of the composite endpoint. Conclusions: In this contemporary real-world registry, asymptomatic AF patients exhibited a lower burden of cardiovascular comorbidities and lower cardiovascular mortality than symptomatic patients, while rates of stroke, heart failure worsening, major bleeding, and arrhythmia recurrence were similar. These findings suggest that prognosis is influenced predominantly by baseline comorbidity burden, and the independent contribution of symptom status itself, although statistically significant, appears modest and should be interpreted with caution given the observational design. Full article

(This article belongs to the Section Cardiovascular Disease)

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26 pages, 2810 KB

Open AccessReview

High-Dose Intravenous Vitamin C in Critical Illness: A Translational Exposure–Response Framework for Biomarker-Guided Precision Therapy

by Dejana Bajić, Ljiljana Andrijević, Nemanja Todorović, Mladena Lalić-Popović, Bojan Zarić, Stefan Dimić, Jelena Stojčević Maletić, Dajana Lendak, Boris Milijašević and Nataša Milošević

Med. Sci. 2026, 14(3), 400; https://doi.org/10.3390/medsci14030400 - 17 Jul 2026

Viewed by 614

Abstract

High-dose intravenous vitamin C (HDIVC) has been investigated as a potential adjunctive therapy in critical illness, including sepsis, acute respiratory distress syndrome (ARDS), and COVID-19. Despite a strong mechanistic rationale, clinical trials have yielded inconsistent results. From a clinical pharmacology perspective, this variability [...] Read more.

High-dose intravenous vitamin C (HDIVC) has been investigated as a potential adjunctive therapy in critical illness, including sepsis, acute respiratory distress syndrome (ARDS), and COVID-19. Despite a strong mechanistic rationale, clinical trials have yielded inconsistent results. From a clinical pharmacology perspective, this variability may reflect, at least in part, differences in pharmacokinetic exposure, timing of administration, and patient selection rather than a lack of biological activity. Intravenous administration enables plasma concentrations in the millimolar range (≈1–5 mM), far exceeding those achievable with oral dosing (<100 µM), thereby reaching thresholds required for pharmacodynamic effects on oxidative stress, immune signaling, and endothelial function. This exposure-dependent transition distinguishes vitamin C as a pharmacological agent rather than a nutritional supplement in critically ill populations. Therapeutic response may be influenced by timing relative to disease progression, with earlier administration representing a biologically plausible strategy that warrants prospective evaluation rather than a clinically established therapeutic window. Interindividual variability in transporter function, redox status, and genetic background may further contribute to heterogeneous responses. Biomarkers such as interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer, and markers of endothelial injury provide a framework for patient stratification and monitoring of pharmacodynamic effects. Integrated with pharmacokinetic principles, these markers support a shift toward biomarker-guided, precision-based therapeutic strategies. This review synthesizes current clinical and mechanistic evidence through an exposure–response conceptual framework, framing HDIVC as a context-dependent pharmacological intervention and advancing a shift toward biomarker-guided, precision-based therapeutic strategies in critical illness. Full article

(This article belongs to the Special Issue Sepsis Management and Therapeutic Strategies: From Early Recognition to Advanced Interventions)

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13 pages, 447 KB

Open AccessArticle

Association Between Ultra-Processed Food Consumption and Lymphocyte Profile in People Living with HIV: A Cross-Sectional Study

by Sofia Morais Tornis, David Michel de Oliveira, Fábio Morato de Oliveira, Luiz Rodrigo Augustemak de Lima, Mayara Bocchi and Eduardo Vignoto Fernandes

Med. Sci. 2026, 14(3), 399; https://doi.org/10.3390/medsci14030399 - 17 Jul 2026

Viewed by 318

Abstract

Introduction: Ultra-processed foods (UPFs) are characterized by high levels of additives such as sugars, fats, and preservatives and, due to their composition, represent a major public health concern, being associated with several adverse effects, including impacts on the immune system. People living with [...] Read more.

Introduction: Ultra-processed foods (UPFs) are characterized by high levels of additives such as sugars, fats, and preservatives and, due to their composition, represent a major public health concern, being associated with several adverse effects, including impacts on the immune system. People living with HIV (PLHIV) present immune dysfunctions resulting from viral infection and may therefore be particularly vulnerable to the effects of UPF consumption. In this context, investigating this association is necessary to support healthcare strategies and improve assistance for PLHIV. Objective: To investigate the relationship between UPF consumption and the lymphocyte profile of PLHIV. Methods: This was a cross-sectional study. PLHIV receiving outpatient follow-up care for at least six months participated in the study and were categorized according to UPF consumption (≤2 times/week; >2 times/week). Sociodemographic data, UPF consumption assessed through a food frequency questionnaire, anthropometric measurements, and blood samples were collected. Association, comparison, and correlation tests were performed, with statistical significance set at p < 0.05. After adjustment, lymphocyte percentage remained independently associated with UPF consumption. Results: A total of 92 PLHIV participated in the study, with a mean age of 43.0 ± 12.0 years. PLHIV with higher UPF consumption presented lower counts of CD3+ lymphocytes (p = 0.03), CD45+ lymphocytes (p = 0.01), and total lymphocytes (p = 0.03) compared to those with lower UPF consumption. UPF consumption was negatively correlated with CD3+ (r = −0.21; p = 0.04), CD4+ (r = −0.20; p = 0.05), CD45+ (r = −0.23; p = 0.02), and total lymphocyte counts (r = −0.25; p = 0.01). No associations were found between sociodemographic or clinical variables and UPF consumption among PLHIV (p > 0.05). Conclusions: High UPF consumption was associated with lower lymphocyte counts in PLHIV, suggesting a potential association between dietary patterns and immune status. Therefore, the implementation of public health policies and nutritional follow-up is necessary to reduce UPF consumption and promote healthy eating among PLHIV. Full article

(This article belongs to the Section Immunology and Infectious Diseases)

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12 pages, 480 KB

Open AccessReview

Gamma Oscillations, Sensory Stimulation, and Glymphatic Function: Toward User-Friendly Auditory Interventions for Brain Health in Aging and Neurodegeneration

by Peter Wostyn and Piet Goddaer

Med. Sci. 2026, 14(3), 398; https://doi.org/10.3390/medsci14030398 - 17 Jul 2026

Viewed by 521

Abstract

The glymphatic system is a brain-wide clearance pathway that facilitates the removal of interstitial solutes, including amyloid-β, and plays a critical role in maintaining brain homeostasis. Impairments in glymphatic transport have been implicated in aging and neurodegenerative diseases, including Alzheimer’s disease. While glymphatic [...] Read more.

The glymphatic system is a brain-wide clearance pathway that facilitates the removal of interstitial solutes, including amyloid-β, and plays a critical role in maintaining brain homeostasis. Impairments in glymphatic transport have been implicated in aging and neurodegenerative diseases, including Alzheimer’s disease. While glymphatic activity is most pronounced during sleep, emerging evidence suggests that specific patterns of neural activity, including gamma-frequency oscillations entrained by sensory stimulation, can modulate glymphatic transport even during wakefulness. Preclinical studies further indicate that 40 Hz sensory stimulation, delivered via light, sound, or multisensory paradigms, can induce gamma oscillations, reduce pathological protein accumulation, and enhance cognitive performance in animal models of Alzheimer’s disease. Early clinical investigations similarly suggest that gamma-frequency sensory stimulation may improve blood-based biomarkers, neuroimaging measures, and cognitive outcomes in patients with Alzheimer’s disease. To translate gamma-frequency stimulation into broadly applicable preventive or therapeutic strategies, approaches must be both effective and tolerable for long-term use. Conventional auditory gamma stimulation can be perceived as acoustically rough or monotonous, reducing listener comfort and limiting acceptability for prolonged use in broader populations. User-friendly auditory formats, such as “gamma music” and the more recently introduced “immersive gamma music”, have been proposed as potentially useful approaches for delivering gamma-frequency stimulation while improving listening comfort and facilitating sustained use. Collectively, gamma-frequency sensory stimulation represents a promising approach to support healthy brain aging and mitigate neurodegenerative processes, particularly when implemented via user-friendly auditory formats that facilitate repeated and long-term use. While these findings are encouraging, further research is needed to validate these approaches and determine their clinical relevance. Full article

(This article belongs to the Section Neurosciences)

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13 pages, 823 KB

Open AccessArticle

Post-Anesthesia Care Unit Duration After Total Hip Arthroplasty Under Spinal Anesthesia in Routine Hospital Practice: A Comparison with Contemporary Arthroplasty Literature

by Christina Soerensen, Christina Froeslev-Friis, Lisbeth Quitzau, Gunhild Kjaergaard-Andersen, Artur Jawor and Rajesh Prabhakar Bhavsar

Med. Sci. 2026, 14(3), 397; https://doi.org/10.3390/medsci14030397 - 16 Jul 2026

Viewed by 376

Abstract

Background: Post-anesthesia care unit (PACU) duration after total hip arthroplasty (THA) is relevant for ward transfer, early mobilization, and perioperative flow, but is inconsistently reported as a distinct recovery outcome. This study evaluated PACU duration after primary THA under spinal anesthesia in routine [...] Read more.

Background: Post-anesthesia care unit (PACU) duration after total hip arthroplasty (THA) is relevant for ward transfer, early mobilization, and perioperative flow, but is inconsistently reported as a distinct recovery outcome. This study evaluated PACU duration after primary THA under spinal anesthesia in routine hospital-based practice and interpreted the observed duration in relation to contemporary arthroplasty literature. Methods: This retrospective observational cohort study included adult patients undergoing primary THA under spinal anesthesia within two units of a regional hospital. PACU duration was defined as time from PACU arrival until discharge to the orthopedic ward. Demographic, anesthetic, perioperative, and recovery variables were extracted from electronic medical records. Univariate analyses and multivariable linear regression were used to explore factors associated with PACU duration. A focused contextual literature comparison was performed to interpret the observed duration in relation to reported early recovery endpoints, with direct comparison anchored to conventional PACU or recovery-room intervals before ward transfer or immediate pathway progression. Results: Ninety-seven of 150 screened patients were included. Mean PACU duration was 162.3 ± 58.5 min. PACU duration was numerically longer in Unit A than Unit S, but the difference was not statistically significant. Reported early recovery endpoints in the literature were heterogeneous. In univariate analysis, male sex and exploratory spinal local anesthetic dose > 13 mg were associated with longer PACU duration. In multivariable analysis, male sex remained associated with longer PACU duration, whereas spinal dose was not independently associated when analyzed as a continuous variable. Conclusions: PACU duration after THA under spinal anesthesia should be interpreted as a multifactorial, workflow-sensitive outcome rather than a purely anesthetic recovery measure. Differences in discharge criteria, recovery pathways, and endpoint definitions limit direct comparison across studies. PACU duration may be most meaningful as an operational recovery and flow indicator within broadly comparable clinical settings. Full article

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24 pages, 1477 KB

Open AccessReview

Assessment of Sexual Function Following Hysterectomy: A Systematic Review and Meta-Analysis

by Ákos Molnár-Csendom, Balázs Vida, Ferenc Bánhidy, Francis Bánhidy, Sára Káposzta, Lotti Lőczi, Dániel Sándor Veres, Márton Keszthelyi, Balázs Lintner and Richárd Tóth

Med. Sci. 2026, 14(3), 396; https://doi.org/10.3390/medsci14030396 - 16 Jul 2026

Viewed by 508

Abstract

Background: Hysterectomy is one of the most frequently performed major gynecological procedures, yet its effect on sexual quality of life remains unclear. Objective: To evaluate changes in sexual quality of life following hysterectomy and to determine whether cervical preservation is associated with improved [...] Read more.

Background: Hysterectomy is one of the most frequently performed major gynecological procedures, yet its effect on sexual quality of life remains unclear. Objective: To evaluate changes in sexual quality of life following hysterectomy and to determine whether cervical preservation is associated with improved postoperative sexual function. Methods: Five databases were systematically searched from inception to February 2026. Eligible studies reported pre- and postoperative sexual quality-of-life outcomes after hysterectomy using validated or non-validated questionnaires. All surgical indications, approaches, and study designs were included. Risk of bias was assessed using RoB 2 and ROBINS-I. Mean score differences were pooled using random-effects meta-analysis and meta-regression within a frequentist framework. Heterogeneity was assessed with τ², cluster-robust standard errors were applied, and certainty of evidence was evaluated using GRADE. Results: Thirty-four studies were included in the systematic review, among them sixteen studies comprising 2341 patients were included in the statistical synthesis comprising three randomized controlled trials and thirteen observational studies. The Female Sexual Function Index (FSFI) was the most commonly reported outcome. Across all hysterectomy types, including total, abdominal, laparoscopic, and vaginal approaches, no clinically or statistically significant improvement in postoperative sexual function was observed compared with baseline. Subtotal hysterectomy did not demonstrate a meaningful advantage over total hysterectomy. FSFI total scores were consistent with sexual dysfunction at baseline and remained below the established cutoff (≤26.55) during follow-up across all surgical routes. No hysterectomy approach was associated with a clinically relevant change in sexual quality of life. Conclusions: Postoperative changes in sexual function after hysterectomy were small and non-significant overall. Cervical preservation did not provide measurable benefit. Surgical approach selection should therefore not be based on expectations of improved sexual outcomes. Full article

(This article belongs to the Section Gynecology)

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33 pages, 5900 KB

Open AccessReview

Beyond Performance: Cognitive Overload and Related Cognitive, Psychophysiological, and Performance States in Competitive Esports—A Scoping Review

by Maciej Lachowicz, Dariusz Jamro, Anna Zawadka, Zofia Tomala and Grzegorz Żurek

Med. Sci. 2026, 14(3), 395; https://doi.org/10.3390/medsci14030395 - 15 Jul 2026

Viewed by 671

Abstract

Background: Competitive esports represents a rapidly developing digital performance environment in which players must regulate attention, affect, psychophysiological activation, and performance under dynamic, high-demand conditions. Although cognitive overload and related states are increasingly relevant to esports research, these constructs have not been consistently [...] Read more.

Background: Competitive esports represents a rapidly developing digital performance environment in which players must regulate attention, affect, psychophysiological activation, and performance under dynamic, high-demand conditions. Although cognitive overload and related states are increasingly relevant to esports research, these constructs have not been consistently defined, operationalized, or measured. Objective: This scoping review aimed to map empirical evidence on cognitive overload and related states in competitive esports, with emphasis on cognitive demands, psychophysiological and neurophysiological markers, coping and recovery approaches, game genres, and performance outcomes. Methods: The review followed Joanna Briggs Institute guidance and PRISMA-ScR reporting principles. Searches were conducted in Scopus, PubMed, Web of Science, and EBSCOhost on 5 May 2026. Eligible studies were peer-reviewed empirical articles involving ranked, collegiate, semi-professional, professional, elite, or otherwise competitive esports players and included at least one objective or semi-objective indicator relevant to overload-related states. Results: Forty-eight studies were included. Evidence was distributed across in-game performance, stress and arousal, cardiometabolic load, mental workload, sleep and recovery, perceptual-cognitive processing, neurophysiological markers, and intervention-oriented approaches. Heart rate (HR), heart rate variability (HRV), eye-tracking, sleep or wearable measures, electroencephalography (EEG), event-related potential (ERP), cortisol, pupil diameter, electrodermal activity (EDA), cognitive tasks, and in-game metrics were used across the literature. However, these measures were rarely integrated into unified, multimodal models. Conclusions: Cognitive overload in esports is best understood as a dynamic, multidimensional state emerging from interactions between game demands, competitive context, player regulation, and performance consequences. Future research should develop genre-sensitive, multimodal, and time-synchronized models that distinguish workload, stress, fatigue, arousal, tilt, and performance decline. Full article

(This article belongs to the Section Neurosciences)

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18 pages, 971 KB

Open AccessArticle

Vasopressor Dosing Trajectories in Septic Shock According to Initial Antimicrobial Susceptibility and Infection Source Concordance: A Retrospective Observational Study

by Yurina Yamaya, Tsukasa Kuwana, Kosaku Kinoshita, Ken Takahashi, Hayato Nakabayashi and Toru Imai

Med. Sci. 2026, 14(3), 394; https://doi.org/10.3390/medsci14030394 - 15 Jul 2026

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Background/Objectives: Septic shock carries high mortality. Although guidelines recommend early empiric antibiotics, early identification of the infection source and selection of appropriate initial antibiotic therapy remain challenging. This study examined whether vasopressor trajectories, quantified as norepinephrine equivalent (NEE), differed according to initial [...] Read more.

Background/Objectives: Septic shock carries high mortality. Although guidelines recommend early empiric antibiotics, early identification of the infection source and selection of appropriate initial antibiotic therapy remain challenging. This study examined whether vasopressor trajectories, quantified as norepinephrine equivalent (NEE), differed according to initial antimicrobial susceptibility and concordance between presumed and final infection sources. Methods: This single-center retrospective observational study included adults with Sepsis-3 septic shock admitted to the intensive care unit between 2017 and 2023. Patients were classified into the appropriate-management group when the initial antibiotic therapy covered the subsequently identified causative pathogen and the initially presumed infection source was concordant with the final infection source; all others were classified into the inappropriate-management group. Primary outcomes were Max NEE duration and the times from Max NEE to 75%, 50%, 25%, and discontinuation of NEE. Results: Among 132 patients analyzed, 101 were classified into the appropriate-management group and 31 into the inappropriate-management group. Max NEE duration was shorter in the appropriate-management group (median (IQR), 4 (2–7) h vs. 6 (3–20) h; p = 0.0100) and remained shorter after excluding deaths during the Max NEE period (n = 119; 6 (2–11) h vs. 11 (5–14) h; p = 0.0314). Time to NEE reduction from Max NEE was shorter in the appropriate-management group, with significant differences at 75% (7 (4–13) h vs. 13 (9–23) h; p = 0.0066) and 25% (19 (13–29) h vs. 31 (16–46) h; p = 0.0247). Conclusions: Prolonged Max NEE duration and delayed NEE reduction were associated with inadequate coverage by initial antibiotic therapy or discordant infection source identification in this selected cohort. Vasopressor trajectories may help prompt reassessment of antibiotic therapy and infection source evaluation. Full article

(This article belongs to the Special Issue Sepsis Management and Therapeutic Strategies: From Early Recognition to Advanced Interventions)

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17 pages, 885 KB

Open AccessArticle

Total Neoadjuvant Therapy Versus Long-Course Chemoradiotherapy in Locally Advanced Rectal Cancer: Real-World Tumor Response and Clinical Outcomes

by Sorinel Lunca, Wee Liam Ong, Stefan Morarasu, Ana Maria Musina, Cristian Ene Roata, Raluca Zaharia and Gabriel Mihail Dimofte

Med. Sci. 2026, 14(3), 393; https://doi.org/10.3390/medsci14030393 - 14 Jul 2026

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Abstract

Background: Total neoadjuvant therapy is becoming a preferred option for locally advanced rectal cancer, particularly in patients with high-risk baseline features. However, real-world evidence comparing tumor response, MRI-defined high-risk feature clearance, surgical outcomes, and survival after total neoadjuvant therapy versus conventional long-course chemoradiotherapy [...] Read more.

Background: Total neoadjuvant therapy is becoming a preferred option for locally advanced rectal cancer, particularly in patients with high-risk baseline features. However, real-world evidence comparing tumor response, MRI-defined high-risk feature clearance, surgical outcomes, and survival after total neoadjuvant therapy versus conventional long-course chemoradiotherapy remains limited. This study aimed to compare outcomes between total neoadjuvant therapy and long-course chemoradiotherapy in patients with locally advanced rectal cancer treated in routine clinical practice. Methods: This is a retrospective, single-centre cohort study focused on patients with stage II–III locally advanced rectal adenocarcinoma treated with curative-intent neoadjuvant therapy using either total neoadjuvant therapy or long-course chemoradiotherapy. Tumor response was assessed using restaging MRI, clinical complete response, and pathological complete response. Surgical outcomes and overall survival were evaluated. Results: A total of 110 patients were included. Patients treated with total neoadjuvant therapy had a higher baseline disease burden reflected by a greater proportion of cT4 tumors (40.6% vs. 19.2%; p = 0.014). Radiologic tumor-length response and clearance of MRI-defined high-risk features were comparable between treatment strategies. Clinical and pathological complete response rates were numerically higher in the total neoadjuvant therapy group, but the differences were not significant (cCR: 15.6% vs. 6.4%, p = 0.151; pCR: 18.5% vs. 9.7%, p = 0.301). Conclusions: In this real-world cohort, TNT was preferentially used in patients with more advanced baseline disease and showed numerically higher complete response rates, although differences were not statistically significant. Radiologic response, surgical outcomes, and short-term survival were comparable between treatment strategies. These findings support the feasibility of TNT in routine clinical practice but should be interpreted as exploratory and hypothesis-generating rather than evidence of treatment superiority. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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13 pages, 1504 KB

Open AccessArticle

Prospective Evaluation of CEUS-URM in Axillary Lymph Nodes with Diffuse Cortical Thickening in Breast Cancer Patients

by Roxana Pintican, Calin Schiau, Nicoleta Antone, Filip Madalina, Andrei Roman, Carmen Lisencu, Ovidiu Balacescu, Vlad-Alexandru Gata, Maximilian Vlad Muntean and Patriciu Achimas-Cadariu

Med. Sci. 2026, 14(3), 392; https://doi.org/10.3390/medsci14030392 - 14 Jul 2026

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Abstract

Background: Conventional axillary ultrasound (US) is least reliable in lymph nodes with diffusely thickened cortex. We evaluated whether contrast-enhanced ultrasound with ultra-resolution microvascular imaging (CEUS-URM) improves discrimination of metastatic nodes in this subgroup. Materials and methods: This was a prospective single-center [...] Read more.

Background: Conventional axillary ultrasound (US) is least reliable in lymph nodes with diffusely thickened cortex. We evaluated whether contrast-enhanced ultrasound with ultra-resolution microvascular imaging (CEUS-URM) improves discrimination of metastatic nodes in this subgroup. Materials and methods: This was a prospective single-center study of patients with histologically confirmed breast cancer; one index (most suspicious) node per patient (unit of analysis = index node). Two separately recruited consecutive cohorts were analyzed: a US-only cohort (n = 181; diffuse-thickening subgroup with histology, n = 52) and a subsequent CEUS-URM cohort (n = 42; 15 metastatic). Surgical histopathology (SLNB/ALND) was the reference standard. A CEUS-URM score was built from data-driven, Youden-optimized cut-offs (URM vessel count ≥8; DV mean density ≥ 13.05) and internally validated by bootstrap with optimism correction. As the cohorts were separate, the US-versus-CEUS comparison is cross-cohort and exploratory. Results: Within the diagnostically challenging subgroup of lymph nodes with diffusely thickened cortex, conventional axillary US alone demonstrated limited discriminatory performance for metastatic involvement (AUC 0.43). CEUS-derived quantitative parameters significantly improved diagnostic accuracy, with the best individual parameter achieving an AUC of 0.68. A simple CEUS score combining hypervascular vessel count and vascular density provided the highest diagnostic performance (AUC 0.81, 95% CI 0.68–0.92). At a low threshold, the CEUS score showed high sensitivity (93%), suitable for screening and exclusion of nodal metastases, while at a higher threshold it achieved high specificity (96%), allowing reliable confirmation of metastatic disease. Conclusions: In this exploratory study, a simple CEUS-URM score improved discrimination of diffusely thickened axillary nodes and may serve as an adjunct to conventional US. The findings are preliminary—derived and tested in the same small cohort—and require external, within-patient paired validation. Full article

(This article belongs to the Section Cancer and Cancer-Related Research)

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14 pages, 238 KB

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Blood sLOX-1 Is Beneficial for Determining Severity of Neonatal Hypoxic–Ischemic Encephalopathy: A Nationwide Prospective Cohort Study

by Takuya Oshima, Yoshinori Aoki, Tomohisa Akamatsu, Yutaka Matsuyama, Naoto Takahashi, Toshimasa Obonai, Masaki Shimizu, Kaoru Okazaki, Jun Shibasaki, Osuke Iwata, Takafumi Sakakibara, Reiko Kushima, Kenichi Masumoto, Masahiro Kinoshita, Daigo Kajikawa, Yumi Kono, Yasuki Maeno, Ken Nagaya, Kentaro Shirai, Atsushi Naito, Akira Oka and Masayuki Itoh Show full author list Hide full author list

Med. Sci. 2026, 14(3), 391; https://doi.org/10.3390/medsci14030391 - 14 Jul 2026

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Abstract

Background/Objectives: Neonatal hypoxic–ischemic encephalopathy (HIE) is a major cause of neurodevelopmental diseases. In a previous retrospective study, we revealed that the levels of the soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) are linked to HIE severity. We conducted a prospective investigation [...] Read more.

Background/Objectives: Neonatal hypoxic–ischemic encephalopathy (HIE) is a major cause of neurodevelopmental diseases. In a previous retrospective study, we revealed that the levels of the soluble form of lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) are linked to HIE severity. We conducted a prospective investigation to evaluate the association between sLOX-1 levels and HIE severity using the Sarnat staging system, as well as a multicenter study to assess neurodevelopmental sequelae in the short term. Methods: A total of 193 infants were enrolled in the study between April 2018 and March 2021. We divided the infants into groups as follows: infants without HIE were assigned to a normal control group, and those with HIE to mild, moderate, and severe HIE groups. We measured 191 samples, excluding three participants. The distribution of 191 participants was as follows: 88 normal samples of 50 umbilical cord (UC) arteries and 38 venous blood samples (control; CTL), as well as 103 HIE samples of 34 mild, 55 moderate, and 14 severe HIE samples. All the plasma samples were collected until 6 h after birth. Results: The mean sLOX-1 value in the CTL group was 613 pg/mL (IQR: 474–925 pg/mL) and that in the UC group was 497 pg/mL (IQR: 337–693 pg/mL), with no significant difference (p = 0.136). The mean sLOX-1 value in the mild HIE group was 1030 pg/mL (IQR: 658–1547 pg/mL), 1026 pg/mL (IQR: 710–2051 pg/mL) in the moderate HIE group, and 1444 pg/mL (IQR: 766–3927 pg/mL) in the severe HIE group. There were significant differences between the CTL and HIE groups (p = 0.006) and between the CTL and mild HIE groups (p < 0.05), but not between the mild HIE and the moderate and severe HIE groups (p = 0.088). The other blood markers exhibited no correlation with Sarnat severity. Interestingly, blood sLOX-1 levels increased with Sarnat severity. Conclusions: The results of this study indicated that sLOX-1 level was correlated with Sarnat severity. Moreover, early assessment of sLOX-1 level may be useful for deciding whether to induce therapeutic hypothermia and/or other treatments, and sLOX-1 may serve as a short-term outcome biomarker of HIE. Full article

33 pages, 19332 KB

Open AccessReview

Imaging-Based Risk Stratification for Sudden Cardiac Death in Hypertrophic Cardiomyopathy: Current Evidence and Clinical Perspectives

by Èlia Rifé-Pardo, Sara Sóñora-López, Guillem Casas, Maria Soledad Ceballos, Leandro Santiago Videla, Javier Limeres-Freire, Gisela Teixidó-Tura, Ignacio Ferreira-González and José F. Rodríguez-Palomares

Med. Sci. 2026, 14(3), 390; https://doi.org/10.3390/medsci14030390 - 14 Jul 2026

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Abstract

Hypertrophic cardiomyopathy (HCM) is a common inherited myocardial disorder and a leading cause of sudden cardiac death (SCD) across all age groups. Accurate risk stratification remains a clinical challenge, as conventional algorithms fail to fully capture the heterogeneous arrhythmic substrate of the disease. [...] Read more.

Hypertrophic cardiomyopathy (HCM) is a common inherited myocardial disorder and a leading cause of sudden cardiac death (SCD) across all age groups. Accurate risk stratification remains a clinical challenge, as conventional algorithms fail to fully capture the heterogeneous arrhythmic substrate of the disease. In recent years, cardiac imaging has emerged as a pivotal tool for refining SCD prediction by providing detailed structural, functional, and tissue-characterisation data. This review offers a comprehensive synthesis of imaging-derived predictors of SCD in HCM. We examine established echocardiographic markers, including maximal left ventricular wall thickness, left ventricular ejection fraction and left ventricular outflow tract obstruction, together with advanced cardiovascular magnetic resonance parameters such as late gadolinium enhancement and apical aneurysm detection. In addition, we discuss the emerging role of extracellular volume expansion, quantitative mapping techniques, and strain abnormalities within the framework of contemporary risk stratification models. By bridging imaging biomarkers with underlying pathophysiological mechanisms, this review highlights current evidence, limitations, and future directions to improve precision in SCD risk assessment in HCM. Full article

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Med. Sci., Volume 14, Issue 3 (July 2026) – 84 articles

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