Journal of Clinical Medicine

20 pages, 553 KB

Open AccessReview

Fingolimod as a Neuroprotective Agent in Ischemic Stroke: A Review of Preclinical and Clinical Evidence

by Alin Ciubotaru, Roxana Covali, Cristina Grosu, Daniel Alexa, Esthir Flavia Pilă, Andrei Ionuț Cucu, Amelian Madalin Bobu, Gabriela Dumachita Sargu, Laura Riscanu, Mihaela Camelia Tirnovanu, Cristina Adam, Radu Popa, Cristiana Filip and Emilian Bogdan Ignat

J. Clin. Med. 2025, 14(19), 6797; https://doi.org/10.3390/jcm14196797 (registering DOI) - 25 Sep 2025

Abstract

Ischemic stroke remains a leading cause of mortality and disability worldwide, with current therapies such as intravenous thrombolysis and mechanical thrombectomy benefiting only a limited proportion of patients. Neuroinflammation is a key contributor to secondary brain injury, creating a strong rationale for adjunctive [...] Read more.

Ischemic stroke remains a leading cause of mortality and disability worldwide, with current therapies such as intravenous thrombolysis and mechanical thrombectomy benefiting only a limited proportion of patients. Neuroinflammation is a key contributor to secondary brain injury, creating a strong rationale for adjunctive therapies targeting immune modulation. Fingolimod, a sphingosine-1-phosphate receptor (S1PR) modulator originally approved for multiple sclerosis, has shown promising effects in both preclinical and early clinical studies of acute ischemic stroke. Methods: We conducted a structured narrative review of preclinical and clinical studies published between 2015 and 2024, using PubMed, Scopus, and Web of Science databases. Inclusion criteria were original studies evaluating fingolimod in ischemic stroke models or human patients, either as monotherapy or in combination with reperfusion therapies. Exclusion criteria included conference abstracts without peer review, studies lacking mechanistic insight, and non-English publications. Results: Preclinical evidence demonstrates that fingolimod reduces infarct size, preserves blood–brain barrier integrity, and modulates neuroinflammation through multiple mechanisms, including T cell sequestration, microglial polarization, and mitochondrial protection. Clinical trials, though limited in size, suggest improved short- and long-term outcomes when fingolimod is used in combination with intravenous thrombolysis or endovascular therapy, with a manageable safety profile. Novel nanotechnology-based delivery systems further enhance central nervous system (CNS) targeting and reduce systemic side effects. Conclusions: Fingolimod represents a promising multi-targeted adjunctive strategy for ischemic stroke, acting at the intersection of immune modulation, vascular protection, and neuroprotection. While current findings are encouraging, larger randomized controlled trials and biomarker-driven patient selection are needed to validate its clinical utility. This review highlights the translational potential of fingolimod and outlines key directions for future research. Full article

(This article belongs to the Special Issue Innovative Approaches to the Challenges of Neurodegenerative Disease)

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10 pages, 266 KB

Open AccessReview

Updated Review of the Management of and Guidelines for Traumatic Brain Injury

by Aaron Rapp, Hassan Kobeissi and Daniel K. Fahim

J. Clin. Med. 2025, 14(19), 6796; https://doi.org/10.3390/jcm14196796 (registering DOI) - 25 Sep 2025

Abstract

Traumatic brain injury (TBI) remains a leading cause of mortality and disability globally, necessitating ongoing research into its pathophysiology and management. This review compiles current knowledge on TBI, focusing on its mechanisms, updated clinical guidelines, and recent clinical trials. A systematic PubMed search [...] Read more.

Traumatic brain injury (TBI) remains a leading cause of mortality and disability globally, necessitating ongoing research into its pathophysiology and management. This review compiles current knowledge on TBI, focusing on its mechanisms, updated clinical guidelines, and recent clinical trials. A systematic PubMed search identified studies on TBI management, guidelines, and trials from 2015 to 2024. TBI initiates with a primary mechanical insult, followed by secondary injury from cerebral edema, elevated intracranial pressure (ICP), and ischemia. Management hinges on stabilizing patients, mitigating secondary injury, and optimizing recovery, guided by the Brain Trauma Foundation’s 2020 guidelines. Key trials, including Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension (RESCUEicp) and Decompressive Craniectomy in Diffuse Traumatic Brain Injury (DECRA), have refined recommendations for decompressive craniectomy, though its role remains debated. Findings indicate that large craniectomies improve mortality in late refractory ICP cases, but early intervention lacks clear benefits. Challenges include access to advanced monitoring and surgical expertise. This review underscores the evolving nature of TBI care and the need for dynamic guidelines to improve patient outcomes. Full article

(This article belongs to the Section Brain Injury)

10 pages, 498 KB

Open AccessArticle

Cyberchondria and Health Anxiety in Patients Visiting Hematology Outpatient Clinic: Reflection of Digitalisation

by Kadir Ilkkilic and Recep Evcen

J. Clin. Med. 2025, 14(19), 6795; https://doi.org/10.3390/jcm14196795 (registering DOI) - 25 Sep 2025

Abstract

Background: Cyberchondria is characterized by heightened health anxiety resulting from excessive online health information seeking, and studies on this topic in the field of hematology are limited. The aim of this study was to examine the levels of cyberchondria and health anxiety among [...] Read more.

Background: Cyberchondria is characterized by heightened health anxiety resulting from excessive online health information seeking, and studies on this topic in the field of hematology are limited. The aim of this study was to examine the levels of cyberchondria and health anxiety among patients attending the hematology outpatient clinic without a diagnosis of malignancy, and to evaluate the relationship between these two factors. Methods: This prospective cross-sectional study was conducted at the hematology outpatient clinic of Recep Tayyip Erdogan University School of Medicine in Rize, Turkey. The 400 patients included in the study were divided into groups according to their reasons for visiting the outpatient clinic: hemoglobin disorders, leukocyte disorders, and platelet disorders. The severity of cyberchondria was assessed using the Cyberchondria Severity Scale-12 (CSS-12), and health anxiety level was assessed using the Short Health Anxiety Inventory (SHAI). Results: The mean age of the 400 patients (255 female, 145 male) was 37.7 ± 11.2 years (18–60 years). The mean SHAI score for patients was 16.1 ± 6.6, and the mean CSS-12 score was 28.7 ± 7.4. Patients presenting with platelet disorders had the highest SHAI scores (18.4 ± 5.6), followed by patients presenting with leukocyte disorders (16.7 ± 6.4) and hemoglobin disorders (15.5 ± 6.8) (p = 0.009). In terms of CSS-12 scores, the highest values were found in patients presenting with leukocyte disorders (31.8 ± 8.5), followed by platelet disorders (30.1 ± 7.7) and hemoglobin disorders (27.6 ± 6.7) (p < 0.001). There was a positive relationship between health anxiety level and the severity of cyberchondria (r = 0.413, p < 0.001) Conclusions: The positive correlation observed between cyberchondria severity and health anxiety level underscores the need to consider psychological effects in hematology patients. This clinical condition may increase the burden of disease and should not be overlooked by physicians. Full article

(This article belongs to the Section Mental Health)

18 pages, 682 KB

Open AccessReview

Resilience in Family Members of ICU Patients: Scoping Review of the Literature

by Sandra Lange, Amelia Dąbrowska, Karolina Koszucka and Wioletta Mędrzycka-Dąbrowska

J. Clin. Med. 2025, 14(19), 6794; https://doi.org/10.3390/jcm14196794 (registering DOI) - 25 Sep 2025

Abstract

Introduction: Hospitalization of a patient in the intensive care unit (ICU) is one of the most stressful events, affecting not only the patient but also their close family members. This situation may lead to the development of anxiety and depressive symptoms, sleep disturbances, [...] Read more.

Introduction: Hospitalization of a patient in the intensive care unit (ICU) is one of the most stressful events, affecting not only the patient but also their close family members. This situation may lead to the development of anxiety and depressive symptoms, sleep disturbances, and, in some cases, even post-traumatic stress disorder (PTSD). In this context, increasing attention is being paid to the importance of psychological resilience—understood as an individual’s ability to effectively adapt to crisis situations and return to a state of relative emotional balance despite adversity. Methods: A scoping review method was used to map terms relevant to the resilience of family members of ICU patients. The aim of this study was to analyze current research on resilience among family members of patients in the intensive care unit (ICU), including measurement tools, facilitating factors, and psychological outcomes. Strict inclusion and exclusion criteria and the PCC framework were used to identify relevant studies. Results: The CD-RISC is the most used tool for assessing resilience in the families of ICU patients. Research suggests that resilience is associated with fewer symptoms of depression, anxiety, and acute stress. The studies indicate that spirituality, social/medical staff support, and involvement in care may be crucial factors for maintaining and increasing resilience. Some socio-demographic factors, such as gender, age, and previous mental disorders, may also influence the level of resilience. Conclusions: This scoping review highlights the need to implement measures aimed at strengthening the resilience of families of intensive care unit patients by promoting behaviors such as social/staff support and spirituality. Research suggests that levels of resilience may be associated with fewer psychological symptoms in family members of intensive care unit patients. Full article

(This article belongs to the Section Intensive Care)

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22 pages, 2104 KB

Open AccessArticle

Evaluation of Pulmonary Blood Flow, Right Atrium, Right Ventricle, and Pulmonary Artery in Patients After Pneumonectomy

by Michał Stępkowski, Małgorzata Edyta Wojtyś, Norbert Wójcik, Krzysztof Safranow, Jarosław Pieróg, Dawid Kordykiewicz, Jacek Szulc, Tadeusz Sulikowski, Konrad Jarosz, Tomasz Grodzki and Janusz Wójcik

J. Clin. Med. 2025, 14(19), 6793; https://doi.org/10.3390/jcm14196793 - 25 Sep 2025

Abstract

Background/Objectives: After pneumonectomy, the right ventricular stroke volume is pumped into pulmonary vessels whose volume has been reduced by approximately 50%. To sustain conditions for pulmonary flow, the flow reserve is increased in the remaining lung, which is conducive to the development [...] Read more.

Background/Objectives: After pneumonectomy, the right ventricular stroke volume is pumped into pulmonary vessels whose volume has been reduced by approximately 50%. To sustain conditions for pulmonary flow, the flow reserve is increased in the remaining lung, which is conducive to the development of pulmonary hypertension symptoms. This study sought to examine pulmonary flow in one lung and the size of the right atrium (RA), right ventricle (RV) and pulmonary artery (PA) in patients who had undergone pneumonectomy and to establish the influence of time since pneumonectomy on these parameters, as well as their potential mutual dependencies. Methods: The retrospective analysis included 34 patients who had undergone pneumonectomy. Pulmonary flow was measured by means of perfusion scintigraphy. The diameters of the RA, RV and PA were evaluated based on computed tomography with contrast. Results: We observed complete or near-complete utilization of flow reserve in 38.2% (13/34) of patients, enlarged transversal and longitudinal dimensions of the RA in 17.6% (6/34) and 32.3% (11/34) of patients, respectively, and enlarged transversal and longitudinal dimension of the RV in 67.6% (23/34) and 44.1% (15/34) of patients, respectively. Dilatation of the PA was discovered in 23.5% (8/34) to 26.5% (9/34) of patients, as well as the presence of an extensive complex of radiographic features of pulmonary hypertension (PH) syndrome in 23.5% (8/34) of cases. Conclusions: Radiological features of PH were present in a significant number of patients. These features developed at varying rates but were present in all patients followed >10 years after the procedure. Full article

(This article belongs to the Special Issue Thoracic Surgery: State of the Art and Future Directions)

13 pages, 1334 KB

Open AccessReview

Artificial Intelligence for Myocardial Infarction Detection via Electrocardiogram: A Scoping Review

by Sosana Bdir, Mennatallah Jaber, Osaid Tanbouz, Fathi Milhem, Iyas Sarhan, Mohammad Bdair, Thaer Alhroob, Walaa Abu Alya and Mohammad Qneibi

J. Clin. Med. 2025, 14(19), 6792; https://doi.org/10.3390/jcm14196792 - 25 Sep 2025

Abstract

Background/Objectives: Acute myocardial infarction (MI) is a major cause of death worldwide, and it imposes a heavy burden on health care systems. Although diagnostic methods have improved, detecting the disease early and accurately is still difficult. Recently, AI has demonstrated increasing capability [...] Read more.

Background/Objectives: Acute myocardial infarction (MI) is a major cause of death worldwide, and it imposes a heavy burden on health care systems. Although diagnostic methods have improved, detecting the disease early and accurately is still difficult. Recently, AI has demonstrated increasing capability in improving ECG-based MI detection. From this perspective, this scoping review aimed to systematically map and evaluate AI applications for detecting MI through ECG data. Methods: A systematic search was performed in Ovid MEDLINE, Ovid Embase, Web of Science Core Collection, and Cochrane Central. The search covered publications from 2015 to 9 October 2024; non-English articles were included if a reliable translation was available. Studies that used AI to diagnose MI via ECG were eligible, and studies that used other diagnostic modalities were excluded. The review was performed per the PRISMA extension for scoping reviews (PRISMA-ScR) to ensure transparent and methodological reporting. Of a total of 7189 articles, 220 were selected for inclusion. Data extraction included parameters such as first author, year, country, AI model type, algorithm, ECG data type, accuracy, and AUC to ensure all relevant information was captured. Results: Publications began in 2015 with a peak in 2022. Most studies used 12-lead ECGs; the Physikalisch-Technische Bundesanstalt database and other public and single-center datasets were the most common sources. Convolutional neural networks and support vector machines predominated. While many reports described high apparent performance, these estimates frequently came from relatively small, single-source datasets and validation strategies prone to optimism. Cross-validation was reported in 57% of studies, whereas 36% did not specify their split method, and several noted that accuracy declined under inter-patient or external validation, indicating limited generalizability. Accordingly, headline figures (sometimes ≥99% for accuracy, sensitivity, or specificity) should be interpreted in light of dataset size, case mix, and validation design, with risks of spectrum/selection bias, overfitting, and potential data leakage when patient-level independence is not enforced. Conclusions: AI-based approaches for MI detection using ECGs have grown quickly. Diagnostic performance is limited by dataset and validation issues. Variability in reporting, datasets, and validation strategies have been noted, and standardization is needed. Future work should address clinical integration, explainability, and algorithmic fairness for safe and equitable deployment. Full article

(This article belongs to the Section Cardiology)

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9 pages, 660 KB

Open AccessArticle

The Effect of a Third In-Ear Microphone on User Satisfaction, Speech Intelligibility, and the Real-Ear Gain of Hearing Aids at a Conversational Level in Patients with Moderate Hearing Loss

by Sang Hyun Kwak, Dongchul Cheon, Seong Hoon Bae, Daeyoung Kim and Jinsei Jung

J. Clin. Med. 2025, 14(19), 6791; https://doi.org/10.3390/jcm14196791 - 25 Sep 2025

Abstract

Background: The microphone & receiver-in-ear (M&RIE) integrates two traditional hearing aid microphones, while an additional in-ear microphone helps preserve natural sound perception. However, the impact of this third microphone on hearing aid amplification remains unclear in patients with moderate hearing loss. Methods: In [...] Read more.

Background: The microphone & receiver-in-ear (M&RIE) integrates two traditional hearing aid microphones, while an additional in-ear microphone helps preserve natural sound perception. However, the impact of this third microphone on hearing aid amplification remains unclear in patients with moderate hearing loss. Methods: In this prospective crossover study, thirty-nine participants with moderate hearing loss and no prior hearing-aid use were randomly assigned to be sequentially fitted with both traditional and M&RIE receivers. The abbreviated profile of hearing aid benefit (APHAB) and word recognition score (WRS) were assessed. Audiological amplification was evaluated using real-ear measurements to determine whether a third in-ear microphone limits real-ear gain. Results: WRSs and APHAB scores showed no significant differences between the standard and M&RIE receivers. In addition, real-ear measurements across all frequencies and earplug types revealed no significant differences in real-ear insertion gain between the two receivers at a conversational level (65 dB SPL). Conclusions: The M&RIE provides amplification comparable to that of the standard receiver while preserving natural sound cues without significant audiological disadvantages. Full article

(This article belongs to the Section Otolaryngology)

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11 pages, 898 KB

Open AccessArticle

Comparison of Aerosol Generation Between Bag Valve and Chest Compression-Synchronized Ventilation During Simulated Cardiopulmonary Resuscitation

by Young Taeck Oh, Choung Ah Lee, Daun Choi and Hang A. Park

J. Clin. Med. 2025, 14(19), 6790; https://doi.org/10.3390/jcm14196790 - 25 Sep 2025

Abstract

Background: Cardiopulmonary resuscitation can generate aerosols, potentially exposing healthcare workers (HCWs) to infection. Bag valve ventilation (BV) is widely used but is prone to aerosol dispersion, whereas chest compression-synchronized ventilation (CCSV) maintains a closed respiratory circuit. In this study, we compared aerosol [...] Read more.

Background: Cardiopulmonary resuscitation can generate aerosols, potentially exposing healthcare workers (HCWs) to infection. Bag valve ventilation (BV) is widely used but is prone to aerosol dispersion, whereas chest compression-synchronized ventilation (CCSV) maintains a closed respiratory circuit. In this study, we compared aerosol generation between CCSV and BV during chest compressions following endotracheal intubation in a simulated resuscitation setting. Methods: In a randomized crossover design, 12 sessions each of CCSV and BV were conducted on an intubated manikin undergoing mechanical chest compressions for 10 min. Aerosols with ≤5-μm diameter were generated using a saline nebulizer and measured every minute with a particle counter positioned 50 cm from the chest compression site. Bayesian linear regression of minute-by-minute log-transformed aerosol particle counts was used to estimate group differences, yielding posterior means, 95% credible intervals, and posterior probabilities. Results: The aerosol particle counts increased during the initial 3 min with the use of both methods. Thereafter, the aerosol particle counts with CCSV stabilized, whereas those with BV continued to increase. From 4 to 10 min, the posterior probability that CCSV generated fewer particles exceeded 0.98, peaking at 9 min. Both peak and time-averaged log-transformed aerosol particle counts were significantly lower with CCSV than with BV (p = 0.010 and p = 0.020, respectively). Conclusions: In this simulation, CCSV generated significantly fewer aerosols than BV did during chest compressions, with differences emerging after 4 min and persisting thereafter. Thus, CCSV may reduce aerosol exposure of HCWs, supporting its early implementation during resuscitation in infectious disease settings. Full article

(This article belongs to the Special Issue Cardiopulmonary Resuscitation—from Research to Clinical Implementation)

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14 pages, 774 KB

Open AccessArticle

Evaluation of Alpha1 Antitrypsin Deficiency-Associated Mutations in People with Cystic Fibrosis

by Jose Luis Lopez-Campos, Pedro García Tamayo, Maria Victoria Girón, Isabel Delgado-Pecellín, Gabriel Olveira, Laura Carrasco, Rocío Reinoso-Arija, Casilda Olveira and Esther Quintana-Gallego

J. Clin. Med. 2025, 14(19), 6789; https://doi.org/10.3390/jcm14196789 - 25 Sep 2025

Abstract

Background: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their impact on [...] Read more.

Background: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their impact on CF. Methods: The study Finding AAT Deficiency in Obstructive Lung Diseases: Cystic Fibrosis (FADO-CF) is a retrospective cohort study evaluating people with CF from November 2020 to February 2024. On the date of inclusion, serum levels of AAT were measured and a genotyping of 14 mutations associated with AATD was performed. Historical information, including data on exacerbations, microbiological sputum isolations, and lung function, was obtained from the medical records, aiming at a temporal lag of 10 years. Results: The sample consisted of 369 people with CF (40.9% pediatrics). Of these, 58 (15.7%) cases presented at least one AATD mutation. The AATD allelic combinations identified were PI*MS in 47 (12.7%) cases, PI*MZ in 5 (1.4%) cases, PI*SS in 3 (0.8%) cases, PI*SZ in 2 (0.5%) cases, and PI*M/P_lowell in 1 (0.3%) case. The optimal cutoff value for AAT levels to detect AATD-associated mutation carriers was 129 mg/dL in the overall cohort (sensitivity of 73.0%; specificity 69.2%) and 99.5 mg/dL when excluding PI*MS cases (sensitivity 98.0%; specificity 90.9%), highlighting the need for lower thresholds in clinically severe genotypes to improve case detection. The number of mild exacerbations during the follow-up appeared to be associated with AATD mutations. Conclusions: AATD mutations are prevalent in CF and may impact certain clinical outcomes. If systematic screening was to be planned, we recommend considering the proposed cut-off points to select the population for genetic studies. Full article

(This article belongs to the Special Issue Cystic Fibrosis: Clinical Manifestations and Treatment)

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15 pages, 4216 KB

Open AccessSystematic Review

Comparative Outcomes of 1-Level vs. 2-Level Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-Analysis

by Joseph E. Nassar, Ashley Knebel, Manjot Singh, Michael J. Farias, Nicolas L. Carayannopoulos, Zvipo M. Chisango, Negin Fani, Mohammad Daher, Eren O. Kuris, Bassel G. Diebo and Alan H. Daniels

J. Clin. Med. 2025, 14(19), 6788; https://doi.org/10.3390/jcm14196788 - 25 Sep 2025

Abstract

Background/Objectives: Cervical spine disease requiring surgical intervention is a major cause of disability. Anterior cervical discectomy and fusion (ACDF) is a well-established procedure for treating cervical pathology; however, there remains no consensus on whether 1-level versus 2-level ACDF yields comparable outcomes. This [...] Read more.

Background/Objectives: Cervical spine disease requiring surgical intervention is a major cause of disability. Anterior cervical discectomy and fusion (ACDF) is a well-established procedure for treating cervical pathology; however, there remains no consensus on whether 1-level versus 2-level ACDF yields comparable outcomes. This study compares 1-level versus 2-level ACDF by evaluating surgery-related and postoperative outcomes, radiographic parameters, and patient-reported outcome measures (PROMs). Methods: PubMed, Embase, Scopus, and Cochrane Library were searched through 10 July 2024. Studies comparing 1-level with 2-level ACDF were included. Data on operating room (OR) time, estimated blood loss (EBL), length of hospital stay (LOS), complications, and PROMs, including Neck Disability Index (NDI) and Visual Analogue Scale (VAS) for neck and arm pain, were extracted. Results: Thirteen studies met our inclusion criteria, comprising 2091 patients (1078 undergoing 1-level and 1013 2-level ACDF). No statistically significant differences were observed in EBL or LOS between the cohorts. However, the 2-level ACDF group showed significantly longer OR times (p-value < 0.001) and higher odds of developing dysphagia (p-value = 0.05). Patients undergoing 2-level ACDF showed greater correction in cervical lordosis. Both cohorts reported similar statistically and clinically significant improvements in VAS neck and NDI scores at final follow-up. There was no difference in adjacent segment disease or revision surgery at final follow-up. Conclusions: Both 1-level and 2-level ACDF improve clinical and radiographic outcomes. The choice should be tailored to the patient’s pathology and anatomy while considering the higher dysphagia risk with additional fusion levels. This study highlights the importance of individualized surgical planning to optimize postoperative outcomes while minimizing complications. Full article

(This article belongs to the Section Orthopedics)

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14 pages, 547 KB

Open AccessArticle

Trajectory of Iron and Red Cell Parameters in Moderately Anemic Iron-Deficient Pregnant Women Receiving Daily Iron–Folic Acid Supplementation: A Prospective Cohort Study

by J. P. Akshaykirthan, Manjunath S. Somannavar, S. Yogeshkumar, M. S. Deepthy, Umesh Charantimath, Amaresh Patil, Mrutyunjaya B. Bellad, Richard Derman and Shivaprasad S. Goudar

J. Clin. Med. 2025, 14(19), 6787; https://doi.org/10.3390/jcm14196787 - 25 Sep 2025

Abstract

Background/Objectives: The objective is to study the trajectories of hematologic and biochemical markers in moderately anemic pregnant women receiving oral iron supplementation throughout pregnancy. Methods: This prospective cohort study was conducted from August 2021 to September 2023 involving 315 pregnant women from [...] Read more.

Background/Objectives: The objective is to study the trajectories of hematologic and biochemical markers in moderately anemic pregnant women receiving oral iron supplementation throughout pregnancy. Methods: This prospective cohort study was conducted from August 2021 to September 2023 involving 315 pregnant women from rural areas of Belgaum, Karnataka, India, with hemoglobin levels between 7.0 and 9.9 g/dL and serum ferritin < 30 ng/mL and/or TSAT < 20%. Participants received iron–folic acid supplementation (IFAS) as per Anaemia Mukt Bharat guidelines. Blood samples were collected to measure various hematologic and iron markers and compared across each visits. Results: We report a complete adherence rate of 95.3% for iron and 97.8% for folic acid supplementation throughout pregnancy and also observed significant improvements in hemoglobin (9.36 (8.55, 9.74) to 12.03 (11.49, 12.72)) g/dL, hematocrit (29.93 ± 2.87 to 33.71 ± 3.69) %, MCV (72.16 ± 7.90 to 83.47 ± 7.65) fL, MCH (22.44 ± 3.01 to 26.77 ± 3.08) pg levels from the early second to the early third trimester of pregnancy with significant difference (<0.001). Increased erythropoiesis was reported by a higher reticulocyte hemoglobin (23.30 ± 3.03 to 27.84 ± 3.83) pg and immature reticulocyte fractions (6.90 (4.30, 9.50) to 7.30 (4.3, 11.0)) %. Initially, iron, ferritin and TSAT levels increased but later stabilized or slightly declined towards the end of pregnancy. Conclusions: Daily IFAS in moderately anemic pregnant women improved the trajectory of iron parameters, with peak gains in early third trimester. High adherence via counselling supports targeted monitoring and trimester-specific strategies to reduce maternal anemia and may improve outcomes. Full article

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

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12 pages, 669 KB

Open AccessStudy Protocol

Balancing Rehabilitation Dose in Acute Stroke Decision-Making and Global Assessment (The BRIDGE Study)

by Shinichi Watanabe, Wataru Yamauchi, Katsuma Shoka, Asahi Kawashima, Shogo Sawamura, Kousuke Kanamori, Tetsuya Furukawa, Yuji Naito, Naoki Takeshita, Keita Utiyama, Rtota Imai, Kanari Kiritani, Naoyuki Hashimoto, Hideaki Tanaka, Yushi Mitani, Takayuki Kitano, Daisuke Hori, Tatsuya Hayashi, Kenji Tsujimoto and Yasunari Morita

J. Clin. Med. 2025, 14(19), 6786; https://doi.org/10.3390/jcm14196786 - 25 Sep 2025

Abstract

Background/Objectives: Stroke remains a leading cause of disability in Japan, and early mobilization is an important strategy to prevent muscle atrophy and promote independence. However, the optimal intensity and duration of early rehabilitation remain unclear. This study aims to examine the association between [...] Read more.

Background/Objectives: Stroke remains a leading cause of disability in Japan, and early mobilization is an important strategy to prevent muscle atrophy and promote independence. However, the optimal intensity and duration of early rehabilitation remain unclear. This study aims to examine the association between rehabilitation dose during the acute phase of stroke and functional outcomes at 90 days post-onset. Methods: This multicenter prospective cohort study will enroll patients from twelve acute care hospitals across Japan, beginning in June 2026. Eligible patients are aged ≥ 18 years, expected to be hospitalized for ≥7 days, and initiated rehabilitation by day 2 after stroke onset. Rehabilitation dose will be quantified using the Mobilization Quantification Score (MQS). The primary outcome is functional status measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes include muscle atrophy assessed by ultrasound, the Barthel Index, and physical performance measures. Subgroup analyses will evaluate how stroke severity modifies the dose–response relationship. Results: As this is a study protocol, results are not yet available. The study is designed to clarify the relationship between early rehabilitation dose and functional recovery after stroke. Conclusions: This is the first large-scale Japanese study to assess early stroke rehabilitation dosage using a standardized tool. Findings are expected to provide evidence for individualized, evidence-based mobilization strategies to optimize functional outcomes in stroke patients. Full article

(This article belongs to the Special Issue Advancements in Gait Rehabilitation: Innovative Approaches and Clinical Insights)

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11 pages, 499 KB

Open AccessArticle

High Salivary 3-Nitrotyrosine Levels in Periodontitis

by Leonardo Lorente, Esther Hernández Marrero, Pedro Abreu González, Angel Daniel Lorente Martín, Agustín F. González-Rivero, María José Marrero González, Carmen Hernández Marrero, Olga Hernández Marrero, Alejandro Jiménez and Cándido Manuel Hernández Padilla

J. Clin. Med. 2025, 14(19), 6785; https://doi.org/10.3390/jcm14196785 - 25 Sep 2025

Abstract

Background: Tyrosine, a non-essential amino acid involved in protein biosynthesis, can undergo oxidative modification upon exposure to reactive species like the peroxynitrite radical (ONOO⁻), resulting in the formation of 3-nitrotyrosine (3-NT). High concentrations of 3-NT have been found in the periodontal [...] Read more.

Background: Tyrosine, a non-essential amino acid involved in protein biosynthesis, can undergo oxidative modification upon exposure to reactive species like the peroxynitrite radical (ONOO⁻), resulting in the formation of 3-nitrotyrosine (3-NT). High concentrations of 3-NT have been found in the periodontal tissues of rats with periodontitis and in one study involving twelve patients with periodontitis; further, a correlation between 3-NT concentrations in periodontal tissues and clinical indices of periodontitis was found in 24 patients with periodontitis. The objectives of our study were to compare salivary 3-NT concentrations in subjects with and without periodontitis, to determine whether an association exists between salivary 3-NT concentrations and periodontitis, and to evaluate the potential of salivary 3-NT concentrations for the diagnosis of periodontitis. Material and Methods: This prospective study involved the measurement of salivary 3-NT concentrations in individuals diagnosed with periodontitis—defined by the presence of periodontal tissue loss—and in individuals without periodontitis, characterized by either periodontal health or localized gingivitis affecting fewer than 30% of sites. A total of 66 participants without periodontitis and 60 with periodontitis were included. To identify variables independently linked to periodontitis, multivariate logistic regression was applied. Additionally, a receiver operating characteristic (ROC) analysis was carried out to assess the ability of salivary 3-NT levels to discriminate between the two groups. Results: Multivariate logistic regression analysis showed that the variables independently associated with periodontitis were salivary 3-NT concentrations > 4.25 ng/mL (OR = 3.22; 95% CI = 1.180–8.789; p value = 0.02), age (years) (OR = 1.12; 95% CI = 1.064–1.168; p value < 0.001), and being a never smoker (OR = 0.36; 95% CI = 0.129–0.989; p value = 0.048). The area under the curve (AUC) of salivary 3-NT concentrations for the diagnosis of periodontitis was 62% (95% CI = 53–70%; p value = 0.02). Conclusions: Our findings showed that salivary 3-NT concentrations were higher in subjects with periodontitis than in those without, that there is an association between high salivary 3-NT concentrations and periodontitis, and that salivary 3-NT concentrations may be useful for diagnosing periodontitis. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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14 pages, 664 KB

Open AccessArticle

Non-Thyroidal Illness Syndrome and Thyroid Autoimmunity in Hospitalized COVID-19 Patients: A Retrospective Study

by Ewa Kozłowska, Milena Małecka-Giełdowska and Olga Ciepiela

J. Clin. Med. 2025, 14(19), 6784; https://doi.org/10.3390/jcm14196784 - 25 Sep 2025

Abstract

Background: Thyroid dysfunction, including non-thyroidal illness syndrome (NTIS), is commonly observed in critically ill patients and has been reported in COVID-19, particularly in those with severe disease. NTIS is defined by low free triiodothyronine (fT3) with normal or low thyroid-stimulating hormone (TSH) [...] Read more.

Background: Thyroid dysfunction, including non-thyroidal illness syndrome (NTIS), is commonly observed in critically ill patients and has been reported in COVID-19, particularly in those with severe disease. NTIS is defined by low free triiodothyronine (fT3) with normal or low thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels. Thyroid autoantibodies may also reflect immune system activation. The relationship between thyroid hormone alterations, autoimmunity, and clinical severity in COVID-19 remains incompletely understood. Methods: We conducted a retrospective study of 276 patients hospitalized with COVID-19, including 138 in the intensive care unit (ICU) and 138 in general wards. A control group of 110 hospitalized, non-infected patients was also analyzed. Serum concentrations of TSH, fT3, fT4 and reverse T3 (rT3) were measured. The presence of anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-Tg), and thyrotropin receptor antibodies (TRAb) was assessed. Results: NTIS was observed in 44.2% of ICU patients, 18.1% of non-ICU patients, and 1.8% of controls. The fT3/rT3 ratio was lowest in ICU patients (median 0.11 vs. 0.16 in non-ICU and 0.22 in controls). Thyroid autoantibodies were significantly more prevalent in COVID-19 patients than in controls, with anti-TPO antibodies being the most frequently detected. Their presence, even in patients without known thyroid disease, may reflect immune activation associated with SARS-CoV-2 infection. Conclusions: NTIS and thyroid autoimmunity are frequent in hospitalized COVID-19 patients and may reflect disease severity and immune activation. Our study highlights the prognostic relevance of routine thyroid testing, including the fT3/rT3 ratio and combined autoantibody positivity (notably the triple-positive pattern), by directly comparing ICU and non-ICU patients with a non-COVID control group. Full article

(This article belongs to the Special Issue COVID-19 and Endocrine Complications)

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9 pages, 207 KB

Open AccessArticle

Utility of the Shock Index as a Prognostic Predictor in Patients Undergoing Emergency Surgery for Trauma: A Single Center, Retrospective Study

by Byungchul Yu, Chun Gon Park, Kunhee Lee and Youn Yi Jo

J. Clin. Med. 2025, 14(19), 6783; https://doi.org/10.3390/jcm14196783 - 25 Sep 2025

Abstract

Background: Shock index (SI) is calculated by dividing heart rate (HR) by systolic blood pressure (sBP) and is a useful tool for predicting the prognosis of trauma patients. This study aimed to determine whether SI is useful in predicting mortality in patients undergoing [...] Read more.

Background: Shock index (SI) is calculated by dividing heart rate (HR) by systolic blood pressure (sBP) and is a useful tool for predicting the prognosis of trauma patients. This study aimed to determine whether SI is useful in predicting mortality in patients undergoing emergency surgery for trauma. Methods: We analyzed 1657 patients who underwent emergency surgery for trauma. Patients were divided into SI < 1 and SI ≥ 1 groups and the Glasgow Coma Scale (GCS), Injury Severity Score (ISS), revised trauma score (RTS), Korean Triage and Acuity Scale (KTAS), transfusion amount, and mortality were compared. Binary logistic regression analysis was performed to identify factors associated with mortality. Results: There were significant differences in GCS, ISS, RTS, and KTAS in the SI ≥ 1 group compared to the SI < 1 group (all p-values < 0.001). In the SI < 1 cohort, the mortality rate was 11% (144/1283), and in the SI ≥ 1 group the mortality rate was 33% (125/374) (p < 0.001). Age, GCS, ISS, SI ≥ 1, and KTAS were determined to be predictors of mortality by logistic regression analysis. In particular, SI ≥ 1 group members exhibited a high association with elevated mortality (OR, 2.498; 95% CI, 1.708–3.652; p < 0.01). Conclusions: Although SI alone has limitations in predicting the patient’s prognosis, patients with SI ≥ 1 upon arrival at the emergency room are associated with mortality of patients undergoing emergency surgery for trauma, along with already known trauma assessment systems such as GCS, ISS, and KTAS. Full article

(This article belongs to the Special Issue Acute Care for Traumatic Injuries and Surgical Outcomes: 2nd Edition)

14 pages, 398 KB

Open AccessArticle

Fetuin-A Concentration in the Perinatal Period and Maternal BMI Dynamics During Pregnancy, Labor, and Early Postpartum: Is ΔBMI a Parameter Worth Considering?

by Aleksandra Obuchowska-Standyło, Żaneta Kimber-Trojnar, Monika Czuba, Katarzyna Trojnar and Bożena Leszczyńska-Gorzelak

J. Clin. Med. 2025, 14(19), 6782; https://doi.org/10.3390/jcm14196782 - 25 Sep 2025

Abstract

Background/Objectives: Fetuin-A is a multifunctional glycoprotein involved in metabolic and inflammatory regulation. Although its role in insulin resistance, type 2 diabetes, and cardiovascular disease is well recognized, its relationship with pregnancy-related body mass changes remains unclear. This study aimed to explore associations [...] Read more.

Background/Objectives: Fetuin-A is a multifunctional glycoprotein involved in metabolic and inflammatory regulation. Although its role in insulin resistance, type 2 diabetes, and cardiovascular disease is well recognized, its relationship with pregnancy-related body mass changes remains unclear. This study aimed to explore associations between maternal BMI dynamics during and shortly after pregnancy and serum fetuin-A concentrations. Methods: Fifty-five healthy Caucasian women with term singleton pregnancies were enrolled. BMI was recorded at three time points: pre-pregnancy, before delivery, and 48 h postpartum. Based on ΔBMI (postpartum minus pre-pregnancy BMI), participants were divided into two groups: ΔBMI ≤ 1 kg/m² (n = 32) and ΔBMI > 1 kg/m² (n = 23). Serum fetuin-A levels were measured before delivery and postpartum using ELISA. Additional laboratory parameters and body composition were assessed postpartum via standard tests and bioelectrical impedance analysis (BIA). Results: No significant differences were found between groups in BMI at any single time point or in laboratory or BIA-derived parameters. However, all three BMI change indices (ΔBMI_gestational, ΔBMI_puerperal, and ΔBMI) differed significantly between groups. Fetuin-A concentrations did not differ significantly between groups. Importantly, fetuin-A levels decreased significantly after delivery in both groups, suggesting a potential role of the placenta in its regulation. A significant correlation was observed between pre-delivery fetuin-A and postpartum uric acid in Group ΔBMI > 1 kg/m² (p = 0.016), indicating a possible link in women with greater gestational weight gain. Conclusions: While fetuin-A was not directly associated with BMI changes, its peripartum dynamics and correlation with uric acid may reflect underlying metabolic-inflammation pathways. ΔBMI indices may offer a more individualized measure of weight dynamics in pregnancy research. Full article

(This article belongs to the Special Issue Pregnancy Complications and Maternal-Perinatal Outcomes)

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10 pages, 515 KB

Open AccessArticle

Metastatic Potential of Very Small (≤2 cm) Renal Cell Carcinoma: Insights from a Single-Center Experience and Review of the Literature

by Lorenzo Giuseppe Luciani, Tommaso Ceccato, Tommaso Cai, Stefano Chiodini, Simone Botti, Valentino Vattovani, Marco Puglisi, Andrea Abramo and Daniele Mattevi

J. Clin. Med. 2025, 14(19), 6781; https://doi.org/10.3390/jcm14196781 - 25 Sep 2025

Abstract

Background/Objectives: Small renal masses (SRMs) are being detected more often due to the increasing use of imaging techniques. Many of these lesions are benign or grow slowly, but a small proportion can exhibit aggressive behavior. Several reports have shown that synchronous metastases may [...] Read more.

Background/Objectives: Small renal masses (SRMs) are being detected more often due to the increasing use of imaging techniques. Many of these lesions are benign or grow slowly, but a small proportion can exhibit aggressive behavior. Several reports have shown that synchronous metastases may occur even in small renal cell carcinomas (RCCs). Our aim is to assess the malignant potential and the metastatic risk of very small RCCs (≤2 cm). Methods: We reviewed consecutive patients who underwent partial nephrectomy for SRMs at our tertiary referral center between 2005 and 2024, focusing on those with a maximum pathologic diameter ≤ 2 cm. Clinical and pathological data were collected, and cases with aggressive features were described. In addition, a literature search on the Medline/PubMed database was performed to identify previously published cases of RCC ≤ 2 cm and to assess their risk of synchronous metastases (SM). Results: Among 578 patients who underwent partial nephrectomy, 116 patients (20%) had tumors ≤ 2 cm, 90 (77.5%) of which were malignant, whereas 22.5% were benign (oncocytoma = 13%; angiomyolipoma = 5%). Median age and tumor size were 51 yrs and 1.7 cm, respectively. Histology showed clear cell (72.2%), papillary (20%), chromophobe (6.6%), and mixed (0.9%). Two patients (2.2%) experienced aggressive disease: one with synchronous metastases and one with recurrence and later progression. From the literature, we identified 16 additional cases of RCC ≤ 2 cm with synchronous metastases and found an important heterogeneity of results regarding the metastatic potential of SRMs. Conclusions: Although uncommon, synchronous metastases can occur in RCCs even smaller than 1–2 cm. Reported rates for SM of SRMs across the literature range between 1% and 13%, with higher risk observed in tumors larger than 3 cm, but without an absolute safe cutoff. Tumor size alone is therefore insufficient to exclude aggressive potential. Clinical decision-making should consider histology, grade, patient age, radiologic features, and emerging molecular markers to guide surveillance and treatment in this growing patient population. Full article

(This article belongs to the Special Issue Clinical Advancements in Urologic Surgery)

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15 pages, 1002 KB

Open AccessArticle

The Platelet-to-Hemoglobin Ratio as a Prognostic Marker in Patients with Diabetes Mellitus and Acute Coronary Syndrome

by Christos Kofos, Panagiotis Stachteas, Barbara Fyntanidou, Andreas S. Papazoglou, Athanasios Samaras, Athina Nasoufidou, Aikaterini Apostolopoulou, Paschalis Karakasis, Alexandra Arvanitaki, Marios G. Bantidos, Dimitrios V. Moysidis, Nikolaos Stalikas, Dimitrios Patoulias, Marios Sagris, Apostolos Tzikas, George Kassimis, Nikolaos Fragakis and Efstratios Karagiannidis

J. Clin. Med. 2025, 14(19), 6780; https://doi.org/10.3390/jcm14196780 - 25 Sep 2025

Abstract

Background: The platelet-to-hemoglobin ratio (PHR) has emerged as a potential prognostic marker in various cardiovascular contexts, but its role in acute coronary syndrome (ACS), particularly among patients with diabetes mellitus (DM), remains unclear. Methods: In this retrospective cohort study, 843 ACS patients admitted [...] Read more.

Background: The platelet-to-hemoglobin ratio (PHR) has emerged as a potential prognostic marker in various cardiovascular contexts, but its role in acute coronary syndrome (ACS), particularly among patients with diabetes mellitus (DM), remains unclear. Methods: In this retrospective cohort study, 843 ACS patients admitted to the 2nd Cardiology Department at Hippokration Hospital of Thessaloniki, Greece, between 2017 and 2023 were evaluated. PHR was calculated from admission complete blood counts. The primary endpoint was all-cause mortality during a median follow-up of 25 months. Multivariate logistic and Cox regression analyses, receiver operating characteristic (ROC) curves, Kaplan–Meier survival analyses, and restricted cubic spline (RCS) models were employed, with subgroup analyses by DM status. Results: Higher PHR was independently associated with increased mortality in the overall cohort (adjusted hazard ratio [aHR] 1.35, p < 0.001). This association showed stronger predictive value in DM patients, reflected in both a higher aHR (1.52 vs. 1.36 in non-DM patients, p < 0.001 and p = 0.018, respectively) and superior discriminative performance on ROC analysis (AUC 0.707 vs. 0.600 overall, p = 0.0006). Kaplan–Meier analysis confirmed poorer survival in high-PHR groups, especially in DM patients. RCS analysis revealed a J-shaped relationship, with risk increasing markedly beyond PHR values of 2.2. Conclusions: PHR is an independent predictor of long-term mortality in ACS, with greater prognostic significance in DM patients. Its simplicity, low cost, and availability from routine blood tests make it a promising tool for risk stratification in ACS. Full article

(This article belongs to the Special Issue Advances in Diagnosis, Risk Stratification, and Personalized Management in Acute Coronary Syndromes)

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17 pages, 271 KB

Open AccessReview

Isolated Polyethylene Exchange in Revision Total Knee Arthroplasty: A Review of Indications and Outcomes

by Alex M. Moses, Michaela E. Cushing, Mason A. Fawcett, Nicolas Dohse, Obinna O. Adigweme and Cameron K. Ledford

J. Clin. Med. 2025, 14(19), 6779; https://doi.org/10.3390/jcm14196779 - 25 Sep 2025

Abstract

Introduction: The use of modular components provides several advantages in total knee arthroplasty (TKA), including exchange of the polyethylene insert while retaining the stable components in the revision TKA. Compared to full, non-modular component revision TKA, isolated polyethylene exchange (IPE) has the advantage [...] Read more.

Introduction: The use of modular components provides several advantages in total knee arthroplasty (TKA), including exchange of the polyethylene insert while retaining the stable components in the revision TKA. Compared to full, non-modular component revision TKA, isolated polyethylene exchange (IPE) has the advantage of decreased morbidity, faster rehabilitation, and acceptable outcomes. Methods: A review of published literature on revision TKA was conducted, with a specific focus on studies evaluating the use of IPE for managing complications such as stiffness, instability, and periprosthetic joint infection (PJI). Results: IPE with downsizing may be considered for patients with mild stiffness and stable, well-positioned implants that have increased polyethylene thickness, though expectations for motion gain should be cautious. There is no clear consensus on IPE for instability. Some studies report high re-revision rates, while others show clinical and functional improvement when the TKA is well-aligned, well-fixed, and intraoperative gap balance is achieved. Additionally, irrigation and debridement with polyethylene exchange (IDPE) may be effective for acute TKA PJI management, particularly within the first two weeks of symptom onset. Conclusions: Based on current literature, IPE in aseptic TKA revisions may be effective for stiffness or instability when implants are well-fixed and well-aligned—particularly if polyethylene constraint can be adjusted for instability or downsized for stiffness. The role of IDPE in acute TKA PJI is better defined in the literature, with strong emphasis on its time-sensitive effectiveness—most notably within the first two weeks of symptom onset. Full article

(This article belongs to the Section Orthopedics)

11 pages, 614 KB

Open AccessArticle

Factors Influencing the Healing of Maxillary Sinusitis of Endodontic Origin After Non-Surgical Endodontic Treatment

by Paweł Szczurowski, Krzysztof Gronkiewicz and Barbara Czopik

J. Clin. Med. 2025, 14(19), 6778; https://doi.org/10.3390/jcm14196778 - 25 Sep 2025

Abstract

Background/Objectives: The purpose of this study was to indicate factors influencing the healing of maxillary sinusitis of endodontic origin (MSEO) after non-surgical endodontic treatment. Methods: The study was performed retrospectively on medical records and CBCT data of 114 teeth in 114 [...] Read more.

Background/Objectives: The purpose of this study was to indicate factors influencing the healing of maxillary sinusitis of endodontic origin (MSEO) after non-surgical endodontic treatment. Methods: The study was performed retrospectively on medical records and CBCT data of 114 teeth in 114 patients, who were referred to endodontic treatment between 2016 and 2024, performed by the same operator and according to the same treatment protocol. Fifteen factors were chosen for their possible influence on the healing of MSEO. Results: The rate of the complete healing of MSEO after RCT was 76.32%. The healing of MSEO was higher when CHX was applied in the final irrigation protocol (p = 0.022) and was less likely when there was a flare-up in-between visits or after obturation of the canals (p = 0.002). MSEO was more likely to heal when a tooth was treated in two appointments than with single-visit RCT (p = 0.012). The number of endodontic interventions significantly influenced the healing of MSEO, as it was less likely to heal when there was more than one endodontic retreatment for a tooth (p = 0.01). Conclusions: Within the limitations of this retrospective study, four factors significantly influenced the healing of MSEO, and these should be taken into consideration in obtaining treatment protocols for dental-induced sinusitis and the better assessment of the possible success of this non-invasive treatment approach. Full article

(This article belongs to the Special Issue Endodontic and Periodontal Medicine: Systemic Implications of Oral Infections)

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12 pages, 3099 KB

Open AccessArticle

Evaluation of [¹¹C]-Methionine Positron Emission Tomography and Cerebral Blood Volume Imaging in the Diagnosis of Non-Contrast-Enhanced Gliomas

by Naoya Imai, Hirohito Yano, Yuka Ikegame, Shoji Yasuda, Ryo Morishima, Soko Ikuta, Noriyuki Nakayama, Takashi Maruyama, Naoyuki Ohe, Morio Kumagai, Yoshihiro Muragaki, Jun Shinoda and Tsuyoshi Izumo

J. Clin. Med. 2025, 14(19), 6777; https://doi.org/10.3390/jcm14196777 - 25 Sep 2025

Abstract

Background/Objectives: Methionine (MET) positron emission tomography (PET) and cerebral blood volume (CBV) imaging provide complementary glioma assessment. This study compared MET and CBV across glioma subtypes defined by the 2021 World Health Organization Classification. Methods: This retrospective study enrolled 106 patients [...] Read more.

Background/Objectives: Methionine (MET) positron emission tomography (PET) and cerebral blood volume (CBV) imaging provide complementary glioma assessment. This study compared MET and CBV across glioma subtypes defined by the 2021 World Health Organization Classification. Methods: This retrospective study enrolled 106 patients (mean age 41.9 ± 12.4 years; 57 males) with MRI non-contrast-enhanced gliomas: 21 glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (G); 50 astrocytoma, IDH-mutant (A); and 35 oligodendrogliomas, IDH-mutant, and 1p/19q-codeleted (O). Relative CBVs (rCBVs) were measured in VOI-T2 and VOI-MET, and the MET tumor-to-normal (T/N) ratio was calculated. Results: MET and rCBV were significantly correlated (r = 0.5, p < 0.001); rCBV was higher in MET-positive tumors and predicted MET accumulation (area under the curve [AUC] = 0.72, cutoff = 2.99). In VOI-T2, rCBV and MET T/N ratio were the highest in G and lowest in A (p < 0.001). Receiver operating characteristic analyses showed no overall significant difference between MET and rCBV for differentiating G/A/O, but rCBV trended toward higher AUC values in key distinctions, such as G (0.736 vs. 0.612) or grade 4 (0.718 vs. 0.617). The increase in rCBV within the MET-positive region (VOI-MET/VOI-T2 rCBV ratio) was significantly higher in A (119.8%, p = 0.002) than in the other groups (p = 0.01). Conclusions: rCBV differentiated glioma subtype with accuracy comparable to MET and could predict MET accumulation. However, its reliability for identifying MET-positive regions varied by subtype, being useful in A but limited in O. Recognizing these subtype-specific differences, rCBV can serve as a practical tool for evaluating non-contrast-enhanced gliomas. Full article

(This article belongs to the Special Issue Revolutionizing Neurosurgery: Cutting-Edge Techniques and Innovations)

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15 pages, 1363 KB

Open AccessArticle

Intrafamilial Patterns of Oral Health: A Cross-Sectional Study of Dental Status Associations Among Children, Parents, and Siblings

by Zuzanna Borawska, Kinga Wnorowska, Kamila Suchodolska, Justyna Magdalena Hermanowicz, Joanna Bagińska and Magdalena Nowosielska

J. Clin. Med. 2025, 14(19), 6776; https://doi.org/10.3390/jcm14196776 - 25 Sep 2025

Abstract

Background/Objectives: Untreated dental caries, the single most common health condition globally, is strongly associated with behavioural factors. This study examined dental status and oral health habits in child–parent and sibling pairs. Methods: We retrospectively analysed records from a dental practice in [...] Read more.

Background/Objectives: Untreated dental caries, the single most common health condition globally, is strongly associated with behavioural factors. This study examined dental status and oral health habits in child–parent and sibling pairs. Methods: We retrospectively analysed records from a dental practice in northeastern Poland, including 90 child–parent pairs and 27 sibling pairs. Dental status was assessed using the Decayed-Missing-Filled Teeth (DMFT) index, and treatment completion was measured with the Dental Treatment Index (DTI). Oral health behaviours were also evaluated. Results: Significant differences between children and parents were observed only in the mild-to-moderate caries groups (DMFT I: 27 children vs. 12 parents; DMFT II: 15 children vs. 32 parents). No differences were found in the severe caries or caries-free groups. Children had lower treatment completion than parents in the poorest care group (DTI 1: 20 children vs. 7 parents), but similar outcomes in higher DTI categories. Among siblings, differences appeared only in the DMFT I group, with no differences in treatment completion or behaviours. Conclusions: Strong similarities in extreme dental characteristics between children and parents, comparable DTI values in most groups, and consistent sibling outcomes suggest that family environment strongly influences oral health. Full article

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

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19 pages, 312 KB

Open AccessReview

Beyond Da Vinci: Comparative Review of Next-Generation Robotic Platforms in Urologic Surgery

by Stamatios Katsimperis, Lazaros Tzelves, Georgios Feretzakis, Themistoklis Bellos, Panagiotis Triantafyllou, Polyvios Arseniou and Andreas Skolarikos

J. Clin. Med. 2025, 14(19), 6775; https://doi.org/10.3390/jcm14196775 - 25 Sep 2025

Abstract

Robotic surgery has become a cornerstone of modern urologic practice, with the da Vinci system maintaining dominance for over two decades. In recent years, however, a new generation of robotic platforms has emerged, introducing greater competition and innovation into the field. These systems [...] Read more.

Robotic surgery has become a cornerstone of modern urologic practice, with the da Vinci system maintaining dominance for over two decades. In recent years, however, a new generation of robotic platforms has emerged, introducing greater competition and innovation into the field. These systems aim to address unmet needs through features such as modular architectures, enhanced ergonomics, haptic feedback, and cost-containment strategies. Several platforms—including Hugo™ RAS, Versius™, Avatera™, REVO-I, Hinotori™, Senhance™, KangDuo, MicroHand S, Dexter™, and Toumai^®—have entered clinical use with early results demonstrating perioperative and short-term oncologic outcomes broadly comparable to those of established systems, particularly in procedures such as radical prostatectomy, partial nephrectomy, and radical cystectomy. At the same time, they introduce unique advantages in workflow flexibility, portability, and economic feasibility. Nevertheless, important challenges remain, including the need for rigorous comparative trials, standardized training curricula, and long-term cost-effectiveness analyses. The integration of artificial intelligence, augmented reality, and telesurgery holds the potential to further expand the role of robotics in urology, offering opportunities to enhance precision, improve accessibility, and redefine perioperative care models. This review summarizes the evolving landscape of robotic platforms in urology, highlights their clinical applications and limitations, and outlines future directions for research, training, and global implementation. Full article

(This article belongs to the Special Issue The Current State of Robotic Surgery in Urology)

16 pages, 302 KB

Open AccessReview

New Developments in the Treatment of IgG4-Related Disease: A Comprehensive Clinical Approach

by Andrés González-García, Grisell Starita-Fajardo, David Lucena López, María Pilar Iranzo Alcolea, María López-Paraja, Mercedes Peña-Rodríguez, Francisco Lirola Sánchez, María Sánchez, Adrián Viteri-Noël, Martin Fabregate-Fuente, Mónica López-Rodríguez, José Luis Calleja-López and Luis Manzano Espinosa

J. Clin. Med. 2025, 14(19), 6774; https://doi.org/10.3390/jcm14196774 - 25 Sep 2025

Abstract

Immunoglobulin G4–related disease (IgG4-RD) is an uncommon fibro-inflammatory process characterized by the infiltration of tissues and organs and a typically dramatic response to glucocorticoids. Its relapsing–remitting course, multisystemic involvement, and variability in epidemiological and prognostic features pose a significant diagnostic challenge for clinicians. [...] Read more.

Immunoglobulin G4–related disease (IgG4-RD) is an uncommon fibro-inflammatory process characterized by the infiltration of tissues and organs and a typically dramatic response to glucocorticoids. Its relapsing–remitting course, multisystemic involvement, and variability in epidemiological and prognostic features pose a significant diagnostic challenge for clinicians. Despite their effectiveness in symptom relief, prolonged glucocorticoid use remains a challenge in IgG4-RD management, prompting the search for steroid-sparing alternatives. Although rituximab has recently demonstrated efficacy in the treatment of IgG4-RD, no consensus exists regarding the optimal maintenance regimen. The emergence of new B-cell–targeted therapies and other immunomodulators represents a promising step toward more personalized treatment approaches. In this review, we provide an updated and integrative overview of the emerging treatment strategies for IgG4-RD, highlighting future directions towards individualized management. Full article

(This article belongs to the Section Immunology & Rheumatology)

13 pages, 314 KB

Open AccessArticle

The Psychosocial Burden of Breast Cancer: A Cross-Sectional Study of Associations Between Sleep Quality, Anxiety, and Depression in Turkish Women

by Ömer Acar, Gamze Goksel, Erol Ozan, Ahmet Anıl Altunbaş, Mustafa Serkan Karakaya, Ferhat Ekinci and Atike Pınar Erdoğan

J. Clin. Med. 2025, 14(19), 6773; https://doi.org/10.3390/jcm14196773 - 25 Sep 2025

Abstract

Background/Objectives: Breast cancer remains the most common malignancy among women worldwide, with many patients experiencing persistent psychological symptoms that extend beyond active treatment. Among these, sleep disturbances, anxiety, and depression frequently co-occur and can significantly impair quality of life and treatment adherence. [...] Read more.

Background/Objectives: Breast cancer remains the most common malignancy among women worldwide, with many patients experiencing persistent psychological symptoms that extend beyond active treatment. Among these, sleep disturbances, anxiety, and depression frequently co-occur and can significantly impair quality of life and treatment adherence. This study aimed to assess the prevalence of poor sleep quality and examine its associations with anxiety and depression in a large cohort of Turkish women with breast cancer. Additionally, the study sought to identify sociodemographic and clinical predictors of sleep disturbance. Methods: In this cross-sectional study, 601 women with histologically confirmed breast cancer who were undergoing or had completed active treatment were recruited from a tertiary oncology center in Turkey between January 2023 and December 2023. The mean age of participants was 54 years (range 25–83). More than half of the patients were postmenopausal (56.3%), and 6% had stage IV disease. Sleep quality and psychological distress were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Hospital Anxiety and Depression Scale (HADS). Descriptive statistics, correlation analyses, and multivariate regression models were employed to identify significant predictors. Results: Poor sleep quality (PSQI > 5) was identified in 33.2% of participants. Patients with poor sleep reported significantly higher anxiety and depression scores (p < 0.001). Multivariate analysis revealed that being single, having children, undergoing breast-conserving surgery, and elevated anxiety scores were independent predictors of poor sleep. Additionally, marital status, menopausal status, and treatment modality were significantly associated with anxiety and depression scores. Conclusions: One-third of Turkish breast cancer patients experience clinically relevant sleep disturbances, which are strongly linked to psychological distress, particularly anxiety. These findings underscore the importance of incorporating routine psychological screening into oncologic care and highlight the need for individualized psychosocial support strategies that aim to improve both emotional well-being and overall clinical outcomes. Full article

(This article belongs to the Section Oncology)

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30 pages, 18339 KB

Open AccessCase Report

Simplified Vertical Ridge Augmentation in Severely Resorbed Alveolar Ridges Using a Novel Wide-Head Tenting Pole Screw: Clinical and Histomorphometric Analysis—A Case Series

by Hyung-Gyun Kim, Yong-Suk Moon and Dong-Seok Sohn

J. Clin. Med. 2025, 14(19), 6772; https://doi.org/10.3390/jcm14196772 - 25 Sep 2025

Abstract

Background/Objectives: Vertical ridge augmentation remains a challenging procedure in alveolar bone reconstruction, with existing techniques often limited by surgical complexity, graft instability, and high resorption rates. This study evaluates the clinical and histological outcomes of a novel vertical ridge augmentation technique using [...] Read more.

Background/Objectives: Vertical ridge augmentation remains a challenging procedure in alveolar bone reconstruction, with existing techniques often limited by surgical complexity, graft instability, and high resorption rates. This study evaluates the clinical and histological outcomes of a novel vertical ridge augmentation technique using a wide-head tenting pole screw (WHTPS) combined with sticky bone graft material. Methods: Five patients with vertical bone deficiencies (6–10 mm) in the maxilla or mandible underwent augmentation using a single WHTPS (rectangular or round wide-head type). Sticky bone was prepared using autologous tooth bone, allografts, or xenografts, combined with fibrin glue and covered with concentrated growth factor (CGF) membranes and/or resorbable collagen membranes. After 5–6 months of healing, the WHTPS was removed, and bone biopsies were taken for histological analysis. Results: Radiographic and histological evaluations confirmed successful ridge augmentation in all cases. Newly formed bone ranged from 21.2% to 57.5%. All patients proceeded to implant placement without complications. Radiographic, clinical, and histological assessments consistently showed that new bone formation extended up to the level of the screw head, indicating complete vertical fill of the augmented space. Histology showed well-integrated, mineralized bone with no signs of inflammation. The wide-head tenting pole screw was observed to support stable space maintenance and facilitate surgical handling and favorable outcomes in vertical ridge augmentation. Conclusions: In this case series, a single wide-head tenting pole screw appeared sufficient to maintain space and resist soft tissue pressure in wide alveolar bone defects during healing. This case series suggests that the wide-head tenting pole screw technique may be a feasible option for managing severe alveolar bone deficiencies. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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16 pages, 811 KB

Open AccessArticle

Twelve-Month Outcomes of Anti-VEGF Therapy for nAMD with Brolucizumab, Aflibercept, and Ranibizumab in the Polish National Registry: A Multicenter Database Study

by Sławomir Teper, Daniel Ledwoń, Patrycja Romaniszyn-Kania, Adam Sendecki, Aleksandra Tuszy, Julia Nycz, Andrzej W. Mitas, Małgorzata Figurska, Edward Wylęgała and Marek Rękas

J. Clin. Med. 2025, 14(19), 6771; https://doi.org/10.3390/jcm14196771 - 25 Sep 2025

Abstract

Background/Objectives: Real-world registries of neovascular age-related macular degeneration (nAMD) treatments provide critical insights for optimizing patient care and resource allocation. This study evaluates one-year outcomes of anti-VEGF therapy with aflibercept, ranibizumab, and brolucizumab in the Polish Therapeutic Program Monitoring System between 1 January [...] Read more.

Background/Objectives: Real-world registries of neovascular age-related macular degeneration (nAMD) treatments provide critical insights for optimizing patient care and resource allocation. This study evaluates one-year outcomes of anti-VEGF therapy with aflibercept, ranibizumab, and brolucizumab in the Polish Therapeutic Program Monitoring System between 1 January 2016 and 31 October 2023. Methods: We analyzed data from 51,902 treatment-naïve patients with nAMD, comparing baseline characteristics and outcomes across drugs, as well as between those who discontinued therapy early and those treated for at least one year. Results: No significant baseline differences were found between drug groups. One-year follow-up was available for 40,396 eyes; 3184 were lost to follow-up, and 8322 discontinued treatment: 14.4% for those receiving aflibercept, 24.1% for those receiving brolucizumab, and 20.1% for those receiving ranibizumab. Early discontinuers were older and had higher baseline visual acuity (aflibercept, ranibizumab). Twelve-month treatment outcomes, particularly visual acuity gains and injection frequency (~6–7/year), were similar across agents. Only ~22% achieved at least 0.3 logMAR improvement, underscoring real-world treatment challenges. Conclusions: System-level support, appropriate treatment intensification, and strategic use of newer, durable agents like brolucizumab are crucial to narrowing the gap between clinical trial efficacy and real-world effectiveness, ultimately improving long-term outcomes in nAMD care. Full article

(This article belongs to the Section Ophthalmology)

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19 pages, 783 KB

Open AccessArticle

Self-Perceived Health Status of Patients with Newly Diagnosed Diabetes in Spain: Associated Factors and Sex Differences

by Pilar Vich-Pérez, Belén Taulero-Escalera, Paula Regueiro-Toribio, Isabel Prieto-Checa, Victoria García-Espinosa, Laura Villanova-Cuadra, Ignacio Sevilla-Machuca, Julia Timoner-García, Mario Martínez-Grandmontagne, Tania Abós-Pueyo, Cristina Álvarez-Hernández-Cañizares, Germán Reviriego-Jaén, Alberto Serrano-López-Hazas, Inés Gala-Molina, Mar Sanz-Pascual, María José Guereña-Tomás, Ana Isabel González-González, Miguel Angel Salinero-Fort and on behalf of the LADA-PC Consortium

J. Clin. Med. 2025, 14(19), 6770; https://doi.org/10.3390/jcm14196770 - 25 Sep 2025

Abstract

Background/Objectives: Multiple studies indicate that self-perceived health accurately reflects a person’s overall health, and that poor self-perceived health is associated with chronic diseases, the use of health services, increased health expenditure, and mortality. There is little research on this topic in people [...] Read more.

Background/Objectives: Multiple studies indicate that self-perceived health accurately reflects a person’s overall health, and that poor self-perceived health is associated with chronic diseases, the use of health services, increased health expenditure, and mortality. There is little research on this topic in people with newly diagnosed diabetes mellitus (DM). The objectives of this study were to analyse self-perceived health in adult patients with newly diagnosed DM (mostly T2DM, but also T1DM), identify associated characteristics, including a Mediterranean diet and physical activity, and examine differences by sex. Methods: This is a cross-sectional study of 796 patients. Participants were evaluated through physical examination, electronic medical records, self-perceived health assessment, lifestyle, personal and family history, and laboratory parameters. A multivariate analysis was performed on the total sample and on sex subgroups to identify factors associated with self-perceived health. Results: In total, 25.8% of participants reported poor/fair health (33.4% women, 20.2% men). The variables associated with poorer self-reported health were being female, a lack of family support, morbid obesity, low physical activity, and anxiety/depression. In women: morbid obesity, cancer, and antiplatelet therapy. In men: lack of family support, age < 60, anxiety/depression, low physical activity, and previous treatment with ACEIs/ARBs. Conclusions: Poor self-perceived health is common in patients newly diagnosed with diabetes, similar to the general population. The factors found explained 24.2% of the variance and showed different associations by sex. The cross-sectional design did not allow for inferences of causality. These findings could suggest personalised interventions to address psychosocial and lifestyle factors at the onset of diabetes. Full article

(This article belongs to the Section Endocrinology & Metabolism)

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13 pages, 958 KB

Open AccessBrief Report

INTegrated Assessment of intERmediate Coronary Stenoses by Fractional Flow rEserve and Near-infraREd Spectroscopy: The INTERFERE Study

by Andrea Picchi, Gianluca Campo, Leonardo Misuraca, Pasquale Baratta, Antonio Biancofiore, Paolo Calabria, Alberto Massoni and Ugo Limbruno

J. Clin. Med. 2025, 14(19), 6769; https://doi.org/10.3390/jcm14196769 - 25 Sep 2025

Abstract

Background/Objectives: Fractional flow reserve (FFR) is the most widely used intracoronary physiological index to guide coronary revascularization but does not allow for a precise assessment of plaque morphology. The combined use of near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) can detect angiographically non-obstructive [...] Read more.

Background/Objectives: Fractional flow reserve (FFR) is the most widely used intracoronary physiological index to guide coronary revascularization but does not allow for a precise assessment of plaque morphology. The combined use of near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) can detect angiographically non-obstructive lesions with high lipid content and large plaque burden, which are associated with an increased risk of future adverse cardiac events. The aim of this study is to perform an integrated assessment of angiographically intermediate coronary lesions using both FFR and IVUS-NIRS, in order to evaluate the distribution of plaque vulnerability features—assessed by IVUS-NIRS—in functionally significant and non-significant lesions. Methods: This was a double-center, observational, prospective study including patients undergoing coronary angiography for both stable coronary artery disease and acute coronary syndrome, provided they had at least one angiographically borderline (40–70%) stenosis. The index lesion was evaluated with both FFR and IVUS-NIRS; revascularization decisions were guided by the FFR result. The following features were considered markers of plaque vulnerability: minimal lumen area (MLA) < 4.0 mm², plaque burden (PB) > 70%, and maximum lipid core burden index within any 4 mm segment (maxLCBI4mm) > 325. High-risk plaques were defined by the simultaneous presence of all three criteria. Results: A total of 57 patients were enrolled (mean age: 66 years; 18% women), and 57 lesions were assessed using both FFR and IVUS-NIRS. Acute coronary syndrome was the admission diagnosis in 72% of patients. Twenty-five lesions with FFR < 0.80 were classified as Group A, while the remaining thirty-two lesions with FFR > 0.80 were labeled as Group B. The percentage of lesions with MLA < 4 mm² and plaque burden > 70% was 72% and 67%, respectively, with no significant differences between Groups A and B. On NIRS analysis, 23% of lesions had a maxLCBI4mm > 325, again with no significant difference between the two groups. High-risk plaques—defined by the concurrent presence of MLA < 4 mm², plaque burden > 70%, and maxLCBI4mm > 325—were identified in 18% of patients. The prevalence of high-risk plaques did not differ significantly between Groups A and B (12% vs. 22%, p = 0.33). Conclusions: Plaque vulnerability criteria are equally distributed between functionally significant and non-significant coronary lesions, and the prevalence of high-risk plaques (defined by the simultaneous presence of MLA < 4 mm², PB > 70%, and maxLCBI4mm > 325) does not differ significantly between the two groups. Notably, 22% of FFR-negative lesions managed conservatively are characterized by the presence of high-risk plaques. Further studies are needed to determine whether these lesions warrant interventional treatment or a more intensive pharmacological approach. (ClinicalTrials.gov # NCT02985112). Full article

(This article belongs to the Section Cardiovascular Medicine)

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16 pages, 1582 KB

Open AccessArticle

Periodontal Status and Gingival Crevicular Fluid Fusobacterium nucleatum and Cathepsin K Assessment in Patients with Gastric Cancer

by Flavia Mirela Nicolae, Mihai Cucu, Sandu Râmboiu, Virgil Mihail Boldeanu, Adina Turcu-Stiolica, Valeriu Marin Șurlin, Dorin Nicolae Gheorghe, Dora Maria Popescu, Victor Dan Eugen Strâmbu, Radu Petre, Andreea Cristiana Didilescu and Petra Șurlin

J. Clin. Med. 2025, 14(19), 6768; https://doi.org/10.3390/jcm14196768 - 25 Sep 2025

Abstract

Background/Objectives: Periodontal disease, the most widespread chronic inflammatory non-communicable disease, is caused by the host-mediated inflammatory and immune responses to the bacterial biofilm. Fusobacterium nucleatum contributes to its progression and is associated with gastrointestinal cancers, including gastric cancer (GC), by promoting inflammation [...] Read more.

Background/Objectives: Periodontal disease, the most widespread chronic inflammatory non-communicable disease, is caused by the host-mediated inflammatory and immune responses to the bacterial biofilm. Fusobacterium nucleatum contributes to its progression and is associated with gastrointestinal cancers, including gastric cancer (GC), by promoting inflammation and immune evasion. Additionally, cathepsin K (CTSK) enhances tumor invasiveness and metastasis, playing a crucial role in GC progression. Aim: The present study was carried out to evaluate the possible association between the amount of F. nucleatum from gingival crevicular fluid and the periodontal status with the characteristics of GC. Methods: This cross-sectional study included 48 GC patients with periodontal changes, presenting to the Surgery Department in Craiova, Romania, from March 2023 to February 2024. Clinical assessments, where the number of teeth present, probing depth (PD), and bleeding on probing (BOP) were recorded, gingival crevicular fluid sampling, qPCR for Fusobacterium nucleatum, and ELISA for cathepsin K were performed. Histological analysis evaluated tumor characteristics, where tumor dimension (TD) and differentiation grade (DG) were recorded, and statistical analysis was conducted using R software. Results: Smokers presented higher PD and F. nucleatum levels than non-smokers. Gender had no impact on PD, BOP, CTSK, F. nucleatum, or TD. PD correlated with F. nucleatum, TD, and CTSK. F. nucleatum strongly correlated with CTSK and TD, and CTSK was strongly correlated with TD. Conclusions: These results suggest an association between F. nucleatum, periodontal parameters, and characteristics of GC but future studies are needed. Full article

(This article belongs to the Special Issue Interaction Between Systemic Diseases and Oral Diseases)

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J. Clin. Med., Volume 14, Issue 19 (October-1 2025) – 109 articles

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