Medicina

14 pages, 1411 KiB

Open AccessSystematic Review

Systematic Review and Meta-Analysis of Acute Mortality and Complication Rates Following Leadless Pacemaker Placement Using National-Level Data

by Akmoldir Sarsenbayeva, Adil Baimbetov, Aras Puodziukynas, Bolatbek Baimakhanov, Alexander Sapunov and Kenzhebek Bizhanov

Medicina 2025, 61(6), 974; https://doi.org/10.3390/medicina61060974 (registering DOI) - 25 May 2025

Abstract

Background and Objectives: Leadless pacemakers provide an innovative alternative to traditional transvenous pacemakers for managing cardiac arrhythmias. The objective of this systematic review is to conduct a meta-analysis comparing acute complication and mortality rates associated with leadless pacemakers versus transvenous pacemaker placements [...] Read more.

Background and Objectives: Leadless pacemakers provide an innovative alternative to traditional transvenous pacemakers for managing cardiac arrhythmias. The objective of this systematic review is to conduct a meta-analysis comparing acute complication and mortality rates associated with leadless pacemakers versus transvenous pacemaker placements using national-level data. Specifically, we aim to summarize the current evidence and calculate pooled odds ratios for acute overall complications, acute device-related complications, and acute mortality to assess the early safety outcomes of leadless pacemaker placement relative to traditional transvenous pacemakers. Materials and Methods: A systematic search of PubMed, Scopus, ScienceDirect, and Google Scholar was conducted by two independent researchers using a predefined search protocol. The search included articles published up to 10 October 2024, without limits on review depth. Studies were included if they provided national-level data comparing leadless pacemaker and traditional pacemaker recipients in terms of acute mortality, acute overall complications, and acute device-related complications. Outcomes were pooled to calculate odds ratios using a random-effects model in RStudio (version 2024.12.1+563). Results: A total of five studies met the eligibility criteria. The pooled odds ratio for acute mortality was 2.03 (95% CI: 0.65–6.34, I² = 99%; p < 0.01), for acute overall complications was 1.08 (95% CI: 0.45–2.61, I² = 99%; p < 0.01), and for acute device-related complications was 1.02 (95% CI: 0.23–4.44, I² = 99%; p < 0.01). Conclusions: The reviewed studies suggest that leadless pacemakers offer a promising alternative to transvenous pacemakers, offering a comparable short-term safety profile. Ongoing technological advancements may further enhance their applicability in clinical practice. Full article

(This article belongs to the Special Issue Minimally Invasive Procedures in Cardiac Care)

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12 pages, 765 KiB

Open AccessArticle

Accuracy Verification of a Computed Tomography-Based Navigation System for Total Hip Arthroplasty in Severe Hip Dysplasia: A Simulation Study Using 3D-Printed Bone Models of Crowe Types II, III, and IV

by Ryuichiro Okuda, Tomonori Tetsunaga, Kazuki Yamada, Tomoko Tetsunaga, Takashi Koura, Tomohiro Inoue, Yasutaka Masada, Yuki Okazaki and Toshifumi Ozaki

Medicina 2025, 61(6), 973; https://doi.org/10.3390/medicina61060973 (registering DOI) - 24 May 2025

Abstract

Background and Objective: The use of computed tomography (CT)-based navigation systems has been shown to improve surgical accuracy in total hip arthroplasty. However, there is limited literature available about the application of CT-based navigation systems in severe hip dysplasia. This study aimed to [...] Read more.

Background and Objective: The use of computed tomography (CT)-based navigation systems has been shown to improve surgical accuracy in total hip arthroplasty. However, there is limited literature available about the application of CT-based navigation systems in severe hip dysplasia. This study aimed to evaluate the accuracy of a CT-based navigation system in patients with severe hip dysplasia using three-dimensional (3D)-printed bone models. Methods: 3D-printed bone models were generated from CT data of patients with severe hip dysplasia (Crowe type II, 10 hips; type III, 10 hips; and type IV, 10 hips). The accuracy of automatic segmentation, success rate, point-matching accuracy across different registration methods, and deviation values at reference points after registration were assessed. Results: For the combined cohort of Crowe II, III, and IV cases (n = 30), the Dice Similarity Coefficient and Jaccard Index were 0.99 ± 0.01 and 0.98 ± 0.02, respectively. These values indicate a high level of segmentation accuracy. The “Matching with true and false acetabulum + iliac crest” method achieved a 100% success rate across all groups, with mean deviations of 0.08 ± 0.28 mm in the Crowe II group, 0.12 ± 0.33 mm in the Crowe III group, and 0.14 ± 0.50 mm in the Crowe IV group (p = 0.572). In the Crowe IV group, the anterior superior iliac spine deviation was significantly lower using the “Matching with true and false acetabulum + iliac crest” method compared to the “Matching with true and false acetabulum” method (0.28 ± 0.49 mm vs. 3.29 ± 2.56 mm, p < 0.05). Conclusions: This study demonstrated the high accuracy of automatic AI-based segmentation, with a Dice Similarity Coefficient of 0.99 ± 0.01 and a Jaccard Index of 0.98 ± 0.02 in the combined cohort of Crowe type II, III, and IV cases (n = 30). The matching success rate was 100%, with additional points on the iliac crest, which improved matching accuracy and reduced deviations, depending on the case. Full article

(This article belongs to the Special Issue Clinical Research in Orthopaedics and Trauma Surgery)

14 pages, 929 KiB

Open AccessArticle

Associations Between Cerebral Perfusion Pressure, Hemodynamic Parameters, and Cognitive Test Values in Normal-Tension Glaucoma Patients, Alzheimer’s Disease Patients, and Healthy Controls

by Akvile Stoskuviene, Edvinas Chaleckas, Evelina Grusauskiene, Laimonas Bartusis, Guven Celikkaya, Ingrida Januleviciene, Antanas Vaitkus, Arminas Ragauskas and Yasin Hamarat

Medicina 2025, 61(6), 972; https://doi.org/10.3390/medicina61060972 (registering DOI) - 24 May 2025

Abstract

Background/Objectives: Glaucoma and Alzheimer’s disease (AD) are neurodegenerative conditions with vascular underpinnings. This study aimed to explore the relationship between blood pressure parameters such as mean arterial pressure (MAP), pulse pressure (PP), and cerebral perfusion pressure (CPP) and cognitive performance in patients [...] Read more.

Background/Objectives: Glaucoma and Alzheimer’s disease (AD) are neurodegenerative conditions with vascular underpinnings. This study aimed to explore the relationship between blood pressure parameters such as mean arterial pressure (MAP), pulse pressure (PP), and cerebral perfusion pressure (CPP) and cognitive performance in patients with AD, normal-tension glaucoma (NTG), and healthy controls. We hypothesized that NTG patients, like those with mild cognitive impairment (MCI), may experience subtle cognitive changes related to vascular dysregulation. Methods: Ninety-eight participants (35 NTG, 17 AD, 46 controls) were assessed for CPP, MAP, OPP, and cognitive performance. Statistical analyses compared groups and examined correlations. Results: AD patients showed lower CPP and MAP (p < 0.001), indicating systemic vascular dysfunction, while NTG patients had higher ocular perfusion pressure (OPP) (p = 0.008), suggesting compensatory mechanisms. CPP correlated with visuospatial abilities in AD (r = 0.492, p = 0.045). MAP correlated with the Clock drawing test (CDT) scores in the NTG group (r = 0.378, p = 0.025). PP negatively correlated with cognition in AD (r = −0.527, p = 0.016 for CDT scores) and controls (r = −0.440, p = 0.002 for verbal fluency and r = −0.348, p = 0.019 for total ACE scores). Conclusions: The study highlights distinct hemodynamic profiles: systemic dysfunction in AD and localized dysregulation in NTG. These findings emphasize the role of vascular dysregulation in neurodegeneration, with implications for personalized treatment approaches targeting vascular health in neurodegenerative conditions. Full article

(This article belongs to the Section Ophthalmology)

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12 pages, 487 KiB

Open AccessArticle

Longitudinal Outcomes of Left Ventricular Outflow Tract Obstruction in Aortic Stenosis Versus Hypertrophic Obstructive Cardiomyopathy

by Joy Yi-Shan Ong, Tony Yi-Wei Li, Aloysius Sheng-Ting Leow, Swee-Chye Quek, William Kok-Fai Kong, Weiqin Lin, Ping Chai, Tiong-Cheng Yeo, Raymond Ching-Chiew Wong, Ching-Hui Sia and Kian-Keong Poh

Medicina 2025, 61(6), 971; https://doi.org/10.3390/medicina61060971 (registering DOI) - 23 May 2025

Abstract

Background and Objectives: Aortic stenosis (AS) and hypertrophic obstructive cardiomyopathy (HOCM) are two disease entities that result in left ventricular outflow tract (LVOT) obstruction. We sought to evaluate the longitudinal outcomes of fixed obstruction in severe valvular AS versus dynamic flow obstruction [...] Read more.

Background and Objectives: Aortic stenosis (AS) and hypertrophic obstructive cardiomyopathy (HOCM) are two disease entities that result in left ventricular outflow tract (LVOT) obstruction. We sought to evaluate the longitudinal outcomes of fixed obstruction in severe valvular AS versus dynamic flow obstruction in HOCM. Materials and Methods: Consecutive data with index echocardiographic diagnoses of severe AS and HOCM were collected in a tertiary academic centre between 2010 and 2017. Demographics, comorbidities and clinical outcomes were compared. Results: A total of 134 patients were studied. In the AS group, the mean MPG was 57.2 mmHg ± 13.9, the mean AVA was 0.7 cm² ± 0.2, and the mean Vmax was 4.7 m/s ± 0.5 (p < 0.001). In the HOCM group, the mean LVOT gradient was 60.1 mmHg ± 35.5, the mean IVSd was 17.5 mm ± 4.6, and the mean LVPWd was 12.9 mm ± 2.9 (p < 0.001). Kaplan–Meier curves showed lower cumulative survival with an early separation in heart failure outcomes in the AS arm compared with the HOCM arm (p = 0.023). Similarly, there were higher rates of all-cause mortality for AS compared with HOCM (p = 0.001). For the multivariable Cox regression analysis, AS was significantly associated with a higher incidence of heart failure compared with HOCM after adjusting for the baseline demographics, comorbidities and echocardiographic parameters. There were no significant differences in terms of stroke or cardiovascular (CV) hospitalisation outcomes between the two cohorts. Conclusions: Fixed LVOT obstruction in AS was associated with worse outcomes of heart failure and all-cause mortality compared with dynamic LVOT obstruction in HOCM. Severe AS was an independent predictor of heart failure outcomes after adjustments. Full article

(This article belongs to the Section Cardiology)

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Graphical abstract

28 pages, 820 KiB

Open AccessReview

Characteristics of Physical Exercise Programs and Their Effects on Quality of Life and Functional Capacity in Individuals with Chronic Obstructive Pulmonary Disease: A Scoping Review

by Rafael Oliveira, João Paulo Brito, Halil İbrahim Ceylan, Maria de Brito Soares, Alexandre Duarte Martins, Tiago Vasconcelos, João Moutão and Susana Alves

Medicina 2025, 61(6), 970; https://doi.org/10.3390/medicina61060970 (registering DOI) - 23 May 2025

Abstract

Background and Objectives: Individuals with chronic obstructive pulmonary disease (COPD) often exhibit some degree of intolerance to physical exercise and several limitations in daily activities. Therefore, the objective of this study was to conduct a scoping review on the characteristics—frequency, intensity, time, and [...] Read more.

Background and Objectives: Individuals with chronic obstructive pulmonary disease (COPD) often exhibit some degree of intolerance to physical exercise and several limitations in daily activities. Therefore, the objective of this study was to conduct a scoping review on the characteristics—frequency, intensity, time, and type (FITT)—and the effects of exercise programs on quality of life and functional capacity in individuals with COPD. Materials and Methods: The present review included 21 studies that were scoping-reviewed to describe their main findings and training characteristics. Results: The participants across studies ranged in age from ~39 to 76 years with mild to very severe COPD stages. The results showed that, among all studies, eleven used cardiorespiratory training (e.g., walking or cycling), five used strength training (e.g., exercises with elastic bands or traditional resistance training), and five implemented combined training (i.e., cardiorespiratory and strength exercises). Conclusions: Overall, all training protocols improved aerobic capacity (cardiorespiratory training), strength (resistance training), and both capacities together (combined training). In conclusion, this review provided complementary insights to existing exercise prescription guidelines, particularly concerning cardiorespiratory, strength, and combined training in individuals with COPD. However, the methodologies of the training protocols varied widely, and detailed descriptions of FITT components were often incomplete or lacking clarity, especially regarding the specific exercises used. Future research should include more comprehensive spirometry variables such as forced expiratory volume 1 or forced vital capacity, as these are critical for determining COPD stages. Thus, there is a clear need for more high-quality research with robust methodological design in the context of exercise interventions for individuals with COPD. Full article

(This article belongs to the Section Sports Medicine and Sports Traumatology)

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16 pages, 809 KiB

Open AccessArticle

An Investigation into the Effects of Frailty and Sarcopenia on Postoperative Anesthesia Recovery and Complications Among Geriatric Patients Undergoing Colorectal Malignancy Surgery

by Rüştü Özdemir and Ferda Yaman

Medicina 2025, 61(6), 969; https://doi.org/10.3390/medicina61060969 (registering DOI) - 23 May 2025

Abstract

Backgrounds and Objectives: In this study, we aimed to assess preoperative frailty among hospitalized patients over 60 undergoing colorectal cancer surgery. We investigated the impacts of frailty and sarcopenia on postoperative recovery, complications, and discharge time, while also identifying a cost-effective, bedside-accessible USG [...] Read more.

Backgrounds and Objectives: In this study, we aimed to assess preoperative frailty among hospitalized patients over 60 undergoing colorectal cancer surgery. We investigated the impacts of frailty and sarcopenia on postoperative recovery, complications, and discharge time, while also identifying a cost-effective, bedside-accessible USG parameter for diagnosing sarcopenia among patients assessed using the “Sonographic Thigh Adjustment Ratio” method. Materials and Methods: In this prospective study, we investigated the impacts of frailty and sarcopenia on the postoperative outcomes of 42 geriatric patients (with American Society of Anesthesiologists (ASA) scores of I–III) undergoing colorectal cancer surgery under general anesthesia. Frailty was assessed using the FRAIL scale, and sarcopenia was evaluated using the STAR (sonographic thigh adjustment ratio). Ultrasonographic measurements of rectus femoris and vastus intermedius muscle thicknesses were taken, and thigh lengths (TLs) were recorded. Ratios, including rectus femoris thickness/TL (RFT/TL), vastus intermedius thickness/TL (VIT/TL), and total muscle thickness/TL (TMT/TL), were calculated. Postoperative anesthesia recovery was monitored using the Modified Aldrete Score, indicating the time until discharge from the recovery unit. Complications were classified using the Clavien–Dindo system, and hospital discharge times were noted. Results: We observed significant differences between frailty status and ASA scores, as well as between age and frailty status. Muscle thickness significantly differed between the frail and pre-frail patients. Among the sarcopenic patients, age differences were significant. In men, VIT/TL was significantly correlated with sarcopenia diagnosis, whereas, in women, RFT/TL, VIT/TL, and TMT/TL were all correlated with sarcopenia. Conclusions: Based on our results, we conclude that VIT/TL measurement can serve as a predictive marker for preoperative sarcopenia, optimizing patient health before surgery. Full article

(This article belongs to the Section Intensive Care/ Anesthesiology)

15 pages, 715 KiB

Open AccessArticle

Salivary 1,5-Anhydroglucitol and AGEs Are Associated with Postural Instability in Diabetic Foot Patients

by Lorenzo Brognara, Mar Sempere-Bigorra and Omar Cauli

Medicina 2025, 61(6), 968; https://doi.org/10.3390/medicina61060968 (registering DOI) - 23 May 2025

Abstract

Background and Objectives: Gait and posture alterations are reported in patients with diabetic foot. We evaluated whether gait and postural parameters are associated with a well-known parameter, e.g., glycated hemoglobin levels in blood, and the salivary markers 1,5-anhydro-D-glucitol (1,5-AG) and Advanced Glycation [...] Read more.

Background and Objectives: Gait and posture alterations are reported in patients with diabetic foot. We evaluated whether gait and postural parameters are associated with a well-known parameter, e.g., glycated hemoglobin levels in blood, and the salivary markers 1,5-anhydro-D-glucitol (1,5-AG) and Advanced Glycation End-Products (AGEs) measured in saliva samples. Materials and Methods: Gait and postural impairment was assessed using a wearable inertial sensor, and the evaluation of balance/gait and risk of fall was determined by the Tinetti Scale and Downton Index, respectively. Glycemic control was measured by glycated hemoglobin concentration and fasting glycemia. The salivary concentration of 1,5-AG and AGEs was measured using an enzyme-linked immunosorbent assay. Results: Eighty-five patients were evaluated, revealing significant associations (p < 0.05) between salivary 1,5-AG and sway path displacement along the medio-lateral axis (rho = 0.365, p = 0.017) and sway area (rho = 0.334, p = 0.031) during tandem position tests with eyes closed. Salivary AGEs were significantly associated with sway path displacement along the anterior–posterior axis (rho = 0.419, p = 0.004) and medio-lateral axis (rho = 0.436, p = 0.002) in the tests performed with eyes closed, feet close together, and foam pads, as well as with sway area (rho = 0.387, p = 0.007). The concentration of HbA1c was significantly correlated with sway path displacement along the anterior–posterior axis in the tests performed with eyes closed, feet close together, and foam pads (rho = 0.236, p = 0.043), as well as with sway area (rho = −0.236, p = 0.043). A significant difference was observed in the salivary AGE concentration between patients with previous ulcers versus those without (p = 0.035). By applying Bonferroni correction for multiple comparisons, the associations remained significant (p < 0.05) for AGE concentration in saliva and postural instability parameters. Conclusions: The results suggest a link between salivary glycemic control biomarkers, in particular AGEs and postural changes in patients with diabetic foot, indicating a new interesting filed for further studies on fall risk. Full article

(This article belongs to the Special Issue Physical Therapy: A New Perspective)

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11 pages, 288 KiB

Open AccessArticle

Oxidative Stress in Psoriasis Vulgaris Patients: Analysis of Asymmetric Dimethylarginine, Malondialdehyde, and Glutathione Levels

by Neşe Göçer Gürok, Selda Telo, Büşra Genç Ulucan and Savaş Öztürk

Medicina 2025, 61(6), 967; https://doi.org/10.3390/medicina61060967 (registering DOI) - 23 May 2025

Abstract

Background and Objectives: Psoriasis vulgaris (PV) is a chronic inflammatory disease associated with oxidative stress. It has been reported that oxidative stress caused by disruption of redox signaling can cause molecular damage, activate dendritic cells, lymphocytes, and keratinocytes, and lead to angiogenesis, inflammation, [...] Read more.

Background and Objectives: Psoriasis vulgaris (PV) is a chronic inflammatory disease associated with oxidative stress. It has been reported that oxidative stress caused by disruption of redox signaling can cause molecular damage, activate dendritic cells, lymphocytes, and keratinocytes, and lead to angiogenesis, inflammation, cell necrosis, and apoptosis by increasing the levels of lipid peroxidation products. In this study, serum levels of asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), and reduced glutathione (GSH) were analyzed to gain insight into the oxidative balance in patients with PV. Materials and Methods: This prospective study included 59 PV patients and 40 healthy volunteers as the healthy control group. Age, gender, body mass index (BMI), waist circumference, routine hematologic parameters [fasting blood glucose, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), blood lipid levels, hemogram parameters], disease duration, and disease severity were recorded on data forms. The levels of ADMA, MDA, and GSH were analyzed using the high-performance liquid chromatography (HPLC) method. Results: When analyzed in terms of demographic characteristics, no statistically significant difference was observed between the patient and control groups. When examined in terms of biochemical variables, white blood cell (WBC) values were found to be significantly higher in the patient group (t: 2.825; p < 0.05). Although waist circumference, BMI, glucose, CRP, ESR, lipids, platelet count, and systolic and diastolic blood pressure were higher in the patient group, this difference was not statistically significant (p > 0.05). ADMA (t: 4.532; p < 0.05) and MDA (t: 9.598; p < 0.05) values were found to be higher and GSH (t: −4.717; p < 0.05) values were found to be lower in the patient group compared to the control group. When correlation analysis was performed between the parameters, a significant relationship was found only between GSH values and ADMA values (r: −0.256; p < 0.05). Accordingly, as the patients’ GSH values increased, ADMA values decreased. Conclusions: Increased WBC, ADMA, and MDA levels, and decreased GSH levels in PV patients reveal the critical role of oxidative stress and inflammation in the disease process. Evaluation of these biomarkers may contribute to the identification of new targets for the treatment of PV and the development of more effective management strategies. Full article

(This article belongs to the Section Dermatology)

24 pages, 361 KiB

Open AccessArticle

Dance and Somatic-Informed Movement in an Acute Inpatient Stroke Unit

by Lucie Beaudry, Céline Odier and Sylvie Fortin

Medicina 2025, 61(6), 966; https://doi.org/10.3390/medicina61060966 (registering DOI) - 23 May 2025

Abstract

Background and Objectives: Stroke units rely on interdisciplinary teams. Professionals with complementary alternative practices may join the team since such approaches are increasingly supporting the stroke recovery process. The aim of this study was to develop a better understanding of how a [...] Read more.

Background and Objectives: Stroke units rely on interdisciplinary teams. Professionals with complementary alternative practices may join the team since such approaches are increasingly supporting the stroke recovery process. The aim of this study was to develop a better understanding of how a dance and somatic-informed movement intervention could be utilized in an inpatient setting as an adjunct to post-stroke therapy. We sought to identify (1) what knowledge we could draw on to develop the content and pedagogy for the intervention, (2) what helped/hindered the intervention aimed at functional recovery, as perceived by the practitioner-researchers, and (3) the relationships experienced with the various stakeholders. Materials and Methods: This exploratory qualitative study used the enhanced critical incident technique to collect retrospective self-report data from two practitioner-researchers engaged in delivering the intervention over two months. The data underwent thematic analysis. Patients (n = 6) in a stroke unit were selected within ≤72 h of hospital admission. The intervention was conducted four to six times a week until the vascular neurologist (co-researcher) authorized their transfer to a rehabilitation hospital. Results: The intervention evolved from crafting content and pedagogy at the intersection of different areas of knowledge (dance, somatics, neuroscience, and stroke). It was based on active, assisted, and passive movements. Verbal, tactile, visual, and imaginary inputs used to enhance body awareness were perceived as potentially helping patients recover some range of motion, quality of movements, and voluntary movement control, and fostering calmness and motivation. The intervention was well received by stakeholders. Conclusions: Dance and somatic-informed movement can be a complementary therapy in stroke units, although it requires a delicate juggling of time allocation within the interdisciplinary team. Further studies should be conducted with a larger number of patients and different practitioners. Collaboration between qualitative and quantitative researchers is needed to make a robust case for such interventions. Full article

(This article belongs to the Special Issue Advances and Challenges in Stroke Rehabilitation)

22 pages, 3362 KiB

Open AccessArticle

A Bioelectrically Enabled Smart Bandage for Accelerated Wound Healing and Predictive Monitoring

by Ahmad F. Turki and Aziza R. Alrafiah

Medicina 2025, 61(6), 965; https://doi.org/10.3390/medicina61060965 (registering DOI) - 23 May 2025

Abstract

Background and Objectives: Chronic wounds pose a significant healthcare burden due to their prolonged healing times and susceptibility to infection. Electric field (EF)-enabled smart bandages offer a promising solution by combining therapeutic stimulation with real-time physiological monitoring. Materials and Methods: This study assessed [...] Read more.

Background and Objectives: Chronic wounds pose a significant healthcare burden due to their prolonged healing times and susceptibility to infection. Electric field (EF)-enabled smart bandages offer a promising solution by combining therapeutic stimulation with real-time physiological monitoring. Materials and Methods: This study assessed a smart bandage integrating spiral stainless steel electrodes delivering a 200 millivolts per millimeter (mV/mm) EF for 5 hours daily over 14 days to full-thickness excisional wounds in 100 Sprague–Dawley rats. Vital signs including heart rate (BPM), oxygen saturation (SpO₂), and temperature were monitored continuously. Machine learning models were trained on these data to predict wound healing status. Results: By Day 7, EF-treated wounds demonstrated significantly faster healing, achieving an average wound closure rate of 82.0% ± 2.1% compared to 70.75% ± 2.3% in the control group (p < 0.05). By Day 14, wounds in the experimental group had significantly reduced to 0.01 ± 0.005 cm², while the control group retained a wound size of 0.24 ± 0.03 cm² (p < 0.05). Histological analysis revealed enhanced neovascularization, collagen alignment, and epithelial regeneration in the EF group. Physiological data showed no systemic inflammatory response. Predictive modeling using XGBoost and Random Forest achieved >98% accuracy, with SHAP (SHapley Additive exPlanations) analysis identifying EF exposure and treatment duration as key predictors. Conclusions: The findings demonstrate that EF-based smart bandages significantly enhance wound healing and enable highly accurate prediction of outcomes through machine learning models. This bioelectronic approach holds strong potential for clinical translation. Full article

12 pages, 944 KiB

Open AccessArticle

Dynamic Lipid–Glycaemic Index and Inflammation—Endothelial Shifts and Fetal Aortic Wall Thickening: A Repeated-Measures Gestational Phenotyping Study

by Maria Cezara Muresan, Biliana Belovan, Ioan Sîrbu, Zoran Laurentiu Popa, Cosmin Citu, Ioan Sas and Adrian Ratiu

Medicina 2025, 61(6), 964; https://doi.org/10.3390/medicina61060964 (registering DOI) - 23 May 2025

Abstract

Background and Objectives: Maternal dyslipidaemia and low-grade inflammation are recognised drivers of in utero vascular remodelling, yet composite dynamic markers that integrate lipid–glycaemic, inflammatory and endothelial signals have not been evaluated. We investigated whether eight-week trajectories in the triglyceride–glucose index (TyG), interleukin-6 [...] Read more.

Background and Objectives: Maternal dyslipidaemia and low-grade inflammation are recognised drivers of in utero vascular remodelling, yet composite dynamic markers that integrate lipid–glycaemic, inflammatory and endothelial signals have not been evaluated. We investigated whether eight-week trajectories in the triglyceride–glucose index (TyG), interleukin-6 (IL-6) and flow-mediated dilation (FMD) outperform single-timepoint lipids for predicting fetal aortic remodelling. Materials and Methods: In a prospective repeated-measures study, 90 singleton pregnancies were examined at 24–26 weeks (Visit-1) and 32–34 weeks (Visit-2). At each visit, we obtained fasting lipids, TyG index, hsCRP, IL-6, oxidative-stress markers (MDA, NOx), brachial flow-mediated dilation (FMD), carotid IMT and uterine-artery Doppler, together with advanced fetal ultrasonography (abdominal-aorta IMT, ventricular strain, Tei-index, fetal pulse-wave velocity). Mothers were grouped by k-means clustering of the visit-to-visit change (Δ) in TG, TyG, hsCRP, IL-6 and FMD into three Metabolic-Inflammatory Response Phenotypes (MIRP-1/2/3). Linear mixed-effects models and extreme-gradient-boosting quantified associations and predictive performance. Results: Mean gestational TG rose from 138.6 ± 14.1 mg/dL to 166.9 ± 15.2 mg/dL, TyG by 0.21 ± 0.07 units and FMD fell by 1.86 ± 0.45%. MIRP-3 (“Metabolic + Inflammatory”; n = 31) showed the largest change (Δ) Δ-hsCRP (+0.69 mg/L) and Δ-FMD (–2.8%) and displayed a fetal IMT increase of +0.17 ± 0.05 mm versus +0.07 ± 0.03 mm in MIRP-1 (p < 0.001). Mixed-effects modelling identified Δ-TyG (β = +0.054 mm per unit), Δ-IL-6 (β = +0.009 mm) and Δ-FMD (β = –0.007 mm per %) as independent determinants of fetal IMT progression. An XGBoost model incorporating these Δ-variables predicted high fetal IMT (≥90th percentile) with AUROC 0.88, outperforming logistic regression (AUROC 0.74). Conclusions: A short-term surge in maternal TyG, IL-6 and endothelial dysfunction delineates a high-risk phenotype that doubles fetal aortic wall thickening and impairs myocardial performance. Composite dynamic indices demonstrated superior predictive value compared with individual lipid markers. Full article

(This article belongs to the Section Obstetrics and Gynecology)

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21 pages, 859 KiB

Open AccessReview

Phospholipase Cζ, the Molecular Spark of Fertilization and Male Infertility: Insights from Bench to Bedside

by Aris Kaltsas, Maria-Anna Kyrgiafini, Zissis Mamuris, Fotios Dimitriadis, Athanasios Zachariou, Michael Chrisofos and Nikolaos Sofikitis

Medicina 2025, 61(6), 963; https://doi.org/10.3390/medicina61060963 (registering DOI) - 23 May 2025

Abstract

Phospholipase C zeta (PLCζ) has emerged as a pivotal sperm-specific factor responsible for triggering oocyte activation, a process essential for successful fertilization and early embryogenesis. A narrative review was conducted to examine the molecular architecture and biochemical features of PLCζ, with particular emphasis [...] Read more.

Phospholipase C zeta (PLCζ) has emerged as a pivotal sperm-specific factor responsible for triggering oocyte activation, a process essential for successful fertilization and early embryogenesis. A narrative review was conducted to examine the molecular architecture and biochemical features of PLCζ, with particular emphasis on how its distinctive structural domains facilitate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP₂) and the induction of calcium (Ca²⁺) oscillations in the oocyte. Notably, PLCζ exhibits unique sensitivity to basal Ca²⁺ levels and the capacity to sustain repetitive intracellular Ca²⁺ transients that drive meiotic progression and block polyspermy. Clinically, PLCζ deficiency—whether caused by genetic mutations, reduced expression, or improper localization—represents a unifying explanation for certain forms of male infertility, including total fertilization failure (TFF) following intracytoplasmic sperm injection (ICSI). Globozoospermia is a prime example; this condition is characterized by round-headed sperm devoid of acrosomes and exhibiting significantly reduced or absent PLCζ and often results in fertilization failure. Diagnostic methods such as immunofluorescence, Western blotting, and the mouse oocyte-activation test collectively support the identification and characterization of PLCζ-related defects, while genetic testing for mutations in the PLCZ1 gene has proven valuable for identifying hereditary causes of sperm-borne oocyte-activation deficiency (OAD). Therapeutic approaches range from assisted oocyte activation (AOA) with calcium ionophores to emerging interventions that introduce functional PLCζ protein or mRNA directly into the oocyte. These advancements demonstrate the rapid translation of foundational discoveries into clinically actionable interventions. Future investigations are poised to refine diagnostic assays, standardize measurement protocols, and explore the potential of gene therapy or CRISPR/Cas9-mediated correction for heritable PLCζ abnormalities. By addressing both the molecular basis and translational applications of PLCζ, recent findings underscore its indispensable role in fertility care and lay out a path toward further innovation in assisted reproductive technologies. Full article

(This article belongs to the Special Issue From Conception to Birth: Embryonic Development and Disease)

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9 pages, 251 KiB

Open AccessArticle

CalR and MPL Driver Mutations and Their Role in the Diagnosis and Clinical Course of JAK2-Unmutated Chronic Myeloproliferative Neoplasm: Results from a Pilot Single-Center Study

by Tarık Onur Tiryaki, Aynur Dağlar Aday, Meliha Nalçacı and Akif Selim Yavuz

Medicina 2025, 61(6), 962; https://doi.org/10.3390/medicina61060962 - 23 May 2025

Abstract

Background and Objectives: Philadelphia (Ph)-negative myeloproliferative neoplasms can exhibit defects in Janus kinase 2 (JAK2), Calreticulin (CalR), and MPL genes. It is possible that the presence of other driver mutations may influence diagnosis and prognosis in patients who do not have a [...] Read more.

Background and Objectives: Philadelphia (Ph)-negative myeloproliferative neoplasms can exhibit defects in Janus kinase 2 (JAK2), Calreticulin (CalR), and MPL genes. It is possible that the presence of other driver mutations may influence diagnosis and prognosis in patients who do not have a JAK2 gene mutation. The purpose of this study was to assess the frequency of CalR and MPL gene mutations and the clinical effects of these mutations in JAK2 gene-unmutated MPN patients from a single center. Materials and Methods: We examined 46 patients (ET/PMF: 34/12) diagnosed with MPNs regarding their genetic conditions, diagnoses, and complications. Results: CalR Type 1 gene mutation was detected in 26.1% of cases, CalR Type 2 gene mutation in 13.0%, MPL-L gene mutation in 2.2%, and MPL-K gene mutation in 6.5%. In total, 56.5% of patients were triple-negative. The presence of CalR Type 1 and Type 2 mutations was significantly more prevalent in patients with essential thrombocytosis (ET), although the difference did not reach statistical significance (p = 0.51, p = 0.57). In contrast, MPL mutations were only observed in patients with primary myelofibrosis (PMF). Conclusions: We found no correlation between thrombosis, leukemic transformation, and driver mutations. MPL gene mutation was present in only myelofibrosis patients, and CALR gene mutation was present in one of the three cases of leukemic transformation. The triple-negative group had a lower survival rate, but this difference was not statistically significant (110.3 months vs. 121.4 months, respectively, p = 0.53). However, the sample size was quite small. Our limited observations suggest a possible trend that requires confirmation. Full article

(This article belongs to the Topic Cancer Biology and Radiation Therapy: 2nd Edition)

16 pages, 2738 KiB

Open AccessReview

Epicardial Adipose Tissue: A Multimodal Imaging Diagnostic Perspective

by Giancarlo Trimarchi, Maria Ludovica Carerj, Concetta Zito, Gianluca Di Bella, Giovanni Taverna, Maurizio Cusmà Piccione, Pasquale Crea, Stefania Lo Giudice, Angela Buonpane, Michela Bonanni, Davide Restelli, Umberto Paradossi, Angelo Monteleone, Antonio Micari and Scipione Carerj

Medicina 2025, 61(6), 961; https://doi.org/10.3390/medicina61060961 - 23 May 2025

Abstract

Epicardial adipose tissue (EAT), strategically located between the myocardium and the visceral pericardial layer, is increasingly recognized as an active player in cardiovascular health rather than a passive fat depot. EAT secretes a notable array of bioactive molecules known as adipokines, which exert [...] Read more.

Epicardial adipose tissue (EAT), strategically located between the myocardium and the visceral pericardial layer, is increasingly recognized as an active player in cardiovascular health rather than a passive fat depot. EAT secretes a notable array of bioactive molecules known as adipokines, which exert critical exocrine and paracrine effects. Recent research has focused on pericoronary adipose tissue (PCAT)—the EAT surrounding coronary arteries—demonstrating its intricate bidirectional relationship with the vascular wall. Under normal physiological conditions, this interaction promotes vascular homeostasis; however, dysfunctional PCAT can release pro-inflammatory adipokines implicated in the pathogenesis of atherogenesis. Notably, PCAT inflammation has emerged as a significant factor associated with the development of coronary artery disease (CAD) and major cardiovascular events. This review seeks to elucidate the imaging methodologies employed to evaluate EAT, emphasizing cardiac computed tomography (CCT) as the preeminent imaging modality. Unlike echocardiography and cardiac magnetic resonance imaging, CCT not only visualizes and quantifies EAT but also concurrently assesses coronary arteries and PCAT. Recent findings have established the potential of CCT-derived PCAT attenuation as a noninvasive biomarker for coronary inflammation, offering prospects for monitoring therapeutic responses to innovative anti-inflammatory interventions in CAD management. Full article

(This article belongs to the Special Issue Multimodal Imaging Techniques in Myocardial Ischemia: Current Applications and Future Prospects)

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16 pages, 3366 KiB

Open AccessArticle

Antitumor Effects of Hesperidin and Cisplatin on Human Osteosarcoma Cells Through Inhibiting Proliferation and Inducing Mitochondrial-Mediated Apoptosis

by Mehmet Onur Ziyadanoğulları, Mehmet Cudi Tuncer and İlhan Özdemir

Medicina 2025, 61(6), 960; https://doi.org/10.3390/medicina61060960 - 23 May 2025

Abstract

Background and Objectives: Osteosarcoma is a primary malignant bone tumor characterized by the proliferation of malignant mesenchymal cells and primarily affects children and adolescents. Hesperidin (Hes) interacts with various cellular targets and inhibits cancer cell proliferation by inducing apoptosis. However, the precise [...] Read more.

Background and Objectives: Osteosarcoma is a primary malignant bone tumor characterized by the proliferation of malignant mesenchymal cells and primarily affects children and adolescents. Hesperidin (Hes) interacts with various cellular targets and inhibits cancer cell proliferation by inducing apoptosis. However, the precise mechanisms underlying Hes-induced cell death in osteosarcoma cells remain unclear. This study aimed to investigate the effects of Hes and cisplatin (Cis) on the Bax/Bcl-2 apoptotic pathway in osteosarcoma cells. Materials and Methods: The human osteosarcoma cell line U2OS (Uppsala 2 Osteosarcoma) was treated with IC₅₀ concentrations of Hes and Cis for 48 h. Changes in the mRNA expression levels of Bax, Bcl-2, Caspase-3, and Survivin—key regulators of apoptosis—were analyzed using quantitative real-time PCR (qPCR). The synergistic and/or antagonistic interactions of the Hes and Cis combination were evaluated using Combenefit v2.021 software (Cambridge, UK). Results: The dose–response curve for Hes revealed a gradual reduction in cell viability, with an IC₅₀ value of 106 µM, while the IC₅₀ value for Cis was 4.83 µM. The levels of the inflammatory cytokines IL-1β, TNF-α, and IFN-γ were significantly decreased in the treatment groups compared to the control (p = 0.01). IL-6 levels also showed a marked decrease, particularly in the Hes and Cis groups, with high statistical significance (p = 0.002). Treatment with Hes and Cis significantly upregulated the mRNA expression of Bax and Caspase-3, while significantly downregulating Bcl-2 and Survivin mRNA levels (p < 0.05). Notably, Bax expression was highest in the Hes + Cis combination group. The combination treatment exhibited enhanced cytotoxicity, especially at higher concentrations, indicating a synergistic effect between the two compounds. Conclusions: This study is the first to demonstrate that Hes induces apoptosis in U2OS osteosarcoma cells and that its combination with Cis may enhance anticancer efficacy by activating apoptosis-related cell death pathways. Given the growing focus on combination therapies and cell death mechanisms in cancer research, these findings provide valuable insights into potential novel strategies for osteosarcoma treatment. Full article

(This article belongs to the Section Oncology)

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14 pages, 1916 KiB

Open AccessArticle

Clinical Characteristics and Genetic Variants in Children with PAX2 Mutation-Associated Disorders

by Yanyan Jin, Na Li, Zipei Chen, Ke Zeng, Jingjing Wang, Aiqin Sheng, Haidong Fu, Lidan Hu and Jianhua Mao

Medicina 2025, 61(6), 959; https://doi.org/10.3390/medicina61060959 - 22 May 2025

Abstract

Background and Objectives: PAX2 serves as a critical transcription factor integral to the process of embryogenesis. Variations in the PAX2 gene could result in the aberrant development of numerous organs. Despite the identification of numerous mutations within the PAX2 gene, the correlation between [...] Read more.

Background and Objectives: PAX2 serves as a critical transcription factor integral to the process of embryogenesis. Variations in the PAX2 gene could result in the aberrant development of numerous organs. Despite the identification of numerous mutations within the PAX2 gene, the correlation between specific genotypes has yet to be fully clarified. The objective of this study was to examine the clinical phenotypes and genotypes associated with PAX2 mutation-induced disorders in pediatric patients of Chinese descent. The aim of our study was to forecast the pathogenic potential of these genetic mutations and to ascertain possible correlations between genotypic variations and the clinical manifestations of disorders linked to PAX2 mutations. Materials and Methods: We recruited 14 pediatric subjects with PAX2 mutations, meticulously examining the clinical characteristics and genetic alterations present in these individuals. Computational techniques were utilized to evaluate the pathogenicity, stability, and biophysical characteristics. A range of computational tools were employed for this assessment, including PredictSNP, MAGPIE, iStable, Align GVGD, ConSurf, and SNP effect. Results: The age at onset ranged from prenatal to 12 years. Five patients progressed to end-stage renal disease. Proteinuria and bilateral renal hypoplasia were observed in 92% of cases. Ocular and auditory abnormalities were also noted. We identified eleven different PAX2 mutations, including five novel variants not previously reported in the literature. We predicted that all mutations, with the exception of p.F27-L33 del and N188S, exhibited high pathogenicity scores. In particular, R117P and R140W are strongly associated with disease pathogenicity and are likely to cause more significant damage than other gene mutants. Conclusions: This study expands the mutational and phenotypic spectrum of PAX2-related disorders in the pediatric population. The identification of five novel variants enhances our understanding of the genetic basis of these conditions. Despite recurrent mutations, marked phenotypic heterogeneity persists, underscoring the need for further research. Full article

(This article belongs to the Section Pediatrics)

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16 pages, 2553 KiB

Open AccessArticle

The Harmony and Balance of the Facial Organs for a Natural Face Beauty: A Novel Perspective for Cosmetic/Aesthetic Interventions

by Serdar Babacan and Mustafa Deniz

Medicina 2025, 61(6), 958; https://doi.org/10.3390/medicina61060958 - 22 May 2025

Abstract

Background and Objectives: Facial beauty has attracted the attention of human societies for centuries, but there is not yet a common universal consensus on the perception of beauty. The first stage of facial analysis is a frontal examination of the face. Therefore, [...] Read more.

Background and Objectives: Facial beauty has attracted the attention of human societies for centuries, but there is not yet a common universal consensus on the perception of beauty. The first stage of facial analysis is a frontal examination of the face. Therefore, determining the morphometric characteristics of the face and facial organs will help to perceive the nuances that influence the aesthetics specific to each person. The aim of our study is to develop regression equations that will design personalized morphometric features for reconstructive and aesthetic applications that will adapt to each individual’s personal face and facial organs and incorporate cultural elements. Materials and Methods: The study was conducted with 100 volunteers, 50 males (mean age = 21.48 ± 1.54 years) and 50 females (mean age = 21.26 ± 0.66 years). We took facial photographs of the participants in the Frankfurt Horizontal plane so that measurements of the face and facial organs could be made on digital media. We measured forty parameters (eight for face, twelve for eyes, eight for nose, and twelve for lips). We used Image J (ver. 1.51) software for the measurements. We used SPSS Ver. 28.0 for the statistical analysis of the data. Results: As a result of the comparative statistical analysis, statistically significant (p < 0.05) differences were found between men and women in the F5—lower face height, E5—palpebral fissure height, E6—distance between the margin of the upper eyelid and the eyebrow, E8—distance between the midpoint of the eye and the edge of the lower eyelid, N3—alar width, and N5—nasal root angle variables. Conclusions: On the basis of the correlation analyses, linear regression equations were developed to estimate the ideal natural facial morphometry of men and women by the means of variables that were highly correlated with each other. The equations developed will estimate the optimum morphometric features of a person for natural harmony and balance between the face and facial organs in accordance with the individual’s population and gender. We believe that our study will guide medical professionals who perform cosmetic/aesthetic interventions and also inspire software or artificial intelligence applications related to facial or facial organ design. Full article

(This article belongs to the Special Issue The Aesthetic Face of Orthognathic Surgery)

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19 pages, 3439 KiB

Open AccessSystematic Review

Virtual Reality Distraction for Reducing Pain and Anxiety During Percutaneous Cardiovascular Interventions: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

by Ebraheem Albazee, Abdullhadi Alrajehi, Fahad M. Alsahli, Abdillatef Alqemlas, Ahmad Aldhaen, Abdullah Alkandari, Hamad Alkandari and Waleed Alkanderi

Medicina 2025, 61(6), 957; https://doi.org/10.3390/medicina61060957 - 22 May 2025

Abstract

Background and Objectives: Percutaneous cardiovascular interventions (PCIs) have become a cornerstone in the management of cardiovascular diseases. However, patients often experience significant anxiety and pain during these procedures, which can negatively impact their overall experience and clinical outcomes. Virtual reality (VR) is an [...] Read more.

Background and Objectives: Percutaneous cardiovascular interventions (PCIs) have become a cornerstone in the management of cardiovascular diseases. However, patients often experience significant anxiety and pain during these procedures, which can negatively impact their overall experience and clinical outcomes. Virtual reality (VR) is an emerging non-pharmacological intervention designed to alleviate procedural anxiety and pain through immersive distraction techniques. Materials and Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) identified from PubMed, CENTRAL, Scopus, Google Scholar, and Web of Science up to November 2024. Primary outcomes were peri-procedural anxiety and pain; secondary outcomes included vital signs, procedure duration, and safety (e.g., delirium). Continuous data were pooled using a random-effect model and reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs) in Stata MP v.17. Certainty of evidence was assessed using the GRADE approach. Results: Ten RCTs involving 890 patients were included. VR distraction significantly reduced peri-procedural anxiety (SMD: –0.70; 95% CI: –1.15 to –0.26; p < 0.001). However, no significant differences were observed between groups for peri-procedural pain (SMD: –0.64; 95% CI: –1.45 to 0.16; p = 0.12), systolic blood pressure (SMD: –0.31; 95% CI: –1.23 to 0.61; p = 0.50), diastolic blood pressure (SMD: –0.25; 95% CI: –1.07 to 0.56; p = 0.54), heart rate (SMD: –0.44; 95% CI: –0.93 to 0.05; p = 0.08), respiratory rate (SMD: –0.93; 95% CI: –2.18 to 0.31; p = 0.14), or procedure duration (SMD: 0.07; 95% CI: –1.14 to 0.28; p = 0.49). Conclusions: VR significantly ameliorated peri-procedure anxiety in patients undergoing PCIs; however, it had no effect on peri-procedure pain or vital signs. This is based on uncertain evidence from heterogeneous studies, warranting further confirmation through large-scale RCTs. Full article

(This article belongs to the Section Cardiology)

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19 pages, 661 KiB

Open AccessArticle

Effect of Daily Lactococcus cremoris spp. Consumption Immobilized on Oat Flakes on Blood and Urine Biomarkers: A Randomized Placebo-Controlled Clinical Trial

by Panoraia Bousdouni, Aikaterini Kandyliari, Anastasia Kargadouri, Panagiota Potsaki, Olga I. Papagianni, Maria-Eleni Stylianou, Nikoletta Stathopoulou, Panagiota Andrianopoulou, Maria Kapsokefalou, Vasiliki Bountziouka, Anastasia Kolomvotsou, Ioanna Prapa, Gregoria Mitropoulou, Chrysoula Pavlatou, Andreas G. Tzakos, Panayiotis Panas, Yiannis Kourkoutas and Antonios E. Koutelidakis

Medicina 2025, 61(6), 956; https://doi.org/10.3390/medicina61060956 - 22 May 2025

Abstract

Background and Objectives: The development of non-dairy probiotic products is a challenge for the food industry, while cereals, as probiotic carriers, provide the means to incorporate probiotics, prebiotics, and fiber into the human diet. The present study investigated the effects of Lactococcus [...] Read more.

Background and Objectives: The development of non-dairy probiotic products is a challenge for the food industry, while cereals, as probiotic carriers, provide the means to incorporate probiotics, prebiotics, and fiber into the human diet. The present study investigated the effects of Lactococcus cremoris spp. immobilized on oat flakes on blood and urine biomarkers in a randomized placebo-controlled single-blind clinical trial. Materials and Methods: Fifty-four eligible participants were randomized into a placebo or probiotic group that consumed 5 g of oat flakes daily for 12 weeks. Blood and urine samples were collected at the baseline, 6 weeks, and 12 weeks to assess the glycemic, lipemic, inflammatory, immunological, and antioxidant biomarkers, as well as the vitamin levels. Results: The intervention group exhibited a significant reduction in their hs-CRP levels (p = 0.002) and a trend toward decreased IL-6 levels (p = 0.035) at week 12 compared to the control group, suggesting a potential anti-inflammatory effect. Additionally, a significant reduction in insulin levels was observed in the probiotic group at week 6, with a clinical trend toward differentiation despite the absence of statistically significant differences between the groups. Furthermore, there were promising results regarding certain biomarkers, such as vitamin B12 and cortisol levels, in the probiotic group. Conclusions: The twelve-week consumption of Lactococcus cremoris spp. immobilized on oat flakes resulted in improvements in inflammatory, metabolic, and stress-related biomarkers. These results support the examined concept of non-dairy probiotic products, though further research is needed to confirm their efficacy and clarify their underlying mechanisms. Full article

(This article belongs to the Special Issue Public Health in the Post-pandemic Era)

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