Editor’s Choice Articles

Background: Regenerative therapies have emerged in recent years. In particular, their utility in managing androgenetic alopecia—the most prevalent hair loss condition worldwide, affecting up to half of adults—is an active area of research. Navigating this space can be challenging for physicians due to widespread commercialization, lack of high-quality evidence, and an evolving regulatory landscape. Objective: To critically review recently published evidence (2020–2025) on platelet-rich plasma, photobiomodulation, stem cells, and exosomes for the treatment of androgenetic alopecia. Methods: A scoping review was conducted using PubMed, Embase (Ovid) and the Cochrane Controlled Register of Trials in February and November of 2025. Combination therapies were excluded. Results and Conclusions: Platelet-rich plasma is the most studied modality, with emerging investigations into newer formulations such as leukocyte-rich and pure platelet-rich plasma. However, recent studies are limited by inconsistent reporting of cellular composition, short follow-up durations, and a lack of comparative data on treatment protocols. The efficacy of photobiomodulation as a monotherapy remains debated, with inconsistent reporting of device parameters. Stem cells and exosomes show promising, though still limited, clinical evidence in inducing hair regrowth. Standardization of these therapies is crucial, with emphasis on transparency, reproducibility, and patient safety. Full article

Background and objectives: Pain neuroscience education (PNE) is a therapeutic strategy aimed at reconceptualizing pain in patients with chronic low back pain (CLBP). This systematic review with a meta-analysis (SRMA) aimed to assess the effectiveness of PNE in reducing pain, disability, kinesiophobia, and catastrophizing in patients with CLBP at the end of the intervention, and at 1 and 3 months of follow-up. Materials and Methods: Following PRISMA guidelines, an SRMA was conducted after searching in PubMed Medline, Scopus, Web of Science, and PEDro databases from inception up to June 2025. The inclusion criteria agreed with the PICOS tool: population (patients with CLBP), intervention (PNE), comparator (physiotherapy or non-intervention), outcomes (pain, disability, kinesiophobia, and catastrophizing), and study design (randomized controlled trials (RCTs) and pilot RCTs). The PEDro scale was used to assess the methodological quality and risk of bias of the RCTs included. The pooled effect was assessed using the Cohen standardized mean difference (SMD) and its 95% confidence interval (95% CI) in a random-effects model. Results: Fifteen RCTs, including data from 810 patients (43.7 ± 5.2 years; 61% female) with CLBP were included. The mean methodological quality of the RCTs included was good (6.8 ± 1.1 on the PEDro scale). Selection, performance, and detection were the most important biases identified. Our meta-analysis demonstrated, at the end of the intervention, and at 1 and 3 months of follow-up, respectively, that PNE is effective in reducing pain intensity (SMD = −0.65, p = 0.005; SMD = −1.1, p < 0.001; SMD = −1; p < 0.001), disability (SMD = −0.6, p = 0.009; SMD = −0.78, p = 0.002; SMD = −0.84; p = 0.004), and kinesiophobia (SMD = −1.12, p < 0.001; SMD = −1.51, p < 0.001; SMD = −1.57; p = 0.001). In reducing catastrophizing, PNE was largely effective at the end of intervention (SMD = −0.9, p = 0.016) and at 1 month of follow-up (SMD = −1.36, p = 0.007). Conclusions: Our findings demonstrate that PNE is an effective therapeutic approach for the management of CLBP, reducing pain, disability, kinesiophobia, and catastrophizing in patients with CLBP. Full article

Background: Chronic pain affects nearly one in five adults worldwide and remains a major healthcare burden due to its persistence, multidimensional impact, and resistance to conventional therapies. The opioid crisis has further highlighted the urgent need for safer and more effective alternatives. Psilocybin, a serotonergic psychedelic compound, has re-emerged as a potential therapeutic option for chronic pain given its effects on neuroplasticity, neuroinflammation, and emotional regulation. Methods: This narrative review synthesized evidence from published preclinical and clinical studies. The focus was on the mechanisms of action of psilocybin, animal models of neuropathic and inflammatory pain, and early human trials exploring its effects on pain, mood, and quality of life. Results: Preclinical studies demonstrated that psilocybin promotes synaptogenesis via BDNF-TrkB signalling, modulates 5-HT2A receptor activity, and reduces neuroinflammatory processes, leading to persistent analgesic and anxiolytic effects. Animal models of chemotherapy-induced neuropathy and inflammatory pain showed long-lasting antinociceptive responses. Clinical studies, though limited, reported improvements in depression, anxiety, resilience, and quality of life in patients with advanced cancer and chronic conditions, with preliminary evidence of analgesic benefit. Conclusions: Psilocybin shows promise as a multidimensional therapy for chronic pain, addressing both sensory and affective components. However, ethical issues, safety concerns, and regulatory barriers necessitate careful management, and robust randomized controlled trials are essential to confirm efficacy and guide clinical translation. Full article

Background/Objectives: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly evolved from a theoretical concept to a crucial component of modern metabolic care. This review explores the comprehensive development journey of semaglutide, drawing on evidence from medicinal chemistry, animal studies, initial human trials, the pivotal SUSTAIN and STEP programs, and real-world post-marketing surveillance. Methods: We conducted a detailed analysis of preclinical data sets, Phase I–III clinical trials, regulatory documents, and pharmaco-epidemiological studies published between 2008 and 2025. Results: Through strategic molecular modifications, such as specific amino-acid substitutions and the addition of a C18 fatty-diacid side chain to enhance albumin binding, the half-life of the peptide was extended to approximately 160 h, allowing for weekly dosing. Studies in rodents and non-human primates showed that semaglutide effectively lowered blood glucose levels, reduced body weight, and preserved β-cells while maintaining a favorable safety profile. Phase I trials confirmed consistent pharmacokinetics and tolerability, while Phase II trials identified 0.5 mg and 1.0 mg once weekly as the most effective doses. The extensive SUSTAIN program validated significant reductions in HbA1c levels and weight loss compared to other treatments, as well as a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). Subsequent STEP trials expanded the use of semaglutide to chronic weight management, revealing that nearly two-thirds of patients experienced a body weight reduction of at least 15%. Regulatory approvals from the FDA, EMA, and other regulatory agencies were obtained between 2017 and 2021, with ongoing research focusing on metabolic dysfunction-associated steatohepatitis, cardiovascular events, and chronic kidney disease. Conclusions: The trajectory of semaglutide exemplifies how intentional peptide design, iterative translational research, and outcome-driven clinical trial design can lead to groundbreaking therapies for complex metabolic disorders. Full article

Fuchs endothelial corneal dystrophy (FECD) is the leading cause of endothelial failure requiring keratoplasty in industrialised nations. Descemet membrane endothelial keratoplasty (DMEK) has become the gold-standard surgical therapy, yet it is constrained by limited donor tissue and a steep learning curve. This narrative review summarises current and emerging therapeutic strategies for FECD. We describe conventional endothelial keratoplasty and its outcomes, tissue-sparing procedures such as descemetorhexis without endothelial keratoplasty (DWEK) and quarter-DMEK, regenerative approaches including cultured endothelial cell injection and synthetic corneal substitutes, and adjunctive innovations ranging from Rho-associated kinase inhibitors to artificial intelligence-assisted diagnostics. Challenges surrounding donor shortages, variable clinical outcomes, regulatory hurdles and cost are critically appraised. We conclude by outlining future directions that are likely to combine advanced surgical techniques with cell-based and biomaterial solutions to deliver accessible, long-term restoration of vision for patients with FECD. Full article

Background: The incidence and prognosis of high-grade gliomas differ according to histopathological and molecular features. The WHO 2021 CNS classification emphasized IDH status, but historical cohorts often lacked systematic molecular profiling. Methods: We conducted a retrospective population-based study including adult patients diagnosed with IDH-wildtype glioblastoma or IDH-mutant astrocytoma in a Spanish tertiary center (2011–2021). Incidence trends and survival outcomes were analyzed according to treatment modality and sex. Results: A total of 1057 patients were included: 530 (50.1%) with IDH-wildtype glioblastoma and 137 (13%) with IDH-mutant astrocytoma. Incidence of both subtypes significantly increased during the study period (p < 0.01). Median overall survival (OS) was 12.3 months for IDH-wildtype glioblastoma and 38.4 months for IDH-mutant astrocytoma. Multimodal therapy (surgery, radiotherapy, chemotherapy) significantly improved OS and progression-free survival (PFS) in both subgroups (p < 0.001). Male sex was associated with longer OS in both tumor types (p < 0.05). Conclusions: IDH-wildtype glioblastoma shows persistently poor outcomes despite increasing incidence, while IDH-mutant astrocytoma demonstrates better survival, particularly in male patients and those receiving multimodal therapy. These findings reflect real-world practice and provide epidemiological and survival data from Southern Europe to guide future clinical and public health strategies. Full article

Background: This narrative review examines the role of artificial intelligence (AI) in bowel sound analysis for the diagnosis and management of inflammatory bowel disease (IBD). Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, presents a significant clinical burden due to its unpredictable course, variable symptomatology, and reliance on invasive procedures for diagnosis and disease monitoring. Despite advances in imaging and biomarkers, tools such as colonoscopy and fecal calprotectin remain costly, uncomfortable, and impractical for frequent or real-time assessment. Meanwhile, bowel sounds—an overlooked physiologic signal—reflect underlying gastrointestinal motility and inflammation but have historically lacked objective quantification. With recent advances in artificial intelligence (AI) and acoustic signal processing, there is growing interest in leveraging bowel sound analysis as a novel, non-invasive biomarker for detecting IBD, monitoring disease activity, and predicting disease flares. This approach holds the promise of continuous, low-cost, and patient-friendly monitoring, which could transform IBD management. Objectives: This narrative review assesses the clinical utility, methodological rigor, and potential future integration of artificial intelligence (AI)-driven bowel sound analysis in inflammatory bowel disease (IBD), with a focus on its potential as a non-invasive biomarker for disease activity, flare prediction, and differential diagnosis. Methods: This manuscript reviews the potential of AI-powered bowel sound analysis as a non-invasive tool for diagnosing, monitoring, and managing inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Traditional diagnostic methods, such as colonoscopy and biomarkers, are often invasive, costly, and impractical for real-time monitoring. The manuscript explores bowel sounds, which reflect gastrointestinal motility and inflammation, as an alternative biomarker by utilizing AI techniques like convolutional neural networks (CNNs), transformers, and gradient boosting. We analyze data on acoustic signal acquisition (e.g., smart T-shirts, smartphones), signal processing methodologies (e.g., MFCCs, spectrograms, empirical mode decomposition), and validation metrics (e.g., accuracy, F1 scores, AUC). Studies were assessed for clinical relevance, methodological rigor, and translational potential. Results: Across studies enrolling 16–100 participants, AI models achieved diagnostic accuracies of 88–96%, with AUCs ≥ 0.83 and F1 scores ranging from 0.71 to 0.85 for differentiating IBD from healthy controls and IBS. Transformer-based approaches (e.g., HuBERT, Wav2Vec 2.0) consistently outperformed CNNs and tabular models, yielding F1 scores of 80–85%, while gradient boosting on wearable multi-microphone recordings demonstrated robustness to background noise. Distinct acoustic signatures were identified, including prolonged sound-to-sound intervals in Crohn’s disease (mean 1232 ms vs. 511 ms in IBS) and high-pitched tinkling in stricturing phenotypes. Despite promising performance, current models remain below established biomarkers such as fecal calprotectin (~90% sensitivity for active disease), and generalizability is limited by small, heterogeneous cohorts and the absence of prospective validation. Conclusions: AI-powered bowel sound analysis represents a promising, non-invasive tool for IBD monitoring. However, widespread clinical integration requires standardized data acquisition protocols, large multi-center datasets with clinical correlates, explainable AI frameworks, and ethical data governance. Future directions include wearable-enabled remote monitoring platforms and multi-modal decision support systems integrating bowel sounds with biomarker and symptom data. This manuscript emphasizes the need for large-scale, multi-center studies, the development of explainable AI frameworks, and the integration of these tools within clinical workflows. Future directions include remote monitoring using wearables and multi-modal systems that combine bowel sounds with biomarkers and patient symptoms, aiming to transform IBD care into a more personalized and proactive model. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide. This study evaluates the predictive value of Carcinoembryonic Antigen (CEA) in identifying CRC recurrence following surgical resection. Methods: This retrospective study was realized in the Oncology Institute in Cluj-Napoca and included 88 patients diagnosed with CRC. Clinical, demographic, and tumor-specific data were collected, including TNM staging, tumor histology. CEA levels were recorded before surgery. Receiver Operating Characteristic (ROC) analysis was performed to determine the diagnostic accuracy of CEA in predicting tumor relapse, and the sensitivity and specificity of various CEA cut-off values were assessed. Results: Most patients presented with advanced-stage tumors (T3/T4, 80.6%). CEA levels were significantly higher in patients with lymphatic and perineural invasion and in those with metastases (mean CEA: 45.0 ng/mL for M1 vs. 13.2 ng/mL for M0, p = 0.032). ROC analysis revealed an area under the curve (AUC) of 0.877 (95% CI: 0.763–0.949). A CEA cut-off value of 11.73 ng/mL yielded 100% sensitivity and 74.5% specificity for detecting recurrence; Conclusions: CEA is a valuable non-invasive biomarker for predicting CRC relapse, with high sensitivity and acceptable specificity. Regular CEA monitoring post-surgery can facilitate early detection of recurrence, improving prognosis. Full article

Wharton’s jelly (WJ), the mucoid connective tissue of the umbilical cord, provides essential protection to the umbilical vessels against mechanical stress. While research into WJ-derived stem cells for regenerative medicine has surged, the clinical significance of its in utero pathologies remains less explored. This review synthesizes the current literature on the pathophysiology of WJ abnormalities and their direct impact on fetal and neonatal outcomes. Pathologies are broadly categorized as quantitative (absence/reduction or excess/edema) and structural (pseudocysts, mucoid degeneration). A reduction or segmental absence of WJ critically compromises cord integrity, leading to vascular compression and is a direct cause of stillbirth, fetal growth restriction (FGR), and intrapartum distress. Conversely, excessive WJ or edema is associated with maternal diabetes and fetal hydrops and can also impair hemodynamics. Umbilical cord pseudocysts, arising from focal WJ degeneration, are significant markers for severe chromosomal abnormalities, particularly Trisomy 18 and 13, and other structural defects, especially when persistent or multiple. Sonographic measurement of WJ area shows promise as a surrogate for placental function, with decreased area correlating with placental pathology and FGR. However, significant diagnostic challenges persist, particularly the prenatal detection of segmental WJ absence, a “silent” pathology often discovered only after a catastrophic event. This review highlights the critical role of WJ integrity in determining perinatal outcomes and underscores the urgent need for improved diagnostic modalities and standardized management protocols to mitigate associated risks. Full article

Introduction: This study will explore the effectiveness of current extracorporeal shockwave therapies in ulcer healing in diabetic foot disease compared to the standard of care. Methods: The systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. The electronic databases WoS, EMBASE, MEDLINE Complete, CINAHL Complete, Academic Search Ultimate, AMED-The Allied and Complementary Medicine Database, Scopus and PubMed searched for the outcome rate of complete ulcer healing. The risk of bias assessment was conducted using the tool recommended by the Cochrane Collaboration (Robvis Tool). Statistical analysis included the individual and combined result of the studies, heterogeneity test, the effect size, sensitivity analysis, and publication bias tests. Results: Eight randomized controlled trials (RCTs) with a total of 672 patients were included in this study. This meta-analysis showed a higher rate of complete ulcer healing in groups receiving extracorporeal shockwave therapies (OR = 2.747 [1.965, 3.841], p < 0.01, I² =0.02) compared to control groups. Conclusions: In conclusion, the results of this meta-analysis show that extracorporeal shockwave therapies, when used as an adjunctive treatment, demonstrate significantly higher ulcer healing rates compared to standard of care. Extracorporeal shockwave therapies should be taken into account as a valuable adjunct to standard care for diabetic foot ulcer treatment. Full article

Right heart failure (RHF) remains an under-recognized yet devastating condition in critically ill and chronic patients, frequently complicating cardiac surgery, pulmonary embolism, advanced heart failure, sepsis and left ventricular assist device (LVAD) implantation. Despite growing awareness, clinical decision making is still hampered by the complex pathophysiology, limitations in diagnosis and a fragmented therapeutic landscape. In recent years, progress in hemodynamic phenotyping, advanced echocardiographic and biomarker-based assessment, and the development of mechanical circulatory support (MCS) systems, including percutaneous and surgical right ventricle assist devices (RVAD), veno-arterial extracorporeal membrane oxygenation (V-A ECMO), Impella RP (right percutaneous) or BiPella (Impella CP/5.0/5.5 + Impella RP) has expanded the armamentarium for managing RHF. This review synthetizes current evidences on the anatomical, physiological and molecular underpinnings of RHF, delineates the distinction and continuum between acute and chronic forms and provides a comparative analysis of diagnostic tools and MCS strategies. By integrating mechanistic insights with emerging clinical frameworks, the review aims to support earlier recognition, tailored management and innovative therapeutic approaches for this high-risk population. Full article

Left ventricular diastolic dysfunction (LVDD) is characterized by impaired ventricular relaxation and increased chamber stiffness during diastole, resulting in increased left ventricular filling pressures. It represents a highly prevalent yet frequently underdiagnosed cardiac condition with significant clinical implications, serving as a major contributor to heart failure with preserved ejection fraction (HFpEF), particularly among elderly individuals and those with hypertension, diabetes mellitus, obesity, or coronary artery disease. Multiple studies have identified the progression of LVDD as a marker of adverse prognosis, associated with increased morbidity and mortality, highlighting the importance of early recognition and targeted therapeutic strategies to improve diastolic function and clinical outcomes. This review summarizes the pathophysiology, current diagnostic strategies, and treatment options for LVDD, emphasizing its importance in clinical practice. Full article

Background: Juvenile fibromyalgia (JFM) is a chronic pain disorder characterised by widespread musculoskeletal pain, functional impairment, fatigue, and mood disturbances. Treatment remains challenging, considering the multifactorial nature of the condition and the limited high-quality evidence supporting pharmacological or non-pharmacological interventions. Objectives: This review aimed to critically appraise level I evidence from randomised controlled trials assessing the efficacy and safety of pharmacological and non-pharmacological treatments for adolescents with JFM. Methods: Seven published peer-reviewed clinical trials were examined, including studies investigating duloxetine, milnacipran, pregabalin, cognitive-behavioural therapy (CBT), and the integrated Fibromyalgia Integrative Training Teens (FIT) program, which combines CBT with neuromuscular training. Outcomes of interest included pain intensity, functional disability, depression symptoms, physical activity, and adverse events. Results: Pharmacological agents such as duloxetine, milnacipran, and pregabalin demonstrated modest improvements in pain, but failed to produce consistent benefits in function or mood, and were associated with a high incidence of adverse effects. CBT significantly improved functional disability and depression symptoms, yet it had a limited impact on pain reduction or objectively measured activity levels. The FIT Teens program showed superior outcomes in pain intensity and biomechanical function compared to CBT alone, suggesting a synergistic effect of combining psychological and physical reconditioning strategies. Conclusions: Current evidence supports the use of multimodal treatment approaches in JFM. Non-pharmacological interventions, particularly when integrated with structured exercise, offer meaningful benefits with minimal safety concerns. Larger, methodologically rigorous trials are needed to establish optimal treatment pathways and long-term outcomes for this complex and underserved paediatric population. Full article

Background: Brain metastases (BMs) are a common and challenging complication of non-small cell lung cancer (NSCLC), historically associated with a poor prognosis. The development of targeted therapies, specifically tyrosine kinase inhibitors (TKIs) for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene alterations, has significantly improved treatment outcomes. Methods: This article reports and evaluates the efficacy of different generations of TKIs for NSCLC with BMs. The primary endpoints assessed are intracranial objective response rates (IC-ORR), progression-free survival (PFS), and overall survival (OS). The analysis considers TKIs as monotherapy and in combination with radiotherapy. It also examines the impact of newer generation TKIs with enhanced blood–brain barrier (BBB) penetration on intracranial control. The report further discusses the integration of systemic therapy with local modalities like stereotactic radiosurgery (SRS) and the safety profiles of these agents, including central nervous system (CNS) and metabolic adverse events. Results: Newer generation TKIs demonstrate significantly enhanced BBB penetration, resulting in superior intracranial control compared to older generations. These agents show remarkable intracranial activity, contributing to improved IC-ORR, PFS, and OS. The optimal integration of systemic therapy with local modalities, such as SRS, is still under investigation. Treatment with these TKIs is associated with distinct safety profiles, including novel CNS and metabolic adverse events, which require careful management due to prolonged treatment durations. Conclusions: The management of CNS metastases in NSCLC is evolving towards more proactive and personalized therapeutic strategies. Newer generation TKIs have profoundly reshaped the treatment landscape by offering superior intracranial control. Further research is needed to determine the optimal integration of these systemic therapies with local modalities and to effectively manage the associated adverse events. Full article

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent condition characterized by pelvic pain and urinary symptoms with multifactorial aetiology. Standard treatments, including alpha-blockers, often have limited long-term effectiveness. This study aimed to evaluate the efficacy and safety of a standardized pollen extract (Deprox^® 500), alone or in combination with alpha-blockers, in reducing CP/CPPS symptoms and the need for rescue medication. Methods: This prospective, multicentre study included 207 male patients with CP/CPPS treated at two Romanian urology centres between January 2023 and January 2025. Patients were divided into three groups: Group A—alpha-blocker monotherapy; Group B—standardized pollen extract monotherapy; and Group C—combination therapy with standardized pollen extract and alpha-blocker. Symptom severity and treatment response were evaluated using the validated English versions of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), and International Index of Erectile Function-5 (IIEF-5), all of which were translated into Romanian for use in this study. Results: Groups B and C both demonstrated significantly greater reductions in pelvic pain and urinary symptoms compared to Group A (p = 0.01), with marked improvements in NIH-CPSI and IPSS. Conclusions: A standardized pollen extract used alone or in combination with an alpha-blocker significantly improved CP/CPPS symptoms and reduced the need for NSAID rescue medication. These findings support its potential as a safe and effective therapeutic option. Full article

This review explores the impact of maternal obesity on pregnancy outcomes, emphasizing its significant global health challenge and profound implications for both mothers and infants. It influences the timing and mode of childbirth, elevating the risk of conditions like hypertensive disorders, cesarean delivery, and gestational diabetes mellitus. The review focuses on analyzing how maternal obesity affects postpartum recovery, birth timing, and delivery methods. Relevant studies were identified using PubMed and Scopus. Findings indicate that obese pregnant women are at higher risk for medically indicated preterm birth, scheduled and emergency cesarean sections, and labor induction. Postpartum recovery is often prolonged due to breastfeeding challenges, infection risks, and delayed wound healing. Additionally, maternal obesity increases the likelihood of fetal complications such as macrosomia and long-term metabolic disorders. These results highlight the importance of personalized treatments and early weight control to improve the health of both mother and baby. A comprehensive approach integrating clinical care, public health initiatives, and policy measures is essential to reduce pregnancy complications associated with obesity. Full article

Background/Objectives: The reciprocal relationship between Systemic Lupus Erythematosus (SLE) and pregnancy continues to elude the scientific community’s approaches for a clear understanding. Multiple studies have reached dissimilar results regarding the impact that SLE exerts on pregnancy, whilst the potential risks of lupus pregnancies continue to encumber women of childbearing age. Whether SLE predisposes to a complicated pregnancy and conversely whether pregnancy impacts the progression of the disease is aimed to be assessed by this systematic review. Methods: A thorough search of original research articles was conducted using online databases (PubMed, Google Scholar), initially identifying 877 potential studies. Results: Upon further assessment for relevance and eligibility, 65 articles were selected for detailed analysis. Conclusions: We concluded that, even though advanced approaches have optimized SLE prognosis and treatment, the complexity of the disease requires further extensive study in order to grasp the mechanism behind the susceptibility to adverse complications. SLE pregnancy cannot be considered without risk. Comprehensive, multidisciplinary, and continuous monitoring of the disease course prior to, during, and after pregnancy is necessary to ensure optimal recovery and minimal maternal and fetal complications. Tailored treatments and novel biomarkers would move us towards precise patient-centered care that addresses each patient’s unique disease profile and pregnancy needs, ultimately improving both maternal and fetal outcomes in women with systemic lupus erythematosus. Full article

Background: Chronic pain represents a major therapeutic challenge due to the limited efficacy and tolerability of conventional pharmacological treatments. Equisetum arvense L., a medicinal plant with potent antioxidant properties, and palmitoylethanolamide (PEA), an endogenous fatty acid amide with well-established anti-inflammatory and analgesic effects, are increasingly recognised as promising nutraceutical agents. Methods: This prospective, single-centre clinical trial aimed to evaluate the efficacy and safety of a novel oral supplement (Assonal^®PEA) combining 600 mg of PEA and 300 mg of Equisetum arvense L. in improving the reduction of pain and quality of life in patients with chronic pain, also obtaining information on the patient’s state of satisfaction after the treatment. Fifty patients suffering from chronic pain (low back pain and radiculopathy) for two months were enrolled and received the supplement over eight weeks in a tapered regimen (two tablets daily for two weeks, followed by one tablet daily). Results: Clinical outcomes were evaluated using validated instruments, including the Numeric Pain Rating Scale (NPRS), Verbal Rating Scale (VRS), Short-Form McGill Pain Questionnaire (SF-MPQ), Global Perceived Effect (GPE), and EuroQol-5D-5L. Results showed a significant decrease in pain intensity (NPRS: −3.8 points; VRS: −2.1 points; p < 0.0001), along with meaningful improvements in patient-perceived benefit, pain descriptors, and quality of life (EQ-5D-5L: +35%; p < 0.0001). Conclusions: These findings endorse the use of this novel PEA–Equisetum arvense formulation as a safe, well-tolerated, and potentially effective supplementary intervention for managing chronic pain. No adverse events were reported, and the overall response rate reached 94%. Full article

Background: Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous neurodegenerative disorder with highly variable progression and survival. Identifying early prognostic indicators is essential for patient stratification and management. Objectives: To evaluate clinical, respiratory, and functional predictors of survival in a prospective cohort of ALS patients over a three-year period. Methods: A cohort of 44 ALS patients was followed from 2022 to 2025. Demographic and anthropometric characteristics, clinical data including ALS subtypes and phenotypes, site of onset, revised ALS functional rating scale (ALSFRS-R) and subscores, ALSFRS-R progression rate, time to diffusion and generalization, spirometric parameters, and progression patterns were assessed. Survival analysis was performed using Kaplan–Meier estimates and univariate and multivariate Cox proportional hazard regression analysis. Results: The overall median survival time was 53 months. Univariate Cox regression revealed that older age at onset, shorter diagnostic delay, lower respiratory function, lower vitamin D levels, and rapid vertical progression were associated with reduced survival. Bulbar-onset phenotype and rapid disease progression rate (ΔPR) were significant predictors of mortality. Specific ALSFRS-R subscores also showed prognostic relevance. A longer time to diffusion as well as a longer time to generalization were significantly associated with prolonged survival. Multivariate analysis confirmed the independent prognostic value of ΔPR, time to diagnosis, and ALSFRS-R swallowing and handwriting subscores. Conclusions: This study supports the prognostic value of previously studied clinical and paraclinical markers in ALS and proposes novel predictors, ALSFRS-R handwriting, and time to diffusion, which require further validation in larger prospective cohorts. Full article

Background/Objectives: Tubal dysfunction may be a contributing factor in up to 35% of infertility cases, rendering tubal patency assessment a vital component of the infertility workup. In this review we examined the diagnostic efficacy and tolerability of hysterosalpingo-foam sonography (HyFoSy) and compared it to hysterosalpingography (HSG) and hysterosalpingo-contrast sonography (HyCoSy). Methods: Online databases were systematically searched and evaluated according to the PRISMA 2020 guidelines. Statistical heterogeneity was assessed. Diagnostic sensitivity, specificity and inter-method agreement were evaluated, along with mean pain scores. Results: This analysis included data from 9 studies and 1354 patients with conclusive diagnostic data from 2422 tubes and 1294 patients with data on intra-procedural pain. With regard to HyFoSy and HyCoSy comparison, pooled sensitivity was 87% and 69%, respectively (p = 0.074), while pooled specificity was 95% and 85%, respectively, favoring HyFoSy (p < 0.001). HyFoSy was more tolerable with regard to pain, but this was not statistically significant. Regarding the HyFoSy and HSG comparison, pooled Cohen’s k was 0.38, indicating fair-moderate agreement. In subsequent analysis, with HSG as a reference standard, HyFoSy demonstrated low sensitivity (61%) but high specificity (87%). With regard to experienced pain, HyFoSy and HSG had a difference of 2.4 units on a 10-point scale, favoring HyFoSy (p < 0.001). Conclusions: HyFoSy was superior to HyCoSy and may be used as a first-line tubal assessment method, with HSG being utilized in inconclusive cases. However, further research is still required due to the small number of available studies. Full article

Background: The use of benzodiazepines among university students has been scarcely investigated. This situation raises particular concerns in medical students, due to their exposure to stressful situations and, especially, their familiarity with psychotropic drugs. Material and methods: A descriptive cross-sectional observational study was conducted using an anonymous online survey disseminated among universities in the Community of Madrid during April 2024. Results: 25.07% of students stated they had used benzodiazepines at least once, especially from the third academic year onwards. The prevalence was higher among medical students (32.34%). Use was mainly occasional, although 20.21% reported daily use. Among the reasons for use, managing academic stress reached 45.74%. Up to 15.96% of respondents reported a feeling of dependence, and 32.26% noticed concentration difficulties as a side effect of benzodiazepine use. Conclusions: Benzodiazepine use is a relevant phenomenon among university students, with particular incidence in medical degrees. Its onset usually coincides with advanced stages of the degree, which underscores the need for preventive interventions tailored to the academic environment and for the rational use of psychotropic drugs in young populations. Full article

Objective. This randomized controlled trial evaluated the efficacy of lavender–neroli oil aromatherapy in managing dental anxiety and pain in children undergoing inferior alveolar nerve block (IANB) anesthesia. Methods. Fifty-four children aged 6–11 years were randomly assigned to either a control group or an aromatherapy group. Children in the control group were asked to wear a regular scented-free nitrous oxide mask. Children in the control group were asked to wear a regular scented-free nitrous oxide mask. Children in the intervention group inhaled lavender–neroli oil via a nitrous oxide nasal mask for 5 min before and during IANB administration. Anxiety and pain levels were assessed pre-and post-treatment using the Facial Image Scale (FIS), Face–Legs–Activity–Cry–Consolability (FLACC) scale, and vital signs (heart rate, blood pressure, oxygen saturation). The collected data were statistically analyzed using SPSS software 20. The Mann–Whitney U test was used for analyzing FIS results, and the independent T test and T Paired test were used for analyzing heart rate, blood pressure, and oxygen saturation results. Results. Results demonstrated significantly lower anxiety, heart rate, blood pressure, and pain scores in the aromatherapy group compared to the control group (p < 0.05), with no significant change in oxygen saturation. Conclusions. Lavender–neroli aromatherapy is a safe, low-cost, and effective adjunct to reduce anxiety and discomfort during pediatric dental anesthesia. Full article

Background/Objectives: Balance, postural control, and functional independence are essential components for the autonomy of people with neurological conditions. Robotic technologies such as the Lokomat^® have emerged as promising tools in rehabilitation, but their effectiveness when integrated into functional programs requires further evidence. The objective of this study was to evaluate the impact of an intensive robotic intervention on these three functional variables. Methods: A single-group, quasi-experimental pretest–posttest study was conducted with 136 participants who received a robotic rehabilitation intervention using the Lokomat^® device, and focused on functional tasks over several weeks. Balance (using the Berg scale), postural control (using the PASS), and functional independence (using the Barthel index) were assessed, comparing pre- and post-intervention results using parametric and non-parametric tests. Results: The results showed statistically significant improvements in all three variables after the intervention. The mean Berg score increased from 11.76 to 21.91 points (p < 0.001), postural control increased from 15.53 to 21.90 points (p < 0.001), and the Barthel index increased from 24.71 to 41.76 points (p < 0.001). In all cases, the effect sizes were large (d > 0.90). Conclusions: A rehabilitation program including intensive, task-oriented Lokomat^® training was associated with improvements in balance, postural control, and functional independence. Given the single-group design without a control arm, these findings reflect associations and do not establish causality. Full article

Thoracic aortic aneurysm and dissection (TAAD) encompasses a clinically heterogeneous group of diseases characterized by high morbidity and mortality. Genetic studies over the past two decades have significantly expanded our understanding of the molecular landscape underlying heritable TAAD, revealing contributions from multiple interconnected biological pathways. This review systematically summarizes more than 75 genes implicated in TAAD pathogenesis, categorizing them according to major mechanistic roles including TGF-β signaling, extracellular matrix remodeling, smooth muscle cell contractility and cytoskeletal regulation, cell–matrix and cell–cell adhesion, metabolic processes, ion transport, and transcriptional regulation. Special emphasis is placed on emerging genes with variable or overlapping clinical phenotypes, dual-mechanism candidates, and their implications for personalized clinical management, including surveillance and surgical intervention thresholds. The integration of molecular insights into clinical practice, along with cautious consideration of genes of uncertain significance, promises to enhance diagnostic precision and risk stratification in individuals and families affected by heritable aortic disease. Full article

Pirfenidone (PFD) is a pyridine-like compound most well-known for its use in idiopathic pulmonary fibrosis (IPF). However, its broad anti-inflammatory and anti-fibrotic actions make PFD a candidate for other scarring diseases. This review examines the use of PFD for dermatologic conditions. The literature supports the potential for PFD to decrease scarring in a variety of skin conditions. Both oral and topical preparations have been shown to be effective at aiding skin healing. Early clinical evidence demonstrates significant improvements in hypertrophic burn scars, reduction in fibrosis in localized scleroderma, and accelerated epithelialization of skin graft donor sites. These clinical outcomes are supported by PFD’s modulation of the transforming growth factor-beta (TGF-β) pathway, which plays a central role in skin fibrosis and scarring. Evidence in this review suggests topical PFD can be used to fill a clinical need for local anti-fibrotic therapies. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) complicates approximately 14% of pregnancies worldwide, its prevalence rising with increasing maternal age and obesity. While maternal hyperglycemia is traditionally associated with fetal overgrowth and large-for-gestational-age (LGA) neonates, emerging evidence indicates that GDM may also contribute to small-for-gestational-age (SGA) outcomes. Methods: A comprehensive literature search was conducted using multiple databases, including PubMed, Web of Science, and ScienceDirect, to identify studies related to gestational diabetes mellitus, fetal growth outcomes such as small for gestational age and large for gestational age, and associated pathophysiological mechanisms. Results: This narrative review explores the mechanisms by which GDM influences fetal growth, emphasizing the dual risk of excessive and restricted intrauterine growth. Fetal macrosomia typically results from chronic maternal hyperglycemia, leading to increased transplacental glucose delivery and fetal hyperinsulinemia. In contrast, SGA outcomes are a consequence of vascular and endothelial dysfunction, placental insufficiency, or excessively restrictive glycemic control that limit the availability of nutrients. Both extremes of fetal growth carry a myriad of significant perinatal and long-term metabolic risks. Conclusions: Understanding the diverse pathways through which GDM affects fetal growth is essential for developing individualized clinical strategies. Full article

Background: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy characterized by rapid growth, early metastatic dissemination, and a dismal prognosis. For decades, treatment paradigms remained largely stagnant, particularly for extensive-stage disease (ES-SCLC). However, the last five years have witnessed a significant evolution in the therapeutic landscape. Methods: The information for this article was gathered by synthesizing data from several key sources. This article synthesizes the evidence supporting current standards of care for both limited-stage (LS-SCLC) and ES-SCLC, incorporating data from pivotal clinical trials, a network meta-analysis of first-line chemoimmunotherapy regimens, and a critical appraisal of international treatment guidelines, and a critical analysis of international treatment guidelines from prominent organizations like the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO). This comprehensive approach allows for a robust and well-supported summary of the current therapeutic landscape. Results: For limited-stage SCLC (LS-SCLC), concurrent chemoradiotherapy (cCRT) remains the curative-intent standard, but its efficacy is now being augmented by consolidative immunotherapy, as demonstrated by the landmark ADRIATIC trial. The role of prophylactic cranial irradiation (PCI) in LS-SCLC is being re-evaluated in the era of high-sensitivity brain imaging and concerns over neurotoxicity. For ES-SCLC, the treatment paradigm has been fundamentally transformed by the integration of immune checkpoint inhibitors (ICIs) with platinum–etoposide chemotherapy, establishing a new standard of care that offers a modest but consistent survival benefit. Conclusions: The treatment of SCLC has been significantly advanced by the integration of immunotherapy, particularly for extensive-stage disease, which has established a new standard of care and improved patient outcomes. Looking to the future, the quest for predictive biomarkers and the development of novel therapeutic classes, such as Bi-specific T-cell Engagers (BiTEs) and antibody–drug conjugates, promise to build upon recent progress and offer new hope for improving the dismal prognosis associated with this disease. Full article

Substance use disorders (SUDs) remain a major public health challenge, with existing pharmacotherapies offering limited long-term efficacy. Traditional treatments focus on dopaminergic systems but often overlook the complex interplay between metabolic signals, neuroplasticity, and conditioned behaviors that perpetuate addiction. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for type 2 diabetes and obesity, have recently emerged as promising modulators of reward-related brain circuits. This review synthesizes current evidence on the role of glucagon-like peptide-1 (GLP-1) and its receptor in modulating craving and substance-seeking behaviors. We highlight how GLP-1 receptors are expressed in addiction-relevant brain regions, including the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC), where their activation influences dopaminergic, glutamatergic, and GABAergic neurotransmission. In addition, we explore how GLP-1 signaling affects reward processing through gut–brain vagal pathways, hormonal crosstalk, and neuroinflammatory mechanisms. Preclinical studies demonstrate that GLP-1RAs attenuate intake and relapse-like behavior across a range of substances, including alcohol, nicotine, and cocaine. Early-phase clinical trials support their safety and suggest potential efficacy in reducing craving. By integrating findings from molecular signaling, neurocircuitry, and behavioral models, this review provides a translational perspective on GLP-1RAs as an emerging treatment strategy in addiction medicine. We propose that targeting gut–brain metabolic signaling could provide a novel framework for understanding and treating SUDs. Full article

Enhanced Recovery After Surgery (ERAS) is an evidence-based, holistic perioperative recovery protocol intended to improve patient outcomes and decrease postoperative complication rates. While ERAS protocols were first introduced in 1997, specific guidelines for cardiac surgery were not established until 2019. Although the core principles of ERAS remain constant across surgical disciplines, ERAS guidelines for cardiac surgery have remained relatively understudied, likely due to the unique complexities posed by cardiac procedures. Within this comprehensive narrative review, we aimed to explore the current guidelines and evidence for ERAS in both cardiac and non-cardiac surgeries. In non-cardiac surgeries, ERAS has been shown to improve various outcomes, including ICU length of stay, patient satisfaction, and pain management. ERAS for cardiac surgery has also shown encouraging results, including shorter ICU and hospital stays, reduced postoperative opioid use, and faster recovery times. However, there is limited consensus across studies, particularly regarding its impact on morbidity and mortality, with mixed results reported. Furthermore, the limited data on the efficacy of ERAS in minimally invasive cardiac surgeries makes it difficult to establish well-supported guidelines for these procedures. Despite its limitations, the overall outcomes of ERAS for cardiac surgery remain promising. As our understanding and application of ERAS in cardiac surgery continue to evolve, these protocols have the potential to redefine cardiac surgical care standards. Full article

Background: Hyperemesis gravidarum (HG) is the leading cause of hospitalization during early pregnancy, affecting approximately 0.3–3% of pregnancies. It represents the most severe end of the nausea and vomiting in pregnancy (NVP) spectrum and is associated with substantial maternal morbidity and potential adverse fetal outcomes. Despite extensive research, the exact pathophysiology remains poorly understood, and optimal management strategies continue to be debated. Methods: This narrative review synthesizes current evidence on the complications and treatment approaches for HG. A literature search was conducted in PubMed, Scopus, and Medline up to October 2024 using predefined keywords. Eligible sources included observational studies, cohort studies, descriptive studies, and case reports. Systematic reviews, meta-analyses, and non-English articles were excluded. Results: HG is associated with a broad spectrum of complications, including dehydration, electrolyte imbalances, Wernicke’s encephalopathy, cardiac arrhythmias, thromboembolism, and adverse pregnancy outcomes such as fetal growth restriction and preterm birth. Pharmacological treatments—most notably doxylamine-pyridoxine (the only FDA-approved therapy), ondansetron, metoclopramide, and corticosteroids—have demonstrated varying efficacy and safety profiles. Non-pharmacological interventions such as acupressure, dietary adjustments, psychotherapy, and hypnosis have also been studied, although evidence remains limited. Conclusions: HG requires a comprehensive and individualized management approach. While doxylamine-pyridoxine remains the cornerstone of therapy, other pharmacologic and supportive measures may offer additional benefit. Continued research is essential to clarify the underlying mechanisms, improve therapeutic efficacy, and develop evidence-based guidelines that integrate both medical and psychosocial care for affected women. Full article

Modern society faces a growing prevalence of mental disorders, with stress emerging as a critical factor affecting mental well-being. In recent years, breathwork has gained public and scientific recognition as a promising approach for enhancing psychological health. Despite the rapid growth in research, the field remains fragmented due to the diversity of breathing techniques. Moreover, recent findings have challenged several foundational concepts traditionally believed to underlie the therapeutic effects of breathwork. This review offers a comprehensive overview and comparison of the most widely practiced breathing techniques, with a focus on addressing key theoretical issues. We examine the primary psychophysiological pathways and mechanisms of breathwork, highlighting its influence on the nervous system as central to its effectiveness. We critically evaluate the role of breathing variables, including pace, ratio, breathing route, attention, and the use of biofeedback, in promoting the long-term neurobiological changes that have been associated with improved mental health. We argue that most breathwork techniques share core neurophysiological mechanisms that benefit well-being, regardless of the theoretical differences between specific techniques. Accumulating evidence suggests breathwork may serve as both a preventive and adjunctive therapy for chronic stress, anxiety, and depression, given its potential to target key risk factors and produce clinically relevant outcomes. Contemporary breathwork research, however, is limited by inconsistent study quality and methodological heterogeneity. By synthesizing current evidence and identifying critical knowledge gaps, this review aims to guide future research and advance understanding of breathwork’s therapeutic potential. Full article

Background: Facial nerve palsy is a relatively common complication following open rigid internal fixation (ORIF) of a mandibular condylar fracture. The aim of this study was to investigate the risk factors that influence post-operative facial nerve function and the recovery process. Methods: A retrospective study was conducted based on the medical records of 329 patients who underwent ORIF treatment for condyle fractures, with the follow-up period being 24 months long. Results: During the initial post-operative examination, 50.45% of patients exhibited some signs of facial nerve dysfunction, ranging from slight to severe, and 48.63% of patients presented transient palsy, while only 1.82% presented permanent facial nerve palsy. Female patients were found to be more susceptible to post-operative facial nerve palsy. Patients with multiple mandibular fractures and bilateral condyle fractures had a worse prognosis. The preauricular approach and its modifications were identified as posing the greatest risk to the facial nerve. The safest approach was the retromandibular approach. Patients treated for injuries resulting from traffic accidents or falls had a worse prognosis than those treated for assault injuries. Conclusions: Post-operative facial nerve palsy following ORIF of the mandibular condyle is, in most cases, transient and can be effectively treated. However, it is important to choose the safest possible surgical approach. The safer approach, the retromandibular approach, should be considered when possible. Full article

Sleep disorders and stroke are intricately linked through a complex, bidirectional relationship. Sleep disturbances such as obstructive sleep apnea (OSA), insomnia, and restless legs syndrome (RLS) not only increase the risk of stroke but also frequently emerge as consequences of cerebrovascular events. OSA, in particular, is associated with a two- to three-fold increased risk of incident stroke, primarily through mechanisms involving intermittent hypoxia, systemic inflammation, endothelial dysfunction, and autonomic dysregulation. Conversely, stroke can disrupt sleep architecture and trigger or exacerbate sleep disorders, including insomnia, hypersomnia, circadian rhythm disturbances, and breathing-related sleep disorders. These post-stroke sleep disturbances are common and significantly impair rehabilitation, cognitive recovery, and quality of life, yet they remain underdiagnosed and undertreated. Early identification and management of sleep disorders in stroke patients are essential to optimize recovery and reduce the risk of recurrence. Therapeutic strategies include lifestyle modifications, pharmacological treatments, medical devices such as continuous positive airway pressure (CPAP), and emerging alternatives for CPAP-intolerant individuals. Despite growing awareness, significant knowledge gaps persist, particularly regarding non-OSA sleep disorders and their impact on stroke outcomes. Improved diagnostic tools, broader screening protocols, and greater integration of sleep assessments into stroke care are urgently needed. This narrative review synthesizes current evidence on the interplay between sleep and stroke, emphasizing the importance of personalized, multidisciplinary approaches to diagnosis and treatment. Advancing research in this field holds promise for reducing the global burden of stroke and improving long-term outcomes through targeted sleep interventions. Full article

Wound care in military and combat environments poses distinct challenges that set it apart from conventional medical practice in civilian settings. The nature of injuries sustained on the battlefield—often complex, contaminated, and involving extensive tissue damage—combined with limited access to immediate medical intervention, significantly increases the risk of infection, delayed healing, and adverse outcomes. Traditional wound dressings frequently prove inadequate under such extreme conditions, as they have not been designed to address the specific physiological and logistical constraints present during armed conflicts. This review provides a comprehensive overview of recent progress in the development of advanced wound dressings tailored for use in military scenarios. Special attention has been given to multifunctional dressings that go beyond basic wound coverage by incorporating biologically active macromolecules such as collagen, chitosan, thrombin, alginate, therapeutic peptides, and growth factors. These compounds contribute to properties including moisture balance control, exudate absorption, microbial entrapment, and protection against secondary infection. This review highlights the critical role of advanced wound dressings in improving medical outcomes for injured military personnel. The potential of these technologies to reduce complications, enhance healing rates, and ultimately save lives underscores their growing importance in modern battlefield medicine. Full article

Background/Objectives: The aim of our study was to evaluate clinical outcomes in patients with small pleomorphic adenoma (PA) after extracapsular dissection (ED) versus superficial parotidectomy (SP). Methods: Following the PRISMA guidelines, a systematic review covering the years from 1950 to 2025 was conducted using the Pubmed/MEDLINE, Cochrane Library, Scopus, Ovid MEDLINE and Embase databases. A single-arm meta-analysis was performed to evaluate intraoperative capsular rupture, recurrence, transient and permanent facial nerve palsy, Frey’s syndrome, salivary fistula, seroma and hematoma of patients who underwent ED vs. those who underwent SP, and funnel plots were constructed to evaluate the robustness of the findings. Results: Of the 1793 identified papers, 21 articles met the inclusion criteria. The meta-analysis (2507 patients) reported the following: (1) the risk of recurrence is similar in patients treated with ED and SP; (2) the transient facial nerve palsy rate is lower after ED (p < 0.05), while the permanent facial nerve palsy rate is similar with ED and SP; (3) post-operative complications, especially Frey’s syndrome (p < 0.05), are more common after SP. Conclusions: Given the similar recurrence rate and the lower morbidity compared to SP, ED could be considered the treatment of choice for pleomorphic adenomas of the parotid gland that are up to 3 cm in size, mobile and located in the superficial lobe of the parotid gland. Full article

Cardiac arrhythmias remain a major source of morbidity and mortality, often stemming from molecular and structural abnormalities that are insufficiently addressed by current pharmacologic and interventional therapies. Gene therapy has emerged as a transformative approach, offering precise and durable interventions that directly target the arrhythmogenic substrate. Across the spectrum of inherited and acquired arrhythmias—including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation, and post-infarction ventricular tachycardia—gene-based strategies such as allele-specific silencing, gene replacement, CRISPR-mediated editing, and suppression-and-replacement constructs are showing growing translational potential. Advances in delivery platforms, including cardiotropic viral vectors, lipid nanoparticle-encapsulated mRNA, and non-viral reprogramming tools, have further enhanced the specificity and safety of these approaches. Additionally, innovative applications such as biological pacemaker development and mutation-agnostic therapies underscore the versatility of genetic modulation. Nonetheless, significant challenges remain, including vector tropism, immune responses, payload limitations, and the translational gap between preclinical models and human electrophysiology. Integration of patient-derived cardiomyocytes, computational simulations, and large-animal studies is expected to accelerate clinical translation. This review provides a comprehensive synthesis of the mechanistic rationale, therapeutic strategies, delivery platforms, and translational frontiers of gene therapy for cardiac arrhythmias. Full article

Background: Premature ventricular contractions (PVCs) are common arrhythmias associated with symptoms such as fatigue and, in severe cases, PVC-induced cardiomyopathy. Catheter ablation (CA) is a primary treatment for symptomatic PVCs, particularly when pharmacological therapies fail or are undesired. While improvements in: quality-of-life following ablation are documented, its impact on functional capacity remains underexplored. Objectives: This study evaluated the impact of CA on functional capacity and cardiac stress markers in patients with symptomatic PVCs using cardiopulmonary exercise testing (CPET) and NT-proBNP levels. Methods: A total of 30 patients underwent successful PVC ablation and completed baseline and follow-up CPET evaluations under the Bruce protocol. PVC burden, left ventricular ejection fraction (LVEF), NT-proBNP levels, and CPET parameters, including VO₂ max, METS, ventilatory efficiency, and anaerobic threshold (AT), were analyzed pre- and post-ablation. Results: PVC burden significantly decreased post-ablation (23,509.3 ± 10,700.47 to 1759 ± 1659.15, p < 0.001). CPET revealed improved functional capacity, with VO₂ max increasing from 24.97 ± 4.16 mL/kg/min to 26.02 ± 4.34 mL/kg/min (p = 0.0096) and METS from 7.16 ± 1.17 to 7.48 ± 1.24 (p = 0.0103). NT-proBNP significantly decreased (240.93 ± 156.54 pg/mL to 138.47 ± 152.91 pg/mL, p = 0.0065). LVEF and ventilatory efficiency metrics (VE/VO₂ and VE/VCO₂) remained stable. Conclusions: Catheter ablation improves functional capacity, reduces cardiac stress, and minimizes medication dependency in patients with symptomatic PVCs. These findings support the utility of ablation in enhancing aerobic capacity and overall exercise performance. Full article

Background: Severe maternal hypertension is linked to adverse perinatal outcomes. Both nifedipine and hydralazine are commonly used antihypertensive agents in this setting. Methods: A comprehensive literature search was conducted in PubMed, Cochrane Library, and EMBASE from inception to April 2024 to identify randomized controlled trials comparing oral or sublingual nifedipine with intravenous hydralazine for the management of severe hypertension, with or without preeclampsia/eclampsia. A random-effects meta-analysis was performed using RevMan. Results: Seven randomized controlled trials were included. The pooled analysis demonstrated no significant difference between the two agents regarding time to achieve optimal blood pressure control (MD = −1.08 min, 95% CI = −6.66 to 4.49), caesarean delivery (OR = 0.62, 95% CI = 0.38 to 1.03), neonatal birth weight (MD = 57.65 g, 95% CI = −209.09 to −324.40), NICU admissions (OR = 0.90, 95% CI = 0.41 to 1.98), and 5-min APGAR scores (MD = 0.1, 95% CI = −0.20 to 0.39). However, patients receiving nifedipine had significantly lower odds of experiencing medication-related adverse events (OR = 0.62, 95% CI = 0.40 to 0.97). Conclusions: Nifedipine and intravenous hydralazine showed comparable efficacy in achieving optimal blood pressure control and similar maternal and neonatal outcomes. However, nifedipine was associated with significantly fewer maternal adverse effects, indicating superior tolerability. Full article

Hip fractures are among the most serious health events in older adults, frequently leading to disability, loss of independence, and elevated mortality. In 2019, an estimated 9.6 million new cases occurred globally among adults aged ≥ 55 years, with an incidence rate of 681 per 100,000. Despite improved surgical care, one-year mortality remains high (15–30%), and fewer than half of survivors regain their pre-fracture functional status. Traditionally regarded as mechanical injuries, hip fractures are now increasingly recognized as systemic events reflecting and accelerating biological vulnerability and frailty progression. We synthesize evidence across biological, clinical, and social domains to explore the systemic implications of hip fracture, from the acute catabolic response and immune dysfunction to long-term functional decline. The concept of intrinsic capacity, introduced by the World Health Organization, offers a resilience-based framework to assess the multidimensional impact of hip fracture on physical, cognitive, and psychological function. We highlight the importance of orthogeriatric co-management, early surgical intervention, and integrated rehabilitation strategies tailored to the individual’s functional reserves and personal goals. Innovations such as digital health tools, biological aging biomarkers, and personalized surgical approaches represent promising avenues to enhance recovery and autonomy. Ultimately, we advocate for a shift toward interdisciplinary, capacity-oriented models of care that align with the goals of healthy aging and enable recovery that transcends survival, focusing instead on restoring function and quality of life. Full article

Introduction: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Even though surgery and chemotherapy are the mainstay of treatment, immunotherapy, and more specifically anti-tumor vaccination, has gained popularity over the past years due to the lower related toxicity and fewer long-term side effects. Dendritic cell (DC) vaccines have been shown to induce tumor specific cytotoxic T-cell (CTL) responses both in vitro and in vivo; however, due to the nature of the disease, resistance to immunotherapy is often developed. Various modifications, such as the implementation of viral vectors, tumor RNA, or even tumor-specific peptides (neoantigens), have been studied as a means to avoid resistance and enhance the effectiveness of the vaccines. In this review, we aim to assess the effects of neoantigen-loaded DC vaccines (naDCVs) on the immune response against gastric cancer cells. Materials and methods: A thorough literature search was conducted on PubMed and clinicaltrials.gov for studies assessing the efficacy of naDCVs against gastric cancer both in vivo and in vitro. The studies were assessed for eligibility by two independent reviewers based on predetermined inclusion and exclusion criteria. The search was completed following the PRISMA guidelines. Results: Eleven studies were included in our systematic review. In five of the studies, the effects of the naDCVs were tested in vitro; in two and in four they were examined both in vitro and in vivo. The in vitro studies showed that the naDCVs resulted in a more robust immune response against the cancer cells in the study groups compared to the control groups. The in vivo studies conducted on mice showed that tumor volume was reduced in the groups treated with the naDCV compared to the untreated groups. What is more, the cytotoxic effect of CTLs against tumor cells was also increased in the vaccine groups. One of the studies was conducted on humans as a phase I study. The results show increased CTL proliferation and cytokine production in the vaccinated group compared to the control, but no difference regarding the tumor size was observed. Conclusions: Neoantigen-loaded DC vaccines can stimulate a strong immune response against specific gastric cancer cell peptides and enhance tumor cell lysis, therefore hindering or even reversing disease progression, offering great potential for the treatment of patients with gastric cancer. Full article

Diabetic vascular diseases have emerged as a significant concern in medical research due to their considerable impact on human health. The challenge lies in the insufficient understanding of the intricate pathophysiological mechanisms associated with different forms of diabetic vascular diseases, which hampers our ability to identify effective treatment targets. Addressing this knowledge gap is essential for developing successful interventions. Unraveling the molecular pathways through which diabetes leads to microvascular and macrovascular complications in vital organs such as the heart, brain, kidneys, retina, and extremities is crucial. Notably, oxidative stress resulting from hyperglycemia is the key factor in initiating these complications. This review aims to elucidate the specific molecular mechanisms by which oxidative stress drives microvascular and macrovascular diseases and to highlight promising therapeutic advancements that offer hope for effective treatment solutions. Full article

Background: Emergency laparoscopic cholecystectomy (ELC) has emerged as a viable alternative to delayed elective surgery for acute gallstone disease, although its widespread adoption is hindered by cultural barriers. This study compares outcomes between elective and emergency laparoscopic cholecystectomy and evaluates the impact of implementing an ELC pathway on elective waiting times, patient outcomes, and overall service delivery. Methods: A prospective cohort study was conducted between December 2021 and December 2023, including all patients undergoing emergency or elective laparoscopic cholecystectomy. One-to-one propensity score matching, correlation statistics, and multivariate logistic regression were used to analyse outcomes. Results: Of 585 patients, 314 (53.4%) underwent emergency and 271 (46.3%) elective cholecystectomies. After matching, 474 patients were analysed (237 per group). The ELC pathway achieved an 81.4% first-presentation procedure rate, with 69.2% managed as day cases and 84.4% discharged the following day. Emergency cases had longer operative times (+9 min), higher rates of subtotal cholecystectomy (8.9% vs. 3.0%, p < 0.001), and more frequent postoperative ERCP (16.9% vs. 4.6%, p < 0.001). Other outcomes were comparable. Introduction of the ELC pathway significantly reduced elective waiting times from a median of nine to three months (R = −0.219, R² = 0.059, p < 0.001) and preoperative admissions (IQR 0–1, R = −0.223, R² = 0.050, p = 0.002). Conclusions: An ELC pathway is a safe and effective alternative to elective gallstone surgery, offering substantial benefits to patients and healthcare systems, while serving as a strategic, cost-conscious approach to reducing surgical waiting times and preoperative admissions. Its success hinges upon surgical expertise in acute decision making, skill in performing subtotal cholecystectomy, and access to institutional resources such as advanced imaging and ERCP services. Full article

Background/Objectives: The presence of Ehlers–Danlos Syndromes (EDSs) has significant effects on overall health and results in varying levels of pain and disability. The effects of sleep are not well documented in this population. The purpose of this study is to report the sleep characteristics of people with EDS. Methods: An electronic survey regarding sleep characteristics was created and distributed through the EDS website. Results: Sleep disturbance is common in people with EDS, with 65.3% of respondents sleeping fewer than 8 h and 26.2% averaging fewer than 6 h. Those who slept fewer than 6 h reported more days of poor mental and physical health days. Sleep aids were commonly used with 41.40% of patients regularly taking prescription medication to get to sleep. Sleep latency of greater than 30 min was also found in 67.5% of subjects. Conclusions: The results demonstrate an association between people with EDS and poorer sleep duration, increased sleep latency, and increased use of sleep aids including prescription sleep medication compared to the general population. While more research needs to be completed in this area, sleep may be an important aspect to address in the management of EDS. Full article

The rise of antibiotic resistance and the limitations of conventional therapies for managing biofilm-related oral infections highlight the urgent need for novel solutions, with low-temperature plasma (LTP) emerging as a promising alternative due to its potent antimicrobial effects, tissue-safety, and reduced risk of fostering resistance. This scoping review investigates the efficacy of LTP application for the management of oral biofilms associated with dental caries, peri-implantitis, endodontic infections, and oral candidiasis. This review was conducted in accordance with the PRISMA-ScR guidelines and registered with the Open Science Framework (OSF). Studies were identified through comprehensive searches of PubMed/MEDLINE, EBSCO (Medline Ultimate and e-journals), and Google Scholar, with no publication date restrictions, and were supplemented by manual reference screening. Eligible studies included original research, published in English, examining LTP’s effectiveness in oral biofilms. After systematically screening the literature, 51 studies were included in this scoping review, comprising mostly in vitro research, alongside ex vivo, in situ, and clinical studies. Data extraction revealed LTP’s broad-spectrum antimicrobial potential and promising clinical implications for dentistry. This review highlights key findings, identifies research gaps, and underscores the therapeutic potential of LTP in managing complex oral biofilm-related infections. Full article

Background. Establishing prompt vascular access facilitates resuscitation for out-of-hospital cardiac arrest (OHCA). While intraosseous access may decrease the time to vascular access, the impact on clinical outcomes in OHCA is unclear. Therefore, we aim to compare the effect of intraosseous (IO) versus intravenous (IV) vascular access on clinical outcomes after OHCA resuscitation. Methods. A systematic review and meta-analysis were performed to synthesize evidence from randomized controlled trials (RCTs) obtained from PubMed, CENTRAL, Scopus, and Web of Science until January 2025. Using Stata MP v. 17, we used the fixed-effects model to report dichotomous outcomes using the risk ratio (RR) and continuous outcomes using the mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42024627354. Results. Four RCTs and 9475 patients were included. There was no difference between both groups regarding the prehospital return of spontaneous circulation (ROSC) (RR: 0.97, 95% CI [0.91, 1.03], p = 0.33), maintained ROSC (RR: 0.94, 95% CI [0.87, 1.01], p = 0.09), survival to discharge (RR: 1.03 with 95% CI [0.88, 1.21], p = 0.71), 30-day survival (RR: 0.98, 95% CI [0.82, 1.17], p = 0.79), or favorable neurological recovery (RR: 1.07, 95% CI [0.90, 1.29], p = 0.44). However, IO access significantly increased first-attempt access (RR: 1.24, 95% CI [1.19, 1.29], p < 0.001), decreased time to vascular access (MD: −0.24 min with 95% CI [−0.48, −0.01], p = 0.04), and decreased time to drug administration (MD: −0.38, 95% CI [−0.66, −0.10], p = 0.01). Conclusions. IO and IV vascular accesses showed similar clinical outcomes in OHCA patients, with no difference in ROSC, survival, or neurological recovery. Still, IO access showed a better procedural outcome with increased first-attempt success rates, faster access, and faster drug administration. Full article

Background: Next-generation sequencing (NGS), particularly whole-exome sequencing (WES), has become a powerful diagnostic tool for rare genetic conditions. However, its success rate varies based on the underlying genetic etiology and the population studied. Methods: This retrospective study evaluated the diagnostic yield of NGS in a cohort of 137 pediatric patients with suspected rare genetic disorders in Bulgaria, a setting where such testing is not reimbursed and must be self-funded. The patients underwent either WES or targeted gene panel testing based on clinical presentation, family history, and genetic evaluation. Results: The overall diagnostic yield was 45.99%, with WES achieving 51.25% and targeted testing achieving 38.60%. The highest yield was observed in patients presenting with both dysmorphic features and neurodevelopmental delays (62.5%), while the lowest was observed among those with isolated neurodevelopmental issues (10%). A significant portion of the identified variants (35.9%) were novel. Eight patients were diagnosed with copy number variants (CNVs) detected only through WES. Conclusions: Our findings illustrate the value of WES as a first-line test and highlight the impact of deep phenotyping on diagnostic success. This study also emphasizes the need for a population-specific reference genome and equal access to genomic diagnostics in all European countries. Full article

About 5–20% of patients who undergo colonoscopy, in the days and weeks following the procedure, develop various symptoms (abdominal pain, bloating, and bowel alteration) mainly related to dysbiosis induced by the propaedeutic intestinal preparation. Some studies have positively evaluated the impact of the administration of different mixtures of probiotics in preventing and/or limiting this symptomatology. The aim of this review is to evaluate and summarize the available scientific evidence supporting the use of probiotics post-colonoscopy and to define their real efficacy as a routine treatment in a clinical setting. Full article

Artificial intelligence (AI) is rapidly transforming diagnostic approaches in different fields of medical sciences, demonstrating an emerging potential to revolutionize dermatopathology due to its capacity to process large amounts of data in the shortest possible time, both for diagnosis and research purposes. Different AI models have been applied to neoplastic skin diseases, especially melanoma. However, to date, very few studies have investigated the role of AI in dermatoses. Herein, we provide an overview of the key aspects of AI and its functioning, focusing on medical applications. Then, we summarize all the existing English-language literature about AI applications in the field of non-neoplastic skin diseases: superficial perivascular dermatitis, psoriasis, fungal infections, onychomycosis, immunohistochemical characterization of inflammatory dermatoses, and differential diagnosis between the latter and mycosis fungoides (MF). Finally, we discuss the main challenges related to AI implementation in pathology. Full article

Background/Objectives: Peripheral prosthetic vascular graft infection represents a very serious complication after lower limb revascularization, with amputation and mortality rates up to 70% and 30%, respectively. This study was designed to determine the incidence of prosthetic graft infection, amputation, and mortality rate in our institution, analyzing different types of treatment. Methods: A retrospective cohort single institution review of peripheral prosthetic bypass grafts evaluated patient demographics, comorbidities, indications, location of bypass, type of prosthetic material, and case urgency and evaluated the incidence of graft infections, amputations, and mortality. Results: Between January 2016 and December 2021, a total of 516 bypasses were recorded (318 male, 198 female, mean age 74.2): 320 bypasses in venous material and 196 prosthetic bypasses using Dacron or PTFE. Among patients with a prosthetic bypass, 16 (8.2%) presented a graft infection at a mean follow-up of 39 months. Thirteen other patients who submitted to prosthetic peripheral bypass in other centers presented to our institution with a graft infection, so a total of 29 infected grafts were treated. Infected grafts were removed in 20 patients (68.9%), while a conservative treatment was helpful in nine cases (31.1%). The germs involved were Gram-negative in 27.6% and Gram-positive in 41.4%. During follow-up, we recorded five deaths (17.2%) and six amputations (20.7%) directly after bypass excision; another two amputations (6.9%) occurred after failure of the new bypass replacing the prosthesis removed. Conclusions: Redo-bypass, active infection at the time of bypass, and advanced gangrene were associated with a higher risk for prosthetic graft infection and major extremity amputation. Complete graft removal and replacement by venous material or Omniflow II represents the typical treatment. However, aggressive local treatment including drainage, debridement, vacuum-assisted closure therapy application, and muscle transposition seem to be a better solution in selected patients without the need for graft removal and with rates of limb salvage superior to those obtained with excisional therapy. Full article

Uterine fibroids represent a prevalent category of tumors encountered in females of reproductive age, may present as singular or multiple entities and can manifest a variety of symptoms, which can negatively affect women’s daily lives. Pharmacological interventions may prove to be ineffective, occasionally costly, and associated with adverse effects. In instances where symptoms escalate in severity, myomectomy becomes a requisite as uterine-preserving operative therapy. Myomectomy can be performed utilizing laparoscopic, robotic, laparotomic, vaginal or hysteroscopic techniques. Given the abundant vascular supply to the myometrium, with blood being delivered to the uterus via the uterine arteries, myomectomy carries a considerable risk of significant hemorrhage during and subsequent to the surgical procedure, with the related complications. This paper aims to elucidate the conventional methodologies employed to mitigate hemorrhage during myomectomy and in the immediate postoperative phase, evaluating the effect of chemical interventions (such as vasopressin, octreotide, tranexamic acid, and uterotonics) alongside mechanical strategies (including uterine artery clamps, embolization, and tourniquets) to curtail bleeding during the myomectomy process. Furthermore, the potential of employing the intracapsular myomectomy technique without reliance on other traditional approaches was explored. This surgical method is grounded in the principles of the biological and anatomical characteristics of the fibroid, facilitating the enucleation of the myoma from its pseudocapsule. This anatomical entity, which is formed by the myoma throughout its development within the myometrium, enables the fibroid to be detached from the uterine musculature and supplies the requisite neurovascular support for its sustenance. Finally, the narrative review also shows how the intracapsular approach, which uses the fibroid’s biology, reduces bleeding during myomectomy. Full article