Search Results (127)

Background/Objectives: Acne vulgaris is a widespread, chronic inflammatory skin condition that significantly impacts patients’ quality of life. Although oral isotretinoin remains the most effective treatment, recent evidence suggests that H₁-antihistamines such as desloratadine and levocetirizine may enhance acne therapy. This study assesses whether combining H₁-antihistamines to isotretinoin enhances treatment efficacy in acne vulgaris compared to isotretinoin alone. Methods: Our analysis included 10 randomized controlled trials involving 675 patients collectively, predominantly from Asia and the Middle East. Data were extracted by two independent reviewers, with discrepancies resolved by a third. Risk of bias was assessed using the Cochrane RoB 2 tool. Analyses were performed using RevMan 5.4 with random-effects models, and heterogeneity was evaluated via I² and Q tests. Sensitivity analyses were conducted to assess result robustness. Results: Combination therapy with isotretinoin and desloratadine showed a significantly greater reduction in GAGS (Global Acne Grading Scale) score by week 12 (p < 0.00001; MD 2.68, 95% CI 1.60 to 3.75; I² = 0%) while earlier timepoints showed non-significant or borderline results. For inflammatory lesions, significant improvements with desloratadine emerged at weeks 4, 8, and 12 after excluding an influential outlier, with low heterogeneity and consistent direction of effect. Non-inflammatory lesions did not differ significantly at weeks 4 or 8. At week 12, a significant reduction was seen in the desloratadine subgroup (OR 2.61, p = 0.003, I² = 11%) and in overall pooled analysis (OR 2.77, p < 0.0001, I² = 2%). Among side effects, acne flare-ups, pruritus, and cheilitis were significantly reduced in the desloratadine group, as well as in pooled analysis. Xerosis did not consistently differ between groups. Overall, desloratadine improved tolerability and reduced mucocutaneous adverse events more than levocetirizine. Conclusions: Current evidence suggests that combining oral antihistamines with isotretinoin may offer therapeutic benefits in acne management, particularly in enhancing tolerability and potentially improving clinical outcomes, as reflected by significant reductions in GAGS scores and mucocutaneous adverse effects such as cheilitis, pruritus, and acne flare-ups. Full article

Background/Objectives: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have revolutionized heart failure (HF) therapies and are an essential component of guideline-directed medical therapy (GDMT); however, their significance in arrhythmia prevention is still uncertain. This meta-analysis evaluates the benefits of SGLT2i on arrhythmias in HF. Methods: A comprehensive examination was performed with PubMed, ScienceDirect, PLOS One, Cochrane, Google Scholar, and ClinicalTrials.gov from January 2014 to March 2025, complying with PRISMA guidelines. Randomized controlled trials (RCTs) comparing SGLT2i with placebo were incorporated. Primary results included ventricular arrhythmias (VA), sudden cardiac death (SCD), atrial arrhythmias, and conduction disorders. Subgroup analyses investigated the effects on arrhythmias in HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Results: A total of 11 RCTs involving 23,701 patients, 11,848 on SGLT2i (mean age: 68.26 ± 10 yrs, 53.5% males) and 11,853 on placebo (mean age: 67.91 ± 10 yrs, 53% males), were analyzed with a mean follow-up of 2.71 yrs. No significant differences were reported between SGLT2i and placebo for VA [relative risk (RR): 1.02, 95% confidence interval (CI): 0.83–1.25], I² =0%), atrial arrhythmias (RR: 0.92 [CI: 0.67–1.27], I² = 65.3%), or conduction disorders (RR:1.22 [CI: 0.86–1.73], I² = 10.4%). Notably, significant reductions in risk of SCD (RR: 0.68 [CI: 0.49–0.93], I² = 0%) and in the risk of atrial arrhythmias in HFrEF (RR: 0.66 [CI: 0.49–0.89], I² = 10.3%) were witnessed, although no such reduction was seen in HFpEF (RR: 1.14 [CI: 0.94–1.40], I² = 33.8%). Conclusions: SGLT2i do not reduce overall arrhythmia or conduction disorder risk in HF but significantly reduce the risk of SCD and atrial arrhythmias in HFrEF patients. These results highlight potential arrhythmia prevention benefits in HFrEF, warranting further targeted studies. Full article

Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare and biologically distinct subset of urothelial malignancies, comprising approximately 5–10% of urothelial cancers. UTUC presents unique diagnostic and therapeutic challenges, with both a higher likelihood of invasive disease at presentation and a less favorable prognosis compared to urothelial carcinoma of the bladder. Current treatment strategies for UTUC are largely derived from bladder cancer studies, underscoring the need for UTUC-directed research. This review provides a comprehensive overview of UTUC, encompassing diagnostic approaches, systemic and intraluminal therapies, surgical management, and future directions. Methods: A narrative review was conducted synthesizing evidence from guideline-based recommendations, retrospective and prospective clinical studies, and ongoing trials focused on UTUC. Results: Neoadjuvant cisplatin-based chemotherapy is increasingly preferred in UTUC due to the risk of postoperative renal impairment that may preclude adjuvant cisplatin use. Surgical management includes kidney-sparing approaches and radical nephroureterectomy (RNU), with selection guided by tumor risk and patient comorbidities. While endoscopic management (EM) preserves renal function, it carries a higher recurrence and surveillance burden; RNU remains standard for high-risk cases. Systemic therapy for advanced and metastatic UTUC mirrors that of bladder urothelial carcinoma. Enfortumab vedotin (EV) plus pembrolizumab showed superior efficacy over chemotherapy in the EV-302 trial, with improved response rate, progression-free survival, and overall survival across subgroups, including UTUC. For patients ineligible for EV, the CheckMate-901 study supported first-line chemoimmunotherapy with gemcitabine, cisplatin, and nivolumab. Further systemic therapy strategies include maintenance avelumab post-chemotherapy (JAVELIN Bladder 100), targeted therapies such as erdafitinib (THOR trial), and trastuzumab deruxtecan (DESTINY-PanTumor02) in FGFR2/3-altered and HER2-positive disease, respectively. Conclusions: Historically, the therapeutic landscape of UTUC has been extrapolated from bladder cancer; however, ongoing research specific to UTUC is deriving more precise regimens involving the use of immune checkpoint inhibitors, antibody–drug conjugates, and biomarker-driven therapies. Full article

Background/objectives: Oral lichen planus (OLP) is a chronic autoimmune disorder affecting various age groups and is associated with multiple factors. Conventional therapies often encounter complications from opportunistic infections, particularly oral candidiasis. This study examines the relationships between Candida colonization and oral microbiome composition in OLP patients. Through meta-analysis, we clarify these interactions and their implications for OLP progression. Methods: The PICOS is a systematic research strategy, following PRISMA 2020 and MeSH descriptors: oral lichen planus, oral microbiome, oral fungal, and non-Candida oral fungal. Results: A search of CINAHL, EMBASE, PubMed, Science Direct, and Web of Science identified 313 studies. Twelve studies were suitable for a systematic review, with four appropriate for meta-analysis. Findings showed a significant association between OLP and oral microbiota, with an OR of 4.155 (95% CI: 1.278–13.511, p = 0.024). Although analyses of C. albicans and non-albicans species lacked significance, particular non-albicans species were noted. The subgroup analysis of oral microbiota approached significance, indicated by an OR of 11.739 (95% CI: 0.654–210.713, p = 0.059). Conclusions: This study highlights the roles of Candida species and the oral microbiota in OLP, revealing a complex interaction between Candida colonization and the oral microbiome. Full article

This retrospective study aimed to assess the effectiveness of prophylactic hepatoprotective therapy in decreasing the incidence of drug-induced liver injury (DILI) among patients with cervical cancer undergoing chemotherapy. The analysis was performed on patients with cervical cancer who received chemotherapy at a tertiary hospital between September 2019 and August 2020. Propensity score matching (PSM) was utilized to equilibrate baseline characteristics between the treatment group, which received prophylactic hepatoprotective drugs, and the control group, which did not receive prophylaxis. The incidence and severity of liver injury were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Out of the 609 patients initially screened, 299 were included following PSM, with 105 in the treatment group and 194 in the control group. There were no significant differences in the incidence of liver injury (21.90% vs. 18.04%, p = 0.420) or its severity (p = 0.348) observed between the groups. Furthermore, none of the subgroups exhibited a significant reduction in DILI risk with prophylaxis. However, the number of patients experiencing an increase in their grade of liver injury was significantly higher in the treatment group (18.10% vs. 13.40%, p = 0.002), with these patients also exhibiting increased levels of alkaline phosphatase (ALP) and direct bilirubin (DBIL) post-chemotherapy (p < 0.05). Hepatoprotective drugs are not associated with a reduced risk of DILI and may in fact increase risk. Full article

(1) Background: Biofeedback and neurofeedback are gaining attention as non-invasive rehabilitation strategies in Parkinson’s disease (PD) treatment, aiming to modulate motor and non-motor symptoms through the self-regulation of physiological signals. (2) Objective: This review explores the application of biofeedback techniques, electromyographic (EMG) biofeedback, heart rate variability (HRV) biofeedback, and electroencephalographic (EEG) neurofeedback in PD rehabilitation, analyzing their impacts on motor control, autonomic function, and cognitive performance. (3) Methods: This review critically examined 15 studies investigating the efficacy of electromyographic (EMG), heart rate variability (HRV), and electroencephalographic (EEG) feedback interventions in PD. Studies were selected through a systematic search of peer-reviewed literature and analyzed in terms of design, sample characteristics, feedback modality, outcomes, and clinical feasibility. (4) Results: EMG biofeedback demonstrated improvements in muscle activation, gait, postural stability, and dysphagia management. HRV biofeedback showed positive effects on autonomic regulation, emotional control, and cardiovascular stability. EEG neurofeedback targeted abnormal cortical oscillations, such as beta-band overactivity and reduced frontal theta, and was associated with improvements in motor initiation, executive functioning, and cognitive flexibility. However, the reviewed studies were heterogeneous in design and outcome measures, limiting generalizability. Subgroup trends suggested modality-specific benefits across motor, autonomic, and cognitive domains. (5) Conclusions: While EMG and HRV systems are more accessible for clinical or home-based use, EEG neurofeedback remains technically demanding. Standardization of protocols and further randomized controlled trials are needed. Future directions include AI-driven personalization, wearable technologies, and multimodal integration to enhance accessibility and long-term adherence. Biofeedback presents a promising adjunct to conventional PD therapies, supporting personalized, patient-centered rehabilitation models. Full article

Background: Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer frequently involves liver metastases, which are linked to poor outcomes. The optimal first-line treatment strategy in this subgroup remains unclear. Methods: This multicenter, retrospective study evaluated 121 patients with HR-positive, HER2-negative breast cancer and liver metastasis who had not received prior systemic chemotherapy or cyclin-dependent kinase (CDK) 4/6 inhibitors (e.g., palbociclib, ribociclib). Patients were classified based on their initial treatment during the liver metastatic phase (CDK4/6 inhibitors or chemotherapy). Clinical characteristics, treatment patterns, and survival outcomes were assessed. Cox regression analysis identified independent prognostic factors. Results: The median age was 53 years; 62% were postmenopausal. Chemotherapy was administered to 36.4%, and CDK4/6 inhibitors to 63.6% of patients. Most cases (59.5%) were recurrent disease. Baseline characteristics were comparable, except for the use of local liver-directed therapies. Progression-free survival favored CDK4/6 inhibitors (10.9 vs. 4.8 months; p < 0.01), while overall survival favored chemotherapy (42.2 vs. 25.9 months; p = 0.042). In multivariate analysis, initial treatment modality, local liver-directed therapy, hormonal status, and the size of the largest liver lesion were independent predictors of survival. Conclusions: In patients with HR-positive, HER2-negative breast cancer and liver metastasis, first-line chemotherapy was associated with improved overall survival compared to CDK4/6 inhibitors. Local liver-directed therapies contributed to longer survival, while larger liver lesions and endocrine-resistant disease correlated with worse outcomes. These findings support considering chemotherapy as first-line treatment in selected patients with aggressive liver metastatic disease. Full article

In agreement with WHO recommendations, the Emilia-Romagna Region, Italy, implemented a population-wide HCV screening program for the treatment of the large asymptomatic infected population. From January 2022, the free-of-charge screening targeted all residents born between 1969 and 1989, prison inmates, and injection drug users. Participants were recruited using phone messages, electronic health record notifications, public advertisement, and direct contact with general practitioners. A single blood sample was collected for anti-HCV IgG testing and, if positive, for reflex HCV–RNA testing. Infected subjects were offered an evidence-based therapeutic pathway. By June 2024, 72.8% of high-risk subjects (n = 19,732), and 36.9% of the general population (n = 488,065) had been screened. A total of 1032 individuals were positive based on the HCV–RNA test, and the detection rate widely differed between the high-risk and the general population (23.8‰ vs. 1.2‰, respectively). Of the infected individuals, 88.1% were seen by a specialist physician, and 74.3% (n = 767) started antiviral therapy. Thanks to multiple recruitment approaches, over one third of the general population participated in HCV screening. The program performance was substantially greater among high-risk individuals compared to the general population. To achieve WHO targets, policymakers might consider expanding the screening to other high-risk subgroups and/or adapting birth cohorts. Full article

Purpose: This article aims to harmonize the current data from the literature, describe baseline severity, and discuss potential treatment considerations for cases of triple infection. Patients and Methods: We undertook a retrospective, observational study on 1244 patients with viral hepatitis study subgroups: chronic replicative hepatitis with HCV—679 patients, HBV—98 patients, HBV/HCV—25 patients, HBV/HDV—14 patients, and 2 patients with triple-infection (HBV, HCV, and HDV), hospitalized in the Second Department of “Sf. Cuv. Parascheva” Infectious Diseases Clinical Hospital of Galați, Romania, between 1 April 2017 and 1 March 2025. Results: Comparative analysis of biochemical parameters and liver fibrosis—at the initial testing—i.e., at the beginning of the specific antiviral therapy—with direct-acting antivirals on HCV (DAAs) or nucleos(t)ide analogues (NUCs): Entecavir (ETV) or Tenofovir Disoproxyl fumarate (TDF), for HBV, Bulevirtide (BLV) for HDV—revealed clinical forms with higher severity in the case of triple and double infections, in comparison to individuals who have had only one hepatotropic virus infection. Conclusions: Compared to patients with a single hepatotropic viral infection, those with a double or triple infection had more severe hepatic damage. Concomitant therapy with Bulevirtide, DAAs, and NUCs is possible and the therapeutic results from clinical studies, with single-infection patients showing great potential for improving the prognosis of these patients. Full article

Background/Objectives: Mucinous ovarian carcinoma (MOC) is a rare and biologically distinct subtype of epithelial ovarian cancer, typically presenting at an early stage in younger women. Unlike high-grade serous carcinoma, MOC is characterized by unique molecular features—including frequent KRAS mutations and HER2 amplifications—and exhibits limited sensitivity to platinum-based chemotherapy. These differences highlight the need for individualized treatment strategies guided by molecular and histological profiling. This review aims to integrate current evidence on the clinical management of MOC with emerging insights into its molecular biology, with a focus on how these factors influence surgical decision-making, fertility preservation, and adjuvant therapy selection. Methods: We performed a comprehensive narrative review of the literature, synthesizing findings from retrospective cohorts, molecular studies, and clinical guidelines relevant to the surgical, reproductive, and therapeutic management of MOC. Results: Histologic subtype—expansile versus infiltrative—plays a critical role in guiding lymphadenectomy as lymph node metastases are rare (<1%) in expansile tumors but occur in up to 23% of infiltrative cases. Complete surgical staging remains essential for accurate prognostication, yet tailored approaches may reduce overtreatment in low-risk patients. Fertility-sparing surgery (FSS) appears safe in FIGO stage IA expansile MOC, with favorable reproductive outcomes, while higher-stage or infiltrative cases warrant caution. Given MOC’s chemoresistance, the role of adjuvant therapy in early-stage disease remains debated. Targeted strategies, including MEK inhibitors and HER2-directed therapies, are under investigation and may benefit selected molecular subgroups. Conclusions: MOC requires a nuanced, biomarker-informed approach. This review advocates for personalized, evidence-based management supported by multidisciplinary evaluation while underscoring the urgent need for prospective studies and biomarker-driven clinical trials. Full article

Background: Medulloblastoma is the most common malignant brain tumor in children, classified into four primary molecular subgroups: WNT, SHH, Group 3, and Group 4, each exhibiting significant molecular heterogeneity and varied survival outcomes. Accurate classification of these subgroups is crucial for optimizing treatments and improving patient outcomes. DNA methylation profiling is a promising approach for subgroup classification; however, its application is still evolving, with ongoing efforts to improve accessibility and develop more accurate classification methods. Objectives: This study aims to develop a supervised machine learning-based framework using Illumina 450K methylation data to classify medulloblastoma into seven molecular subgroups: WNT, SHH-Infant, SHH-Child, Group3-LowRisk, Group3-HighRisk, Group4-LowRisk, and Group4-HighRisk, incorporating age and risk factors for enhanced subgroup differentiation. Methods: The proposed model leverages six metagenes, capturing the underlying patterns of the top 10,000 probes with the highest variances from Illumina 450K data, thus enhancing methylation data representation while reducing computational demands. Results: Among the models evaluated, the SVM achieved the highest performance, with a mean balanced accuracy 98% and a macro-averaged AUC of 0.99 in an independent validation. This suggests that the model effectively captures the relevant methylation patterns for medulloblastoma subgroup classification. Conclusions: The developed SVM-based model provides a robust framework for accurate classification of medulloblastoma subgroups using DNA methylation data. Integrating this model into clinical decision making could enhance subgroup-directed therapies and improve patient outcomes. Full article

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, often involving a strong genetic background. Polygenic risk scores (PRSs) combine the cumulative effects of multiple genetic variants to quantify an individual’s susceptibility to CVD. Pharmacogenomics (PGx) can further personalize treatment by tailoring medication choices to an individual’s genetic profile. Even with these potential benefits, the extent to which PRS can be integrated into the PGx of CVD remains unclear. Our review provides an overview of current evidence on the application of PRS in the PGx of CVD, examining clinical utility and limitations and providing directions for future research. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews protocol, we conducted a comprehensive literature search in PubMed, EMBASE, and the Web of Science. Studies investigating the relationship between PRS in predicting the efficacy, adverse effects, or cost-effectiveness of cardiovascular medications were selected. Of the 1894 articles identified, 32 met the inclusion criteria. These studies predominantly examined lipid-lowering therapies, antihypertensives, and antiplatelets, although other medication classes (e.g., rate-control drugs, ibuprofen/acetaminophen, diuretics, and antiarrhythmics) were also included. Our findings showed that PRS is most robustly validated in lipid-lowering therapies, especially statins, where studies reported that individuals with higher PRSs derived the greatest reduction in lipids while on statins. Studies analyzing antihypertensives, antiplatelets, and antiarrhythmic medications demonstrated more variable outcomes, though certain PRSs did identify subgroups with significantly improved response rates or a higher risk of adverse events. Though PRS was a strong tool in many cases, we found some key limitations in its applicability in research, such as the under-representation of non-European-ancestry cohorts in the examined studies and a lack of standardized outcome reporting. In conclusion, though PRS offers promise in improving the efficacy of PGx of CVD by enhancing the personalization of medication on an individual level, several obstacles, such as the need for including a broader ancestral diversity and more robust cost-effectiveness data remain. Future research must (i) prioritize validating PRS in ethnically diverse populations, (ii) refine PRS derivation methods to tailor them for drug response phenotypes, and (iii) establish clear and attainable guidelines for standardizing the reporting of outcomes. Full article

Lennox–Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, cognitive impairment, and distinctive electroencephalographic patterns. Current treatments primarily focus on symptom management through antiseizure medications (ASMs), dietary therapy, epilepsy surgery, and neuromodulation, but often fail to address the underlying pathophysiology or improve cognitive outcomes. As genetic causes are identified in 30–40% of LGS cases, precision therapeutics targeting specific molecular mechanisms are emerging as promising disease-modifying approaches. This narrative review explores precision therapeutic strategies for LGS based on molecular pathophysiology, including channelopathies (SCN2A, SCN8A, KCNQ2, KCNA2, KCNT1, CACNA1A), receptor and ligand dysfunction (GABA/glutamate systems), cell signaling abnormalities (mTOR pathway), synaptopathies (STXBP1, IQSEC2, DNM1), epigenetic dysregulation (CHD2), and CDKL5 deficiency disorder. Treatment modalities discussed include traditional ASMs, dietary therapy, targeted pharmacotherapy, antisense oligonucleotides, gene therapy, and the repurposing of existing medications with mechanism-specific effects. Early intervention with precision therapeutics may not only improve seizure control but could also potentially prevent progression to LGS in susceptible populations. Future directions include developing computable phenotypes for accurate diagnosis, refining molecular subgrouping, enhancing drug development, advancing gene-based therapies, personalizing neuromodulation, implementing adaptive clinical trial designs, and ensuring equitable access to precision therapeutic approaches. While significant challenges remain, integrating biological insights with innovative clinical strategies offers new hope for transforming LGS treatment from symptomatic management to targeted disease modification. Full article

The therapeutic landscape for multiple myeloma has gradually expanded in recent decades, leading to unprecedented deep and sustained responses as well as remarkable improvements in patient survival. Nonetheless, changes in treatment algorithms have raised new demands for patients with relapsed/refractory disease, as prior exposure and refractoriness to prior therapies impact the choice of subsequent treatments. In particular, refractoriness to lenalidomide—an established backbone of treatment in both front-line and maintenance settings and a key component of many approved regimens used in relapsed disease—is associated with suboptimal clinical outcomes. Therefore, identifying the most appropriate management in lenalidomide-refractory patients, and even more so in patients who are refractory to more than one agent, is critical. At present, treatment options for this growing subgroup of patients are still limited; however, recent data from clinical research are promising. Herein, we summarized the currently available treatment options and discuss future directions based on the latest results from ongoing clinical trials. Full article

 Background/Objectives: Extrapulmonary neuroendocrine carcinomas (EP-NECs) are rare, aggressive malignancies with no standardized treatment approach. Although platinum-based chemotherapy is considered the first-line therapy, overall survival (OS) and progression-free survival (PFS) remain limited. This study aims to evaluate the clinical and pathological characteristics of EP-NEC patients, their treatment responses, and survival outcomes. Methods: This retrospective observational study included 29 EP-NEC patients diagnosed and followed between 2015 and 2024. Clinical and demographic data, tumor localization, disease stage, administered treatments, and survival outcomes were analyzed. Kaplan–Meier survival analysis was used to assess OS and PFS, with subgroup comparisons performed via the log-rank test. Results: The most common primary tumor sites were the pancreas (21%), prostate (17%), and cervix (14%). At diagnosis, 55.2% of patients had metastatic disease. First-line platinum-based chemotherapy achieved an objective response rate of 82.1%, with a median PFS of 8.16 months and a median OS of 14.16 months. Surgical intervention significantly improved survival (p = 0.020), while a high Ki-67 proliferation index (>80%) was associated with worse PFS (p = 0.032). Other factors, including smoking status and liver-directed therapies, had no significant impact on survival. Conclusions: EP-NECs present with a poor prognosis despite platinum-based chemotherapy achieving high response rates. Surgical resection improves survival outcomes, whereas high Ki-67 expression is associated with a worse prognosis. These findings highlight the need for further research into novel therapeutic strategies for EP-NECs. Full article