Search Results (513)

Background: Multiple myeloma (MM) is an incurable plasma cell dyscrasia with particularly adverse prognosis in relapsed, multi-drug refractory settings. The management of those patients is challenging as treatment options are limited. In this context, bispecific antibodies (BsAbs) have recently emerged as promising therapeutic agents, and several have gained regulatory approval. To better understand their impact in MM landscape, we performed a systematic review and meta-analysis assessing their efficacy and safety in patients with relapsed/refractory MM (RRMM). Methods: A systematic search was conducted in the PubMed, ScienceDirect, Scopus and ClinicalTrials.gov databases for clinical trials investigating BsAbs for RRMM. Pooled estimates in terms of proportions along with 95% confidence intervals were calculated with random-effects models. The present meta-analysis was performed following PRISMA guidelines and was registered in PROSPERO (ID: CRD420251028553). Results: Based on data from six clinical trials involving 850 patients, the pooled overall response and complete response or better rates were 69% and 42%, respectively, whereas the pooled rate of duration of response for at least one year was 71%. The estimated one-year progression-free survival and overall survival were 56% and 72%, respectively. Neutropenia was the most frequently observed severe hematological toxicity, with a pooled incidence of 46%. Grade ≥3 infections occurred in 29%, while any-grade CRS occurred in 69%, as per pooled analysis. Finally, an exploratory minimal residual disease (MRD) analysis in four of the six studies yielded a pooled MRD-negativity rate of 24%. Conclusions: BsAbs demonstrated commendable efficacy in heavily pretreated RRMM patients, in terms of response rates and survival outcomes. However, notable rates of hematologic toxicity, infections, and CRS were recorded. These findings support the clinical utility of BsAbs in RRMM, while highlighting the need for comprehensive toxicity management. Full article

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with a heterogeneous clinical course that may progress to end-stage kidney disease (ESKD) in approximately 20% of patients. Despite recent advances, including the U.S. Food and Drug Administration (FDA) approval of three novel agents, optimal therapeutic strategies remain uncertain, and access to new drugs is often limited. This underscores the need to evaluate established and widely available options such as mycophenolate mofetil (MMF). The aim of this review is to critically assess the role of MMF, either as monotherapy or in combination with systemic corticosteroids, in the treatment of IgAN based on evidence cited in the KDIGO 2024 Draft Guidelines. We analyzed seven major clinical studies—five randomized controlled trials and two long-term observational studies—with particular focus on the influence of histological activity on treatment outcomes. The Oxford classification was applied to explore whether specific histological variables correlate with prognosis and predict treatment response. Trials conducted in Chinese cohorts demonstrated significant benefits of MMF, including proteinuria reduction, delayed progression to ESKD, and improved long-term renal outcomes, particularly in patients with recent disease onset and active proliferative lesions such as endocapillary hypercellularity and crescent formation. In contrast, studies from Western populations generally failed to demonstrate comparable benefit possibly due to differences in disease chronicity, histopathological patterns, and genetic background. Overall, MMF appears most effective when initiated early and in patients with histologic evidence of intraglomerular inflammation. It may represent a viable steroid-sparing option in appropriately selected patients, particularly where access to newly approved agents is restricted. These population- and pathology-based differences highlight the need for individualized treatment decisions and further research to refine the therapeutic role of MMF in IgAN. 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

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are among the most widespread drugs for the prevention of cardiovascular mortality and morbidity. Nevertheless, they are known to cause bradykinin (BK)-mediated angioedema (AE), a paroxysmal, localized, self-limiting, and potentially fatal swelling of the subcutaneous and/or submucosal tissue, due to a temporary increase in vascular permeability. Unlike hereditary angioedema (HAE), which can be mediated similarly by BK, no diagnostic tools, guidelines, or drugs have yet been approved for the diagnosis and treatment of acute non-allergic drug-induced AE. Besides ACEIs and ARBs, inhibitors of dipeptidyl peptidase-IV, neprilysin inhibitors, and tissue plasminogen activators are known to cause AE as an adverse effect. Currently, there are insufficient data on the prevention of AE caused by pharmacological therapies. In addition, the molecular mechanisms underlying BK-mediated AE caused by drugs, which are discussed here, are not fully explained. Specific approved drugs and a structured diagnostic workflow are unmet needs and are required for the management of this kind of AE. The aim of this review is to provide physicians with accurate knowledge of potentially life-threatening drug reactions so that they can be better understood and managed. Full article

Background: Statins exhibit pleiotropic anti-inflammatory, antioxidant, and immunomodulatory effects, suggesting their potential in non-cardiovascular conditions. However, evidence supporting their repurposing remains limited, and off-label prescribing policies vary globally. Objective: To systematically review evidence on statin repurposing in oncology and infectious diseases, and to assess Hungarian regulatory practices regarding off-label statin use. Methods: A systematic literature search (PubMed, Web of Science, Scopus, ScienceDirect; 2010–May 2025) was conducted using the terms “drug repositioning” OR “off-label prescription” AND “statin” NOT “cardiovascular,” following PRISMA guidelines. Hungarian off-label usage data from the NNGYK (2008–2025) were also analyzed. Results: Out of 205 publications, 12 met the inclusion criteria—75% were oncology-focused, and 25% focused on infectious diseases. Most were preclinical (58%); only 25% offered strong clinical evidence. Applications included hematologic malignancies, solid tumors, Cryptococcus neoformans, SARS-CoV-2, and dengue virus. Mechanisms involved mevalonate pathway inhibition and modulation of host immune responses. Hungarian data revealed five approved off-label statin uses—three dermatologic and two pediatric metabolic—supported by the literature and requiring post-treatment reporting. Conclusions: While preclinical findings are promising, clinical validation of off-label statin use remains limited. Statins should be continued in cancer patients with cardiovascular indications, but initiation for other purposes should be trial-based. Future directions include biomarker-based personalization, regulatory harmonization, and cost-effectiveness studies. Full article

Background: Uterine fibroids (UFs) and endometriosis are gynecological conditions that significantly increase morbidity among women of reproductive age. Relugolix, a novel gonadotropin-releasing hormone receptor antagonist, is approved in combined therapy for the management of symptoms related to these disorders. However, its potential impact on bone mineral density (BMD) and osteoporosis risk should be considered when using a gonadotropin-releasing hormone (GnRH) antagonist. This systematic review aims to evaluate the effects of daily relugolix intake in monotherapy and combination therapy on BMD, ensuring safe long-term management. Methods: A systematic literature review was conducted following PRISMA 2020 guidelines. Searches were performed in PubMed, Medline, and the Cochrane Library. Relevant clinical guidelines from international societies were also reviewed. Studies assessing the impact of relugolix on BMD were selected, and data on treatment efficacy, adverse effects, and bone health outcomes were synthesized. Results: Relugolix monotherapy has been associated with significant BMD loss due to its potent estrogen-suppressing effect. To mitigate this, combination therapy with estradiol and norethisterone acetate has been developed. Although initial monotherapy before transitioning to combination therapy results in transient BMD reduction, clinical trials have demonstrated that relugolix combination therapy maintains BMD over two years while effectively reducing endometriosis- and UF-related symptoms. Conclusions: Relugolix combination therapy is an effective and well-tolerated treatment for UFs and endometriosis, minimizing the risk of hypoestrogenism-related bone loss while maintaining clinical benefits. Although monotherapy may lead to transient BMD reduction, combination therapy appears to stabilize bone health. Full article

Research results suggest the potential of topical adenosine as a hair-promoting agent. The aim of this study was to examine the available clinical evidence of the efficacy of topical adenosine products in hair loss. This systematic review was conducted in accordance with PRISMA and PICO guidelines and included articles indexed in PubMed, Scopus, and Web of Science. The strength of evidence was assessed according to the GRADE system. Wherever feasible, data were extracted for a meta-analysis. Among 8625 articles returned by the query, 7 clinical trials were identified of topical adenosine (lotion, shampoo) in hair loss. They unanimously reported on a reduction in hair loss and increase in hair density (strength of evidence very low to moderate). A meta-analysis of three eligible trials showed a tendency to increased hair density (OR = 1.03, 95% CI: 0.89–1.20, p = 0.68), an increase in thick hair (OR = 1.4, 95% CI: 0.82–2.38, p = 0.21) and a decrease in thin hairs (OR = 0.93, 95% CI: 0.61–1.43, p = 0.75) after 6 months of alopecia treatment with a 0.75% adenosine lotion. The results from clinical trials published until now suggest that topical adenosine increases hair thickness, reduces excessive hair loss, stimulates hair regrowth, and increases hair density. The overall strength of evidence remains low due to flawed design and small sample sizes in most trials. Nevertheless, topical adenosine products seem worth trying, especially in the case of contraindications or adverse effects to approved medicinal products for hair loss. Further, better designed trials of adenosine in hair loss are warranted. Full article

Background: There has been a reduction in successful H. pylori eradication rates recently, which is largely attributed to increasing antibiotic resistance. In areas of high dual clarithromycin and metronidazole resistance such as ours, Maastricht VI/Florence guidelines recommend bismuth quadruple therapy (BQT) as first line of therapy; however, the availability of bismuth was poor in Ireland until recently. Similarly, tetracycline, a component of BQT, is restricted locally, with doxycycline (D) being approved and reimbursed for most indications. Aims: To assess the efficacy of BQT-D therapy for H. pylori eradication in an Irish cohort. Methods: All patients testing positive for H. pylori in three Irish referral centres by urea breath test, stool antigen, or histology were treated prospectively with BQT-D (bismuth subcitrate 120 mg QDS, metronidazole 400 mg TDS, doxycycline 100 mg BD and esomeprazole 40 mg BD) for 14 days. Eradication was evaluated with a urea breath test (UBT) >4 weeks after therapy cessation or by stool antigen testing, as available. Outcomes were recorded and analysed according to demographics and H. pylori treatment history of the patients. Results: 217 patients completed post-eradication testing. Of which, 124 (57%) were female, with a mean age 52 years. 180 patients (83%) were treatment-naïve. A total of 165/180 (92%) of the treatment-naïve patients had successful eradication. There was no association between eradication and gender or age in this cohort (p = 0.3091, p = 0.962 respectively). A total of 29 patients received this therapy as second-line therapy, of which 22 (76%) had successful eradication. Eight patients received the regimen as rescue therapy, with seven (88%) having successful eradication. No serious adverse events were reported. Eleven individuals (6.5%) commented on the complicated nature of the regimen, with 11 tablets being taken at five intervals daily. Conclusions: BQT-D as first-line therapy for H. pylori infection is highly effective in a high dual-resistance population, achieving >90% eradication. BQT-D as a second-line treatment performed less well. Our data support BQT-D as a first-line treatment. Full article

Background: The European League Against Rheumatism (EULAR), in collaboration with the European Scleroderma Trial and Research group (EUSTAR), published the first set of treatment recommendations for systemic sclerosis (SSc) in 2009, with subsequent updates in 2016 and 2023. Objectives: This study aimed to evaluate how rheumatologists’ clinical approaches to the treatment of SSc evolved following the 2016 update of the clinical management guidelines. Methods: Medication use for SSc was analyzed in a cohort of 378 patients. The patients were stratified based on enrollment before (233 patients) and after (145 patients) the guideline update, and medication usage was compared between the two groups. Results: Although all patients presented with Raynaud’s phenomenon (RP), only 35% received calcium channel blockers. Medications such as iloprost, phosphodiesterase type 5 (PDE-5) inhibitors, fluoxetine, and bosentan, recommended for the treatment of RP and digital ulcers, were not approved for SSc by the Republic Health Insurance Fund. Treatment for pulmonary arterial hypertension (PAH) was administered to only 16 patients (4.2%), including 2 who received bosentan, 10 who received PDE-5 inhibitors, and 4 who were treated with riociguat. The use of PDE-5 inhibitors increased following the 2016 update of the guidelines. Cyclophosphamide was consistently prescribed for interstitial lung disease (ILD), with an increased frequency observed after the guideline update. No significant differences were observed in the use of methotrexate for skin involvement, ACE inhibitors for scleroderma renal crisis, or antibiotics for gastrointestinal symptoms. Proton pump inhibitors (PPIs) were prescribed to 87.3% of patients with gastrointestinal involvement, with an increase in use of both PPIs and prokinetic agents following the guideline update. Conclusions: Rheumatologists’ adherence to the EULAR/EUSTAR guidelines varied considerably, with 25% to 100% of eligible patients receiving the recommended treatments. Concordance improved in the management of PAH, ILD, and gastrointestinal involvement after the 2016 guideline update. Full article

Background: Female Sexual Dysfunction (FSD) encompasses a range of conditions that can profoundly impact quality of life and intimate relationships. The primary classifications of FSD include female sexual interest and arousal disorder (FSIAD), genitopelvic pain and penetration disorder (GPPPD), female orgasmic disorder (FOD), and substance or medication-induced sexual dysfunction (SM-ISD). Despite its prevalence, FSD is often underdiagnosed and undertreated. Objectives: This scoping review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the existing literature on both U.S. Food and Drug Administration (FDA)-approved and off-label pharmacotherapies for FSD by study type, outcomes, and limitations. Eligibility Criteria: Eligible studies comprised randomized controlled trials (RCTs), systematic reviews, and cohort studies involving adult women (≥18 years) with any subtype of FSD. These studies assessed pharmacologic interventions against a comparator and reported at least one treatment efficacy outcome. Studies outside this scope were excluded. Sources of Evidence: A 25-year literature search was conducted using PubMed/MEDLINE, the Cochrane Library, reference lists of relevant articles, academic handbooks, and targeted journals. Charting Methods: Three independent reviewers screened and extracted data. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Findings were organized into summary tables and categorized by pharmaceutical agent, pertinent study information, outcomes, and limitations. Results: A total of 44 human-based pharmacologic studies met inclusion criteria. FDA-approved agents were the most thoroughly studied pharmacotherapies. Hormonal, topical, and adjunctive agents demonstrated less robust evidence. Heterogeneity in outcome measures and inadequate long-term data were common limitations. Conclusions: Pharmacologic treatment for FSD shows promise but requires further research. Individualized, multifaceted care is essential for optimizing FSD outcomes. Full article

Microbial biofilms present a formidable challenge in ophthalmology. Their intrinsic resistance to antibiotics and evasion of host immune defenses significantly complicate treatments for ocular infections such as conjunctivitis, keratitis, blepharitis, and endophthalmitis. These infections are often caused by pathogens, including Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, particularly in patients using contact lenses or intraocular implants—devices that serve as surfaces for biofilm formation. The global rise in antimicrobial resistance has intensified the search for alternative treatment modalities. In this regard, plant-derived antimicrobials have emerged as promising candidates demonstrating broad-spectrum antimicrobial and antibiofilm activity through different mechanisms from those of conventional antibiotics. These mechanisms include inhibiting quorum sensing, disrupting established biofilm matrices, and interfering with microbial adhesion and communication. However, the clinical translation of phytochemicals faces significant barriers, including variability in chemical composition due to environmental and genetic factors, difficulties in standardization and reproducibility, poor water solubility and ocular bioavailability, and a lack of robust clinical trials evaluating their efficacy and safety in ophthalmic settings. Furthermore, regulatory uncertainties and the absence of unified guidelines for approving plant-derived formulations further hinder their integration into evidence-based ophthalmic practice. This review synthesizes the current knowledge on the pathogenesis and treatment of biofilm-associated ocular infections, critically evaluating plant-based antimicrobials as emerging therapeutic agents. Notably, resveratrol, curcumin, abietic acid, and selected essential oils demonstrated notable antibiofilm activity against S. aureus, P. aeruginosa, and C. albicans. These findings support the potential of phytochemicals as adjunctive or alternative agents in managing biofilm-associated ocular infections. By highlighting both their therapeutic promise and translational limitations, this review contributes to the ongoing discourse on sustainable, innovative approaches to managing antibiotic-resistant ocular infections. Full article

Background: Remdesivir (RDV) is a broad-spectrum antiviral prodrug, which is rapidly metabolized in vivo within cells to the pharmacologically active triphosphate metabolite, GS-443902. On the other hand, the dephosphorylated metabolite GS-441524 is the main form detected in plasma. RDV acts against RNA viruses, and it was the first antiviral drug to receive EMA and FDA approval for treating COVID-19. Nevertheless, its intracellular pharmacokinetics in real life are poorly explored, particularly due to technical challenges. Methods: The aim of this study was to validate an HPLC-MS/MS method for the direct quantification of GS-443902 in peripheral blood mononuclear cells (PBMCs) with a chromatographic separation of 15 min. Results: The method was validated following EMA and FDA guidelines in terms of sensitivity, specificity, accuracy, precision, matrix effect, recovery, carryover, and stability, and then applied to PBMC isolates from a small cohort of patients with severe COVID-19 who received RDV. Conclusions: This work represents the first method for the direct quantification of GS-443902 in PBMCs, with possible future application to intracellular pharmacokinetic studies in different scenarios, such as new oral prodrugs or drug–drug interaction studies. Full article

Background/Objectives: The relationship between OSA and adult hypertension has been extensively studied; however, it remains understudied in pediatric patients without OSA. The aim of this study is to identify factors associated with pediatric hypertension without OSA, through an IRB-approved retrospective chart review of patients who underwent polysomnography at Nemours Children’s Hospital, DE/NJ between January 2020 and July 2023. Methods: Eligibility criteria included children 8–17 years, completed PSG, and clinic visit blood pressure (BP). Anthropometrics, demographics, social determinants, and medical history were obtained from electronic medical records. Hypertension was defined as the average systolic and/or diastolic BP that is ≥95th percentile for gender, age, and height based on AAP Clinical Practice Guidelines. All variables were checked for normality. Chi-square tests for categorical data and Wilcoxon rank sum tests for continuous data were used to test significance between non-OSA non-hypertensives (NH) and hypertensives (H). p < 0.05 is considered significant. Results: Of 285 charts evaluated, 137 were classified as non-OSA. Patient information, including parents in household, smoking exposure, and food allergies, were statistically significant (p < 0.05) in hypertensive pediatric patients without OSA. Hypertension was significantly correlated (p < 0.05) with birth weight, BMI, daytime heart rate, systolic BP, and diastolic BP. Statistically significant differences (p < 0.05) were found in mental illnesses, neurological disease, and respiratory disease. Among polysomnography parameters, only nighttime heart rate was found to be statistically significant. Conclusions: The data suggests that in pediatric patients without OSA, there are multiple factors and co-morbidities associated with hypertension. These factors and co-morbidities warrant additional follow up in clinical practice to mitigate the risks of hypertension in pediatric patients. Full article

Introduction: The health emergency caused by the pandemic led to severe health issues in populations across many countries worldwide, including widespread morbidity and significant mortality. Nevertheless, several countries succeeded in keeping infection rates remarkably low before the approval of vaccines and the initiation of vaccinations in early 2021. We aim to identify the success factors of health policies in managing the impact of the health emergency across a selection of countries, focusing on how they protected their populations. Our study presents outcomes of sustainable health policy measures, along with health and social system challenges, and economic responses during the global health emergency. We sometimes found it difficult to define what counted as a success factor in some countries. Method: Our study draws upon a selection of reports and documents published by various ministries and economic, social, and health authorities, which we collected online. We structured our study into three phases to frame and contextualize the impact of health policy measures and countermeasures as follows: (i) observations and content analysis; (ii) empirical support through illustrative examples; and (iii) development of a health emergency toolkit of assessment. The documents were not always easy to compare because they differed in format and detail. Results: Our study outlines ten success factors for sustainable health policy measures and countermeasures: (i) preparedness; (ii) control; (iii) precaution; (iv) proactive decision-making; (v) synchronization; (vi) adequate legislation; (vii) goal fulfillment; (viii) digital health technology; (ix) empirical evidence; (x) ethical and moral virtues. Sometimes we struggled to separate what was ethical guidance from what was simply practical advice. Conclusion: We argue that the relevance of the health emergency toolkit of assessment outlined in our study demonstrates clearly that the success factors related to sustainable health policy measures and countermeasures can be applied and adapted to the societal conditions of individual countries. These factors may form a foundation for the development of a health emergency toolkit of assessment for future health emergencies. We also maintain that these factors may serve as a platform for establishing sustainable plans across health, social, and economic domains, with clear guidelines for implementation, management, and control. It is our hope that future health systems will make use of these findings before the next crisis emerges. Full article

Photosafety assessments are a key requirement for the safe development of pharmaceuticals, cosmetics, and agrochemicals. Although in vitro methods are widely used for phototoxicity and photoallergy testing, their limited applicability and predictive power often necessitate supplemental in vivo studies. To address this, we developed the PhotoChem Reference Chemical Database, comprising 251 reference compounds with curated data from in vitro, in vivo, and human studies. Using this database, we evaluated the predictive capacity of three OECD in vitro test guidelines—TG 432 (3T3 NRU), TG 495 (ROS assay), and TG 498 (reconstructed human epidermis)—by comparing the results against human and animal data. Against human reference data, all three test methods showed high sensitivity (≥82.6%) and strong overall accuracy: TG 432 (accuracy: 94.2% (49/52)), TG 495 (100% (27/27)), and TG 498 (86.7% (26/30)). In comparison with animal data, sensitivity remained high for all tests (≥92.0%), while specificity varied: TG 432 (54.3% (19/35)), TG 495 (63.6% (7/11)), and TG 498 (90.5% (19/21)). TG 498 demonstrated the most balanced performance in both sensitivity and specificity across datasets. We also analyzed 106 drug approvals from major regulatory agencies to assess real-world application of photosafety testing. Since the mid-2000s, the use of in vitro phototoxicity assays has steadily increased in Korea, particularly following the 2021 revision of the MFDS regulations. Test method preferences varied by region, with 3T3 NRU and ROS assays most widely used to evaluate phototoxicity, while photo-LLNA and guinea pig tests were frequently employed for photoallergy assay. Collectively, this study provides a valuable reference for optimizing test method selection and supports the broader adoption of validated, human-relevant non-animal photosafety assessment strategies. Full article