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Metformin for COVID-19: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Rev Med Virol. 2026 Jul;36(4):e70172. doi: 10.1002/rmv.70172.

ABSTRACT

Metformin has been shown to reduce hospitalisation and symptom duration among adults with COVID-19, but the effect has not been studied. We conducted this meta-analysis to assess the efficacy and safety of metformin in patients with COVID-19. Randomized controlled trials (RCTs) comparing metformin with placebo in COVID-19 were identified through major databases through November 2025. We performed statistical analyses using RevMan 5.4, employing the random-effects model, along with Risk Ratio (RR) and Mean Difference (MD) as the effect measures. Our meta-analysis of four RCTs showed that metformin did not significantly reduce the composite outcome of hospitalisation, emergency department (ED) visits, or death, compared with placebo (RR 0.60, 95% CI 0.40-0.90.21). The incidence of all-cause mortality (RR 1.00; 95% CI 0.06-15.91) and serious adverse events (RR 2.86; 95% CI 0.76-10.76) was also comparable between the two groups. Our meta-analysis, with low to moderate certainty, found that metformin may provide modest benefit in reducing hospitalisation, ED visits, or mortality in patients with COVID-19 without an association with increased serious adverse events. However, these findings should be interpreted cautiously, given the limited number of trials, low event rates, and clinical heterogeneity across studies. Further large RCTs are needed before metformin can be considered for use in COVID-19.

PMID:42250263 | DOI:10.1002/rmv.70172

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Resource Use in Swedish Nursing Homes: A Repeated Cross-Sectional Follow-Up Study

Int J Geriatr Psychiatry. 2026 Jun;41(6):e70228. doi: 10.1002/gps.70228.

ABSTRACT

OBJECTIVES: Nursing homes in Sweden provide housing and care for people aged 65 years or older who require assistance with everyday activities. An increasing number of nursing home residents have cognitive and functional decline, which can result in additional time needed for care provision. This study aimed to explore changes in resource use and associated factors in Swedish nursing homes over a 5-year period.

METHODS: This repeated cross-sectional study analyzed baseline (2013-2014) and follow-up (2018-2019) proxy-rated data from 4599 participants from the Swedish National Inventory of Care and Health in Residential Aged Care study. Resource use was measured using the Resource Use in Dementia scale. Descriptive statistics, t-tests, chi-square tests, and multiple linear regressions were performed.

RESULTS: Total resource use increased from 7.15 h/day to 7.83 h/day between baseline and follow-up. The number of residents living in a dementia unit increased from 34.6% to 43%. Higher independence in activities of daily living was associated with lower total resource use at follow-up while living in a dementia unit was associated with higher total resource use. Higher total resource use was associated with seven neuropsychiatric symptoms. For residents living in a dementia unit, four neuropsychiatric symptoms were associated with higher total resource use.

CONCLUSIONS: Resource use in Swedish nursing homes increased between baseline and follow-up. These results may inform future policy, financing, and implementation decisions to support resource utilization in nursing homes.

PMID:42250257 | DOI:10.1002/gps.70228

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Efficacy and Safety of Double Filtration Plasmapheresis and Single Plasma Exchange in Patients with Lupus Nephritis: A Single-center, Real-world Retrospective Study

Blood Purif. 2026 Jun 6:1-17. doi: 10.1159/000552429. Online ahead of print.

ABSTRACT

Background Single plasma exchanges (SPE) and double filtration plasmapheresis (DFPP) are commonly used in clinical practice. However, there haven’t been clear recommendations on the selection of SPE or DFPP in treating lupus nephritis (LN) in existing Therapeutic plasma exchange(TPE) related guidelines. Therefore, we aimed to evaluate the efficacy and safety of DFPP and SPE in patients with LN, and analyze the risk factors of ineffective DFPP and SPE in the treatment of LN. Methods: In this single-center, real-world retrospective study, we assessed safety and efficacy of therapy with SPE or DFPP in 67 patients with LN. Changes of laboratory test indicators and statistical indicators before and after treatment were compared, and the occurrence of adverse events (AEs) was observed in these patients. Results: 24 patients were treated with DFPP and 43 patients with SPE. DFPP and SPE showed a comparatively significant treatment response. The effective rate of DFPP was higher than that of SPE (P< 0.05), but the difference was not statistically significant. In both groups, platelet, potassium, chloride, APTT, Fib were significantly lower at baseline, and sodium was significantly higher at baseline (P<0.05), and the difference was statistically significant. The incidence of AEs in DFPP group was lower than in SPE group. The amount of plasma used in DFPP group was significantly less than that in SPE group during hospitalization. Economic cost of hospitalization and remission rate were no significant difference between the two groups. Length of hospital stay and serum creatinine both were the risk factors of ineffective short-term plasma exchange(PE)in the treatment of LN. Conclusions: In summary, both DFPP and SPE were effective and safe procedures for treating LN. However, DFPP did not depend on plasma, and could reduce the incidence of adverse reactions, it should be promoted.

PMID:42250236 | DOI:10.1159/000552429

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A body roundness index (BRI)-based predictive model for metabolic syndrome in perimenopausal and postmenopausal women-from a cross-sectional machine learning study to a longitudinal dynamic assessment

Ann Med. 2026 Dec;58(1):2682583. doi: 10.1080/07853890.2026.2682583. Epub 2026 Jun 6.

ABSTRACT

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is highly prevalent among perimenopausal and postmenopausal women and poses a major public health challenge because of its association with cardiovascular disease, type 2 diabetes, and premature mortality. However, prediction tools for this population remain limited. Therefore, this study aimed to develop a Body Roundness Index (BRI)-based prediction model for MetS by integrating cross-sectional machine learning and longitudinal assessment.

METHODS AND RESULTS: Cross-sectional models were trained using NHANES 2007-2020 and validated in the Affiliated Hospital of Dalian University (2023-2024). Sixteen predictors were selected via LASSO and Boruta, and eight models were evaluated using AUC, calibration, and decision curve analysis. SHAP ranked high-contribution factors. Longitudinal analysis used a 10-year cohort. Annualized change rates and cumulative exposure metrics of five key predictors were combined with baseline values to build Cox models, compared by C-index and time-dependent ROC.The artificial neural network (ANN) demonstrated optimal cross-sectional performance (internal AUC: 0.854; external AUC: 0.878) with good calibration and clinical benefit. SHAP identified BRI, WBC, ALT, MCV, and AST as top contributors, with BRI showing the strongest impact. Longitudinal analysis revealed that integrating annual change rates and annual cumulative exposure of these five predictors achieved optimal discriminative ability (C-index: 0.847), with time-dependent AUCs of 0.853, 0.859, and 0.847 at 1, 3, and 5 years, respectively.

CONCLUSION: BRI is significantly associated with MetS in perimenopausal and postmenopausal women. The ANN model provides an efficient cross-sectional screening tool, while incorporating longitudinal trajectories of BRI and key laboratory indicators enhances long-term MetS risk prediction.

PMID:42250232 | DOI:10.1080/07853890.2026.2682583

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Sericin-based biomaterial for craniomaxillofacial regeneration: Preclinical evidence and translational potential

J Biomater Appl. 2026 Jun 6:8853282261459552. doi: 10.1177/08853282261459552. Online ahead of print.

ABSTRACT

Significant craniomaxillofacial (CMF) bone defects after trauma, tumor removal, or congenital disabilities are a major clinical challenge. Therefore, new methods are continually sought to improve treatment effectiveness. In this context, next-generation biomaterials deserve special attention. Sericin, a protein component of silk, demonstrates regenerative potential. Current evidence suggests that sericin actively stimulates osteogenesis by promoting the differentiation of osteoprogenitor cells and upregulating key markers, including Runx2, osteocalcin, and osteopontin. In addition, it exhibits a favorable biocompatibility profile and promising immunomodulatory properties. By exerting anti-inflammatory effects, sericin may promote a pro-healing polarization of M2 macrophages and reduce TNF-α expression. The antimicrobial potential of sericin-based biomaterials is also highlighted, though the evidence remains debated and further validation is needed, particularly for grafts and scaffolds used in CMF regeneration. Sericin also appears to promote angiogenesis and the organized deposition of mineralized extracellular matrix, which are crucial factors in bone regeneration. In preclinical animal models, sericin-based biomaterials have shown statistically significant improvements in the healing of calvarial, alveolar, and long bone defects. Despite these encouraging findings, the translation of sericin into clinical practice remains limited, with only two human studies available, primarily for minor applications in oral surgery. This review summarizes the current literature focusing on sericin-based biomaterials and relates the available evidence to potential applications in CMF regeneration. In a structured manner, it begins with the physical and biological properties of sericin, proceeds to cellular and tissue interactions, and presents preclinical and clinical evidence, critically evaluating the advantages and limitations.

PMID:42250217 | DOI:10.1177/08853282261459552

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Association between systemic oxidative stress imbalance and inflammatory markers in gouty patients: a cross-sectional case-control study in Yemen

Clin Rheumatol. 2026 Jun 6. doi: 10.1007/s10067-026-08177-w. Online ahead of print.

ABSTRACT

BACKGROUND: Gout is increasingly recognized as a systemic metabolic and inflammatory disorder. The urate paradox-where uric acid shifts from a plasma antioxidant to an intracellular pro-oxidant-remains a clinical challenge in managing systemic complications.

OBJECTIVE: This study evaluates the association between systemic oxidative stress imbalance and high-sensitivity C-reactive protein (hs-CRP) as a marker of inflammatory burden in gouty patients.

METHODS: A case-control study was conducted on 200 participants (100 gouty patients and 100 healthy controls) in Yemen. Biomarkers including malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione (GSH), and hs-CRP were quantified. Multivariate linear regression was used to assess the independent predictive value of MDA for hs-CRP.

RESULTS: Gouty patients exhibited significantly elevated MDA (6.45 ± 1.55 nmol/mL) and hs-CRP (14.2 ± 5.1 mg/L) compared to controls (P < 0.001). Conversely, a profound depletion in TAC and GSH was observed. A statistically significant positive correlation (r = 0.78, P < 0.001) was observed between MDA and hs-CRP. In multivariate analysis, MDA remained a significant independent associate, explaining approximately 61% of the variance in hs-CRP levels (R2 = 0.61, P < 0.001).

CONCLUSION: Gout is characterized by a significant systemic oxidative stress imbalance which is independently associated with systemic inflammation. Clinical management should transcend urate-lowering therapy to include strategies aimed at restoring antioxidant capacity to mitigate systemic inflammatory damage. Key Points • Gouty patients exhibit a profound state of systemic redox exhaustion, characterized by depleted antioxidant defenses. • Lipid peroxidation (MDA) is strongly associated with the systemic inflammatory burden (hs-CRP) in gouty cohorts. • The robust correlation between oxidative stress and inflammatory markers suggests their potential as biomarkers for assessing disease status. • Systemic inflammation in gout appears to be closely linked to the severity of oxidative stress imbalance.

PMID:42250201 | DOI:10.1007/s10067-026-08177-w

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Handling missing data in fibromyalgia clinical trials-considerations for the use of linear mixed models in longitudinal analyses: perspectives in rheumatology

Clin Rheumatol. 2026 Jun 6. doi: 10.1007/s10067-026-08193-w. Online ahead of print.

ABSTRACT

OBJECTIVE: To critically examine current statistical practices for handling missing data in fibromyalgia randomized controlled trials (RCTs) and to provide practical guidance for the implementation of linear mixed models (LMMs).

METHODS: This methodological and narrative perspective reviews recent RCTs in fibromyalgia, highlighting common limitations in the handling of missing data and longitudinal analyses. We contrast traditional approaches, such as repeated-measures ANOVA, with LMM-based strategies within the intention-to-treat (ITT) framework. Additionally, we provide a step-by-step guide for implementing LMMs in SPSS.

RESULTS: Evidence indicates that many fibromyalgia RCTs continue to rely on suboptimal statistical methods, including the exclusion of participants with incomplete data and the use of ANOVA-based approaches. These practices may reduce consistency with the ITT principle, decrease statistical efficiency, and contribute to potentially biased treatment effect estimates. In contrast, LMMs can incorporate partially observed longitudinal data, explicitly model within-subject correlations, and accommodate unbalanced longitudinal designs under the Missing At Random (MAR) assumption. However, their validity depends on correct model specification and the plausibility of underlying assumptions.

CONCLUSIONS: The persistent gap between methodological recommendations and analytical practices in fibromyalgia RCTs may compromise the interpretability and reliability of treatment effect estimates. LMMs may represent a more flexible and methodologically appropriate approach for longitudinal analyses involving incomplete follow-up data, particularly when aligned with study design characteristics and available statistical expertise. Improving statistical rigor in this field remains essential to support more reliable clinical interpretation and evidence-informed decision-making.

PMID:42250200 | DOI:10.1007/s10067-026-08193-w

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Antimicrobial synergism of silver and zinc oxide nanoparticles with antibiotics against clinical isolate of Cutibacterium acnes

Int Microbiol. 2026 Jun 6. doi: 10.1007/s10123-026-00849-6. Online ahead of print.

ABSTRACT

BACKGROUND: The need to develop alternative treatment approaches to acne vulgaris and other skin infections is becoming increasingly urgent due to the rising prevalence of antibiotic resistance in Cutibacterium acnes (a key pathogen related to such conditions). Nanoparticles (NPs) have shown great potential as antimicrobial agents that could improve the effectiveness of traditional antibiotics when administered together. This research examines antibacterial activity of silver NPs (Ag-NPs) and zinc oxide NPs (ZnO-NPs), both independently and when used collaboratively with common anti-acne antibiotics used to treat C. acnes.

METHODS: Ag-NPs and ZnO-NPs were biosynthesized using aqueous Peganum harmala extract as a reducing and stabilizing agent. The synthesized nanoparticles were characterized using UV-Vis spectroscopy, X-ray diffraction (XRD), scanning/transmission electron microscopy (SEM/TEM), and dynamic light scattering (DLS). This research examined two C. acnes clinical isolates (P1 and P2) and one reference strain (NCTC747) were used in this research. Broth microdilution assays were employed to determine minimum inhibitory concentrations (MICs). Checkerboard assays and fractional inhibitory concentration index (FICI) analysis were performed to explore synergy between antibiotics and NPs.

RESULTS: A successful formation of spherical Ag-NPs and hexagonal ZnO-NPs has been confirmed, with average crystallite sizes of approximately 13-14 nm and 53-55 nm, respectively. Both Ag-NPs and ZnO-NPs were found to exhibit strong antibiotic activity. The MICs of the tested antibiotics were significantly reduced when used in combination with AgNPs. The reduction was up to 2-8 fold compared to antibiotic monotherapy. Moreover, most Antibiotic-Ag-NPs combinations exhibited synergistic interactions in the FICI analysis (FICI ≤ 0.5). Meanwhile, there are increased moderate effects resulted from the ZnO-NP combinations. The Antibiotic MIC generally values reduced two-to-four-fold. The relevant FICI values suggested that the interactions were primarily additive (FICI ≈ 0.75), although there was some evidence of strain-dependent variations. A two-way ANOVA test showed that the MIC values reductions for both antibiotics and nanoparticles were statistically significant (p < 0.001).

CONCLUSION: The potential of biosynthesized NPs as adjunct therapeutic agents for the management of acne-associated infections was suggested by their promising antibacterial and antibiotic-enhancing effects against C acnes.

PMID:42250195 | DOI:10.1007/s10123-026-00849-6

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Patient Profile and Treatment Characteristics of Adults and Adolescents Prescribed Ritlecitinib for Alopecia Areata in the USA

Dermatol Ther (Heidelb). 2026 Jun 6. doi: 10.1007/s13555-026-01808-9. Online ahead of print.

ABSTRACT

INTRODUCTION: In June 2023, the US Food and Drug Administration (FDA) approved ritlecitinib (50 mg once daily) for treatment of severe alopecia areata (AA) in patients ≥ 12 years. This study aimed to assess the characteristics of patients prescribed ritlecitinib within the first 10 months following approval.

METHODS: This retrospective study analyzed data from the Komodo Healthcare Map® (Komodo) and OMNY Health Foundation databases. Patients were aged ≥ 12 years with ≥ 1 ritlecitinib prescription on or after June 23, 2023, ≥ 1 AA diagnoses on or before index date (first prescription date), and ≥ 12 months of continuous enrollment before study entry. Two cohorts were assessed: patients with Komodo data (cohort 1) and linked Komodo and OMNY data (cohort 2). Clinical characteristics and AA treatment history were assessed over the 12-month pre-index period and stratified by age (12-17 and ≥ 18 years).

RESULTS: Cohort 1 included 2562 patients; of these, 61.8% were prescribed ritlecitinib by a dermatologist, 58.9% were female, and 35.2% were adolescents. Approximately 24% had alopecia totalis/alopecia universalis as the closest diagnosis prior to index, 12.4% had ≥ 1 other autoimmune disorder, 23.9% had ≥ 1 atopic disorder, and 23.7% had ≥ 1 diagnosis of a mental health condition captured. In cohort 1 during the 12 months before index date, 26.6% of patients received no AA treatments, 31.9% received systemic immunomodulators, and 31.3% received injectable corticosteroids. Cohort 2 included 381 patients; of those in cohort 2 with reported disease location, hair loss primarily occurred on the scalp (90.5%) and face (43.2%). In cohort 2, 77.2% of patients with a scalp hair loss (SHL) assessment had ≥ 50% SHL.

CONCLUSIONS: In the first 10 months following US approval, ritlecitinib was prescribed to a broad range of patients, including those with and without prior treatments and comorbidities. This suggests that ritlecitinib may provide new opportunities to engage or re-engage patients in AA-directed care.

PMID:42250189 | DOI:10.1007/s13555-026-01808-9

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Is tattooing associated with an increased risk of cancer? A systematic review and meta-analysis

Clin Transl Oncol. 2026 Jun 6. doi: 10.1007/s12094-026-04388-4. Online ahead of print.

ABSTRACT

BACKGROUND: Tattoo inks may contain carcinogenic compounds, and pigment migration to lymphatic tissues raises concerns regarding potential cancer risk. Epidemiological evidence remains inconclusive.

OBJECTIVES: To assess the association between tattoo exposure and the incidence of skin cancer and hematological malignancies.

METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to January 2026 for cohort and case-control studies comparing cancer incidence in tattooed versus non-tattooed adults. Random-effects meta-analyses using restricted maximum-likelihood estimators were performed to pool odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was quantified using I2 statistics. Risk of bias was assessed using ROBINS-E, and certainty of evidence was evaluated with GRADE. Leave-one-out sensitivity analyses were conducted.

RESULTS: Seven observational studies including 140,841 participants were analyzed. Tattoo exposure was not associated with overall skin cancer (OR 0.92; 95%CI 0.83-1.04; I2 = 0%; p = 0.179). Stratified analyses by number of tattoo sessions showed no significant associations: one session (OR 1.08; 95%CI 0.55-2.12; I2 = 92.4%), two-to-three sessions (OR 0.90; 95%CI 0.62-1.32; I2 = 63.2%), and ≥ 4 sessions (OR 0.70; 95%CI 0.29-1.70; I2 = 88.5%). For hematological malignancies, pooled analysis showed no significant association (OR 1.02; 95%CI 0.78-1.32; I2 = 64.9%; p = 0.910). Subtype analyses were non-significant: non-Hodgkin lymphoma (OR 1.00; 95%CI 0.73-1.36; I2 = 3.7%), Hodgkin lymphoma (OR 1.19; 95%CI 0.59-2.40; I2 = 91.7%), diffuse large B-cell lymphoma (OR 0.90; 95%CI 0.57-1.44; I2 = 61.7%), T-cell lymphoma (OR 1.07; 95%CI 0.61-1.88; I2 = 0%), and follicular lymphoma (OR 0.99; 95%CI 0.72-1.36; I2 = 1.9%). Sensitivity analysis excluding one influential study rendered the association for overall hematological malignancies statistically significant (OR 1.20; 95%CI 1.05-1.39; I2 = 0%). Certainty of evidence ranged from low to moderate.

CONCLUSIONS: Tattoo exposure was not associated with increased skin cancer risk and showed no significant association with hematological malignancies in primary analyses. A significant association emerged only after sensitivity analysis, warranting cautious interpretation and further prospective investigation.

PMID:42250187 | DOI:10.1007/s12094-026-04388-4