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Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial.

OBJECTIVE: Stratification of therapeutic responses may help identify efficacious therapies for osteoarthritis (OA). In the PROMOTE randomised trial, participants with elevated baseline high-sensitivity C-reactive protein (hs-CRP) showed greater pain reduction after methotrexate treatment. We set out to interrogate a broader panel of serum/plasma inflammatory response markers relevant to methotrexate actions as potential biomarkers of therapeutic effect. Our objectives were to: (i) characterize changes in these systemic markers during methotrexate treatment; determine whether (ii) baseline levels or (iii) changes in any marker during treatment were associated with treatment response; and (iv) compare these findings with the more established clinical inflammatory marker, hs-CRP. DESIGN: Plasma/serum samples from participants in PROMOTE's biological substudy were analysed for 35 inflammatory markers at baseline (pre-treatment) and at 6-months (post-treatment), by MesoScale V-plex multiplex assay. Those with paired biological and clinical data at both baseline and 6-months were included in the substudy analysis set. Relationships between markers and overall data structure were assessed by Pearson correlation and Principal Component analysis. Associations between markers (baseline levels or change over time) and change in average knee pain severity in past week (numerical rating scale, NRS) were evaluated by univariable linear regression, adjusting for baseline age, sex, and body mass index. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling enabled marker selection. Benjamini-Hochberg correction adjusted for multiple testing (Padj). RESULTS: 87 participants with paired blood marker and clinical data were eligible for substudy analysis. 18/35 markers were quantifiable and analysed. Systemic IL-8 and TNF-α levels decreased (Padj=0.015, 0.048 respectively) while IL-15 increased (Padj=0.033) with methotrexate treatment over 6-months. Analysing within this active treatment randomised arm, higher baseline IFN-γ was associated with greater reduction in NRS pain change (0.66 [0.01, 1.31], P=0.047), as was decreasing TNF-α over 6-months (2.25 [0.00, 4.5], P=0.049). LASSO identified higher IFN-γ, lower plasma IL-15 and IL-16, and younger age as the most important baseline predictors of pain improvement. hs-CRP was highly selected by LASSO for treatment response in both arms. In a secondary univariate treatment arm-by-biomarker interaction analysis, of the 19 markers, only hs-CRP showed consistent effects in adjusted models (at baseline, coeffic. 2.34 [0.53, 4.15], P=0.001; change over 6-months, (0.36 [0.06, 0.66], P=0.018). CONCLUSIONS: Blood measurement of IFN-γ, TNF-α, IL-15 and IL-16 as well as hs-CRP could act as potential markers to stratify the treatment response by average knee pain to methotrexate in knee osteoarthritis.

Humans

The radiographic effect of cage subsidence on neuroforamina after anterior cervical discectomy and fusion.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: The objective of this study is to investigate the effect of cage subsidence on neuroforaminal area after anterior cervical discectomy and fusion (ACDF) utilizing computed tomography (CT). SUMMARY OF BACKGROUND DATA: Restoration of disc height via implantation of an interbody device provides an indirect decompression of the cervical neuroforamina. Interbody cage subsidence is a potential postoperative occurrence, but the effect of this on neuroforaminal area has yet to be characterized. METHODS: A retrospective review was conducted of patients who underwent one- to four-levels of ACDF utilizing an interbody device with anterior plating. Cage subsidence, neuroforaminal area, height and width were measured on CT scans preoperatively and at least 6&#xa0;months postoperatively. Levels with a cumulative sum of cranial and caudal subsidence greater than 4&#xa0;mm were classified as severely subsided, while levels with cumulative subsidence less than 4&#xa0;mm were classified as non-severely subsided. RESULTS: A total of 83 patients (151 levels) were included in this retrospective analysis. Average endplate subsidence was 3.2&#xa0;&#xb1;&#xa0;1.9&#xa0;mm. Non-severely subsided levels demonstrated a greater perioperative increase in neuroforaminal area (7.9 vs 2.1&#xa0;mm2, p&#xa0;<&#xa0;0.001), neuroforaminal height (1.1 vs 0.4&#xa0;mm, p&#xa0;<&#xa0;0.001) and neuroforaminal width (0.7 vs 0.1&#xa0;mm, p&#xa0;<&#xa0;0.001) compared to severely subsided levels. Interbody subsidence significantly predicted a decreased change in neuroforaminal height, width and area (p&#xa0;<&#xa0;0.001). Severe subsidence was associated with an increased rate of pseudarthrosis, but similar reoperation rates and recurrent neurologic deficits between the two groups. CONCLUSIONS: Severe subsidence of interbody cages after an ACDF was associated with a decreased perioperative change in neuroforaminal dimensions. This decrease in the size of the neuroforamen may reduce the effect of indirect decompression of the nerve root.

Humans

Vestibular schwannoma associated normal pressure hydrocephalus: clinical features and shunt responsiveness compared with idiopathic NPH.

BACKGROUND: Vestibular schwannoma (VS) is commonly associated with obstructive hydrocephalus due to mass effect; however, a rarer communicating form resembling normal pressure hydrocephalus (NPH) has also been described, possibly related to impaired CSF absorption from elevated CSF protein. We aimed to characterize the clinical and imaging features of VS-associated NPH (VS-NPH) and compare them with those of an idiopathic NPH (iNPH) cohort. METHODS: We retrospectively analyzed 18 patients with VS-NPH identified between 2008 and 2024. For comparison, 41 iNPH patients were drawn from a prospective longitudinal study at our center. Variables included demographics, tumor size, VS treatment modality, CSF parameters, Radscale imaging features, and shunt responsiveness. RESULTS: VS-NPH patients had markedly higher CSF protein levels than patients with iNPH (median 100 vs. 51&#xa0;mg/dL, p&#xa0;<&#xa0;0.001). Radiological features largely overlapped; however, parasagittal sulcal narrowing was more frequent in VS-NPH (61&#xa0;% vs.13&#xa0;%, p&#xa0;=&#xa0;0.002). These differences remained significant in the sensitivity analysis excluding the two patients without gait impairment. VS-NPH patients were younger in the primary analysis (66.8 vs. 72.0&#xa0;years, p&#xa0;=&#xa0;0.03), while exploratory associations between larger tumor size and both earlier NPH symptom onset (r&#xa0;=&#xa0;-0.48, p&#xa0;=&#xa0;0.049) and smaller callosal angle (r&#xa0;=&#xa0;-0.49, p&#xa0;=&#xa0;0.048) attenuated to non-significant trends in the sensitivity analysis. Tumor size was&#xa0;<&#xa0;30&#xa0;mm in 89&#xa0;% of patients. Ventriculoperitoneal shunt (VPS) resulted in clinical improvement in both groups, although response rates were numerically lower in VS-NPH than in iNPH (63&#xa0;% vs.75&#xa0;%). CTT was positive in 9 of 11 VS-NPH patients who underwent testing, although improvement after shunting also occurred in patients with negative CTT results or without prior CTT. CONCLUSIONS: VS-NPH may represent a secondary subtype of NPH with distinct biochemical and subtle imaging features. Elevated CSF protein may contribute to altered CSF dynamics. These findings are exploratory and require confirmation in larger prospective studies.

Humans

Psychometric Evaluation of the Breast Inflammatory Symptom Severity Index Versions 2 and 3 Among Lactating Women.

OBJECTIVE: To evaluate the psychometric properties of Versions 2 and 3 of the Breast Inflammatory Symptom Severity Index (BISSI). DESIGN: Secondary data analysis of clinical trial data. SETTING: Private physiotherapy practices, a public tertiary hospital, and a community in Melbourne, Australia. PARTICIPANTS: Women more than 7 days after birth with inflammatory conditions of the lactating breast (N = 43). METHODS: We performed confirmatory factor analysis of the BISSI Version 2 to examine item loading, which informed development of the BISSI Version 3 (V3). We assessed convergent validity by comparing total BISSI V3 scores with human milk sodium to potassium ratio (Na+:K+) at Trial Days 1, 3, and 10 using Bland-Altman plots. We compared item-level scores for size of affected area with objective receiver operating characteristic curve analysis to assess discriminant validity for symptom severity and Cronbach's alpha for internal reliability. RESULTS: After confirmatory factor analysis, we removed two items, resulting in a six-item BISSI V3. All retained items demonstrated comparable loading on the overall scale. Limits of agreement for total BISSI V3 scores and item-level scores for size of affected area were acceptable at all time points, with more than 90% of observations falling within 2 standard deviations of the mean difference, supporting convergent validity. Discriminant validity of the BISSI V3 was supported. We found high internal reliability at both time points CONCLUSION: Our findings provide evidence for the validity and reliability of the BISSI V3 and support its continued development and for clinical use of the BISSI V3 and human milk Na+:K+ analysis to enhance management of inflammatory conditions of the lactating breast.

breastfeeding

Bipolar circumcision with mucocutaneous plane separation: A safe, precise, blood-sparing, dressing-free approach.

Conventional circumcision techniques may result in bleeding, limited control of the mucosal collar, and the need for dressings. We describe a modified bipolar technique enabling near-bloodless dissection with precise mucosal trimming. Following bipolar division of the preputial skin, the inner mucosa is separated using two forceps and retracted proximally, creating a protective plane for safe skin adjustment. The mucosal collar is trimmed with scissors. The wound is closed with sutures and 2-octyl cyanoacrylate, avoiding dressings. This technique has been performed in 55 consecutive cases (median age: 2 years and 2 months; range: 0 days-17 years and 5 months) with no reported complications over a median follow-up of 2 years and 7 months (range: 3 months-4 years and 1 month).

Humans

A randomized study of antibiotic prophylaxis after hypospadias repair in children.

BACKGROUND AND OBJECTIVE: Antibiotic resistance is a challenge in contemporary world. Urethroplasty for hypospadias is one of the most common urological surgeries performed around the world, yet, there is still no consensus on the use of antibiotics pre- and post-operatively. Our objective was to analyze the effectiveness of antibiotic prophylaxis and therapy before, during, and after hypospadias repair in children. METHODS: A prospective randomized trial was carried out including patients with coronal hypospadias who underwent urethroplasty performed by one surgeon. Urethral catheters were used in all cases for 10 days. Study participants were randomly assigned in a 1:1:1 ratio to receive a single intraoperative administration of antibiotics (Group I); an intraoperative antibiotic prophylaxis and antibiotic therapy for 10 days until the removal of urethral catheter (Group II); no antibiotic administration (Group III). Randomization was performed using computer-generated permuted blocks with randomly varying block sizes, prepared by an independent statistician. The results were analyzed using the analysis of variance (ANOVA). The following criteria were compared: postoperative functional complications, such as: urethral fistula, stenosis, diverticulum; wound infection symptoms: hyperemia of surgical site, pain during palpation, and symptomatic urinary tract infection. RESULTS: A total of 300 patients were included in the study. Two patients (2%) in Group I, two patients (2%) in Group II, and four patients (4%) in Group III had urethral fistulas, requiring surgery 6 months after primary repair, yet without statistical difference between groups. We found no significant difference in frequency of symptomatic UTIs between three groups (p = 0.182). CONCLUSION: There is no effect of antibiotic prophylaxis and therapy on the frequency of postoperative surgical and infectious complications after urethroplasty for coronal hypospadias repair in children.

Humans

Factors associated with additional intervention requirement following ESWL in pediatric patients with urolithiasis.

OBJECTIVE: To identify predictors of additional intervention following extracorporeal shock wave lithotripsy (ESWL) in pediatric patients and to develop a clinically applicable predictive model. MATERIALS AND METHODS: This retrospective cohort study included 647 pediatric patients who underwent ESWL between 2015 and 2025. Demographic, clinical, and radiological variables were analyzed. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of additional intervention. Model performance was evaluated using receiver operating characteristic curve analysis. RESULTS: Additional intervention was required in 65 patients (10.0%). On multivariable analysis, stone size 10-20 mm (OR: 3.04, p = 0.003), moderate (OR: 2.16, p = 0.049) and severe hydronephrosis (OR: 6.05, p < 0.001), and multiple stones (OR: 3.52, p = 0.030) were identified as independent risk factors. Increasing age (OR: 0.84, p = 0.026), history of urolithiasis (OR: 0.41, p = 0.006), and lower calyx location (OR: 0.14, p = 0.034) were associated with a reduced risk. The model demonstrated good discriminative performance (AUC: 0.794), with a sensitivity of 72% and specificity of 75%. Internal validation using bootstrap resampling demonstrated stable model performance, yielding a corrected AUC of 0.732. CONCLUSION: Stone burden, hydronephrosis severity, and stone multiplicity are key determinants of additional intervention after ESWL in pediatric patients. The proposed model shows good predictive performance and may support individualized risk stratification and clinical decision-making.

Humans

Comparison of deep and nondeep hypothermia in thoracic and thoracoabdominal aortic surgery: A systematic review and meta-analysis.

OBJECTIVE: Deep hypothermic circulatory arrest (DHCA) remains a cornerstone technique for neuroprotection and end-organ preservation during ascending aorta and arch surgeries. However, its benefits and risks compared with non-DHCA strategies in thoracic and thoracoabdominal aortic aneurysm (TAAA) repair are uncertain owing to conflicting evidence and variable institutional practices. METHODS: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Cochrane guidelines. PubMed, Embase, and Cochrane Library were searched for comparative studies evaluating DHCA and non-DHCA techniques for open thoracic and TAAA repair. Random-effects models were applied to calculate pooled effect estimates. Effect sizes were risk ratio (RR) for binary end points and mean difference for continuous end points, both with 95% confidence intervals. Statistical significance was set at P < .05. Between-study heterogeneity was estimated using the I2 statistic. Metaregression analyses were used to explore the sources of heterogeneity. RESULTS: Nine observational studies, including 1041 patients, were analyzed. DHCA use was associated with a significantly lower risk of spinal cord injury (RR, 0.44; P = .012) compared with non-DHCA. However, DHCA was also associated with prolonged postoperative ventilation time (RR, 1.34; P = .003). No significant differences were observed in overall mortality, length of hospital and intensive care unit stay, stroke, or renal complications. Metaregression identified patient age as a moderator of length of stay variability, with older cohorts demonstrating longer recovery periods. CONCLUSIONS: DHCA is associated with a lower risk of spinal cord injury during TAAA repair without increasing mortality or stroke risk, although it is associated with longer ventilation times.

Humans

The musculoskeletal pain literacy questionnaire (MSK-PLq) - Part 1: Development of a preliminary version through a systematic review and Delphi consensus.

OBJECTIVE: Chronic musculoskeletal (MSK) pain is a leading cause of disability worldwide, and self-management is a first-line approach recommended by international clinical guidelines. Access to evidence-based information that enhances health literacy may support patients' engagement in their self-management and treatment decision-making, potentially reducing disease burden and pain. However, no tool currently exists to assess health literacy specifically in MSK pain. This study aimed to develop and describe the preliminary version of a knowledge-based questionnaire to evaluate MSK pain literacy, the Musculoskeletal Pain-Literacy questionnaire (MSK-PLq). METHODS: A systematic literature review identified existing health literacy instruments and generated a preliminary list of domains. A two-round Delphi study with 22 panellists (19 experts and three people living with chronic MSK pain), followed by consensus meetings, was used to refine domains and items (&#x2265;70% agreement). Readability was assessed using the Flesch Reading Ease (FRE) score and three stakeholders were consulted to review the questionnaire for comprehensibility, clarity, and face validity. RESULTS: Six domains were retained (Understand, Access, Appraise, Apply, Digital, Beliefs), comprising 20 items in the preliminary version of MSK-PLq. Readability was acceptable (mean FRE 74, indicating fairly easy reading), and subject feedback supported the questionnaire's clarity and face validity. CONCLUSIONS: The preliminary version of the MSK-PLq is proposed as the first knowledge-based tool to assess functional, interactive, and critical aspects of MSK pain literacy. It may have applications in clinical practice, research, education, and digital health, by informing tailored patient education and supporting self-management strategies, although further psychometric validation is required.

Humans

Prophylactic folinic acid prevents pemetrexed myelosuppression: A randomized trial toward safer treatment with chemotherapy in non-small cell lung cancer.

Background Pemetrexed is a cornerstone in advanced non-small cell lung cancer treatment. Although generally well tolerated, severe myelosuppression occurs in 26% of patients. Preventing chemotherapy-associated toxicity has become increasingly important with the introduction of osimertinib combined with pemetrexed-based chemotherapy. Due to substantial toxicity, this regimen is often not administered to frail patients. Folinic acid prophylaxis can mitigate pemetrexed-induced toxicity, however its preventive use has not been routinely studied. We aimed to investigate the efficacy of folinic acid prophylaxis to reduce myelosuppression. Methods Fifty patients treated with pemetrexed were randomized (1:1) to receive pemetrexed with or without oral folinic acid prophylaxis on days 2-4 after each chemotherapy cycle. The primary endpoint was absolute neutrophil count (ANC) after the first chemotherapy cycle. Secondary endpoints included ANC after the second cycle, grade neutropenia, treatment efficacy, renal function and incidence of dose modifications. Results Twenty-four patients received folinic acid and twenty-six served as controls. Higher ANC were observed in the folinic acid group after the first cycle (median 3.79; IQR 2.22-4.93 vs. 1.85; IQR 1.43-3.78; p.

Humans

Modulating sentence comprehension in people with aphasia through anodal tDCS: A double-blind randomized cross-over study.

This double-blind randomized cross-over study investigated the effects of perilesional anodal transcranial direct current stimulation (AtDCS) combined with speech-language therapy on sentence comprehension in eight individuals with chronic nonfluent agrammatic aphasia. The behavioral therapy consisted of an intensive comprehension treatment including drilling in sentence-to-picture matching and Mapping Therapy. Each participant underwent both the anodal tDCS and sham stimulation conditions (five received sham first followed by real stimulation, and the remaining three the reverse sequence), with each condition paired with the same behavioral treatment and separated by a four-month washout period. Stimulation was applied over the perilesional area (left BA6) for 20&#x202f;min during daily 40-min therapy sessions over four consecutive weeks. Sentence comprehension was assessed with the RiComprendo battery and functional communication with the Communicative Effectiveness Index (CETI). Data were analyzed using paired t-tests, Bayesian analyses, and linear mixed-effects models to control for baseline performance and individual variability. Both stimulation conditions produced significant pre-to-post improvements in sentence comprehension, particularly for syntactically complex structures such as passives and center-embedded object relatives. However, gains were overall greater following AtDCS, as reflected in larger effect sizes, stronger Bayes factors, and a significant treatment effect in the mixed-effects models. Only the AtDCS condition yielded significant improvements in self-perceived comprehension abilities on the CETI. These findings suggest that AtDCS over perilesional cortical areas may boost the effects of traditional language therapy on sentence comprehension, supporting its feasibility and potential as an adjuvant intervention in post-stroke aphasia rehabilitation.

Humans

Exploring the role of successful exercise-induced body weight loss on cardiometabolic health in individuals with metabolic syndrome.

BACKGROUND AND AIM: High-intensity interval training (HIIT) is known to improve cardiorespiratory fitness (i.e., VO2MAX), a key marker of cardiometabolic health in individuals with metabolic syndrome (MetS). Nonetheless, body weight loss is widely recognized as a crucial factor in reducing insulin resistance and improving metabolic risk factors. Thus, we aimed to determine the importance of body weight loss following exercise training on improving MetS. METHODS AND RESULTS: Two hundred and twenty-eight adults (55.3&#xa0;&#xb1;&#xa0;7.9&#xa0;yr) with overweight/obesity (32.5&#xa0;&#xb1;&#xa0;4.6&#xa0;kg&#xb7;m-2) and MetS were randomized to: a) standard health care non-exercise group (CONTROL group, N=58) or b) standard health care plus 16 weeks of HIIT (EXER group, N=170). MetS (MetS z-score), insulin resistance (HOMA-IR), cardiorespiratory fitness (VO2PEAK), maximal cycling power (WPEAK), and body weight/composition were assessed. After intervention, EXER group participants were divided according to their weight loss response to training: i) those achieving the weight loss predicted from estimated exercise energy expenditure (-BW group, n=78; -3.3&#xa0;&#xb1;&#xa0;2.2&#xa0;kg); ii) those not reaching the expected weight loss (=BW group, n=38; -0.7&#xa0;&#xb1;&#xa0;0.5&#xa0;kg); iii) and those who gained weight (+BW group, n=54; 1.1&#xa0;&#xb1;&#xa0;1.0&#xa0;kg). VO2PEAK significantly improved regardless of body weight loss response (-BW, 0.3&#xa0;&#xb1;&#xa0;0.3; =BW, 0.2&#xa0;&#xb1;&#xa0;0.3; +BW, 0.3&#xa0;&#xb1;&#xa0;0.2&#xa0;L&#xb7;min-1; all p&#xa0;<&#xa0;0.001) compared to CONTROL group (0.0&#xa0;&#xb1;&#xa0;0.3&#xa0;L&#xb7;min-1). However, significant improvements in MetS z-score (-0.31&#xa0;&#xb1;&#xa0;0.41) and HOMA-IR (-0.7&#xa0;&#xb1;&#xa0;1.6) were observed only in the -BW group (both p&#xa0;<&#xa0;0.001). CONCLUSIONS: Exercise recommendations should consider that greater improvements in MetS are observed when interventions are accompanied by successful body weight loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05120778.

Humans

Acute and chronic effects of mixed nuts on energy metabolism in women at cardiometabolic risk: a randomized clinical trial.

BACKGROUND AND AIMS: The effect of consuming a mix of Brazilian nuts on energy metabolism has not been explored. Thus, the present study aimed to evaluate the effects of acute and chronic consumption of mixed nuts on markers of energy metabolism in women with overweight/obesity. METHODS AND RESULTS: This is a randomized, controlled, and parallel clinical trial with adult women. In an acute study, participants received a beverage containing mixed nuts (30&#xa0;g of cashew nuts&#xa0;+&#xa0;15&#xa0;g of Brazil nuts) or a control beverage, and energy metabolism markers were assessed for up to 3&#xa0;h postprandially. For the chronic study, participants received 45&#xa0;g of a mix of nuts/day and a -500kcal energy-restricted diet (MNG) or only a -500kcal energy-restricted diet free of nuts (CTG) for 8 weeks, and energy metabolism was assessed before and after the intervention period. In the postprandial period, fat oxidation was higher in the MNG than in the CTG (piAUC: 47.53&#xa0;&#xb1;&#xa0;5.78&#xa0;mg/min vs. 27.93&#xa0;&#xb1;&#xa0;6.98&#xa0;mg/min; p&#xa0;=&#xa0;0.048). After 8 weeks of the intervention, fasting fat oxidation increased in the MNG (+16.0&#xa0;&#xb1;&#xa0;7.0&#xa0;mg/min) and decreased in the CTG (-5.0&#xa0;&#xb1;&#xa0;6.0&#xa0;mg/min), with no significant difference between groups. Other acute and chronic markers also showed no significant changes between groups. CONCLUSION: The acute consumption of mixed nuts increased postprandial fat oxidation, whereas chronic intake within an energy-restricted diet did not affect energy metabolism markers in women at cardiometabolic risk. REGISTRATION NUMBER FOR BRAZILIAN REGISTRY OF CLINICAL TRIALS: RBR-3ntxrm.

Humans

Comparative safety of lipid-lowering drugs alone or in combination: insights from a systematic review and network meta-analysis.

BACKGROUND AND AIMS: Although the safety profile of lipid-lowering therapies (LLTs) is known, there are no comprehensive comparative assessments. We aimed to compare the risk of muscle-related events, diabetes, liver dysfunction, and cognitive disorders among LLTs through a network meta-analysis. METHODS AND RESULTS: Databases were searched from inception to May 2025. Eligible studies included adult patients, using statins, ezetimibe, PCSK9 monoclonal antibodies (PCSK9mAbs), inclisiran, bempedoic acid, or their combinations as intervention, reporting the information about any of the selected adverse events, a total sample size of &#x2265;200 subjects, and had &#x2265;1 month of intervention. Pooled estimates were assessed by fixed effects model within a frequentist setting. Pooled relative risks (RR) and their 95% confidence interval were estimated. A total of 303,397 subjects from 153 RCTs were included. Bempedoic acid ranked the lowest risk of myalgia (vs PCSK9mAbs, RR 0.80 [0.69, 0.93]). PCSK9mAbs were associated with lower incidence of creatine kinase (CK) elevation, diabetes, and liver dysfunction comparing to statins (statins vs PCSK9mAbs, RR 1.44 [1.14, 1.81], RR 1.13 [1.05, 1.22], and RR 1.38 [1.17, 1.62], respectively). In terms of muscle-related events and cognitive disorders, no significant risk differences were found among treatments and their combinations. CONCLUSIONS: PCSK9mAbs appear to have a more favourable safety profile regarding the risk of CK elevation, diabetes, and liver dysfunction. Bempedoic acid seem to be a better choice for subjects with high risk of myalgia. This information can be valuable when selecting therapy for specific patient subgroups at higher risk of certain adverse events.

Humans

Effectiveness of kinesiologic tape in the management of postoperative trismus, discomfort, and edema in mandibular fractures: a randomized controlled trial.

OBJECTIVE: This study compared kinesiologic taping (KT) with conventional elastic adhesive bandaging in managing postoperative morbidity following open reduction and internal fixation. STUDY DESIGN: In this prospective, randomized controlled trial conducted at KLE Dr Prabhakar Kore Hospital, 26 patients with unilateral mandibular fractures were allocated into two groups: Group 1 received an elastic adhesive bandage (n = 13) and Group 2 used KT (n = 13). Pain (Visual Analog Scale), facial swelling (standardized linear measurements), and maximum interincisal distance were recorded at baseline and on postoperative Days 2 and 5. Data were analyzed using repeated measures ANOVA and independent t tests (p < .05). RESULTS: The KT group showed significantly lower pain scores and reduced facial edema at Days 2 and 5 compared with controls (P < .05). Trismus improved in both groups without significant intergroup differences. No adverse effects were observed. CONCLUSIONS: KT is a safe and effective adjunct for reducing early postoperative pain and edema after mandibular fracture fixation.

Humans

Disparities in guideline-adherent cardiovascular preventive care for people with diabetes: A systematic review and meta-analysis.

BACKGROUND: Clinical practice guidelines offer guidance on delaying the progression of cardiovascular disease in people living with diabetes. We sought to determine whether guideline-recommended cardiovascular preventive care for people living with diabetes differs according to sociodemographic indicators, globally. METHODS: We conducted a systematic review of studies that compared the sociodemographic characteristics of people diagnosed with type 1 or 2 diabetes who received cardiovascular preventive care as recommended by guidelines to those who did not. Sociodemographic predictors were defined by PROGRESS+ (an equity framework). We searched MEDLINE, EMBASE, and APA PsychInfo from 2010 to January 21, 2026. Studies were screened independently by two people. One person assessed the risk of bias and extracted data, and another verified. We pooled results using a random-effects model and assessed the certainty of evidence using GRADE. RESULTS: Twenty-five studies were included. Meta-analyses showed female, Black, and Hispanic individuals had slightly lower odds of receiving guideline-recommended prescriptions for lipid-lowering medication compared to Male, and White individuals, respectively (OR:0.89, 95%CI:0.79,1.00, moderate certainty; OR:0.78, 95%CI:0.74,0.81, high certainty; OR:0.86, 95%CI:0.59,1.26, low certainty). Individuals aged 18-45 years had moderately lower odds (OR:0.33, 95%CI:0.19,0.57, moderate certainty), no observed association for Asian individuals. Asian individuals had moderately lower odds of antihypertensive medication prescription (OR:0.42, 95%CI:0.38,0.46, high certainty). Evidence suggests likely no association between HbA1c testing and sex/gender or between sex/gender and lipid panel testing. CONCLUSIONS: Some disparities in guideline-recommended cardiovascular preventive care among people living with diabetes were found. These results are consistent with previous reviews and highlight the need to ensure guidelines consider equity and with improved dissemination.

Humans

The effectiveness of digital health interventions for type 2 diabetes in underserved populations: A systematic review and meta-analysis.

This systematic review and meta-analysis of 12 randomized controlled trials (1835 participants) evaluated whether digital health interventions (DHIs) improve glycemic control among underserved adults with type 2 diabetes (T2D), including racial/ethnic minority, low-income, Medicaid-insured, rural, and low-health-literacy populations. Searches of PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to December 20, 2025 identified eligible parallel-group randomized controlled trials reporting change in hemoglobin A1c (HbA1c). Two reviewers independently screened studies, extracted data, and assessed risk of bias using the revised Cochrane Risk of Bias 2 tool. Random-effects meta-analysis showed that DHIs produced a modest but statistically significant HbA1c reduction versus control (mean difference, -0.37 %age points; 95% CI, -0.44 to -0.30; P&#x202f;<&#x202f;.0001; equivalent to -4.0&#x202f;mmol/mol). Heterogeneity was moderate-to-substantial (I&#xb2; = 69.9%). Subgroup analyses suggested directionally similar effects by population group and intervention modality, but interpretation was limited by study-level data and the small number of trials. Funnel-plot inspection and Egger's test (P&#x202f;=&#x202f;.31) did not suggest major small-study effects, although power was limited. Overall certainty for HbA1c was moderate. DHIs may support more equitable diabetes care when implemented with cultural tailoring, language access, digital-literacy support, and technology-access safeguards.

Humans

Efficacy and safety of JAK inhibitors in Beh&#xe7;et syndrome: systematic literature review.

OBJECTIVES: Given the active role of the JAK signaling pathway and the multifactorial immune mediators observed in Beh&#xe7;et syndrome (BS), JAK inhibitors (JAKi) may be promising agents. In this systematic literature review (SLR), we aim to evaluate the efficacy and safety of JAKi in BS. METHODS: A systematic literature search was conducted in Embase, PubMed, and the Cochrane Library to identify all reports on the efficacy and safety of JAKi in patients with BS. The SLR protocol was registered with the International Prospective Registry of Systematic Reviews (CRD420251000172). We additionally presented our patient with gastrointestinal involvement treated with upadacitinib. RESULTS: Among the 92 patients (48 men, mean (SD) age 38.5 (13.5) years), 46 used tofacitinib, 31 used baricitinib, and 15 used upadacitinib. All but 1 patient had used at least one previous conventional immunosuppressive, and 57.6% were refractory to at least one prior tumor necrosis factor inhibitor. JAKi were used in combination with conventional immunosuppressive and/or glucocorticoids in 90.6% of the patients. The primary indication for JAKi initiation was gastrointestinal involvement in 46 (50%) patients including our patient, vascular involvement in 22 (23.9%), uveitis in 19 (20.6%), and mucocutaneous and/or articular involvement in 5 (5.6%) patients. The remission rates for overall, gastrointestinal, vascular, and eye involvement were 85.9%, 82.6%, 90.9%, and 84.2%. Serious adverse events were observed in 5.4% of the patients. No thrombotic events were reported. CONCLUSION: This SLR showed that JAKi may be effective in refractory BS patients with a favorable safety profile.

Humans