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Systematic reviews

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PubMed2026

Polygenic risk scores in major depressive disorder: A systematic review across diagnostic, treatment, course/severity, and subtype domains.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous across diagnostic, treatment-related, course/severity, and subtype domains. Polygenic risk score (PRS) studies have examined these domains, but differences in PRS sources, samples, methods, and endpoint definitions have fragmented the evidence. We synthesised findings and examined potential contributors to heterogeneity. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science were searched for studies published from January 2016 through 25 November 2025. Result records were synthesised using SWiM, and certainty was assessed with an adapted GRADE framework. RESULTS: Sixty studies contributed 493 retained records; 450 were descriptively classified as positive, null, or reverse, although records were not independent. Positive findings accounted for 44/56 diagnostic, 61/273 treatment-related, 64/100 course/severity, and 14/21 subtype records. For MDD/depression-derived PRSs and case-control MDD status, all 10 contributing studies showed higher liability in cases (exploratory exact sign test p = 0.002; FDR q = 0.004). The same PRS group showed positive findings for overall depressive symptom severity (14/18), although the study-level test was imprecise (5/5 studies; p = 0.063). Pharmacological response/remission findings for these PRSs were mostly null or directionally mixed (10 positive, 18 null, and 9 reverse). Treatment-resistant depression (TRD) findings differed by operational definition. Atypical and psychotic subtype signals arose mainly from single-study PRS and endpoint contrasts. CONCLUSIONS: PRS evidence was clearest for MDD diagnostic status and showed a tentative pattern for overall symptom burden. Treatment and subtype findings were less consistent or less replicated. Larger, ancestrally diverse studies with standardised endpoints and transparent PRS methods are needed.

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PubMed2026

Anabolic androgen therapy in critically ill adults: A systematic review and meta-analysis.

Critical illness is characterized by a catabolic, proinflammatory state. Anabolic agents, such as testosterone, have therefore been proposed as therapeutic targets. Our objectives were to assess the effects of testosterone in critically ill populations on patient-important outcomes and identify design limitations to inform future studies. We searched for randomized control trials (RCTs) through Medline, Embase, and EBM Reviews databases from inception through February 24, 2026, including English language articles enrolling adults (≥18 years) admitted to ICU where anabolic androgen therapies (AAT) were compared with placebo or standard of care. Studies had to report at least one of: mortality, ICU and hospital lengths of stay, or duration of mechanical ventilation. We extracted data independently using a standardized data extraction tool, and feedback was received from all co-authors to ensure agreement. For each outcome, we performed meta-analyses using a random-effects model with inverse variance weighting in RevMan. We used the GRADE approach to assess certainty in pooled estimates of effect. Of 1325 screened articles, we found 4 that fit our inclusion criteria. Together, we judged risk of bias as 'some concerns' in 3 trials and 'high' in the final trial, and ultimately found that the effects of anabolic-androgen therapy on patient-important outcomes uncertain. With the uncertainty of current evidence for the effects of anabolic-androgen therapy in critically ill adults, there is insufficient support for its routine use. Future randomized evidence is needed to determine whether anabolic-androgen therapy improves clinically-important outcomes and better define its safety profile in critically ill adults.

Humans↗

PubMed2026

Understanding FDA's reasons for nonapproval: A systematic review of complete response letters in cell and gene therapy.

BACKGROUND AIMS: Cell and gene therapy products face unique regulatory challenges due to their biological complexity and the stringent expectations for manufacturing control, analytical testing, and clinical assessment. As the pipeline grows, understanding the drivers of FDA non‑approval is increasingly important for improving first‑cycle success and reducing development delays. In this study, we aimed to characterize the frequency and impact of refuse‑to‑file actions, major amendments, and complete response letters issued for biologics licensing applications; and to identify recurring patterns of deficiencies contributing to delayed approval. METHODS: Publicly available documents were extracted from the FDA website. Data from each approved cell and gene therapy product's regulatory history-including complete responses, major amendments, inspection timing, and cited deficiencies-were compiled and categorized across clinical, quality, and labeling domains. RESULTS: Analysis showed that informational deficiencies were common across modalities. Major amendments occurred in roughly half of applications, and complete responses had the most significant impact. Quality deficiencies appeared in all complete responses and were the predominant barrier, while clinical and labeling issues were less frequent but meaningful when present. CONCLUSION: Overall, these findings highlight the need for proactive FDA engagement, comprehensive readiness, and early inspection preparation to reduce regulatory risk and improve first cycle approval outcomes.

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PubMed2026

Vertical distribution of accessory canals in different tooth types: A systematic review and meta-analysis.

OBJECTIVE: To systematically analyze the vertical distribution of accessory canals and propose potential root-end resection levels in different tooth types. DATA: Proportional distribution of accessory canals (PD-AC) in 1 mm intervals, cumulative proportions within 2 mm and 3 mm (CP-AC0-2 and CP-AC0-3), mean distance from accessory foramen to root apex or main foramen (MD-AF), and prevalence of accessory canals in 2D cross-sections (PR-AC-2D). SOURCES: A systematic search of electronic databases was conducted through December 25, 2025. The review was registered in PROSPERO (CRD420251107855). STUDY SELECTION: Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the AQUA tool. Nineteen studies were included for qualitative synthesis, of which eleven provided sufficient data for meta-analysis. A random-effects model was used, and subgroup analyses were stratified by tooth type, accessory canal type, and country. Within 0-1 mm, 1-2 mm, 2-3 mm, and 3-4 mm from the apex, 41.5%, 34.3%, 9.9%, and 4.4% of accessory canals were located, respectively. Molars had significantly higher proportions than anterior teeth both within 2 mm (90.0% vs. 72.4%) and 3 mm (96.9% vs. 87.5%). Of apical ramifications, 86.4% were within 2 mm. The pooled MD-AF was 1.472 mm. PR-AC-2D decreased from 29.3% at 1 mm to 1.3% at 5 mm. All studies presented moderate to high risk of bias. CONCLUSIONS: A 2 mm root-end resection level may be sufficient for molars, whereas anterior teeth may require a higher level. Further randomized controlled trials are needed. CLINICAL SIGNIFICANCE: A 2 mm resection may adequately expose or remove most accessory canals in molars, potentially preserving more root length while maintaining treatment efficacy. In anterior teeth, a traditional 3 mm resection remains advisable until further evidence becomes available.

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PubMed2026

Socioeconomic differences in the effectiveness of oral health programs for dental caries prevention in Europe: A systematic review and meta-analysis.

AIM: The meta-analysis systematically summarized evidence on how socioeconomic status (SES), access to dental care, and oral health programs (OHP) affect caries prevalence and severity among children and adults in Europe. METHODS: Four electronic databases (PubMed, Scopus, Cochrane Library and Embase) were systematically screened from 1947-2026, supplemented by cross-referencing and manual searches, without language restrictions. Study selection, data extraction and quality assessment were done in duplicate. Methodological quality was assessed using the NHLBI Study Quality Assessment Tools according to study design. Certainty of evidence was graded using GRADE Profiler 3.6. Mean differences (MD) were calculated for changes in DMFT, and odds ratios (OR) for the presence of dental caries in individuals using fixed-or random-effects models. RESULTS: Electronic searching identified 1800 articles; 23 studies were included in the review (>169,000 participants) and 14 in the meta-analyses (>88,000). Nine studies evaluated the effectiveness of OHP stratified by SES, and ten examined OHP in low-SES populations. Among low-SES individuals, participation in OHP was associated with a significantly lower increase in DMFT (MD[95% CI]=-0.63[-0.94;-0.31];very low certainty) and significantly lower odds of having dental caries (OR[95% CI]=0.61[0.52;0.73];very low) compared with non-participation. Among program participants, individuals with low SES showed a significantly greater increase in DMFT than those with high SES (MD[95% CI]=0.79[0.30;1.21];very low) and had significantly higher odds of having dental caries (OR[95% CI]= 2.88[1.97;4.22];very low). CONCLUSION: Participation in OHP may be associated with reducing dental caries in European populations, but benefits are unequally distributed and increase with higher SES. However, this conclusion is based on a limited number of well-conducted trials.

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PubMed2026

Efficacy of sodium-glucose cotransporter 2 inhibitors after acute myocardial infarction: Are the benefits limited to patients with diabetes? A systematic review and meta-analysis.

BACKGROUND: Acute myocardial infarction remains one of the leading causes of death worldwide. Recently, studies have focused on evaluating the effectiveness of SGLT2 inhibitors in this scenario. Objectives We aimed to perform a meta-analysis comparing the efficacy of SGLT2 inhibitors vs standard care. METHODS: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) and observational studies comparing patients with acute myocardial infarction using iSGLT2 inhibitors and standard care. Statistical analyses were conducted using R software (v 4.3.2) and a random-effects model was employed for all outcomes. RESULTS: A total of 31,378 patients were included, with 10,897 (34.7%) assigned to the SGLT2 inhibitor group. Among these studies, three were randomized controlled trials (RCTs). There was a significant difference in reduction of HF readmissions (OR 0.61; p < 0.01), all-cause mortality (OR 0.62; p < 0.01;) and stroke (OR 0.67; p < 0.01;). However, there was no significant difference in cardiovascular death, rehospitalization for any cause and recurrence of acute MI. Meta regression and subgroup analysis showed a trend toward better outcomes in the diabetic and non-STEMI population. CONCLUSIONS: SGLT2 inhibitors were associated with lower HF rehospitalization, stroke, and all-cause mortality after acute MI, mainly in observational studies. Benefits appeared greater in diabetic and non-STEMI patients. Dedicated RCTs focusing on diabetic, particularly non-STEMI, populations are needed to confirm these findings. KEY POINTS: What is already known on this topic: SGLT2 inhibitors have demonstrated cardiovascular and renal benefits in patients with heart failure and type 2 diabetes mellitus. However, their role in the acute myocardial infarction (AMI) setting remains uncertain, particularly regarding post-AMI outcomes such as heart failure readmissions, mortality, and recurrent ischemic events, with current evidence derived from heterogeneous and predominantly observational studies. WHAT THIS STUDY ADDS: This meta-analysis, including over 31,000 patients, suggests that SGLT2 inhibitors are associated with reductions in heart failure readmissions, all-cause mortality, and stroke following AMI. These associations were more consistently observed in patients with type 2 diabetes and in non-ST-segment elevation myocardial infarction (NSTEMI) populations. However, randomized controlled trials showed neutral results, and the observed benefits were mainly driven by observational studies. Meaning: These findings should be interpreted as hypothesis-generating. While SGLT2 inhibitors may represent a potential therapeutic strategy in selected post-AMI populations, particularly patients with diabetes and NSTEMI, current evidence does not support routine early in-hospital initiation. Dedicated randomized trials specifically enrolling diabetic post-AMI patients are required to clarify optimal timing and clinical benefit.

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PubMed2026

Effects of phytosterols supplementation on hepatic lipid metabolism and metabolic outcomes in obese rodent models: a systematic review and meta-analysis.

This study aimed to synthesize and quantitatively assess the available evidence on the effects of phytosterol supplementation on hepatic lipid metabolism and obesity-related metabolic outcomes in obese rodent models, integrating biochemical, histological, and molecular evidence. A systematic search was conducted in electronic databases (PubMed, EMBASE, and Web of Science). Data on study design, population, intervention, outcomes, and risk of bias were extracted and analyzed. A quantitative meta-analysis was performed. Meta-analysis showed reductions in body weight, serum triglycerides, total cholesterol, LDL-C, VLDL-C, glucose, liver weight, hepatic cholesterol, hepatic triglycerides, and nonalcoholic fatty liver disease activity score. No significant changes were observed for adiposity index, HDL-C, insulin, or hepatic expression of PPARα, FAS, and SREBP1c. Conversely, CPT1A expression was significantly increased following PS supplementation. Subgroup analyses indicated that the beneficial effects on lipid and hepatic outcomes were generally consistent across rodent species (mice, rats, and hamsters), obesity induction models, and routes of administration, although the magnitude of responses varied between strains, with C57BL/6 mice showing more pronounced metabolic improvements. Additional analyses suggested that treatment duration and phytosterol composition may modulate specific outcomes, whereas dose-response meta-regression identified dose-dependent associations for serum and hepatic cholesterol, and PPARα expression in dietary supplementation studies. Overall, the available preclinical evidence suggests that phytosterol supplementation may improve several metabolic and hepatic outcomes in rodent models of obesity. However, the substantial heterogeneity across studies highlights the need for standardized experimental protocols and future clinical studies before these findings can be translated to human health.

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PubMed2026

Prognostic value of the Island sign for hematoma expansion and functional outcome after intracerebral hemorrhage: a systematic review and meta-analysis.

PURPOSE: The Island Sign (IS) is a radiological finding observed in patients with intracerebral hemorrhage (ICH). This meta-analysis aimed to evaluate the association between IS and both hematoma expansion (HE) and functional outcomes by comparing ICH patients with and without IS. METHODS: We searched PubMed, Embase and Cochrane Library for studies of intracerebral hemorrhage reporting the IS. The primary outcomes were functional status and hematoma expansion, secondary outcome was mortality. Statistical analysis was performed using RStudio, effect sizes were calculated as odds ratios (ORs) with 95% confidence interval (95% CIs), and heterogeneity was assessed with I2 statistics. In addition, meta-regression and sensitivity analyses were performed, and publication bias was assessed through funnel plots and Egger's regression test. RESULTS: We included 21 observational studies with a total of 9,459 patients with spontaneous ICH, 1,769 of them had IS, while 7,690 did not. The mean age was 63.5 ± 13.2 and 5,835 (61.7%) were male. Poor functional outcomes (OR 2.77, 95% CI: 2.14-3.58, p < 0.0001, I2 = 4.9%) and hematoma expansion (OR 2.75, 95% CI: 1.87-4.03, p < 0.0001, I2 = 77.4%) were substantially higher in patients with IS, as well as the overall mortality rate (OR 2.54, 95% CI: 1.55-4.17, p = 0.0002, I2 = 0%). Meta-regression analysis showed no statistically significant association between imaging-related timing variables and hematoma expansion. Furthermore, the leave-one-out sensitivity analyses showed that no single study exerted a disproportionate influence on the overall effect for the examined outcomes, and Egger's linear regression tests were not statistically significant for both outcomes. CONCLUSION: Patients with the Island Sign are associated with higher rates of poor functional outcomes and hematoma expansion. Thus, IS is a relevant radiological finding with potential to support early risk stratification and optimize patient management and treatment selection.

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PubMed2026

Comparison of Ketamine and Pregabalin on Postoperative Opioid Usage and Pain Management in Spinal Fusion: Systematic Review and Network Meta-analysis.

BACKGROUND CONTEXT: Spinal fusion is associated with substantial early postoperative pain and opioid exposure. Both ketamine and pregabalin are widely incorporated into Enhanced Recovery After Surgery (ERAS) protocols as opioid-sparing adjuncts. However, their comparative efficacy and safety in this specific setting remain uncertain. Our objective was to compare ketamine and pregabalin indirectly for early postoperative opioid consumption, pain, and adverse events in adults undergoing spinal fusion. METHODS: Pubmed, Embase, and Cochrane Trials were searched from inception through October 2025. Eligible studies were randomized trials enrolling adults undergoing instrumented spinal fusion, randomized to perioperative ketamine, pregabalin, or control, and reported extractable 24-hour opioid consumption or pain outcomes. Continuous outcomes were pooled as mean differences in MME or VAS units, and adverse events were reported descriptively. A connected treatment network was analyzed using random-effects models. Risk of bias (RoB) was assessed with the Cochrane RoB 2 tool. RESULTS: Thirteen trials (n=879) were included: ketamine (n=210), pregabalin (n=271), and control (n=398). Six trials contributed opioid data (3 ketamine, 3 pregabalin). Using pregabalin 150 mg as reference, ketamine was associated with lower 0-24-hour opioid use (MD -56.99 mg MME; 95% CI -99.56 to -14.43). Control (MD +21.31; 95% CI -1.05 to +43.66) and pregabalin 300 mg (MD -13.22; 95% CI -40.41 to +13.96) did not significantly differ from pregabalin 150 mg. Seven trials contributed 24-hour VAS data, with control being associated with higher pain versus pregabalin 150 mg (MD +0.84; 95% CI +0.01 to +1.66), while ketamine and pregabalin 300 mg were not k significantly different. Adverse events were generally infrequent and similar to control. CONCLUSIONS: Both ketamine and pregabalin provide early opioid sparing with comparable 24-hour analgesia. Ketamine showed a larger opioid-sparing point estimate, but indirect comparisons are imprecise. Adequately powered head-to-head trials with standardized protocols and adverse event reporting are needed.

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PubMed2026

Obesity in obstetric anesthesia: A systematic review.

Maternal obesity presents complex challenges for anesthetic management, with implications spanning neonatal, cardiovascular, airway, neuraxial, and procedural domains. This review synthesizes evidence on how elevated maternal body mass index (BMI) impacts perioperative evaluations, risks, complications, and outcomes, in addition to anesthetic modalities and efficacy in the pregnant population. Given the increasing global prevalence of maternal obesity, anesthesiologists must refine clinical practices, employing tailored, evidence-based strategies to mitigate risks and enhance patient outcomes. This review aims to provide anesthesiologists and obstetricians with key considerations and best practices for managing obstetric anesthesia patients with obesity. Clinical recommendations herein are based on current research and evaluated using Oxford Centre for Evidence-Based Medicine for level of evidence and class of recommendation.

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PubMed2026

Stapled versus hand-sewn intestinal anastomosis in pediatric surgery: A systematic review and meta-analysis.

BACKGROUND: Intestinal anastomosis is a core procedure in pediatric gastrointestinal surgery, performed for conditions such as necrotizing enterocolitis, intestinal atresia, Hirschsprung's disease, and inflammatory bowel disease. Although stapled anastomosis (SA) may improve operative efficiency, its safety and effectiveness compared with hand-sewn anastomosis (HA) in children remain uncertain. This meta-analysis compared clinical outcomes of SA and HA in pediatric patients. METHODS: The study followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251177257). A systematic search of PubMed, Dimensions, and the Cochrane Library was conducted through June 2025. Studies including children under 7 years undergoing intestinal SA or HA were eligible. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using ROB 2 and ROBINS-I tools. Statistical analysis was conducted using Comprehensive Meta-Analysis software (v3) with a random-effects model. RESULTS: Eleven studies involving 903 patients met inclusion criteria, including two randomized controlled trials. Of these, 333 patients underwent SA and 570 underwent HA. SA was associated with significantly shorter operative time (mean difference [MD] = -19.26 min; 95% CI: -24.24 to -14.28; p < 0.001) and earlier initiation of oral feeding (MD = -2.32 days; 95% CI: -3.78 to -0.86; p = 0.002). No significant differences were found in anastomotic leakage, stricture formation, reoperation rate, or length of hospital stay. CONCLUSIONS: Stapled anastomosis appears as safe as hand-sewn techniques in pediatric intestinal surgery while offering shorter operative duration and faster postoperative feeding recovery. Selective use of stapled techniques is supported when anatomically feasible, though further multicenter randomized trials are needed.

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PubMed2026

Should we consider excessive weights in pediatric kidney transplant recepient candidates?: A systematic review and meta-analysis of kidney transplantation outcomes.

INTRODUCTION: In adult populations, excess body weight has been associated with an increased risk of adverse clinical outcomes and mortality following kidney transplantation. In contrast, the influence of obesity on transplantation outcomes among pediatric populations is not yet fully understood. This study aimed to evaluate the association between pre-transplant excess weight and post-transplant outcomes in pediatric kidney transplant recipients. MATERIAL & METHODS: A systematic literature search was performed across PubMed, ScienceDirect, and the Cochrane Library, covering publications up to December 31, 2025. The quality of the included studies was evaluated using the ROBINS-E tool. Statistical analysis was conducted using Review Manager version 5.4. RESULTS: From a total of 1465 records screened, six studies that included 65,483 participants were selected in the meta-analysis. The results indicated that pre-transplant excess weight was significantly associated with an increased risk of acute rejection (OR = 1.09; P = 0.009), delayed graft function (OR = 1.17; P < 0.00001), 1-year graft failure (OR = 1.16; P = 0.0002), and 5-year graft failure (OR = 1.13; P = 0.009). Although 5-year mortality was also higher among recipients with excess weight, this association was not statistically significant (OR = 1.08; P = 0.11). CONCLUSION: Pediatric patients with pre-transplant excess weight had higher post-transplant odds of acute rejection, delayed graft function, and both 1-year and 5-year graft failure compared to those without excess weight. These findings highlight the importance of assessing and managing excess weight prior to kidney transplantation to help prevent adverse outcomes in the future.

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PubMed2026

Impact of smoking on structural failure after arthroscopic rotator cuff repair: a systematic review and meta-analysis.

BACKGROUND: Rotator cuff tears cause significant shoulder pain and functional limitation. Arthroscopic rotator cuff repair improves symptoms, yet structural failure rates remain substantial. Smoking may impair tendon-to-bone healing, but clinical studies report mixed findings due to heterogeneous methodology. Therefore, a systematic synthesis of imaging-confirmed outcomes is needed to clarify the association between smoking and structural failure after arthroscopic rotator cuff repair. METHODS: This review followed PRISMA 2020 and was registered in PROSPERO (CRD420251246197). PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to 12 December 2025. Comparative clinical studies of adults undergoing arthroscopic rotator cuff repair that reported imaging-confirmed structural integrity (magnetic resonance imaging or ultrasonography) at ≥6 months were included. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale. The primary outcome (structural failure) was pooled as risk ratios using a random-effects model with the restricted maximum likelihood estimator and Hartung-Knapp adjustment. Secondary continuous outcomes were synthesized using Bayesian random-effects models; subgroup, sensitivity, and meta-regression analyses explored heterogeneity. RESULTS: Ten cohort studies (1,683 shoulders) were included. Smoking was associated with a higher risk of imaging-confirmed structural failure (risk ratio 1.53; 95% confidence interval 1.13-2.08; P = .011) with low heterogeneity (I2 = 24.7%). Subgroup and sensitivity analyses supported robustness, with no evidence of effect modification by region, follow-up duration, tear size, or smoking definition. Meta-regression showed no significant influence of age, smoking prevalence, or diabetes prevalence on the pooled effect. Secondary outcomes (3 studies) suggested slightly lower postoperative American Shoulder and Elbow Surgeons scores among smokers, while visual analog scale pain scores and forward flexion showed no clear between-group differences. No publication-bias signals were detected for the primary outcome. CONCLUSION: Smoking is associated with a higher risk of imaging-confirmed structural failure after arthroscopic rotator cuff repair. Functional outcomes were broadly similar between groups, with only a small, likely clinically negligible reduction in American Shoulder and Elbow Surgeons scores among smokers. These findings support careful smoking history assessment and perioperative risk modification, including smoking cessation strategies.

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PubMed2026

Impact of education protocols and physiotherapeutic management in improving pain, symptoms, activities of daily living, and quality of life in patients with knee osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis is a debilitating condition of the knee joint and the major cause of disability globally, with an increased economic burden on healthcare. Patient education (PE) has emerged as a primary care treatment approach in chronic conditions. This review aims to evaluate the effectiveness of PE along with exercise in reducing pain, alleviating symptoms, improving activities of daily living, and promoting quality of life among individuals with knee osteoarthritis. METHOD: A systematic search was conducted across three electronic databases, PubMed, Cochrane Library, and PEDro. The search was limited to between 2020 and 2025, and included only randomized controlled trials. The Cochrane Risk of Bias Tool and the PEDro Scale were used to evaluate the methodological evidence. Statistical synthesis was analysed using mean differences (MDs) with 95% confidence intervals (CIs) under a random-effects model. RESULTS: Eight trials were included, of which four studies evaluated the four Knee Injury and Osteoarthritis Outcome Score (KOOS) domains, and three studies evaluated the Visual Analogue Scale (VAS) and KOOS activities of daily living domain in patients with knee osteoarthritis. For the meta-analysis, we assessed all five domains of the KOOS scale and VAS. Statistical analysis of the studies showed a significant reduction in pain (VAS) for the PE along with exercise group (MD = -3.28, 95% CI (-4.85; -1.70), and I2 = 69.6%), but there was no significant improvement in the domains of the KOOS scale. CONCLUSION: The study highlights the importance of PE along with exercise in reducing pain. It might not be more effective when compared with exercise therapy as a standalone intervention in improving ADLs, QoL, and symptoms, but it has demonstrated some degree of effectiveness. It additionally promotes self-management and self-efficacy as a physiotherapeutic rehabilitation treatment intervention.

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PubMed2026

Alignment strategies in total knee arthroplasty and the patellofemoral joint: A systematic review.

BACKGROUND: Different alignment strategies in total knee arthroplasty (TKA) may affect the patellofemoral joint. Mechanical alignment (MA) is commonly used but may alter native anatomy. Newer strategies such as kinematic alignment (KA), restricted kinematic alignment (rKA), and functional alignment (FA) aim to better restore native joint mechanics. This study provides an overview of the effects of alignment strategies on patellofemoral outcomes after TKA. METHODS: A literature search in July 2025 identified studies comparing patellofemoral outcomes in TKA using different alignment strategies. Of 166 studies screened, eight met inclusion criteria. Three studies were considered medium quality and five studies low quality. RESULTS: KA and rKA more closely restored native trochlear morphology than MA and FA, reducing outliers in the anterior trochlear line compared with MA and FA. MA showed greater trochlear translation, suggesting worse patellar tracking. Trochlear angles were more anatomical in KA and rKA. However, KA was associated with increased internal femoral component rotation and more outliers beyond safe thresholds. FA showed more consistent rotational positioning, generally within safe limits. Lateral patellar shift and intraoperative lateral release rates did not differ significantly between KA and MA. Only one study reported patella-specific clinical outcome scores, finding no difference between FA and adjusted MA. CONCLUSION: KA and rKA better restore trochlear morphology, but risk excessive internal femoral component rotation. FA provides a more balanced approach. MA, while widely used, is linked to altered trochlear shape and worse patellar tracking. The clinical impact of these radiological differences remains unclear, and higher-quality studies are needed.

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PubMed2026

Sex-stratified analyses of femoral intercondylar notch morphology and ACL injury risk: a systematic review and meta-analysis.

BACKGROUND: Anterior cruciate ligament (ACL) injury is more common in females. Although ACL injury risk is multifactorial, involving neuromuscular, hormonal, and biomechanical factors, femoral intercondylar notch morphology is a proposed non-modifiable anatomical contributor that may help explain this disparity. This review synthesizes evidence on its association with ACL injury risk, analyses stratified by male and female sex. METHODS: A literature search of PubMed, Web of Science, and Scopus was conducted through January 2026. After duplicate removal, 527 unique records were screened and 134 full texts assessed for eligibility. Twenty-four studies met inclusion criteria, with 22 providing quantitative data. Data were extracted on ACL-injured (ACLi) and control (ACLc) knees, stratified by sex. RESULTS: ACLi knees had narrower notch widths than ACLc knees in both females (MD -1.74 mm, 95% CI -2.54 to -0.95) and males (MD -1.31 mm, 95% CI -1.94 to -0.68), with substantial heterogeneity (I2 81-95%). NWI differences were significant in males (MD -0.01, 95% CI -0.02 to 0.00) but not females. Limited notch shape data suggested higher ACL injury odds with A-shaped notches in females (OR 2.85, 95% CI 0.07-110.66) and males (OR 1.67, 95% CI 0.00-3.98 × 105). CONCLUSION: Narrower femoral intercondylar notch width was consistently associated with ACL injury in both sexes, whereas findings for NWI and notch shape were limited by heterogeneity and sparse data. These results provide a structured synthesis of sex-specific anatomical risk factors and support femoral notch narrowing as a shared contributor, while highlighting the need for prospective, standardized studies in the future.

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PubMed2026

Exploring the dose-response relationship between prenatal exercise and postpartum depression: A systematic review and meta-analysis of randomized controlled trials.

IMPORTANCE: Postpartum depression (PPD) is a hidden and widespread global public health crisis affecting millions of mothers and infants annually. Prenatal exercise is a potentially accessible nonpharmacological strategy for PPD prevention, but its optimal dose remains uncertain. OBJECTIVE: To explore the dose-response relationship between prenatal exercise and the incidence of PPD through meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library using MeSH terms and keywords related to "pregnant women," "prenatal exercise," and "postpartum depression," up to June 23, 2025. STUDY SELECTION: RCTs included examined prenatal exercise interventions in pregnant women without a history of depression, with PPD incidence reported using validated depression scales (such as EPDS, CES-D). Non-RCT studies, duplicate publications, and studies with insufficient data were excluded. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted data according to the PRISMA guidelines. A random-effects model was used to pool odds ratios (OR) and their 95% confidence intervals (CI). Linear and nonlinear dose-response models were employed to analyze and evaluate the relationship between exercise dose (measured in METs-min/week) and the incidence of PPD. MAIN OUTCOME(S) AND MEASURE(S): The primary outcome is the incidence of PPD, analyzing its relationship with prenatal exercise dose. RESULTS: Eight RCTs involving 2231 pregnant women were included. The pooled analysis showed that prenatal exercise was associated with a potential reduction in PPD incidence, although the overall effect did not reach statistical significance (OR=0.58, 95% CI [0.33, 1.02]). In dose-stratified analysis, exercise doses ≥500 METs-min/week were associated with significantly lower PPD incidence (OR=0.44, 95% CI [0.24, 0.78]). Subgroup analyses suggested trends toward greater benefits among women aged ≥30 years and those initiating exercise between 14 and 28 weeks of gestation; however, subgroup differences did not reach statistical significance. The linear dose-response trend did not reach statistical significance (p = 0.0533), and neither the overall spline association (p = 0.1704) nor the test for nonlinearity (p = 0.6361) was statistically significant. CONCLUSIONS AND RELEVANCE: Prenatal exercise may be associated with a lower risk of PPD, but the overall pooled effect did not reach statistical significance. Findings concerning ≥500 METs-min/week and the apparent flattening of the dose-response curve should be considered exploratory and require confirmation in larger trials.

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PubMed2026

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 (≥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.

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