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The Natural History of Residual and Recurrent Disease in Advanced Juvenile Nasopharyngeal Angiofibroma: A Systematic Review.

OBJECTIVE: This systematic review explores the natural history of residual and recurrent juvenile nasopharyngeal angiofibromas (JNAs) to inform clinical decision-making. DATA SOURCES: PubMed, Embase, Scopus, and Web of Science. REVIEW METHODS: A systematic literature review was conducted according to PRISMA guidelines across PubMed, Embase, Scopus, and Web of Science from inception to February 20, 2025 and was re-run on September 21, 2025. Studies included patients with advanced JNA and documented follow-up of residual or recurrent disease. Descriptive statistics, chi-squared analysis, and analysis of variance were used to evaluate treatment outcomes across different modalities including surgery, radiotherapy, gamma knife surgery, and medical therapies. RESULTS: Twenty-one studies encompassing 131 male patients (mean age 16.3 years) were included. Residual or recurrent disease demonstrated complete involution in 41%, stable disease in 29%, and reduction in size in 25% of cases. Only 2% of patients had progressive disease. A statistically significant association was observed between treatment modality and outcome (p = 0.015), with radiotherapy, either alone, or as part of a multimodal approach, showing the highest rates of spontaneous involution. CONCLUSION: Residual and recurrent JNAs often remain stable or regress without further intervention. Close surveillance with imaging is a safe and effective strategy for asymptomatic patients, minimizing the risks of additional treatment in a young patient population with disease near critical anatomical structures.

Humans

Early mobilization within 24 to 48 h improves postoperative clinical outcomes in older adults with hip fracture: A systematic review and meta-analysis.

BACKGROUND: Hip fracture is a major public health concern among older adults, often resulting in prolonged disability, institutionalization, and increased healthcare burden. Early mobilization has been widely recommended to enhance postoperative recovery; however, there is a lack of consolidated evidence quantifying its impact on clinical and functional outcomes. This study aimed to synthesize and evaluate the impact of early mobilization following hip fracture surgery in older adults and to explore potential sources of heterogeneity to better inform clinical and nursing practice. METHODS: A comprehensive literature search was conducted across seven databases (PubMed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Emcare) from inception to June 15, 2025. Eligible studies included randomized controlled trials and observational cohort studies comparing early mobilization (defined as ambulation within 24 to 48&#xa0;h postoperatively) to delayed or usual mobilization in patients undergoing hip fracture surgery. Primary outcomes included mortality, discharge destination, and length of hospital stay. Secondary outcomes included postoperative complications, functional recovery, and readmission. Risk of bias was assessed using funnel plots and Egger's test. RESULTS: Twenty-six studies involving 297,435 patients were included. Compared with delayed mobilization, early mobilization significantly reduced 30-day mortality (relative risk&#xa0;=&#xa0;0.40, 95% confidence interval: 0.25-0.64) and 1-year mortality (relative risk&#xa0;=&#xa0;0.57, 95% confidence interval: 0.40-0.80) (both p&#xa0;<&#xa0;0.05). In regional analyses of pooled mortality, similar reductions were observed across Asia-Pacific, North America, and Europe. Patients receiving early mobilization were more likely to be discharged home and had shorter hospital stays. Early mobilization also resulted in a reduced risk of postoperative complications (relative risk&#xa0;=&#xa0;0.79, 95% confidence interval: 0.74-0.84, p&#xa0;<&#xa0;0.05), with specific improvements in pneumonia and thromboembolism rates. Functional independence was significantly improved, as shown by higher Barthel Index scores and increased odds of achieving Functional Independence Measure &#x2265;5 at discharge. No significant difference was observed in readmission rates. CONCLUSIONS: lization within 24 to 48&#xa0;h following hip fracture surgery was associated with favorable outcomes, including reduced mortality, improved functional independence, higher rates of discharge to home, shorter hospital length of stay, and fewer postoperative complications. Although heterogeneity across studies and the predominance of observational evidence warrant cautious interpretation, these findings support current recommendations for early mobilization and highight the potential value of structured and standardized mobilization protocols in routine postoperative hip fracture care.

Humans

The role of particle therapy in the treatment of locally recurrent rectal cancer: a systematic review.

BACKGROUND: Colorectal cancer is a common malignancy. Advancements in multimodality treatment have improved outcomes. About 2-10% of patients will have a local recurrence even after optimal treatment. Salvage surgical treatment is the treatment of choice, however, in posterior and lateral recurrences, surgery is linked to a high rate of treatment-related morbidity. Some recurrences remain unresectable even after neoadjuvant treatment. MATERIALS AND METHODS: A systematic literature review was performed to search for studies on curative-intent radiation therapy (RT) with photons, stereotactic body radiation therapy (SBRT) and particle beam therapy. The aim of the literature search was to define the role of particle therapy in the treatment of patients with unresectable or inoperable local recurrences of rectal cancer where neoadjuvant treatment is unlikely to result in downstaging, leaving patients with RT as the only curative treatment option. RESULTS: 32 studies which fulfil the criteria were identified. In general, SBRT and particle beam therapy permitted the application of significantly higher doses to the target without a concomitant increase in treatment-related toxicities. CONCLUSIONS: For unresectable and inoperable locally recurrent rectal cancer ablative radiotherapy techniques such as SBRT and particle beam therapy offer a curative treatment approach as an alternative to surgery. SBRT can be offered for small local and nodal recurrences, while particle beam therapy can be offered for larger recurrences and complex shapes spanning several anatomical compartments as well. Further research is needed to stratify patients according to their need and eligibility for the different possible modalities of curative-intent RT.

Humans

The Impact of Oncological Treatments on Return to Work, Work Ability, and Sickness Absence in Breast Cancer Survivors: A Systematic Review.

PURPOSE: Returning to work and maintaining an adequate ability to work serve as key indicators of quality of life, psychological well-being and psychosocial adjustment. Therefore, this study aims to analyze the impact of breast cancer treatments on return to work (RTW), work ability (WA), and sick leave (SL) among breast cancer survivors. METHODS: A systematic review was conducted according to the PRISMA guidelines. The sample consisted of 26 studies published between 2016 and 2025, including prospective multicenter cohorts and national registries from fifteen countries across four continents, with more than 25,000 participants. A methodological quality assessment and a narrative synthesis were performed to synthesize the results. RESULTS: Chemotherapy is the most consistent predictor of prolonged SL, delayed RTW, and significantly reduced WA. Radical surgery and axillary lymph node dissection (ALND) are associated with a significantly delayed RTW due to physical sequelae. While outcomes showed strong relationship with clinical factors, certain psychosocial variables such as depression, anxiety, and low self-efficacy seemed to act as important secondary factors that can further complicate the process. CONCLUSION: The findings suggest that more invasive or aggressive treatments (chemotherapy, ALND, and radical surgery) were associated with poorer outcomes on RTW, WA, and SL. Furthermore, the clinical recovery associated with treatment completion did not necessarily equate to a functional recovery in WA that facilitated a successful RTW. Thus, it is necessary to explore in depth the impact of cancer treatments on WA, alongside psychosocial variables, to design multidisciplinary interventions that enable sustainable occupational reintegration. REGISTRATION: PROSPERO 2026 (CRD420261322638).

Breast cancer survivors

Adjuvant CDK4/6 inhibitors in early-stage breast cancer: Clinical evidence and considerations for risk stratification and treatment selection.

Hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer is the most common biologic subtype and carries a persistent risk of recurrence, particularly in patients with high-risk, early-stage disease. Cyclin-dependent kinase 4 and 6 inhibitors, initially established as a standard component of first-line therapy in the metastatic setting based on improvements in progression-free and overall survival, have since been evaluated in the adjuvant setting. While adjuvant palbociclib did not improve invasive disease-free survival, the monarchE and NATALEE trials demonstrated that abemaciclib and ribociclib, respectively, reduce recurrence risk in patients with high-risk, early-stage disease, with emerging overall survival data further supporting their use. However, the absolute magnitude of benefit varies substantially with baseline risk, and treatment-related toxicity and adherence challenges must be considered, as approximately 20% to 25% of patients discontinue therapy before completion. The integration of these agents into clinical practice also intersects with ongoing efforts to deescalate axillary surgery, as treatment eligibility has been largely defined by anatomic staging, particularly nodal status. Available data suggest that the incremental impact of axillary surgery on identifying candidates for cyclin-dependent kinase 4 and 6 inhibition is modest, especially among the favorable-risk populations now eligible for surgical deescalation. As the field evolves, advances in molecular risk stratification, genomic profiling, and dynamic biomarkers are poised to shift treatment selection from anatomic staging toward biologically driven approaches. Multidisciplinary decision-making that integrates tumor biology, anticipated absolute benefit, toxicity, patient preferences, and surgical considerations will be essential to ensure individualized care.

Humans

Endoscopic submucosal dissection for locally recurrent gastric neoplasia following endoscopic resection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for locally recurrent gastric neoplasia following endoscopic resection (ER) is technically challenging because of scar-related submucosal fibrosis. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of salvage ESD in this setting. METHODS: Multiple databases were searched through December 2025 for studies reporting ESD outcomes for locally recurrent gastric lesions at or contiguous with a prior ER scar. Primary outcome was curative resection and need for surgery. Secondary outcomes were en bloc and R0 resection, local recurrence, delayed bleeding, and perforation. Meta-analyses were performed using a random effects model. Heterogeneity was assessed using I2. RESULTS: Seven studies (259 patients; 265 ESDs) were included. Across 5 studies and 243 ESDs, pooled curative resection rate was 69.7% (95% CI, 60.6-78.1; I2 = 38%), while 8.2% (95% CI, 3.3-14.6; I2 = 38.4%) required surgery. En bloc resection rate was 92.3% (95% CI, 79.1-99.7; I2 = 83.7%) across 6 studies, and pooled R0 resection rate was 87.5% (95% CI, 82.1-92.2; I2 = 0%) across 4 studies. Over a mean follow-up of 42 months, pooled local recurrence was 2.0% (95% CI, 0.0-9.7; I2 = 54.1%) across 6 studies. Delayed bleeding was 4.1% (95% CI, 0.8-9.0; I2 = 40.8%) and perforation was 4.1% (95% CI, 1.6-7.3; I2 = 0%). CONCLUSIONS: ESD for locally recurrent gastric neoplasia after ER achieves acceptable curative resection, high en bloc/R0 resection, and low local recurrence and morbidity. It is a viable organ-preserving option for appropriately selected patients, ideally performed at expert centers with close surveillance.

Humans

Efficacy and safety of pantoprazole for stress-ulcer prophylaxis in critically ill patients: A systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: Stress-related mucosal damage (SRMD) is common in critically ill patients, and pharmacologic prophylaxis remains essential. This study evaluated the efficacy and safety of pantoprazole for stress-ulcer prophylaxis in ICU patients. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted per PRISMA-2020 guidelines. PubMed, Scopus, and CENTRAL were searched for studies comparing pantoprazole with placebo in adult and pediatric ICU patients. The primary outcome was clinically important gastrointestinal (GI) bleeding; secondary outcomes included mortality, ventilator-associated pneumonia (VAP), and Clostridioides difficile infection. RESULTS: Seven RCTs (n&#xa0;&#x2248;&#xa0;9127; pantoprazole&#xa0;=&#xa0;4575; placebo&#xa0;=&#xa0;4552) were included. Pantoprazole significantly reduced clinically important GI bleeding (RR&#xa0;=&#xa0;0.53; 95% CI 0.29-0.94; p&#xa0;=&#xa0;0.03) without affecting overall mortality (RR&#xa0;&#x2248;&#xa0;0.99 [95% CI 0.92-1.05]; p&#xa0;=&#xa0;0.68). Infection rates were similar between groups (VAP: RR&#xa0;=&#xa0;0.99; p&#xa0;=&#xa0;0.78; C. difficile: RR&#xa0;=&#xa0;1.11; p&#xa0;=&#xa0;0.73). Sensitivity analyses confirmed robustness. CONCLUSIONS: Pantoprazole effectively reduces clinically important GI bleeding without increasing infection or overall mortality.

Pantoprazole

Optimizing Initial Dosing for Tacrolimus and Mycophenolate in Living Donor Liver Transplantation: A Systematic Critical Review.

BACKGROUND: The pharmacokinetics (PK) of immunosuppressive agents in living donor liver transplantation (LDLT) recipients are expected to differ from those in deceased donor liver transplantation (DDLT) recipients because of the smaller initial liver volume transplanted and pathophysiological changes during liver regeneration. Consequently, the hepatic metabolism, CYP enzyme activity, and glucuronidation may be reduced. The PK of tacrolimus (metabolized by CYP3A5) and mycophenolate (metabolized through glucuronidation) are expected to be affected early post-LDLT. However, the initial dosing recommendations for post-LDLT remain unclear. PURPOSE: This study aimed to recommend initial dosing approaches for tacrolimus and mycophenolate in LDLT recipients based on available PK data in humans. METHODS: A PubMed search was conducted in March 2025 to identify studies investigating the PK data of immediate-release tacrolimus and mycophenolate in pediatric or adult LDLT recipients. RESULTS: After screening, 8 and 8 articles on tacrolimus and mycophenolates, respectively, met the review criteria. The current literature suggests that LDLT recipients require lower tacrolimus doses than DDLT recipients, particularly in the early post-transplant period. In addition, CYP3A5 polymorphisms in both donors and recipients contribute to interindividual variability in tacrolimus exposure, further complicating tacrolimus management. Studies on mycophenolate use in LDLT recipients are limited, with insufficient evidence to support dose reduction. CONCLUSIONS: Reducing the initial tacrolimus dose in LDLT recipients by 30%-50% compared with that in DDLT recipients would be reasonable while maintaining the same initial dose of mycophenolate between LDLT and DDLT recipients.

Humans

Descemet Stripping Only in Fuchs Endothelial Corneal Dystrophy: Results of a Randomized Clinical Trial of Topical Ripasudil and Directions for Future Innovation.

PURPOSE: To review history of Descemet stripping only (DSO) in Fuchs endothelial corneal dystrophy, describe the results of a clinical trial of topical ripasudil after DSO (K-321-201 study), and discuss future directions. METHODS: A 1-year, phase 2, randomized, placebo-controlled multicenter clinical trial of two doses of K-321 (ripasudil) administered for 12 weeks after DSO surgery in Fuchs endothelial corneal dystrophy was performed. The primary endpoint, central corneal endothelial cell density (ECD) at 12 weeks after surgery, was determined by an independent reading center that was masked to study group assignment. Duration of corneal edema, need for medical or surgical rescue therapy, corneal thickness, and central ECD throughout the entire study period were also examined. Adverse events and exploratory endpoints were collected. RESULTS: Sixty-five subjects were enrolled (21 in the QID group, 22 in the BID, and in the placebo group). Over 95% of subjects completed the trial. The QID group had a higher central ECD 12 weeks after DSO than the placebo group (531 &#xb1; 312 cells/mm2 vs 228 &#xb1; 298 cells/mm2, P = .0065). Corneal edema cleared in 17/21 (81.0%) of the QID group at 12 weeks, compared with 2/22 (9.1%) of the placebo group (P < .0001). Rescue was required in 2/21 (9.5%) subjects in the QID group and 6/22 (27.3%) subjects in the placebo group (P = .0092). Adverse events were mild and did not lead to discontinuation of treatment. CONCLUSIONS: Topical K-321 given QID improves DSO outcomes, as demonstrated by a higher ECD, more rapid resolution of corneal edema, and reduced failure rate. The medication was well-tolerated.

Humans

Liposomal bupivacaine versus ropivacaine for surgical site infiltration in lumbar fusion: a prospective randomized controlled trial.

INTRODUCTION: Effective postoperative pain control after lumbar spine surgery remains challenging, and excessive opioid use is associated with adverse outcomes. Evidence comparing liposomal bupivacaine (LB) with conventional long-acting local anesthetics in spine surgery is limited. PATIENTS AND METHODS: In this single-center, prospective, randomized, patient- and outcome assessor-blinded trial, adult undergoing one- or two-level posterior lumbar decompression and fusion were assigned (1:1) to surgical site infiltration with either LB (266&#x2009;mg) plus 25&#x2009;mg plain bupivacaine (LB group) or ropivacaine (R group). The primary outcome was 72&#x2009;h cumulative opioid consumption (morphine milligram equivalents, MME). Secondary outcomes included time-profile opioid consumption, pain scores, rescue analgesia, safety, and functional recovery. RESULTS: A total of 202 patients were included in the modified intention-to-treat analysis. Cumulative MME within 72&#x2009;h was significantly lower in the LB group compared with the R group [43.0 (37.0, 58.0) mg vs. 58.0 (46.0, 73.0) mg], corresponding to a 22% relative reduction (GMR 0.78, 95% CI 0.71-0.85; p&#x2009;<&#x2009;0.001). The reduction was most pronounced during 8-24&#x2009;h and 24-48&#x2009;h postoperatively. Overall pain scores at rest and with movement, as well as 72-h pain AUC, were lower in the LB group. No significant between-group differences were observed in rescue analgesia, adverse events and functional recovery. CONCLUSION: In patients undergoing one- or two-level posterior lumbar decompression and fusion, surgical site infiltration with an LB-based combined regimen, compared with ropivacaine monotherapy, reduced 72-h opioid consumption and cumulative postoperative pain burden without an observed increase in adverse events or impairment of early functional recovery.

Humans

Neuromuscular blocking agents for tracheal intubation of critically ill adults: a systematic review and meta-analysis.

BACKGROUND AND IMPORTANCE: Emergency tracheal intubation in critically ill adults is associated with a high risk of peri-intubation adverse events, making first-attempt success a key safety target. OBJECTIVE: This study aimed to evaluate whether the use of neuromuscular blocking agents (NMBAs) improves the proportion of first-attempt success and reduces adverse events during emergent intubations outside the operating room. METHODS: This was a systematic review and meta-analysis of randomized clinical trials or nonrandomized studies comparing sedative-hypnotic plus NMBA versus sedative-hypnotic alone in critically ill adults undergoing emergency endotracheal intubation in nonoperative settings. Animal, cadaveric, manikin/simulation, and pediatric studies were excluded. Articles were screened on 21 August 2025, in Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, and the Web of Science Core Collection. MAIN RESULTS: Of 4736 screened citations, 13 studies (8 cohort; 5 before-after studies) were included in the quantitative analysis, with 14&#x2005;072 participants. NMBA use was associated with higher first-attempt success, which ranged from 69 to 92% (pooled odds ratio, 2.72; 95% onfidence interval: 1.42-5.21; low-certainty evidence). Secondary outcomes related to adverse events were rated as very low certainty due to sparse data, inconsistent reporting, and serious imprecision. CONCLUSION: NMBA use during emergency intubation was associated with improved first-attempt success, although the certainty of evidence was low.

Humans

Complement component C4 and neuroimaging in psychiatry: A systematic review.

INTRODUCTION: Genomic, transcriptomic, and proteomic studies suggest that the complement system contributes to the pathophysiology of various psychiatric disorders partly through neurodevelopmental effects linked to C4A protein levels variations. We conducted a systematic review to characterize how brain micro- and macrostructure and connectivity vary with proxies of in vivo brain C4A protein levels in both psychiatric and general-population cohorts. METHODS: We used Medline, Web of Science, and Embase, and included all studies published before April 14, 2025. Inclusion criteria were: (1) inclusion of healthy controls and/or individuals with psychiatric disorders assessed according to recognized diagnostic manuals (DSM or ICD); (2) use of MRI-based neuroimaging; and (3) use of genomic, transcriptomic and/or proteomic approaches as proxies of in vivo brain C4A proteins levels. RESULTS: From 317 identified articles, 11 were included. Associations between C4A levels and brain structure were heterogeneous across regions. Only the mOFC, dlPFC, and entorhinal cortex were implicated in more than one study. Findings for the mOFC and dlPFC varied by the type of metrics and clinical status, whereas higher C4A levels were more consistently associated with smaller entorhinal cortex surface area and cortical thickness in pediatric, middle-aged, and older general-population cohorts. In addition, one study found higher genetically predicted C4A expression to be associated with higher TSPO levels. CONCLUSION: The limited number of available studies and their methodological heterogeneity make synthesis challenging. However, biological hypotheses such as excessive synaptic pruning or broader inflammatory effects on the brain may provide plausible explanatory frameworks for the reported associations.

Humans

MIS-TLIF Versus Open TLIF in Combined Lumbar Stenosis and Low-Grade Spondylolisthesis : Of Discharge Timing and Treatment Pricing.

STUDY DESIGN: An open-label, randomized, noninferiority clinical trial. OBJECTIVE: To determine the effectiveness of the MIS-TLIF over the O-TLIF in patients with symptomatic lumbar stenosis combined with low-grade spondylolisthesis by comparing the clinical efficacy and safety. SUMMARY OF BACKGROUND DATA: In patients with combined lumbar spinal stenosis and spondylolisthesis, it remains uncertain whether minimally invasive fusion surgery is noninferior to the open approach. MATERIALS AND METHODS: We conducted an open-label, noninferiority trial involving patients with symptomatic lumbar stenosis combined with low-grade spondylolisthesis. Patients were randomly assigned in a 1:1 ratio to undergo either MIS-TLIF or open TLIF surgery. The primary endpoint was the reduction in the Oswestry disability index (ODI) score from baseline to three months postsurgery, with a noninferiority margin of 12 points. Secondary outcomes included three-month changes from baseline in back and leg pain, neuropathic pain, satisfaction with treatment, intraoperative data, and cost-effectiveness. RESULTS: In the modified intention-to-treat population, the mean difference was 0.4, with the corresponding 90% CI of -5.7 to 6.5, having a lower bound below the noninferiority margin of 12. Similar results were obtained by analysis of the per-protocol population. 82.8% of patients achieved the MCID for the ODI. Results for secondary outcomes (clinical scales, complications) showed no significant differences between the treatment groups (all P >0.05). Although the open TLIF group had a hospital stay that was 1.5 days longer ( P =0.005) and required additional analgesia more frequently ( P =0.026), direct costs were 10.5% higher in the MIS-TLIF group ( P <0.001). CONCLUSIONS: This is the first high-quality study comparing open TLIF and MIS-TLIF with a validated primary endpoint. Among patients with combined lumbar degenerative stenosis and degenerative spondylolisthesis, MIS-TLIF resulted in clinical outcomes at three months that were noninferior to those with open TLIF.

Humans

Quantification of appetite-regulating hormones in children with hypothalamic and common obesity.

CONTEXT: The pathophysiology of hypothalamic obesity (HyOb) remains incompletely understood with no effective treatments. OBJECTIVE: We examined differences in appetite-regulating hormone concentrations between patients with HyOb, common obesity, and lean controls. DESIGN: Multiway cross-sectional case-control study of patients aged 2 through 19 years. SETTING: Two tertiary pediatric endocrinology centers. PATIENTS: Cases were obese (body mass index [BMI] > +2 SD score [SDS], "HyOb") and lean ("HyLean") patients with congenital (septo-optic dysplasia) or acquired (suprasellar brain tumor) hypothalamic disorders. Controls had common obesity ("Ob") or nonhypothalamic disorders and normal BMI ("Lean"). MAIN OUTCOME MEASURES: Relationships between the Dykens' Hyperphagia Questionnaire Score (DHQS), plasma or serum concentrations of leptin, insulin, &#x3b1;-melanocyte stimulating hormone (&#x3b1;MSH), brain-derived neurotrophic factor, oxytocin, acylated ghrelin, agouti-related peptide and copeptin, and BMI SDS. RESULTS: Dykens' Hyperphagia Questionnaire Score did not differ between HyOb and Ob patients (24 [17-34] vs 24 [18-31]) but correlated with BMI SDS in patients with hypothalamic disorders (P = 0.02). HyOb and Ob patients exhibited similarly increased anorexigens (insulin, leptin) and decreased orexigens (ghrelin, agouti-related peptide) compared to HyLean and Lean patients. The rate of BMI increase was independently associated with lower &#x3b1;MSH (&#x3b2; = -0.23 [-0.36 to -0.11], P = .0007) and ghrelin (&#x3b2;=-0.004 [-0.01 to 0.00], P = .001) concentrations, suggesting that &#x3b1;MSH replacement may be a therapeutic target for HyOb. HyLean patients demonstrated intermediate insulin responses to glucose compared to other subcohorts. CONCLUSION: In our cohort, patients with HyOb appeared indistinguishable from Ob in terms of their appetite and appetite-regulating neuroendocrine circuitry. Higher &#x3b1;MSH concentrations are associated with reduced weight gain and may be a target for therapeutic intervention.

alpha-MSH

Social Responsiveness as a Mediator in Adapted Cognitive Behavioral Therapy for Autistic Youth with Maladaptive and Interfering Anxiety.

Numerous adaptations to interventions have been included in cognitive behavioral therapy (CBT) for autistic youth. This study examines the degree to which CBT adapted to the social needs of autistic youth confers significant benefit by promoting social responsiveness. A secondary analysis was conducted on a multisite randomized clinical trial (Wood et al. in JAMA Psychiatry 77:474-483, 2020) comparing adapted CBT with standard-of-practice CBT and treatment-as-usual (TA). Autistic youth (N&#x2009;=&#x2009;167; aged 7-13) with maladaptive and interfering anxiety participated. The adapted CBT (BIACA) uses a modular format, with an emphasis on supplementing common CBT practice elements (reframing and graded exposure) with social skill supports. The primary outcome measure was the Pediatric Anxiety Rating Scale. Social responsiveness was assessed with the Social Responsiveness Scale, Second Edition. Participants' general mental health was assessed as a secondary outcome using the Brief Problem Checklist. Mediation was tested using the SPSS PROCESS macro. Analyses suggested that the effect of adapted CBT on anxiety was mediated by its effects on social responsiveness, with a statistically significant indirect effect. Youth randomly assigned to adapted CBT exhibited better overall mental health at posttreatment compared to those randomized to the other conditions, and this effect was also mediated by improved social responsiveness. CBT adapted to address some of the social needs of autistic youth may enhance mental health outcomes by supporting social responsiveness, perhaps increasing the ease and effectiveness with which some youth can navigate potentially stressful situations such as entering and participating in group activities.

Humans

Application of musculoskeletal ultrasound in postoperative rehabilitation assessment and monitoring after rotator cuff repair: A systematic review.

BACKGROUND: The development of rehabilitation protocols after rotator cuff repair has long lacked objective benchmarks. Traditional time&#x2011;based regimens are limited by considerable inter&#x2011;individual variability and an increased risk of re&#x2011;tear. Musculoskeletal ultrasound allows dynamic assessment of tendon healing and muscle morphology, yet evidence for directly linking its use to rehabilitation decisions remains scarce. OBJECTIVE: To systematically synthesize the evidence on the use of musculoskeletal ultrasound monitoring to inform rehabilitation decision&#x2011;making after rotator cuff repair. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta&#x2011;Analyses (PRISMA) guidelines, we searched PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Data from January 2020 to April 2026. Original studies were included if they involved patients who had undergone rotator cuff repair, used musculoskeletal ultrasound (including gray&#x2011;scale ultrasound, elastography, etc.) to evaluate the rotator cuff tendons or shoulder muscles, and reported at least one parameter related to rehabilitation decision-making or functional outcomes. RESULTS: Eleven studies were included. Shear wave velocity (SWV), cross&#x2011;sectional area (CSA), and echo intensity (EI) were the most frequently reported ultrasound parameters. Available evidence indicated that SWV increased progressively after surgery, with an overall increase of approximately 22% to 25% from one week to 12 months postoperatively. This dynamic trajectory may serve as a reference baseline for judging rehabilitation progress. An abnormally elevated SWV in the early postoperative period was associated with an increased risk of re&#x2011;tear, suggesting that a more conservative rehabilitation strategy should be adopted. Tendon stiffness measured at 12 weeks after surgery independently predicted long&#x2011;term return to sport. Regarding muscle parameters, changes in CSA and EI were positively correlated with shoulder function scores, and the combination of these two parameters effectively identified patients with rehabilitation bottlenecks. CONCLUSION: Musculoskeletal ultrasound parameters are associated with the initiation of active movement, adjustment of exercise load, prediction of return&#x2011;to&#x2011;sport prognosis, and identification of retear risk. Among these, SWV shows particular promise as an objective monitoring parameter for supporting rehabilitation assessment after rotator cuff repair. Future randomized controlled trials are needed to determine whether ultrasound-informed assessment can improve rehabilitation outcomes compared with traditional time-based regimens, and to establish standardized measurement protocols and clinically applicable reference values. Key findings of this review are summarized in S1 File.

Humans

Comparison of immunogenicity, safety, and efficacy of EVA71 vaccine in children: a systematic review and meta-analysis.

INTRODUCTION: Enterovirus 71 (EV-A71) is a principal cause of hand, foot, and mouth disease (HFMD), potentially leading to severe neurological complications in children. Inactivated EV-A71 vaccines have been introduced. This study compares the immunogenicity, safety, and efficacy of EV-A71 vaccines versus placebo in pediatric populations. RESEARCH DESIGN AND METHODS: Following a PROSPERO-registered protocol, RCTs involving EV-A71 in children were identified via PubMed, Scopus, Cochrane, and ClinicalTrials.gov. Two independent reviewers performed screening, extraction, and RoB assessments (RoB 2.0). RESULTS: Five phase III RCTs involving 36,659 children were included. EV-A71 vaccination significantly increased seropositivity across follow-up periods, including early (RR 5.8), medium-term (RR 3.09), and long-term (RR 2.95) response. Seroconversion was significantly higher in the vaccinated group (pooled RR 13.04, 95% CI 2.80-60.61; p&#x2009;<&#x2009;0.001). Geometric mean titers, analyzed using the ratio of means approach, were significantly higher in the vaccinated group during early and medium-term follow-up. Vaccine efficacy against EV-A71-associated HFMD exceeded 98% (pooled RR 0.02, 95% CI 0.01-0.09; p = 0.0028; I2&#x2009;=&#x2009;50%). Solicited local and systemic adverse events were mild and comparable between groups. CONCLUSION: Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children. Future studies should explore long-term protection, booster schedules, and multivalent formulations against non-EV-A71 serotypes.

Humans

Integrated exome and mitochondrial genome sequencing reveals the genetic landscape of primary mitochondrial diseases: findings from a large Tunisian cohort.

Primary mitochondrial diseases are a heterogeneous group of neurometabolic disorders recognized as the most common metabolic genetic diseases. They manifest at any age, affecting any tissue or organ, especially those with high energy demands, and are caused by pathogenic variants in both mitochondrial and nuclear genomes. Here, we aimed to describe the genetic spectrum of a Tunisian pediatric cohort with suspected mitochondrial diseases. We recruited 47 unrelated families who underwent exome sequencing as a first-tier test followed by whole mitochondrial genome sequencing for unsolved cases. Dedicated bioinformatic pipelines and prediction tools were used to determine the potential disease-causing variants. Sanger sequencing confirmed the presence and segregation within parents. For the newly identified variants, structural modeling was conducted to study the impact of these variants on protein structure and motions. Dual genome sequencing yielded a molecular diagnosis in 33/47 families (70%) and 18/47 (38%) showed disease-causing variants in genes encoding mitochondrial proteins. Among them, four families disclosed novel variants in FASTKD2, SERAC1 and GATB, which were supported by in-depth in silico and structural analyses demonstrating their deleterious effect. The remaining families (32%, 15/47) disclosed other metabolic and neurological disorders. An exome-first strategy delivers a high diagnostic yield in Tunisia, where consanguinity remains high and simultaneously captures mitochondrial and non-mitochondrial etiologies. Mitochondrial sequencing remains indispensable in the case of an inconclusive exome. Thus, our data expand the clinical and genetic spectrum of primary mitochondrial diseases in Tunisia, an underrepresented and admixed population.

Humans