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PubMed2026

Assessing time to symptomatic progression, a patient-relevant efficacy endpoint, in the MARIPOSA study in non-small cell lung cancer.

INTRODUCTION: In the phase 3 randomized MARIPOSA study, amivantamab and lazertinib combination therapy demonstrated improved progression-free survival (PFS) and overall survival (OS) versus osimertinib in participants with previously untreated, epidermal growth factor receptor-mutated advanced non-small cell lung cancer. Time to symptomatic progression (TTSP) was introduced to assess clinical worsening and complement endpoints that investigate radiographic disease progression and patient-reported outcomes. TTSP provides an easily interpretable measure of disease-specific symptom worsening to further support patient experience. METHODS: In MARIPOSA, TTSP was quantitatively assessed as a secondary efficacy endpoint and defined as the time from randomization until participants experience disease-specific symptom worsening requiring a clinical intervention or treatment change, or death. To evaluate the impact of amivantamab and lazertinib on TTSP considering its established OS benefit against osimertinib, an exploratory analysis censoring death events was performed. RESULTS: At the final protocol-specified OS analysis (median follow up: 37.8 months), median TTSP was 43.6 months with amivantamab and lazertinib versus 29.3 months with osimertinib (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.57-0.83; p < 0.0001). Amivantamab and lazertinib reduced deaths following a TTSP event compared to osimertinib. A strong correlation between TTSP and PFS or OS was observed. CONCLUSIONS: Amivantamab and lazertinib significantly delayed TTSP versus osimertinib. TTSP offers a clinician-validated measurement of disease-specific symptom worsening, capturing symptoms perceived by patients that prompt clinical action. TTSP is highly correlated with PFS and OS, providing complementary insights alongside traditional endpoints. TTSP enhances understanding of treatment benefit and supports informed clinical decision-making by integrating patient experience.

Humans↗

PubMed2026

Timing and Dose Matter: Late High-Speed Exposure and Higher High-Intensity Acceleration Volumes Reduce Hamstring Reinjury Risk in Elite Male Football (Soccer).

OBJECTIVES: The aims of this study were to (a) investigate whether the timing and magnitude of exposure to high-speed running (HSR), sprinting, and high-intensity accelerations during on-field rehabilitation after hamstring strain injury were associated with reinjury risk and (b) examine changes in match running performance upon return to play (RTP). DESIGN: Retrospective cohort study. METHODS: Data from 95 elite male football (soccer) players from five professional clubs competing in major European and Middle Eastern leagues were analyzed. Players with complete rehabilitation load profiles were included in the 2-month and 6-month reinjury analysis. Modified Poisson regression assessed associations between rehabilitation load characteristics and reinjury risk. Match running performance (HSR distance, sprint distance, and high-intensity accelerations per minute) during the five matches before injury and the first five matches after RTP was compared using paired t-tests for the entire cohort. RESULTS: Late introduction of HSR, sprinting, and high-intensity accelerations during rehabilitation (ie, ≥ 60% of rehabilitation progression) was associated with a significantly lower reinjury risk at 2 months (relative risk [RR] range = 0.948-0.969; P < .01) and 6 months (RR range = 0.964-0.979; P < .05). Higher daily exposure to high-intensity accelerations once introduced was protective (RR = 0.861 (0.778-0.951)). There were no meaningful associations between total volume of HSR or sprinting and reinjury. Match running performance metrics did not differ between pre-injury and post-RTP matches (all P > .05). Changes in performance were not correlated with rehabilitation load characteristics. CONCLUSION: The timing of high-intensity running exposure during on-field rehabilitation appeared associated with a lower hamstring reinjury risk. Delaying the introduction of HSR, sprinting, and accelerations, followed by a structured and progressive build-up, was associated with lower risk of reinjury without compromising the subsequent match performance of elite male football players. J Orthop Sports Phys Ther 2026;56(9):611-621. Epub 7 Jul 2026. doi:10.2519/jospt.2026.14077.

Humans↗

PubMed2026

Determinants of Nonspecific Response to Treatment in Randomized Controlled Trials of Major Depressive Disorder: A Narrative Review.

The design, conduct, and interpretation of double-blind randomized placebo-controlled clinical trials in major depressive disorder (MDD) are complicated by determinants of nonspecific response to treatment (NSRT). This narrative review provides a comprehensive overview of the determinants of NSRT in randomized controlled trials (RCTs) for MDD, including the placebo effect, factors related to measurement of the primary endpoint, the inclusion of misdiagnosed patients, the relapsing-remitting course of MDD, and factors related to functional unblinding. Potential strategies to reduce the impact of the determinants of NSRT and to improve the interpretation of RCT outcomes in MDD are also summarized. These strategies include use of centralized rating and standardized rater training, independent diagnostic confirmation, optimized site selection, minimizing financial incentives, exclusion of subjects participating in multiple clinical trials, exclusion of patients with unstable major depressive episode trajectories, and use of active placebo and alternative trial designs. Uniformity among experts in the definitions of determinants of NSRT and related concepts, as well as in strategies to address them, may facilitate progress in the development of novel treatments for MDD.

Humans↗

PubMed2026

Low-Dose Perineural Dexamethasone Enhances Analgesia After Pediatric Hand Surgery Without Elevating Systemic Stress Markers: A Randomized Controlled Trial.

BACKGROUND: Supraclavicular brachial plexus block is a widely used technique for upper limb surgery in children. Although perineural dexamethasone has demonstrated efficacy in prolonging analgesia in adults, data on its optimal dosing and systemic safety in pediatric patients are limited. This study aimed to evaluate whether low-dose perineural dexamethasone can prolong postoperative analgesia without increasing systemic stress markers in young children undergoing hand or wrist surgery. METHODS: In this triple-blinded, randomized controlled trial (ClinicalTrials.gov Identifier: NCT06086392), 90 children aged 3 months to 6 years undergoing elective upper extremity surgery were assigned to receive supraclavicular brachial plexus block with 0.2% ropivacaine combined with either normal saline (control), dexamethasone 0.05 mg/kg, or dexamethasone 0.1 mg/kg. The primary outcome was time from arrival in the postanesthesia care unit to first administration of rescue opioid analgesia. Secondary outcomes included total opioid consumption, postoperative pain intensity using the FLACC scale, blood glucose levels, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and time to motor recovery. RESULTS: Both dexamethasone groups demonstrated significantly prolonged time to first opioid use compared with the control group (mean±SD: 19.4±2.2 h in the 0.1 mg/kg group, 16.0±1.9 h in the 0.05 mg/kg group, and 8.5±1.3 h in controls; P <0.0001). Total opioid consumption was significantly reduced in the dexamethasone groups. Postoperative pain scores were lower in both intervention groups, especially during the first 12 hours. No significant differences were found among groups in blood glucose, inflammatory markers, or incidence of nerve deficits. Motor recovery was delayed in the dexamethasone groups but did not interfere with early mobilization. CONCLUSIONS: Low-dose perineural dexamethasone (0.05 to 0.1 mg/kg) safely and effectively prolongs postoperative analgesia and reduces opioid needs in children undergoing upper limb surgery, without causing systemic metabolic or inflammatory disturbances. The 0.05 mg/kg dose may offer a more favorable balance between analgesic efficacy and motor recovery time. LEVEL OF EVIDENCE: Level I-randomized controlled trial.

Humans↗

PubMed2026

Access to palliative care in rural settings: A mixed-methods systematic review.

BACKGROUND: Rural populations experience persistent inequities in access to palliative care. Existing evidence often describes individual barriers separately, with less attention to how access breaks down across the care pathway or how different service configurations shape access. OBJECTIVES: To synthesise evidence on access to palliative care in rural settings and examine how access barriers, service models, and implementation conditions interact across the care pathway. METHODS: A mixed-methods systematic review using a convergent integrated approach searched nine databases (PubMed, Embase, CINAHL, Web of Science, Scopus, PsycINFO, CNKI, WanFang, SinoMed) from inception to 15 March 2026, supplemented by hand-searching. Eligible studies were primary qualitative, quantitative, and mixed-methods studies on access to palliative care for adults in rural or non-urban settings. Two reviewers independently screened studies, extracted data, and assessed quality using the Mixed Methods Appraisal Tool. Findings were mapped to the Levesque access framework, analysed using the updated Consolidated Framework for Implementation Research, and integrated through mixed-methods synthesis, with additional coding of service models. RESULTS: Thirty-four studies were included, of which 26 were conducted in high-income countries and eight in low- and middle-income countries. Service configurations included specialist or hospice-oriented care, generalist or primary-care-oriented care, mixed specialist-generalist models, home-based and caregiver-centred care, nurse-coordinated services, telehealth-supported care, and community or implementation-oriented approaches. Access broke down cumulatively across four interdependent stages: recognition, entry, reach, and use and continuity, with affordability constraining every stage. Recognition was limited by low awareness, poor service visibility, and delayed identification of need. Entry was shaped by stigma, trust, family expectations, and unclear referral processes. Reach was constrained by distance, transport, workforce shortages, limited specialist capacity, and weak infrastructure. Use and continuity were affected by fragmented coordination, weak transitions, unstable follow-up, and reliance on family caregivers. Access problems varied across service configurations. Evidence on service innovations was methodologically less certain, and the overall evidence base remained concentrated in high-income countries. CONCLUSIONS: Access to palliative care in rural settings is best understood as a pathway and service-configuration problem rather than simply a deficit in service availability. Improving access requires earlier recognition, clearer referral routes, stronger specialist-generalist and nursing links, better support for family caregivers, and greater attention to affordability, continuity, and rural settings with limited resources. REGISTRATION: International Prospective Register of Systematic Reviews: CRD420261340783.

Health Services Accessibility↗

PubMed2026

Hip Arthroscopy During Female Menstruation: A Retrospective Analysis of Safety and Clinical Outcomes With 24-Month Follow-Up.

OBJECTIVES: To investigate the safety and clinical outcomes of hip arthroscopy performed during menstruation in reproductive-age female patients, and to determine whether surgery during menstruation increases intraoperative risks or adversely affects postoperative recovery. Currently, clear clinical guidelines regarding the timing of elective orthopedic surgeries relative to the menstrual cycle are lacking, often leading to unnecessary surgical rescheduling. Therefore, this study aimed to provide evidence-based guidance for perioperative management and optimal surgical scheduling, thereby addressing a critical clinical need. METHODS: This retrospective cohort study included reproductive-age female patients who underwent hip arthroscopy at the First Medical Center of Chinese PLA General Hospital, the Fourth Medical Center of Chinese PLA General Hospital, and the Department of Sports Medicine at the Second Hospital of Shandong University from December 2018 to September 2023. Patients were categorized into the menstruation group (MP) and the non-menstruation group (NMP) based on whether they were menstruating on the day of surgery. The NMP group consisted of equally sized ovulatory (OP) and luteal (LP) phases. Perioperative outcomes included: intraoperative blood loss, anesthetic dosage, operative time, hemoglobin (Hb) change (within 24 h postoperatively), prothrombin time (PT), and activated partial thromboplastin time (APTT). Postoperative outcomes included analgesic consumption, duration of analgesic use, time to first unassisted weight-bearing ambulation, complications, and urinary tract infections. Functional outcomes were assessed at 24-month follow-up using the Visual Analog Scale (VAS), Modified Harris Hip Score (mHHS), International Hip Outcome Tool-12 (iHOT-12), Hip Outcome Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sports Specific Subscale (HOS-SSS). RESULTS: Of 884 eligible patients, 28 were included in the MP group and 56 matched patients in the NMP group. Operative time, anesthetic use, Hb change, PT, and APTT were comparable between the two groups (all p > 0.05). No serious complications or urinary tract infections occurred in either group. At the 24-month follow-up, both groups demonstrated significant improvements in VAS, mHHS, iHOT-12, HOS-ADL, and HOS-SSS (all p < 0.001), with no statistically significant differences observed between the groups. CONCLUSIONS: Hip arthroscopy during menstruation does not increase intraoperative bleeding, impair coagulation, or delay functional recovery for female patients. Menstruation should not be considered a contraindication when appropriate perioperative management is applied.

Humans↗

PubMed2026

Extended Long-Term Effects of Cognitive and Aerobic Training on Cognitive Function in Patients With Stress-Related Exhaustion Disorder: A 4.5-Year Follow-Up of a Randomized Controlled Trial.

Stress-related conditions like clinical burnout and exhaustion disorder (ED) are associated with enduring cognitive problems. We have previously demonstrated that the addition of computerised cognitive training (CCT) and aerobic training (AT) to a multimodal rehabilitation programme (MMR) yielded greater improvements in cognitive function compared to MMR alone in patients with ED. These effects were maintained at the 1-year follow-up for CCT, but not for AT. Building on these findings, the present study examined the extended long-term effects of CCT and AT on cognitive function, psychological health, and work ability, 4.5 years after the interventions. Participants were recruited from a stress-rehabilitation clinic and 56 of the initial 132 participants returned for the 4.5-year follow-up. Assessments were conducted before (T1), immediately after (T2), 1-year after (T3) and 4.5-years after (T4) the interventions. Mixed model analyses assessed changes in the intervention groups relative to the control group from T1 to T4, with follow-up comparisons examining within-group stability of outcomes between T3 to T4. The primary outcome was cognitive performance on a global cognitive score. Secondary outcomes included domain-specific cognitive functioning, self-reported cognitive function, psychological health (burnout, depression, anxiety, and fatigue), and work ability. The analysis revealed sustained long-term effects on the global cognitive score, a trained updating task and episodic memory in the CCT group, with stable performance between one- and 4.5-year follow-up. The addition of AT did not yield any extended long-term effects on cognitive performance. Both groups showed extended long-term improvements in self-reported memory problems, although findings were mixed. Extended long-term improvements were observed on burnout for both groups, with additional effects on anxiety and work ability in the AT group. Notably, these effects were not present at the 1-year follow-up and are more plausibly explained by selective attrition rather than a delayed intervention effect. In conclusion, the result indicates that cognitive interventions such as CCT can have lasting positive effects on cognitive function in patients with ED, whereas the long-term psychological effects should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073772.

Adult↗

PubMed2026

Surgical management of jugular foramen meningiomas: a function-prioritized perioperative workflow.

OBJECTIVE: Jugular foramen meningiomas are challenging because of their deep, neurovascularly crowded location and multicompartment extension; hyperostosis and rigid dural attachment further narrow the corridor and increase the risk of lower cranial nerve morbidity, causing dysphagia and airway complications that may rarely require tracheostomy. This study aimed to describe a contemporary function-first workflow integrating compartment-based anatomy, venous sinus status, preoperative embolization, and continuous vagus nerve monitoring and its relation to clinically actionable recovery endpoints. METHODS: The authors retrospectively reviewed 26 consecutive patients who underwent primary surgery for jugular foramen meningiomas (2014-2025). Tumors were classified as intradural + intrajugular (IJ) or intradural + intrajugular + extracranial extension (IJE). Retrosigmoid, suprajugular, or transjugular approaches were selected by tumor extension and sigmoid-jugular venous status. Selective embolization and continuous vagus nerve monitoring were used when feasible. Outcomes included extubation timing, time to oral intake, 1-year swallowing/voice severity, extent of resection, and salvage stereotactic radiosurgery (SRS) for progression/regrowth. RESULTS: Twenty tumors were IJ and 6 were IJE. Selective embolization was performed in 16 patients (62%) without complications. Continuous vagus nerve monitoring was implemented in 16 patients (62%); lower preservation rates showed an exploratory association with worse 1-year swallowing. All patients were extubated immediately after surgery. Oral intake began by postoperative day ≤ 7 in 20 patients (77%); only 1 required > 14 days before resuming oral intake. At 1 year, swallowing and hoarseness remained worse in 54% and 46% of patients, respectively, but almost all cases were mild; the same patient had moderate dysphagia/hoarseness, and none required tracheostomy, gastrostomy, long-term tube feeding, or phonosurgery. Simpson grade IV comprised 69% of cases but predominantly reflected intrajugular/extracranial residual rather than persistent intradural disease. No patient without preoperative facial nerve palsy developed new palsy; serviceable hearing was preserved in 70%, and 38% with preoperative nonserviceable hearing improved to serviceable hearing. During a median 55.6-month follow-up, 3 patients (12%) underwent salvage SRS for regrowth; none required reoperation. CONCLUSIONS: A function-first workflow guided by anatomical compartment extension and intraoperative monitoring can support rapid recovery and durable functional independence in jugular foramen meningiomas. The IJE phenotype identifies a higher-risk subgroup for delayed oral intake and postoperative subjective dysphagia/hoarseness, while continuous vagus nerve monitoring may provide actionable insights to calibrate surgical aggressiveness and support function-prioritized acceptance of intrajugular/extracranial residual with close surveillance and salvage SRS when needed.

Humans↗

PubMed2026

Emphysematous pyelonephritis in children: Lessons from a case report and systematic review.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a rare, life-threatening gas-producing renal infection. Literature on pediatric EPN remains scarce. OBJECTIVE: To describe a case of pediatric EPN and systematically review the data on clinical presentations, diagnostic modalities, management strategies, and prognosis in pediatric emphysematous pyelonephritis. METHODS: A comprehensive search in PubMed, Embase and Web of Science using defined search terms was done, along with the Joanna Briggs Institute (JBI) critical appraisal checklist for quality assessment. RESULTS: Of 100 records, 20 studies (n = 21) were included in the review. The median (IQR) age of presentation was 48 (8-138) months. The major risk factor was reflux/obstructive nephropathy (52.3 %), and E. coli was the common organism. Management included antibiotics (47.6 %), minimally invasive procedures (33.3 %), or nephrectomy (19 %). We additionally report an adolescent girl with Type 1 diabetes mellitus and class 3A right-sided EPN. She improved with antibiotics and percutaneous nephrostomy (PCN) insertion. CONCLUSION: Obstructive or reflux nephropathy is a major risk factor for pediatric EPN. Antibiotics are the mainstay for treatment with supportive management. Refractory cases may require percutaneous drainage or partial/total nephrectomy.

Humans↗

PubMed2026

An impact assessment of the European medical device regulations implementation - the current status quo.

BACKGROUND: This research aims to assess the current impact of the medical and in-vitro diagnostic devices regulations (MDR/IVDR) on the device industry in the EU, under the lens of postimplementation and the amending regulation, and in advance of the final transition to the IVDR/MDR in the future. RESEARCH DESIGN AND METHODS: A quantitative survey was administered to a diverse cohort of medical device enterprises, ranging from micro to large organizations. RESULTS: The survey indicates that the MDR/IVDR has harmed innovation, leading many manufacturers to seek initial device approval and launch elsewhere before in Europe. There is evidence that some manufacturers have rationalized their existing product portfolios and removed devices from the market as they stated they would in previous industry surveys. The MDR/IVDR has been shown to negatively impact manufacturers, with increased costs related to notified body (NB) fees, maintaining and updating documentation, recertification fees, and hiring additional staff. CONCLUSION: This study provides a current status of the effects of MDR/IVDR on manufacturers and finds that despite amending regulations and other interventions taken by the EU to mitigate regulatory burden, ensure product availability, and address stakeholder concerns, the EU is no longer the market of choice for new products.

Equipment and Supplies↗

PubMed2026

Ramu stunt virus genome reveals previously unreported segments and nucleocapsid domain duplication in Mechlorovirus.

Ramu stunt virus (RmSV), a member of the genus Mechlorovirus within the family Phenuiviridae, was previously described as a six-segmented RNA virus infecting sugarcane. In this study, we re-examined type material and additional isolates using high-throughput sequencing and RT-PCR validation, revealing that RmSV possesses a nine-segmented genome, making it the largest reported in the Phenuiviridae. This expanded architecture includes duplicated RNA segments (RNA 2a and RNA 2b) encoding nucleocapsid-like proteins and two novel segments (RNA 7 and RNA 8). Comparative analysis showed that RNA 2a and 2b share about 84% amino acid identity, while RNA 5 encodes a third nucleocapsid homolog, indicating unprecedented domain redundancy. Structural modeling confirmed that all three nucleocapsid proteins maintain a conserved fold despite low sequence identity, with electrostatic mapping suggesting differential RNA-binding potential. Additionally, RNA 6 encodes a hypothetical protein structurally similar to the rice stripe virus disease-specific S-protein, implicating a role in symptom development. Transcript abundance analysis revealed RNA 6 as the most highly expressed segment across isolates. These findings revise the genomic composition of RmSV, highlight mechanisms of genome plasticity and adaptive evolution in plant-infecting bunyaviruses, and underscore practical implications for diagnostic assay design, resistance breeding, and biosecurity surveillance.

Genome, Viral↗

PubMed2026

Comparison of Adult Tracheostomy Outcomes Before and After Implementation of a Dedicated Tracheostomy Team.

OBJECTIVE: (A) Determine patient and institutional factors associated with increased length of stay (LOS) and complications of tracheostomy, (B) Develop data-driven quality improvement in tracheostomy care. DESIGN: Mixed methods protocol used cross-sectional survey assessing institutional trends in tracheostomy-specific care. Retrospective chart review compared tracheostomy patient outcomes prior to and during implementation of a multidisciplinary tracheostomy care team and standardized guidelines. PARTICIPANTS: Patients undergoing tracheostomy from January 2019 to December 2021 at a tertiary hospital. METHODS: Patient factors, procedure type and indication, tracheostomy tube size, management timeline, insurance, and disease severity using Acute Physiology and Chronic Health Evaluation II (APACHE II) score were analyzed for associations with LOS and adverse events. Multivariate analyses controlled for APACHE II score and payer source. LOS and complications were compared between patients before and during implementation of multidisciplinary tracheostomy care team and standardized guidelines. RESULTS: Three-hundred and eighteen patients met criteria with a 21.7% complication rate, average LOS of 24 days (SD = 28.523), and median LOS post-tracheostomy of 14 days (IQR 7, 29). Departments without standardized protocols had greater LOS (F[1,316] = 28.706, P < .001]) and complication odds (OR = 2.92, P = .015, 95% CI[1.231, 6.930]). Larger tracheostomy tube size was linked to increased LOS (β = .253, t(314) = 4.741, P < .001, 95% CI[4.137, 10.081]). Delays from ventilation discontinuation to cuffless tube exchange and decannulation correlated with increased LOS (β = .406, t(184) = 6.321, P < .001, 95% CI[.928, 1.771]); (β = .554, t(129) = 7.625, P < .001, 95% CI[1.008, 1.715]). When focusing on a single department, comparing 2019 patients to 2021 patients (pre- and post-guideline and care team), overall, LOS decreased from 33.08 to 30.83 days (P = .586). When excluding patients discharged on a ventilator, the 2019 group had average LOS of 37.938 days versus 33.41 days in 2021 (P = .344). CONCLUSIONS: Standardized tracheostomy care guidelines and multidisciplinary care teams are critical to improving institutional outcomes. Data-driven approaches to quality improvement ensure efficient and targeted methods to improving patient care. LEVEL OF EVIDENCE: 4.

Humans↗

PubMed2026

Factors Associated With Accelerated Fracture Healing in Patients With Traumatic Brain Injury and Extremity Comminuted Fractures: A Retrospective Case-Control Study.

OBJECTIVE: Although traumatic brain injury (TBI) has been clinically associated with accelerated bone healing, the factors that determine which patients experience this phenomenon remain poorly defined, and previous findings are conflicting. This study aimed to investigate the clinical factors associated with accelerated fracture healing in patients with TBI combined with comminuted fractures of the limbs, so as to provide an evidence-based foundation for elucidating the clinical phenomenon of TBI-promoted fracture healing. METHODS: A retrospective case-control study design was employed. Patients between January 2020 and April 2024 with concurrent diagnoses of TBI and comminuted fractures were included. Based on radiographic findings and RUST/mRUST scores, patients were divided into an accelerated healing group (AHG) and a normal/delayed healing group (NDHG). Clinical data including demographics (age, sex, BMI), TBI characteristics (injury site, GCS score), admission laboratory indices (blood count, coagulation function, inflammatory markers), and fracture site/local soft tissue conditions, as well as functional outcomes assessed by the Short Musculoskeletal Function Assessment (SMFA) questionnaire at final follow-up were collected. Univariate analysis and multivariate logistic regression analysis were used to identify independent factors influencing accelerated fracture healing. Receiver operating characteristic (ROC) curves were plotted to evaluate their predictive value. RESULTS: A total of 119 patients were included, with 69 in the AHG and 50 in the NDHG. Significant differences were observed between the two groups in terms of age, BMI, GCS score, and platelet count (p < 0.05). Univariate analysis showed that age, BMI, GCS score, red blood cell count, and platelet count were associated with accelerated fracture healing (p < 0.20). Multivariate logistic regression analysis indicated that younger age (OR = 0.875, 95% CI: 0.821-0.934) and lower GCS score (indicating more severe TBI; OR = 0.490, 95% CI: 0.339-0.707) were independent predictors of accelerated fracture healing. ROC curve analysis showed that the area under the curve (AUC) for age and GCS score in predicting accelerated healing were 0.893 and 0.851, respectively. CONCLUSIONS: In patients with TBI combined with comminuted fractures, younger age and greater TBI severity (lower GCS score) are independent predictors of accelerated fracture healing. These findings assist clinicians in the early identification of patients with high healing potential to optimize treatment strategies, facilitate the early identification of high-risk patients, and provide clinical clues for further exploration of the molecular mechanisms underlying neurohumoral regulation of bone regeneration.

Humans↗

PubMed2026

Influenza as a Less Commonly Recognized Cause of Hemophagocytic Lymphohistiocytosis: A Systematic Review of Case Reports and Case Series.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory condition that can be triggered by viral infections. However, influenza is not commonly recognized as a cause of HLH, and there is no comprehensive synthesis of influenza-associated HLH in the literature to guide clinicians. We conducted a systematic search of Pubmed and Embase to identify case reports and case series on influenza-associated HLH, and included 29 articles involving 47 patients. Their age ranged from 2 months to 72 years. 67% were males. Influenza A accounted for 91.3% of the cases, predominantly H1N1 (90.2%). All patients had fever, 60% had anemia, 69.7% had thrombocytopenia, 46.6% had leukopenia, 61.3% had splenomegaly, 71.4% had hypertriglyceridemia, and 94.7% had elevated ferritin levels. 97.6% had hemophagocytosis on biopsy. Antiviral therapy was administered in 89.5% of patients. HLH-directed therapy included corticosteroids (77%), intravenous immunoglobulin (36%), and etoposide (23.1%). Intensive care was required in 95.2% of cases. Overall survival was 53.2%. Survival rate was 50% among patients who received either antiviral therapy alone or HLH-directed therapy alone, compared with 65.4% among those who received both. Further studies are necessary to establish standardized diagnostic and therapeutic protocols for influenza-associated HLH.

Humans↗

PubMed2026

A systematic review of human avoidance learning: Cognition, computation, and methods.

Avoidance behaviour is fundamental for survival but can become maladaptive in clinical conditions. A large body of literature has accumulated on the dynamics of human avoidance learning. However, current theories and overviews do not provide an exhaustive account of this evidence. In this systematic review, we identify N = 116 studies on human avoidance learning. We analyse these studies with the goal of distilling robust empirical phenomena as a basis for theory-building, and examine their diagnostic value in differentiating between competing theories. We find that the evidence is difficult to reconcile with foundational two-factor and classical safety-signal accounts, and most strongly supports expectancy- and inference-based views, in which avoidance responses are selected with respect to represented consequences. At the same time, no current framework provides a complete account of the evidence: several findings point to an additional role for operant valuation, Pavlovian influences, and contextual or latent-state control over the expression of avoidance. Methodologically, we observe that the problem setting in the most common experimental paradigms is radically simpler than real-world avoidance and therefore unlikely to expose the limits of inferential or reflective mechanisms. Consequently, we argue that paradigms with greater computational demands and more realistic action affordances are required to identify the mechanisms underlying avoidance learning. Collectively, these insights provide a foundation for theoretical refinement, computational modelling, and methodological innovation, with implications for advancing interventions targeting maladaptive avoidance.

Humans↗

PubMed2026

Long-term glycemic variability and risk of peripheral artery disease: a systematic review and meta-analysis of cohort studies.

BACKGROUND: A systematic review and meta-analysis to evaluate the impact of long-term glucose variability (GV) on the risk of developing peripheral artery disease (PAD). METHODS: The protocol was prospectively registered in PROSPERO (ID: CRD420251148763). Relevant longitudinal studies were identified through comprehensive searches of PubMed, Embase, and Web of Science. The primary outcome was the risk ratio (RR) of PAD comparing participants with high versus low GV. Summary effect sizes were calculated using a random-effects model to account for between-study heterogeneity. RESULTS: Eleven cohorts were included. Higher GV showed a positive association with PAD risk (RR: 1.42; 95% CI [1.21-1.66] p < 0.001), although substantial heterogeneity was present (I 2 = 91%). This association was consistent across subgroups defined by region (Asian vs. Western), study design, diabetic status, GV metrics, PAD diagnostic methods, and adjustment for HbA1c (all p for subgroup differences > 0.05), except for follow-up duration. Studies with follow-up < 8 years showed a stronger association than those with ≥ 8 years (RR: 1.64 vs. 1.19; p for subgroup difference = 0.006). CONCLUSIONS: Elevated long-term GV appears to be associated with an increased risk of PAD. However, substantial heterogeneity across studies suggests that the magnitude of this association should be interpreted with caution.

Humans↗

PubMed2026

Multisensory stimulation for promoting development and preventing morbidity in preterm infants.

RATIONALE: Multisensory stimulation is a structured, developmentally appropriate intervention that provides simultaneous or sequential stimulation of two or more senses (e.g. tactile, auditory, visual, or vestibular) in a controlled and non-stressful manner, with the aim of supporting early neurodevelopment in preterm infants. It has the potential to enhance physiological regulation in preterm infants by stabilizing key functions, such as respiratory patterns, heart rate, and oxygen saturation; reducing the need for respiratory support; and improving feeding performance and sleep regulation. Targeted multisensory interventions have also been associated with improved neurodevelopmental outcomes, including enhanced psychomotor development and visual function. OBJECTIVES: To assess the benefits and harms of multisensory stimulation compared to any single sensory intervention or standard care on major neurodevelopmental disability, mortality, and growth in preterm infants. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Emcare, CINAHL, Epistemonikos, two trial registries, and conference abstracts up to 28 November 2025. We checked reference lists of included trials, and systematic reviews on sensory interventions. ELIGIBILITY CRITERIA: We included 18 randomized controlled trials (RCTs) comparing multisensory stimulation in preterm infants with no intervention (placebo or standard care), and one RCT comparing multisensory stimulation with single-sense stimulation (tactile stimulation). OUTCOMES: Our critical outcomes were major neurodevelopmental disability at 18 to 24 months: cerebral palsy (CP), developmental delay, intellectual impairment, blindness, sensorineural deafness; death during initial hospitalization; and total weight gain (grams), assessed at discharge. When comparing multisensory stimulation with single-sense intervention, we also included weight gain during the intervention, an outcome added during the post-hoc analysis. Important outcomes were duration of hospital stay, of NICU stay, and of respiratory support; and time until full oral feeding. RISK OF BIAS: We used the Cochrane tool, RoB 2. SYNTHESIS METHODS: We conducted meta-analyses using fixed-effect models to calculate risk ratios (RR) for dichotomous data, and mean differences (MDs) for continuous data, each with its 95% confidence intervals (CIs). We assessed statistical heterogeneity by calculating the I2 statistic when we included more than two trials in a meta-analysis. We evaluated the certainty of evidence using GRADE. INCLUDED STUDIES: We included 19 trials (1554 newborn infants): 18 studies compared multisensory stimulation with standard care; one compared multisensory stimulation with single-sensory stimulation (tactile). In 10 studies, the primary aim was to assess the neurobehavioral outcomes of multisensory stimulation on preterm neo-nates. The other nine studies aimed to assess the impact of multisensory stimulation on weight gain during the intervention, weight gain until hospital discharge, length of neonatal intensive care unit (NICU) stay, length of hospital stay, time until full oral feeding, length of respiratory support, or a combination. In the abstract we report results for the critical outcomes only. We identified 13 ongoing studies. Four studies are awaiting assessment. SYNTHESIS OF RESULTS: Multisensory stimulation compared to standard care No studies reported on these major neurodevelopmental disabilities, assessed at 18 to 24 months' corrected age (CA): developmental delay, intellectual impairment, blindness, or sensorineural deafness. One study reported on rates of CP at 12 months of age. The evidence is very uncertain about the effect of multisensory stimulation on CP (RR 0.67, 95% CI 0.28 to 1.58; I² not applicable; 1 study, 18 participants; very low-certainty evidence). The evidence suggests that multisensory stimulation may result in little to no difference in death during initial hospitalization (RR 0.97, 95% CI 0.54 to 1.73; I² not applicable; 1 study, 395 participants; low-certainty evidence). Multisensory stimulation may increase total weight gain prior to discharge (MD 72.67, 95% CI 68.23 to 77.12; I² = 0%; 3 studies, 474 participants; low-certainty evidence). Multisensory stimulation compared to single-sense (tactile) stimulation No studies reported on major neurodevelopmental disability, assessed at 18 to 24 months' CA, or death during initial hospitalization. The evidence is very uncertain about the effect of multisensory stimulation compared to tactile stimulation on weight gain during the intervention (MD -175.00, 95% CI -376.60 to 26.60; I² not applicable; 1 study, 20 participants; very low-certainty evidence). The certainty of the evidence was low to very low across outcomes, primarily due to risk of bias, imprecision from small sample sizes and wide CIs, and in some cases, inconsistency. The evidence base was also limited by the lack of reporting of relevant outcomes and reliance on surrogate outcomes or shorter follow-up periods. AUTHORS' CONCLUSIONS: The available evidence on multisensory stimulation in preterm infants is limited and of low to very low certainty. No included studies reported on major neurodevelopmental disabilities at 18 to 24 months' CA, which represented a critical outcome for this review. Evidence regarding the effect of multisensory stimulation on CP is very uncertain, as it is based on a single small study reporting a surrogate outcome at 12 months. Multisensory stimulation may result in little to no difference in mortality during the initial hospitalization. It may increase total weight gain prior to discharge. However, the clinical significance of this finding is uncertain, particularly given the low certainty of the evidence and the multifactorial nature of growth in preterm infants. The evidence is very uncertain about the effect of multisensory stimulation compared to single-sense (tactile) stimulation on weight gain during the intervention. The only included study did not report major neurodevelopmental disabilities at 18 to 24 months' CA, mortality during the initial hospitalization, or total weight gain prior to discharge, which represented the critical outcomes for this review. Overall, the current evidence does not allow firm conclusions about the effectiveness of multisensory stimulation in promoting development or preventing morbidity in preterm infants. Future studies on multisensory stimulation should use more rigorous designs, larger samples, and report interventions using the template for intervention description and replication (TIDieR) checklist to ensure transparency. They should also report essential outcomes, such as neonatal death, major neurodevelopmental disabilities, length of hospital and NICU stay, time to full oral feeding, duration of respiratory support, and weight gain, to better assess the long‑term effects of multisensory stimulation in preterm infants. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD016073.

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PubMed2026

Quality of life and gender identity in females with congenital adrenal hyperplasia after genital restoration surgery: A single-center experience.

BACKGROUND: Legislation restricting surgical interventions in children with differences of sex development (DSD) has intensified debate about female genital restoration surgery (FGRS) in patients with congenital adrenal hyperplasia (CAH). Long-term patient-reported outcomes are needed regarding the optimal timing of surgery. OBJECTIVE: We aimed to assess health-related quality of life (HRQoL), gender identity, and family satisfaction regarding surgical timing and outcome in females with CAH following genital restoration surgery. STUDY DESIGN: Cross-sectional survey of CAH patients who underwent surgery between January 2007 to December 2016 at our institution. Validated instruments (KINDL questionnaire for HRQoL, Utrecht Gender Dysphoria Scale, UGDS) and structured telephone interviews were employed. RESULTS: Data on HRQoL was available for 25 patients (self- and/or parent-reported) out of 56 eligible patients (45% response rate). Median age at first surgery was 6 months (range: 3-137 months). Patients' age at time of participation ranged from 2 to 28 years. All had 21-hydroxylase deficiency (92% salt-wasting form) with Prader grades ranging from II-V. Wound dehiscence requiring secondary suturing occurred in 15% of patients with primary surgery at our center, while only one (4%) patient developed vaginal stenosis after early primary vaginoplasty. Two additional patients (8%) with prior outside surgery required vaginal revision after FGRS at age 12. HRQoL scores were comparable to healthy reference populations across most age groups. Children aged 3-6 and adolescents and young adults showed no significant difference from reference values, while children aged 7-13 showed a slight elevation. None of five patients ≥14 years demonstrated gender dysphoria (all UGDS scores <40, threshold ≥40). 14 patients and families were also interviewed by telephone. All preferred early surgical timing. No family expressed regret about the decision or preferred delayed surgery. DISCUSSION: This study provides validated intermediate-term patient- and parent-reported outcomes after FGRS in CAH. Key limitations include the small sample size, single-center design, and young age of most patients. Selection bias may exist, though participating families included those who underwent revision surgery. The absence of a non-operated comparison group reflects current clinical reality, as nearly all CAH patients with urogenital sinus underwent surgical correction. CONCLUSIONS: Females with CAH reported normal HRQoL and a comfortable female gender identity after early FGRS. The patients and their families expressed a preference for early surgery. However, there is need for longer-term follow-up to assess sexual function and reproductive outcomes as well comparison of outcomes with a non-operated group.

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