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PubMed2026

Pharmacological therapies for the prevention of fractures in men.

RATIONALE: Pharmacological therapies for fracture prevention usually target osteoporosis, a skeletal disorder characterised by compromised bone mass or quality (or both). As most participants in osteoporosis trials are women, a review of pharmacological therapies for fracture prevention in men was warranted. OBJECTIVES: To determine the benefits and harms of bisphosphonates, parathyroid (PTH) or parathyroid-related protein (PTHrP) analogues, denosumab, and romosozumab therapy for the prevention of fractures in men. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and WHO ICTRP) until 14 October 2025, with no restrictions on date or language of publication. ELIGIBILITY CRITERIA: We included randomised controlled trials that compared bisphosphonates, PTH or PTHrP analogues, denosumab, or romosozumab (alone or with calcium or vitamin D, or both) with placebo, other drugs, or non-pharmacological therapies in men aged 50 years or older. Our primary comparison was bisphosphonates versus placebo. OUTCOMES: Critical outcomes were incidence of hip fractures, symptomatic vertebral fractures, other (not hip or vertebral) fractures, disability, participants with adverse events, study withdrawals due to adverse events, and participants with serious adverse events. Our primary time point was the final time point reported in the trials. RISK OF BIAS: We used Cochrane's RoB 2 tool to assess risk of bias. SYNTHESIS METHODS: We used a random-effects model for meta-analysis employing the Mantel-Haenszel approach, and the DerSimonian and Laird method to estimate between-trial variance. We assessed the certainty of evidence using GRADE. INCLUDED STUDIES: Seventeen trials (4132 participants) met our inclusion criteria. The average age of participants ranged from 52 to 73 years. Twelve trials used a placebo comparator versus bisphosphonate (7 trials, 2548 participants), PTH or PTHrP analogues (4 trials, 569 participants), denosumab (1 trial, 240 participants), and romosozumab (1 trial, 244 participants). For the other planned comparisons, a bisphosphonate was compared to vitamin D/vitamin D analogues (2 trials, 434 participants), to calcitonin (1 trial, 32 participants), to PTH or PTHrP analogues (1 trial, 19 participants), or to another bisphosphonate (1 trial, 301 participants), and one trial compared a bisphosphonate plus calcium to calcium tablets alone (46 participants). SYNTHESIS OF RESULTS: Placebo-controlled trials were largely susceptible to bias in selection of the reported result (83%), while most trials without a placebo control were also susceptible to bias arising from the randomisation process (100%) and in measurement of the outcome (80%). We are very uncertain about the effect of bisphosphonates on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures compared to placebo at the final follow-up (up to two years). We downgraded the certainty of evidence once for risk of bias, twice for imprecision (very low event rates), and once for suspected publication bias. The certainty of evidence for incidence of other fractures was further downgraded for indirectness, as it was unclear if hip fractures were also included in the outcome. At up to two years, 2/875 participants (2 per 1000) in the bisphosphonate group reported hip fractures compared with 2/760 (3 per 1000) in the placebo group (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.06 to 8.51; I² = 36%; 4 trials, 1635 participants); 5/1021 (4/1000) participants in the bisphosphonate group had a symptomatic vertebral fracture compared to 7/855 (8/1000) participants in the placebo group (RR 0.49, 95% CI 0.14 to 1.74; I² = 0%; 5 trials, 1876 participants); 25/1130 participants (16/1000) in the bisphosphonate group reported other (non-hip non-vertebral) fractures compared to 19/913 participants (21/1000) in the placebo group (RR 0.78, 95% CI 0.42 to 1.45; I² = 0%; 6 trials, 2043 participants). Bisphosphonates probably do not increase the risk of adverse events: 1024/1374 participants (746/1000) receiving bisphosphonates reported adverse events compared to 826/1174 participants (704/1000) receiving placebo (RR 1.06, 95% CI 0.93 to 1.19; I² = 75%; 7 trials, 2548 participants; moderate-certainty evidence) or serious adverse events: 329/1329 participants (272/1000) receiving bisphosphonate reported serious adverse events compared to 323/1128 participants (286/1000) receiving placebo (RR 0.95, 95% CI 0.84 to 1.08; I² = 0%; 6 trials, 2457 participants; moderate-certainty evidence). We downgraded the certainty of evidence once due to potential bias for adverse events and serious adverse events. We are very uncertain if bisphosphonates result in more withdrawals due to adverse events: 41/1374 participants (25/1000) in the bisphosphonate group withdrew due to adverse events compared with 43/1174 participants (37/1000) in the placebo group (RR 0.68, 95% CI 0.39 to 1.18; I² = 37%; 7 trials, 2548 participants; very low-certainty evidence). We downgraded the certainty of evidence once for risk of bias, once for indirectness, and once for imprecision. No trial reported disability. We are very uncertain about the effects of PTH or PTHrP analogues, denosumab, or romosozumab compared to placebo on fracture outcomes. We are very uncertain about the effects of PTH/PTHrP analogues on total adverse events, withdrawals due to adverse events, and serious adverse events. Denosumab may not increase the risk of adverse events or serious adverse events compared to placebo, while the evidence for withdrawals due to adverse events is very uncertain. Romosozumab probably does not increase the risk of adverse events and may not increase the risk of serious adverse events or result in more withdrawals due to adverse events. AUTHORS' CONCLUSIONS: We are very uncertain about the effects of bisphosphonates compared to placebo on the incidence of hip fractures, symptomatic vertebral fractures, or other (non-hip non-vertebral) fractures in men at up to two years of use. Bisphosphonates probably do not increase the risk of adverse events or serious adverse events, and we are very uncertain if they result in more withdrawals due to adverse events. We downgraded the certainty of evidence for indirectness, imprecision (low event rate), and serious risk of bias in selection of the reported result, as it was unclear if all studies fully reported every fracture. We found similar results for PTH or PTHrP analogues, denosumab, or romosozumab versus placebo. Larger, longer placebo-controlled studies are needed to determine whether pharmacological therapies are beneficial for reducing fractures in men. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2021): https://doi.org/10.1002/14651858.CD014707.

Humans↗

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

CT-Derived pelvic morphometry for preoperative risk assessment of recurrent unilateral inguinal hernia.

BACKGROUND: Recurrent inguinal hernia remains a significant challenge in abdominal wall surgery despite advances in mesh-based repair techniques and minimally invasive approaches. Although pelvic skeletal morphology has been implicated in inguinal hernia development, its association with recurrent disease remains incompletely understood. This study aimed to evaluate computed tomography (CT)-derived pelvic morphometric parameters and investigate their potential value in preoperative recurrence risk assessment. METHODS: This retrospective study included 251 male patients with preoperative abdominal CT examinations and complete clinical records who underwent elective inguinal hernia repair at a tertiary referral center. After applying the predefined eligibility criteria, 188 patients with unilateral inguinal hernias constituted the primary study cohort, including 162 primary and 26 recurrent unilateral hernias. The Radoievitch angle and Ami's line were measured independently by two blinded radiology residents using a standardized CT-based pelvic morphometric measurement protocol, and the mean values were used for analysis. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the association between pelvic morphometric parameters and recurrent inguinal hernia. RESULTS: Patients with recurrent unilateral inguinal hernias demonstrated significantly greater affected-side Ami's line measurements (8.27 ± 0.63 vs. 7.90 ± 0.71 cm, p = 0.014) and larger Radoievitch angles (40.68 ± 4.02° vs. 38.80 ± 3.68°, p = 0.018) than patients with primary unilateral hernias. Both the Radoievitch angle (OR 1.14, 95% CI 1.01-1.28, p = 0.033) and Ami's line (OR 2.26, 95% CI 1.14-4.49, p = 0.020) remained independently associated with recurrent inguinal hernia after adjustment for age and body mass index. ROC analysis demonstrated modest discriminatory performance (AUC 0.634 for the Radoievitch angle and 0.633 for Ami's line), while the multivariable model incorporating age, body mass index, and Ami's line showed slightly improved discrimination (AUC 0.655). CONCLUSION: CT-derived pelvic morphometric parameters were independently associated with recurrent unilateral inguinal hernia. Although their individual discriminatory performance was modest, standardized CT-based pelvimetry may serve as an objective adjunctive tool for individualized preoperative recurrence risk assessment in patients who already undergo CT imaging for unrelated clinical indications. Prospective multicenter studies are warranted to validate these findings and determine their clinical applicability.

Humans↗

PubMed2026

Preoperative Proximal Migration of the Radial Head as an Independent Predictor of Suboptimal Outcomes After Osteochondral Autograft Transplantation for Capitellar Osteochondritis Dissecans: A Retrospective Cohort Study.

BACKGROUND: Osteochondral autograft transplantation (OAT) is widely performed for capitellar osteochondritis dissecans (OCD). However, preoperative predictors of suboptimal postoperative outcomes remain unclear. PURPOSE/HYPOTHESIS: The authors aimed to evaluate clinical outcomes after OAT for capitellar OCD and identify preoperative risk factors associated with suboptimal outcomes. They hypothesized that radiographic indicators of disease severity, including preoperative proximal migration of the radial head, lesion size, and lateral wall disruption, would be associated with suboptimal postoperative clinical outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The records of adolescent athletes who underwent OAT for capitellar OCD with a minimum 2-year follow-up were retrospectively reviewed. Clinical outcomes included elbow range of motion (ROM) and Timmerman-Andrews (T-A) score. A suboptimal outcome was defined as a postoperative T-A score <160. Preoperative radiographs were used to measure proximal migration of the radial head relative to the coronoid process, hypertrophy of the radial head, OCD lesion area, and a 5-grade lateral wall disruption classification; measurement reliability was assessed. Multivariate logistic regression analysis was performed to identify independent predictors of a suboptimal outcome, and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for proximal migration. RESULTS: A total of 69 elbows (mean age, 13.6 years; mean follow-up, 48 months) were included. ROM and T-A scores improved significantly after OAT, and all athletes returned to any sports. Of these, 50 elbows (72%) achieved good outcomes, whereas 19 (28%) had suboptimal outcomes. Preoperative proximal migration was significantly greater in the suboptimal outcome group compared with the good outcome group (mean, 2.1 ± 2.3 vs 0.5 ± 1.7 mm; P = .002), as were lesion area (mean, 70 ± 16 vs 58 ± 20 mm2; P = .02) and lateral wall disruption grade (median, 5 vs 3; P = .01). On multivariate analysis, proximal migration of the radial head was the only independent predictor of a suboptimal outcome (adjusted OR, 1.47 per 1-mm increase; 95% CI, 1.03-2.09; P = .033). ROC analysis showed an area under the curve of 0.72 with an optimal cutoff of 2.2 mm (sensitivity, 56%; specificity, 84%). CONCLUSION: OAT resulted in significant clinical improvement in adolescents with capitellar OCD; however, 28% of patients were classified as having suboptimal outcomes. Preoperative proximal migration of the radial head is an independent predictor of a suboptimal postoperative outcome. A value >2.2 mm may indicate advanced radiocapitellar incongruity, a condition in which OAT may be less effective.

Humans↗

PubMed2026

Endocrine Phenotypes and Hormonal Treatment in Meier-Gorlin Syndrome: Report of Two Cases and a Systematic Review of Literature.

BACKGROUND: Meier-Gorlin-syndrome (MGORS) is a rare cause of primordial dwarfism stemming from pathogenic variants in genes involved in DNA replication. The classic clinical triad is microtia, absent patella and short stature. MGORS can mimic endocrine causes of short stature or delayed/atypical pubertal development. METHODS: We report two new cases of MGORS. A systematic literature search of all cases published up to 31 March 2026 was done to identify the cases reporting any endocrinopathy or hormonal therapy, focussing on growth-hormone-deficiency (GHD) and response to growth hormone (GH). RESULTS: We describe a 14 year-old girl, the first MGORS case with CDC6 variant and mammary hypoplasia. Another 11-year old boy with GMNN variant had severe short-stature with GHD and had significant height improvement with GH. Among 29 cases (out of ~150 published), the classic triad was absent in 18.5%. Short stature was almost universal (median height-Z-score -4.4), with 70% exhibiting delayed bone age, 42.9% low IGF-1 and 35.3% GHD. Among 10 GH-treated cases with response data, 6 had reported improvement in height-SDS/growth-velocity. Those with GHD and delayed bone age were more likely to benefit from GH. Among females, all post-pubertal cases had mammary hypoplasia, while 23.5% had clitoromegaly with hypoplastic labia. Among males, cryptorchidism, hypoplastic scrotum and micropenis were common. However, gonadal hormones and gonadotrophins were normal. Data on the effect of estrogen on hypoplastic mammary glands or labia was variable. CONCLUSION: MGORS should be kept in mind as a differential of multiple endocrinopathies. Cases of MGORS should undergo screening for GHD. Available data, mostly from case-reports or small series, suggest that response to GH has been reported in some individuals, particularly where GHD or delayed bone age was present, but evidence remains very limited.

Humans↗

PubMed2026

GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood. OBJECTIVE: This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid® platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082). RESULTS: From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I2 88%, p-value for heterogeneity <0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness. CONCLUSIONS: This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. Further studies in this field, including those looking at muscle function, strength or performance and using multivariate models considering confounding are needed to better reinforce the models and final findings.

Journal Article↗

PubMed2026

Arthroscopic Correction of Pincer-Type FAI in the Presence of Acetabular Retroversion Results in Excellent Patient-Reported Outcomes With Low Risk of Reoperation or Conversion to Arthroplasty at Minimum 5 Years.

BACKGROUND: Acetabular retroversion is a distinct morphologic variation that may result in pincer-type femoroacetabular impingement (FAI). The role of arthroscopic management within this cohort is not fully understood. PURPOSE: To assess patient-reported outcome measures (PROMs) and survivorship at 5-year follow-up in a series of cases undergoing arthroscopic correction of pincer-type FAI with acetabular retroversion. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A single-center, prospective hip preservation registry was reviewed for all cases undergoing primary hip arthroscopy for symptomatic FAI between January 2014 and July 2020, with documented radiographic assessment of acetabular retroversion (ie, presence or absence of crossover sign, ischial spine sign, and/or posterior wall sign on a standing, standardized anteroposterior radiograph). Exclusion criteria were Tönnis grade >1, concomitant pathologies (protrusio, Perthes disease, avascular necrosis), excessive pelvic rotation or tilt on radiographs, and/or no crossover sign. Cases were assigned to 1 of 2 groups: moderate-global retroversion group (study group: crossover sign plus either or both ischial spine sign and posterior wall sign) or control group (crossover sign only). Case-control (1:1) fuzzy matching was performed based on age (±2 years), sex, and Tönnis grade (exact). Clinical outcome evaluation included assessment of PROMs (modified Harris Hip Score [mHHS], 36-item Short Form [SF36], University of California-Los Angeles Activity Scale [UCLA], Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), achievement of Patient Acceptable Symptom State (PASS), satisfaction, rates of revision arthroscopy, and arthroplasty-free survivorship, both preoperatively and 5 years postoperatively. Statistical analysis was performed using SPSS v29. RESULTS: A total of 201 cases (120 global, 81 moderate) in the moderate-global retroversion group were matched with 201 control cases. Mean age was 30.6 ± 10.2 years; the sample was 90% male. The rate of revision arthroscopy was similar: n = 11 (6%) in both groups (P = .974). No conversion to periacetabular osteotomy (PAO) occurred in either group. Arthroplasty-free survivorship was 98.2% (retroversion group) and 98.8% (control group) (χ2 = 0.189; df = 1; P = .664). Significant improvements in PROMs from baseline were noted (P < .001 for all, in both groups). In total, 81% (moderate-global retroversion group) and 73% (control group) were satisfied at 5 years (P = .103). No significant difference was seen in PASS achievement rates for any of the PROMs between groups: mHHS, 62.1% versus 65.9% (P = .498); UCLA, 60.0% versus 52.2% (P = .192); SF36, 59.8% versus 64.7% (P = .458); WOMAC, 63.5% versus 67.3% (P = .553), for moderate-global retroversion and control groups, respectively. CONCLUSION: Hip arthroscopy for moderate and global acetabular retroversion resulted in significant improvement in clinical outcomes, with high satisfaction and arthroplasty-free survivorship at 5 years, consistent with a case-control matched group without acetabular retroversion (focal retroversion, pincer FAI). Arthroscopy alone, without anteverting PAO, was an effective surgical management approach for symptomatic FAI in the presence of acetabular retroversion.

Humans↗

PubMed2026

Evaluation of intravenous sedation in dental implant surgeries: A prospective cohort study.

PURPOSE: This study aimed to evaluate the impact of intravenous sedation on patient-centered outcomes during implant and bone augmentation surgeries. METHOD: A prospective observational cohort study included 40 patients undergoing placement of ≥3 implants, with or without bone augmentation. Patients underwent surgery under either intravenous sedation (n = 20) or local anesthesia alone (n = 20), according to routine clinical decision-making and patient preference. The sedation group received intravenous sedation with a multimodal regimen comprising remimazolam, dexmedetomidine, alfentanil, and low-dose esketamine, whereas the control group received local anesthesia only. Patient-reported outcome measures, hemodynamic parameters (SBP, DBP, HR, SpO2), postoperative pain (0-10 scale), and OHRQoL (OHIP-14) were recorded from baseline through 7 days post-surgery. RESULTS: Intravenous sedation was associated with significantly lower intraoperative pain (0.5 [IQR: 0∼2.75] vs. 3.25 ± 2.40, p = 0.003), anxiety (1 [IQR: 0∼2.75] vs. 4 [IQR: 3∼6], p = 0.001), and experienced discomfort (2 [IQR: 1∼3.75] vs. 4.15 ± 2.16, p = 0.016), and shortened perceived treatment duration (2.90 ± 2.34 vs. 5 [IQR: 4∼5], p = 0.020). Early postoperative pain was lower in the sedation group from Days 1-4 (p = 0.003-0.010). Hemodynamic parameters were more stable under sedation, with lower SBP (116.42 ± 13.32 vs. 144.11 ± 17.42 mmHg, p < 0.001), DBP (73.21 ± 10.28 vs. 82.37 ± 11.03 mmHg, p = 0.012), and HR (71.00 [IQR: 62.50∼79.25] vs. 85.00 ± 10.72 bpm, p = 0.021). OHRQoL scores favored the sedation group in swallowing, diet, malaise, and daily activities, particularly during the first three postoperative days (p=0.006-0.040). CONCLUSION: Intravenous sedation may enhance the patient experience during implant and/or bone augmentation procedures by reducing intraoperative pain and anxiety, improving hemodynamic stability, and promoting better early-postoperative recovery and OHRQoL. These findings suggest that intravenous sedation provides a safe and effective alternative for implant dentistry surgery, particularly for anxious or pain-sensitive individuals.

Humans↗

PubMed2026

Orbital involvement in sickle cell disease: A systematic review.

Orbital involvement in sickle cell disease (SCD) is rare but potentially vision-threatening and is often misdiagnosed due to overlap with infectious orbital disease. We conducted a systematic review of case reports and series describing orbital complications in patients with confirmed SCD, following PRISMA and MOOSE guidelines. Across 53 studies, 76 cases were identified. Patients were predominantly male (77.6%), with an average age of 13.2 years. Orbital disease was the initial SCD manifestation in 6.6%. Presentations included periorbital edema in all, proptosis in 64.1%, restricted ocular motility in 56.5%, reduced visual acuity in 28.1%, and bilateral involvement in 38.2%. Laboratory findings commonly included leukocytosis (73%) and raised inflammatory markers (86.7%). Radiologically, orbital subperiosteal hematoma were observed in 70%, combined orbital bone infarction and hematoma in 38.2%, and orbital bone infarction alone in 19.7%. Magnetic resonance imaging is critical for accurate diagnosis. Intracranial hemorrhage was present in 9.2%. Less frequent manifestations included orbital apex syndrome, lacrimal gland disease, and nonspecific soft tissue swelling. Management was primarily conservative (82.9%), and surgery was reserved for vision-threatening or intracranial complications. Complete recovery was achieved in 93.1% of cases. While severe vision-threatening complications are uncommon, early recognition remains critical to optimising outcomes in sickle cell orbitopathy.

Humans↗

PubMed2026

Weight-bearing locomotion mitigates the progression of post-traumatic knee osteoarthritis in male rodents: A systematic review and meta-analysis.

OBJECTIVE: Although knee post-traumatic osteoarthritis (PTOA) has been associated with altered loading, how weight-bearing (WB) activities should be modulated post-injury to preserve knee health remains unknown. This systematic review and meta-analysis examined the effects of WB locomotion on knee PTOA in rodents to provide insight into potential clinical implications. DESIGN: Studies published in PubMed, Cochrane Library, Embase, and CINAHL through 02/2025 and meeting the following criteria were included: 1) rodents with knee PTOA, 2) compared locomotor exercises (treadmill/wheel) to no exercise, 3) outcome measures of PTOA (OARSI/Mankin OA scores, bone quality, osteophyte condition, cartilage quality/morphology). If significant heterogeneity across studies was observed, locomotion speed, time/number of intervention sessions, frequency and duration of intervention, exercise initiation, follow-up time, animal species, PTOA model were analyzed as potential moderator variables that may influence findings. RESULTS: Twenty-two studies met the criteria, resulting in a total of 156 effect sizes (ESs) for meta-analysis (all males). A positive ES denotes less PTOA. Based on the CAMARADES checklist, 5 studies were ranked low risk of bias and 14 studies were ranked moderate risk of bias. Locomotion significantly reduced PTOA severity evaluated using OARSI/Mankin scores (ES=0.927, 95% CI: [0.590, 1.264]) and improved bone quality (ES=0.379, 95% CI: [-0.023, 0.780]) with substantial heterogeneity across studies. Follow-up analyses indicated that greater ESs for reducing OA scores were associated with a shorter duration of each training session, more training sessions, longer intervention duration, and longer follow-up time (all P≤0.004). Greater ESs for improving bone quality were associated with a longer follow-up time and later exercise initiation post-injury (both P≤0.014). Locomotion resulted in small to moderate but non-significant positive effects for isolated measures assessing osteophyte condition (ES=0.379, 95% CI: [-0.023, 0.780]), cartilage quality (ES=0.430, 95% CI: [-0.034, 0.893]), and cartilage morphology (ES=0.464, 95% CI: [-0.006, 0.934]). CONCLUSION: WB locomotion reduced the overall degree of knee PTOA in male rodents. Composite knee OA scores may be more responsive to exercise interventions than isolated cartilage/osteophyte measures. The benefits of locomotion may be more prominent with a longer follow-up time or with exercise protocols consisting of shorter but more individual sessions and longer overall intervention durations.

Animals↗

PubMed2026

A Letter Matters: ADRB2 rs1042713 c.46A Modulates Anti-osteogenic Effect of Epinephrine in Human Mesenchymal Stem Cells.

Osteoporosis (OP) is a systemic bone disease affecting millions worldwide, characterized by long-term asymptomatic development that manifests in low-energy fractures. Due to their high stability, genetic markers represent a promising strategy for early diagnostics. The ADRB2 rs1042713 polymorphism is one such marker, considered as a potential predictor for OP. Although the anti-osteogenic role of the β2-adrenergic receptor is well-established, debate continues on which allele (G or A) of this polymorphism drives bone deterioration. In this study, we examined the influence of the ADRB2 rs1042713 G/G and A/A variants on osteogenic differentiation in patient-derived mesenchymal stem cells (MSCs) under treatment with the endogenous agonist epinephrine. We show that epinephrine (whose levels are often elevated in comorbid conditions) drastically impairs osteogenic differentiation, specifically at the matrix mineralization stage in MSCs A/A. Epinephrine fails to activate the canonical β2-adrenergic receptor pathway and promotes receptor perinuclear and nuclear localization in MSCs A/A. Crucially, metformin, a common anti-diabetic drug, rescues this anti-osteogenic effect. These results open new perspectives for early diagnostics by identifying epinephrine sensitivity as a critical factor, while also suggesting a potential therapeutic strategy to counteract epinephrine detrimental effect in individuals carrying the ADRB2 rs1042713 A-allele.

Humans↗

PubMed2025

Double-Axis Maxillary Skeletal Expander Suggests Higher Expansion Efficiency in Early Activation: A Finite Element Analysis.

INTRODUCTION: Conventional single-axis maxillary skeletal expanders (MSE) have some drawbacks, such as limited control over maxillary expansion and possible asymmetric expansion between the anterior nasal spine (ANS) and posterior nasal spine (PNS). This report introduces a double-axis maxillary skeletal expander (DAMSE) concept to overcome these drawbacks and enhance the efficiency of maxillary skeletal expansion. MATERIALS AND METHODS: Five different DAMSE designs were compared with a conventional single-axis MSE. Finite element analysis was performed to analyse their expansion efficiency, stress magnitude and distribution occurring in a simplified bone model. RESULTS: DAMSE outperformed the single-axis MSE and provided better control over ANS and PNS expansion. During early activation, the highest expansion efficiency (31.7%) was achieved by DAMSE Model V, 13% more efficient than the single-axis MSE. This efficiency was increased to 100.8% by combining the DAMSE Model V with midpalatal suture surgery. However, with the simplified bone model, the current study could not demonstrate that DAMSE can resolve the issue of asymmetric expansion between ANS and PNS. CONCLUSIONS: An appropriately designed DAMSE can be a promising tool for maxillary expansion treatment. DAMSE offers more efficient treatment than the conventional single-axis MSE while maintaining similar levels of patient comfort and invasiveness.

Finite Element Analysis↗

PubMed2026

Assessing the effects of non-invasive transcranial electrical stimulation (tACS and tDCS) on electrophysiological sleep parameters - a systematic review.

Transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), is considered a safe method to modulate cortical activity and endogenous brain oscillations. Given the therapeutic potential of tES across various clinical conditions and the central role of sleep in restoration and memory consolidation, numerous studies have investigated its effects on sleep and sleep-related parameters, yielding inconsistent results. This systematic review provides an up-to-date synthesis of 51 studies assessing the impact of tES on objectively measured electrophysiological sleep outcomes in both healthy individuals and clinical populations. The reviewed studies demonstrate heterogeneous effects, reflecting substantial variability in study designs. Nonetheless, consistent trends emerge, including reduced NREM1 and increases in total sleep time, NREM2, and NREM3 following tES. Moreover, slow-oscillatory tES increased slow-wave power during sleep. Here we show that tES, particularly slow-oscillatory tES, may positively influence sleep architecture and continuity by modulating endogenous brain oscillations. However, due to heterogeneous stimulation protocols, inconsistent findings, the limited number of significant effects and substantial risk of bias the current evidence remains inconclusive. Well-designed, large-scale trials targeting specific sleep outcomes are needed to clarify the therapeutic potential of tES.

Humans↗

PubMed2026

Seed-derived mucilage polysaccharides as biomaterials for in vivo tissue regeneration: A systematic review.

Chronic wounds, bone defects, and cartilage injuries represent persistent clinical challenges requiring biomaterial platforms that actively regulate inflammation, oxidative stress, angiogenesis, and extracellular matrix remodeling. Conventional synthetic dressings often provide limited biological activity in these contexts. Seed-derived mucilages - polysaccharide-rich hydrocolloids obtained from chia (Salvia hispanica), flaxseed (Linum usitatissimum), fenugreek (Trigonella foenum-graecum), psyllium (Plantago ovata), guar (Cyamopsis tetragonoloba), quince (Cydonia oblonga) etc. - have emerged as biocompatible, biodegradable, and chemically versatile platforms for tissue engineering. This systematic review, conducted according to PRISMA 2020 guidelines, synthesized in vivo evidence on seed-derived mucilage-based biomaterials across wound healing, bone repair, cartilage regeneration, and related applications. PubMed, Scopus, and Web of Science Core Collection were searched for original in vivo experimental studies published in English between 2020 and 2026. Eligible studies reported at least one measurable regenerative outcome. Data were extracted independently by two reviewers, and methodological quality was assessed using the SYRCLE Risk of Bias tool. Forty-three studies were included. Hydrogels were the dominant biomaterial format, followed by films, scaffolds, sponges, nanoparticle systems, and bilayer or Janus composites. Included systems generally improved wound closure, re-epithelialization, collagen deposition, angiogenesis, antioxidant defense, and inflammatory regulation. However, most studies used small animals with short follow-up periods, and many incorporated nanoparticles or bioactive agents, limiting attribution of efficacy to the mucilage matrix alone. Risk of bias was predominantly unclear due to insufficient reporting of randomization and blinding. Blank mucilage controls, standardized characterization, long-term biosafety data, and clinically relevant models are essential prerequisites for translational progress.

Humans↗

PubMed2026

Safety and Stability of a Combined C2 Screw Placement Strategy With Vertebral Artery Mobilization.

BACKGROUND: Although C2 pedicle screws are considered the gold standard for atlantoaxial fixation, the optimal fixation strategy for patients with high-riding vertebral arteries (HRVA) or narrow C2 pedicles (NC2P) remains controversial because of the increased risk of vertebral artery injury and the limitations of alternative fixation techniques. OBJECTIVE: To evaluate the safety, stability, and clinical efficacy of an individualized C2 screw fixation strategy incorporating vertebral artery mobilization for complex upper cervical anatomy. METHODS: A retrospective study was conducted in 312 patients who underwent C2 fixation between 2017 and 2025. Patients were categorized according to fusion method, screw laterality, and VA transposition requirement. Bone fusion rates and screw accuracy (Gertzbein-Robbins grading) were compared across groups using χ2, Fisher's exact, and multivariate logistic regression analyses to control confounders. RESULTS: All procedures were successfully completed without permanent neurovascular injury. At 6 months, the fusion rate with an atlantoaxial fusion cage was significantly higher than with interlaminar bone grafting (92.3% vs. 51.0%, p < 0.001). Unilateral C2 pedicle screw fixation combined with a contralateral alternative screw achieved comparable stability to bilateral fixation (p > 0.05). Screw placement accuracy was 100% clinically acceptable in normal anatomy and 60% in cases requiring VA mobilization, with no VA injury or blood flow compromise. CONCLUSION: The proposed multi-strategy C2 screw placement protocol-integrating fusion cage support and VA mobilization-achieves superior fusion, reliable fixation, and high safety, even in anatomically challenging conditions. This approach provides a reproducible and versatile solution for C2 instrumentation in complex craniovertebral junction surgery.

Humans↗

PubMed2026

Orthoplastic management of open calcaneal fractures: A systematic review of flap selection and complications.

BACKGROUND: Open calcaneal fractures are rare, high-energy injuries involving extensive soft-tissue loss and comminuted bone disruption. Successful management depends on coordinated orthoplastic reconstruction to achieve stable fixation and durable coverage. Multiple flap types have been described, yet comparative outcomes remain poorly defined. METHODS: A systematic review was performed in accordance with PRISMA guidelines (PROSPERO: CRD420251138394). MEDLINE, Embase, Cochrane CENTRAL, and Scopus were searched from January 2000 to July 2025. Studies reporting flap-based reconstruction for open calcaneal fractures in adults were included. Extracted data included flap type, fixation method, follow-up duration, and complications such as infection, necrosis, vascular crises, flap loss, and amputation. RESULTS: Thirteen studies comprising 88 major flap reconstructions were analysed. Overall flap survival was 97.7%, with two failures (both muscle/myocutaneous). Fasciocutaneous flaps showed the lowest complication rates (8.3%) with no reported cases of infection, while muscle/myocutaneous flaps demonstrated cases of infection (20%) and accounted for both flap failures and the only reported amputation. Chimeric flaps were increasingly used in recent series (n = 32), achieving reliable survival but higher vascular compromise (6.3%). Osteocutaneous flaps were rare (n = 4) and primarily used for defects with bone loss, showing infection in 50% of cases. Meta-analysis was not possible due to heterogeneity and small sample sizes. CONCLUSIONS: Fasciocutaneous flaps provide reliable, low-complication coverage for clean wounds, while muscle flaps remain valuable for contamination or complex cases with extensive tissue loss. Chimeric, and osteocutaneous flaps show promise, but larger, standardised studies are needed to clarify their roles in hindfoot reconstruction.

Humans↗

PubMed2026

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-κB, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans↗

PubMed2026

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↗