Brandt, Sallee

Background/Objectives: Diagnostic evaluation and management of nontraumatic osteonecrosis of the femoral head (ONFH) vary substantially. This systematic review was conducted to inform development of the Association Research Circulation Osseous (ARCO) clinical practice guideline for diagnosis and treatment of ARCO stages I to III ONFH. Methods: We searched MEDLINE, EMBASE, Web of Science, SCOPUS, Global Index Medicus, and the Cochrane Library for studies evaluating imaging modalities and treatments for adult ONFH. We assessed risk of bias using the QUADAS-2, the ROB-2, and the ROBINS-I tools; conducted meta-analyses using random-effects regression; and evaluated certainty of evidence using GRADE methodology. Results: Among 36 included studies, 18 addressed diagnostic test accuracy and 18 addressed comparative effectiveness of treatments. Magnetic resonance imaging (MRI) demonstrated the highest pooled sensitivity (0.91; 95% confidence interval (CI), 0.87 to 0.94) and specificity (0.96; 95% CI, 0.87 to 0.99) for ONFH diagnosis. Bone marrow edema and grade 2+ joint effusion on MRI differentiated symptomatic versus asymptomatic disease. Computed tomography and MRI better detected subchondral fractures than plain radiography. Very low-grade evidence suggested lower rates of femoral head collapse with core decompression plus bone marrow concentrate compared with core decompression alone (pooled relative risk [RR], 0.55; 95% CI, 0.36 to 0.83), and with vascularized versus non-vascularized bone grafting (RR, 0.35; 95% CI, 0.14 to 0.84) over a ≤5-year follow-up. Based on three non-comparative case series, osteotomies might have a lower risk of collapse over a 10- to 20-year follow-up, but this needs to be evaluated in future comparative research. Inconsistent outcome reporting hindered treatment outcome pooling. There were no comparative studies that evaluated observation only versus intervention in asymptomatic disease or strategies for monitoring treatment response. Conclusions: Evidence supporting optimal imaging modalities and early joint-preserving interventions remains limited and predominantly observational, underscoring the need for high-quality comparative studies with consistently defined core outcomes to guide clinical decision-making.

Background The optimal timing and type of venous thromboembolism chemoprophylaxis (VTEp) for adults with acute traumatic brain injury (TBI) remains unknown. This systematic review synthesized evidence on the timing and type of VTEp in adults with TBI and highlights evidence gaps. Methods We searched Ovid MEDLINE, Embase, and the Cochrane Library through November 4, 2024 for English language, randomized or non-randomized studies with a comparator that reported VTEp timing or agent in adults with acute TBI, and reported intracranial hemorrhage progression (ICHP), VTE, pulmonary embolism (PE), deep vein thrombosis (DVT), neurosurgical intervention (NSI), adverse events (AEs), length of stay (LOS), function, or mortality. Risk of bias (ROB) was assessed with ROBINS-I as low, moderate, serious, or critical risk in studies that used advanced analytic methods (AAMs) to control selection bias; all other studies were deemed critical risk. We qualitatively synthesized evidence and focused text reporting on studies with AAM. Results From 738 citations, 21 non-randomized studies met criteria (1 moderate, 20 critical ROB): 16 on VTEp timing, 7 on agents. Seven studies used AAM. For VTEp timing (five AAM studies), one study of adults with mostly mild TBI found no significant difference between Early and Late VTEp on ICHP (moderate ROB); no timing studies with AAM reported ICHP for adults with moderate or severe TBI. Findings were mixed for VTE timing on NSI and PE. Early VTEp was associated with fewer DVTs. There was no difference in mortality or serious AEs by VTEp timing. For VTEp agents, three studies with AAM found no significant difference between low molecular weight heparin (LMWH) and unfractionated heparin (UH) on ICHP, PE, DVT, and serious or overall AEs. Results were mixed for LMWH versus UH effects on NSI after VTEp, VTE, LOS and mortality. TBI severity labeling varied across studies and within measures, reducing comparability. Conclusions Clinical evidence on the timing and type of VTEp for adults with acute TBI is of insufficient quality for clinical decision-making. Prospective research designs, standardization of TBI severity labeling, and improved reporting of interventions and outcomes would advance the field. PROSPERO registration number CRD42023421534 Level of evidence Systematic Review, Level IV