Purpose To determine whether early radiographic trajectory data can predict the timing of stability in conservatively managed distal radius fractures (DRFs) and to identify which clinical and radiographic features most influence stabilization timing. Methods This retrospective cohort study analyzed data from 1,585 adult patients with conservatively managed DRFs collected from a single-institution fracture registry (2020−2024). Radiographic stability was classified according to predefined parameters of radial height, volar tilt, radial inclination, and ulnar variance at weekly follow-ups. An explainable machine learning model incorporating demographics, fracture characteristics, comorbidities, and early radiographic changes was developed to predict stability at various weeks. Predictive performance was evaluated using area under the receiver operating characteristic curve, calibration plots, Brier scores, decision curve analysis, and SHapley Additive exPlanations. Results Among 1,585 patients, 40% of fractures achieved radiographic stability by week 3. Baseline radiographic measurements did not differ across stability groups, but first-week displacement differed significantly across all parameters. A combined model incorporating early radiographic changes substantially outperformed a baseline-only model. Decision curve analysis demonstrated a superior net benefit compared with routine imaging strategies. SHapley Additive exPlanations analysis identified early changes in volar tilt as the single most influential predictor, followed by changes in radial inclination, patient age, and dorsal comminution. Conclusions Early radiographic trajectory, particularly first-week changes in volar tilt, predicts the timing of stability far more accurately than baseline features alone. A substantial proportion of conservatively managed DRFs stabilize earlier than conventional protocols assume, suggesting that a trajectory-guided approach could safely reduce late follow-up imaging and immobilization duration in selected patients. Prospective validation is needed before clinical implementation. Clinical relevance First-week radiographic displacement, particularly changes in volar tilt, may be more informative than traditional baseline instability criteria for guiding follow-up frequency and immobilization duration in conservatively managed DRFs. Level of evidence Prognostic/III.
Identification and development of physiologically relevant in vitro models are critical for the advancement of creating platforms suitable for tissue engineering, drug testing, and mechanistic research on pathologies. This study focuses on skeletal muscle pathologies and establishes a topography-integrated screening platform combining 96-well plates with an aligned surface topography with pattern dimensions ranging from 0 to 23.3 & micro;m in wavelength and 0 to 3.15 & micro;m in height. The system enables simultaneous analysis of myoblast responses on 12 different patterns while preventing cross-talk between cells when they are grown on gradient surfaces for screening. Mechanistic analysis demonstrates topography-dependent modulation of focal adhesion distribution and cytoskeletal reorganization. Surface topography directs myotube alignment through contact guidance, achieving orientation control in optimal configurations and wrinkle-induced polarization mimics native tissue architecture more effectively than planar substrates. Micropattern dimensions differentially regulate cellular morphogenesis, with micro-size topography features producing minimal myotubes (reduced area, quantity, and length) versus enhanced differentiation at larger topography dimensions. This model enables rapid generation of morphologically distinct myotube phenotypes through dimensional tuning, providing a physio-mimetic solution for objectively evaluating muscle therapeutics and is expandable toward other cell culture approaches to identify optimum cell stimulation for specialized culture.
Tibial plateau fractures (TPFs) remain challenging injuries due to their complex three-dimensional morphology, frequent posterior column involvement, and high incidence of associated soft-tissue lesions. Flexion-type fractures represent a distinct and often under recognized entity that is inadequately addressed using traditional classification systems. Flexion-valgus and flexion-varus mechanisms generate fundamentally different fracture configurations and soft-tissue injury profiles, with important implications for surgical management and prognosis. This narrative review provides a practical, literature- and experience-based overview of the distinguishing features of flexion-valgus and flexion-varus tibial plateau fractures, focusing on fracture morphology, associated ligamentous and meniscal injuries, and key treatment principles. Flexion-valgus injuries predominantly involve the posterolateral tibial plateau, commonly presenting as split-depression or rim impaction fractures, and are frequently associated with anterior cruciate ligament (ACL) and lateral meniscal pathology. In contrast, flexion-varus injuries typically result in posteromedial shear fractures with metaphyseal comminution, often extending into the posterolateral central segment, demonstrating significantly higher rates of concomitant ligamentous and meniscal injuries, poorer functional outcomes, and increased risk of conversion to total knee arthroplasty (TKA). Accurate recognition of the underlying injury mechanism and fracture morphology, distinguishing flexion-valgus from flexion-varus injuries, is essential to guide preoperative planning, surgical exposure, fixation strategy, and soft-tissue management, with the goal of optimising clinical outcomes.
Background and ObjectivePain management in patients with prostate cancer receiving enzalutamide is challenging owing to its high potential for drug-drug interactions. Morphine is generally preferred because of its favorable metabolic profile, but the effect of enzalutamide on the pharmacokinetics of morphine is unclear. The objective of this study was to assess whether a drug-drug interaction exists between enzalutamide and morphine in patients with prostate cancer.MethodsIn a multicenter two-arm parallel study, 24 men with prostate cancer received morphine with enzalutamide (n = 12) and without enzalutamide (n = 12). Plasma concentrations of morphine and its active metabolite morphine-6-glucuronide were measured. Pharmacokinetic parameters were calculated using a non-compartmental analysis. Geometric mean ratios (GMR) of the area under the plasma concentration-time curves were calculated. No clinically relevant interaction was defined if 90% of the confidence interval (CI) of the GMR of morphine was within the range of 0.5-2.0.ResultsMorphine exposure was similar between both groups, with the 90% CI falling within the range of 0.5-2.0 (GMR 1.01; 90% CI 0.77-1.31). The exposure of morphine-6-glucuronide was increased with enzalutamide (GMR 1.77; 90% CI 1.43-2.17).ConclusionsThe exposure of morphine was unaffected by enzalutamide, while morphine-6-glucuronide exposure was increased. Because of the inconclusive potency of morphine-6-glucuronide and its uncertain ability to cross the blood-brain barrier, the increase is likely of modest clinical significance. Therefore, morphine and enzalutamide can be safely combined when starting at a low dose and titrated based on efficacy and tolerability.Clinical Trial RegistrationNCT05339672.
Lynch syndrome predisposes to multiple cancer types, including urological malignancies. However, no evidence-based recommendations for surveillance of urological malignancies currently exist. In this systematic review, we aim to describe the current evidence regarding surveillance for these cancers. A systematic literature search was conducted using MEDLINE, searching for urological malignancies, Lynch syndrome, and surveillance including the results of the surveillance methods. Sensitivity and specificity were calculated, when possible, preferably for pooled data from each surveillance method. The risk of bias was assessed using the Newcastle–Ottawa Scale. After full text-screening, nine studies published in 2008–2025 met the inclusion criteria, including two on prostate cancer and seven on urothelial cancer. Prostate cancer-antigen (PSA) surveillance led to 38 prostate cancer diagnoses in 865 individuals with Lynch syndrome, with 71
