Surgical Versus Nonsurgical Management of Humeral Shaft Fractures:a systematic review and meta-analysis of randomised trials

Introduction: The aim was to compare operative and non-operative management for adults with humeral shaft fractures, in terms of patient-reported upper limb function, health-related quality of life (HRQoL), radiographic outcomes and complications.Methods: MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), ClinicalTrials.gov, ISRCTN (International Clinical Trials Registry) and OpenGrey (Repository for Grey Literature in Europe) were searched in September 2021. All published prospective randomised trials comparing operative and non-operative management of humeral shaft fractures in adults were included. Of 715 studies identified, five were included in the systematic review and four in the meta-analysis. Data were extracted by two independent reviewers according to the PRISMA statement. Methodological quality was assessed using the revised Cochrane risk-of-bias tool for randomised trials. Pooled data were analysed using a random-effects model.Results: The meta-analysis comprised 292 patients (mean age 41yrs [18-83], 67% male). Surgery was associated with superior DASH and Constant-Murley scores at six months (mean DASH difference 7.6, p=0.01; mean Constant-Murley difference 8.0, p=0.003) but there was no difference at one year (DASH, p=0.30; Constant-Murley, p=0.33). No differences in HRQoL or pain scores were found. Surgery was associated with a lower risk of nonunion (0.7% versus 15.7%; odds ratio [OR] 0.13, p=0.004). The number-needed-to-treat (NNT) with surgery to avoid one nonunion was 7. Surgery was associated with a higher risk of transient radial nerve palsy (17.4% versus 0.7%; OR 8.23, p=0.01) but not infection (OR 3.57, p=0.13). Surgery was also associated with a lower risk of re-intervention (1.4% versus 19.3%; OR 0.14, p=0.04).Conclusions: Surgery may confer an early functional advantage to adults with humeral shaft fractures, but this is not sustained beyond six months. The lower risk of nonunion should be balanced against the higher risk of transient radial nerve palsy.<br/

Operative vs Nonoperative Management of Unstable Medial Malleolus Fractures:A Randomized Clinical Trial

IMPORTANCE: Unstable ankle fractures are routinely managed operatively. However, because of soft tissue and implant-related complications, recent literature has reported on the nonoperative management of well-reduced medial malleolus fractures after fibular stabilization, but with limited evidence supporting the routine application.OBJECTIVE: To assess the superiority of internal fixation of well-reduced (displacement ≤2 mm) medial malleolus fractures compared with nonfixation after fibular stabilization.DESIGN, SETTING, AND PARTICIPANTS: This superiority, pragmatic, parallel, prospective randomized clinical trial was conducted from October 1, 2017, to August 31, 2021. A total of 154 adult participants (≥16 years) with a closed, unstable bimalleolar or trimalleolar ankle fracture requiring surgery at an academic major trauma center in the UK were assessed. Exclusion criteria included injuries with no medial-sided fracture, open fractures, neurovascular injury, and the inability to comply with follow-up. Data analysis was performed in July 2022 and confirmed in September 2023.INTERVENTIONS: Once the lateral (and where appropriate, posterior) malleolus had been fixed and satisfactory intraoperative reduction of the medial malleolus fracture was confirmed by the operating surgeon, participants were randomly allocated to fixation (n = 78) or nonfixation (n = 76) of the medial malleolus.MAIN OUTCOME AND MEASURE: Olerud-Molander Ankle Score (OMAS) 1 year after randomization (range, 0-100 points, with 0 indicating worst possible outcome and 100 indicating best possible outcome).RESULTS: Among 154 randomized participants (mean [SD] age, 56.5 [16.7] years; 119 [77%] female), 144 (94%) completed the trial. At 1 year, the median OMAS was 80.0 (IQR, 60.0-90.0) in the fixation group compared with 72.5 (IQR, 55.0-90.0) in the nonfixation group (P = .17). Complication rates were comparable. Significantly more patients in the nonfixation group developed a radiographic nonunion (20% vs 0%; P &lt; .001), with 8 of 13 clinically asymptomatic; 1 patient required surgical reintervention for this. Fracture type and reduction quality appeared to influence fracture union and patient outcome.CONCLUSIONS AND RELEVANCE: In this randomized clinical trial comparing internal fixation of well-reduced medial malleolus fractures with nonfixation, after fibular stabilization, fixation was not superior according to the primary outcome. However, 1 in 5 patients developed a radiographic nonunion after nonfixation, and although the reintervention rate to manage this was low, the future implications are unknown. These results support selective nonfixation of anatomically reduced medial malleolar fractures after fibular stabilization.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03362229.</p

QuickDASH and PRWE Are Not Optimal Patient-Reported Outcome Measures After Distal Radial Fracture Due to Ceiling Effect:Potential Implications for Future Research

BACKGROUND: The aim of this study was to determine the floor and ceiling effects for both the QuickDASH (shortened version of the Disabilities of the Arm, Shoulder and Hand [DASH] questionnaire) and the PRWE (Patient-Rated Wrist Evaluation) following a distal radial fracture (DRF). Secondary aims were to determine the degree to which patients with a floor or ceiling effect felt that their wrist was "normal" according to the Normal Wrist Score (NWS) and if there were patient factors associated with achieving a floor or ceiling effect.METHODS: A retrospective cohort study of patients in whom a DRF was managed at the study center during a single year was undertaken. Outcome measures included the QuickDASH, PRWE, EuroQol-5 Dimensions-3 Levels (EQ-5D-3L), and NWS.RESULTS: There were 526 patients with a mean age of 65 years (range, 20 to 95 years), and 421 (80%) were female. Most patients were managed nonsurgically (73%, n = 385). The mean follow-up was 4.8 years (range, 4.3 to 5.5 years). A ceiling effect was observed for both the QuickDASH (22.3% of patients with the best possible score) and the PRWE (28.5%). When defined as a score that differed from the best available score by less than the minimum clinically important difference (MCID) for the scoring system, the ceiling effect increased to 62.8% for the QuickDASH and 60% for the PRWE. Patients who had a ceiling score on the QuickDASH and the PWRE had a median NWS of 96 and 98, respectively, and those who had a score within 1 MCID of the ceiling score reported a median NWS of 91 and 92, respectively. On logistic regression analysis, a dominant-hand injury and better health-related quality of life were the factors associated with both QuickDASH and PRWE ceiling scores (all p &lt; 0.05).CONCLUSIONS: The QuickDASH and PRWE demonstrate ceiling effects when used to assess the outcome of DRF management. Some patients achieving ceiling scores did not consider their wrist to be "normal." Future research on patient-reported outcome assessment tools for DRFs should aim to limit the ceiling effect, especially for individuals or groups that are more likely to achieve a ceiling score.LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.</p

Lck is a relevant target in chronic lymphocytic leukaemia cells whose expression variance is unrelated to disease outcome.

Pathogenesis of chronic lymphocytic leukaemia (CLL) is contingent upon antigen receptor (BCR) expressed by malignant cells of this disease. Studies on somatic hypermutation of the antigen binding region, receptor expression levels and signal capacity have all linked BCR on CLL cells to disease prognosis. Our previous work showed that the src-family kinase Lck is a targetable mediator of BCR signalling in CLL cells, and that variance in Lck expression associated with ability of BCR to induce signal upon engagement. This latter finding makes Lck similar to ZAP70, another T-cell kinase whose aberrant expression in CLL cells also associates with BCR signalling capacity, but also different because ZAP70 is not easily pharmacologically targetable. Here we describe a robust method of measuring Lck expression in CLL cells using flow cytometry. However, unlike ZAP70 whose expression in CLL cells predicts prognosis, we find Lck expression and disease outcome in CLL are unrelated despite observations that its inhibition produces effects that biologically resemble the egress phenotype taken on by CLL cells treated with idelalisib. Taken together, our findings provide insight into the pathobiology of CLL to suggest a more complex relationship between expression of molecules within the BCR signalling pathway and disease outcome