Citations

Dual-energy X-ray absorptiometry (DEXA) is reported to be inferior to computed tomography (CT) to measure changes in appendicular soft tissue composition. We compared CT- and DEXA-measured thigh muscle and fat mass to evaluate the random and systematic discrepancies between these two methods. Thigh skeletal muscle area (single-slice CT) was suboptimally ( r2= 0.74, P < 0.0001) related to DEXA-measured thigh fat-free mass (FFM). In contrast, thigh muscle and adipose tissue volumes (multislice CT) were highly related to DEXA-measured thigh FFM and fat (both r2= 0.96, P < 0.0001). DEXA-measured leg fat was significantly less than multislice-CT-measured leg adipose tissue volume, whereas multislice-CT-measured leg muscle mass was less ( P < 0.0001) than DEXA-measured leg FFM. The systematic discrepancies between the two approaches were consistent with the 10–15% nonfat components of adipose tissue. In conclusion, CT and DEXA measures of appendicular soft tissue are highly related. Systematic differences between DEXA and CT likely relate to the underlying principles of the techniques.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is required for normal glucose-stimulated insulin release from pancreatic beta-cells. Biochemical characterization techniques have demonstrated the presence of the 1,25(OH)2D3 receptor (VDR) in homogenates of whole pancreas. Autoradiographic studies using radiolabeled 1,25(OH)2D3 suggest that the VDR is localized to beta-cells but are inconclusive. We used immunohistochemical techniques to stain serial sections from both human and rat pancreas with polyclonal antibodies to human VDR, chick calbindin D28k, insulin, glucagon, and somatostatin. VDR was present in the islet cells and also at low levels in acinar cells of the human and rat pancreas. Calbindin D28k was distributed in a manner similar to the VDR in pancreatic islets but was not present in acini. These results show for the first time that VDR and calbindin D28k are present in human pancreatic tissue. VDR and calbindin D28k are focally distributed throughout pancreatic islet cell types in humans and rats; VDR is also present in the exocrine pancreas. These findings suggest that 1,25(OH)2D3 may influence both endocrine and exocrine pancreatic function.

Purpose To (1) assess clinical outcomes of revision multiligament knee injury (MLKI) reconstruction at a minimum of 2 years' follow‐up and (2) present a standardized treatment algorithm used in treating revision MLKI patients. Methods A retrospective review of our institution's MLKI database was performed to identify all patients who underwent revision MLKI reconstructions (≥2 ligaments reconstructed) after implementation of a standardized treatment algorithm in 2000 and had a minimum of 2 years' follow‐up. Patient demographic information, injury description (mechanism of injury, neurovascular status, knee dislocation grade, associated chondral or meniscal injury), surgical technique (repair vs reconstruction, staged vs nonstaged, concomitant procedures), mechanism of failure, knee stability, and range of motion, as well as International Knee Documentation Committee and Lysholm scores, were obtained. Results We assessed 23 patients (8 female and 15 male patients), with an average age of 26.7 ± 11.5 years at primary surgery and 30.8 ± 11.0 years at revision surgery. The mean follow‐up period was 7.5 ± 5.3 years. Of the 23 patients, 10 (43.4%) underwent staged revision procedures: isolated bone grafting in 3, osteotomy in 4, hardware removal with osteochondral allograft in 1, hardware removal with bone grafting in 1, and meniscus repair for a locked knee in 1. The average International Knee Documentation Committee and Lysholm scores were 74.5 ± 22.3 and 79.4 ± 20.2, respectively. High‐energy injury and increasing age at revision surgery were the only risk factors found to be associated with significantly worse outcomes ( P < .05). Conclusions Patients with recurrent instability after MLKI reconstruction present with many concomitant pathologies, including limb malalignment, bone tunnel widening, retained hardware, meniscal incompetence, and cartilage defects. Revision MLKI reconstruction can provide these patients with modest functional outcomes when a standardized treatment algorithm is used focusing on identification and treatment of the concomitant pathology, often in a staged manner. Level of Evidence Level IV, case series.

ABT-263 blocks BCL-X L to induce apoptosis in human dermal fibroblasts from patients with scleroderma and in myofibroblasts in mice, reversing dermal fibrosis.

Abstract Aims The SERVE-HF trial investigated the impact of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with systolic heart failure. A preplanned substudy was conducted to provide insight into mechanistic changes underlying the observed effects of ASV, including assessment of changes in left ventricular function, ventricular remodelling, and cardiac, renal and inflammatory biomarkers. Methods and results In a subset of the 1325 randomised patients, echocardiography, cardiac magnetic resonance imaging (cMRI) and biomarker analysis were performed at baseline, and 3 and 12 months. In secondary analyses, data for patients with baseline and 12-month values were evaluated; 312 patients participated in the substudy. The primary endpoint, change in echocardiographically determined left ventricular ejection fraction from baseline to 12 months, did not differ significantly between the ASV and the control groups. There were also no significant between-group differences for changes in left ventricular dimensions, wall thickness, diastolic function or right ventricular dimensions and ejection fraction (echocardiography), and on cMRI (in small patient numbers). Plasma N-terminal pro B-type natriuretic peptide concentration decreased in both groups, and values were similar at 12 months. There were no significant between-group differences in changes in cardiac, renal and systemic inflammation biomarkers. Conclusion In patients with systolic heart failure and CSA, addition of ASV to guideline-based medical management had no statistically significant effect on cardiac structure and function, or on cardiac biomarkers, renal function and systemic inflammation over 12 months. The increased cardiovascular mortality reported in SERVE-HF may not be related to adverse remodelling or worsening heart failure.

Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.

Purpose To perform a systematic review to determine if there is (1) an association between decreased hip internal rotation and anterior cruciate ligament (ACL) tear rates; (2) an association between radiographic femoroacetabular impingement (FAI) and ACL tear rates; and (3) biomechanical evidence demonstrating increased strain in the ACL of patients with decreased hip internal rotation. Methods A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Studies investigating relationships between hip motion, hip radiographs, and ACL tear were sought. Studies with Levels of evidence I‐IV were eligible for inclusion. Study methodology/evidence were evaluated using Methodological Index for Non‐Randomized Studies (MINORS), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results Eleven studies were analyzed (2 cadaveric in vitro models, 8 clinical studies measuring hip internal rotation (2 concurrently assessing radiographic FAI), and 1 clinical study assessing radiographic FAI alone). Mean MINORS, STROBE, and GRADE for the studies was 82.4%, 20.9 out of 22, and “low,” respectively. A total of 959 subjects (84.8% male; mean age 23.6 ± 3.8 years) were analyzed. Overall, 378 subjects sustained 427 ACL tears (399 primary ACL ruptures, 28 reruptures). Six of 8 clinical studies identified a significant association between limited rotation (internal rotation [IR; loss greater than 10°‐20°], external rotation [ER], or combined IR + ER [loss greater than 20°]) and ACL tears. Two studies found an association between ACL ruptures and radiographic cam/pincer impingement. Two cadaveric models found a significant association between ACL strain and limited hip internal rotation. Conclusions This systematic review identified a significant association between ACL tear and both limited hip rotation and radiographic FAI. Level of Evidence Level IV, systematic review of Levels II‐IV studies.

Key Clinical Message This case report describes an individual with brain calcifications, cognitive decline, motor dysfunction, and hypocalcaemia. Exome sequencing revealed a previously reported variant in the CASR gene and a variant of uncertain significance in PDGFRB . The clinical phenotype is likely explained by the CASR variant, but we discuss how the PDGFRB variant could also participate in the phenotype.