Citations

Introduction Acetabular component position can be an important determinant of joint stability and bearing surface wear after THA. Nonetheless, the incidence of malpositioning is high. Patient obesity, low surgeon volume, and minimally invasive approaches are known risk factors for malposition. As the incidence of obesity continues to increase, it is important to recognise its effect on intraoperative component positioning in THA. Objectives Our goal was to assess the impact of obesity on component position for a high-volume surgeon using a standard postero-lateral approach. Methods A consecutive series of 120 obese (BMI >30, mean BMI 34.4) and 120 non-obese patients (mean BMI 25.4), who had undergone primary THA by a single surgeon, were included in our retrospective study. AP pelvis and cross-table radiographs obtained at the first postoperative visit were analysed using EBRA software to determine inclination and anteversion angles. Optimal position was defined as 30-45° of inclination and 5-25° of anteversion. Results Mean inclination and anteversion were 40.6 (+/-5.4°) and 16.6 (+/-5.5°) respectively, in the obese group and 39° (+/-5.0°) and 16.2° (+/-7.5°) in the non-obese group. In the obese group 89 (74%) patients were within the desired range for both measurements, 31 (26%) were out of range in at least one, compared to 91 (76%) and 29 (24%) in the non-obese group, respectively. The overall incidence of malpositioning was 25% for both groups. Among outliers, mean deviation from the optimal range was ≤3.8° in both groups. Conclusions The risk of component malpositioning in THA may be reduced when surgery is performed by an experienced, high volume surgeon utilising a standard posterolateral approach. In this setting the deleterious effect of obesity may be overcome.

Background: Contemporary data regarding percutaneous closure of atrial septal defect/patent foramen ovale (ASD/PFO) are lacking. We evaluated the current trends in utilization of ASD/PFO closure in adults and investigated the effect of annual hospital volume on in‐hospital outcomes. Methods: We queried the Nationwide Inpatient Sample between the years 2001 and 2010 using the International Classification of Diseases (ICD‐9‐CM) procedure code for percutaneous closure of ASD/PFO with device. Hierarchical mixed effects models were generated to identify the independent multivariate predictors of outcomes. Results: A total of 7,107 percutaneous ASD/PFO closure procedures (weighted n = 34,992) were available for analysis. A 4.7‐fold increase in the utilization of this procedure from 3/million in 2001 to 14/million adults in 2010 in US (P < 0.001) was noted. Overall, percutaneous ASD/PFO closure was associated with 0.5% mortality and 12% in‐hospital complications. The utilization of intracardiac echocardiography (ICE) increased 15 fold (P < 0.001) during the study period. The procedures performed at the high volume hospitals [2nd (14–37 procedures/year) and 3rd (>38 procedures/year) tertile] were associated with significant reduction in complications, length of stay and cost of hospitalization when compared to those performed at lowest volume centers (<13 procedures/year). Majority (70.5%) of the studied hospitals were found to be performing <10 procedures/year hence deviating from the ACC/AHA/SCAI clinical competency guidelines. Conclusions: Low hospital volume is associated with an increased composite (mortality and procedural complications) adverse outcome following ASD/PFO closure. In the interest of patient safety, implementation of the current guidelines for minimum required annual hospital volume to improve clinical outcomes is warranted. © 2014 Wiley Periodicals, Inc.

PurposeProgression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination.MethodsIndividual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti–epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models.ResultsForty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy.ConclusionIn modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents.

Abstract CD40 and BAFFR signaling play important roles in B cell proliferation and Ig production. In this study, we found that B cells from mice with deletion of Dbc1 gene (Dbc1−/−) show elevated proliferation, and IgG1 and IgA production upon in vitro CD40 and BAFF, but not BCR and LPS stimulation, indicating that DBC1 inhibits CD40/BAFF-mediated B cell activation in a cell-intrinsic manner. Microarray analysis and chromatin immunoprecipitation experiments reveal that DBC1 inhibits B cell function by selectively suppressing the transcriptional activity of alternative NF-κB members RelB and p52 upon CD40 stimulation. As a result, when immunized with nitrophenylated-keyhole limpet hemocyanin, Dbc1−/− mice produce significantly increased levels of germinal center B cells, plasma cells, and Ag-specific Ig. Finally, loss of DBC1 in mice leads to higher susceptibility to experimental autoimmune myasthenia gravis. Our study identifies DBC1 as a novel regulator of B cell activation by suppressing the alternative NF-κB pathway.

Introduction Pulmonary hypertension (PH) is a devastating, progressive disease with increasingly debilitating symptoms and usually shortened overall life expectancy due to a narrowing of the pulmonary vasculature and consecutive right heart failure. Little is known about PH in Africa, but limited reports suggest that PH is more prevalent in Africa compared with developed countries due to the high prevalence of risk factors in the region. Methods and analysis A multinational multicentre registry-type cohort study was established and tailored to resource-constraint settings to describe disease presentation, disease severity and aetiologies of PH, comorbidities, diagnostic and therapeutic management, and the natural course of PH in Africa. PH will be diagnosed by specialist cardiologists using echocardiography (right ventricular systolic pressure >35 mm Hg, absence of pulmonary stenosis and acute right heart failure), usually accompanied by shortness of breath, fatigue, peripheral oedema and other cardiovascular symptoms, ECG and chest X-ray changes in keeping with PH as per guidelines (European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines). Additional investigations such as a CT scan, a ventilation/perfusion scan or right heart catheterisation will be performed at the discretion of the treating physician. Functional tests include a 6 min walk test and the Karnofsky Performance Score. The WHO classification system for PH will be applied to describe the different aetiologies of PH. Several substudies have been implemented within the registry to investigate specific types of PH and their outcome at up to 24 months. Data will be analysed by an independent institution following a data analyse plan. Ethics and dissemination All local ethics committees of the participating centres approved the protocol. The data will be disseminated through peer-reviewed journals at national and international conferences and public events at local care providers.