Citations

ObjectiveTo evaluate the effect of body mass index on the surgical outcomes in ovarian cancer patients. In addition, we performed a systematic review to compare our outcomes with the current literature.DesignRetrospective cohort study and a systematic review of the literature.SettingGynaecology department at the Royal Cornwall Hospital Trust.PopulationSurgically managed stage I‐IV ovarian cancer patients between September 2006 and September 2014.MethodsPrimary and secondary outcome measures were evaluated across BMI categories; BMI <25 kg/m², BMI 25–29.9 kg/m², BMI ≥30 kg/m² and BMI ≥40 kg/m². A systematic review was performed according to Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) guidelines.Main outcome measuresThe primary outcome measure was surgical complications. Secondary outcome measures were other intra‐ and postoperative outcomes.ResultsTwo hundred twenty‐eight women were included in the study, of which 84 had a BMI <25 kg/m², 84 women had a BMI 25–29.9 kg/m², and 60 women were obese (BMI ≥30 kg/m²), 13 of whom were morbidly obese. Morbid obesity was associated with increased rates of wound complications. However, BMI did not show an association with other outcomes. In the review, an increasing BMI was associated with increased rates of wound complications and prolonged hospital stay, but did not impact other surgical outcomes.ConclusionObesity is associated with increased rates of wound complications and a prolonged hospital stay, but does not appear to affect other operative outcomes including cytoreduction status and 30‐day mortality. Therefore, operative management and postoperative care require a multifactorial approach to minimise adverse outcomes.Tweetable abstractObesity is associated with more wound complications and prolonged hospital stay in ovarian cancer surgery.

The cholangiopathies are a group of liver diseases resulting from different etiologies but with the cholangiocyte as the primary target. As a group, the cholangiopathies result in significant morbidity and mortality and represent one of the main indications for liver transplant in both children and adults. Contributing to this situation is the absence of a thorough understanding of their pathogenesis and a lack of adequate diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that modify gene expression post-transcriptionally. They have been implicated in the pathogenesis of many diseases, including the cholangiopathies. Thus, in this review we provide an overview of the literature on miRNAs in the cholangiopathies and discuss future research directions.

Pneumocystis jirovecii is responsible for P. jirovecii pneumonia (PJP) in immunocompromised individuals, with a recent rise of cases noted in non-HIV patients. A middle-aged man presented with new-onset cough, fever, hypoxia and tachypnoea. He was on a tapering course of dexamethasone for amiodarone-induced thyrotoxicosis. He developed worsening airspace disease necessitating mechanical ventilation. Bronchoalveolar lavage (BAL) fluid was positive for P. jirovecii and he was managed with trimethoprim/sulfamethoxazole and pentamidine, but succumbed to cardiorespiratory arrest. One-third of PJP cases occur in non-HIV patients, and have a higher morbidity and mortality. Most immunocompromised patients typically exhibit PJP during a corticosteroid taper. The accurate dose, duration or frequency of steroid use in not well established. Diagnosis of PJP in this population is more challenging due to lower BAL yield with alternate modalities such as serum/BAL β-d-glucan and PCR enhancing the yield. Further studies are needed to highlight PJP prophylaxis in patients with steroid use.

Background The association between resting heart rate and ischemic stroke remains unclear. Aim To examine the association between resting heart rate and ischemic stroke. Methods A total of 24 730 participants (mean age: 64 ± 9·3 years; 59% women; 41% blacks) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were free of stroke at the time of enrollment (2003–2007) were included in this analysis. Resting heart rate was determined from baseline electrocardiogram data. Heart rate was examined as a continuous variable per 10 bpm increase and also as a categorical variable using tertiles (<61 bpm, 61 to 70 bpm, and >70 bpm). First-time ischemic stroke events were identified during follow-up and adjudicated by physician review. Results Over a median follow-up of 7·6 years, a total of 646 ischemic strokes occurred. In a Cox regression model adjusted for socio-demographics, cardiovascular risk factors, and potential confounders, each 10 bpm increase in heart rate was associated with a 10% increase in the risk of ischemic stroke (hazard ratio = 1·10, 95% confidence interval = 1·02, 1·18). In the categorical model, an increased risk of ischemic stroke was observed for heart rates in the middle (hazard ratio = 1·29, 95% confidence interval = 1·06, 1·57) and upper (hazard ratio = 1·37, 95% confidence interval = 1·12, 1·67) tertiles compared with the lower tertile. The results were consistent when the analysis was stratified by age, gender, race, exercise habits, hypertension, and coronary heart disease. Conclusion In REGARDS, high resting heart rates were associated with an increased risk of ischemic stroke compared with low heart rates. Further research is needed to examine whether interventions aimed to reduce heart rate decrease stroke risk.

Summary Unconjugated monoclonal antibodies (mAbs) are an important component of effective combination therapies for chronic lymphocytic leukaemia (CLL). Antibody-dependent phagocytosis (ADP) is a major mediator of mAb cytotoxicity, but there is limited knowledge of the determinants of ADP efficacy. We used macrophages derived in vitro from autologous circulating monocytes to test the effects of mAb structure and concentration, target : effector cell ratio, duration of co-incubation and CLL cell CD20 expression on ADP. Next-generation anti-CD20 mAbs (ofatumumab, ublituximab, obinutuzumab, ocaratuzumab) were significantly more effective at inducing ADP compared to rituximab, but none were as effective as the anti-CD52 mAb alemtuzumab. Ofatumumab (10 μg/ml) used as a representative next-generation anti-CD20 mAb achieved an ADP plateau at 3 h co-incubation with a target : effector ratio of 10 : 1 (mean = 2·1 CLL cells/macrophage, range = 1·5–3·5). At 0·156 μg/ml (the lowest concentration tested) ofatumumab ADP was significantly higher than alemtuzumab. However, ofatumumab-induced ADP did not increase significantly at higher mAb concentrations. We show that anti-CD20 mAb ADP efficacy is determined by the mAb characteristics, target : effector ratio and incubation time. We suggest that preclinical evaluation of anti-CD20 mAbs to understand the determinants of ADP could be useful in designing future combination therapies for CLL.

Abstract Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). Results: We observed no significant association between genetic variants and prostate cancer survival. Conclusions: Common genetic variants with large impact on prostate cancer survival were not observed in this study. Impact: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes. Cancer Epidemiol Biomarkers Prev; 24(11); 1796–800. ©2015 AACR.

Abstract Monoclonal antibodies that target the programmed death-1 (PD-1)–programmed death ligand-1 (PD-L1) axis have antitumor activity against multiple cancers. The presence of sarcomatoid differentiation in renal cell carcinoma (RCC) is associated with resistance to targeted therapy and poor responses to IL2 immunotherapy. Given the aggressive nature of RCC with sarcomatoid differentiation and the exclusion of sarcomatoid histology from metastatic RCC clinical trials, less is understood regarding selection of therapies. Here, we characterized the PD-1/PD-L1 axis in RCC with sarcomatoid differentiation. We directly compared two PD-L1 antibodies and found concordance of PD-L1 positivity in 89% of tested RCCs with sarcomatoid differentiation. Coexpression of PD-L1 on neoplastic cells and the presence of PD-1–positive tumor-infiltrating lymphocytes were identified in 50% (13 of 26) of RCCs with sarcomatoid differentiation. In contrast, only 1 of 29 clear cell RCCs (3%) had concurrent expression of PD-L1 and PD-1 (P = 0.002). Our study suggests that RCC with sarcomatoid differentiation may express PD-1/PD-L1 at a higher percentage than RCC without sarcomatoid differentiation, and patients with these tumors may be good candidates for treatment with anti–PD-1/PD-L1 therapies. Cancer Immunol Res; 3(12); 1303–7. ©2015 AACR.

Background Preoperative assessment of anterior communicating artery (AcoA) aneurysms with cerebral angiography is common, but not without risk. Computed tomography angiography (CTA) is a widely available imaging modality that provides quick acquisition, low morbidity, and low cost. One disadvantage is that it does not provide dynamic information. In this study, the authors sought to determine whether CTA alone can reliably predict the inflow dominance to an AcoA aneurysm. Methods Eighty-three patients with ruptured AcoA aneurysms were reviewed retrospectively. Only those patients with both preoperative CTA and cerebral angiogram were included, thus excluding six patients. Four independent observers reviewed the CTAs and attempted to identify the dominant A1. Additionally, three mathematical models were created to identify the dominant A1. These responses were compared to cerebral angiograms. Results Four observers were correct in judging the dominant A1 an average of 93% of the time. Seventeen cases were read incorrectly by only one of four observers, and three cases were read incorrectly by two observers. For cases with incorrect readings, the average percentage difference in A1 sizes was 19.6%. For cases read unanimously correct, the average percentage difference in A1 sizes was 42.7%. Mathematical model #3 correctly evaluated the dominant A1 in 97% of the cases. Conclusions This study found CT angiograms can be reliable in predicting the inflow dominance to the majority of AcoA aneurysms.

IgG4-related disease is a relatively novel clinical entity whose gastrointestinal manifestations include type 1 autoimmune pancreatitis (AIP) and IgG4-associated sclerosing cholangitis. The presence of elevated serum IgG4 is suggestive but not essential for the diagnosis of type 1 AIP and is a pervasive feature of the proposed diagnostic criteria. The differential diagnosis of type 1 AIP includes malignant conditions, emphasizing the importance of a deliberate, comprehensive evaluation. Management of patients with a suggestive clinical presentation, but without serum IgG4 elevation, is difficult. Here we present three cases of IgG4-seronegative AIP and sclerosing cholangitis that responded to empiric steroid therapy and discuss approach considerations. These cases demonstrate the value of meticulous application of existing diagnostic algorithms to achieve a clinical diagnosis and avoid surgical intervention.

Purpose: This project examined potential changes in health behaviors following wellness coaching. Design: In a single cohort study design, wellness coaching participants were recruited in 2011, data were collected through July 2012, and were analyzed through December 2013. Items in the study questionnaire used requested information about 11 health behaviors, self-efficacy for eating, and goalsetting skills. Setting: Worksite wellness center. Participants: One-hundred employee wellness center members with an average age of 42 years; 90% were female and most were overweight or obese. Intervention: Twelve weeks of in-person, one-on-one wellness coaching. Method: Participants completed study questionnaires when they started wellness coaching (baseline), after 12 weeks of wellness coaching, and at a 3-month follow-up. Results: From baseline to week 12, these 100 wellness coaching participants improved their self-reported health behaviors (11 domains, 0- to 10-point scale) from an average of 6.4 to 7.7 ( p < .001), eating selfefficacy from an average of 112 to 142 (on a 0- to 180-point scale; p < .001), and goal-setting skills from an average of 49 to 55 (on a 16- to 80-point scale; p < .001). Conclusion: These results suggest that participants improved their current health behaviors and learned skills for continued healthy living. Future studies that use randomized controlled trials are needed to establish causality for wellness coaching.