Citations

Background: Treatment with nab-paclitaxel with gemcitabine demonstrates a survival advantage when compared with single-agent gemcitabine. However, the combination is associated with significant toxicities, leading to a high rate of drug discontinuation. We implemented a modified regimen of gemcitabine and nab-paclitaxel (mGNabP) in an attempt to minimize toxicities while maintaining efficacy. Methods: A total of 79 evaluable patients with metastatic pancreatic adenocarcinoma (mPC) treated with a modified regimen of gemcitabine (1000 mg/m 2 ) and nab-paclitaxel (125 mg/m 2 ) on days 1, 15 of every 28-day cycle were identified from our prospective database. A total of 57 patients received this regimen as first-line treatment and were evaluated for toxicities, progression-free survival (PFS), and overall survival (OS). Overall, 22 patients with advanced or metastatic PC treated with the modified regimen outside the first-line setting were only evaluated for toxicities. Results: The median OS and PFS were 10 months [95% confidence interval (CI) 5.9–13 months] and 5.4 months (95% CI 4.1–7.4 months) for patients that received the modified regimen as first-line therapy. Neurotoxicity occurred in 27% with only 1.6% of patients experiencing grade ⩾3 toxicity. The incidence of grade ⩾3 neutropenia was 19%, resulting in growth factor support in 12% of patients. This rate was similar in patients who received the modified regimen for first-line treatment of mPC versus the overall group. Conclusions: A modified regimen of biweekly nab-paclitaxel with gemcitabine is associated with a lower cost, acceptable toxicity profile and appears to be relatively effective in pancreatic cancer. Prospective randomized studies confirming its potential benefits compared with standard weekly mGNabP are warranted.

Aims Total hip arthroplasty (THA) has well known subjective benefits, but little is known objectively about the recovery of mobility in the early post-operative period. Patients and Methods A total of 33 patients aged > 60 years who underwent elective primary THA had their activity monitored for 30 days post-operatively using an at-home (Fitbit) ankle accelerometer. Their mean age was 70.7 years (61 to 86); 15 (45.5%) were female. The rate of compliance and the mean level of activity were determined. Comparisons between subgroups based on age, body mass index (BMI), surgical approach, and the destination of the patients when discharged were also performed. Results The mean compliance over the 30 days was 26.7 days (16 to 30; 89%) of use. The mean number of steps increased from 235 (5 to 1152) to 2563 (87 to 7280) (p < 0.001) between the first and the 30th post-operative day. Age < 70 years and an anterior surgical approach were significantly associated with higher levels of activity (1600 to 2400 (p = 0.016 to 0.031) and 1000 to 1800 (p = 0.017 to 0.037) more steps per day, respectively) between the second and the fourth week post-operatively. There was also a trend towards higher levels of activity in those who were discharged to their home rather than to a nursing facility (a mean of 1500 more steps per day, p = 0.02). BMI greater or less than 30 kg/m 2 was not predictive of activity (p = 0.45 to 0.98). Conclusion At-home remote mobility monitoring using existing commercially available technology is feasible in patients who have undergone THA. It showed a clear trend towards increased activity with the passage of time. Additionally, the remote device was able to detect differences in levels of activity clearly between patients in relation to variables of interest including age, BMI, surgical approach, and the destination of the patient at the time of discharge from hospital. Such monitoring may allow for the early identification and targeted intervention in patients who recover slowly. Cite this article: Bone Joint J 2016;98-B:1450–4.

Introduction: Racial and ethnic groups are under-represented among research subjects who assent to brain donation in Alzheimer disease research studies. There has been little research on this important topic. Although there are some studies that have investigated the barriers to brain donation among African American study volunteers, there is no known research on the factors that influence whether or not Asians or Latinos are willing to donate their brains for research. Methods: African American, Caucasian, Asian, and Latino research volunteers were surveyed at 15 Alzheimer Disease Centers to identify predictors of willingness to assent to brain donation. Results: Positive predictors included older age, Latino ethnicity, understanding of how the brain is used by researchers, and understanding of what participants need to do to ensure that their brain will be donated. Negative predictors included African/African American race, belief that the body should remain whole at burial, and concern that researchers might not be respectful of the body during autopsy. Discussion: The predictive factors identified in this study may be useful for researchers seeking to increase participation of diverse ethnic groups in brain donation.

AbstractIntroductionAfrican Americans' (AAs) late‐onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.MethodsWe conducted a genome‐wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome‐wide set of single‐nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs.ResultsTwo SNPs at novel loci, rs112404845 (P = 3.8 × 10−8), upstream of COBL, and rs16961023 (P = 4.6 × 10−8), downstream of SLC10A2, obtained genome‐wide significant evidence of association with the posterior liability.DiscussionAn informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.

BACKGROUNDStereotactic body radiotherapy (SBRT) is the standard of care for patients with nonoperative, early‐stage non–small cell lung cancer (NSCLC) measuring < 5 cm, but its use among patients with tumors measuring ≥5 cm is considerably less defined, with the existing literature limited to small, single‐institution reports. The current multi‐institutional study reported outcomes evaluating the largest such population reported to date.METHODSClinical/treatment characteristics, outcomes, toxicities, and patterns of failure were assessed in patients with primary NSCLC measuring ≥5 cm without evidence of distant/lymph node metastasis who underwent SBRT using ≤5 fractions. Statistics included Kaplan‐Meier survival analyses and univariate/multivariate Cox proportional hazards models.RESULTSA total of 92 patients treated from 2004 through 2016 were analyzed from 12 institutions. The median follow‐up was 12 months (15 months in survivors). The median age and tumor size among the patients were 73 years (range, 50‐95 years) and 5.4 cm (range, 5.0‐7.5 cm), respectively. The median dose/fractionation was 50 Gray/5 fractions. The actuarial local control rates at 1 year and 2 years were 95.7% and 73.2%, respectively. The disease‐free survival rate was 72.1% and 53.5%, respectively, at 1 year and 2 years. The 1‐year and 2‐year disease‐specific survival rates were 95.5% and 78.6%, respectively. The median, 1‐year, and 2‐year overall survival rates were 21.4 months, 76.2%, and 46.4%, respectively. On multivariate analysis, lung cancer history and pre‐SBRT positron emission tomography maximum standardized uptake value were found to be associated with overall survival. Posttreatment failures were most commonly distant (33% of all disease recurrences), followed by local (26%) and those occurring elsewhere in the lung (23%). Three patients had isolated local failures. Grade 3 to 4 toxicities included 1 case (1%) and 4 cases (4%) of grade 3 dermatitis and radiation pneumonitis, respectively (toxicities were graded according to the Common Terminology Criteria for Adverse Events [version 4.0]). Grades 2 to 5 radiation pneumonitis occurred in 11% of patients. One patient with a tumor measuring 7.5 cm and a smoking history of 150 pack‐years died of radiation pneumonitis.CONCLUSIONSThe results of the current study, which is the largest study of patients with NSCLC measuring ≥5 cm reported to date, indicate that SBRT is a safe and efficacious option. Cancer 2017;123:688–696. © 2016 American Cancer Society.

De novo progressive aortic insufficiency (AI) is a side effect frequently related to prolonged support with continuous-flow left ventricular assist devices (CF-LVAD). Its progression can result in recurrent clinical heart failure symptoms and significantly increased mortality. Recently, percutaneous intervention methods, such as transcatheter aortic valve replacement (TAVR) and percutaneous occluder devices, have emerged. However, given the very scarce global experience with these approaches, evidence in the literature is lacking. We sought to assess the outcomes of CF-LVAD patients who had undergone percutaneous intervention for AI. A systematic search of six databases from inception to April 2016 was performed by two independent reviewers. Eligible studies were those that included series or cases where patients had percutaneous transcatheter interventions for AI in CF-LVAD patients. Data were extracted and meta-analyzed from the identified studies. A total of 29 patients from 15 published studies and 3 unpublished records were included in the analysis. Mean patient age was 56.6 ± 13.7 years, and 72.4% were male. The etiology of heart failure resulting in LVAD placement was ischemic cardiomyopathy in 17.2%. The two intervention groups were TAVR (27.6%) and occluder devices (72.4%). A transfemoral approach (69%), apical approach (10%), brachial approach (7%), subclavian approach (3%), and mini-sternotomy (3%) were used. The preintervention AI grade was severe with a median grade of 4 (interquartile range, 4–4). Postoperatively, the AI grade improved significantly to a median grade of 0 (0–2). At long-term follow-up AI grade was still trivial with a median AI grade of 1 (0–1). Subgrouping the treatments into the occluder device and TAVR, it was found that both interventional techniques were similarly effective in reducing the AI grade from severe to trivial. In terms of complications, from the occluder group, two patients were complicated with device migration and another two with transient hemolysis. In the TAVR cohort, two patients experienced device migration and another had significant postimplant perivalvular leakage. Our results indicate that percutaneous interventions for AI in CF-LVAD patients with TAVR, and closure devices demonstrate similar efficacy in significantly reducing severe AI. Current results are encouraging, potentiating viability as a treatment option, particularly in nonsurgical candidates. Future research with larger patient cohorts and comparative controls is required to sufficiently evaluate the efficacy of this technique and promote its widespread acceptance as a mainstay treatment.

ObjectiveIn observational epidemiologic studies, higher plasma high‐density lipoprotein cholesterol (HDL‐C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL‐C; as such, medicines that inhibit CETP and raise HDL‐C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL‐C also increase risk for ICH.MethodsWe performed 2 candidate‐gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL‐C as well as ICH risk.ResultsTwelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10−4) with no heterogeneity across studies (I2 = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL‐C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10−6).InterpretationGenetic variants in CETP associated with increased HDL‐C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL‐raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730–740

Little is known about which variables put patients with cancer at risk for 30-day hospital readmission. Comanagement of this often complex patient population by specialists and hospitalists has become increasingly common. This retrospective study examined inpatients with cancer comanaged by hospitalists, hematologists, and oncologists to determine the rate of readmission and factors associated with readmission. Patients in this cohort had a readmission rate of 23%. Patients who were discharged to a skilled nursing facility (odds ratio [OR] = 0.34) or hospice (OR = 0.11) were less likely to have 30-day readmissions, whereas patients who had surgery (OR = 3.16) during their index admission were more likely. Other factors, including patient demographics, cancer types, and hospitalization interventions and events, did not differ between patients who were readmitted and those who were not. These findings contribute to a growing body of literature identifying risk factors for readmission in medical oncology and hematology patients.