Citations

Objectives Literature suggests an inconsistent, but largely inverse, association between asthma and risk of glioma, which is primarily due to methodological inconsistency in sampling frame and ascertainment of asthma. The objective of the study was to clarify the association between asthma and risk of glioma by minimising methodological biases (eg, recall and detection bias). Design A population-based case–control study. Setting General population in Olmsted County, Minnesota, USA. Participants All eligible biopsy-proven incident glioma cases (1995–2014) and two sets of controls among residents matched to age and sex (first set: community controls without glioma; second set: MRI-negative controls from the same community). Methods The predetermined asthma criteria via medical record review were applied to ascertain asthma status of cases and controls. History of asthma prior to index date was compared between glioma cases and their matched controls using conditional logistic regression models. Propensity score for asthma status was adjusted for multivariate analysis. Results We enrolled 135 glioma cases (median age at index date: 53 years) and 270 controls. Of the cases, 21 had a history of asthma (16%), compared with 36 of MRI controls (27%) (OR (95% CI) 0.48 (0.26 to 0.91), p=0.03). With MRI controls, an inverse association between asthma and risk of glioma persisted after adjusting for the propensity score for asthma status, but did not reach statistical significance probably due to the lack of statistical power (OR (95% CI) 0.48 (0.21 to 1.09); p=0.08). Based on comparison of characteristics of controls and cases, community controls seem to be more susceptible to a detection bias. Conclusions While differential detection might account for the association between asthma and risk of glioma, asthma may potentially pose a protective effect on risk of glioma. Our study results need to be replicated by a larger study.

The liver performs numerous vital functions, including the detoxification of blood before access to the brain while simultaneously secreting and internalizing scores of proteins and lipids to maintain appropriate blood chemistry. Furthermore, the liver also synthesizes and secretes bile to enable the digestion of food. These diverse attributes are all performed by hepatocytes, the parenchymal cells of the liver. As predicted, these cells possess a remarkably well-developed and complex membrane trafficking machinery that is dedicated to moving specific cargos to their correct cellular locations. Importantly, while most epithelial cells secrete nascent proteins directionally toward a single lumen, the hepatocyte secretes both proteins and bile concomitantly at its basolateral and apical domains, respectively. In this Beyond the Cell review, we will detail these central features of the hepatocyte and highlight how membrane transport processes play a key role in healthy liver function and how they are affected by disease.

Purpose To explore faculty perspectives on which characteristics of high-performing clerkship students are most important when determining an honors or top grade designation for clinical performance. Method In 2016–2017, the authors surveyed faculty (teaching ward attendings) for internal medicine clerkships and 1 pediatrics clerkship in inpatient settings at 5 U.S. academic medical centers. Survey items were framed around competencies, 24 student characteristics, and attitudes toward evaluation. Factor analysis examined constructs defining high-performing students. Results Of 516 faculty invited, 319 (62%) responded. The top 5 characteristics as rated by respondents were taking ownership, clinical reasoning, curiosity, dependability, and high ethical standards (in descending order). Twenty-one characteristics fit into 3 factors (Cronbach alpha, 0.81–0.87). Clinical reasoning did not fit into a factor. Factor 1 was the most important (mean rating, 8.7/10 [95% confidence interval (CI), 8.6–8.8]). It included professionalism components (ownership, curiosity, dependability, high ethical standards), presentation and interviewing skills, seeking feedback, and documentation. Factor 2 (mean, 7.9 [95% CI, 7.7–8.0]) included aspects of teamwork and communication, such as positive attitude and comments from others. Factor 3 (mean, 7.6 [95% CI, 7.4–7.7]) addressed systems-based thinking, including patient safety and care transitions. Conclusions Professionalism components, clinical reasoning, and curiosity were among the most important characteristics distinguishing high-performing clerkship students. These may represent behaviors that are highly valued, observable, and relevant to training stage. Improved definition of the characteristics associated with clinical honors would assist students, faculty, and residency program directors when interpreting clinical performance within core clerkships.

AbstractIntroductionEmerging medical technology has allowed for monitoring of heart rhythm abnormalities using smartphone compatible devices. The safety and utility of such devices have not been established in patients with cardiac implantable electronic devices (CIEDs). We sought to assess the safety and compatibility of the Food and Drug Administration‐approved AliveCor Kardia device in patients with CIEDs.Methods and ResultsWe prospectively recruited patients with CIED for a Kardia recording during their routine device interrogation. A recording was obtained in paced and nonpaced states. Adverse clinical events were noted at the time of recording. Electrograms (EGMs) from the cardiac device were obtained at the time of recording to assess for any electromagnetic interference (EMI) introduced by Kardia. Recordings were analyzed for quality and given a score of 3 (interpretable rhythm, no noise), 2 (interpretable rhythm, significant noise) or 1 (uninterpretable). A total of 251 patients were recruited (59% with a pacemaker and 41% with ICD). There were no adverse clinical events noted at the time of recording and no changes to CIED settings. Review of all EGMs revealed no EMI introduced by Kardia. Recordings were correctly interpreted in 90% of paced recordings (183 had a score of 3, 43 of 2, and 25 of 1) and 94.7% of nonpaced recordings (147 of 3, 15 of 2, and 9 of 1).ConclusionThe AliveCor Kardia device has an excellent safety profile when used in conjunction with most CIEDs. The quality of recordings was preserved in this population. The device, therefore, can be considered for heart rhythm monitoring in patients with CIEDs.

ObjectiveOptimal timing of postoperative radiotherapy (PORT) remains understudied in human papillomavirus (HPV)–related oropharyngeal squamous cell carcinoma. Objectives are to determine if delays between surgery and radiotherapy, breaks during radiotherapy, disease, or patient factors are associated with recurrence or survival decrements in HPV‐related disease.DesignRetrospective review.SettingAcademic medical center.SubjectsA total of 240 cases of HPV‐positive oropharyngeal squamous cell carcinoma from 2000 to 2016.MethodsPatient and tumor characteristics (American Joint Committee on Cancer, eighth edition), delays to radiation initiation, and breaks during radiation were recorded. Overall survival (OS) and recurrence‐free survival (RFS) were analyzed.ResultsRFS and OS were not significantly affected by delays to PORT >6 weeks or by treatment intervals >100 days (surgery to PORT completion). Breaks during PORT significantly imparted an OS detriment (hazard ratio [HR], 2.4; 95% CI, 1.2‐4.8). Advanced‐stage disease was significantly associated with reduced RFS and OS. Subgroup analysis of stage I versus stage II/III disease found that >6 weeks to PORT initiation and treatment intervals >100 days did not significantly decrease RFS or OS in either stage group. Advanced‐stage disease was significantly associated with worsened OS (HR, 6.6; 95% CI, 2.3‐19.1) and RFS (HR, 5.3; 95% CI, 1.5‐18.4). Breaks during PORT significantly reduced RFS (HR, 3.6; 95% CI, 1.2‐10.8) and OS (HR, 3.2; 95% CI, 1.2‐9.0) in the stage II/III subset.ConclusionDelays to radiotherapy initiation and prolonged treatment time did not affect recurrence or survival in HPV‐related oropharyngeal disease. Locoregionally advanced disease was consistently associated with worse outcomes. Breaks during PORT may affect recurrence and survival, although larger studies are needed to confirm this finding.

AbstractBackgroundPatients with chronic intestinal failure who require long‐term parenteral nutrition rely on central venous catheters (CVCs) for access to nutrition and hydration. With prolonged use, complications such as central line–associated bloodstream infection (CLABSI), damage to CVC, and central venous thrombosis (CVT) can threaten the availability of life‐preserving access. Because of this, all efforts should be made to preserve CVCs with techniques such as catheter salvage in case of CLABSI and catheter repair when damaged. The present study was conducted to evaluate the effectiveness and safety of catheter repair in our patient population.MethodsRetrospective review in 1253 adult patients who received home parenteral nutrition at the Mayo Clinic between September 1, 1997, and April 30, 2018, was conducted to determine the incidence of CLABSI and CVT in patients who underwent CVC repair.ResultsFifty‐five CVC repairs were performed in 36 patients (n = 23 female) with mean age of 57.05 ± 16.96 years. A total of 14 catheters (25.45%) were complicated with 24 episodes of CLABSI. CLABSI rate before and after repair was 0.23/1000 catheter days and 0.21/1000 catheter days, respectively. Most common indications for eventual catheter replacement were mechanical damage (32%), infection (32%), and switching to alternate mode of nutrition (24%). We had a 100% success rate of catheter repair procedure, and no post‐procedural complications were present.ConclusionCatheter repair can increase the catheter survival without increasing the risk of CLABSI, providing not only socioeconomic benefit but also decreasing risk of compromising future vascular access.

Abstract Aim A previous study showed significantly greater reductions in number of cigarettes smoked and biomarkers of toxicant and carcinogen exposure in smokers assigned to immediate reduction of nicotine in cigarettes to very low levels versus gradually over time or continued smoking of normal nicotine content cigarettes. This study examines the effects of these approaches on selected biomarkers associated with harmful biological effects. Design Three‐arm, randomized controlled trial. Setting Ten United States academic institutional sites. Participants Daily smokers uninterested in quitting smoking with a mean age of 45.1 [standard deviation (SD) = 13.4)] years and smoking 17.1 (SD = 8.5) cigarettes/day; 43.9% (549 of 1250) female; 60.6% (758 of 1250) white ethnicity. Interventions (1) Smoking cigarettes where nicotine content was immediately reduced to very low levels ( n = 503); (2) smoking cigarettes where nicotine content was gradually reduced, with dose changes occurring monthly ( n = 498); and (3) continued smoking with normal nicotine content cigarettes ( n = 249). Measurements Smokers were assessed at baseline while smoking their usual brand cigarettes, and again at 4, 8, 12, 16 and 20 weeks. Outcomes were areas under the concentration time curve (AUC) for the period of study of biomarkers of inflammation, oxidative stress and hematological parameters. Findings No consistent significant differences were observed across groups (Bayes factors showing data to be insensitive), with the only exception being red blood cell size variability, which was observed to be lower in the immediate versus gradual nicotine reduction [mean difference = −0.11; 95% confidence interval (CI) = –0.18, −0.04, P = 0.004] and normal nicotine control groups (mean difference = − 0.15, 95% CI = –0.23, −0.06, P = 0.001). Conclusion It remains unclear whether switching to very low nicotine cigarettes leads to a short‐term reduction in biomarkers of tobacco‐related harm.

5031 Background: The phase 2 TRITON2 study (NCT02952534) is evaluating the PARP inhibitor rucaparib in patients with mCRPC who have a deleterious germline or somatic alteration in BRCA ( BRCA1 or BRCA2) or 1 of 13 other DNA damage repair genes. Here we present analyses of tumor genomics and baseline clinical characteristics in mCRPC patients with a deleterious alteration in BRCA. Methods: Plasma (baseline) and tissue (archival or baseline) samples from patients with a deleterious alteration in BRCA were analyzed using Foundation Medicine next-generation sequencing assays. The alterations and zygosity of the alterations that were detected, as well as the somatic/germline status from Color Genomics testing, were summarized. Associations between genomic alterations, DNA yield, allele frequency, and baseline clinical characteristics were investigated. Results: Results are shown in the Table for a cohort of 40 BRCA2 and 5 BRCA1 patients enrolled in TRITON2 (Abida W et al. Presented at ESMO 2018. Abst 793PD). A biallelic alteration was observed in 21 of the 22 BRCA2 patients (95%) for whom alteration zygosity could be determined. Among the 5 BRCA1 patients, 1 alteration was monoallelic and 4 were of unknown zygosity. Co-occurring alterations in cancer-related or DNA damage repair genes were observed in many patients with BRCA alterations. At baseline, cell-free DNA (cfDNA) yield correlated positively with the sum of target lesions (STL; P= 0.04), but not with prostate-specific antigen (PSA) levels ( P= 0.86). No correlation was observed between allele frequency of the BRCA alteration baseline STL ( P= 0.68) or PSA levels ( P= 0.97). Conclusions: Patients with a BRCA mutation enrolled in TRITON2 demonstrate a profile of genomic alterations consistent with that of prior studies of patients with mCRPC. Plasma cfDNA profiling showed a correlation between baseline cfDNA yield and measurable tumor burden, but not baseline PSA. Clinical trial information: NCT02952534. [Table: see text]