Citations

Abstract Lung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier function and increases susceptibility to infections. Herein, we hypothesized that somatic mutations together with cigarette smoke create a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from controls (n=33) or cancer cases (n=143), we conducted 16S rRNA gene sequencing (MiSeq), with RNA-seq data from lung cancer cases in The Cancer Genome Atlas (n=1112) serving as the validation cohort. We demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue, indicating a shift in the overall microbial community in lung cancer patients as compared to those without cancer. Lung cancer cases were classified by the relative abundance of two taxa, Variovorax and Streptococcus, with an increase in Variovorax abundance in tumors as compared to non-tumor adjacent paired lung tissue (FDR corrected P=0.013). The species of Variovorax was identified histologically, and also by two additional 16S rRNA strategies (Resphera Insight analysis and PacBio sequencing). A group of taxa were associated with squamous cell carcinoma (SCC), of which Acidovorax were enriched in smokers (P =0.0013). Further, these taxa, including Acidovorax, exhibited higher abundance among the subset of SCC cases with TP53 mutations, an association not seen in adenocarcinomas (AD). Therefore, we observed a microbiome-gene and a microbiome-exposure interaction in SCC lung cancer tissue. Together, these results open the door for future biomarker research that could be used to improve screening and direct mechanistic studies of lung cancer therapy. Citation Format: Leigh Greathouse, James White, Valery Bliskovsky, Ashley Vargas, Eric Polley, Elise Bowman, Mohammed Khan, Ana Robles, Brid Ryan, Amiran Dzutsev, Giorgio Trinchieri, Marbin Pineda, Sven Bilke, Paul Meltzer, Marina Walther-Antonio, Garth Ehrlich, Joshua Mell, Joshua Earl, Sergey Balashov, Archana Bhat, Alex Valm, Clayton Deming, Sean Conlan, Julia Oh, Julie Segre, Curtis Harris. Microbiome-TP53 gene interaction in human lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4925. doi:10.1158/1538-7445.AM2017-4925

ObjectiveTo confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder.MethodData were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth‐cohort, family history, polarity of first episode and country physician density.ResultsThere was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth‐cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth‐cohort (all estimated coefficientsP< 0.001).ConclusionA large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LEDlighting, mobile devices backlit withLEDs) may influence adaptability to a springtime circadian challenge.

Background: Lack of wellness among physicians has been associated with increased risk for physical and mental illness, interpersonal discord, and occupational liability. In academic primary care practices, physician wellness and self-care behaviors have been associated with improved patient outcomes. With the increase in team-based care structures in primary care clinics and residencies there may be opportunities to promote wellness among primary clinicians, particularly among resident physicians who are at increased risk for decreased well being. The primary objective of the study was to test an a priori hypothesis that family medicine residents’ perception of support from preceptor team leads would be associated with wellbeing. A secondary objective of the study was to test a post hoc hypothesis that examined whether the relationship between residents’ perception of support from their preceptor team leads would be associated with residents’ well being, while controlling for self-care behaviors. Methods: Our study utilized a prospective cross-sectional design with purposive sampling to survey family medicine residents. Data were collected in February 2016. The survey was sent out to 58 family medicine residents across three family medicine residencies at Mayo Clinic. The survey response rate was 55% (n=32); Ten (31.3%) residents reported being in their PGY-1, 11 (34.4%) in PGY-2; and 11 (34.4%) in PGY-3; participants included 19 (59.4%) women and 13 (40.6%) men. The Brief Resident Wellness Profile (BRWP) was utilized to assess family medicine residents’ perceived sense of professional accomplishment and mood in the past week. Results: In bivariate correlational analyses, increased perception of support from preceptor team leads (r=.40, P&lt;.01) and reporting a male gender (r=.43, P&lt;.01) was associated with increased resident wellness. In exploratory multivariate analysis, results suggested that while controlling for gender, frequency of self-care behaviors, and perceived preceptor team lead support, a one-point change on rating of perceived team leader support is associated with a 1.69 increase in resident wellness score on the BRWP. Conclusions: Our results provide preliminary evidence to support the relationship between preceptor team lead support and resident wellness in team-based care, above and beyond the impact that self-behaviors have on wellness. Our findings suggest evidence for the subsequent study of the impact of preceptor team lead relationship quality on resident wellness.

Background: The role of diet in multiple sclerosis (MS) is largely uncharacterized, particularly as it pertains to pediatric-onset disease. Objective: To determine the association between dietary factors and MS in children. Methods: Pediatric MS patients and controls were recruited from 16 US centers (MS or clinically isolated syndrome onset before age 18, <4 years from symptom onset and at least 2 silent lesions on magnetic resonance imaging). The validated Block Kids Food Screener questionnaire was administered 2011–2016. Chi-squared test compared categorical variables, Kruskal–Wallis test compared continuous variables, and multivariable logistic regression analysis was performed. Results: In total, 312 cases and 456 controls were included (mean ages 15.1 and 14.4 years). In unadjusted analyses, there was no difference in intake of fats, proteins, carbohydrates, sugars, fruits, or vegetables. Dietary iron was lower in cases ( p = 0.04), and cases were more likely to consume below recommended guidelines of iron (77.2% of cases vs 62.9% of controls, p < 0.001). In multivariable analysis, iron consumption below recommended guidelines was associated with MS (odds ratio = 1.80, p < 0.01). Conclusion: Pediatric MS cases may be less likely to consume sufficient iron compared to controls, and this warrants broader study to characterize a temporal relationship. No other significant difference in intake of most dietary factors was found.

Patient safety secured by constant vigilance remains a primary responsibility of every anesthesia professional. Although significant attention has been focused on patient falls occurring before and after surgery, a potentially catastrophic complication is when patients fall off an operating room or procedure table during anesthesia care. Because such events are (fortunately) uncommon, and because very little information is published in our literature, we queried 2 independent closed claims databases (the American Society of Anesthesiologists Closed Claims Project and the secure records of a private, anesthesia specialty-specific liability insurer) for information. We acquired documentation of patient events where a fall occurred during anesthesia care, noting the surrounding conditions of the provider, the patient, and the environment at the time of the event. We identified 21 claims (1.2% of cases) from the American Society of Anesthesiologists Closed Claims Project, while information from a private liability insurer identified falls in only 0.07% of cases. The percentage of these patients under general, regional, or monitored anesthesia care anesthesia was 71.5%, 19.5%, and 9.5%, respectively. To educate personnel about these uncommon events, we summarized this cohort with illustrative examples in a series of mini-case reports, noting that both inpatients and outpatients undergoing a broad array of procedures with various anesthetic techniques within and outside operating rooms may be vulnerable to patient falls. Based on detailed reports, we created 2 supplementary videos to further illuminate some of the unique mechanisms by which these events and their resulting injuries occur. When such information was available, we also noted the associated liability costs of defending and settling malpractice claims associated with these events. Our goal is to inform anesthesia and perioperative personnel about the common patient, provider, and environmental risk factors that appear to contribute to these mishaps, and suggest key strategies to mitigate the risks.

Abstract Background VELVET Cohort 1 demonstrated the applicability of pertuzumab, trastuzumab, and vinorelbine as an alternative first-line treatment regimen for patients with HER2-positive locally advanced or metastatic breast cancer (MBC) who cannot receive docetaxel. Co-infusion of pertuzumab and trastuzumab may reduce clinic time and medical resource utilization. We report results from Cohort 2, in which pertuzumab and trastuzumab were co-infused, followed by vinorelbine. Patients and Methods During cycle 1, patients with HER2-positive locally advanced or MBC received loading doses of pertuzumab (840 mg) and trastuzumab (8 mg/kg) on consecutive days, followed by vinorelbine (25 mg/m2) on days two and nine. From cycle 2 onwards, patients received a co-infusion of pertuzumab (420 mg) and trastuzumab (6 mg/kg) on day one, followed by vinorelbine (30–35 mg/m2) on days one and eight (or days two and nine). The primary endpoint was objective response rate (ORR) in patients with measurable disease. Secondary endpoints included progression-free survival (PFS) and safety. Results Cohort 2 enrolled 107 patients. The ORR was 63.7% (95% confidence interval [CI] 53.0–73.6) in patients with measurable disease (91/107; 85.0%). Median PFS was 11.5 months (95% CI 10.3–15.8). The most common adverse events [AEs] were diarrhea (57.9%), neutropenia (57.0%), and nausea (41.1%). Grade ≥3 AEs occurred in 85 patients (79.4%) and serious AEs in 44 patients (41.1%). Eighteen patients (16.8%) had AEs suggestive of congestive heart failure. Conclusion These results support the feasibility of pertuzumab and trastuzumab co-infusion from a safety perspective and support Cohort 1 conclusions that vinorelbine offers an alternative chemotherapy companion for pertuzumab and trastuzumab. The Oncologist 2017;22:1160–1168