Citations

Abstract Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Abstract Background Bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is associated with inadequate empirical therapy and substantial mortality in neutropenic patients. Strategies are needed to identify neutropenic patients at high risk of these infections. Methods From April 2014 to September 2016, we collected perianal swabs, both at admission and weekly thereafter, from patients undergoing hematopoietic stem cell transplantation (HSCT). Patients received prophylactic levofloxacin while neutropenic. Swabs were plated onto selective agar, colonies were identified and underwent antimicrobial susceptibility testing, and phenotypic ESBL testing and polymerase chain reaction for β-lactamase genes were performed on ceftriaxone-resistant Enterobacteriaceae. We then determined the prevalence of pre-transplant ESBL-E colonization and risk of ESBL-E bacteremia. Colonizing and bloodstream isolates from patients with ESBL-E bacteremia underwent multilocus sequence typing and pulsed-field gel electrophoresis. Results We analyzed 312 patients, including 212 allogeneic and 100 autologous HSCT recipients. Ten percent (31/312) of patients had pre-transplant ESBL-E colonization. Susceptibility rates of colonizing ESBL-E were: levofloxacin, 25%; cefepime, 9%; piperacillin-tazobactam, 84%; and meropenem, 97%. Of 31 patients colonized with ESBL-E pre-transplant, 10 (32%) developed ESBL-E bacteremia during their transplant admission, compared to 1 (0.4%) of 281 patients not colonized with ESBL-E (P &lt; .001). All bloodstream ESBL-E were levofloxacin-resistant and colonizing and bloodstream isolates from individual patients had identical genotypic profiles. Conclusions HSCT recipients who are colonized with levofloxacin-resistant ESBL-E pre-transplant and receive levofloxacin prophylaxis have high rates of bacteremia from their colonizing strain during neutropenia. Assessing for ESBL-E colonization in neutropenic patients could lead to optimization of empirical antibacterial therapy.

Objectives Helicopter air ambulance (HAA) of pediatric trauma patients is a life-saving intervention. Triage remains a challenge for both scene transport and interhospital transfer of injured children. We aimed to understand whether overtriage or undertriage was a feature of scene or interhospital transfer and how in or out of state transfers affected these rates. Methods Children (<18 years) who underwent trauma activation at a level I trauma center between 2011 and 2013 were identified and reviewed. Patients transported by HAA were compared with those transported by ground ambulance (GA). Results Of 399 pediatric patients (median age, 10.4 years; range, 0.1–17 years; 264 male [66%]), 71 (18%) were transported by HAA. Seventy-two percent of HAA patients went to the intensive care unit or the operating room from the trauma bay or suffered in-hospital mortality (vs 42% GA, P < 0.001). More patients were overtriaged (HAA with injury severity score [ISS] of <15) from interhospital transfers than from the scene (25% vs 3%, P = 0.002). Undertriage (GA with ISS >15) was acceptable at 5% from the scene and 14% from interhospital transfers (P = 0.08). Overtriage of patients with ISS less than 15 to HAA was significantly lower from in-state hospitals (22%) than out-of-state hospitals (45%) (P = 0.02). Undertriage of patients with ISS greater than 15 to GA was also lower from in-state hospitals (20%) versus out-of-state hospitals (38%) (P = 0.03). Conclusions Triage of pediatric trauma patients to HAA remains difficult. There remains potential for improvement, particularly as regards interhospital HAA overtriage, but well developed transfer protocols (such in-state protocols) may help.

Accessible summaryWhat is known on the subject? Weight suppression (WS) has been suggested to predict outcome following psychological treatment for an eating disorder (ED). Some findings are contradictory and have not been considered systematically. What the paper adds to existing knowledge? The review suggests that weight gain at post‐treatment is reliably predicted by pretreatment WS, but findings regarding other outcomes (e.g., treatment dropout) are less consistent. Approximate effect sizes for observed relationships are identified, alongside support for biobehavioural theories of metabolic adaptation to weight loss. What are the implications for practice? Degree of WS at pretreatment is associated with weight gain and is important for clinicians to consider before offering treatment to patients with EDs. Patients high in WS might benefit from further support (e.g., psychoeducation) prior to beginning treatment. AbstractIntroductionWeight suppression (WS—the difference between highest body weight and current body weight) has been proposed as a predictor of treatment outcome within eating disorders (EDs), although this hypothesis has not been consistently supported.Aim/QuestionReview the association between pretreatment WS and outcome following psychological treatment for EDs.MethodA comprehensive electronic database search for published and unpublished literature from 1979 to 2017. Reference lists were also inspected. Eligibility criteria were determined according to relevant guidelines and a quality appraisal was conducted.ResultsTwelve studies met inclusion criteria (one was subsequently excluded based on insufficient data). Greater WS was generally associated with weight gain at post‐treatment although not with other treatment outcomes.DiscussionThe existing evidence, with data from 1,566 participants, is summarized according to three main post‐treatment outcomes: weight change; treatment completion; and symptom abstinence. Patients with disordered eating and greater WS may need to gain more weight than others during treatment to achieve good outcomes. Recommendations for future studies are provided.Implications for practiceEvidence‐based treatments for EDs may benefit from considering WS when planning treatment, such as further psychoeducation on weight changes. Societal interventions regarding promotion of healthy eating may also draw on these findings.

AbstractTo determine whether CSF leucine‐rich glioma‐inactivated 1(LGI1)‐IgG titer, index or IgG subclass has prognostic significance, we tested serum and CSF specimens collected concomitantly from 39 seropositive patients. LGI1‐IgG index was elevated (>1) in 21 patients (54%), suggesting intrathecal synthesis. Patients with worse outcome at last follow‐up (modified Rankin Scale >2) had significantly higher index (median 6.57 vs. 0.5, P = 0.048) compared to those with better outcome. Higher CSF LGI1‐IgG4 subclass‐specific titer and index correlated with worse outcome (P < 0.005 for both). These data suggest that evidence of intrathecal LGI1‐IgG synthesis may correlate with neuronal injury and warrant consideration of aggressive immunotherapy.

Abstract Yoga is increasing in popularity in the United States and across the globe. However, most yoga programs are provided outside the worksite; although many companies offer worksite wellness programs, at present there is limited documentation regarding the potential benefits of participating in a worksite yoga program. Therefore, the purpose of this project was to examine the potential effect of a worksite yoga program on self-acceptance, quality of life, and perceived stress. A prospective cohort pilot study that examined a structured worksite yoga program was designed and tailored to individuals new to yoga. The 8-week Yoga Foundations program was conducted at an academic medical center's worksite wellness center with 86 subjects. Outcome measures were the 36-item Self-Acceptance Scale; a six-item quality-of-life measure that assesses overall, social, mental, physical, emotional, and spiritual well-being; and the ten-item Perceived Stress Scale. Participants demonstrated significant improvement in their overall self-acceptance (p &lt; 0.001), quality of life (p &lt; 0.001), and perceived stress (p &lt; 0.001) levels. They also highly rated the yoga instructors and the weekly format of the program. Participation in a Yoga Foundations program was associated with improvements in self-acceptance, quality of life and stress levels in worksite wellness center members. Future studies should use randomized designs and examine other wellness domains to learn more about the potential benefits of worksite yoga programs.

Abstract Background After radical prostatectomy (RP), erectile dysfunction, often necessitating the need for inflatable penile prosthesis (IPP) insertion, and urinary incontinence and climacturia can ensue. Aim To assess the efficacy and safety of the mini-jupette, a mesh used to approximate the medial aspects of the 2 corporotomies at the time of IPP insertion, for the management of climacturia and urine leakage in patients with minimal incontinence. Methods We conducted a pilot multicenter study of patients with post-RP erectile dysfunction and climacturia and/or mild urinary incontinence (≤2 pads/day [ppd]) undergoing IPP insertion with concomitant placement of a mini-jupette graft. Outcomes Pre- and postoperative erectile function, continence and climacturia, and overall surgical outcomes were assessed. Results 38 patients underwent the mini-jupette procedure. The mean age of the population was 65.3 years (SD = 7.7). 30 had post-RP climacturia and 32 patients had post-RP incontinence (mean = 1.3 ppd, SD = 0.8). 31 patients received Coloplast Titan, 4 received AMS 700 LGX, and 3 received AMS 700 CX IPPs. Mean corporotomy size was 2.9 cm (SD = 1.0). Mean graft measurements were 3.2 cm (SD = 0.9) for width, 3.3 cm (SD = 1.3) for length, and 11.0 cm2 (SD = 5.1) for surface area. At a mean follow-up of 5.1 months (SD = 6.9), there were 5 postoperative complications (13.2%) of which 4 required explantation. Climacturia and incontinence were subjectively improved in 92.8% and 85.7%, respectively. Mean ppd decreased by 1.3 postoperatively. Clinical Implications The Andrianne mini-jupette is a feasible adjunct to IPP placement that can be used for subsets of patients with post-RP climacturia and/or minimal incontinence. Strengths and Limitations Strengths of this study include the novel nature of this intervention, the multi-institutional nature of the study, and the promising results demonstrated. Limitations include the retrospective nature of the study and the heterogeneity of the techniques and grafts used by different surgeons involved. Conclusion Longer follow-up and larger patient cohorts are needed to confirm the long-term safety and benefits of this intervention.

Key Points Hematology-oncology fellowship graduates spend a relatively small proportion of their time practicing nonmalignant hematology. Factors that may increase interest in nonmalignant hematology include better access to mentors and improved opportunities for career growth.