Mt. Washington Pediatric Hospital

Acute diarrhoea is a serious cause of infant morbidity and mortality, and the development of preventive measures remains an important goal. Bifidobacteria (which constitute the predominant intestinal flora of breastfed infants), as well as other lactic-acid-producing organisms such as Streptococcus thermophilus, are thought to have a protective effect against acute diarrhoeal disease. However, their efficacy has not been assessed in controlled trials. In a double-blind, placebo-controlled trial, infants aged 5-24 months who were admitted to a chronic medical care hospital were randomised to receive a standard infant formula or the same formula supplemented with Bifidobacterium bifidum and S thermophilus. Patients were evaluated daily for occurrence of diarrhoea, and faecal samples, obtained weekly, were analysed for rotavirus antigen by enzyme immunoassay. Faecal samples were also obtained during an episode of diarrhoea for virological and bacteriological analyses. 55 subjects were evaluated for a total of 4447 patient-days during 17 months. 8 (31%) of the 26 patients who received the control formula and 2 (7%) of 29 who received the supplemented formula developed diarrhoea during the course of the study (p = 0.035, Fisher's exact test, two-tailed). 10 (39%) of the subjects who received the control formula and 3 (10%) of those who received the supplemented formula shed rotavirus at some time during the study (p = 0.025). The supplementation of infant formula with B bifidum and S thermophilus can reduce the incidence of acute diarrhoea and rotavirus shedding in infants admitted to hospital.

INTRODUCTION: The purpose of this study was to develop an evidence-based guideline for the use of neuromuscular ultrasound in the diagnosis of carpal tunnel syndrome (CTS). METHODS: Two questions were asked: (1) What is the accuracy of median nerve cross-sectional area enlargement as measured with ultrasound for the diagnosis of CTS? (2) What added value, if any, does neuromuscular ultrasound provide over electrodiagnostic studies alone for the diagnosis of CTS? A systematic review was performed, and studies were classified according to American Academy of Neurology criteria for rating articles of diagnostic accuracy (question 1) and for screening articles (question 2). RESULTS: Neuromuscular ultrasound measurement of median nerve cross-sectional area at the wrist is accurate and may be offered as a diagnostic test for CTS (Level A). Neuromuscular ultrasound probably adds value to electrodiagnostic studies when diagnosing CTS and should be considered in screening for structural abnormalities at the wrist in those with CTS (Level B).

Chronic abdominal pain, defined as long-lasting intermittent or constant abdominal pain, is a common pediatric problem encountered by primary care physicians, medical subspecialists and surgical specialists. Chronic abdominal pain in children is usually functional-that is, without objective evidence of an underlying organic disorder. The Subcommittee on Chronic Abdominal Pain of the American Academy of Pediatrics and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has prepared this report based on a comprehensive, systematic review and rating of the medical literature. This report accompanies a clinical report based on the literature review and expert opinion. The subcommittee examined the diagnostic and therapeutic value of a medical and psychologic history, diagnostic tests, and pharmacological and behavioral therapy. The presence of alarm symptoms or signs (such as weight loss, gastrointestinal bleeding, persistent fever, chronic severe diarrhea and significant vomiting) is associated with a higher prevalence of organic disease. There was insufficient evidence to state that the nature of the abdominal pain or the presence of associated symptoms (such as anorexia, nausea, headache and joint pain) can discriminate between functional and organic disorders. Although children with chronic abdominal pain and their parents are more often anxious or depressed, the presence of anxiety, depression, behavior problems or recent negative life events does not distinguish between functional and organic abdominal pain. Most children who are brought to the primary care physician's office for chronic abdominal pain are unlikely to require diagnostic testing. Pediatric studies of therapeutic interventions were examined and found to be limited or inconclusive.

BACKGROUND: Pneumococcal conjugate vaccines (PCV) are emerging as one of the most promising means to prevent pediatric disease. The 7-valent PCV (PCV-7) has been extensively evaluated in clinical trials, and recent evidence from the introduction of PCV-7 through national immunization programs has demonstrated impact on pneumococcal disease. METHODS: Clinical trials have shown PCV-7 to be effective against the more severe forms of pneumococcal infections: pneumonia and invasive pneumococcal disease (IPD), as well as overall child mortality. A review shows the tremendous impact PCV-7 has had to date, and the potential further benefits of the emerging multi-valent vaccines. RESULTS: Since its introduction, the PCV-7 has substantially reduced the incidence of IPD, hospital admissions due to pneumonia and acute otitis media in numerous, mostly high income, low-disease burden countries. The reductions in IPD and pneumonia have also been observed among unvaccinated age groups in countries with routine use of PCV-7, demonstrating that PCV-7 provides herd immunity. Some settings observed an increase in rate of nonvaccine serotype IPD, yet rates of overall and vaccine-serotype IPD show marked reductions post-PCV-7 introduction. Limited data are available on the impact of PCV-7 in lower income countries. The available data from efficacy trials from The Gambia and South Africa suggest that PCV-7 will have substantial impact on reducing pneumococcal disease. CONCLUSION: PCV-7 has shown dramatic reduction in disease and mortality rates in the countries in which it has been introduced. The newly introduced 10-valent and 13-valent pneumococcal vaccines are expected to have substantial disease impact, but monitoring is essential to determine their true impact and sustain further introduction of pneumococcal conjugate vaccines.

BACKGROUND: The goal of this study was to investigate the surgical management and outcomes of patients with primary colorectal cancer (CRC) and synchronous liver metastasis (sCRLM). STUDY DESIGN: Using a multi-institutional database, we identified 1,004 patients treated for sCRLM between 1982 and 2011. Clinicopathologic and outcomes data were evaluated with uni- and multivariable analyses. RESULTS: A simultaneous CRC and liver operation was performed in 329 (33%) patients; 675 (67%) underwent a staged approach ("classic" staged approach, n = 647; liver-first strategy, n = 28). Patients managed with the liver-first approach had more hepatic lesions and were more likely to have bilateral disease than those in the other 2 groups (p < 0.05). The use of staged operative strategies increased over the time of the study from 58% to 75% (p < 0.001). Liver-directed therapy included hepatectomy (90%) or combined resection + ablation (10%). A major resection (>3 segments) was more common with a staged approach (39% vs 24%; p < 0.001). Overall, 509 patients (50%) received chemotherapy in either the preoperative (22%) or adjuvant (28%) settings, with 11% of patients having both. There were 197 patients (20%) who had a complication in the postoperative period, with no difference in morbidity between staged and simultaneous groups or major vs minor hepatectomies (p > 0.05). Ninety-day postoperative mortality was 3.0%, with no difference between simultaneous and staged approaches (p = 0.94). The overall median and 5-year survivals were 50.9 months and 44%, respectively; long-term survival was the same regardless of the operative approach (p > 0.05). CONCLUSIONS: Simultaneous and staged resections for sCRLM can be performed with comparable morbidity, mortality, and long-term oncologic outcomes.

OBJECTIVE: To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome. METHODS: Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of > or =9) were enrolled at 2 hospitals during 2002-2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 microg/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation. RESULTS: The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8-15 days]) than in the placebo group (15 days [95% confidence interval: 12-17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age. CONCLUSIONS: In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.

Dodson, Rebecca M. MD; Weiss, Matthew J. MD; Cosgrove, David MD; Herman, Joseph M. MD, MSc; Kamel, Ihab MD; Anders, Robert MD, PhD; Geschwind, Jean-Francois H. MD; Pawlik, Timothy M. MD, MPH, PhD, FACS Author Information

Abstract Purpose: Microsatellite instability (MSI) and high tumor mutation burden (TMB-High) are promising pan-tumor biomarkers used to select patients for treatment with immune checkpoint blockade; however, real-time sequencing of unresectable or metastatic solid tumors is often challenging. We report a noninvasive approach for detection of MSI and TMB-High in the circulation of patients. Experimental Design: We developed an approach that utilized a hybrid-capture–based 98-kb pan-cancer gene panel, including targeted microsatellite regions. A multifactorial error correction method and a novel peak-finding algorithm were established to identify rare MSI frameshift alleles in cell-free DNA (cfDNA). Results: Through analysis of cfDNA derived from a combination of healthy donors and patients with metastatic cancer, the error correction and peak-finding approaches produced a specificity of &amp;gt;99% (n = 163) and sensitivities of 78% (n = 23) and 67% (n = 15), respectively, for MSI and TMB-High. For patients treated with PD-1 blockade, we demonstrated that MSI and TMB-High in pretreatment plasma predicted progression-free survival (hazard ratios: 0.21 and 0.23, P = 0.001 and 0.003, respectively). In addition, we analyzed cfDNA from longitudinally collected plasma samples obtained during therapy to identify patients who achieved durable response to PD-1 blockade. Conclusions: These analyses demonstrate the feasibility of noninvasive pan-cancer screening and monitoring of patients who exhibit MSI or TMB-High and have a high likelihood of responding to immune checkpoint blockade. See related commentary by Wang and Ajani, p. 6887

The American Cancer Society periodically assembles an expert advisory committee to evaluate recent evidence and update the American Cancer Society's guidelines for diet, nutrition, and cancer prevention. This year's update presents four broad guidelines to reduce cancer risk and provides information on a wide variety of topics concerning nutrition and cancer.

Defining the complex role of the microbiome in colorectal cancer and the discovery of novel, protumorigenic microbes are areas of active investigation. In the present study, culturing and reassociation experiments revealed that toxigenic strains of Clostridioides difficile drove the tumorigenic phenotype of a subset of colorectal cancer patient-derived mucosal slurries in germ-free ApcMin/+ mice. Tumorigenesis was dependent on the C. difficile toxin TcdB and was associated with induction of Wnt signaling, reactive oxygen species, and protumorigenic mucosal immune responses marked by the infiltration of activated myeloid cells and IL17-producing lymphoid and innate lymphoid cell subsets. These findings suggest that chronic colonization with toxigenic C. difficile is a potential driver of colorectal cancer in patients. SIGNIFICANCE: Colorectal cancer is a leading cause of cancer and cancer-related deaths worldwide, with a multifactorial etiology that likely includes procarcinogenic bacteria. Using human colon cancer specimens, culturing, and murine models, we demonstrate that chronic infection with the enteric pathogen C. difficile is a previously unrecognized contributor to colonic tumorigenesis. See related commentary by Jain and Dudeja, p. 1838. This article is highlighted in the In This Issue feature, p. 1825.

BACKGROUND: Graft losses due to leaks, bleeding, thrombosis, infections, and early pancreatitis are grouped together under the category of technical failure. Among these complications, massive vascular thrombosis continues to be the most important cause of early graft loss due to technical failure. Pathological evaluation of most allografts lost early in the posttransplantation period shows vascular thrombosis with associated proportional parenchymal necrosis. The morphological findings in allografts that are considered to be lost due to technical failure has not been systematically addressed. In particular, the role of acute rejection in early graft loss has not been well studied. METHODS: Seventy-four consecutive pancreas graft pancreatectomies were studied histologically to evaluate for thrombosis (recent versus organized), type of vessel involved by thrombosis (arteries, veins, or both), acute rejection grade, chronic rejection grade, endotheliitis, transplant arteritis, coagulation necrosis, acute pancreatitis, presence of infectious organisms, transplant (obliterative) arteriopathy, neoplasia, relative proportions of alpha and beta islet cells, and immunoglobulin and complement deposition. The histological findings were correlated with donor and recipient data as well as clinical presentation. RESULTS: In 23 out of 39 grafts lost in the first 4 weeks posttransplantation, the only pathological changes found were vascular thrombosis and bland ischemic parenchymal necrosis. In these cases, no underlying vascular pathology or any other specific histological change was identified. Most of these grafts (78%) were lost in less than 48 hr and all in the first 2 weeks posttransplantation. Massive vascular thrombosis occurring in an otherwise histologically normal pancreas was the most common cause of graft loss in the first 4 weeks posttransplantation (59%). In most of the remaining cases (33%), although the clinical presentation suggested technical failure, there was clear histological evidence that the massive thrombosis resulted from vascular injury due to immune damage (acute and hyperacute rejection). Increased incidence of early graft thrombosis was seen in grafts from older donors and longer cold ischemia times. After the first month posttransplantation, graft pancreatectomies revealed a wider variety of pathological processes that included severe acute rejection, combined acute and chronic rejection, chronic rejection, and infections. Acute and chronic vascular thrombosis in large and small vessels was commonly seen at all times posttransplantation; chronic, organized thrombosis was strongly associated with chronic rejection. CONCLUSIONS: (a) Early acute thrombosis occurring in a histologically normal pancreas defines a true technical failure. This study showed that acute rejection leading to massive thrombosis, which clinically simulates technical failure, results in a significant proportion of early graft losses. (b) Systematic histological evaluation of failed grafts is absolutely necessary for the accurate classification of the cause of graft loss. (c) There is morphological evidence that chronically ongoing thrombosis is an important, common, contributing factor for late graft loss.

Mechanical factors related to patellofemoral pain syndrome and maltracking are poorly understood. Clinically, the Q-angle, J-sign, and lateral hypermobility commonly are used to evaluate patellar maltracking. However, these measures have yet to be correlated to specific three-dimensional patellofemoral displacements and rotations. Thus, we tested the hypotheses that increased Q-angle, lateral hypermobility, and J-sign correlate with three-dimensional patellofemoral displacements and rotations. We also determined whether multiple maltracking patterns can be discriminated, based on patellofemoral displacements and rotations. Three-dimensional patellofemoral motion data were acquired during active extension-flexion using dynamic MRI in 30 knees diagnosed with patellofemoral pain and at least one clinical sign of patellar maltracking (Q-angle, lateral hypermobility, or J-sign) and in 37 asymptomatic knees. Although the Q-angle is assumed to indicate lateral patellar subluxation, our data supported a correlation between the Q-angle and medial, not lateral, patellar displacement. We identified two distinct maltracking groups based on patellofemoral lateral-medial displacement, but the same groups could not be discriminated based on standard clinical measures (eg, Q-angle, lateral hypermobility, and J-sign). A more precise definition of abnormal three-dimensional patellofemoral motion, including identifying subgroups in the patellofemoral pain population, may allow more targeted and effective treatments.

OBJECTIVE: The author compares the outcome of therapy in patients with massive burns with or without cultured autologous epithelial autografts. SUMMARY BACKGROUND DATA: The use of cultured keratinocytes has been controversial because of poor take and fragility. There have been no prospective series comparing the use of this technology with standard burn wound coverage. METHODS: During a 5-year period, 22 patients with an average burn size of 71.8% were treated with cultured keratinocytes and compared with a group of 42 controls with an average burn size of 61.6%. RESULTS: There was no significant difference in age, sex distribution, or third-degree component of the burn between the two groups. There was a significantly higher incidence of smoke inhalation in the cultured epithelial autograft group. There was a reduction in mortality in the cultured epithelial autograft group compared with controls, from 48% to 14% (p < 0.007). There was no difference between the two groups in other major complications, or in readmission for breakdown. CONCLUSIONS: Coverage of patients who sustain massive burns with cultured autologous epithelial cells is an important and significant advance in management.

secondary prevention E levated low-density lipoprotein cholesterol (LDL-C) is associated with an increased risk of adverse ischemic outcomes in the early post-acute coronary syndrome (ACS) period. he EVACS trial (Evolocumab in Acute Coronary Syndrome; ClinicalTrials.gov, Unique identifier: NCT03515304) enrolled patients with non-ST-segment-elevation myocardial infarction and troponin I of 5ng/mL and randomly assigned them in a 1:1 ratio to a single dose of evolocumab SQ 420 mg or matching placebo within 24 hours of presentation. We present here the LDL-C, the primary, and other atherogenic lipid outcomes, and interpret them in the clinical context by reporting the proportion of patients in each group achieving LDL-C AHA/ACC (<70 mg/dL) and ESC (<55 mg/dL for very high risk) targets at hospital discharge and 30-day follow-up. All patients received high-intensity statins unless contraindicated and were treated in accordance with current ACS guidelines. An independent Data Safety and Monitoring Board monitored the progress of the study, which was approved by the Johns Hopkins Institutional Review Board. All participants gave informed consent.

Epidemiologic and serologic data were obtained on 422 household contacts of 157 blood donor candidates in the Baltimore Regional Red Cross Blood Program who were asymptomatic chronic carriers of hepatitis B surface antigen (HBsAg) (index carriers), and on 318 household contacts of 157 blood donors who were negative for serologic markers of hepatitis B virus (index controls). Index carriers were matched to index controls and their household contacts were similar with respect to race, sex, and education level completed. HBsAg prevalence was 6.8 times higher, and antibody to HBsAg (anti-HBs) prevalence 2.7 times higher among the contacts of carriers. The combined prevalence for au hepatitis B virus markers was 29.9% among the contacts of carriers compared to 8.8% among the contacts of controls (p < 0.001). Being non-white, the sibling of a carrier, of older age, of lower educational status, and a member of a small household were significantly associated with either a higher antibody or combined hepatitis B prevalence rate. The contacts of female carriers had an HBsAg prevalence rate 4.7 times greater than the contacts of male carriers. Children who had a mother as their index carrier had an eleven fold higher HBsAg prevalence than did children who had a father as their index carrier (18.0% vs. 1.6%, p <0.005). Epidemiologic characteristics of the contacts or their Index carriers, such as the sharing of Items belonging to the index carrier, the type and frequency of sexual relations, and the frequency of potential exposure to body fluids of the index carriers were examined. Contacts of carriers who had had skin lesions in the past year had a higher prevalence of serologic markers for hepatitis B than contacts of carriers without such lesions. No sex-related factors among spouses were significantly associated with an increased prevalence of serologic markers. These data give further support to the concept that person-to-person modes of transmission are important in the spread of hepatitis B within households. The patterns of hepatitis B serologic markers observed here suggest that mother to child transmission is most important in accounting for the high HBsAg prevalence among the contacts; other presently unidentified but close types of contact best explain the patterns of antibody prevalence.

Objectives: Diverticulitis is a common disease with high clinical burden. We evaluated the joint contribution of multiple lifestyle factors to risks of incident diverticulitis. We also estimated the proportion of diverticulitis preventable by lifestyle modifications. Methods: We prospectively examined the association between lifestyle factors (red meat, dietary fiber intake, vigorous physical activity (activity with metabolic equivalent ≥6), body mass index (BMI), and smoking) and risk of diverticulitis among participants in the Health Professionals Follow-Up Study. Results: We documented 907 incident cases of diverticulitis during 757,791 person-years. High intake of red meat, low intake of dietary fiber, low vigorous physical activity, high BMI, and smoking were independently associated with increased risks of diverticulitis (allP<0.05). Low-risk lifestyle was defined as average red meat intake <51 g per day, dietary fiber intake in the top 40% of the cohort (about 23 g per day), vigorous physical activity in the highest 50% among participants with non-zero vigorous physical activity (roughly 2 h of exercise weekly), normal BMI between 18.5–24.9 kg m−2, and never-smoker. There was an inverse linear relationship between number of low-risk lifestyle factors and diverticulitis incidence (Pfor trend<0.001). Compared with men with no low-risk lifestyle factors, the multivariable relative risks of diverticulitis were 0.71 (95% confidence interval (CI): 0.59–0.87) for men with 1 low-risk lifestyle factor; 0.66 (95% CI: 0.55–0.81) for 2 low-risk factors; 0.50 (95% CI: 0.40–0.62) for 3 low-risk factors; 0.47 (95% CI: 0.35–0.62) for 4 low-risk factors, and 0.27 (95% CI: 0.15–0.48) for 5 low-risk factors. Adherence to a low-risk lifestyle could prevent 50% (95% CI: 20–71%) of incident diverticulitis. Conclusions: Adherence to a low-risk lifestyle is associated with reduced incidence of diverticulitis.

OBJECTIVE: The aim of this study was to determine whether hospital volume was associated with mortality in breast cancer, and what thresholds of case volume impacted survival. BACKGROUND: Prior literature has demonstrated improved survival with treatment at high volume centers among less common cancers requiring technically complex surgery. METHODS: All adults (18 to 90 years) with stages 0-III unilateral breast cancer diagnosed from 2004 to 2012 were identified from the American College of Surgeons National Cancer Data Base (NCDB). A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital volume and overall survival, after adjusting for measured covariates. Intergroup comparisons of patient and treatment characteristics were conducted with X and analysis of variance (ANOVA). The log-rank test was used to test survival differences between groups. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HRs) associated with each volume group. RESULTS: One million sixty-four thousand two hundred and fifty-one patients met inclusion criteria. The median age of the sample was 60 (interquartile range 50 to 70). Hospitals were categorized into 3 groups using restricted cubic spline analysis: low-volume (<148 cases/year), moderate-volume (148 to 298 cases/year), and high-volume (>298 cases/year). Treatment at high volume centers was associated with an 11% reduction in overall mortality for all patients (HR 0.89); those with stage 0-I, ER+/PR+ or ER+/PR- breast cancers derived the greatest benefit. CONCLUSIONS: Treatment at high volume centers is associated with improved survival for breast cancer patients regardless of stage. High case volume could serve as a proxy for the institutional infrastructure required to deliver complex multidisciplinary breast cancer treatment.

BACKGROUND: Surgery remains the only potentially curative option for patients with hepatocellular carcinoma (HCC) and fibrolamellar carcinoma (FLC). We sought to investigate the differences over time in surgically managed FLC compared with conventional HCC using population-based data. STUDY DESIGN: Using SEER data, we identified 7,225 patients with surgically managed FLC or HCC from 1986 to 2008. We examined differences in clinicopathologic and surgical factors associated with long-term survival. RESULTS: Of the 7,225 patients, the majority had HCC (n = 7,135; 99%) vs FLC (n = 90; 1%). Patients with FLC were younger (25 years vs 59 years) and more often were women (44% vs 27%) than patients with HCC (both p < 0.001). Regional disease was more common among patients with FLC (42.2%) vs patients with HCC (22.1%) (p < 0.001). More than one-third of patients with FLC (36.9%) were operatively managed with a hemihepatectomy compared with patients with HCC, who were more often managed with a liver transplant (p < 0.001). On univariable analysis, there was a marked difference in overall survival, with patients with FLC surviving a median of 75 months vs 43 months for HCC (hazard ratio [HR]: 0.59; p = 0.001). There was a marked difference in survival when patients were stratified by localized (FLC, 78 months vs HCC, 49 months; p = 0.012) vs regional disease (FLC, 46 months vs HCC, 23 months; p = 0.002. CONCLUSIONS: Patients with FLC have many clinicopathologic features that are different from those of patients with HCC, including younger age and female sex. Despite a higher likelihood of advanced disease at the time of diagnosis, surgically treated FLC patients had better long-term outcomes than patients with conventional HCC.

OBJECTIVE: The purpose of this study is to evaluate two updated measures of diabetes regimen adherence. The Diabetes Self-Management Profile (DSMP) is a widely used, structured interview. Limitations include a substantial interviewer and respondent time burden and the need for well-trained interviewers to use appropriate prompts and score the open-ended responses. The Diabetes Behavior Rating Scale (DBRS) is a self-administered, fixed-choice survey. RESEARCH DESIGN AND METHODS: Both measures were administered to 146 youth with type 1 diabetes (aged 11-18 years) and their parents. Items were added to the DBRS to allow for both flexible and conventional regimens, and the DSMP was modified to use standardized wording across items, accommodate flexible regimens, and permit administration by nonmedical interviewers. RESULTS: Both measures had good evidence of internal consistency (for the DSMP: parent 0.75 and youth 0.70; for the DBRS: parent 0.84 and youth 0.84). Scores on the DSMP and the DBRS were significantly related (r = 0.72 for parents and 0.74 for youth). There was moderate agreement between parent and youth (DSMP, r = 0.51; DBRS, r = 0.48). The measures were correlated with HbA1c for both parent (DSMP, r = -0.35; DBRS, r = -0.35) and youth (DSMP, r = -0.36; DBRS, r = -0.34) reports. CONCLUSIONS: Both measures exhibit good psychometric properties and good criterion validity but varied in terms of respondent and interviewer burden, issues that should be considered in selecting assessment procedures.

Abstract Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in BRAF are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (MinApcΔ716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas. Herein, we report that the addition of the BRAFV600E mutation to this model results in the emergence of a distinct locus of midcolon tumors. In ETBF-colonized BRAFV600ELgr5CreMin (BLM) mice, tumors have similarities to human BRAFV600E tumors, including histology, CpG island DNA hypermethylation, and immune signatures. In comparison to Min ETBF tumors, BLM ETBF tumors are infiltrated by CD8+ T cells, express IFNγ signatures, and are sensitive to anti–PD-L1 treatment. These results provide direct evidence for critical roles of host genetic and microbiota interactions in colorectal cancer pathogenesis and sensitivity to immunotherapy. Significance: Colorectal cancers with BRAF mutations have distinct characteristics. We present evidence of specific colorectal cancer gene–microbial interactions in which colonization with toxigenic bacteria drives tumorigenesis in BRAFV600ELgr5CreMin mice, wherein tumors phenocopy aspects of human BRAF-mutated tumors and have a distinct IFNγ-dominant immune microenvironment uniquely responsive to immune checkpoint blockade. This article is highlighted in the In This Issue feature, p. 1601