Racial and Ethnic Segregation in Primary Care and Association of Practice Composition With Quality of Care.

OBJECTIVE: To assess the extent of segregation between racial and ethnic minority and White patients across primary care physicians and the association of practice panel racial/ethnic composition with the quality of care delivered. RESEARCH DESIGN: We examined the degree of racial/ethnic dissimilarity (a measure of segregation) in visits and the allocation of patient visits by different groups across primary care physicians (PCPs). We assessed the regression-adjusted relationship between the racial/ethnic composition of PCP practices and measures of the quality of care delivered. We compared outcomes in the pre-Affordable Care Act (ACA) and post-ACA (2006-2010/2011-2016) periods. SUBJECTS: We analyzed data on all primary care visits to office-based practitioners in the 2006-2016 National Ambulatory Medical Care Survey. PCPs were defined as general/family practice or internal medicine physicians. We excluded cases with imputed race or ethnicity information. For the quality of care analyses, we limited the sample to adults. RESULTS: Racial and ethnic minority patients remain concentrated within a small group of PCPs: 35% of PCPs accounted for 80% of non-White patients' visits; 63% of non-White (or White) patients would need to switch physicians to make the distribution of visits across PCPs proportional between the groups. We observed little correlation between the PCPs panel's racial/ethnic composition and quality of care. These patterns did not change substantially over time. CONCLUSIONS: PCPs remain segregated, but the racial/ethnic composition of a practice panel is not associated with the quality of health care that individual patients receive in either the pre or post-ACA passage periods.

Facilitating diabetic retinopathy screening using automated retinal image analysis in underresourced settings.

AIM: To evaluate an automated retinal image analysis (ARIA) of indigenous retinal fundus images against a human grading comparator for the classification of diabetic retinopathy (DR) status. METHODS: Indigenous Australian adults with type 2 diabetes (n = 410) from three remote and very remote primary-care services in the Northern Territory, Australia, underwent teleretinal DR screening. A single, central retinal fundus photograph (opportunistic mydriasis) for each eye was later regraded using a single ARIA and a UK human grader and national DR classification system. The sensitivity and specificity of ARIA were assessed relative to the comparator. Proportionate agreement and a Kappa statistic were also computed. RESULTS: Retinal images from 391 and 393 participants were gradable for 'Any DR' by the human grader and ARIA grader, respectively. 'Any DR' was detected by the human grader in 185 (47.3%) participants and by ARIA in 202 (48.6%) participants (agreement =88.0%, Kappa = 0.76,), whereas proliferative DR was detected in 31 (7.9%) and 37 (9.4%) participants (agreement = 98.2%, Kappa = 0.89,), respectively. The ARIA software had 91.4 (95% CI, 86.3-95.0) sensitivity and 85.0 (95% CI, 79.3-89.5) specificity for detecting 'Any DR' and 96.8 (95% CI, 83.3-99.9) sensitivity and 98.3 (95% CI, 96.4-99.4) specificity for detecting proliferative DR. CONCLUSIONS: This ARIA software has high sensitivity for detecting 'Any DR', hence could be used as a triage tool for human graders. High sensitivity was also found for detection of proliferative DR by ARIA. Future versions of this ARIA should include maculopathy and referable DR (CSME and/or PDR). Such ARIA software may benefit diabetes care in less-resourced regions.

Post-renal transplant urolithiasis in children: an increasingly diagnosed complication: a retrospective cohort study.

OBJECTIVE: Urolithiasis in renal transplant (RTx) recipients is a potential cause of allograft loss if obstruction is untreated. It is not clear if paediatric transplant recipients are following the global trend for increased prevalence of urolithiasis over time. DESIGN/SETTING/PATIENTS: A retrospective chart review was undertaken to evaluate the frequency, risk factors and characteristics of post-RTx urolithiasis over two decades (1995-2016), in a tertiary Australian paediatric hospital. RESULTS: Stones were diagnosed in 8 of 142 (5.6%) recipients, 6 of whom were transplanted in the latter decade. All patients were male, with a median age 4.9 years and median weight 11.8 kg. Presentation was with haematuria (n=4), pain (n=2), dysuria (n=2), stone passage (n=1) and asymptomatic (n=1). Time to presentation was bimodal; three stones were identified in the initial 3 months post RTx and the remainder after 31-53 months. Two stones were in association with retained suture material and two patients had recurrent urinary tract infections. The average stone size was 8.4 mm. Five stones were analysed; all contained calcium oxalate, three were mixed, including one with uric acid. Five (83.3%) children had hypercalciuria but none had hypercalcaemia. Cystolithotripsy was the the most common treatment (n=5), in combination with citrate supplementation. No graft was lost due to stones. CONCLUSIONS: Calculi occur with increasing frequency after renal transplantation. Clinicians need a high index of suspicion as symptoms may be atypical in this population. The cause for the increased frequency of stones in transplant recipients is not clear but is in keeping with the increase seen in the general paediatric population.

Histopathological Predictors of Recurrence in Stage III Colon Cancer: Reappraisal of Tumor Deposits and Tumor Budding Using AJCC8 Criteria.

Patients with stage III colonic adenocarcinoma have a spectrum of risk for recurrent disease, and histopathological variables that predict recurrence can help stratify patients into prognostic groups. To identify histopathological predictors of recurrence, we investigated the effect of implementation of the eighth edition of the American Joint Committee on Cancer (AJCC8) staging system definition of tumor deposits and International Tumor Budding Consensus Conference (ITBCC) criteria for tumor budding compared with other known prognostic variables in 256 resected colonic adenocarcinomas, including 150 stage III and 106 stage II tumors. In stage III colon cancer, tumor deposits and high tumor budding were the only independent histological variables that predicted disease recurrence. In a multivariable analysis in stage III colon cancer, tumor deposits and high tumor budding were associated with a 2.2- and 1.5-fold increased risk of developing disease recurrence, respectively (95% CI = 1.1-4,2, P = .02, and 95% CI = 1.1-2.1, P = .01, respectively). The negative prognostic effect of tumor deposits was most pronounced in patients with stage IIIB disease in which tumor deposits were associated with a 3.2-fold increased risk of disease recurrence (95% CI = 1.4-7.1; P = .005). Within the N1 cohort, patients with tumor deposits without concurrent positive lymph nodes (N1c) had a significantly decreased disease-free survival compared with patients with N0 tumors ( P < .001) and patients with N1a/b tumors ( P = .02). As independent risk factors for recurrence, tumor deposits and high tumor budding are important histopathological variables and should be included as a part of a routine comprehensive pathological risk assessment in stage III colon cancer.

Intra-abdominal Complications After Pediatric Kidney Transplantation: Incidence and Risk Factors.

BACKGROUND: The incidence and types of intra-abdominal complications after pediatric transplantation are not well established, and specific risk groups have not been clearly identified. METHODS: A retrospective chart review of all pediatric transplant recipients between 1995 and 2016 was undertaken. Intra-abdominal complications were grouped into 4 categories: fluid collections, gastrointestinal, vascular, and urogenital. Donor, recipient, and transplant characteristics were evaluated using univariate and multivariate logistic regressions. RESULTS: There were 146 transplants meeting the inclusion criteria. The mean follow-up time was 4.6 ± 3.7 years (range, 0.3-18 y). The mean weight at transplantation was 31.5 ± 16.5 kg (range, 9-78), with 24 (16%) recipients being <15 kg and 23% younger than 5 years. Thirty-four (23%) patients had previous abdominal surgery. There were 32 complications identified in 27 (18%) transplant recipients. Fluid collections requiring surgical drainage developed in 9 (6.2%), gastrointestinal surgical complications in 12 (8.2%), vascular complications in 5 (3.5%), and urogenital complications in 6 (4.1%). There were only 3 graft losses due to abdominal complications, all after renal vein thrombosis. Weight <15 kg at the time of transplant (P = 0.016), previous abdominal surgery (P = 0.047), and intraperitoneal surgical technique (P = 0.008) were risk factors in the univariate analysis using Cox regression models, whereas only weight <15 kg (P = 0.003) and previous abdominal surgery (P = 0.008) were retained in the multivariate analysis. CONCLUSIONS: Intraabdominal complications occur in almost 1 in 5 pediatric renal transplant recipients. Weight <15 kg and previous abdominal surgery are risk factors for developing such complications.

Site-specific Differences in Colonic Adenocarcinoma: KRAS Mutations and High Tumor Budding Are More Frequent in Cecal Adenocarcinoma.

Recent literature indicates that adenocarcinomas of the cecum differ with respect to molecular alterations compared with noncecal proximal colon adenocarcinomas and that cecal tumor site may be a prognostically relevant variable. We compared molecular alterations, histopathologic features, and disease-specific survival in a series of 328 colonic adenocarcinomas identified over a 2-year period and stratified by tumor location (cecum, right colon, and left colon). Overall, cecal adenocarcinomas demonstrated the highest frequency of molecular abnormalities with 74% harboring either a KRAS exon 2 or 3 mutation, a BRAF mutation, or DNA mismatch repair protein deficiency. KRAS mutations were more frequently seen in the cecum compared with all other tumor sites (P=0.03). KRAS mutations were identified in 46% of cecal adenocarcinomas compared with only 25% of adenocarcinomas of the right colon (P=0.004). Cecal adenocarcinomas more frequently displayed adverse histopathologic features, in particular high tumor budding (31%), compared with tumors of the right colon (18%; P=0.04) and tumors of the left colon (17%; P=0.02). Overall stage was the most important independent predictor of disease-specific survival in the multivariable analysis; however, cecal tumor site and high tumor budding were also predictive of poor survival, particularly in patients with stage III or IV tumors. In conclusion, cecal adenocarcinomas are characterized by a high frequency of KRAS mutations compared with noncecal right colon tumors, frequently display high tumor budding, and may be a prognostically relevant variable, particularly in patients with stage III or IV disease.

Mucinous and Signet Ring Cell Differentiation Affect Patterns of Metastasis in Colorectal Carcinoma and Influence Survival.

Peritoneal metastasis in colorectal carcinoma is associated with a dismal prognosis; however, features that correlate with patterns of metastatic spread are not well characterized. We analyzed the clinicopathologic and molecular features of 166 patients with colorectal carcinomas stratified by metastases to the peritoneum or liver. Mucinous and signet ring cell differentiation were more frequently observed in colorectal carcinoma with peritoneal dissemination compared to colorectal carcinoma with liver metastasis (mucinous differentiation: 62% vs 23%, P < .001; signet ring cell differentiation: 21% vs 0%, P < .0001). The significant association of mucinous differentiation with peritoneal dissemination compared with liver metastasis was identified in patients with both synchronous and metachronous development of metastasis ( P < .01). In contrast, colorectal carcinomas with liver metastasis were more frequently low-grade (90% vs 72%, P = .005) and associated with dirty necrosis (81% vs 56%, P = .001) compared with colorectal carcinomas with peritoneal dissemination. No significant differences were identified between colorectal carcinoma with peritoneal metastasis versus liver metastasis with respect to KRAS mutations, BRAF mutation, or high levels of microsatellite instability. Patients with tumors involving the peritoneum had a significantly worse overall survival in comparison to patients with liver metastasis lacking peritoneal involvement ( P = .02). When including only those patients with peritoneal metastasis, the presence of any mucinous or signet ring cell differentiation was associated with a significantly worse overall survival ( P = .006). Our findings indicate that mucinous and signet ring cell differentiation may be histologic features that are associated with an increased risk of peritoneal dissemination and poor overall survival in patients with peritoneal metastasis.

Programmed Death-Ligand 1 Expression Is Common in Gastric Cancer Associated With Epstein-Barr Virus or Microsatellite Instability.

Blockade of the programmed death 1 (PD-1) pathway has emerged as a novel therapy for cancer. Therefore, development of biomarkers for response prediction, such as PD-ligand 1 (PD-L1) expression by immunohistochemistry, may help to stratify patients. Solid tumors with CD8 T-cell rich tumor microenvironment have been implicated to be associated with increased PD-L1 expression. We hypothesized that gastric cancers associated with Epstein-Barr virus infection (EBV+) or microsatellite instability (MSI), both of which are known to harbor such tumor microenvironment, are associated with increased PD-L1 expression. Forty-four resected gastric cancers including 7 EBV+, 16 MSI, and 21 microsatellite stable cancers without EBV (EBV-/MSS) were studied for PD-L1 expression and T-cell subpopulations by immunohistochemistry. Positive PD-L1 expression (PD-L1+), defined as membranous staining in either tumor cells or tumor immune infiltrates, was seen in 32 (72%) gastric cancers. EBV+ or MSI cancers showed significantly higher rates of PD-L1+ compared with EBV-/MSS cancers (7/7, 100%; 14/16, 87%; 11/21, 52%; P=0.013). PD-L1+/EBV+ and PD-L1+/MSI cancers had significantly more CD8 T cells at tumor invasive front than PD-L1+/EBV-/MSS cancers (P<0.001). PD-L1+ was not associated with the depth of invasion or nodal metastasis (P=0.534, 0.288). Multivariate analysis showed PD-L1+ was not an independent predictor of disease-free survival while MSI was (P=0.548, 0.043). In summary, EBV+ or MSI gastric cancers are more likely to express PD-L1 and have increased CD8 T cells at tumor invasive front than EBV-/MSS cancers. Our results suggest EBV infection and MSI should be investigated for predicting response to PD-1 blockade.

Do intermittent diets provide physiological benefits over continuous diets for weight loss? A systematic review of clinical trials.

Energy restriction induces physiological effects that hinder further weight loss. Thus, deliberate periods of energy balance during weight loss interventions may attenuate these adaptive responses to energy restriction and thereby increase the efficiency of weight loss (i.e. the amount of weight or fat lost per unit of energy deficit). To address this possibility, we systematically searched MEDLINE, PreMEDLINE, PubMed and Cinahl and reviewed adaptive responses to energy restriction in 40 publications involving humans of any age or body mass index that had undergone a diet involving intermittent energy restriction, 12 with direct comparison to continuous energy restriction. Included publications needed to measure one or more of body weight, body mass index, or body composition before and at the end of energy restriction. 31 of the 40 publications involved 'intermittent fasting' of 1-7-day periods of severe energy restriction. While intermittent fasting appears to produce similar effects to continuous energy restriction to reduce body weight, fat mass, fat-free mass and improve glucose homeostasis, and may reduce appetite, it does not appear to attenuate other adaptive responses to energy restriction or improve weight loss efficiency, albeit most of the reviewed publications were not powered to assess these outcomes. Intermittent fasting thus represents a valid--albeit apparently not superior--option to continuous energy restriction for weight loss.

Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade.

Previous studies have demonstrated that the prognosis of disseminated mucinous appendiceal neoplasms is highly dependent upon tumor grade. Reflecting this, the 7th edition of the American Joint Committee on Cancer (AJCC) staging system now incorporates a three-tier grading system for prognostic staging of mucinous appendiceal tumors. However, the grading criteria are not well described. In order to address this issue, we evaluated clinicopathologic and molecular features of 219 cases from 151 patients with widely disseminated appendiceal mucinous neoplasia treated at our institution between 2004 and 2012. We identified histologic features that were associated with worse overall survival on univariate analysis: destructive invasion, high cytologic grade, high tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cell component (all with P<0.0001). We used these morphologic characteristics to classify neoplasms into three grades: AJCC grade G1 lacked all adverse histologic features; AJCC grade G2 had at least one adverse histologic feature (except a signet ring cell component); and AJCC grade G3 were defined by the presence of a signet ring cell component. Patients with AJCC grade G2 and grade G3 adenocarcinomas had a significantly worse prognosis compared with AJCC grade G1 (P<0.0001 for each). A trend toward worse overall survival was identified for patients with AJCC grade G3 adenocarcinomas compared with AJCC grade G2 adenocarcinomas (P=0.07). Our multivariate analysis found that this three-tier grading system was a significant predictor of outcome (P=0.008), independent of other prognostic variables. After controlling for other prognostic variables, AJCC grade G2 was associated with a 2.7-fold increased risk of death (95% confidence interval (CI), 1.2-6.2) and AJCC grade G3 was associated with a 5.1-fold increased risk of death (95% CI, 1.7-14) relative to grade G1 tumors. Our results indicate that evaluation of a limited set of adverse histologic features allows for the separation of disseminated mucinous neoplasms of appendiceal origin into three morphologically defined and prognostically relevant grades as advocated by the AJCC.