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Identification of chromosomal aneuploidies and copy number variants that are associated with fetal structural anomalies has substantial value. Although whole-exome sequencing (WES) has been applied to case series of a few selected prenatal cases, its value in routine clinical settings has not been prospectively assessed in a large unselected cohort of fetuses with structural anomalies. We therefore aimed to determine the incremental diagnostic yield (ie, the added value) of WES following uninformative results of standard investigations with karyotype testing and chromosomal microarray in an unselected cohort of sequential pregnancies showing fetal structural anomalies. In this prospective cohort study, the parents of fetuses who were found to have a structural anomaly in a prenatal ultrasound were screened for possible participation in the study. These participants were predominantly identified in or were referred to the Columbia University Carmen and John Thain Center for Prenatal Pediatrics (New York, NY, USA). Fetuses with confirmed aneuploidy or a causal pathogenic copy number variant were excluded from WES analyses. By use of WES of the fetuses and parents (parent–fetus trios), we identified genetic variants that indicated an underlying cause (diagnostic genetic variants) and genetic variants that met the criteria of bioinformatic signatures that had previously been described to be significantly enriched among diagnostic genetic variants. Between April 24, 2015, and April 19, 2017, 517 sequentially identified pregnant women found to have fetuses with a structural anomaly were screened for their eligibility for inclusion in our study. 71 (14%) couples declined testing, 87 (17%) trios were missing at least one DNA sample (from either parent or the fetus), 69 (13%) trios had a clinically relevant abnormal karyotype or chromosomal microarray finding, 51 (10%) couples did not consent to WES or withdrew consent, and five (1%) samples were not of good enough quality for analysis. DNA samples from 234 (45%) eligible trios were therefore used for analysis of the primary outcome. By use of trio sequence data, we identified diagnostic genetic variants in 24 (10%) families. Mutations with bioinformatic signatures that were indicative of pathogenicity but with insufficient evidence to be considered diagnostic were also evaluated; 46 (20%) of the 234 fetuses assessed were found to have such signatures. Our analysis of WES data in a prospective cohort of unselected fetuses with structural anomalies shows the value added by WES following the use of routine genetic tests. Our findings suggest that, in cases of fetal anomalies in which assessment with karyotype testing and chromosomal microarray fail to determine the underlying cause of a structural anomaly, WES can add clinically relevant information that could assist current management of a pregnancy. The unique challenges of WES-based prenatal diagnostics require analysis by a multidisciplinary team of perinatal practitioners and laboratory specialists. Institute for Genomic Medicine (Columbia University Irving Medical Center).

The wearable cardioverter defibrillator (WCD) is used to protect patients at risk for sudden cardiac arrest. We examined defibrillation efficacy and safety of a biphasic truncated exponential waveform designed for use in a contemporary WCD in three animal studies and a human study. Animal (swine) studies: #1: Efficacy comparison of a 170J BTE waveform (SHOCK A) to a 150J BTE waveform (SHOCK B) that approximates another commercially available waveform. Primary endpoint first shock success rate. #2: Efficacy comparison of the two waveforms at attenuated charge voltages in swine at three prespecified impedances. Primary endpoint first shock success rate. #3: Safety comparison of SHOCK A and SHOCK B in swine. Primary endpoint cardiac biomarker level changes baseline to 6 and 24 hours post-shock. Human Study: Efficacy comparison of SHOCK A to prespecified goal and safety evaluation. Primary endpoint cumulative first and second shock success rate. Safety endpoint adverse events. Animal Studies #1: 120 VF episodes in six swine. First shock success rates for SHOCK A and SHOCK B were 100%; SHOCK A non-inferior to SHOCK B (entire 95% CI of rate difference above -10% margin, p < .001). #2: 2,160 VF episodes in thirty-six swine. Attenuated SHOCK A was non-inferior to attenuated SHOCK B at each impedance (entire 95% CI of rate difference above -10% margin, p < .001). #3: Ten swine, five shocked five times each with SHOCK A, five shocked five times each with SHOCK B. No significant difference in troponin I (p = 0.658) or creatine phosphokinase (p = 0.855) changes from baseline between SHOCK A and SHOCK B. Human Study: Thirteen patients, 100% VF conversion rate. Mild skin irritation from adhesive defibrillation pads in three patients. The BTE waveform effectively and safely terminated induced VF in swine and a small sample in humans. Human study clinical trial registration: URL: https://clinicaltrials.gov; Unique identifier: NCT04132466.

•28% of resected colon cancer patients received a transfusion.•Transfusion is associated with age, female sex, advanced disease and open resection.•Transfusion is associated with worse overall survival and cancer specific survival. Literature suggests that peri-operative blood transfusion among patients with resected colon cancer may be associated with inferior long-term survival. The study objective was to characterize this association in our population. This is a retrospective cohort study using the population-based Ontario Cancer Registry (2002–2008). Pathology reports were obtained for a 25% random sample of all cases and constituted the study population. Log binomial regression was used to identify factors associated with transfusion. Cox proportional hazards model explored the association between transfusion and cancer specific survival (CSS) and overall survival (OS). The study population included 7198 patients: 18% stage I, 36% stage II, 40% stage III, and 6% stage IV. Twenty-eight percent of patients were transfused. Factors independently associated with transfusion included advanced age (p<0.001), female sex (p<0.001), greater comorbidity (p<0.001), more advanced disease (p<0.001) and open surgical resection (p<0.001). Transfusion was associated with inferior CSS (HR 1.51, 95% CI 1.38–1.65) and OS (HR 1.52, 95% CI 1.41–1.63), after adjusting for important confounders. Peri-operative transfusion rates among patients with colon cancer have decreased over time. Transfusion is associated with inferior long-term CSS and OS.

Urachal mucinous tumors are rare neoplasms with behaviour that can range from relatively benign to malignancy that can spread distantly or throughout the peritoneum as pseudomyxoma peritonei or peritoneal carcinomatosis. Here we describe a unique case of urachal mucinous cystic tumor of low malignant potential confined to an intact cyst at the dome of the urinary bladder, without rupture or peritoneal spread. The urachal mucinous tumor was an incidental finding on a staging CT scan performed for sigmoid colon adenocarcinoma. We believe that this case illustrates a potential diagnostic pitfall which could have prognostic and therapeutic implications. Due to the intestinal phenotype of these neoplasms, a urachal tumor of low malignant potential could be mistaken for metastatic spread from a colonic adenocarcinoma in the rare situation such as this case, where the two neoplasms occur concurrently.

Background Identifying optimal chemotherapy (CT) utilization rates can drive improvements in quality of care. We report a benchmarking approach to estimate the optimal rate of perioperative CT for muscle‐invasive bladder cancer (MIBC). Methods The Ontario Cancer Registry and linked treated records were used to identify neoadjuvant and adjuvant CT rates among patients with MIBC during 2004‐2013. Monte Carlo simulation was used to estimate the proportion of observed rate variation that could be due to chance alone. The criterion‐based benchmarking approach was used to explore whether social and health‐system factors were associated with CT rates. We also used the “pared‐mean” approach to identify a benchmark population of hospitals with the highest treatment rates. Hospital CT rates were adjusted for case mix and simulated using a multi‐level multivariable model and a parametric bootstrapping approach. Results The study population included 2581 patients; perioperative CT was delivered to 31% (798/2581). Multivariate analysis showed that treatment was strongly associated with patient socioeconomic status and hospital teaching status. The benchmark rate was 36%. Unadjusted CT rates were significantly different across hospitals (range 0%‐52%, P < .001). The unadjusted benchmark perioperative CT rate was 45% (95% CI 40%‐50%); utilization rate in nonbenchmark hospitals was 28% (95% CI 26%‐30%). When using simulated CT rates adjusted for case mix, the benchmark CT rate was 41% (95% CI 35%‐47%) and the nonbenchmark hospital CT rate was 30% (95% CI 28%‐32%). The simulation analysis suggested that the observed component of variation (38%) was outside the 95% CI (22%‐28%) of what could be expected due to chance alone. Conclusions There is significant systematic variation in perioperative CT rates for MIBC across hospitals in routine practice. The benchmark perioperative CT rate for MIBC is 36%‐41%. Identifying optimal chemotherapy (CT) utilization rates can drive improvements in quality of care. In this benchmarking study of neoadjuvant chemotherapy for muscle‐invasive bladder cancer (MIBC), we found that treatment was strongly associated with patient socioeconomic status and hospital teaching status. The benchmark rate of neoadjuvant chemotherapy for MIBC was 36%‐41%.

Introduction One way to examine the extent to which the stress associated with a breast cancer experience (BC) impacts stress-related physiological mechanisms is to study the secretion patterns of associated biomarkers. Unlike cortisol and α-amylase (sAA), biomarkers of immune functioning such as secretory immunoglobulin A (SIgA) have rarely been examined in BC survivors. Aim of the study This study had two principal aims: the first was to evaluate the basal secretion profiles of SIgA as well as its response to an acute stressor as a marker of immune health in BC survivors and women with no history of BC, and the second was to determine how SIgA stress-related patterns compare to published cortisol and sAA patterns in the same women. Results Overall, the findings indicate that BC survivors exhibit a blunted cortisol reaction to an acute stressor, a generally elevated diurnal sAA concentration pattern, and normal SIgA profiles, compared to women with no history of cancer. This study serves as a foundation for future research to elucidate the relationships between BC experience variables, stress biomarkers, and health outcomes in BC survivors.

Background Identifying optimal chemotherapy utilization rates can drive improvements in quality of care. We report a benchmarking approach to estimate the optimal rate of adjuvant chemotherapy (ACT) for stage III colon cancer. Methods The Ontario Cancer Registry and linked treated records were used to identify ACT utilization. Monte Carlo simulation was used to estimate the proportion of ACT rate variation that could be due to chance alone. The criterion‐based benchmarking approach was used to explore whether socioeconomic or system‐level factors were associated with ACT. We also used the “pared‐mean” approach to identify a benchmark population of hospitals with the highest ACT rates. Results The study population included 2801 patients; ACT was delivered to 66% (1861/2801). Monte Carlo simulation suggested that the observed component of variation (15.6%) in ACT rates was within the 95% CI (11.5%‐17.3%) of what could be expected due to chance alone; the nonrandom component of ACT rate variation across hospitals was only 1.5%. There was no difference in hospital ACT rate by teaching status (P = .107), cancer center status (P = .362), or having medical oncology on site (P = .840). Unadjusted ACT rates varied across hospitals (range 44%‐91%, P = .017). The unadjusted benchmark ACT rate was 81% (95%CI 76%‐86%); utilization rate in non‐benchmark hospitals was 65% (95%CI 63%‐66%). However, after adjusting for case mix, the difference in ACT utilization between benchmark and non‐benchmark populations was significantly smaller. Conclusions We did not find any system‐level factors associated with the utilization of ACT. Our results suggest that the observed variation in hospital ACT rate is not significantly different from variation due to chance alone. Using the “pared‐mean” approach may significantly overestimate optimal treatment rates if case mix is not considered. Identifying optimal chemotherapy utilization rates can drive improvements in quality of care. This benchmarking study of adjuvant chemotherapy (ACT) rates for stage III colon cancer showed that there were no system‐level factors associated with the utilization of ACT and that “pared‐mean” approach may significantly overestimate optimal treatment rates if case mix is not considered.