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).
Recent data have suggested that disease biology and outcome of colon cancer may differ between right-sided and left-sided tumors. However, the literature on the prognostic value of tumor laterality ...is conflicting.
To explore differences in laterality based on disease characteristics and outcomes in a population-based cohort of early-stage colon cancer.
This investigation was a population-based retrospective cohort study of patients with early-stage colon cancer from the province of Ontario, Canada. Electronic records of treatment were linked to the Ontario Cancer Registry to identify all patients with colon cancer who underwent resection between January 1, 2002, and December 31, 2008. The date of the final analysis was October 20, 2016. The study population included a 25% random sample of all patients with resected stage I to III disease. Right-sided colon cancer was defined as any tumor arising in the cecum, ascending colon, hepatic flexure, or transverse colon. Left-sided colon cancer was defined as any tumor arising in the splenic flexure, descending colon, sigmoid colon, or rectosigmoid colon.
Overall survival (OS) and cancer-specific survival (CSS) measured from the time of resection.
This study identified 6365 patients with early-stage colon cancer (48.7% 3098 of 6365 female). Their median age was 72 years, and 51.7% (3291 of 6365) had right-sided disease. Stage distribution was 18.3% (1163 of 6365) stage I, 38.4% (2446 of 6365) stage II, and 43.3% (2756 of 6365) stage III. Patients with right-sided colon cancer were more likely to be older (median age, 73 vs 70 years; P < .001) and female (54.4% 1790 of 3291 vs 42.6% 1308 of 3074, P < .001) and have greater comorbidity. Right-sided cancers were more likely to be T4 (19.2% 631 of 3291 vs 15.9% 490 of 3074, P < .001) and poorly differentiated (21.1% 695 of 3291 vs 9.6% 295 of 3074, P < .001) but less likely to be node positive (42.0% 1383 of 3291 vs 44.7% 1373 of 3074, P = .03) compared with left-sided disease. In adjusted analyses, there was no difference in long-term survival for right-sided compared with left-sided colon cancer: the hazard ratios were 1.00 (95% CI, 0.92-1.08) for OS and 1.00 (95% CI, 0.91-1.10) for CSS. These results were consistent when the survival analyses were restricted to stage III disease: the hazard ratios were 1.03 (95% CI, 0.93-1.14) for OS and 1.10 (95% CI, 0.97-1.24) for CSS.
In this population-based cohort of early-stage resected colon cancer, disease laterality was not associated with long-term OS or CSS.
Those with cirrhosis who develop colorectal cancer (CRC) are an understudied group who may tolerate treatments poorly and are at risk of worse outcomes. This is a retrospective cohort study of 842 ...individuals from Ontario, Canada, with a pre-existing diagnosis of cirrhosis who underwent surgery for CRC between 2009 and 2017. Practice patterns, overall survival, and short-term morbidity and mortality were assessed. The most common cirrhosis etiology was non-alcoholic fatty liver disease (NAFLD) (52%) and alcohol-associated liver disease (29%). The model for end-stage liver disease score (MELD-Na) was available in 42% (median score of 9, IQR7-11). Preoperative radiation was used in 62% of Stage II/III rectal cancer patients, while postoperative chemotherapy was used in 42% of Stage III colon cancer patients and 38% of Stage II/III rectal cancer patients. Ninety-day mortality following surgery was 12%. Five-year overall survival was 53% (by Stages I-IV, 66%, 55%, 50%, and 11%, respectively). Those with alcohol-associated cirrhosis (HR 1.8, 95% CI 1.5-2.2) had lower survival than those with NAFLD. Those with a MELD-Na of 10+ did worse than those with a lower MELD-Na score (HR 1.9, 95% CI 1.4-2.6). This study reports poor survival in those with cirrhosis who undergo treatment for CRC. Caution should be taken when considering aggressive treatment.
Self-report measures of adult attachment are typically scored in ways (e.g., averaging or summing items) that can lead to erroneous inferences about important theoretical issues, such as the degree ...of continuity in attachment security and the differential stability of insecure attachment patterns. To determine whether existing attachment scales suffer from scaling problems, the authors conducted an item response theory (IRT) analysis of 4 commonly used self-report inventories: Experiences in Close Relationships scales (
K. A. Brennan, C. L. Clark, & P. R. Shaver, 1998
), Adult Attachment Scales (
N. L. Collins & S. J. Read, 1990
), Relationship Styles Questionnaire (
D. W. Griffin & K. Bartholomew, 1994
) and
J. Simpson's (1990)
attachment scales. Data from 1,085 individuals were analyzed using
F. Samejima's (1969)
graded response model. The authors' findings indicate that commonly used attachment scales can be improved in a number of important ways. Accordingly, the authors show how IRT techniques can be used to develop new attachment scales with desirable psychometric properties.
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.
Prior work has shown associations between blood transfusion (BT) and inferior outcomes during resection for colorectal cancer liver metastases (CRLM). Herein, we describe short and long-term outcomes ...relating to perioperative BT in routine clinical practice.
All CRLM resections in Ontario, Canada from 2002 to 2009 were identified using the Ontario Cancer Registry. Log-binomial regression and Cox regression were used to explore factors associated with receipt of BT and the association of BT with 5-year cancer specific (CSS) and overall survival (OS), respectively.
The study included 1310 patients; 31% (403/1310) had perioperative BT. Transfused patients had longer median length of stay (9 vs. 7 days, p < 0.001), higher 90-day mortality (9% vs. 1%, p < 0.001), greater 90-day readmission (28% vs. 16%, p < 0.001), and inferior 5-year CSS (41% vs. 48%, p = <0.001) and OS (38% vs. 47%, p < 0.001). Transfusion was independently associated with inferior CSS (HR = 1.35, 95% CI: 1.11–1.63) and OS (HR = 1.30, 95% CI: 1.10–1.53), however, excluding 90-day postoperative deaths showed these associations were no longer significant.
Perioperative BT is common in patients undergoing resection of CRLM. While transfusion is associated with greater morbidity, mortality, and inferior survival, after excluding early postoperative deaths, BT does not appear to be independently associated with CSS or OS.
Objective
The experience of a cancer diagnosis and receiving treatment can have profound impacts on health and subsequently patients may require significant support. Often, these needs are not ...identified or addressed. Given that less is known about the follow‐up requirements for head and neck cancer patients, this study aimed to describe their follow‐up needs and preferences.
Methods
In Ontario, Canada from 2012–2014, 175 patients completed a questionnaire at an appointment one year after treatment. To identify associations between characteristics and follow‐up needs, bivariate analyses and ordinal logistic regression models were employed.
Results
A diversity of follow‐up requirements was found. The most commonly reported follow‐up needs were having imaging tests performed (66%), receiving information on treatment side effects (84%) and prognosis details (95%). Many patients experienced an improvement in their health (79%) but notably, not all. Characteristics such as psychosocial and well‐being measures (functional status, anxiety, fear of recurrence, quality of life), attitudes towards follow‐up (reassurance, communication), demographics (age, sex, marital status), and stage of disease predicted needs and preferences for follow‐up care (p < 0.05).
Conclusion
While awaiting top‐level evidence, this work demonstrates the variation in needs and supports the identification of patients with higher follow‐up requirements by screening for well‐being and enquiring about expectations in follow‐up care.
Mesh infection after abdominal wall reconstruction is a rare and usually devastating complication. Herein, we describe a unique case of a delayed and non-lethal Candida albicans mesh infection after ...abdominal wall reconstruction with placement of a biologic graft impregnated with antibiotics. Mesh explantation was not required, and the wound healed by secondary intention. This work suggests that locally delivered antibiotics may change the culprit microbes of skin infections to more unusual species such as Candida spp. Future research is required to study the effect of including antifungal agents in the locally delivered antimicrobials for abdominal wall reconstructions with biological meshes.
PDF
