Implications of missing data on reported breast cancer mortality.

BACKGROUND: National cancer registries are valuable tools to analyze patterns of care and clinical outcomes; yet, missing data may impact the accuracy and generalizability of these data. We sought to evaluate the association between missing data and overall survival (OS). METHODS: Using the NCDB (National Cancer Database) and SEER (Surveillance, Epidemiology, End Results Program), we assessed data missingness among patients diagnosed with invasive breast cancer from 2010 to 2014. Key variables included demographic (age, race, ethnicity, insurance, education, income), tumor (grade, ER, PR, HER2, TNM stages), and treatment (surgery in both databases; chemotherapy and radiation in NCDB). OS was compared between those with and without missing data using Cox proportional hazards models. RESULTS: Overall, 775,996 patients in the NCDB and 263,016 in SEER were identified; missing at least 1 key variable occurred for 29% and 13%, respectively. Of those, the overwhelming majority (NCDB 80%; SEER 88%) were missing tumor variables. When compared to patients with complete data, missingness was associated with a greater risk of death: NCDB HR 1.23 (99% CI 1.21-1.25) and SEER HR 2.11 (99% CI 2.05-2.18). Patients with complete tumor data had higher unadjusted OS estimates than that of the entire sample: NCDB 82.7% vs 81.8% and SEER 83.5% vs 81.7% for 5-year OS. CONCLUSIONS: Missingness of select variables is not uncommon within large national cancer registries and is associated with a worse OS. Exclusion of patients with missing variables may introduce unintended bias into analyses and result in findings that underestimate breast cancer mortality.

Preoperative Body Image Factors Are Associated with Complications after Breast Reconstruction.

BACKGROUND: Psychological factors are broadly understood to contribute to overall health, but their contribution to wound healing is less well defined. Limited data exist on the association of preoperative psychological factors such as body image and postoperative complications. The present study analyzed the association between preoperative body image factors and postoperative complications following breast reconstruction. METHODS: This was a prospective cohort study of 302 breast cancer patients undergoing breast reconstruction from 2011 to 2015. All patients completed the BREAST-Q; demographics, surgical details, and postoperative complications were recorded. The association of body image factors by means of the BREAST-Q and postoperative complications was analyzed. RESULTS: On univariate analysis, patients who reported lower preoperative satisfaction with how they appeared in the mirror unclothed, or felt less self-confident or attractive, were significantly more likely to develop an infection postoperatively. Preoperative satisfaction scores were not associated with complications when analyzed in a multivariate fashion. On binomial logistic regression analysis, after controlling for age, body mass index, reconstruction technique, and use of radiotherapy, patients who reported less preoperative satisfaction with how comfortably bras fit or how they appeared in a mirror unclothed were at an increased risk for delayed wound healing. CONCLUSIONS: Patients with lower preoperative body satisfaction were found to have an increased incidence of infections and delayed wound healing. Although postoperative outcomes are multifactorial, the data suggest that baseline psychological factors such as body image may play a role in postoperative outcomes. Broader use of prehabilitative therapies, targeted at psychosocial factors, may warrant further investigation to optimize postoperative outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Vascularized composite allotransplantation in the United States: A retrospective analysis of the Organ Procurement and Transplantation Network data after 5 years of the Final Rule.

On July 3, 2014, the Organ Procurement and Transplantation Network (OPTN) began overseeing vascularized composite allotransplantation/allografts (VCA) in the United States. For the past 6 years, centers performing VCAs have been requested to submit data into a biometric repository, in parallel with systems used by solid organ transplant centers. Currently, 62 VCAs are reported in the entire OPTN database, with 36 of these transplants reported as performed after VCA was added to the OPTN Final Rule. Of these 36 recipients, 16 received uterus transplants, most of which (11) occurred from living donors. Ten patients received hand transplants and 6 received face transplants. Two patients received abdominal wall transplants, 1 patient received a scalp transplant, and 1 patient received a penile transplant. The present manuscript represents the query of a nationalized database for VCA type, immunosuppression treatment, and clinical outcomes for VCAs. This manuscript provides a report of the current VCA data reported to the OPTN after the Final Rule.

Extracellular vesicles from bone marrow-derived mesenchymal stromal cells support ex vivo survival of human antibody secreting cells.

Extracellular vesicles (EVs) from bone marrow (BM)-derived mesenchymal stromal cells (BM-MSC) are novel mechanisms of cell-cell communication over short and long distances. BM-MSC have been shown to support human antibody secreting cells (ASC) survival ex vivo, but whether the crosstalk between the MSC-ASC interaction can occur via EVs is not known. Thus, we evaluated the role of EVs in ASC survival and IgG secretion. EVs were isolated from irradiated and non-irradiated primary BM-MSC and were quantified. They were further characterized by electron microscopy (EM) and CD63 and CD81 immuno-gold EM staining. Human ASC were isolated via fluorescence-activated cell sorting (FACS) and cultured ex vivo with the EV fractions, the EV-reduced fractions, or conventional media. IgG Elispots were used to measure the survival and functionality of the ASC. Contents of the EV fractions were evaluated by proteomics. We saw that both irradiated and non-irradiated MSC secretome preparations afforded vesicles of a size consistent with EVs. Both preparations appeared comparable in EM morphology and CD63 and CD81 immuno-gold EM. Both irradiated and non-irradiated EV fractions supported ASC function, at 88% and 90%, respectively, by day 3. In contrast, conventional media maintained only 4% ASC survival by day 3. To identify the specific factors that provided in vitro ASC support, we compared proteomes of the irradiated and non-irradiated EV fractions with conventional media. Pathway analysis of these proteins identified factors involved in the vesicle-mediated delivery of integrin signalling proteins. These findings indicate that BM-MSC EVs provide an effective support system for ASC survival and IgG secretion.

The IDO inhibitor 1-methyl tryptophan activates the aryl hydrocarbon receptor response in mesenchymal stromal cells.

The catabolism of tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is a key step in tolerance effected by a variety of cell types, including mesenchymal stromal cells (MSCs). Trp catabolism generates molecules known as kynurenines, whose tolerance mechanisms involve activation of the Aryl Hydrocarbon Receptor (AHR). A synthetic analog of Trp, 1-methyl tryptophan (1MT), is a selective inhibitor of IDO enzymatic activity being utilized in cancer immunotherapy trials. We hypothesized 1MT might activate AHR independently of its effects on IDO. We demonstrate MSCs express AHR protein, and that in vitro treatment with 1MT causes AHR nucleotranslocation. Upon analyzing mRNA, we observed transcriptional upregulation of cytochrome p450 1a1 and 1b1 by 1MT racemic mixture (R-MT), consistent with AHR-activation. RNA-sequencing identified Nrf2, MAPK12 and IL-1a as downstream targets of 1MT. We demonstrate 1a1 and 1b1 activation by 1MT in IDO+ MSC following interferon-γ (IFN-γ) activation, suggesting AHR signaling is uncoupled from IDO catalytic function. Such a mechanism of action for 1MT may extend its usage to a wider range of patients, irrespective of tumor IDO expression. These observations support a novel paradigm by which AHR-activating compounds like 1MT can be used in cancer immunotherapy to stimulate a pro-inflammatory response.

Sleep deprivation and false memories.

Many studies have investigated factors that affect susceptibility to false memories. However, few have investigated the role of sleep deprivation in the formation of false memories, despite overwhelming evidence that sleep deprivation impairs cognitive function. We examined the relationship between self-reported sleep duration and false memories and the effect of 24 hr of total sleep deprivation on susceptibility to false memories. We found that under certain conditions, sleep deprivation can increase the risk of developing false memories. Specifically, sleep deprivation increased false memories in a misinformation task when participants were sleep deprived during event encoding, but did not have a significant effect when the deprivation occurred after event encoding. These experiments are the first to investigate the effect of sleep deprivation on susceptibility to false memories, which can have dire consequences.