An independent comparison of the Novolytix salivary melatonin radioimmunoassay with the new Novolytix salivary melatonin enzyme-linked immunosorbent assay.

The dim light melatonin onset (DLMO) is the current gold standard biomarker of the timing of the central circadian clock in humans and is often assessed from saliva samples. To date, only one commercially available salivary melatonin assay is considered accurate at the low daytime levels required to accurately detect the DLMO (Novolytix RIA RK-DSM2). The aim of this study was to conduct the first independent evaluation of a newly improved enzyme-linked immunosorbent assay (ELISA; Novolytix MLTN-96) and compare it with the recommended radioimmunoassay (RIA)-both in terms of melatonin concentrations and derived DLMOs. Twenty participants (15 females, 18-59 years old) provided saliva samples every 30 min in dim light starting 6 h before their habitual bedtime, yielding a total of 260 saliva samples. Both the RIA and ELISA yielded daytime melatonin concentrations <2 pg/mL, indicating adequate accuracy to detect the DLMO. The melatonin concentrations from the two assays were highly correlated (r = .94, p < .001), although the RIA yielded lower levels of melatonin concentration than the ELISA, on average by 0.70 pg/mL (p = .006). Seventeen DLMOs were calculated from the melatonin profiles and the DLMOs from both assays were not statistically different (p = .36) and were highly correlated (r = .97, p < .001). Two DLMOs derived from the RIA occurred more than 30 min earlier than the DLMO derived from the ELISA. These results indicate that the new Novolytix ELISA is an appropriate assay to use if the Novolytix RIA is not feasible or available.

DNA Methylation Is a Potential Biomarker for Cardiometabolic Health in Mexican Children and Adolescents.

DNA methylation (DNAm) is a plausible mechanism underlying cardiometabolic abnormalities, but evidence is limited among youth. This analysis included 410 offspring of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort followed up to two time points in late childhood/adolescence. At Time 1, DNAm was quantified in blood leukocytes at long interspersed nuclear elements (LINE-1), H19, and 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD-2), and at Time 2 in peroxisome proliferator-activated receptor alpha (PPAR-α). At each time point, cardiometabolic risk factors were assessed including lipid profiles, glucose, blood pressure, and anthropometry. Linear mixed effects models were used for LINE-1, H19, and 11ß-HSD-2 to account for the repeated-measure outcomes. Linear regression models were conducted for the cross-sectional association between PPAR-α with the outcomes. DNAm at LINE-1 was associated with log glucose at site 1 [ß = -0.029, p = 0.0006] and with log high-density lipoprotein cholesterol at site 3 [ß = 0.063, p = 0.0072]. 11ß-HSD-2 DNAm at site 4 was associated with log glucose (ß = -0.018, p = 0.0018). DNAm at LINE-1 and 11ß-HSD-2 was associated with few cardiometabolic risk factors among youth in a locus-specific manner. These findings underscore the potential for epigenetic biomarkers to increase our understanding of cardiometabolic risk earlier in life.

A nationally representative sample of veteran and matched non-veteran college students: Mental health symptoms, suicidal ideation, and mental health treatment.

Objective To assess mental health symptoms, suicidal ideation/behaviors, and treatment among a nationally representative probability sample of student veterans. Participants: Student veterans enrolled in post-secondary educational institutions and matched comparison students. Methods: Sampled participants completed an online survey (n = 1,838). Analyses accounted for the complex sample design and non-response. Results: Substantial percentages of student veterans screened positive for: depression (36.9%, 95% CI: 31.1-42.7), PTSD (35.7%, 95% CI 29.9-41.5), anxiety (29.5%, 95% CI 26.8-32.2), and suicidal ideation (14.6%, 95% CI 12.1-17.1), with student veterans having odds ratios between 1.7 to 2.4 for positive screens compared to non-veteran students. Only 41.5% (95% CI 33.0-50.0) of student veterans with positive screens received treatment, although they had 50% higher odds of receiving treatment than non-veteran students. Conclusions: Student veterans have high rates of mental health symptoms and low rates of treatment. However, they are more likely to receive treatment than comparison students.

Perceived versus Patient-Reported Significance of Surgeon Gender in Breast Reconstruction.

BACKGROUND: Previous investigators demonstrated that female patients often prefer female providers. However, these studies have not determined whether there are gender preferences for breast reconstruction surgeons or whether the effects of surgeon gender impacts patient-reported outcomes. METHODS: Adult women were crowdsourced using Amazon Mechanical Turk to characterize societal preferences for the gender of breast and plastic surgeons in a hypothetical scenario. The authors also used data from the Mastectomy Reconstruction Outcomes Consortium to determine the association between surgeon gender and patient satisfaction after breast reconstruction. The BREAST-Q questionnaire was used to assess patient-reported outcomes at 3 months and 2 years following reconstruction. Regression analyses were performed to investigate the effects of surgeon gender on patient-reported outcomes. RESULTS: In total, 1413 surveys were collected. Forty-two percent preferred female plastic surgeons, 5 percent preferred male surgeons, and 53 percent reported no preference. The Mastectomy Reconstruction Outcomes Consortium analysis included 2236 patients of 55 male and nine female plastic surgeons. In this cohort, 1921 patients (82.2 percent) had male surgeons, whereas 415 patients (17.8 percent) had female surgeons. Regression analysis at 2 years revealed no differences in satisfaction with surgeon, outcome, or psychosocial well-being. Only satisfaction with information differed, as patients of female surgeons reported greater satisfaction in this category, with an adjusted mean difference of 2.82 (p = 0.018). CONCLUSIONS: Although nonpatient women hypothetically prefer female providers, surgeon gender makes little difference in actual patient satisfaction with breast reconstruction. More investigation is needed to determine whether the difference in information delivery is clinically significant and whether it reflects variations in practices between male and female surgeons. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Association of Clinical Complications of Chemotherapy and Patient-Reported Outcomes After Immediate Breast Reconstruction.

Importance: Women undergoing immediate breast reconstruction often require chemotherapy. The effects of chemotherapy on reconstruction are not well described. Objective: To evaluate the association of neoadjuvant and adjuvant chemotherapy with complications and patient-reported outcomes (PROs) in immediate reconstruction. Design, Setting, and Participants: The Mastectomy Reconstruction Outcomes Consortium Study is a cohort study that prospectively assessed PROs and retrospectively evaluated complications in patients undergoing immediate implant-based or autologous reconstruction at 11 centers from January 1, 2012, to December 31, 2017. Women 18 years or older undergoing immediate reconstruction after mastectomy with 2 years of follow-up were included. Patients were excluded if they had prophylactic mastectomy; delayed reconstruction; mixed-timing reconstruction; mixed reconstruction; a latissimus dorsi, superior gluteal artery perforator, or inferior gluteal artery perforator flap; or both neoadjuvant and adjuvant chemotherapy. Data were analyzed from May 1 to June 30, 2018. Main Outcomes and Measures: Complications and PROs (satisfaction with breast and physical, psychosocial, and sexual well-being) using the BREAST-Q questionnaire, a validated, condition-specific PRO measure. Baseline patient characteristics were collected. Results: A total of 1881 women were included in the analysis (mean [SD] age, 49.9 [9.9] years). Of these, 1373 (73.0%) underwent implant-based procedures; 508 (27.0%), autologous reconstruction; 200 (10.6%), neoadjuvant chemotherapy; 668 (35.5%), adjuvant chemotherapy; and 1013 (53.9%), no chemotherapy. Patients without chemotherapy were significantly older (mean [SD] age, 51.6 [9.4] years; P < .001), and patients with chemotherapy were more likely to have received radiotherapy (108 of 200 [54.0%] for neoadjuvant chemotherapy and 321 of 668 [48.1%] for adjuvant chemotherapy; P < .001). Among the cohort undergoing implant-based reconstruction, the rates of any complication were significantly different, with higher rates seen for adjuvant (153 of 490 [31.2%]) and neoadjuvant (44 of 153 [28.8%]) chemotherapy compared with no chemotherapy (176 of 730 [24.1%]; P = .02). On multivariable analysis, these differences were not statistically significant. For autologous reconstruction, no significant differences in complications were observed. Controlling for clinical covariates, no significant differences were seen across chemotherapy groups for the BREAST-Q subscales except for sexual well-being in the implant cohort, in which adjuvant chemotherapy had significantly lower scores (ß, -4.97 [95% CI, -8.68 to -1.27]; P = .009). Conclusions and Relevance: In this cohort study, neither neoadjuvant nor adjuvant chemotherapy was associated with the likelihood of complications in patients undergoing implant-based or autologous reconstruction, and chemotherapy was not associated with patient satisfaction with reconstruction or psychosocial well-being. This information can help patients and clinicians make informed decisions about breast reconstruction in the setting of chemotherapy.

Comparing Nipple-sparing Mastectomy to Secondary Nipple Reconstruction: A Multi-institutional Study.

OBJECTIVE: The primary aim of this study was to compare patient-reported outcomes (PROs) of women who underwent immediate implant-based breast reconstruction (IBBR) after receiving either: (1) nipple-sparing mastectomy (NSM) or (2) simple mastectomy with subsequent nipple reconstruction (SNR). BACKGROUND: The goal of post-mastectomy breast reconstruction is to restore body image and quality-of-life after mastectomy, but removal of the nipple-areolar complex may have its own negative psychosocial consequences. NSM may have increased in popularity due to its perceived oncologic safety in many women and to reports of superior aesthetic results with this technique. Despite the increased utilization of NSM, few studies have evaluated the impact of NSM on PROs and complications in women undergoing immediate IBBR. METHODS: We performed a secondary analysis of the Mastectomy Reconstruction Outcomes Consortium study, a multicenter, prospective cohort study that recruited patients between February 2012 and July 2015. The primary aim of this study was to compare PROs as measured by BREAST-Q scores between women who underwent IBBR after NSM versus SNR. The secondary aim was to compare complication rates. Mixed-effects regression models controlled for demographic and clinical covariates. RESULTS: Of the 600 women in the study, 286 (47.7%) underwent NSM. After controlling for baseline patient characteristics, we found no significant differences in satisfaction with breast, psychosocial well-being, physical well-being or sexual well-being between women undergoing NSM versus SNR. Mastectomy type was not a significant predictor of complications or reconstructive failure. CONCLUSIONS: Despite reports of superior aesthetics for NSM over simple mastectomy with nipple reconstruction in immediate IBBR, we found no significant differences at 2 years after reconstruction in patient satisfaction, quality-of-life, or complication rates.

Development of an evidence-based approach to the use of acellular dermal matrix in immediate expander-implant-based breast reconstruction.

BACKGROUND: Although acellular dermal matrix (ADM) is widely used in expander-implant-based breast reconstructions, previous analyses have been unable to demonstrate improvements in patient-reported outcomes (PROs) with this approach over non-ADM procedures. This study aims to develop a more selective, evidence-based approach to the use of ADM in expander-implant-based breast reconstruction by identifying patient subgroups in which ADM improved clinical outcomes and PROs. STUDY DESIGN: The Mastectomy Reconstruction Outcomes Consortium Study prospectively evaluated immediate expander-implant reconstructions at 11 centers from 2012 to 2015. Complications (any/overall and major), and PROs (satisfaction, physical, psychosocial, and sexual well-being) were assessed two years postoperatively using medical records and the BREAST-Q, respectively. Using mixed-models accounting for centers and with interaction terms, we analyzed for differential ADM effects across various clinical subgroups, including age, body mass index, radiation timing, and chemotherapy. RESULTS: Expander-implant-based breast reconstruction was performed in 1451 patients, 738 with and 713 without ADM. Major complication risk was higher in ADM users vs. nonusers (22.9% vs. 16.4% and p = 0.04). Major complication risk with ADM increased with higher BMI (BMI=30, OR=1.70; BMI=35, OR=2.29, interaction p = 0.02). No significant ADM effects were observed for breast satisfaction, psychosocial, sexual, and physical well-being within any subgroups. CONCLUSION: In immediate expander-implant-based breast reconstruction, ADM was associated with a greater risk of major complications, particularly in high-BMI patients. We were unable to identify patient subgroups where ADM was associated with significant improvements in PROs. Given these findings and the financial costs of ADM, a more critical approach to the use of ADM in expander-implant reconstruction may be warranted.

Arrhythmia exacerbation after post-infarction ventricular tachycardia ablation: prevalence and prognostic significance.

AIMS: Catheter ablation is an effective treatment for post-infarction ventricular tachycardia (VT). However, some patients may experience a worsened arrhythmia phenotype after ablation. We aimed to determine the prevalence and prognostic impact of arrhythmia exacerbation (AE) after post-infarction VT ablation. METHODS AND RESULTS: A total of 1187 consecutive patients (93% men, median age 68 years, median ejection fraction 30%) who underwent post-infarction VT ablation at six centres were included. Arrhythmia exacerbation was defined as post-ablation VT storm or incessant VT in patients without prior similar events. During follow-up (median 717 days), 426 (36%) patients experienced VT recurrence. Events qualifying as AE occurred in 67 patients (6%). Median times to VT recurrence with and without AE were 238 [interquartile range (IQR) 35-640] days and 135 (IQR 22-521) days, respectively (P = 0.25). Almost half of the patients (46%) who experienced AE experienced it within 6 months of the index procedure. Patients with AE had had longer ablation times during the ablation procedures compared to the rest of the patients (median 42 vs. 34 min, P = 0.02). Among patients with VT recurrence, the risk of death or heart transplantation was significantly higher in patients with than without AE (hazard ratio 1.99, 95% CI 1.28-3.10; P = 0.002) after adjusting for age, gender, ejection fraction, cardiac resynchronization therapy, post-ablation non-inducibility, and post-ablation amiodarone use. CONCLUSION: Arrhythmia exacerbation after ablation of infarct-related VT is infrequent but is independently associated with an adverse long-term outcome among patients who experience a VT recurrence. The mechanisms and mitigation strategies of AE after catheter ablation require further investigation.

Patient-Reported Outcomes after Irradiation of Tissue Expander versus Permanent Implant in Breast Reconstruction: A Multicenter Prospective Study.

BACKGROUND: Whether to irradiate the tissue expander before implant exchange or to defer irradiation until after exchange in immediate, two-stage expander/implant reconstruction remains uncertain. The authors evaluated the effects of irradiation timing on complication rates and patient-reported outcomes in patients undergoing immediate expander/implant reconstruction. METHODS: Immediate expander/implant reconstruction patients undergoing postmastectomy radiation therapy at 11 Mastectomy Reconstruction Outcomes Consortium sites with demographic, clinical, and complication data were analyzed. Patient-reported outcomes were assessed with BREAST-Q, Patient-Reported Outcomes Measurement Information System, and European Organisation for Research and Treatment of Cancer Breast Cancer-Specific Quality-of-Life Questionnaire surveys preoperatively and 2 years postoperatively. Survey scores and complication rates were analyzed using bivariate comparison and multivariable regressions. RESULTS: Of 317 patients who met inclusion criteria, 237 underwent postmastectomy radiation therapy before expander/implant exchange (before-exchange cohort), and 80 did so after exchange (after-exchange cohort). Timing of radiation had no significant effect on risks of overall complications (OR, 1.25; p = 0.46), major complications (OR, 1.18; p = 0.62), or reconstructive failure (OR, 0.72; p = 0.49). Similarly, radiation timing had no significant effect on 2-year patient-reported outcomes measured by the BREAST-Q or the European Organisation for Research and Treatment of Cancer survey. Outcomes measured by the Patient-Reported Outcomes Measurement Information System showed less anxiety, fatigue, and depression in the after-exchange group. Compared with preoperative assessments, 2-year patient-reported outcomes significantly declined in both cohorts for Satisfaction with Breasts, Physical Well-Being, and Sexual Well-Being, but improved for anxiety and depression. CONCLUSIONS: Radiation timing (before or after exchange) had no significant effect on complication risks or on most patient-reported outcomes in immediate expander/implant reconstruction. Although lower levels of anxiety, depression, and fatigue were observed in the after-exchange group, these differences may not be clinically significant. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Outcomes of Immediate Implant-Based Mastectomy Reconstruction in Women with Previous Breast Radiotherapy.

BACKGROUND: The objective of this study was to determine whether women with a history of radiation therapy before mastectomy experience a risk for postoperative complications and patient-reported outcomes similar to those of women undergoing postmastectomy radiation therapy in the setting of immediate implant reconstruction. METHODS: The cohort included patients undergoing immediate implant reconstruction at 11 centers across North America. Women were categorized into three groups: prior breast conservation therapy, postmastectomy radiation therapy, and no radiation therapy. Mixed effect logistic regressions were used to analyze the effects of radiation therapy status on complication rates and patient-reported outcomes. RESULTS: ONE THOUSAND FIVE HUNDRED NINETY-FOUR: patients were analyzed, including 84 women with prior breast conservation therapy, 329 women who underwent postmastectomy radiation therapy, and 1181 women with no history of radiation therapy. Compared with postmastectomy radiation therapy, breast conservation was associated with lower rates of all complications and major complications (OR, 0.65; 95 percent CI, 0.37 to 1.14; p = 0.13; and OR, 0.61; 95 percent CI, 0.33 to 1.13; p = 0.12). These differences were not statistically significant. Rates of reconstructive failure between the two cohorts were comparable. Before reconstruction, satisfaction with breasts was lowest for women with prior breast conservation therapy (p < 0.001). At 2 years postoperatively, satisfaction with breasts was lower for women with postmastectomy radiation therapy compared with breast conservation patients (p = 0.007). CONCLUSIONS: Higher postoperative complication rates were observed in women exposed to radiation therapy regardless of timing. Although women with prior breast conservation experienced greater satisfaction with their breasts and fewer complications when compared to women undergoing postmastectomy radiation therapy, there was a similar risk for reconstruction failure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Obesity and Breast Reconstruction: Complications and Patient-Reported Outcomes in a Multicenter, Prospective Study.

BACKGROUND: The authors' purpose was to evaluate the effects of body mass index, as defined by World Health Organization criteria, on complications and patient-reported outcomes in implant-based and autologous breast reconstruction. METHODS: Complications and BREAST-Q patient-reported outcomes were analyzed 2 years after breast reconstruction for women from 11 participating sites. Separate mixed-effects regressions were performed to assess body mass index effects on outcomes. RESULTS: A total of 2259 patients (1625 implant-based and 634 autologous) were included. Women with class II/III obesity had higher risks of any complication in both the implant (OR, 1.66; p = 0.03) and autologous (OR, 3.35; p < 0.001) groups, and higher risks of major complications in both the implant (OR, 1.71, p = 0.04) and autologous (OR, 2.72; p = 0.001) groups, compared with underweight/normal weight patients. Both class I (OR, 1.97; p = 0.03) and class II/III (OR, 3.30; p = 0.001) obesity patients experienced higher reconstructive failures in the implant cohort. Class I obesity implant patients reported significantly lower Satisfaction with Breasts scores (mean difference, -5.37; p = 0.007). Body mass index did not significantly affect patient-reported outcomes for autologous reconstruction patients. CONCLUSIONS: Obesity was associated with higher risks for complications in both implant-based and autologous breast reconstruction; however, it only significantly affected reconstruction failure and patient-reported outcomes in the implant reconstruction patients. Quality-of-life benefits and surgical risk should be presented to each patient as they relate to her body mass index, to optimize shared decision-making for breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, I.

Elective Revisions after Breast Reconstruction: Results from the Mastectomy Reconstruction Outcomes Consortium.

BACKGROUND: Rates of breast reconstruction following mastectomy continue to increase. The objective of this study was to determine the frequency of elective revision surgery and the number of procedures required to achieve a stable breast reconstruction 2 years after mastectomy. METHODS: Women undergoing first-time breast reconstruction after mastectomy were enrolled and followed for 2 years, with completion of reconstruction occurring in 1996. Patients were classified based on the absence or presence of complications. Comparisons within cohorts were performed to determine factors associated with revisions and total procedures. Mixed-effects regression modeling identified factors associated with elective revisions and total operations. RESULTS: Overall, 1534 patients (76.9 percent) had no complications, among whom 40.2 percent underwent elective revisions. The average number of elective revisions differed by modality (p < 0.001), with abdominally based free autologous reconstruction patients undergoing the greatest number of elective revisions (mean, 0.7). The mean total number of procedures also differed (p < 0.001), with tissue expander/implant reconstruction patients undergoing the greatest total number of procedures (mean, 2.4). Complications occurred in 462 patients (23.1 percent), with 67.1 percent of these patients undergoing elective revisions, which was significantly higher than among patients without complications (p < 0.001). The mean number of procedures again differed by modality (p < 0.001) and followed similar trends, but with an increased mean number of revisions and procedures overall. Mixed-effects regression modeling demonstrated that patients experiencing complications had increased odds of undergoing elective revision procedures (OR, 3.2; p < 0.001). CONCLUSIONS: Breast reconstruction patients without complications undergo over two procedures on average to achieve satisfactory reconstruction, with 40 percent electing revisions. If a complication occurs, the number of procedures increases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Hospital Variations in Clinical Complications and Patient-reported Outcomes at 2 Years After Immediate Breast Reconstruction.

OBJECTIVE: Our objectives were to investigate case-mix adjusted hospital variations in 2-year clinical and patient-reported outcomes following immediate breast reconstruction. BACKGROUND: Over the past few decades, variations in medical practice have been viewed as opportunities to promote best practices and high-value care. METHODS: The Mastectomy Reconstruction Outcomes Consortium Study is an National Cancer Institute-funded longitudinal, prospective cohort study assessing clinical and patient-reported outcomes of immediate breast reconstruction after mastectomy at 11 leading medical centers. Case-mix adjusted comparisons were performed using generalized linear mixed-effects models to assess variation across the centers in any complication, major complications, satisfaction with outcome, and satisfaction with breast. RESULTS: Among 2252 women in the analytic cohort, 1605 (71.3%) underwent implant-based and 647 (28.7%) underwent autologous breast reconstruction. There were significant differences in the sociodemographic and clinical characteristics, and distribution of procedure types at the different Mastectomy Reconstruction Outcomes Consortium Study centers. After case-mix adjustments, hospital variations in the rates of any and major postoperative complications were observed. Medical center odds ratios for major complication ranged from 0.58 to 2.13, compared with the average major complication rate across centers. There were also meaningful differences in satisfaction with outcome (from the lowest to highest of -2.79-2.62) and in satisfaction with breast (-2.82-2.07) compared with the average values. CONCLUSIONS: Two-year postoperative complications varied widely between hospitals following post-mastectomy breast reconstruction. These variations represent an important opportunity to improve care through dissemination of best practices and highlight the limitations of extrapolating single-institution level data and the ongoing challenges of studying hospital-based outcomes for this patient population.

Comparison of 2-Year Complication Rates Among Common Techniques for Postmastectomy Breast Reconstruction.

Importance: In breast reconstruction, it is critical for patients and surgeons to have comprehensive information on the relative risks of the available options. However, previous studies that evaluated complications were limited by single-center designs, inadequate follow-up, and confounding. Objective: To assess 2-year complication rates across common techniques for postmastectomy reconstruction in a multicenter patient population. Design, Setting, and Participants: This longitudinal, multicenter, prospective cohort study conducted from February 1, 2012, through July 31, 2015, took place at the 11 study sites associated with the Mastectomy Reconstruction Outcomes Consortium study. Eligible patients included women 18 years and older presenting for first-time breast reconstruction with at least 2 years of follow-up. Procedures evaluated included direct-to-implant (DTI) technique, expander-implant (EI) technique, latissimus dorsi (LD) flap, pedicled transverse rectus abdominis myocutaneous (pTRAM) flap, free transverse rectus abdominis myocutaneous (fTRAM) flap, deep inferior epigastric perforator (DIEP) flap, and superficial inferior epigastric artery (SIEA) flap. Interventions: Postmastectomy breast reconstruction. Main Outcomes and Measures: Development of complications, reoperative complications, and wound infections during 2-year follow-up. Mixed-effects logistic regression analysis controlled for variability among centers and for demographic and clinical variables. Results: A total of 2343 patients (mean [SD] age, 49.5 [10.1] years; mean [SD] body mass index, 26.6 [5.7]) met the inclusion criteria. A total of 1525 patients (65.1%) underwent EI reconstruction, with 112 (4.8%) receiving DTI reconstruction, 85 (3.6%) pTRAM flaps, 95 (4.1%) fTRAM flaps, 390 (16.6%) DIEP flaps, 71 (3.0%) LD flaps, and 65 (2.8%) SIEA flaps. Overall, complications were noted in 771 (32.9%), with reoperative complications in 453 (19.3%) and wound infections in 230 (9.8%). Two years postoperatively, patients undergoing any autologous reconstruction type had significantly higher odds of developing any complication compared with those undergoing EI reconstruction (pTRAM flap: odds ratio [OR], 1.91; 95% CI, 1.10-3.31; P = .02; fTRAM flap: OR, 2.05; 95% CI, 1.24-3.40; P = .005; DIEP flap: OR, 1.97; 95% CI, 1.41-2.76; P < .001; LD flaps: OR, 1.87; 95% CI, 1.03-3.40; P = .04; SIEA flap: OR, 4.71; 95% CI, 2.32-9.54; P < .001). With the exception of LD flap reconstructions, all flap procedures were associated with higher odds of reoperative complications (pTRAM flap: OR, 2.48; 95% CI, 1.33-4.64; P = .005; fTRAM flap: OR, 3.02; 95% CI, 1.73-5.29; P < .001; DIEP flap: OR, 2.76; 95% CI, 1.87-4.07; P < .001; SIEA flap: OR, 2.62; 95% CI, 1.24-5.53; P = .01) compared with EI techniques. Of the autologous reconstructions, only patients undergoing DIEP flaps had significantly lower odds of infection compared with those undergoing EI procedures (OR, 0.45; 95% CI, 0.25-0.29; P = .006). However, DTI and EI procedures had higher failure rates (EI and DTI techniques, 7.1%; pTRAM flap, 1.2%; fTRAM flap, 2.1%; DIEP flap, 1.3%; LD flap, 2.8%; and SIEA flap, 0%; P < .001). Conclusions and Relevance: Significant differences were noted across reconstructive procedure types for overall and reoperative complications, which is critically important information for women and surgeons making breast reconstruction decisions.

Long-term Patient-Reported Outcomes in Postmastectomy Breast Reconstruction.

Importance: Previous outcome studies comparing implant and autologous breast reconstruction techniques have been limited by short-term follow-up, single-center design, and a lack of rigorous patient-reported outcome data. An understanding of the expected satisfaction and breast-related quality of life associated with each type of procedure is central to the decision-making process. Objective: To determine outcomes reported by patients undergoing postmastectomy breast reconstruction using implant or autologous techniques 2 years after surgery. Design, Setting, and Participants: Patients were recruited from 11 centers (57 plastic surgeons) across North America for the Mastectomy Reconstruction Outcomes Consortium study, a prospective, multicenter trial, from February 1, 2012, to July 31, 2015. Women undergoing immediate breast reconstruction using implant or autologous tissue reconstruction after mastectomy for cancer treatment or prophylaxis were eligible. Overall, 2013 women (1490 implant and 523 autologous tissue reconstruction) met the inclusion criteria. All patients included in this analysis had 2 years of follow-up. Exposures: Procedure type (ie, implant vs autologous tissue reconstruction). Main Outcomes and Measures: The primary outcomes of interest were scores on the BREAST-Q, a validated, condition-specific, patient-reported outcome instrument, which were collected prior to and at 2 years after surgery. The following 4 domains of the BREAST-Q reconstruction module were evaluated: satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being. Responses from each scale were summed and transformed on a 0 to 100 scale, with higher numbers representing greater satisfaction or quality of life. Results: Of the 2013 women in the study (mean [SD] age, 48.1 [10.5] years for the group that underwent implant-based reconstruction and 51.6 [8.7] years for the group that underwent autologous reconstruction), 1217 (60.5%) completed questionnaires at 2 years after reconstruction. After controlling for baseline patient characteristics, patients who underwent autologous reconstruction had greater satisfaction with their breasts (difference, 7.94; 95% CI, 5.68-10.20; P < .001), psychosocial well-being (difference, 3.27; 95% CI, 1.25-5.29; P = .002), and sexual well-being (difference, 5.53; 95% CI, 2.95-8.11; P < .001) at 2 years compared with patients who underwent implant reconstruction. Conclusions and Relevance: At 2 years, patients who underwent autologous reconstruction were more satisfied with their breasts and had greater psychosocial well-being and sexual well-being than did those who underwent implant reconstruction. These findings can inform patients and their clinicians about expected satisfaction and quality of life outcomes of autologous vs implant-based procedures and further support the adoption of shared decision making in clinical practice.

Microbial metabolites, short-chain fatty acids, restrain tissue bacterial load, chronic inflammation, and associated cancer in the colon of mice.

The intestinal immune system is regulated by microbes and their metabolites. The roles of gut microbial metabolites in regulating intestinal inflammation and tumorigenesis are incompletely understood. We systematically studied the roles of short-chain fatty acids (SCFAs) and their receptors (GPR43 or GPR41) in regulating tissue bacterial load, acute versus chronic inflammatory responses, and intestinal cancer development. SCFA receptor-, particularly GPR43-, deficient mice were defective in mounting appropriate acute immune responses to promote barrier immunity, and developed uncontrolled chronic inflammatory responses following epithelial damage. Further, intestinal carcinogenesis was increased in GPR43-deficient mice. Dietary fiber and SCFA administration suppressed intestinal inflammation and cancer in both GPR43-dependent and independent manners. The beneficial effect of GPR43 was not mediated by altered microbiota but by host tissue cells and hematopoietic cells to a lesser degree. We found that inability to suppress commensal bacterial invasion into the colonic tissue is associated with the increased chronic Th17-driven inflammation and carcinogenesis in the intestine of GPR43-deficient mice. In sum, our results reveal the beneficial function of the SCFA-GPR43 axis in suppressing bacterial invasion and associated chronic inflammation and carcinogenesis in the colon.

Nonresponse bias in survey research: lessons from a prospective study of breast reconstruction.

BACKGROUND: Survey-based research is essential for evaluating the outcomes of health care in an era of patient-centered care. However, many such studies are hampered by poor response rates in completion of study questionnaires, thus limiting the generalizability of any findings. The objectives of this analysis were to identify independent variables associated with nonresponse to surveys following breast reconstruction to improve future patient-reported outcomes research. MATERIALS AND METHODS: The Mastectomy Reconstruction Outcomes Consortium is a prospective cohort study involving 11 leading medical centers from the United States and Canada. Nonresponse rates for surveys assessing satisfaction with breast, satisfaction with care (BREAST-Q), depression (Patient Health Questionnaire-9), and anxiety (Generalized Anxiety Disorder-7) were measured at 1 y and 2 y postoperatively. Clinical complication rates were compared between responders and nonresponders, and multivariable models were used to assess predictors of nonresponse. RESULTS: Among 2856 women in the analytic cohort, 1882 (65.9%) underwent implant-based, 817 (28.6%) received autologous, and 157 (5.5%) underwent latissimus dorsi myocutaneous flap breast reconstructions. Nonresponse rates to surveys at 1 y and 2 y were 27.8% and 34.4%, respectively. Race, ethnicity, and annual household income were associated with nonresponse to surveys. Women who underwent implant-based procedures were less likely to complete long-term surveys. CONCLUSIONS: As survey-based research plays an increasingly prominent role in evaluating the outcomes of breast reconstruction, we found socioeconomic and procedure-related differences in survey response rates. Investigators must consider systematic differences in response rates among particular groups of women on the generalizability and validity of findings and perform rigorous nonresponse bias analyses.

Impact of Radiotherapy on Complications and Patient-Reported Outcomes After Breast Reconstruction.

Background: Patients considering postmastectomy radiation and reconstruction require information regarding expected outcomes to make preference-concordant decisions. Methods: A prospective multicenter cohort study of women diagnosed with breast cancer at 11 centers between 2012 and 2015 compared complications and patient-reported outcomes of 622 irradiated and 1625 unirradiated patients who received reconstruction. Patient characteristics and outcomes between irradiated and unirradiated patients were analyzed using ttests for continuous variables and chi-square tests for categorical variables. Multivariable mixed-effects regression modelsassessed the impact of reconstruction type and radiotherapy on outcomes after adjusting for relevant covariates. All statistical tests were two-sided. Results: Autologous reconstruction was more commonly received by irradiated patients (37.9% vs 25.0%, P < .001). Immediate reconstruction was less common in irradiated patients (83.0% vs 95.7%, P < .001). At least one breast complication had occurred by two years in 38.9% of irradiated patients with implant reconstruction, 25.6% of irradiated patients with autologous reconstruction, 21.8% of unirradiated patients with implant reconstruction, and 28.3% of unirradiated patients with autologous reconstruction. Multivariable analysis showed bilateral treatment and higher body mass index to be predictive of developing a complication, with a statistically significant interaction between radiotherapy receipt and reconstruction type. Among irradiated patients, autologous reconstruction was associated with a lower risk of complications than implant-based reconstruction at two years (odds ratio [OR] = 0.47, 95% confidence interval [CI] = 0.27 to 0.82, P = .007); no between-procedure difference was found in unirradiated patients. The interaction was also statistically significant for satisfaction with breasts at two years (P = .002), with larger adjusted difference in satisfaction between autologous vs implant approaches (63.5, 95% CI = 55.9 to 71.1, vs 47.7, 95% CI = 40.2 to 55.2, respectively) in irradiated patients than between autologous vs implant approaches (67.6, 95% CI = 60.3 to 74.9, vs 60.5, 95% CI = 53.6 to 67.4) in unirradiated patients. Conclusions: Autologous reconstruction appears to yield superior patient-reported satisfaction and lower risk of complications than implant-based approaches among patients receiving postmastectomy radiotherapy.

Complications in Postmastectomy Breast Reconstruction: One-year Outcomes of the Mastectomy Reconstruction Outcomes Consortium (MROC) Study.

OBJECTIVE: In postmastectomy reconstruction, procedure choice is heavily influenced by the relative risks of the various options. This study sought to evaluate complications in a large, multicenter patient population. SUMMARY OF BACKGROUND DATA: Previous studies have reported widely varying complication rates, but have been limited by their single center designs and inadequate controlling for confounders in their analyses. METHODS: Eleven sites enrolled women undergoing first time, immediate, or delayed reconstruction following mastectomy for cancer treatment or prophylaxis. Procedures included expander/implant, latissimus dorsi (LD), pedicle transverse rectus abdominis musculocutaneous (PTRAM), free TRAM (FTRAM), and deep inferior epigastric perforator (DIEP) techniques. Data were gathered pre- and postoperatively from medical records. Separate logistic regressions were conducted for all complications and major complications (those requiring rehospitalization and/or reoperation) within 1 year. Odds ratios (ORs) were calculated for procedure type, controlling for site, demographic, and clinical variables. RESULTS: Complication rates for 2234 patients were analyzed. Compared with expander/implant reconstructions, LD (OR) 1.95, P = 0.026), PTRAM (OR 1.89, P = 0.025), FTRAM (OR 1.94, P = 0.011), and DIEP (OR 2.22, P < 0.001) procedures were associated with higher risks of complications. Significantly higher risks were also associated with older age, higher body mass index (BMI), immediate reconstruction, bilateral procedures, and radiation. For major complications, regression showed significantly greater risks for PTRAM (OR 1.86, P = 0.044) and DIEP (OR 1.75, P = 0.004), than expander/implant reconstructions. Failure rates were relatively low, ranging from 0% for PTRAM to 5.9% for expander/implant reconstructions. CONCLUSION: In this multicenter analysis, procedure choice and other patient variables were significant predictors of 1-year complications in breast reconstruction. These findings should be considered in counseling patients on reconstructive options.