Developmental origins of metabolic diseases.

Almost 2 billion adults in the world are overweight, and more than half of them are classified as obese, while nearly one-third of children globally experience poor growth and development. Given the vast amount of knowledge that has been gleaned from decades of research on growth and development, a number of questions remain as to why the world is now in the midst of a global epidemic of obesity accompanied by the "double burden of malnutrition," where overweight coexists with underweight and micronutrient deficiencies. This challenge to the human condition can be attributed to nutritional and environmental exposures during pregnancy that may program a fetus to have a higher risk of chronic diseases in adulthood. To explore this concept, frequently called the developmental origins of health and disease (DOHaD), this review considers a host of factors and physiological mechanisms that drive a fetus or child toward a higher risk of obesity, fatty liver disease, hypertension, and/or type 2 diabetes (T2D). To that end, this review explores the epidemiology of DOHaD with discussions focused on adaptations to human energetics, placental development, dysmetabolism, and key environmental exposures that act to promote chronic diseases in adulthood. These areas are complementary and additive in understanding how providing the best conditions for optimal growth can create the best possible conditions for lifelong health. Moreover, understanding both physiological as well as epigenetic and molecular mechanisms for DOHaD is vital to most fully address the global issues of obesity and other chronic diseases.

Model to predict major complications following liver resection for HCC in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Preconception Micronutrient Supplementation Affects Maternal BMI and Body Composition Postpartum: A Randomized Controlled Trial in Vietnam.

BACKGROUND: Although there is growing evidence on the role of preconception nutrition for birth outcomes, limited evidence exists for its effects on maternal health. OBJECTIVES: This study evaluates the impact of preconception micronutrient supplementation on maternal BMI (kg/m2) and body composition at 6 to 7 y postpartum (PP). METHODS: We followed females who participated in a randomized controlled trial of preconception supplementation in Vietnam and delivered live offspring (n = 1599). Females received weekly supplements containing either 2800 µg folic acid (FA) only, 60 mg iron and 2800 µg FA (IFA), or multiple micronutrients (MMs) (15 micronutrients including IFA) from baseline until conception followed by daily prenatal IFA supplements until delivery. Height, weight, mid-upper arm circumference, triceps skinfold, and waist-hip circumference were measured at recruitment and at 1, 2, and 6 to 7 y PP. Body fat was assessed using bioelectric impedance at 6 to 7 y PP (n = 867). Group comparisons were made using analysis of variance or chi-square tests and general linear models for adjusted models. RESULTS: At 6 to 7 y PP, we found significant differences (P < 0.05) by treatment group for mean percent fat (MM: 29.2%; IFA: 27.6%; FA: 27.8%), absolute fat mass (MM: 15.1 kg; IFA: 14.0 kg; FA: 14.3 kg), and prevalence of underweight based on BMI < 18.5 (MM: 5.8%; IFA: 10.3%; FA: 14.3%). Mean BMI and triceps skinfold thickness were higher in the MM group, but these differences were not statistically significant; the differences in absolute fat mass were also attenuated after controlling for body weight. No differences were observed for fat-free mass, prevalence of overweight (BMI >23), or other anthropometric measurements. CONCLUSIONS: Preconception MM supplementation was associated with lower prevalence of underweight and higher percent fat when compared with IFA and/or FA only. Preconception micronutrient interventions may have long-term effects on maternal health and merit further examination. This trial was registered at clinicaltrials.gov as NCT01665378.

Disruptions to sleep and circadian rhythms are associated with poorer athlete mental health in female, but not male, elite Australian Rules footballers.

Elite athletes are vulnerable to sleep and circadian disruption and associated mental health symptoms. This study aimed to investigate sex differences in sleep, circadian rhythms, and mental health, as well as the moderating role of sex in the prediction of mental health, among male professional and female semi-professional elite athletes. Participants were 87 elite Australian Rules football (ARF) athletes (43% female; mean [standard deviation] age 24.0 [4.1] years). Participants completed baseline questionnaires, 2 weeks of sleep/wake monitoring via actigraphy, and a circadian phase assessment (dim-light melatonin onset [DLMO]). Cross-sectional data were collected in training-only Australian Football League (AFL) Men's and Women's pre-season periods, with 53 providing data in two pre-seasons. Female athletes, relative to males, reported poorer mental health (a higher athlete psychological strain score), had a later mid-sleep time (by 28 min), reported a greater preference towards eveningness, and displayed a later circadian phase (by 33 min). For female athletes, lower sleep efficiency and lower sleep regularity were associated with poorer mental health. For female athletes, there were U-shaped relationships between both morningness-eveningness and phase angle (interval between sleep onset and DLMO time) and mental health. No significant relationships were found for male athletes. In summary, elite female ARF athletes reported poorer mental health, relative to males, especially when experiencing sleep or circadian disruption. Lifestyle factors associated with sex differences in ARF professionalism (scheduling, finances, supports) may contribute to these findings. Programmes to improve sleep, circadian alignment, and mental health among female semi-professional elite athletes should be strongly considered.

Estimating the Burden and Distribution of Post-COVID-19 Condition in Washington State, March 2020-October 2023.

Introduction: After SARS-CoV-2 infection, some people will experience long-term sequelae known as post-COVID-19 condition (PCC). Although PCC is recognized as a public health problem, estimates of the prevalence of PCC are sparse. We described a framework for estimating the incidence and prevalence of PCC by population subgroups and geography over time in Washington State. Methods: We collected data on reported COVID-19 cases and hospitalizations and estimated SARS-CoV-2 infections in Washington State from March 2020 through October 2023. The reported case data were incorporated with parameter estimates from published articles and prevalence estimates from the Household Pulse Survey into a mathematical compartmental model of PCC progression. The model used differential equations to describe how the population of people with PCC moved through the model's various stages. This framework allowed us to integrate data on age group, sex, race and ethnicity, vaccination status, and county to estimate incidence and prevalence of PCC for each subgroup. Results: Our model indicated that 6.4% (95% CI, 5.9%-6.8%) of all adults in Washington State were experiencing PCC as of October 2023. In addition to temporal differences in PCC prevalence and incidence, we found substantial differences across age groups, race and ethnicity, and sex. Geographic heterogeneity was pronounced, with the highest rates of PCC in central and eastern Washington. Conclusion: Estimation of PCC prevalence is essential for addressing PCC as a public health problem. Responding to PCC will require continued surveillance, research, and dedicated financial and public health action. This analysis, accounting for heterogeneities, highlights disparities in the prevalence, incidence, and distribution of PCC in Washington State and can better guide awareness and response efforts.

Using the Comprehensive Complication Index to Rethink the ISGLS Criteria for Post-hepatectomy Liver Failure in an International Cohort of Major Hepatectomies.

OBJECTIVE: To compare different criteria for post-hepatectomy liver failure (PHLF) and evaluate the association between International Study Group of Liver Surgery (ISGLS) PHLF and the Comprehensive Complication Index (CCI)" and 90-day mortality. SUMMARY OF BACKGROUND DATA: PHLF is a serious complication following hepatic resection. Multiple criteria have been developed to characterize PHLF. METHODS: Adults who underwent major hepatectomies at twelve international centers (2010-2020) were included. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) Balzan (INR > 1.7 and bilirubin > 2.92mg/dL) or 3) Mullen (peak bilirubin >7mg/dL). We compared the 90-day mortality and major morbidity predicted by each definition. We then used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grades. RESULTS: Among 1646 included patients, 19 (1.1%) met Balzan, 68 (4.1%) met Mullen, and 444 (27.0%) met ISGLS criteria for PHLF. Of the three definitions, the ISGLS criteria best predicted 90-day mortality (AUC = 0.72; sensitivity 69.4%). Patients with ISGLS grades B&C were at increased odds of CCI > 40 (grade B OR 4.0; 95% CI: 2.2-7.2; grade C OR 137.0; 95% CI: 59.2-317.4). Patients with ISGLS grade C were at increased odds of 90-day mortality (OR 113.6; 95% CI: 55.6-232.1). Grade A was not associated with CCI> 40 or 90-day mortality. CONCLUSIONS: In this diverse international cohort of major hepatectomies, ISGLS grade A was not associated with 90-day mortality or high CCI, calling into question the current classification of patients in this group as having clinically significant PHLF.

Minimally Invasive Versus Open Liver Resections for Hepatocellular Carcinoma in Patients With Metabolic Syndrome.

OBJECTIVE: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). BACKGROUND: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. MATERIAL AND METHODS: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. RESULTS: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P =0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P =0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P =0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P =0.015), posthepatectomy liver failure (0.6% vs 4.3%, P =0.008), and bile leaks (2.2% vs 6.4%, P =0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P =0.002) and day 3 (3.1% vs 11.4%, P <0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P <0.001). There was no significant difference in overall survival and disease-free survival. CONCLUSIONS: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.

A Machine Learning Approach to Predict Postoperative Pancreatic Fistula After Pancreaticoduodenectomy Using Only Preoperatively Known Data.

BACKGROUND: Clinically-relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) is a major postoperative complication and the primary determinant of surgical outcomes. However, the majority of current risk calculators utilize intraoperative and postoperative variables, limiting their utility in the preoperative setting. Therefore, we aimed to develop a user-friendly risk calculator to predict CR-POPF following PD using state-of-the-art machine learning (ML) algorithms and only preoperatively known variables. METHODS: Adult patients undergoing elective PD for non-metastatic pancreatic cancer were identified from the ACS-NSQIP targeted pancreatectomy dataset (2014-2019). The primary endpoint was development of CR-POPF (grade B or C). Secondary endpoints included discharge to facility, 30-day mortality, and a composite of overall and significant complications. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated and a user-friendly risk calculator was then developed. RESULTS: Of the 8666 patients who underwent elective PD, 13% (n = 1160) developed CR-POPF. XGBoost was the best performing model (AUC = 0.72), and the top five preoperative variables associated with CR-POPF were non-adenocarcinoma histology, lack of neoadjuvant chemotherapy, pancreatic duct size less than 3 mm, higher BMI, and higher preoperative serum creatinine. Model performance for 30-day mortality, discharge to a facility, and overall and significant complications ranged from AUC 0.62-0.78. CONCLUSIONS: In this study, we developed and validated an ML model using only preoperatively known variables to predict CR-POPF following PD. The risk calculator can be used in the preoperative setting to inform clinical decision-making and patient counseling.

Early initiation of electrical stimulation paired with range of motion after a volumetric muscle loss injury does not benefit muscle function.

NEW FINDINGS: What is the central question of this study? First, how does physical rehabilitation influence recovery from traumatic muscle injury? Second, how does physical activity impact the rehabilitation response for skeletal muscle function and whole-body metabolism? What is the main finding and its importance? The most salient findings were that rehabilitation impaired muscle function and range of motion, while restricting activity mitigated some negative effects but also impacted whole-body metabolism. These data suggest that first, work must continue to explore treatment parameters, including modality, time, type, duration and intensity, to find the best rehabilitation approaches for volumetric muscle loss injuries; and second, restricting activity acutely might enhance rehabilitation response, but whole-body co-morbidities should continue to be considered. ABSTRACT: Volumetric muscle loss (VML) injury occurs when a substantial volume of muscle is lost by surgical removal or trauma, resulting in an irrecoverable deficit in muscle function. Recently, it was suggested that VML impacts whole-body and muscle-specific metabolism, which might contribute to the inability of the muscle to respond to treatments such as physical rehabilitation. The aim of this work was to understand the complex relationship between physical activity and the response to rehabilitation after VML in an animal model, evaluating the rehabilitation response by measurement of muscle function and whole-body metabolism. Adult male mice (n = 24) underwent a multi-muscle, full-thickness VML injury to the gastrocnemius, soleus and plantaris muscles and were randomized into one of three groups: (1) untreated; (2) rehabilitation (i.e., combined electrical stimulation and range of motion, twice per week, beginning 72 h post-injury, for ∼8 weeks); or (3) rehabilitation and restriction of physical activity. There was a lack of positive adaption associated with electrical stimulation and range of motion intervention alone; however, maximal isometric torque of the posterior muscle group was greater in mice receiving treatment with activity restriction (P = 0.008). Physical activity and whole-body metabolism were measured ∼6 weeks post-injury; metabolic rate decreased (P = 0.001) and respiratory exchange ratio increased (P = 0.022) with activity restriction. Therefore, restricting physical activity might enhance an intervention delivered to the injured muscle group but impair whole-body metabolism. It is possible that restricting activity is important initially post-injury to protect the muscle from excess demand. A gradual increase in activity throughout the course of treatment might optimize muscle function and whole-body metabolism.

Greater male variability in daily energy expenditure develops through puberty.

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.

Sleep patterns before and after competition: A real-world examination of elite athletes.

Good sleep before and after competitions is crucial to cognitive, physiological performance and recovery. Yet, elite athletes face a unique set of challenges when acquiring good sleep before and after competitions, and indeed commonly report sleep problems when it matters most. This study examined the sleep of elite athletes before and after competition compared to before and after free days. A total of 1808 unique nights of actigraphy (n = 1495) and sleep diary (n = 1335) data from elite Australian Football League and National Rugby League male athletes (N = 85, M-age = 24.4 ± 3.6) were collected and analysed using multi-level mixed models. On nights before competitions, athletes advanced sleep timings (p < .001, d = 0.63) and increased total sleep time (p < .001, d = 0.65) compared to nights before free days. On nights after competitions, athletes delayed sleep timings (p < .001, d = 1.64), reduced total sleep time (p < .001, d = 1.28), and had significantly worse quality sleep (p < .001, d = 0.71) compared to nights after free days. Sleep was especially worse following night competitions. While elite athletes and organisations may be implementing effective sleep strategies to optimise sleep the night before competitions, strategies to improve sleep after competitions may be lacking. We discuss potential factors contributing to this asymmetry and propose areas for research moving forward.

Matters of Frequency, Immediacy and Regularity: Engagement in an Online Asynchronous Course.

Many models of online student engagement posit a "more is better" relationship between students' course-related actions and their engagement. However, recent research indicates that the timing of engagement is also an important consideration. In addition to the frequency (how often) of engagement, two other constructs of timing were explored in this study: immediacy (how early) and regularity (in what ordered pattern). These indicators of engagement were applied to three learning assessment types used in an online, undergraduate, competency-based, technology skills course. The study employed advanced data collection and learning analytics techniques to collect continuous behavioral data over seven semesters (n = 438). Results revealed that several indicators of engagement predicted academic success, but significance differed by assessment type. "More" is not always better, as some highly engaged students earn lower grades. Successful students tended to engage earlier with lessons regardless of assessment type.

Preoperative MRI and Its Impact on Surgical Outcomes in Patients with Triple Negative Breast Cancer Treated with Primary Surgery: Did New Margin Guidelines or Cavity Shave Margins Practice Diminish the Role of Preoperative MRI?

BACKGROUND: Results of an earlier retrospective study from our institution suggested that patients with triple negative breast cancer (TNBC) who had preoperative MRI may have had an improved local recurrence rate (LRR) after breast conserving surgery (BCS). We aimed to clarify the impact of preoperative MRI on surgical outcomes in an expanded TNBC cohort treated by BCS in a contemporary era. METHODS: Our study cohort comprised 648 patients with TNBC who underwent BCS between 2009 and 2018. Demographic and clinical characteristics were compared between those with (n = 292, 45.1%) and without (n = 356, 54.9%) preoperative MRI. Multivariable logistic regression was performed to assess the association of preoperative MRI with surgical outcomes. RESULTS: The crude LRR of 3.5% was lower than previously reported. Univariable analyses demonstrated that the LRR and re-excision rates in the MRI and no-MRI groups were 3.4 and 3.7%, 21.6% and 27.2%, p = 0.876 and p = 0.10, respectively. Multivariable logistic regression analyses demonstrated that preoperative MRI was not associated with a lower LRR: odds ratio (OR) = 1.42 (p = 0.5). During our study period, new margin guidelines and shave margins practice were adopted in 2014 and 2015. To account for their effects, the year of diagnosis/surgery and other clinical variables were adjusted in multivariable logistic regression and inverse probability weighting models to demonstrate that preoperative MRI remained associated with a lower re-excision risk, OR 0.56, p = 0.04l; and a lower re-excision rate, 23.15% versus 36.0%, p < 0.01, respectively. CONCLUSIONS: Our findings suggested that patients with TNBC anticipating BCS may benefit from preoperative MRI.

Temporal changes in the muscle extracellular matrix due to volumetric muscle loss injury.

PURPOSE/AIM: Volumetric muscle loss (VML) is a devastating orthopedic injury resulting in chronic persistent functional deficits, loss of joint range of motion, pathologic fibrotic deposition and lifelong disability. However, there is only limited mechanistic understanding of VML-induced fibrosis. Herein we examined the temporal changes in the fibrotic deposition at 3, 7, 14, 28, and 48 days post-VML injury. MATERIALS AND METHODS: Adult male Lewis rats (n = 39) underwent a full thickness ~20% (~85 mg) VML injury to the tibialis anterior (TA) muscle unilaterally, the contralateral TA muscle served as the control group. All TA muscles were harvested for biochemical and histologic evaluation. RESULTS: The ratio of collagen I/III was decreased at 3, 7, and 14 days post-VML, but significantly increased at 48 days. Decorin content followed an opposite trend, significantly increasing by day 3 before dropping to below control levels by 48 days. Histological evaluation of the defect area indicates a shift from loosely packed collagen at early time points post-VML, to a densely packed fibrotic scar by 48 days. CONCLUSIONS: The shift from early wound healing efforts to a fibrotic scar with densely packed collagen within the skeletal muscle occurs around 21 days after VML injury through dogmatic synchronous reduction of collagen III and increase in collagen I. Thus, there appears to be an early window for therapeutic intervention to prevent pathologic fibrous tissue formation, potentially by targeting CCN2/CTGF or using decorin as a therapeutic.

The relationship between total energy expenditure and physical activity level in women living in an impoverished Brazilian urban area.

OBJECTIVE: This study aimed to describe how strong is the relationship between TEE and PAL in women living in an impoverished Brazilian urban area. METHODS: Anthropometric, hormonal (insulin, TSH, FT4 , and FT3 ), body composition (deuterium), TEE (doubly labeled water) and PAL (metabolic equivalent task [MET]-7-day triaxial accelerometer, ActivPAL®) data were collected from 55 women (mean age: 31y, mean BMI: 27.4 kg/m2 ). Adjusted-TEE models were calculated incorporating the residuals of anthropometric, hormonal, and body composition variables in the TEE, to assess the relation between MET and adjusted-TEE, through three different analyzes: linear regression, nonlinear regression and change-point regression. RESULTS: Most participants (89.1%, n = 49) were classified as low-active. There was no association between crude TEE and MET.h/d (R2  = 0.05; p = 0.09). There was a positive, although weak, linear relationship between adjusted-TEE and MET.h/d (ß = 2705.26 kcal; 95% CI: 436.25; 4974.27; adj-R2  = 0.08). A change point of this relationship was identified in the MET.h/d value of 1.53 (SD = 0.02; adj-R2 = 0.13). The association between adjusted-TEE and MET.h/d before the change point (ß = 5101.46 kcal; 95%CI: 978.84; 9224.08; adj-R2  = 0.11) was stronger than the association in the full linear model, nevertheless, it was still weak. This association stop existing when it is assessed in individuals after the change point (ß = -6609.92 kcal; 95%CI: -16773.24; 3553.40; adj-R2  = 0.08). CONCLUSIONS: These results suggest that the relationship between TEE and PAL is weak and it is not completely linear in women living in an impoverished Brazilian urban area.

Home is where the hustle is: the influence of crowds on effort and home advantage in the National Basketball Association.

Studies have consistently shown crowds contribute to home advantage in the National Basketball Association (NBA) by inspiring home team effort, distracting opponents, and influencing referees. Quantifying the effect of crowds is challenging, however, due to potential co-occurring drivers of home advantage (e.g., travel, location familiarity). Our aim was to isolate the crowd effect using a "natural experiment" created by the Coronavirus disease 2019 (COVID-19) pandemic, which eliminated crowds in 53.4% of 2020/2021 NBA regular season games (N = 1080). Using mixed linear models, we show, in games with crowds, home teams won 58.65% of games and, on average, outrebounded and outscored their opponents. This was a significant improvement compared to games without crowds, of which home teams won 50.60% of games and, on average, failed to outrebound or outscore their opponents. Further, the crowd-related increase in rebound differential mediated the relationship between crowds and points differential. Taken together, these results suggest home advantage in the 2020/2021 NBA season was predominately driven by the presence of home crowds and their influence on the effort exerted to rebound the basketball. These findings are of considerable significance to a league where marginal gains can have immense competitive, financial, and historic consequences.

Immediate Breast Reconstruction for Inflammatory Breast Cancer: Trends in Use and Clinical Outcomes 2004-2016.

INTRODUCTION: National guidelines specify against immediate breast reconstruction (IBR) among inflammatory breast cancer (IBC) patients. However, limited data exist regarding this practice. We report practice patterns and oncologic outcomes among nonmetastatic IBC patients receiving trimodality therapy, with or without IBR. METHODS: Using the National Cancer Database, we identified nonmetastatic IBC patients treated with trimodality therapy from 2004 to 2016. Primary outcome was overall survival (OS), assessed on unadjusted analysis using Kaplan-Meier estimates and on adjusted analysis using multivariable Cox proportional hazards and inverse probability weighting (IPW) models. OS analysis was also conducted with propensity score matched (PSM) cohorts. Secondary outcomes included IBR utilization rates, time to postmastectomy radiotherapy (PMRT), and surgical outcomes. RESULTS: 6589 women were included, including 5954 (90.4%) non-reconstructed and 635 (9.6%) IBR. Among IBR recipients, 250 (39.4%) underwent autologous reconstruction, 171 (26.9%) underwent implant-based reconstruction, and 214 (33.7%) unspecified. IBR utilization increased from 6.3% to 10.1% from 2004 to 2016 at a 4% average annual growth rate (P < 0.001). Median follow-up was 43 and 45 months for IBR and non-reconstructed patients, respectively (P = 0.29). On Cox multivariable analysis, IBR was associated with improved OS (HR 0.63, 95% CI 0.44-0.90, P = 0.01), but this association was not significant on IPW analysis (P = 0.06). In PSM cohorts, this association remained significant (HR 0.60, 95% CI 0.40-0.92, P = 0.02). Margin status, time to PMRT, 30-day readmission, and 30-/90-day mortality did not differ between groups (all P > 0.05). CONCLUSION: Although not endorsed by national guidelines, IBR is increasing among IBC patients; however, more granular data are needed to determine oncologic safety.

Pre-pregnancy dietary pattern is associated with newborn size: results from ProcriAr study.

Babies born small-for-gestational age (SGA) have an increased risk of mortality, morbidity and adverse functional consequences. Studies suggest that pre-pregnancy maternal diet may influence newborns' size. This study aimed to determine whether maternal pre-pregnancy dietary patterns (DP) are associated with delivering SGA newborns in the ProcriAr Cohort Study, Sao Paulo-Brazil. Pre-pregnancy DP of 299 women were investigated using factor analysis with principal component's estimation, based on intake reported on a validated 110-item FFQ. Newborns were classified as SGA if their weight and/or length, adjusted by gestational age and sex, were below the 10th percentile of the INTERGROWTH-21st standards. Multivariate Poisson regression modelling with robust error variance was performed to examine associations between the different DP (in quintiles) and SGA. In a model adjusted by maternal sociodemographic and health behaviours, women who scored in the highest quintile of the DP 'Snacks, sandwiches, sweets and soft drinks' (in relation to the women who scored in the lowest quintile) were significantly more likely to deliver SGA babies (relative risk 1·92; 95 % CI 1·08, 3·39). This study verified that women's pre-pregnancy dietary behaviour characterised by an energy-dense nutrient-poor food intake was a risk factor for delivering SGA newborns. Investments in education and improved access to healthful food and nutritional information before pregnancy should be prioritised due to their potential positive impact on child health. However, further studies are warranted to identify specific metabolic pathways that may be underlying these associations.

CDH2/N-cadherin and early diagnosis of invasion in patients with ductal carcinoma in situ.

PURPOSE: This proof-of-concept study investigates gene expression in core needle biopsies (CNB) to predict whether individuals diagnosed with ductal carcinoma in situ (DCIS) on CNB were affected by invasion at the time of diagnosis. METHODS: Using a QuantiGene Plex 2.0 assay, 14 gene expression profiling was performed in 303 breast tissue samples. Preoperative diagnostic performance of a gene was measured by area under receiver-operating characteristic curve (AUC) with 95% confidence interval (CI). The gene mRNA positivity cutoff was computed using Gaussian mixture model (GMM); protein expression was measured by immunohistochemistry; DNA methylation was evaluated by targeted bisulfite sequencing. RESULTS: mRNA from 69% (34/49) mammoplasties, 72% (75/104) CNB DCIS, and 89% (133/150) invasive breast cancers (IBC) were analyzed. Based on pre-and post-surgery DCIS chart reviews, 21 cases were categorized as DCIS synchronous with invasion and 54 DCIS were pure DCIS without pathologic evidence of invasive disease. The ectopic expression of neuronal cadherin CDH2 was probable in 0% mammoplasties, 6% pure DCIS, 29% synchronous DCIS, and 26% IBC. The CDH2 mRNA positivity in preoperative biopsies showing pure DCIS was predictive of a final diagnosis of invasion (AUC = 0.67; 95% CI 0.53-0.80; P = 0.029). Site-specific methylation of the CDH2 promoter (AUC = 0.76; 95% CI 0.54-0.97; P = 0.04) and measurements of N-cadherin, a pro-invasive cell-cell adhesion receptor encoded by CDH2 (AUC = 0.8; 95% CI 0.66-0.99; P < 0.005) had a discriminating power allowing for discernment of CDH2-positive biopsy. CONCLUSIONS: Evidence of CDH2/N-cadherin expression, predictive of invasion synchronous with DCIS, may help to clarify a diagnosis and direct the course of therapy earlier in a patient's care.

Development of population-specific prediction equations for bioelectrical impedance analyses in Vietnamese children.

There is a need for accurate, inexpensive and field-friendly methods to assess body composition in children. Bioelectrical impedance analysis (BIA) is a promising approach; however, there have been limited validation and use among young children in resource-poor settings. We aim to develop and validate population-specific prediction equations for estimating total fat mass (FM), fat free-mass (FFM) and percentage body fat (PBF) in Vietnamese children (4-7 years) using reactance and resistance from BIA, anthropometric variables and demographic information. We conducted a cross-sectional survey of 120 children. Body composition was measured using dual-energy X-ray absorptiometry (DXA), BIA and anthropometry. To develop prediction equations, we split all data into development (70 %) and validation datasets (30 %). The model performance was evaluated using predicted residual error sum of squares, root mean squared error (RMSE), mean absolute error (MAE) and R2. We identified a top performing model with the least number of parameters (age, sex, weight and resistance index or resistance and height), low RMSE (FM 0·70, FFM 0·74, PBF 3·10), low MAE (FM 0·55, FFM 0·62, PBF 2·49), high R2 (FM 0·95, FFM 0·92, PBF 0·82) and the least difference between predicted values and actual values from DXA (FM 0·03 kg or 0·01 sd, FFM 0·06 kg or 0·02 sd, PBF 0·27 % or 0·04 sd). In conclusion, we developed the first valid and highly predictive equations to estimate FM, FFM and PBF in Vietnamese children using BIA. These findings have important implications for future research on the double burden of disease and risks associated with overweight and obesity in young children.