Impact of cardiac surgical timing on the neurodevelopmental outcomes of newborns with Complex congenital heart disease (CHD).

Background: More than half of infants with complex congenital heart disease (CHD) will have a neurodevelopmental disorder of multifactorial causes. The preoperative period represents a time-window during which neonates with complex CHD are in a state of hypoxia and hemodynamic instability, which fosters the emergence of brain injuries and, thus, affects early brain networks and neurodevelopmental outcomes. Currently, there is no consensus regarding the optimal age for cardiac surgery in terms of neurodevelopmental outcomes, and its definition is a real challenge. Our aim is to determine the relationship between cardiac surgical timing and long-term neurodevelopmental outcomes for various types of complex CHD. Methods: We hypothesize that earlier surgical timing could represent a neuroprotective strategy that reduces perioperative white matter injuries (WMIs) and postoperative morbidity, leading to improved neurodevelopmental outcomes in infants with complex CHD. Firstly, our prospective study will allow us to determine the correlation between age at the time of surgery (days of life) and neurodevelopmental outcomes at 24 months. We will then analyze the correlation between age at surgery and (i) the incidence of WMIs (through pre- and postoperative MRIs), (ii) postoperative morbidity, and (iii) the duration of the hospital stay. Implications and Dissemination: This research protocol was registered in the Clinical Trial Registry (National Clinical Trial: NCT04733378). This project aims to help launch the first Neurocardiac Investigation Clinic in Marseille - AP-HM - to propose an overall personalized monitoring and treatment program for patients operated on for complex CHD.

Comparison of Short and Long Term Cardiovascular Outcomes After Bariatric Surgery in Patients With vs Without Coronary Artery Disease.

There is little data regarding the risks and benefits of bariatric surgery in patients with coronary artery disease (CAD). We aimed to assess the short- and long-term cardiovascular outcomes of patients with CAD undergoing bariatric surgery. Patients with a history of CAD were identified from a dedicated database with prospectively collected outcomes, comprising all 6795 patients who underwent bariatric surgery between January 1992 and October 2017. Patients were matched with patients who did not have CAD before the bariatric surgery procedure. The primary endpoints were mortality (cardiac and noncardiac) and major adverse cardiocerebral events (MACCE), including all-cause death, myocardial infarction, stroke, and myocardial revascularization at 30 days after bariatric surgery and throughout follow-up. After propensity score matching, 249 patients with chronic CAD were matched with 249 patients without CAD. Throughout follow-up (7.4 years; interquartile range 4.1 to 11.5, maximum 22 years), mortality (mainly cardiac mortality) remained significantly higher in the CAD compared with the non-CAD group (18% vs 10%, hazard ratio [HR] 1.70, 95% confidence interval [CI]: 1.03 to 2.79, p = 0.037). At 30 days, MACCE rate was significantly higher in the CAD compared with the non-CAD group (3.6% vs 0.4%, p = 0.011), essentially driven by non-ST elevation myocardial infarctions. After 30 days, MACCE rates remained significantly higher in the CAD group (30% vs 14%, HR 2.18, 95% CI: 1.45-3.28, p = 0.0002). In conclusion, patients with severe obesity and CAD referred to bariatric surgery were at a higher risk of early and late MACCE compared with non-CAD severely obese patients. Further study is required to define how this cardiovascular risk compares with nonoperated patients.

Outcome Comparison in Children Undergoing Extracorporeal Life Support Initiated at a Local Hospital by a Mobile Cardiorespiratory Assistance Unit or at a Referral Center.

PURPOSE: To compare characteristics and outcome in children undergoing extracorporeal life support initiated in an extracorporeal life support center or at the patient's bedside in a local hospital, by means of a mobile cardiorespiratory assistance unit. METHODS: A retrospective study in a single PICU during 6 years. Extracorporeal life support was started either in our center (control group) or in the local hospital (mobile cardiorespiratory assistance unit group). The data collected were demographics, markers of patient's preextracorporeal life support condition, and outcome. RESULTS: One hundred twenty-six children underwent extracorporeal life support, 105 in the control group and 21 in the mobile cardiorespiratory assistance unit group. There was no difference between groups in terms of age, weight, or Pediatric Risk of Mortality II score. There was a significant difference in organ failure etiology between groups, with more respiratory cases in the mobile cardiorespiratory assistance unit group (76.2%) and more cardiac surgery cases in the control group (60%; p < 0.001). The duration of extracorporeal life support was longer in the mobile cardiorespiratory assistance unit group than in the control group (10 [1-36] vs 5 [0-33] d; p = 0.003). PICU length of stay and mortality (60% vs 47.6%; p = 0.294) were not significantly different between the two groups. To allow comparison of a more homogenous population, a subgroup analysis was performed including only respiratory failure patients from the two groups (R-control group [n = 22] and R-mobile cardiorespiratory assistance unit group [n = 16]). PICU length of stay was 17 (3-64) days in the R-control group and 23 (1-45) days in the R-mobile cardiorespiratory assistance unit group (p = 0.564), and PICU mortality rate was 54.5% in the R-control group and 43.8% in the R-mobile cardiorespiratory assistance unit group (p = 0.511). There was no difference between the R-groups for age, weight, Pediatric Risk of Mortality II score, and markers of kidney or liver dysfunction, and lactate blood levels. CONCLUSION: Extracorporeal life support can be safely initiated at children's bedside in the local hospital and then transported to the specialized referral center. Our results support the validity of an interregional organization of mobile cardiorespiratory assistance unit teams.

Metabolic changes induced by the biliopancreatic diversion in diet-induced obesity in male rats: the contributions of sleeve gastrectomy and duodenal switch.

The mechanisms underlying the body weight and fat loss after the biliopancreatic diversion with duodenal switch (BPD/DS) remain to be fully delineated. The aim of this study was to examine the contributions of the two main components of BPD/DS, namely sleeve gastrectomy (SG) and duodenal switch (DS), on energy balance changes in rats rendered obese with a high-fat (HF) diet. Three different bariatric procedures (BPD/DS, SG, and DS) and three sham surgeries were performed in male Wistar rats. Sham-operated animals fed HF were either fed ad libitum (Sham HF) or pair weighed (Sham HF PW) by food restriction to the BPD/DS rats. A group of sham-operated rats was kept on standard chow and served as normal diet control (Sham Chow). All three bariatric surgeries resulted in a transient reduction in food intake. SG per se induced a delay in body weight gain. BPD/DS and DS led to a noticeable gut malabsorption and a reduction in body weight and fat gains along with significant elevations in plasma levels of glucagon-like peptide-1(7-36) and peptide YY. BPD/DS and DS elevated energy expenditure above that of Sham HF PW during the dark phase. However, they reduced the volume, oxidative metabolism, and expression of thermogenic genes in interscapular brown adipose tissue. Altogether the results of this study suggest that the DS component of the BPD/DS, which led to a reduction in digestible energy intake while sustaining energy expenditure, plays a key role in the improvement in the metabolic profile led by BPD/DS in rats fed a HF diet.

Pathways of adipose tissue androgen metabolism in women: depot differences and modulation by adipogenesis.

The objective was to examine pathways of androgen metabolism in abdominal adipose tissue in women. Abdominal subcutaneous (SC) and omental (OM) adipose tissue samples were surgically obtained in women. Total RNA was isolated from whole adipose tissue samples and from primary preadipocyte cultures before and after induction of differentiation. Expression levels of several steroid-converting enzyme transcripts were examined by real-time RT-PCR. Androgen conversion rates were also measured. We found higher expression levels in SC compared with OM adipose tissue for type 1 3beta-hydroxysteroid dehydrogenase (3beta-HSD-1; P < 0.05), for aldo-keto reductase 1C3 (AKR1C3; P < 0.0001), for AKR1C2 (P < 0.0001), and for the androgen receptor (P < 0.0001). 17beta-HSD-2 mRNA levels were lower in SC adipose tissue (P < 0.05). Induction of adipocyte differentiation led to significantly increased expression levels in SC cultures for AKR1C3 (4.7-fold, P < 0.01), 11-cis-retinol dehydrogenase (6.9-fold, P < 0.02), AKR1C2 (5.6-fold, P < 0.004), P-450 aromatase (5.7-fold, P < 0.02), steroid sulfatase (3.1-fold, P < 0.02), estrogen receptor-beta (11.8-fold, P < 0.01), and the androgen receptor (4.0-fold, P < 0.0005). Generally similar but nonsignificant trends were obtained in OM cultures. DHT inactivation rates increased with differentiation, this effect being mediated by dexamethasone alone, through a glucocorticoid receptor-dependent mechanism. In conclusion, higher mRNA levels of enzymes synthesizing and inactivating androgens are found in differentiated adipocytes, consistent with higher androgen-processing rates in these cells. Glucocorticoid-induced androgen inactivation may locally modulate the exposure of adipose cells to active androgens.

Impact of bariatric surgery--induced weight loss on heart rate variability.

Obesity is associated with an increased risk of sudden death that may be due to abnormal cardiac vagal modulation reflected by reduced heart rate variability (HRV). Few studies have been conducted analyzing the effect of bariatric surgery-induced weight loss on HRV assessed by 24-hour Holter monitoring. The aim of this study was to assess weight loss effect after bariatric surgery on HRV and ventricular size and function. Ten morbidly obese patients, 6 women and 4 men aged 24 to 47 years, underwent bariatric surgery. Seven morbidly obese patients without active obesity treatment were used as controls. Twenty-four-hour Holter monitoring and echocardiogram were obtained before and at 6 to 12 months after surgery or at follow-up in control patients. Changes in minimal, maximal, and mean heart rate along with HRV during daytime and nighttime were compared before and after surgery. Baseline characteristics in the control group did not differ significantly from the treatment group. Average weight in the treatment group was 141 +/- 31 kg (mean +/- SD) at baseline and decreased to 101 +/- 18 kg at follow-up, corresponding to a body mass index of 52.3 +/- 7.6 kg/m(2) at baseline and 37.7 +/- 5.3 kg/m(2) at follow-up. There was a decrease in minimal heart rate (48 +/- 10 vs 40 +/- 6 beats per minute, P = .021) and mean heart rate (82 +/- 7 vs 66 +/- 10 beats per minute, P < .001) during the Holter monitoring. Spectral analysis showed a significant enhancement in HRV parameters (high- and low-frequency power) because there was an increase in the standard deviation of normal to normal R-R intervals (116 +/- 25 vs 174 +/- 56 milliseconds, P < .001), the standard deviation of the mean R-R intervals calculated over a 5-minute period (104 +/- 25 vs 148 +/- 45 milliseconds, P < .001), the square root of the mean of the squared differences between adjacent normal R-R intervals (25 +/- 8 vs 50 +/- 20 milliseconds, P < .001), and the percentage of differences between adjacent normal R-R intervals exceeding 50 milliseconds (5% +/- 5% vs 22% +/- 13%, P < .001). Echocardiographic measures remained unchanged when comparing the groups. Weight loss after bariatric surgery enhances HRV and decreases mean and minimal heart rate during Holter monitoring through a better cardiac parasympathetic modulation.

Health-related quality of life in morbid obesity.

BACKGROUND: In order to evaluate the impact of severe obesity and its treatment on quality of life (QoL), it would be important to first identify the areas of QoL most likely to be affected by the disease. METHODS: We first constructed a list of 187 items potentially related to QoL of patients with morbid obesity. From this list, consecutive candidates for bariatric surgery were asked to identify what they felt were the most significant items and to grade their importance. The item impact was determined from the proportion of patients who identified it as important, and the mean importance score attributed to this item (impact score = frequency X importance). RESULTS: 100 patients (68 female; mean body mass index 51.5 kg/m(2); mean age 42) were interviewed. Overall, the impact of morbid obesity was more important in women than in men. The areas of impairment were very similar in both groups, with the important difference that women ranked their dissatisfaction with physical appearance higher than men. The items having the most important impact on QoL clustered into 7 domains: 1) activity/mobility; 2) symptoms; 3) personal hygiene/clothing; 4) emotions; 5) social interactions; 6) sexual life; and 7) eating behavior. CONCLUSION: The impact of morbid obesity on QoL is not limited to the activity/mobility domain. Morbid obesity contributes to the impairment of all domains of what is usually referred to as "health-related quality of life".

Asthma and sleep apnea in patients with morbid obesity: outcome after bariatric surgery.

BACKGROUND: Asthma and sleep apnea syndrome (SAS) are frequently reported in obese patients. The authors determined the prevalence of asthma and SAS in morbidly obese patients and the effect of biliopancreatic diversion with duodenal switch (BPD-DS) on these conditions. METHODS: 398 patients were evaluated for bariatric surgery in a university-affiliated tertiary care center. All patients completed a written questionnaire on asthma and SAS before BPD-DS. In addition, 139 patients also completed a questionnaire on their general health status, including asthma and SAS, 2 years after the procedure. RESULTS: For the cohort of 398 patients, the prevalence of self-reported asthma was 30.4% and that of SAS, 32.2%. No significant association was found between asthma and SAS diagnosis (P =0.10). Significant relationships were observed between the diagnosis of asthma and age, hip circumference, waist/hip ratio, weight and BMI of the patients as well as between a diagnosis of SAS and gender, waist circumference, hip circumference, waist/hip ratio, weight and BMI. 2 years after surgery (mean BMI was reduced from 51.4 to 30.5 kg/m(2)), asthma was reported improved in 79.3% of patients and SAS was improved in all but one with this condition; among 29 SAS patients using CPAP before surgery, only 4 were still using this treatment after 2 years. CONCLUSION: The prevalence of asthma and SAS is high in the morbidly obese population and is associated with markers of obesity. We found no association between the diagnosis of asthma and SAS diagnosis in this population. BPD-DS improved self-reported severity of asthma and SAS symptoms.

Metabolic and cardiovascular improvements after biliopancreatic diversion in a severely obese patient.

BACKGROUND: Severe obesity is associated with important morbidity and increased mortality. The successes of lifestyle modifications and drug therapy have been partial and mostly unsustained in reducing obesity and its comorbidities. Bariatric surgery, particularly biliopancreatic diversion with duodenal switch reduces efficiently excess body weight and improves metabolic and cardiovascular functions. CASE PRESENTATION: A 56-year-old man with severe clinical obesity underwent a biliopancreatic diversion with a duodenal switch after unsuccessful treatment with weight loss pharmacotherapy. He had diabetes, hypertension and sleep apnea syndrome and was on three medications for hypertension and two hypoglycemic agents in addition to > 200 insulin units daily. Eleven months after the surgery, he had lost 40% of his body weight. The lipid profile showed great improvement and the hypertension and diabetes were more easily controlled with no more insulin needed. The pseudonormalized pattern of left ventricular diastolic function improved and ventricular walls showed decreased thickness. CONCLUSION: Biliopancreatic diversion may bring metabolic and cardiovascular benefits in severely obese patients from a cardiovascular perspective.