Completion pancreatectomy during pancreatoduodenectomy: A lifesaving solution in high-risk patients.

BACKGROUND: Postoperative pancreatic fistula (POPF) is responsible of most major complications and fatalities after PD. By avoiding POPF, TP may improve operative outcomes in high-risk patients. The aim was to compare total pancreatectomy (TP) and pancreatoduodenectomy (PD) in high-risk patients and evaluate results of implementing a risk-tailored strategy in clinical practice. METHODS: Between 2014 and 2023, 139 patients (76 men, median age 67 years) underwent resection of disease located in the head of the pancreas. Starting January 1, 2022, we offered TP to patients at high POPF risks (fistula risk score (FRS) ≥7) and to patients with intermediate POPF risks (FRS: 3-6) and high risks of failure to rescue (age> 75 years, ASA score ≥3). We compared outcomes of TP and PD and evaluated the results of the new strategy implementation on operative outcomes. Propensity score-based analysis was performed to limit bias of between-group comparison. RESULTS: Eventually, 26 (19%) patients underwent TP and 113 (81%) patients underwent PD. Severe complications occurred in 42 (30%) patients and 13 (9%) patients died. TP resulted in shorter lengths of hospital stay (median: 14 days [11; 18] vs. 17 days [13; 24], p = 0.016) and less risks of post-pancreatectomy hemorrhage (PPH) (0% vs. 20%, p < 0.001) compared to PD. Crude and propensity match analysis showed that the implementation of a risk-tailored strategy led to significant reduction of reoperation, POPF, PPH and mortality rates. CONCLUSION: The use of TP as part of a risk-tailored strategy in high-risk patients can be lifesaving.

Chemogenetic activation of prefrontal astroglia enhances recognition memory performance in rat.

Prefrontal cortex (PFC) inputs to the hippocampus are supposed to be critical in memory processes. Astrocytes are involved in several brain functions, such as homeostasis, neurotransmission, synaptogenesis. However, their role in PFC-mediated modulation of memory has yet to be studied. The present study aims at uncovering the role of PFC astroglia in memory performance and synaptic plasticity in the hippocampus. Using chemogenetic and lesions approaches of infralimbic PFC (IL-PFC) astrocytes, we evaluated memory performance in the novel object recognition task (NOR) and dorsal hippocampus synaptic plasticity. We uncovered a surprising role of PFC astroglia in modulating object recognition memory. In opposition to the astroglia PFC lesion, we show that chemogenetic activation of IL-PFC astrocytes increased memory performance in the novel object recognition task and facilitated in vivo dorsal hippocampus synaptic metaplasticity. These results redefine the involvement of PFC in recognition mnemonic processing, uncovering an important role of PFC astroglia.

Effect of a lifestyle intervention to prevent weight gain at initiation of insulin pump therapy in type 2 diabetes: A randomized, controlled, multicentre trial.

Insulin pump therapy improves glycaemic control in individuals with type 2 diabetes. However, it may be associated with weight gain. AIM: To test the effectiveness of a six-month dietary and physical activity intervention, compared to usual care, on weight gain prevention after initiation of insulin pump. METHODS: Multicentre randomized, controlled trial of 54 individuals. Primary endpoint was between group difference in weight gain at six-months. RESULTS: Weight gain after 6 months of insulin pump treatment did not differ between groups: mean 3.2 (3.9) kg in the control group and 3.9 (3.8) kg in the intervention group, (p = 0.56). HbA1c improved without difference between groups. Post-hoc multivariate analysis of all participants found that weight gain was independently associated with younger age, active smoking, and the magnitude of HbA1c reduction. A 1 % decrease in HbA1c was associated with an increase of 0.94 kg [95 % Confidence Interval 0.47; 1.41], p < 0.001. CONCLUSIONS: Treatment intensification by insulin pump therapy in patients with type 2 diabetes is effective to improve glycaemic control. A gain of about 1 kg per 1 % drop in HbA1c can be expected after insulin treatment intensification. This weight gain was not prevented by a home-base, individualized, 6-months lifestyle intervention program.

High prevalence with no gender difference of likely eating disorders in type 1 mellitus diabetes on insulin pump.

AIM: The aim of this study was to determine the prevalence of likely eating disorders and insulin misuse in a prospective cohort of adults with type 1 diabetes mellitus (T1DM) treated with insulin pump therapy. METHODS: This prospective study was held at the participants' home. The participants completed the SCOFF questionnaire as well as a question related to insulin misuse. Information about lifestyle, medical history, insulin pump and Continuous Glucose Monitoring (CGM) data were collected. RESULTS: The analysis covered 198 participants with a median age of 51 [95% CI 38; 62] years. The prevalence of likely eating disorders was 21.7% (95% CI 16.3; 28.2) in the study population and 20.6% (95% CI 14.3; 28.6) and 24.2% (95% CI 14.6; 37.0) in males and females respectively. The prevalence of insulin misuse was 39.0% (95% CI 30.8; 47.7). There was no significant difference in prevalence between males and females for likely eating disorders and insulin misuse. The analysis of CGM data revealed no factors related to glycaemic control associated with likely eating disorders. CONCLUSION: The results of this study indicate that the prevalence of likely eating disorders is high even in a middle-aged population with a T1DM and satisfactory glucose control.

Regional CZT myocardial perfusion reserve for the detection of territories with simultaneously impaired CFR and IMR in patients without obstructive coronary artery disease: a pilot study.

OBJECTIVES: To assess the diagnostic performances of CZT myocardial perfusion reserve (MPR) for the detection of territories with simultaneous impaired coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients without obstructive coronary artery disease. METHODS: Patients were prospectively included before being referred for coronary angiography. All patients underwent CZT MPR before invasive coronary angiography (ICA) and coronary physiology assessment. Rest and dipyridamole-induced stress myocardial blood flow (MBF) and MPR were quantified using 99mTc-SestaMIBI and a CZT camera. Fractional flow reserve (FFR), Thermodilution CFR, and IMR were assessed during ICA. RESULTS: Between December 2016 and July 2019, 36 patients were included. 25/36 patients presented no obstructive coronary artery disease. A complete functional assessment was performed in 32 arteries. No territory presented a significant ischemia on CZT myocardial perfusion imaging. A moderate yet significant correlation was observed between regional CZT MPR and CFR (r = 0.4, P = .03). Sensitivity, specificity, positive and negative predictive value, and accuracy of regional CZT MPR versus the composite invasive criterion (impaired CFR and IMR) were 87 [47% to 99%], 92% [73% to 99%], 78% [47% to 93%], 96% [78% to 99%], and 91% [75% to 98%], respectively. All territories with a regional CZT MPR ≤ 1.8 showed a CFR < 2. Regional CZT MPR values were significantly higher in arteries with CFR ≥ 2 and IMR < 25 (negative composite criterion, n = 14) than in those with CFR < 2 and IMR ≥ 25 (2.6 [2.1 to 3.6] versus 1.6 [1.2 to 1.8]), P < .01). CONCLUSION: Regional CZT MPR presented excellent diagnostic performances for the detection of territories with simultaneously impaired CFR and IMR reflecting a very high cardiovascular risk in patients without obstructive coronary artery disease.

A comparative study of two automated solutions for cross-sectional skeletal muscle measurement from abdominal computed tomography images.

BACKGROUND: Measurement of cross-sectional muscle area (CSMA) at the mid third lumbar vertebra (L3) level from computed tomography (CT) images is becoming one of the reference methods for sarcopenia diagnosis. However, manual skeletal muscle segmentation is tedious and is thus restricted to research. Automated solutions are required for use in clinical practice. PURPOSE: The aim of this study was to compare the reliability of two automated solutions for the measurement of CSMA. METHODS: We conducted a retrospective analysis of CT images in our hospital database. We included consecutive individuals hospitalized at the Grenoble University Hospital in France between January and May 2018 with abdominal CT images and sagittal reconstruction. We used two types of software to automatically segment skeletal muscle: ABACS, a module of the SliceOmatic software solution "ABACS-SliceOmatic," and a deep learning-based solution called "AutoMATiCA." Manual segmentation was performed by a medical expert to generate reference data using "SliceOmatic." The Dice similarity coefficient (DSC) was used to measure overlap between the results of the manual and the automated segmentations. The DSC value for each method was compared with the Mann-Whitney U test. RESULTS: A total of 676 hospitalized individuals was retrospectively included (365 males [53.8%] and 312 females [46.2%]). The median DSC for SliceOmatic vs AutoMATiCA (0.969 [5th percentile: 0.909]) was greater than the median DSC for SliceOmatic vs. ABACS-SliceOmatic (0.949 [5th percentile: 0.836]) (p < 0.001). CONCLUSIONS: AutoMATiCA, which used artificial intelligence, was more reliable than ABACS-SliceOmatic for skeletal muscle segmentation at the L3 level in a cohort of hospitalized individuals. The next step is to develop and validate a neural network that can identify L3 slices, which is currently a fastidious process.

ODIASP: Clinically Contextualized Image Analysis Using the PREDIMED Clinical Data Warehouse, Towards a Better Diagnosis of Sarcopenia.

Big Data and Deep Learning approaches offer new opportunities for medical data analysis. With these technologies, PREDIMED, the clinical data warehouse of Grenoble Alps University Hospital, sets up first clinical studies on retrospective data. In particular, ODIASP study, aims to develop and evaluate deep learning-based tools for automatic sarcopenia diagnosis, while using data collected via PREDIMED, in particular, medical images. Here we describe a methodology of data preparation for a clinical study via PREDIMED.

Antecubital Vein Cannula Position Impacts Assessment of Forearm Glucose Uptake During an Oral Glucose Challenge in Healthy Volunteers.

INTRODUCTION: Skeletal muscle is a major site for whole-body glucose disposal, and determination of skeletal muscle glucose uptake is an important metabolic measurement, particularly in research focussed on interventions that impact muscle insulin sensitivity. Calculating arterial-venous difference in blood glucose can be used as an indirect measure for assessing glucose uptake. However, the possibility of multiple tissues contributing to the composition of venous blood, and the differential in glucose uptake kinetics between tissue types, suggests that sampling from different vein sites could influence the estimation of glucose uptake. This study aimed to determine the impact of venous cannula position on calculated forearm glucose uptake following an oral glucose challenge in resting and post-exercise states. MATERIALS AND METHODS: In 9 young, lean, males, the impact of sampling blood from two antecubital vein positions; the perforating vein ('perforating' visit) and, at the bifurcation of superficial and perforating veins ('bifurcation' visit), was assessed. Brachial artery blood flow and arterialised-venous and venous blood glucose concentrations were measured in 3 physiological states; resting-fasted, resting-fed, and fed following intermittent forearm muscle contraction (fed-exercise). RESULTS: Following glucose ingestion, forearm glucose uptake area under the curve was greater for the 'perforating' than for the 'bifurcation' visit in the resting-fed (5.92±1.56 vs. 3.69±1.35 mmol/60 min, P<0.01) and fed-exercise (17.38±7.73 vs. 11.40±7.31 mmol/75 min, P<0.05) states. DISCUSSION: Antecubital vein cannula position impacts calculated postprandial forearm glucose uptake. These findings have implications for longitudinal intervention studies where serial determination of forearm glucose uptake is required.

In Underweight Women, Insufficient Gestational Weight Gain Is Associated with Adverse Obstetric Outcomes.

The pre-pregnancy BMI and the gestational weight gain are two important determinants of pregnancy outcomes. The aim of this study was to determine obstetric outcomes associated with insufficient gestational weight gain in women with a pre-pregnancy BMI < 18.5 kg/m2. This study was based on observational routinely collected data from University Hospital Maternity. The participants were allocated to the group sufficient or insufficient gestational weight gain: ≥12.5 kg and <12.5 kg respectively. Primary outcomes were the adjusted birth weight in percentiles (%) and the proportion of SGA newborns. Secondary outcomes were obstetric and perinatal outcomes. A total of 132 participants with a median age of 28 ± 8 years were included. The adjusted birth weight in percentiles was significantly lower in the insufficient gestational weight gain group (27.3 ± 45.0 vs. 46.3 ± 46.2%; p < 0.001). Moreover, the insufficient gestational weight gain is associated with a higher risk of SGA (27.0% vs. 11.6%; p = 0.03). Our study also showed increased risks of premature rupture of membranes, anaemia, and intrauterine growth restriction in women with an insufficient weight gain. Future studies should explore the risk factors associated with insufficient weight gain, in order to develop specific care for underweight pregnant women.

Bariatric surgery short-term outcomes in patients with obstructive sleep apnoea: the Severe Obesity Outcome Network prospective cohort.

BACKGROUND/OBJECTIVES: Although the benefits of bariatric surgery have been clearly established, it is not known whether they are as important in patients with obstructive sleep apnoea (OSA). Primary aim: to evaluate whether patients with moderate-to-severe OSA (apnoea-hypopnea index (AHI) ≥ 15 events/h) treated by continuous positive airway pressure/non-invasive ventilation (median [IQR] adherence 6.5 h/night [5; 7.9] at baseline) lose the same amount of body weight 1 year after bariatric surgery as patients with no or mild OSA. Secondary objectives: to compare the evolution of type 2 diabetes and hypertension after bariatric surgery, and surgical complication rates between groups. METHODS/SUBJECTS: Analyses were performed in 371 patients included in a prospective cohort of bariatric surgery, the Severe Obesity Outcome Network cohort. Subjects having moderate-to-severe OSA (n = 210) at baseline were compared with other subjects (n = 161). RESULTS: Excess weight loss (%EWL) at 1 year was lower in patients with moderate-to-severe OSA than in patients without (64.9%EWL [46.9; 79.5] vs. 73.8%EWL [56.6; 89.3], p < 0.01). Multivariable analysis showed that age, initial body mass index and type of surgery, but not OSA status, were associated with 1-year %EWL. Diabetes remitted in 25 (41%) patients with moderate-to-severe OSA and 16 (48%) patients with no or mild OSA (p = 0.48). Hypertension remitted in 28 (32.9%) patients with moderate-to-severe OSA and 9 (40.9%) with no or mild (p = 0.48). Complication rates were 28 (13.3%) in patients with moderate-to-severe OSA and 12 (7.5%) in patients with no or mild OSA (p = 0.07). CONCLUSIONS: Patients with OSA lose less body weight after bariatric surgery. This was related to older age and a higher baseline body mass index. However, the improvements of diabetes and hypertension were similar to that of patients without OSA, and the risk of surgical complications was not higher.

Impact of Bariatric Surgery on Medication Efficacy: an Analysis of World Health Organization Pharmacovigilance Data.

Bariatric surgery is the most effective treatment of severe obesity. However, this surgery can have an impact on the bioavailability and metabolism of oral drugs as it modifies absorption, intestinal, and hepatic metabolism, and efflux transporter activity. The clinical impact of such modifications often remains unknown. To investigate, we extracted and summarized all reports of changes in drug efficacy associated with bariatric surgery registered in the WHO pharmacovigilance database. We identified 165 drug reports affecting 128 patients. The majority involved gastric bypass surgery (77.3%). Most reports concerned drug ineffectiveness (74.7%). The most frequent modifications concerned psychotropic drugs with a reduction in efficacy. This study underlines the urgent need for more research to better characterize the impact of bariatric surgery on drug pharmacokinetics and clinical efficacy.

A series of severe neurologic complications after bariatric surgery in France: the NEUROBAR Study.

BACKGROUND: Neurologic complications after bariatric surgery are rare, but can have dramatic consequences. Little data are available on this topic. OBJECTIVES: The aim of the Neurologic complications after BARiatric surgery (NEUROBAR) study was to define, which factors (anthropometric, nutritional, surgical, etc.) were frequently associated with neurologic complications after bariatric surgery. SETTINGS: Data were collected by the French Centers of Obesity Care Management hosted in University Hospitals. METHODS: An online standardized questionnaire was designed and submitted to the 37 French Centers of Obesity Management. This questionnaire included items about patient characteristics, bariatric surgery, neurologic complications, nutritional status, and management. Patients were retrospectively included from January 2010 to November 2018. RESULTS: Thirteen centers included 38 patients (34 females and 4 males) with neurologic complications after bariatric surgery. The 2 main bariatric procedures were gastric bypass and sleeve gastrectomy. More than half of the patients with neurologic complications had a surgical complication after bariatric surgery (53%) and gastrointestinal symptoms, including vomiting (53%). Vitamin B deficiencies were frequent (74%) including at least 47% of cases with deficiency in Vitamin B1. CONCLUSION: Early identification of patients with surgical complications and gastrointestinal symptoms after bariatric surgery could help prevent neurologic complications related to nutritional deficiencies.

Benefits and risks of bariatric surgery in patients with bipolar disorders.

The prevalence of bipolar disorders in patients requesting bariatric surgery is estimated to be 1.5% to 3.4%. There are currently no specific recommendations regarding the way bariatric surgery should be managed in the context of bipolar disorder. The aim was to document the benefit-risk of bariatric surgery in patients with bipolar disorders. A systematic literature review was carried out. In addition, results were reported from a survey of current clinical practice in French referent centers for obesity care. Finally, 3 clinical cases from the "Severe Obesity Outcome Network" cohort are described. This systematic review shows there are few studies in the literature regarding the outcomes of bariatric surgery in patients with bipolar disorders and no randomized, controlled trials. Weight loss appeared similar in all patients, but psychiatric complications were sometimes reported in those with bipolar disorders. Almost all 11 referent centers for obesity care that responded had carried out bariatric surgery in patients with stable bipolar disorders. Postsurgical psychiatric destabilization occurred and included, at least, a need to reinforce treatment and follow-up. In the 3 case studies, postsurgical manic or hypomanic decompensation occurred. Thus, although effective in terms of weight loss, bariatric surgery could be a destabilizing factor for those with bipolar disorders. Current practice is to contraindicate surgery in patients with unstable disorders. There are insufficient data to conclude on the benefits and safety of bariatric surgery in patients with stable bipolar disease. Further studies are required to fully determine the benefits and risks.

Hyperphagia in short bowel patients: Fat-free mass is a strong predictor.

OBJECTIVES: Some patients with short bowel syndrome (SBS) develop hyperphagic behavior. Such an increase in food intake stimulates intestinal adaptation and limits dependence on parenteral nutrition (PN). The aim of this study was to determine the factors modulating food consumption in patients with SBS. METHODS: The associations between oral energy intake (OEI) and anthropometric, metabolic, nutritional, and intestinal absorption-related characteristics were determined in a monocentric cohort of patients with SBS on PN with a stable nutritional status. Body composition was assessed by dual x-ray absorptiometry. Data were retrospectively collected from clinical records. RESULTS: After screening, 38 adult patients with a SBS on PN were included in this study. OEI ranged from 577 to 4054kcal/d. OEI correlated positively with weight, fat-free mass, handgrip strength, and resting energy expenditure (REE) and negatively with free triiodothyronine and C-reactive protein using Spearman correlation. Fat-free mass and thyroid-stimulating hormone remained positively correlated with OEI independently of all other parameters in a multilinear regression model. CONCLUSIONS: Fat-free mass is a strong predictor of OEI in patients with SBS on PN and without debilitating gastrointestinal symptoms. Increasing fat-free mass could be a way to stimulate OEI in these patients. Further studies are needed to assess this assumption.

Deep brain stimulation as a therapeutic option for obesity: A critical review.

Despite a better understanding of obesity pathophysiology, treating this disease remains a challenge. New therapeutic options are needed. Targeting the brain is a promising way, considering both the brain abnormalities in obesity and the effects of bariatric surgery on the gut-brain axis. Deep brain stimulation could be an alternative treatment for obesity since this safe and reversible neurosurgical procedure modulates neural circuits for therapeutic purposes. We aimed to provide a critical review of published clinical and preclinical studies in this field. Owing to the physiology of eating and brain alterations in people with obesity, two brain areas, namely the hypothalamus and the nucleus accumbens are putative targets. Preclinical studies with animal models of obesity showed that deep brain stimulation of hypothalamus or nucleus accumbens induces weight loss. The mechanisms of action remain to be fully elucidated. Preclinical data suggest that stimulation of nucleus accumbens reduces food intake, while stimulation of hypothalamus could increase resting energy expenditure. Clinical experience with deep brain stimulation for obesity remains limited to six patients with mixed results, but some clinical trials are ongoing. Thus, drawing clear conclusions about the effectiveness of this treatment is not yet possible, even if the results of preclinical studies are encouraging. Future clinical studies should examine its efficacy and safety, while preclinical studies could help understand its mechanisms of action. We hope that our review will provide ways to design further studies.

An artificial neural network to predict resting energy expenditure in obesity.

BACKGROUND & AIMS: The resting energy expenditure (REE) determination is important in nutrition for adequate dietary prescription. The gold standard i.e. indirect calorimetry is not available in clinical settings. Thus, several predictive equations have been developed, but they lack of accuracy in subjects with extreme weight including obese populations. Artificial neural networks (ANN) are useful predictive tools in the area of artificial intelligence, used in numerous clinical fields. The aim of this study was to determine the relevance of ANN in predicting REE in obesity. METHODS: A Multi-Layer Perceptron (MLP) feed-forward neural network with a back propagation algorithm was created and cross-validated in a cohort of 565 obese subjects (BMI within 30-50 kg m-2) with weight, height, sex and age as clinical inputs and REE measured by indirect calorimetry as output. The predictive performances of ANN were compared to those of 23 predictive REE equations in the training set and in two independent sets of 100 and 237 obese subjects for external validation. RESULTS: Among the 23 established prediction equations for REE evaluated, the Harris & Benedict equations recalculated by Roza were the most accurate for the obese population, followed by the USA DRI, Müller and the original Harris & Benedict equations. The final 5-fold cross-validated three-layer 4-3-1 feed-forward back propagation ANN model developed in that study improved precision and accuracy of REE prediction over linear equations (precision = 68.1%, MAPE = 8.6% and RMSPE = 210 kcal/d), independently from BMI subgroups within 30-50 kg m-2. External validation confirmed the better predictive performances of ANN model (precision = 73% and 65%, MAPE = 7.7% and 8.6%, RMSPE = 187 kcal/d and 200 kcal/d in the 2 independent datasets) for the prediction of REE in obese subjects. CONCLUSIONS: We developed and validated an ANN model for the prediction of REE in obese subjects that is more precise and accurate than established REE predictive equations independent from BMI subgroups. For convenient use in clinical settings, we provide a simple ANN-REE calculator available at: https://www.crnh-rhone-alpes.fr/fr/ANN-REE-Calculator.