Nutritional biomarkers and heart failure requiring hospitalization in patients with type 2 diabetes: the SURDIAGENE cohort.

BACKGROUND: Heart failure (HF) is a growing complication and one of the leading causes of mortality in people living with type 2 diabetes (T2D). Among the possible causes, the excess of red meat and the insufficiency of vegetables consumption are suspected. Such an alimentation is associated with nutritional biomarkers, including trimethylamine N-oxide (TMAO) and its precursors. Here, we aimed to study these biomarkers as potential prognostic factors for HF in patients with T2D. METHODS: We used the SURDIAGENE (SURvival DIAbetes and GENEtics) study, a large, prospective, monocentric cohort study including 1468 patients with T2D between 2001 and 2012. TMAO and its precursors (trimethylamine [TMA], betaine, choline, and carnitine) as well as thio-amino-acids (cysteine, homocysteine and methionine) were measured by liquid chromatography-tandem mass spectrometry. The main outcome was HF requiring Hospitalization (HFrH) defined as the first occurrence of acute HF leading to hospitalization and/or death, established by an adjudication committee, based on hospital records until 31st December 2015. The secondary outcomes were the composite event HFrH and/or cardiovascular death and all-cause death. The association between the biomarkers and the outcomes was studied using cause-specific hazard-models, adjusted for age, sex, history of coronary artery disease, NT-proBNP, CKD-EPI-derived eGFR and the urine albumin/creatinine ratio. Hazard-ratios (HR) are expressed for one standard deviation. RESULTS: The data of interest were available for 1349/1468 of SURDIAGENE participants (91.9%), including 569 (42.2%) women, with a mean age of 64.3 ± 10.7 years and a median follow-up of 7.3 years [25th-75th percentile, 4.7-10.8]. HFrH was reported in 209 patients (15.5%), HFrH and/or cardiovascular death in 341 (25.3%) and all-cause death in 447 (33.1%). In unadjusted hazard-models, carnitine (HR = 1.20, 95% CI [1.05; 1.37]), betaine (HR = 1.34, [1.20; 1.50]), choline (HR = 1.35, [1.20; 1.52]), TMAO (HR = 1.32, [1.16; 1.50]), cysteine (HR = 1.38, [1.21; 1.58]) and homocysteine (HR = 1.28, [1.17; 1.39]) were associated with HFrH, but not TMA and methionine. In the fully adjusted models, none of these associations was significant, neither for HFrH nor for HFrH and/or CV death, when homocysteine only was positively associated with all-cause death (HR = 1.16, [1.06; 1.27]). CONCLUSIONS: TMAO and its precursors do not appear to be substantial prognosis factors for HFrH, beyond usual cardiac- and kidney-related risk factors, whereas homocysteine is an independent risk factor for all-cause death in patients with T2D.

Predictors of treatment outcome for youth receiving intensive residential treatment for obsessive-compulsive disorder (OCD).

Little is known about the predictors of outcome from intensive residential treatment of OCD. This study aimed to examine age, gender, and baseline OCD severity, as well as measures of comorbid anxiety and depressive, internalizing/externalizing, and inattention symptoms, as predictors of treatment outcome in adolescents receiving intensive residential treatment for OCD. The sample comprised 314 adolescents aged 13-17 years with treatment-resistant OCD and a Children's Yale-Brown Obsessive-Compulsive Scale Self-Report (CY-BOCS-SR) total score ≥16. Bivariate and multiple regression models were used to evaluate the predictors of continuous OCD severity outcome and treatment response. Results of the bivariate regression analyses of predictors demonstrated that length of treatment, pre-treatment OCD severity, and symptoms of anxiety and depression significantly predicted post-treatment OCD severity, while only symptoms of depression and anxiety predicted treatment response. When including all predictors in the same model, only baseline OCD severity remained a significant predictor of post-treatment OCD severity, and none of the assessed variables significantly predicted treatment response. Results indicate that low pre-treatment OCD severity predicts lower OCD severity following treatment, although it did not predict treatment response.

Kinetics of plasma apolipoprotein E isoforms by LC-MS/MS: a pilot study.

Human apoE exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in the APOE gene. Total plasma apoE concentrations are closely related to these isoforms, but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used LC-MS/MS to discriminate between isoforms by identifying specific peptide sequences in subjects (three E2/E3, three E3/E3, and three E3/E4 phenotypes) who received a primed constant infusion of 2H3-leucine for 14 h. apoE concentrations and leucine enrichments were measured hourly in plasma. Concentrations of apoE2 were higher than apoE3, and concentrations of apoE4 were lower than apoE3. There was no difference between apoE3 and apoE4 catabolic rates and between apoE2 and apoE3 production rates (PRs), but apoE2 catabolic rates and apoE4 PRs were lower. The mechanisms leading to the difference in total plasma apoE concentrations are therefore related to contrasted kinetics of the isoforms. Production or catabolic rates are differently affected according to the specific isoforms. On these grounds, studies on the regulation of the involved biochemical pathways and the impact of pathological environments are now warranted.

Further Psychometric Evaluation of the Child Disgust Scale.

This study evaluated the psychometric properties of the Child Disgust Scale (CDS) among 457 youth (ages 8-17, M = 14.77 ± 1.98 years) initiating residential treatment for obsessive-compulsive disorder and anxiety disorders. Confirmatory factor analysis supported a bifactor model with two distinct factors of Disgust Avoidance and Disgust Affect, in addition to an overall General Disgust factor. Strong internal consistency was observed for the CDS total and factor scores. In addition, CDS scores demonstrated generally modest and positive correlations with child-reported obsessive-compulsive and anxiety symptoms, weaker correlations with parent-reported anxiety and child-rated impairment, and non-significant correlations with parent-rated impairment. Findings suggest that the CDS displays strong psychometric properties and is developmentally appropriate for use in pediatric clinical populations with obsessive-compulsive and anxiety disorders.

Computer-assisted cognitive behavior therapy for obsessive-compulsive disorder: a randomized trial on the impact of lay vs. professional coaching.

BACKGROUND: The purpose of the study was to examine the impact of computerized cognitive behavior therapy (CBT) self-help treatment for obsessive-compulsive disorder (OCD) (BT Steps) both alone and when supported by coaching from either a lay non-therapist coach or an experienced CBT therapist. METHODS: Eighty-seven subjects with clinically significant OCD were recruited through newspaper ads and randomly assigned to receive 12 weeks of treatment with either BT Steps alone (n = 28), BT Steps with non-therapist coaching (n = 28), or BT Steps with CBT therapist coaching (n = 31). Subjects worked on BT Steps at their own pace. Subjects receiving BT Steps alone received a welcome call from the project manager. Subjects randomized to either of the coaching arms received regularly scheduled weekly phone calls for coaching, encouragement, and support. No formal therapy was provided by the coaches; thus, both lay and CBT coaches completed the same tasks. RESULTS: All three treatment arms showed a significant reduction in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, with mean (SD) changes of 6.5 (5.7), 7.1 (6.1), and 6.5 (6.1) for the no coaching, lay coaching, and therapist coaching arms, respectively (all p's < .001). These represent effect sizes of 1.16, 1.41, and 1.12, respectively. No significant differences were found between treatment arms on YBOCS change scores, F(2) = 0.10, p = .904, or number of exposures sessions done (F(2) = 0.033, p = .967). When asked which method of therapy (computer vs. clinician) they preferred, 48% said computer, 33% said face-to-face therapy, and 19% had no preference. CONCLUSIONS: Results support the use of online self-help for the treatment of moderate OCD. The addition of coaching by either a lay coach or a CBT therapist coach did not significantly improve outcomes.

Precision medicine in endocrinology: Unraveling metabolic health through time-restricted eating.

As a promising avenue in nutrition, intermittent fasting, particularly time-restricted eating like the 8/16 protocol, requires careful individualization. This approach involves voluntary food restriction interspersed with normal eating, aiming to align with inner circadian rhythms for potential benefits in metabolism and weight management. Endocrinologists, responding to patient interest and backed by evidence-based medicine, can now delve into the intricacies of time-restricted eating. They consider each patient's unique medical history and expectations, integrating this approach into tailored treatment plans in a personalized medicine approach. Ongoing research is essential to deepen our comprehension of how time-restricted eating influences metabolic health, enabling the development of precise recommendations suitable for diverse populations and various clinical conditions. While time-restricted eating is a relevant metabolic approach, endocrinologists should exercise caution to prevent the promotion of eating disorders due to its restrictive nature.

Adjuvant Glucose-Like Peptide 1 Receptor Agonist Therapy for Suboptimal Weight Loss After Bariatric Surgery: a Systematic Review.

Addressing suboptimal weight loss post-bariatric surgery poses a challenge. While glucagon-like peptide 1 receptor agonists (GLP1-RA) show promise in managing obesity, their role as an adjuvant treatment after bariatric surgery remains uncertain. We conducted a systematic literature review focused on the efficacy and safety of GLP1-RA in bariatric surgery patients with insufficient weight loss or distant weight regain. Our literature search identified 1167 articles, with 10 (involving 594 patients) meeting inclusion/exclusion criteria for detailed review. GLP1-RA therapy resulted in 5 to 17% weight loss over 6 to 12 months, with 10-50% experiencing non-severe side effects like nausea. Overall, GLP1-RA emerges as an effective adjuvant therapy for patients experiencing inadequate weight loss or regain after bariatric surgery, offering a viable alternative to revision surgery.

Bariatric Surgery in Patients with Achondroplasia, a Feasibility Study of Two Case Studies.

BACKGROUND: Achondroplasia is a common skeletal dysplasia with a high prevalence of obesity in adulthood. Bariatric surgery has been shown to be effective in treating obesity and related comorbidities, but its feasibility and effectiveness in patients with achondroplasia have not been clearly established. OBJECTIVES: The objective of this study was to evaluate the feasibility and effectiveness of bariatric surgery in patients with achondroplasia. SETTING: This study was performed in France, and bariatric surgeons from the Société Française et Francophone de Chirurgie de l'Obésité et des Maladies Métaboliques (French Francophone Society of Surgery for Obesity or Metabolic Diseases) were asked to participate. METHODS: Two adult women with confirmed achondroplasia and a high BMI were selected for laparoscopic sleeve gastrectomy. Preoperative data were collected, including demographic information, comorbidities, and follow-up at 1, 3, and 6 months and 1 year after surgery. Complications were monitored and recorded. RESULTS: Both patients had good excess weight loss outcomes, with an average excess weight loss of 60.5% 1 year after surgery. One patient had a follow-up of 3 years and an excess weight loss of 44%. The surgery was well-tolerated, and no major complications were observed. CONCLUSIONS: Bariatric surgery is feasible and effective in patients with achondroplasia, with good outcomes for excess weight loss and related comorbidities. These findings suggest that bariatric surgery should be considered a treatment option for patients with achondroplasia and obesity.

Out-of-Pocket Expenses in Households of People Living with Obesity in France.

BACKGROUND/OBJECTIVES: Overweight and obesity result in a substantial economic burden in both low- and high-income countries. Moreover, this burden is often underestimated because it only partially accounts for unreimbursed out-of-pocket expenses (OOPE) related to obesity. The objective of our study was not only to evaluate OOPE incurred by people with obesity in relation to their disease with respect to direct medical expenditures and direct non-medical expenditures but also the proportion of people living with obesity who have forgone obesity-related healthcare due to the costs of such care. METHODS: An observational descriptive survey was conducted among people with class II/III obesity attending six obesity treatment centers in France. Volunteer adult participants completed a written/phone questionnaire on their related expenditures over the last 6 months for current expenditures and over the last 5 years for occasional ones. The costs were expressed in 2022 EUR. RESULTS: 299 people participated (age: 46 years [SD: 13.9], women: 72%, BMI ≥40 kg/m2: 62% and 48% with comorbidities). 65% had a professional activity. 83% declared that they had OOPE related to obesity representing annually EUR 2027/individual on average (5% of the household revenue), including weight loss and nutritional products, vitamins, meal programs, gym memberships, psychologists, but mainly adapted clothing, additional travel costs, and others. 15% of the respondents had to modify their professional activity due to obesity and 15% forwent some medical care in the last 12 months. CONCLUSIONS: OOPE is a significant part of the economic burden of obesity. Despite some limitations due to the specificities of the participants and because some costs may be more related to social activities affected by obesity than to healthcare, it seems important to consider these expenditures in cost estimates for obesity.

High preoperative depression, phobic anxiety, and binge eating scores and low medium-term weight loss in sleeve gastrectomy obese patients: a preliminary cohort study.

OBJECTIVE: Although depression, anxiety, and binge eating are prevalent in candidates for bariatric surgery, their impact on weight loss is unknown following sleeve gastrectomy. This study assesses the associations between weight loss and preoperative depression, anxiety, and binge eating scores in patients undergoing sleeve gastrectomy for morbid obesity. METHOD: This cohort study included 34 patients who underwent sleeve gastrectomy for morbid obesity between May 2006 and February 2010 in a French tertiary referral center. We assessed preoperative depression (using the Beck depression inventory and the SCL-90-R depression subscale), anxiety (using the Hamilton anxiety rating scale and the SCL-90-R anxiety subscales), and binge eating (using the bulimic investigatory test, Edinburgh). The primary outcome was the percentage of excess weight loss at 12 months (PEWL). RESULTS: The preoperative mean body mass index (BMI) was 55.3 kg/m2 ± 10.2 kg/m2 and 41.7 kg/m2 ± 8.7 kg/m2 at the 12-month follow-up visit. The mean PEWL was 46.8% ± 15.8%. After adjusting for the preoperative BMI, the PEWL was negatively associated with preoperative scores for depression (ß= -0.357; P < 0.05), phobic anxiety (ß = -0.340; P < 0.05), interpersonal sensitivity (ß = -0.328; P < 0.05), and binge eating (ß = -0.315; P = 0.05). Other forms of anxiety were not correlated with the PEWL. CONCLUSIONS: Higher preoperative depression, phobic anxiety, interpersonal sensitivity, and binge eating scores are associated with low postoperative weight loss in patients undergoing sleeve gastrectomy. Future studies should assess the preoperative prevalence of syndromal or subsyndromal atypical depression and its relationship to postoperative weight loss in bariatric surgery candidates.

Hepatic Fis1 regulates mitochondrial integrated stress response and improves metabolic homeostasis.

Mitophagy and mitochondrial integrated stress response (ISR) are 2 primary protective mechanisms to maintain functional mitochondria. Whether these 2 processes are coordinately regulated remains unclear. Here we show that mitochondrial fission 1 protein (Fis1), which is required for completion of mitophagy, serves as a signaling hub linking mitophagy and ISR. In mouse hepatocytes, high fat diet (HFD) feeding induces unresolved oxidative stress, defective mitophagy and enhanced type I interferon (IFN-I) response implicated in promoting metabolic inflammation. Adenoviral-mediated acute hepatic Fis1 overexpression is sufficient to reduce oxidative damage and improve glucose homeostasis in HFD-fed mice. RNA-Seq analysis reveals that Fis1 triggers a retrograde mitochondria-to-nucleus communication upregulating ISR genes encoding anti-oxidant defense, redox homeostasis, and proteostasis pathways. Fis1-mediated ISR also suppresses expression of IFN-I-stimulated genes through activating transcription factor 5 (Atf5), which inhibits the transactivation activity of interferon regulatory factor 3 (Irf3) known to control IFN-I production. Metabolite analysis demonstrates that Fis1 activation leads to accumulation of fumarate, a TCA cycle intermediate capable of increasing Atf5 activity. Consequently, hepatic Atf5 overexpression or monomethyl fumarate (MMF) treatment improves glucose homeostasis in HFD-fed mice. Collectively, these results support the potential use of small molecules targeting the Fis1-Atf5 axis, such as MMF, to treat metabolic diseases.

Ambulatory percutaneous angioplasty in patients with claudication.

BACKGROUND: The aim of this study was to evaluate the feasibility of outpatient peripheral angioplasty in patients who were treated for lower limb claudication. METHODS: Between February 1 and December 31, 2007, a monocentric observational study was carried out on 98 consecutive patients who presented with claudication (mean age: 63 years [range: 31-90]; 81 men) and were treated by using a percutaneous femoral approach for either iliac (n = 62) or femoropopliteal lesions (n = 36). Exclusion criteria were requiring a renal angioplasty or an associated surgical procedure, having a creatinine clearance value of <30 mL/min/1.73 m(2), body mass index exceeding 35 kg/m(2), and critical ischemia or vascular surgery history at the site of femoral puncture. Treatment involved manual compression and/or use of a closure system, after which the patients were made to wear a compression bandage. After 4 hours, the patients were carefully examined for the presence of a local complication (puncture site), a general complication (thoracic pain), or a complication related to the surgical procedure (early thrombosis). When no complications were detected, the patients were allowed to get up and walk. At the sixth hour, the patients were again examined for the presence of the aforementioned complications. In the absence of any complications, the patients were deemed as "fit to be discharged" and were allowed to stroll about inside the hospital. The following day, a final evaluation was carried out just before their discharge. The risk factors and comorbidities were evaluated. RESULTS: At the sixth postoperative hour, 78 patients (80%) were deemed as "fit to be discharged." The remaining 20 (20%) were deemed as "unfit to be discharged" because of either a major hematoma (n = 3, including two redo surgeries and a blood transfusion) or a minor evolutive hematoma. All the complications (n = 17) occurred before the fourth postoperative hour. Bilateral femoral puncture was the only risk factor found to be associated with contraindication to being discharged in the evening (OR = 3.8, p = 0.02). CONCLUSION: Ambulatory treatment for patients with claudication treated with an endovascular approach was possible because complications that required overnight surveillance always occurred within the first 4 postoperative hours. Bilateral femoral puncture is a potential risk factor for failure of outpatient management.

Daily Timing of Meals and Weight Loss After Bariatric Surgery: a Systematic Review.

The timing of food intake throughout the day can alter circadian clocks and metabolism to modulate the course of obesity. We conducted a systematic literature review to determine whether the timing of meals could alter the change in body weight after bariatric surgery in adults. Twelve cohort studies examined the association between meal timing and changes in body weight after bariatric surgery. Eight studies suggested an association between meal timing and weight loss. All studies examined simple exposure variables such as frequency of breakfast or dinner consumption and overnight meals. Overall, the low-quality evidence that food consumption at the end of the day is associated with lower weight loss after bariatric surgery in adults warrants further research.

Changes in Key Mitochondrial Lipids Accompany Mitochondrial Dysfunction and Oxidative Stress in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a dysmetabolic hepatic damage of increasing severity: simple fat accumulation (steatosis), nonalcoholic steatohepatitis (NASH), and hepatic fibrosis. Oxidative stress is considered an important factor in producing hepatocyte injury associated with NAFLD progression. Studies also suggest a link between the accumulation of specific hepatic lipid species, mitochondrial dysfunction, and the progression of NAFLD. However, it is unclear whether mitochondrial lipid modifications are involved in NAFLD progression. To gain insight into the relationship between mitochondrial lipids and disease progression through different stages of NAFLD, we performed lipidomic analyses on mouse livers at different stages of western diet-induced NAFLD, with or without hepatic fibrosis. After organelle separation, we studied separately the mitochondrial and the "nonmitochondrial" hepatic lipidomes. We identified 719 lipid species from 16 lipid families. Remarkably, the western diet triggered time-dependent changes in the mitochondrial lipidome, whereas the "nonmitochondrial" lipidome showed little difference with levels of hepatic steatosis or the presence of fibrosis. In mitochondria, the changes in the lipidome preceded hepatic fibrosis. In particular, two critical phospholipids, phosphatidic acid (PA) and cardiolipin (CL), displayed opposite responses in mitochondria. Decrease in CL and increase in PA were concurrent with an increase of coenzyme Q. Electron paramagnetic resonance spectroscopy superoxide spin trapping and Cu2+ measurement showed the progressive increase in oxidative stress in the liver. Overall, these results suggest mitochondrial lipid modifications could act as an early event in mitochondrial dysfunction and NAFLD progression.

Timing of Kidney Clamping and Deceased Donor Kidney Transplant Outcomes.

BACKGROUND AND OBJECTIVES: The fact that metabolism and immune function are regulated by an endogenous molecular clock that generates circadian rhythms suggests that the magnitude of ischemia reperfusion, and subsequent inflammation on kidney transplantation, could be affected by the time of the day. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated 5026 individuals who received their first kidney transplant from deceased heart-beating donors. In a cause-specific multivariable analysis, we compared delayed graft function and graft survival according to the time of kidney clamping and declamping. Participants were divided into those clamped between midnight and noon (ante meridiem [am] clamping group; 65%) or clamped between noon and midnight (post meridiem [pm] clamping group; 35%), and, similarly, those who underwent am declamping (25%) or pm declamping (75%). RESULTS: Delayed graft function occurred among 550 participants (27%) with am clamping and 339 (34%) with pm clamping (adjusted odds ratio, 0.81; 95% confidence interval, 0.67 to 0.98; P=0.03). No significant association was observed between clamping time and overall death-censored graft survival (hazard ratio, 0.92; 95% confidence interval, 0.77 to 1.10; P=0.37). No significant association of declamping time with delayed graft function or graft survival was observed. CONCLUSIONS: Clamping between midnight and noon was associated with a lower incidence of delayed graft function, whereas declamping time was not associated with kidney graft outcomes.

Knowledge and competency standards for specialized cognitive behavior therapy for adult obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is a leading cause of disability world-wide (World Health Organization, 2008). Treatment of OCD is a specialized field whose aim is recovery from illness for as many patients as possible. The evidence-based psychotherapeutic treatment for OCD is specialized cognitive behavior therapy (CBT, NICE, 2005, Koran and Simpson, 2013). However, these treatments are not accessible to many sufferers around the world. Currently available guidelines for care are deemed to be essential but insufficient because of highly variable clinician knowledge and competencies specific to OCD. The phase two mandate of the 14 nation International OCD Accreditation Task Force (ATF) created by the Canadian Institute for Obsessive Compulsive Disorders is development of knowledge and competency standards for specialized treatments for OCD through the lifespan deemed by experts to be foundational to transformative change in this field. This paper presents knowledge and competency standards for specialized CBT for adult OCD developed to inform, advance, and offer a model for clinical practice and training for OCD. During upcoming ATF phases three and four criteria and processes for training in specialized treatments for OCD through the lifespan for certification (individuals) and accreditation (sites) will be developed based on the ATF standards.

Improvement in arterial stiffness (pOpmètre®) after bariatric surgery. Results from a prospective study.

BACKGROUND: Arterial stiffness (AS) is an independent predictor of cardiovascular risk, and could be used as a surrogate marker of improvement in cardiovascular risk following bariatric surgery. The aim of this study was to compare AS before and after surgery. METHODS: One hundred and thirty-four patients undergoing bariatric surgery between May 2016 and January 2019 were prospectively included. AS was measured on pulse wave velocity (PWV) with the pOpmètre® device pre- and postoperatively. The main endpoint was change in PWV between baseline and 3 months post-surgery. RESULTS: Overall, mean PWV was 6.87m/s preoperatively and 6.71m/s at 3 months (P=0.7148). Patients with pathologic PWV (>2 standard deviations from expected value for age) showed significant improvement at 3 months (31 patients; 10.1m/s preoperatively vs 7.5m/s at 3 months; P=0.007). These results did not correlate with improvement in other clinical or biological parameters following surgery (excess weight loss, mean blood pressure, fasting blood glucose, waist circumference, body composition). CONCLUSION: These results suggest that pathological arterial stiffness may resolve following bariatric surgery independently of the other factors influencing cardiovascular risk in obesity.