[Interest of a short educational intervention coordinated by community pharmacists for elderly type 2 diabetes patients in a rural area]. / Intérêt d'une séance éducative « flash ¼ coordonnée par des pharmaciens d'officine pour des patients âgés diabétiques de type 2 en milieu rural.

The number of elderly people with type 2 diabetes (T2D) is increasing worldwide. Community pharmacies, thanks to their proximity, provide more easy access to therapeutic education for rural patients. Populations living in isolated areas require specific educational resources related to their condition. The aim of this project was to perform a short (FLASH) educational intervention, coordinated by community pharmacists, and then evaluate the impact of this intervention on patient knowledge of their disease. The study was performed in Issoudun, a rural French town of approximately 10,000 inhabitants. Educational priorities were defined and the project was presented to health authorities and local health professionals. Pharmacies in Issoudun recruited patients, either alone or accompanied by their caregivers. The educational intervention lasted 2h and focused on 4 teaching objectives: knowledge concerning diabetes, diabetic complications and how to monitor them; how to react to hypoglycemia; understanding treatments; and understanding glycated hemoglobin. The impact of this educational intervention was assessed using a questionnaire delivered before the intervention, immediately after, and after 6months. Forty-five patients aged 71±6years with T2D duration of 14±6years were recruited over 6months. Some false beliefs were identified before the intervention. The educational session led to a significant improvement in the percentage of correct answers (before: 60.3%±7.5, after: 99%±0.4, P=0.0002) and at 6months (99.5%±0.3, P=0.0002) compared with the patients' initial knowledge. Almost all false beliefs were corrected by the intervention and patients were able to recall the mechanism of action of their drugs, with the help of a "key and lock" schematic. This short FLASH educational intervention, coordinated by community pharmacists, showed that the model was both interesting to patients and effective. This method could be expanded to other rural communities and medical deserts.

12-Month Real-Life Efficacy of the MiniMed 780G Advanced Closed-Loop System in Patients Living with Type 1 Diabetes: A French Observational, Retrospective, Multicentric Study.

Aim: To evaluate the evolution of glycemic outcomes in patients living with type 1 diabetes (T1D) after 1 year of use of the MiniMed 780G advanced hybrid closed-loop (AHCL) system. Methods: We conducted an observational, retrospective, multicentric study in 20 centers in France. The primary objective was to evaluate the improvement in glycemic control after 1-year use of AHCL. The primary endpoint was the variation of time in range (TIR) between pre-AHCL and after 1-year use of AHCL. Secondary objectives were to analyze the glycemic outcomes after 3, 6, and 12 months of AHCL use, the safety, and the long-term observance of AHCL. Results: Two hundred twenty patients were included, and 200 were analyzed for the primary endpoint. 92.7% of patients continued to use AHCL. After 1 year of use of AHCL, TIR was 72.5% ± 10.6% (+9.1%; 95% confidence interval [CI] [7.6-10.5] compared to pre-AHCL initiation, P < 0.001), HbA1c 7.1% ± 0.7% (-0.5%; 95% CI [-0.6 to -0.4]; P < 0.001), time below range 2.0% [1.0; 3.0] (0.0% [-2.0; 0.0], P < 0.001), and time above range 24.8% ± 10.9% (-7.3%; 95% CI [-8.8 to -5.7]; P < 0.001). More patients achieved the glycemic treatment goals of HbA1c <7.0% (45.1% vs. 18.1%, P < 0.001) and TIR >70% (59.0% vs. 29.5% P < 0.001) when compared with pre-AHCL. Five patients experienced severe hypoglycemia events and two patients experienced ketoacidosis. Conclusion: After 1 year of use of AHCL, people living with T1D safely improved their glucose control and a higher proportion of them achieved optimal glycemic control.

Beyond MEN1, when to think about MEN4? Retrospective study on 5600 patients in the French population & literature review.

CONTEXT: Germline CDKN1B variants predispose patients to multiple endocrine neoplasia type 4 (MEN4), a rare MEN1-like syndrome, with <100 reported cases since its discovery in 2006. Although CDKN1B mutations are frequently suggested to explain cases of genetically-negative MEN1, the prevalence and phenotype of MEN4 patients is poorly known, and genetic counseling is unclear. OBJECTIVE: To evaluate the prevalence of MEN4 in MEN1-suspected patients and characterize the phenotype of MEN4 patients. DESIGN: Retrospective observational nationwide study. Narrative review of literature and variant class reassessment. PATIENTS: We included all adult patients with class 3/4/5 CDKN1B variants identified by the laboratories from the French TENGEN network between 2015 and 2022 through germline genetic testing for MEN1 suspicion. After class reassessment, we compared the phenotype of symptomatic patients with class 4/5 CDKN1B variants, i.e. with genetically-confirmed MEN4 diagnosis, in our series and in literature with 66 matched MEN1 patients from the UMD-MEN1 database. RESULTS: From 5600 MEN1-suspected patients analyzed, four patients with class 4/5 CDKN1B variant were found (0.07%). They presented with multiple duodenal NET, PHPT and adrenal nodule, isolated PHPT, PHPT and pNET. We listed 29 patients with CDKN1B class 4/5 variants from literature. Compared to matched MEN1 patients, MEN4 patients presented lower NET incidence and older age at PHPT diagnosis. CONCLUSION: The prevalence of MEN4 is low. PHPT and PA represent the main associated lesions, NETs are rare. Our results suggest a milder and later phenotype than in MEN1. Our observations will help to improve genetic counseling and management of MEN4 families.

Pituitary apoplexy score, toward standardized decision-making: a descriptive study.

Pituitary apoplexy (PA), a rare and life-threatening complication of pituitary adenomas, prompts urgent glucocorticoid administration. The optimal surgical approach is debated, and the Pituitary Apoplexy Score (PAS) aids decision-making. Our retrospective study (2003-2022) assesses variables in PA patient groups (surgical vs. non-surgical), applying PAS to establish a significant threshold for surgical decisions. Additionally, we aim to compare the rates of ophthalmological and endocrine deficit between both groups and identify any associated variables. PAS discrepancies were observed, with averages of 1.7 ± 1.7 (p < 0.0001) for conservative and 3.9 ± 1.7 (p < 0.0001) for surgical groups, confirmed by multivariate analysis (p = 0.009). A PAS threshold of 5, showing over 80% positive predictive value, was established. Patients with low prolactin levels (< 5 ng/ml) had higher corticotropic deficiency prevalence at 3-month and 1-year follow-ups (p = 0.017 and 0.027). Our study supports PAS as a valuable PA management tool, suggesting potential variable adjustments. Multicenter studies are crucial due to PA's low incidence.

Surgery of primary lung carcinoid tumors at metastatic stage: A national study from the French Group of Endocrine Tumors (GTE) and ENDOCAN-RENATEN network.

The outcome following surgery for patients with primary lung neuroendocrine tumors at metastatic stage remains poorly characterized. We conducted a retrospective national study including patients with metastatic lung neuroendocrine tumors at diagnosis. We performed a safety study to evaluate major morbidity and mortality of surgical resection of the primary tumor and compared patients in the operative to the nonoperative group. A total of 155 patients were included: 41 in the operative group and 114 in the nonoperative group, median age was 64 years. Metastases were mainly located in the liver (74.2%) and the bone (49.7%). The primary endpoint was met as the rate of major complications was 4.9% and there was no postoperative mortality. In the operative group 42.5% of patients had improvement of their pulmonary symptoms versus 14.4% in the nonoperative group. The median overall survival was not reached in the operative group and was 4.3 years (95% CI [3.5;4.9]) in the nonoperative group (univariate analysis, HR = 0.42 95% CI [0.23-0.77], p = .002). After multivariate analysis, only an ECOG-PS ≥1 (vs. 0, HR = 2.44, 95% CI [1.46;4.07], p = .001) and >1 metastatic site (vs. 1; HR = 1.83, 95% CI [1.06;3.16], p = .030) remained significantly associated with overall survival. The resection of the primary tumor was not significantly associated with overall survival (HR = 0.63, 95% CI [0.32;1.24], p = .183). In conclusion, surgery of primary lung neuroendocrine tumors at metastatic stage is a safe option that should be considered in selected patients in order to improve symptoms with a view to improving their quality of life. Larger studies are warranted to evaluate the impact of surgery on survival.

Comparison of four equations for estimation of glomerular filtration rate in predicting cardiovascular events and subclinical vascular disease in patients with type-2 diabetes.

AIMS: Chronic kidney disease (CKD), defined by a low glomerular filtration rate (GFR), is a predictor of cardiovascular disease in patients with type-2 diabetes (T2D). We aimed to compare four GFR equations in predicting future cardiovascular events in T2D and the presence of subclinical vascular disease. METHODS: Four equations were used to estimate GFR in asymptomatic T2D patients consulting our centre for cardiovascular assessment. Follow-up was performed to collect cardiovascular events. Cox proportional hazard ratio (HR) was used to build and compare prediction models, and the incremental value of the addition of GFR with any of the 4 formulas was evaluated. The ability to triage patients with and without CVD events according to GFR were assessed by comparing the receiver operator characteristics (ROC) curves with the 4 models. RESULTS: Among 829 asymptomatic T2D patients, the CKD prevalence was 20.2% for Modification of Diet in Renal Disease (MDRD), 17.3% for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), 20.7% for Lund-Malmö Revised (LMR) and 21.4% for Full Age Spectrum (FAS). All the estimated GFRs were well correlated from one formula to another, with stronger agreement to define CKD (GFR <60 mL/min/1.73 m2) between MDRD and CKD-EPI, and between LMR and FAS. The 5-year incidence of cardiovascular events was 8% (n = 63). After adjustment on covariables, CKD was significantly associated with cardiovascular events when defined by MDRD (HR = 2.04; 1.15-3.60) and CKD-EPI (HR = 1.90; 1.05-3.41) but missed statistical significance when using LMR (HR = 1.74; 0.97-3.14) or FAS (HR = 1.71; 0.94-3.14). Only the prediction models including MDRD and CKD-EPI provided a significant incremental information to the predictive model without GFR, but the area under the ROC curves were similar with the 4 models: 0.60 [0.54-0.68] for MDRD, 0.61 [0.49-0.65] for CKD-EPI and 0.62 [0.55-0.69] for LMR and FAS, without any significant difference among formulas. CONCLUSION: In asymptomatic T2D patients, MDRD and CKD-EPI may be preferable when more specificity is desired (stronger association between GFR and CVD events), while LMR and FAS appear more sensitive by including a higher number of patients with GFR <60 mL/min/1.73 m2.

Alpha-fetoprotein and focal nodular hyperplasia: An unconventional couple.

We report the case of a 36-year-old patient who was initially managed for gynecomastia. The first biological analyses showed a moderately elevated alpha-fetoprotein (AFP) level. After an endocrine etiology was excluded, an abdominal computed tomography scan showed typical focal nodular hyperplasia (FNH) proven by biopsy and showing expression of AFP in FNH cells. After follow-up for 24 months, the serum AFP and liver radiology remained unchanged. The association between an elevated AFP and FNH is rarely described in the medical literature.

Vascular ultrasound for cardiovascular risk stratification in asymptomatic patients with type-2 diabetes.

AIMS: To identify new independent vascular markers to predict cardiovascular events in patients with type-2 diabetes (T2D), and their incremental value compared to the Swedish National Diabetes Register (NDR) risk score. METHODS: A retrospective cohort study was conducted on 1332 asymptomatic patients with T2D, free from prior CV event, assessed for a cardiovascular work-up, including Duplex ultrasonography to detect plaque on carotid and femoral arteries. The extent of atherosclerosis was rated as atherosclerosis burden score (ABS). Patients were followed up to 5 years and the occurrence of cardiovascular events recorded. RESULTS: A total of 82 patients (6.2%) experienced a cardiovascular event, including 34 (2.6%) myocardial infarction, 18 (1.4%) cardiac revascularisation and 17 (1.3%) stroke. The independent determinants of these events were male sex (HR = 1.81 [1.13-2.88], p = 0.013) and ABS ≥ 2 (HR = 1.98 [1.21-3.25], p = 0.007). The NDR risk score performed poorly to predict cardiovascular events (area under the curve = 0.56 [0.49-0.63], p = 0.11), whereas screening for atherosclerotic plaques provided significant incremental prognostic value over the NDR score (model χ2 increase: +231%, p = 0.002). CONCLUSION: Duplex ultrasonography to screen for atherosclerotic plaques improve the estimation of cardiovascular prognosis on top of clinical data and could be routinely used to improve cardiovascular risk stratification.

A MEN1 syndrome with a paraganglioma.

Germline mutations of the MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterized by tumors of the parathyroids, the pancreas, and the anterior pituitary. Paraganglioma (PGL) is a rare endocrine tumor, which can be sporadic or genetically determined. To date, PGL has never been reported as a feature of MEN1.We report here a patient presenting three features of MEN1 syndrome (hyperparathyroidism, pancreatic neuroendocrine tumor, and adrenocortical adenoma) associated with PGL. Genetic analysis of MEN1 gene revealed a new missense mutation in exon 5 (AGGAAG), causing the substitution of arginine by lysine at codon 275. Screening for other genetic disorders (SDHx, TMEM127, MAX, CDKN1B) causing PGL was negative. Immunohistochemical analyses showed normal levels of succinate dehydrogenase (SDH)A and SDHB in the PGL. The proband's sister, bearing the mutation, had primary hyperparathyroidism. It was the first typical MEN1 syndrome reported with an extra-adrenal PGL.

[Personality and risk of dementia]. / Personnalité et risque de démence.

We review the personality construct and its disorders according to the categorical and dimensional approaches, and the present understanding of dementia and its risk factors. This study shows a relationship between pre-morbid personality and risk of developing dementia. Data with speculative character, and indirect proofs from studies on life style, habits and pathological behaviors are reported. Categorical and dimensional parameters of personality are studied respectively by cluster analysis of the DSM classification, and by two contributive instruments: the Cloninger's temperament and character inventory (TCI) with seven dimensions, and the Costa and McCrae's NEO personality inventory (NEO PI) with five factors. Risk of dementia is higher in patients with the DSM C personality cluster, and, by order of severity, the dependent, avoidant and obsessive types of personality. According to the TCI, these three personality types have a high score on the dimension "harm avoidance", which increases the risk of dementia. With the five factor model investigated by the NEO PI, the risk of dementia is increased by low levels of extraversion, openness, agreeableness and conscienciousness, and high level of neuroticism. Biological correlations are mixed up with these two personality models, which have coherent correlations between their respective dimensions. High levels of neuroticism and harm avoidance are associated with low serotonin activity, deficient neuroplasticity, cortisol abnormalities and greater deleterious impact according to the type of stressing situations. Cortisol levels regulation differs according to the type of personality and cortisol axis dysregulation could play a key part in dementia occurrence. Detecting vulnerable personalities should lead to recommendations for dementia prevention.