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BACKGROUND: Cushing's syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients with CS are currently lacking. We aimed to map the current clinical practice for thromboprophylaxis management in patients with CS across reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), which are endorsed specifically for the diagnosis and treatment of CS. Using the EU survey tool, a primary screening survey, and subsequently a secondary, more in-depth survey were developed. RESULTS: The majority of the RCs provided thromboprophylaxis to patients with CS (n = 23/25), although only one center had a standardized thromboprophylaxis protocol (n = 1/23). RCs most frequently started thromboprophylaxis from CS diagnosis onwards (n = 11/23), and the majority stopped thromboprophylaxis based on individual patient characteristics, rather than standardized treatment duration (n = 15/23). Factors influencing the initiation of thromboprophylaxis were 'medical history of VTE' (n = 15/23) and 'severity of hypercortisolism' (n = 15/23). Low-Molecular-Weight-Heparin was selected as the first-choice anticoagulant drug for thromboprophylaxis by all RCs (n = 23/23). Postoperatively, the majority of RCs reported 'severe immobilization' as an indication to start thromboprophylaxis in patients with CS (n = 15/25). Most RCs (n = 19/25) did not provide standardized testing for variables of hemostasis in the postoperative care of CS. Furthermore, the majority of the RCs provided preoperative medical treatment to patients with CS (n = 23/25). About half of these RCs (n = 12/23) took a previous VTE into account when starting preoperative medical treatment, and about two-thirds (n = 15/23) included 'reduction of VTE risk' as a goal of treatment. CONCLUSIONS: There is a large practice variation regarding thromboprophylaxis management and perio

INTRODUCTION : L’hyperplasie macronodulaire bilatérale des surrénales (HMBS) GIP-dépendante avec syndrome de Cushing est due à l’expression ectopique du récepteur du GIP (GIPR) dans ces lésions surrénaliennes. Notre objectif était d’identifier la cause moléculaire de cette pathologie. [...]

OBJECTIF : La métyrapone est un inhibiteur de la stéroïdogenèse approuvé en Europe pour le traitement du syndrome de Cushing endogène, sur la base d’études rétrospectives. Nous présentons les résultats de la première étude prospective sponsorisée par HRA Pharma RD. [...]

BACKGROUND & AIMS: Retrospective cross-sectional studies linked sarcopenia and myosteatosis with metabolic dysfunction-associated fatty liver disease (MAFLD). Here, we wanted to clarify the dynamic relationship between sarcopenia, myosteatosis, and MAFLD. METHODS: A cohort of 48 obese patients was randomised for a dietary intervention consisting of 16 g/day of inulin (prebiotic) or maltodextrin (placebo) supplementation. Before and after the intervention, we evaluated liver steatosis and stiffness with transient elastography (TE); we assessed skeletal muscle index (SMI) and skeletal muscle fat index (SMFI) (a surrogate for absolute fat content in muscle) using computed tomography (CT) and bioelectrical impedance analysis (BIA). RESULTS: At baseline, sarcopenia was uncommon in patients with MAFLD (4/48, 8.3%). SMFI was higher in patients with high liver stiffness than in those with low liver stiffness (640.6 ± 114.3 cm2/ Hounsfield unit [HU] vs. 507.9 ± 103.0 cm2/HU, p = 0.001). In multivariate analysis, SMFI was robustly associated with liver stiffness even when adjusted for multiple confounders (binary logistic regression, p <0.05). After intervention, patients with inulin supplementation lost weight, but this was not associated with a decrease in liver stiffness. Remarkably, upon intervention (being inulin or maltodextrin), patients who lowered their SMFI, but not those who increased SMI, had a 12.7% decrease in liver stiffness (before = 6.36 ± 2.15 vs. after = 5.55 ± 1.97 kPa, p = 0.04). CONCLUSIONS: Myosteatosis, but not sarcopenia, is strongly and independently associated with liver stiffness in obese patients with MAFLD. After intervention, patients in which the degree of myosteatosis decreased reduced their liver stiffness, irrespective of body weight loss or prebiotic treatment. The potential contribution of myosteatosis to liver disease progression should be investigated. CLINICAL TRIALS REGISTRATION NUMBER: NCT03852069. LAY SUMMARY: The fat content in skel

Chronic kidney disease (CKD) is a major public health problem, increasing the risk of cardiovascular events and death and potentially leading to kidney failure. Novel drugs that slow the progression of this non-communicable disease are therefore urgently needed. Initially developed as glucose-lowering drugs, inhibitors of the sodium-glucose cotransporter 2 (SGLT2) drastically reduce the overall mortality and cardiovascular events and slow the progression of CKD. Kidney protection conferred by SGLT2 inhibitors is independent from the presence of diabetes, observed on top of renin-angiotensin system inhibition and consistent across a wide range of categories of glomerular filtration rate and albuminuria. The mechanisms through which SGLT2 inhibitors improve kidney outcomes are likely multifactorial. Inhibition of SGLT2 in the kidney proximal tubule results in natriuresis and glucosuria, with beneficial effects on metabolic control, blood pressure and body weight. In addition, SGLT2 inhibitors also improve intraglomerular hemodynamics, podocyte integrity, cell metabolism, and erythropoiesis and reduce hypoxia, oxidative stress, sympathetic nervous activity, inflammation and fibrosis. The major impact of SGLT2 inhibitors on kidney outcomes, along with the excellent safety profile of this new class of drugs, open novel avenues for the treatment of CKD in patients with and without diabetes.

Little is known about the long-term outcomes of Severe Acute Malnutrition (SAM) during childhood. As such, this study aims to explore the association between childhood SAM and blood pressure (BP) in adulthood in a context without nutrition transition. We identified 524 adults (Median age: 22 years) who were treated for SAM during childhood in Eastern DRC between 1988 and 2007. They were compared with 407 age-and-sex matched subjects with no history of SAM in the community. The variables examined for this study were the systolic (SBP), diastolic (DBP), mean (MBP) blood pressure (BP) and pulse pressure (PP), as well as high blood pressure (HBP) defined as BP ≥ 140/90 mmHg and/or use of BP-lowering drug(s) in adulthood. For comparison, linear and logistic regression models were used for analysing continuous and dichotomous variables, respectively. Of the 524 exposed located, 145 were selected according to age. A total of 97 unexposed were recruited. Compared to unexposed, exposed had slightly higher SBP and PP after adjusting for occupation, body mass index (BMI) and food consumption [SBP = 1.4 mmHg (- 2.2, 4.8) and PP = 2.6 mmHg (- 0.3, 6.0)]. However, their DBP was lower than that of the unexposed [- 1.6 mmHg (- 4.6, 1.5)]. MBP and creatinine levels were similar between the two groups. The prevalence of HBP adjusted for age was higher among exposed than unexposed (9.7% vs 5.3%). In addition, the odds of having HBP was higher among exposed than unexposed, however the observed difference was not statistically significant [Odds Ratio (OR) 1.9 (0.7, 5.6)]. Finally, using multiple regression analysis, although the effect was not significant, SAM was a major contributor to HBP [adjusted OR 3.1 (0.9,10.9), p = 0.064], while only male gender and higher BMI (overweight/obesity) emerged as independent predictors of HBP among this young study population. This study suggests that an episode of SAM in childhood has a weak impact on BP variability in young Congolese adults (from D

OBJECTIVES: Surgery of pheochromocytomas (PCs) still carries a high risk of haemodynamic complications during the perioperative period. We aimed to evaluate the influence of their secretory phenotype and preoperative alpha-blocker treatment on surgical outcome. DESIGN: A retrospective monocentric study at a tertiary medical centre. PATIENTS: In this study, 80 consecutive patients operated by the same team for a PC between 1988 and 2018. RESULTS: Diagnosis was based on typical symptoms and signs in 58 patients, genetic testing in 12 and work-up of an adrenal incidentaloma in 9. It was made during surgery in one patient. A genetic predisposition was found in one-third of index cases (21/62). The majority of the patients (73/79) had a secreting PC; more than 2/3 had an adrenergic phenotype and less than 1/3 a noradrenergic phenotype. The rate of perioperative haemodynamic complications was not influenced by the secretory phenotype, but persistent hypertension after surgery, recurrence and malignancy were more frequently observed in patients with a noradrenergic tumour. Preoperative alpha-blocker treatment was given for ≥ 14 days in 29 patients and, although being more symptomatic at diagnosis, these patients had less haemodynamic complications (3/29 vs 12/51 non-treated patients, P = 0.05). CONCLUSIONS: The occurrence of haemodynamic complications during surgery was not significantly affected by the secretory phenotype in our study, but noradrenergic tumours show a worse post-surgical outcome. Our data also provide additional support in favour of a sufficient preoperative alpha-blockade in patients with pheochromocytoma.

BACKGROUND: Few studies have evaluated the body composition (BC) of adults who suffered from severe acute malnutrition (SAM) during childhood, a population at risk of long-term noncommunicable diseases. OBJECTIVE: We performed an observational cohort study to evaluate BC in a group of young adults aged 11-30 y after nutritional rehabilitation for SAM, in the Democratic Republic of the Congo (DRC). METHODS: We evaluated 151 adults in eastern DRC who were treated for SAM during childhood between 1988 and 2007. They were compared with 120 aged- and sex-matched control adults living in the same community who had not been exposed to malnutrition as children. The main variables of interest were the different compartments of adult BC (fat-free mass [FFM], fat mass [FM], and 2 indices of height-normalized BC: FFM index [FFMI] and FM index [FMI]) measured by deuterium dilution. RESULTS: The mean age in both groups was 23 y, and females represented 49% and 56% of the exposed and nonexposed groups, respectively. SAM-exposed males had lower mean ± SD weight (53.6 ± 6.4 compared with 56.4 ± 7.9 kg, P = 0.029) and lower height (159.9 ± 6.6 compared with 163.6 ± 6.7 cm, P = 0.003) compared to unexposed males. SAM-exposed subjects had less FFM (-1.56 kg [-2.93, -0.20]; P = 0.024) but this observation was more marked in males (45.4 ± 5.4 compared with 48.2 ± 6.9 kg, P = 0.01) than in females. No differences in FM were noted between SAM-exposed and unexposed subjects. Adjusting for height, FFMI and FMI showed no difference between SAM-exposed and unexposed in either sex. CONCLUSION: SAM during childhood is associated with reduced FFM in adulthood which is probably due to a shorter height.

Non-alcoholic fatty liver disease (NAFLD) is a quickly expanding welfare disease. It has been associated with unhealthy high-sugar beverages containing fructose. Here we describe the case of a 64-year-old woman who has been followed at the endocrinology consultation for about 20 years, for a metabolic syndrome associating type 2 diabetes. Due to the development of liver test disturbances, the patient was referred to hepatology and the diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD) was made. Interestingly, the patient denied any major consumption of sweetened beverages or other processed food, but on thorough history mentioned an excessive and uncontrollable consumption of fruits. Psychiatric follow-up was then initiated. After a period of six months, the body weight remained stable, but we found a reduction of fruit consumption, a reduction of insulin resistance and a normalisation of liver blood tests and elasticity. We further describe how fructose has specific metabolic pathways that cause liver damage and similarities with alcohol in terms of addictive potential. In conclusion, this case shows the importance of a detailed and personalised care in NAFLD-MAFLD and considering food addiction (also for foods that are considered “healthy”) as a real substance-use disorder and a potential cause of liver disease.

Obesity is associated with an increased risk of several neurological and psychiatric diseases, but few studies report the contribution of biological features in the occurrence of mood disorders in obese patients. The aim of the study is to evaluate the potential links between serum metabolomics and gut microbiome, and mood disturbances in a cohort of obese patients. Psychological, biological characteristics and nutritional habits were evaluated in 94 obese subjects from the Food4Gut study stratified according to their mood score assessed by the Positive and Negative Affect Schedule (PANAS). The fecal gut microbiota and plasma non-targeted metabolomics were analysed. Obese subjects with increased negative mood display elevated levels of as well as decreased levels of and . Serum metabolite profile analysis reveals in these subjects altered levels of several amino acid-derived metabolites, such as an increased level of L-histidine and a decreased in phenylacetylglutamine, linked to altered gut microbiota composition and function rather than to differences in dietary amino acid intake. Regarding clinical profile, we did not observe any differences between both groups. Our results reveal new microbiota-derived metabolites that characterize the alterations of mood in obese subjects, thereby allowing to propose new targets to tackle mood disturbances in this context. Food4gut, clinicaltrial.gov: NCT03852069.

CONTEXT: Little accurate information is available regarding the risk of hypopituitarism after irradiation of skull base meningiomas. DESIGN: Retrospective study in a single centre. PATIENTS: 48 patients with a skull base meningioma and normal pituitary function at diagnosis, treated with radiotherapy (RXT) between 1998 and 2017 (median follow-up of 90 months). MEASUREMENTS: The GH, TSH, LH/FSH and ACTH hormonal axes were evaluated yearly for the entire follow-up period. Mean doses delivered to the pituitary gland (PitD) and the hypothalamus (HypoD) were calculated, as well as the doses responsible for the development of deficits in 50% of patients after 5 years (TD50). RESULTS: At least one hormone deficit was observed in 38% of irradiated patients and complete hypopituitarism in 13%. The GH (35%), TSH (32%) and LH/FSH axes (28%) were the most frequently affected, while ACTH secretion axis was less altered (13%). The risk of hypopituitarism was independently related to planning target volume (PTV) and to the PitD (threshold dose 45 Gy; TD50 between 50 and 54 Gy). In this series, the risk was less influenced by the HypoD, increasing steadily between doses of 15 and 70 Gy with no clear-cut dose threshold. CONCLUSIONS: Over a median follow-up period of 7.5 years, hypopituitarism occurred in more than one third of patients irradiated for a skull base meningioma, and this prevalence was time- and dose-dependent. In this setting, the risk of developing hypopituitarism was mainly determined by the irradiated target volume and by the dose delivered to the pituitary gland.

Pituitary incidentalomas (PI) are lesions of the pituitary region discovered fortuitously by imaging for reasons unrelated to pituitary disease. They range from small cysts to large invasive adenomas. All over the world, improvements in the quality and availability of radiological examinations are leading to an increase in the discovery of PI. In the last four decades, significant advances have been made in the understanding of PI. Autopsy studies have shown that about 10% of deceased individuals harbour a PI, most often a non-functioning microadenoma. In contrast, modern patient series showed that among PIs that come to endocrinological attention, a significant proportion are macroadenomas, and many patients suffer from asymptomatic or pauci-symptomatic endocrine or ophthalmologic disturbances. Other than adenomas, empty sella, Rathke's cleft cyst, craniopharyngioma and meningioma are the most frequent types of PIs. About 10% of micro-incidentalomas and 25% of macro-incidentalomas grow over time. Most cases can be managed conservatively by mere surveillance. Follow-up is necessary in all patients with macroadenoma, but uncertainty remains for microadenomas as to the extent of endocrinological work-up as well as the necessity and duration of follow-up. Visual and endocrine anomalies constitute the most common indications for surgery. When needed, surgery yields better outcome in PIs than in symptomatic pituitary lesions.

Pregnancies are rare in women with pituitary adenomas, which may relate to hormone excess from secretory subtypes such as prolactinomas or corticotroph adenomas. Decreased fertility may also result from pituitary hormone deficiencies due to compression of the gland by large tumours and/or surgical or radiation treatment of the lesion. Counselling premenopausal women with pituitary adenomas about their chance of conceiving spontaneously or with assisted reproductive technology, and the optimal pre-conception treatment, should start at the time of initial diagnosis. The normal physiological changes during pregnancy need to be considered when interpreting endocrine tests in women with pituitary adenomas. Dose adjustments in hormone substitution therapies may be needed across the trimesters. When medical therapy is used for pituitary hormone excess, consideration should be given to the known efficacy and safety data specific to pregnant women for each therapeutic option. In healthy women, pituitary gland size increases during pregnancy. Since some pituitary adenomas also enlarge during pregnancy, there is a risk of visual impairment, especially in women with macroadenomas or tumours near the optic chiasm. Pituitary apoplexy represents a rare acute complication of adenomas requiring surveillance, with surgical intervention needed in some cases. This guideline describes the choice and timing of diagnostic tests and treatments from the pre-conception stage until after delivery, taking into account adenoma size, location and endocrine activity. In most cases, pregnant women with pituitary adenomas should be managed by a multidisciplinary team in a centre specialised in the treatment of such tumours.

BACKGROUND: GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome is caused by aberrant expression of the GIP receptor in adrenal lesions. The bilateral nature of this disease suggests germline genetic predisposition. We aimed to identify the genetic driver event responsible for GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. METHODS: We conducted a multicentre, retrospective, cohort study at endocrine hospitals and university hospitals in France, Canada, Italy, Greece, Belgium, and the Netherlands. We collected blood and adrenal samples from patients who had undergone unilateral or bilateral adrenalectomy for GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. Adrenal samples from patients with primary bilateral macronodular adrenal hyperplasia who had undergone an adrenalectomy for overt or mild Cushing's syndrome without evidence of food-dependent cortisol production and those with GIP-dependent unilateral adrenocortical adenomas were used as control groups. We performed whole genome, whole exome, and targeted next generation sequencing, and copy number analyses of blood and adrenal DNA from patients with familial or sporadic disease. We performed RNA sequencing on adrenal samples and functional analyses of the identified genetic defect in the human adrenocortical cell line H295R. FINDINGS: 17 patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome were studied. The median age of patients was 43·3 (95% CI 38·8-47·8) years and most patients (15 [88%]) were women. We identified germline heterozygous pathogenic or most likely pathogenic variants in the KDM1A gene in all 17 patients. We also identified a recurrent deletion in the short p arm of chromosome 1 harboring the KDM1A locus in adrenal lesions of these patients. None of the 29 patients in the control groups had KDM1A germline or somatic alterations.

CONTEXT: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. OBJECTIVE: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. DESIGN: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. RESULTS: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. CONCLUSION: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.

Le but de cet article est de proposer un état des lieux actuel de l’insulinothérapie moderne. Dans ce contexte, nous revoyons le catalogue des insulines humaines et des analogues aujourd'hui disponibles en Belgique. Nous résumons également les stratégies thérapeutiques dans le diabète dès lors qu'une insulinothérapie est requise. Que nous apporte cet article ? L’article se veut d'abord un cadastre des insulines modernes (rapides et basales) dans le traitement des diabètes. Il propose également une actualisation des algorithmes thérapeutiques., [Insulinotherapy in 2021] The aim of this paper is to propose a current state of the art in the field of insulin treatment. We describe human insulin and analogs available in Belgium, as well as the current recommendations in terms of insulin strategies in type 1 and type 2 diabetes. What does this article bring up for us? The paper aims to review modern insulins (fast acting and basal) available for the treatment of type 1 and 2 diabetic patients. Current treatment recommendations and insulin algorithms are also discussed.

OBJECTIVES: Nonfunctionning pituitary macroadenomas (NFPMA) are benign tumors that cause symptoms of mass effects including hypopituitarism. Their primary treatment is transsphenoidal surgery. We aimed to determine the outcome of pituitary hormone deficits after surgical treatment of NFPMA and to identify factors predicting hormonal recovery. DESIGN: We retrospectively included 246 patients with NFPMA diagnosed and operated in one of the two participating centers. All hormonal axes were evaluated except growth hormone (GH). Postoperative improvement of pituitary endocrine function was considered if at least one hormonal deficit had recovered and a lower total number of deficits was observed 1 year after surgery. RESULTS: 80% (n = 197) of patients had one or more pituitary deficits and 28% had complete anterior hypopituitarism. Besides GH, the gonadotropic and thyrotropic axes were the most commonly affected (68% and 62%, respectively). The number of hypopituitary patients dropped significantly to 61% at 1 year (p < 0.001) and a significant improvement was observed for all hormonal axes, except central diabetes insipidus. Among patients with preoperative hypopituitarism, 88/175 (50%) showed improved pituitary function at 1 year. Both hyperprolactinemia at diagnosis and a lower tumor diameter independently predicted favorable endocrine outcome. CONCLUSIONS: Hypopituitarism is present in 80% of patients with NFPMA and nearly half of them will benefit from sustained improvement after surgery. Hyperprolactinaemia at diagnosis and lower tumor dimensions are associated with favorable endocrine prognosis. This supports the option of early surgery in NFPMA patients with pituitary deficits independent of the presence of visual disturbances.

To the Editor: Biotin interference has become a matter of concern with immunoassays using the biotin-streptavidin immobilization system because of the risk of falsely low and falsely high results observed in sandwich and competitive assays, respectively (1–4). Therefore, the identification of these interferences is necessary to avoid misleading diagnoses and potential adverse consequences for patients.[...]

PURPOSE: Whereas antithyroid drugs (ATD) are the preferred treatment modality for Graves' hyperthyroidism (GH), there is still controversy about the optimal regimen for delivering ATD. To evaluate whether 'Block and Replace' (B + R) and 'Titration' (T) regimes are equivalent in terms of frequency of euthyroidism and Graves' Orbitopathy (GO) during ATD therapy. METHODS: A prospective multicentre observational cohort study of 344 patients with GH but no GO at baseline. Patients were treated with ATD for 18 months according to B + R or T regimen in line with their institution's policy. RESULTS: Baseline characteristics were similar in both groups. In the treatment period between 6 and 18 months thyrotropin (TSH) slightly increased in both groups, but TSH was on average 0.59 mU/L (95% CI 0.27-0.85) lower in the B + R group at all time points (p = 0.026). Serum free thyroxine (FT4) remained stable during the same interval, with a tendency to higher values in the B + R group. The point-prevalence of euthyroidism (TSH and FT4 within their reference ranges) increased with longer duration of ATD in both groups; it was always higher in the T group than in the B + R group: 48 and 24%, respectively, at 6 months, 81 and 58% at 12 months, and 87 and 63% at 18 months (p < 0.002). There were no significant differences between the B + R and T regimens with respect to the fall in thyrotropin binding inhibiting immunoglobulins (TBII) or thyroid peroxidase antibodies (TPO-Ab). GO developed in 15.9% of all patients: 9.1 and 17.8% in B + R group and T group, respectively, (p = 0.096). GO was mild in 13% and moderate-to-severe in 2%. CONCLUSION: The prevalence of biochemical euthyroidism during treatment with antithyroid drugs is higher during T compared to B + R regimen. De novo development of GO did not differ significantly between the two regimens, although it tended to be higher in the T group. Whether one regimen is clinically more advantageous than the other remains unclear.

OBJECTIVES: We aimed to investigate the clinical, biochemical, histological and radiological characteristics as well as the response to somatostatin analogs (SSA) in a large cohort of acromegaly patients with a paradoxical GH response (PR) to oral glucose tolerance test (OGTT). DESIGN: Retrospective study. METHODS: Of 110 patients with acromegaly included in our study, 30 (PR+; 27%) had a paradoxical GH increase of more than 25% relative to basal GH levels during OGTT. RESULTS: At diagnosis, PR+ patients were older than PR- patients (52 ± 16 years vs 44 ± 14 years, P < 0.05) and had smaller pituitary tumors (40% microadenomas vs 19%, P < 0.05), which were less often invasive (17% vs 35%, P < 0.05), overall more secreting (insulin-like growth factor-1 (IGF-1)/tumoral surface: 2.35 ULN/cm2 (0.28-9.06) vs 1.08 (0.17-7.87), P = 0.011), and more often hypointense on T2-weighted MRI (92% vs 48%, P = 0.001). While the rate of remission after surgery was similar in the two groups (69%), a better response to SSA treatment was observed in PR+ patients, either before (IGF-1 reduction of > 50% after 3-6 months in 77% vs 49%, P = 0.023) or after surgery (normalization of IGF-1 in 100% vs 44%, P = 0.011). CONCLUSIONS: Our study demonstrates that in acromegaly, a paradoxical GH increase during OGTT is associated with particular features of somatotroph adenomas and with a better prognosis in terms of response to SSA.

No abstract available

Obesity could lead to metabolic dysfunction-associated fatty liver disease (MAFLD), which severity could be linked to muscle and gut microbiota disturbances. Our prospective study enrolled 52 obese patients whose MAFLD severity was estimated by transient elastography. Patients with severe steatosis (n = 36) had higher ALAT values, fasting blood glucose levels as well as higher visceral adipose tissue area and skeletal muscle index evaluated by computed tomography. Patients with fibrosis (n = 13) had higher ASAT values, increased whole muscle area and lower skeletal muscle density index. In a multivariate logistic regression analysis, myosteatosis was the strongest factor associated with fibrosis. Illumina sequencing of 16S rRNA gene amplicon was performed on fecal samples. The relative abundance of fecal Clostridium sensu stricto was significantly decreased with the presence of liver fibrosis and was negatively associated with liver stiffness measurement and myosteatosis. In addition, 19 amplicon sequence variants were regulated according to the severity of the disease. Linear discriminant analysis effect size (LEfSe) also highlighted discriminant microbes in patients with fibrosis, such as an enrichment of Enterobacteriaceae and Escherichia/Shigella compared to patients with severe steatosis without fibrosis. All those data suggest a gut-liver-muscle axis in the pathogenesis of MAFLD complications.

The global obesity epidemic continues to rise worldwide. In this context, unraveling new interconnections between biological systems involved in obesity etiology is highly relevant. Dysregulation of the endocannabinoidome (eCBome) is associated with metabolic complications in obesity. This study aims at deciphering new associations between circulating endogenous bioactive lipids belonging to the eCBome and metabolic parameters in a population of overweight or obese individuals with metabolic syndrome. To this aim, we combined different multivariate exploratory analysis methods: canonical correlation analysis and principal component analysis, revealed associations between eCBome subsets, and metabolic parameters such as leptin, lipopolysaccharide-binding protein, and non-esterified fatty acids (NEFA). Subsequent construction of predictive regression models according to the linear combination of selected endocannabinoids demonstrates good prediction performance for NEFA. Descriptive approaches reveal the importance of specific circulating endocannabinoids and key related congeners to explain variance in the metabolic parameters in our cohort. Analysis of quartiles confirmed that these bioactive lipids were significantly higher in individuals characterized by important levels for aforementioned metabolic variables. In conclusion, by proposing a methodology for the exploration of large-scale data, our study offers additional evidence of the existence of an interplay between eCBome related-entities and metabolic parameters known to be altered in obesity. Trial registration: ClinicalTrials.gov NCT02637115.

BACKGROUND AND AIMS: Metabolic and behavioural diseases, which are often related to obesity, have been associated to alterations of the gut microbiota considered as an interesting therapeutic target. We have analyzed in a cohort of obese patients treated with prebiotic inulin versus placebo the potential link between gut microbiota changes occurring upon intervention and their effect on psychological parameters (mood and cognition). METHODS: A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in 106 obese patients assigned to two groups: prebiotic versus placebo, who received respectively 16 g/d of native inulin or maltodextrin combined with dietary advice to consume inulin-rich or -poor vegetables for 3 months as well as to restrict caloric intake. Anthropometric measurements, food intake, psychological questionnaires, serum measures, and fecal microbiome sequencing were performed before and after the intervention. RESULTS: Inulin supplementation in obese subjects had moderate beneficial effect on emotional competence and cognitive flexibility. However, an exploratory analysis revealed that some patients exhibiting specific microbial signature -elevated Coprococcus levels at baseline- were more prone to benefit from prebiotic supplementation in terms of mood. Positive responders toward inulin intervention in term of mood also displayed worse metabolic and inflammatory profiles at baseline (increased levels of IL-8, insulin resistance and adiposity). CONCLUSION: This study shows that inulin intake can be helpful to improve mood in obese subjects exhibiting a specific microbial profile. The present work highlights some microbial, metabolic and inflammatory features (IL-8, insulin resistance) which can predict or mediate the beneficial effects of inulin on behaviour in obesity. Food4gut, clinicaltrial.gov: NCT03852069, https://clinicaltrials.gov/ct2/show/NCT03852069.

Multiple nonspecific symptoms in a patient treated by pembrolizumab Immune checkpoint inhibitors, such as the receptor programmed cell death protein 1 (PD-1) or PD-1 ligand 1 (PD-L1), which are new therapeutic weapons against cancer, which are increasingly sed nowadays. This case report concerns a 72-year-old man treated by pembrolizumab (Keytruda®), a PD-1 inhibitor, in first-line systemic treatment of an Stage IVA lung adenocarcinoma. Three weeks before his eighth cure, the patient’s general condition deteriorated, including loss of appetite, fatigue, nausea, and a slight weigh loss. He also reported headaches. As an adrenal insufficiency was suspected, a substitution treatment consisting of hydrocortisone was initiated. The originality of this case lies in the relevance of also considering non-specific symptoms in cancer patients under immunotherapy, the emergency of the diagnosis, and the recommended medical management. The aim of this article is direct your attention to this rare but potentially fatal adverse event of immunotherapy, with its new treatments that you will encounter increasingly often in your practice, and to revise some cases already published in the literature , in addition to another personal case.

Non-alcoholic fatty liver (NAFL) disease (NAFLD) is the most common chronic liver disease in the world. While most subjects have 'inert' NAFL, a subset will progress to non-alcoholic steatohepatitis (NASH) and its life-threatening complications. A substantial body of literature supports that a low muscle mass, low strength, and/or muscle fatty infiltration (myosteatosis) are associated with NAFLD severity. Here, we evaluated the muscle compartment in NASH preclinical models to decipher the kinetics of muscle alterations in relation with liver disease progression. We developed and validated a micro-computed tomography-based methodology to prospectively study skeletal muscle mass and density in muscle and liver (i.e. reflecting fatty infiltration) in a high-throughput and non-invasive manner in three preclinical NAFLD/NASH rodent models: fat aussie (FOZ) mice fed a high-fat diet (FOZ HF), wild-type (WT) mice fed a high-fat high-fructose diet (WT HFF), and WT mice fed a high-fat diet (WT HF). We compared them with WT mice fed a normal diet (WT ND) used as controls. -FOZ HF with fibrosing NASH had sarcopenia characterized by a reduced muscle strength when compared with WT HF and WT HFF with early NASH and WT ND controls (165.2 ± 5.2 g vs. 237.4 ± 11.7 g, 256 ± 5.7 g, and 242.9 ± 9.3 g, respectively, P 60; 0.001). Muscle mass or strength was not lower in FOZ HF, WT HF, and WT HFF with early NASH than in controls. Myosteatosis was present in FOZ HF with fibrosing NASH, but also in FOZ HF, WT HF, and WT HFF with early NASH (muscle density = 0.50 ± 0.02, 0.62 ± 0.02, 0.70 ± 0.05, and 0.75 ± 0.03, respectively, with P 60; 0.001 when compared with respective controls). Myosteatosis degree was strongly correlated with NAFLD activity score (r = -0.87, n = 67, P 60; 0.001). In multivariate analysis, the association between myosteatosis and NASH was independent from homeostatic model assessment of insulin resistance and visceral fat area (P 60; 0.05). Myosteatosis degree powerful

PURPOSE: Inulin-type fructans (ITF) are prebiotic dietary fibre (DF) that may confer beneficial health effects, by interacting with the gut microbiota. We have tested the hypothesis that a dietary intervention promoting inulin intake versus placebo influences fecal microbial-derived metabolites and markers related to gut integrity and inflammation in obese patients. METHODS: Microbiota (16S rRNA sequencing), long- and short-chain fatty acids (LCFA, SCFA), bile acids, zonulin, and calprotectin were analyzed in fecal samples obtained from obese patients included in a randomized, placebo-controlled trial. Participants received either 16 g/d native inulin (prebiotic n = 12) versus maltodextrin (placebo n = 12), coupled to dietary advice to consume inulin-rich versus inulin-poor vegetables for 3 months, in addition to dietary caloric restriction. RESULTS: Both placebo and prebiotic interventions lowered energy and protein intake. A substantial increase in Bifidobacterium was detected after ITF treatment (q = 0.049) supporting our recent data obtained in a larger cohort. Interestingly, fecal calprotectin, a marker of gut inflammation, was reduced upon ITF treatment. Both prebiotic and placebo interventions increased the ratio of tauro-conjugated/free bile acids in feces. Prebiotic treatment did not significantly modify fecal SCFA content but it increased fecal rumenic acid, a conjugated linoleic acid (cis-9, trans-11 CLA) with immunomodulatory properties, that correlated notably to the expansion of Bifidobacterium (p = 0.031; r = 0.052). CONCLUSIONS: Our study demonstrates that ITF-prebiotic intake during 3 months decreases a fecal marker of intestinal inflammation in obese patients. Our data point to a potential contribution of microbial lipid-derived metabolites in gastro-intestinal dysfunction related to obesity. CLINICALTRIALS. GOV IDENTIFIER: NCT03852069 (February 22, 2019 retrospectively, registered). Neyrinck, Audrey M. & Rodriguez, Julie : Contributed equally

Introduction: Obesity is a growing problem with multiple complications, such as metabolic dysfunction-associated fatty liver disease (MAFLD). Bariatric surgery (BS) has shown efficacy in long-term weight loss achievement. Numerous reports have described MAFLD related cirrhosis at the time of BS, complicated by further liver decompensation, in particular in patients with ancient BS techniques. The exact mechanism is unknown. Sometimes, cirrhosis may be absent. Fatal outcome, liver transplantation and reversal surgery have been reported in those patients. Aim: We wanted to describe the clinical characteristics, histological findings and clinical management of patients without cirrhosis who developed acute hepatic decompensation after BS for severe obesity. Methods: We collected clinical, biological, histological and follow-up data from patients without cirrhosis with acute hepatic decompensation after BS. Results: From December 2014 to October 2019, 6 patients (5 females and 1 male) underwent a transvenous liver biopsy for acute liver decompensation after BS. Four patients had a Roux-en-Y gastric bypass, one patient had a biliopancreatic diversion according to Scopinaro and one patient had a distal gastric bypass. At the time of BS, the mean age was 36 years (31-56), all patients were severely obese (mean body mass index 45 kg/m²) and there was no argument for cirrhosis (FIB-4 score < 1.3). The time between surgery and the onset of acute liver decompensation varied widely (min. 8 months, max. 17 years). Three patients consumed alcohol occasionally and only one patient had a chronic alcohol abuse. All patients described limited oral intake. The mean weight loss at the time of acute liver decompensation was 54.5 kg (31-76). The clinical presentation was as follows: fatigue and jaundice in 3 patients, edema of the lower limbs in 3 patients, ascites in one patient and altered coagulation in all patients. Blood tests showed an acute increase in transaminases (mean ALAT 47

Graves' disease may be associated with thyroid cancer, particularly differentiated thyroid cancer. Medullary thyroid cancer (MTC) is less common. The occurrence of sporadic MTC in Graves' disease in the presence of a RET proto-oncogene has never been reported.: A 63-year-old woman was referred for Graves' disease. A thyroid ultrasound disclosed five nodules, one of which was classified as Eu-Tirads 5 with a size of 6.7 × 6.5× 11 mm. Fine needle aspiration was reported as Bethesda class IV follicular neoplasm of a Hürthle cell subtype. Calcitonin level was found to be elevated. A total thyroidectomy confirmed the diagnosis of MTC and a bilateral cervical lymphadenectomy was performed, with four lymph nodes being infiltrated by MTC. Genetic testing revealed a M918T mutation in the RET proto-oncogene.: MTC may occur in Graves' disease, especially if a nodule is present. In this case, genetic testing should always be performed even if MTC is sporadic. Increased incidence of thyroid cancer in autoimmune thyroid diseases, as well as the link existing between autoimmunity, inflammation and carcinogenesis, leads us to hypothesize that the association here reported is not coincidental.

Background Little is known about the long-term outcome of children treated for severe acute malnutrition (SAM) after nutritional rehabilitation. Objectives To explore the association between SAM in childhood, noncommunicable diseases (NCDs), and low human capital in adulthood. Methods We identified 524 adults (median age: 22 y) who were treated for SAM during childhood in Eastern Democratic Republic of Congo between 1988 and 2007. They were compared with 407 community unexposed age- and sex-matched subjects with no history of SAM. The variables of interest were cardiometabolic risk markers for NCDs and human capital. For the comparison, we used linear and logistic regressions to estimate the association between SAM in childhood and the risk of NCDs and ordinal logistic regression for the human capital. Results Compared with unexposed subjects, the exposed participants had a higher waist circumference [1.2 (0.02, 2.3) cm; P = 0.015], and a larger waist-to-height ratio [0.01 (0.01, 0.02) cm; P < 0.001]. On the other hand, they had a smaller hip circumference [−1.5 (−2.6, −0.5) cm; P = 0.021]. Regarding cardiometabolic markers for NCDs, apart from a higher glycated hemoglobin (HbA1c) [0.4 (0.2, 0.6); P < 0.001], no difference was observed in other cardiometabolic markers for NCD between the 2 groups. Compared with unexposed participants, exposed participants had a higher risk of metabolic syndrome (crude OR: 2.35; 95% CI: 1.22, 4.54; P = 0.010) and visceral obesity [adjusted OR: 1.44 (1.09, 1.89); P = 0.001]. The prevalence of hypertension, diabetes, overweight, and dyslipidaemia was similar in both groups. Last, the proportion of malnutrition survivors with higher socioeconomic status level was lower. Conclusion SAM during childhood was associated with a high risk of NCDs and lower human capital in adulthood. Thus, policymakers and funders seeking to fight the global spread of NCDs in adults in low-resource settings should consider the long-term benefit of reducing ch

We conducted a prospective observational study to evaluate the medium-term impact of the flash glucose monitoring system (FGM) in a type 1 diabetic population. We included 248 patients, switched from conventional blood glucose monitoring (BGM) to FGM. We evaluated glycaemic control at 2-4 (T1) and 5-11 (T2) months after initiation and at the last available visit (T3, 18 ± 4 months). We asked patients to fill in, at T0 and T2, two questionnaires based on the Diabetes Treatment Satisfaction Questionnaire; and on the Hypoglycaemia Fear Survey. Glycaemic control improved, from 8.1 ± 1.3% at T0 to 7.8 ± 1.2% at T1 (p < 0.001) and remained unchanged after. Average number of controls increased from 3.2 ± 1.2 BGM to 7.7 ± 3.9 at T1 (p < 0.001). We observed a modest decrease in daily insulin doses. We evidenced an increase in mild hypoglycaemic events, especially in well-controlled subjects, but no increase of severe events. Satisfaction score improved from 30.5 ± 7.7 points to 38.3 ± 5.1 points (p = 0.018), was correlated with the reduction in and was higher in less controlled patients at inclusion. "Behaviour" score regarding hypoglycaemias decrease from 5.7 ± 4.1 to 4.4 ± 3.6 points (p < 0.001). In conclusion, this 18-months study trial indicates that using the FGM technology in patients with T1D may improve glycaemic control, in real-life conditions, especially in less controlled patients. FGM was associated with an increase of patients' satisfaction regarding treatment. Hypoglycaemic events, however, were not reduced in frequency. Therefore, the need for an educational team and a structure program in the management of this new technology remains mandatory.

BACKGROUND AND AIMS: In type 2 diabetes mellitus (T2DM), sexual dimorphisms modulate the natural histories of hyperglycemia, anthropophysical/cardiometabolic phenotype, and susceptibility to chronic micro and macrovascular complications. The purpose of this work was to revisit known or new dimorphisms within a multiethnic cohort. METHODS: Among 1238 T2DM patients, men (63%) were compared to women (37%), including leading ethnicities: Whites (67.4%; 542 men; 293 women); Maghrebians (9.4%; 62 men; 54 women); and Blacks (12.5%; 92 men; 63 women). RESULTS: Age, BMI, diabetes duration, insulin sensitivity, B-cell function loss, HbA1c, and hyperglycemia index were similar in both genders. All-cause microangiopathy and cerebrovascular disease did not differ between sexes. Women had significantly more retinopathy (27% vs. 21%) and men more microalbuminuria (25% vs. 19%), all-cause macroangiopathy (40% vs. 26%), CAD (29% vs. 17%) and PAD (11% vs. 6%). Among Blacks, sexual dimorphism in terms of retinopathy was more pronounced (24% in women vs. 11%), while there was no sexual dimorphism in all-cause macroangiopathy, CAD or PAD. B-cell function loss was faster among North African men (+15%), who also had more hepatic steatosis (+27%) than women. CONCLUSIONS: T2DM abolishes the CV protection provided by the female gender in Blacks. In White women, the loss of CV protection in diabetes is limited to cerebrovascular disease. In Black women, a markedly increased risk of retinopathy is present, despite glycemic exposure similat to men. Sexual dimorphisms do not affect glucose homeostasis and metabolic control in all ethnicities, except for lesser B-cell function loss in Maghrebian women.

Rationale: Hepatic decompensation can occur in the absence of cirrhosis after bariatric surgery (BS), sometimes leading to death, despite “rescue” transplant treatments. The clinical presentation and management of these patients is poorly understood. Methods: We describe the clinical characteristics, histological findings and clinical management of patients without cirrhosis who developed acute hepatic decompensation after BS in our single tertiary-care hospital. Results: From 2014 to 2019, 6 patients (mean age 44 years) underwent a transvenous liver biopsy for acute liver decompensation after BS. The time between BS and the onset of symptoms varied widely (min. 8 months, max. 17 years). Mean percentage of weight loss was high (43%) with an excess body weight loss of 98%. The clinical presentation was: fatigue and jaundice (5/6), leg edema (3/6) and ascites (1/6). Blood test showed increased transaminases (ALAT 53 UI/L, ASAT 130 UI/L), bilirubin (6 mg/dL) and INR (1.5) with a low albumin level (27 mg/dL). Histology revealed steatosis, hepatocyte ballooning but also portal inflammation with polymorphonuclear cells and bile duct alterations. Mean fibrosis score was 2. Due to the prominent malnutrition among the patients, nutritional treatment was started in all patients (parenteral nutrition only in 2 patients, parenteral and enteral feeding in 3 patients and only oral supplements in 1 patient). Three patients had diuretics and two patients had intravenous albumin supplementation. The clinical course was favorable in all patients with a mean follow-up of 36 months. Conclusion: Acute liver decompensation in the absence of cirrhosis can occur after BS with a highly variable delay. A special histological signature is present with the coexistence of steatosis and bile duct alterations with portal inflammation. Substantial clinical improvement with appropriate refeeding seems to be effective.

Globally, there are prevailing knowledge gaps in the epidemiology, clinical manifestations, and outcomes of SARS-CoV-2 infection among children and adolescents; however, these gaps are especially wide in African countries. The availability of robust age-disaggregated data is a critical first step in improving knowledge on disease burden and manifestations of COVID-19 among children. Furthermore, it is essential to improve understanding of SARS-CoV-2 interactions with comorbidities and co-infections such as HIV, tuberculosis, malaria, sickle cell disease and malnutrition, which are highly prevalent among children in sub-Saharan Africa. The African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on Children and Adolescents is conducting studies across Western, Central, Eastern, and Southern Africa to address existing knowledge gaps. This consortium is expected to generate key evidence to inform clinical practice and public health policymaking for COVID-19, while concurrently addressing other major diseases affecting children in African countries.

BACKGROUND: In Sub-Saharan Africa (SSA), economic conditions often do not always permit the use of modern surgical techniques, especially for hernia treatment. Aim of the study: To demonstrate that a modern technique such as Laparoscopic Total Extraperitoneal inguinal hernioplasty (TEP) can be performed at a significantly lower cost thanks to the use of a less expensive mesh material. SETTINGS: The study was performed in Douala at the Gynaecology-Obstetric and Paediatric University Hospital and at governmental Regional Hospitals of Ayos and Edéa in Cameroon. MATERIAL AND METHODS: Prospective, randomised, double-blind, controlled trial (RCT) including consecutive adult patients presenting with primary inguinal hernia treated by TEP, with implantation of either sterilised mosquito net mesh (MNM) or conventional polypropylene mesh (CPM). RESULTS: 62 patients were enrolled; randomization allocated 32 to MNM and 30 to CPM. Both groups were comparable for age and professional activities. Significant perioperative differences pertained to conversion rate (2/32 MNM), due to external (electrical power) factors and mesh removal for early obstruction (1/30 CPM). Hospital stay was less than 2 days in both groups. All patients resumed their activities after 3 weeks. Costs were significantly lower in the MNM group. No recurrences were noted with a follow-up of median 21(12-30) months. CONCLUSION: This RCT shows that TEP with MNM is feasible, cost-effective with good outcomes in SSA hospital setting.

AIMS: Acutely decompensated heart failure (HF) (ADHF) is a common cause of hospitalization and mortality worldwide. This study explores the epidemiology and prognostic factors of ADHF in Cameroonian patients. METHODS AND RESULTS: This was a retrospective study conducted between January 2003 and December 2013 from the medical files of patients followed at the intensive care and cardiovascular units of Douala General Hospital in Cameroon. Clinical, electrocardiographic, echocardiographic, and biological data were collected from 142 patients (58.5% men; mean age 58 ± 14 years) hospitalized for ADHF with reduced ejection fraction (HFrEF), whose left ventricular ejection fraction was <50%, or alternatively whose shortening fraction was <28%, both assessed by echocardiography. The commonest risk factors associated with HFrEF were hypertension (59.2%), diabetes mellitus (16.2%), tobacco use (14.1%), and dyslipidaemia (7.7%), respectively. The major causes of HF in hospitalized patients were hypertensive heart disease (40%, n = 57); hypertrophic cardiomyopathy (33.8%, n = 48); and ischemic heart disease (21.8%, n = 31). The most frequent comorbid conditions were atrial fibrillation (25.4%, n = 36) and chronic kidney disease (18.3%, n = 26). Major biological abnormalities included increased bilirubinemia >12 mg/L (87.5%, n = 124); hyperuricaemia >70 mg/L (84.9%, n = 121); elevated serum creatinine (65.6%, n = 93); anaemia (59.1%, n = 84); hyperglycaemia on admission >1.8 g/L (42.3%, n = 60); and hyponatraemia <135 mEq/L (26.8%, n = 38). At admission, 33.8% (n = 48) of patients had no pharmacological treatment for HF. The most frequently used therapies upon admission included furosemide (50%, n = 71), angiotensin-converting enzyme inhibitors (ACEIs; 40.1%, n = 57); spironolactone (35.2%, n = 50); digoxin (26%, n = 37); beta-blockers (17.7%, n = 25); angiotensin-receptor blockers (ARBs; 7%, n = 10); and nitrates (7.0%). The overall in-hospital mortality rate was 20.4%. Factors

BACKGROUND AND AIMS: We describe the characteristics and short-term prognosis of in-patients with diabetes and COVID-19 admitted to a Belgian academic care center. METHODS: We retrospectively reviewed the data on admission from patients with known or newly-diagnosed diabetes and confirmed COVID-19. First, survivors were compared to non-survivors to study the predictive factors of in-hospital death in patients with diabetes. Secondly, diabetic patients with SARS-CoV-2 pneumonia were matched for age and sex with non-diabetic patients with SARS-CoV-2 pneumonia, to study the prognosis and predictive factors of in-hospital death related to diabetes. RESULTS: Seventy-three diabetic patients were included. Mean age was 69 (±14) years. Women accounted for 52%. Most patients had type 2 diabetes (89.0%), long-term complications of hyperglycemia (59.1%), and hypertension (80.8%). The case-fatality rate (CFR) was 15%. Non-survivors had more severe pneumonia based on imaging (p 0.029) and were less often treated with metformin (p 0.036). In patients with SARS-CoV-2 pneumonia, CFR was 15.6% in diabetic (n = 64) and 25.0% in non-diabetic patients (n = 128), the difference being non-significant (p 0.194). Predictive factors of in-hospital death were elevated white blood cells count (HR 9.4, CI 1.50-58.8, p 0.016) and severe pneumonia on imaging (HR 25.0, CI 1.34-466, p 0.031) in diabetic patients, and cognitive impairment (HR 5.80, CI 1.61-20.9, p 0.007) and cardiovascular disease (HR 5.63, CI 1.54-20.6, p 0.009) in non-diabetic patients. CONCLUSION: In this monocentric cohort from Belgium, diabetic in-patients with COVID-19 had mostly type 2 diabetes, prevalent hyperglycemia-related vascular complications and comorbidities including hypertension. In this cohort, the CFR was not statistically different between patients with and without diabetes.

Most studies of chronic kidney disease (CKD) in Sub-Saharan Africa (SSA) have been conducted in urban settings. They relied on GFR estimated from serum creatinine alone and on the inexpensive, convenient urinary dipstick to assess proteinuria. The dipstick for proteinuria has not been directly compared with the gold standard albumin-to-creatinine ratio (ACR) in a large-sized study in SSA. We hereby assessed the influence of rural versus urban location on the level, interpretation, and diagnostic performance of proteinuria dipstick versus ACR. In a cross-sectional population-based study of CKD in both urban (n = 587) and rural (n = 730) settings in South-Kivu, Democratic Republic of Congo (DRC), we assessed the prevalence, performance (sensitivity, specificity, positive predictive value and negative predictive value) and determinants of a positive dipstick proteinuria as compared with albuminuria (ACR). Albuminuria was subdivided into: A1 (< 30 mg/g creatinine), A2 (30 to 299 mg/g creatinine) and A3 (≥ 300 mg/g creatinine). The overall prevalence of positive dipstick proteinuria (≥ 1+) was 9.6 % (95 % CI, 7.9-11.3) and was higher in rural than in urban residents (13.1 % vs. 4.8 %, p < 0.001), whereas the prevalence of albuminuria (A2 or A3) was similar in both sites (6 % rural vs. 7.6 % urban, p = 0.31). In both sites, dipstick proteinuria ≥ 1 + had a poor sensitivity (< 50 %) and positive predictive value (< 11 %) for the detection of A2 or A3. The negative predictive value was 95 %. Diabetes [aOR 6.12 (1.52-24.53)] was a significant predictor of A3 whereas alkaline [aOR 7.45 (3.28-16.93)] and diluted urine [aOR 2.19 (1.35-3.57)] were the main predictors of positive dipstick proteinuria. ACR and dipstick proteinuria have similar positivity rates in the urban site whereas, in the rural site, dipstick was 2-fold more often positive than ACR. The poor sensitivity and positive predictive value of the dipstick as compared with ACR makes it unattractive as a screening too

Graves' disease is the most frequent cause of hyperthyroidism in young women. This auto-immune disease is due to the production of class 1 IgG stimulating the TSH receptor. These antibodies are produced secondary to a Th1 immune response in which interferon gamma plays a key role. Vaccination is ongoing worldwide against SARS-CoV-2 and some of the vaccines include mRNA which seems to stimulate the Th1 immune response. Here, we report a case of recurrence of hyperthyroidism due to Graves' disease following mRNA vaccination and discuss the possible implicated mechanism. This observation argues for a systematic study of a population of patients with previous Graves' disease in order to assess the risk of recurrence following vaccination. Graves' disease is a Th1-mediated immune disease in which interferon gamma plays a key role.The recurrence of hyperthyroidism due to Grave's disease should be monitored in patients exposed to risk factors.

The knowledge of physicians regarding nutrition is often far below the expectations of patients, and does not comply with official recommendations. However, poor-quality nutrition and diet represent the first cause of mortality worldwide. As a result of an insufficient training and awareness, many physicians cannot meet patients' expectations. Moreover, nutrition is sometimes felt as a field of low scientific level, thereby opening the area to pseudo-scientific drifts. We advocate an improvement in the training in nutrition during the medical cursus, namely by the transversal integration of nutritional insights into medical courses, and the recognition of post-university training validated by the academic authorities. A clarification of the roles and the recognition of the competency are urgently required to promote the professionalism of nutritional counselling.