Publications by authors named "François Pattou"

290 Publications

The impact of COVID-19 on obesity services across Europe: A physician survey.

Clin Obes 2021 Jul 13:e12474. Epub 2021 Jul 13.

Novo Nordisk North West Europe Pharmaceuticals A/S, Copenhagen, Denmark.

Obesity is a risk factor for severe complications from coronavirus disease 2019 (COVID-19). During the COVID-19 pandemic in Spring 2020, many clinics and obesity centers across Europe were required to close. This study aimed to determine the impact of COVID-19 on the provision of obesity services across 10 European countries via a survey of physicians (n = 102) specializing in treating persons with obesity (PwO). In total, 62-95 out of 102 physicians reported that COVID-19 affected obesity-related services, with cancellations/suspensions ranging from 50% to 100% across the 10 countries. Approximately 75% of cancellations/suspensions were provider- rather than patient-initiated. A median increase of 20%-25% in waiting times was reported for most services across the countries. When services resume, 87 out of 100 physicians consider factors influencing down-stream patient outcomes as the most relevant factors for prioritizing interventional treatment. Responses showed that 65 out of 102 and 36 out of 102 physicians believed it (highly) likely that a change in treatment guidance will occur to prioritize earlier interventional treatment for the management of PwO, by either using bariatric surgery or pharmacotherapy, respectively. Results from this study provide important learnings, such as opportunities for, and discrepancies in, the provision of alternative care in light of services cancellations or delays, which may be important for the future management of obesity, especially during future waves of COVID-19 or other infectious pandemics.
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http://dx.doi.org/10.1111/cob.12474DOI Listing
July 2021

Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle.

J Cachexia Sarcopenia Muscle 2021 Jun 30. Epub 2021 Jun 30.

Institute for Health and Sport (iHeS), Victoria University, Footscray, Melbourne, Vic., Australia.

Background: Knowledge of age-related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans.

Methods: We conducted a large-scale epigenome-wide association study meta-analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18-89 years old). We explored the genomic context of age-related DNA methylation changes in chromatin states, CpG islands, and transcription factor binding sites and performed gene set enrichment analysis. We then integrated the DNA methylation data with known transcriptomic and proteomic age-related changes in skeletal muscle. Finally, we updated our recently developed muscle epigenetic clock (https://bioconductor.org/packages/release/bioc/html/MEAT.html).

Results: We identified 6710 differentially methylated regions at a stringent false discovery rate <0.005, spanning 6367 unique genes, many of which related to skeletal muscle structure and development. We found a strong increase in DNA methylation at Polycomb target genes and bivalent chromatin domains and a concomitant decrease in DNA methylation at enhancers. Most differentially methylated genes were not altered at the mRNA or protein level, but they were nonetheless strongly enriched for genes showing age-related differential mRNA and protein expression. After adding a substantial number of samples from five datasets (+371), the updated version of the muscle clock (MEAT 2.0, total n = 1053 samples) performed similarly to the original version of the muscle clock (median of 4.4 vs. 4.6 years in age prediction error), suggesting that the original version of the muscle clock was very accurate.

Conclusions: We provide here the most comprehensive picture of DNA methylation ageing in human skeletal muscle and reveal widespread alterations of genes involved in skeletal muscle structure, development, and differentiation. We have made our results available as an open-access, user-friendly, web-based tool called MetaMeth (https://sarah-voisin.shinyapps.io/MetaMeth/).
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http://dx.doi.org/10.1002/jcsm.12741DOI Listing
June 2021

Long-Term Analgesia following a Single Application of Fentanyl Transdermal Solution in Pigs.

Eur Surg Res 2021 Jun 24:1-6. Epub 2021 Jun 24.

Université de Lille, Inserm, CHU Lille, Institut Pasteur Lille, Lille, France.

Introduction: In animal research, obtaining efficient and constant pain control is regulatory but challenging. The gold standard pain management consists of opioid analgesic administration, such as buprenorphine or fentanyl extended-release patches. However, as in all drugs with a short half-life time, repeated buprenorphine administrations are needed, leading to multiple injections that affect the research protocol. On the other hand, fentanyl patch efficacy is discussed in some species. These elements highlight the need of an optimal formulation of analgesic drugs for laboratory animals. In this study, we investigated how Recuvyra®, a fentanyl transdermal solution (FTS), validated in dog perioperative pain management, could provide sustained analgesia after a single topical administration in pigs in a surgical context.

Methods: A total of 11 minipigs were used in this study. As a preliminary experiment, two different doses were tested as a single application on five pigs: two pigs at full dose (2.6 mg/kg) and three pigs at half dose (1.3 mg/kg). Plasma fentanyl dosages were performed during 4 consecutive days, using liquid chromatography with tandem mass spectrometry detection. The efficacy of FTS was then evaluated in a perioperative period. Six minipigs benefited from a surgical intervention comprising a laparotomy. The FTS was blotted on the skin in a single application 20 min before the surgical incision and plasma fentanyl dosages, clinical examination (body weight, food intake, heart rate, and body temperature) and pain assessment were performed for 7 consecutive days.

Results: During the preliminary experiment, all fentanyl concentrations reached the minimum effective concentration (MEC) extrapolated in pigs (fentanylemia ≥0.2 ng/mL) throughout the 4 days. The half dose was chosen for the next step of the study. After the surgical intervention, all plasma fentanyl concentrations remained above the MEC up to 7 days post administration. Pig clinical examinations and pain evaluations showed efficient and constant pain control at the half dose, and few adverse events were observed.

Discussion And Conclusion: This study confirms the pharmacological and clinical efficacy of FTS at 1.3 mg/kg in pigs throughout at least 7 postoperative days following laparotomy. The clinical analgesic effect of FTS appears more efficient and well-tolerated than the one observed with repeated injections of buprenorphine. This analgesic drug formulation could be universally used in animal research to provide optimal perioperative pain management and long-term analgesia.
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http://dx.doi.org/10.1159/000516828DOI Listing
June 2021

Long-term outcomes of bariatric surgery in patients with bi-allelic mutations in the POMC, LEPR, and MC4R genes.

Surg Obes Relat Dis 2021 Aug 8;17(8):1449-1456. Epub 2021 May 8.

Assistance Publique-Hôpitaux de Paris, Nutrition Department, Pitié-Salpêtrière Hospital, CRNH Ile de France, F-CRIN/FORCE Network Paris, Paris, France; Sorbonne Université, INSERM, Nutrition and Obesities: Systemic Approaches (NutriOmics) Research Unit, F-CRIN/FORCE Network Paris, Paris, France.

Background: Gene mutations in the leptin-melanocortin signaling cascade lead to hyperphagia and severe early onset obesity. In most cases, multimodal conservative treatment (increased physical activity, reduced caloric intake) is not successful to stabilize body weight and control hyperphagia.

Objectives: To examine bariatric surgery as a therapeutic option for patients with genetic obesity.

Setting: Three major academic, specialized medical centers.

Methods: In 3 clinical centers, we retrospectively analyzed the outcomes of bariatric surgery performed in 8 patients with monogenic forms of obesity with bi-allelic variants in the genes LEPR (n = 5), POMC (n = 2), and MC4R (n = 1).

Results: In this group of patients with monogenic obesity, initial bariatric surgery was performed at a median age of 19 years (interquartile range [IQR], 16-23.8 yr). All patients initially experienced weight loss after each bariatric surgery, which was followed by substantial weight regain. In total, bariatric surgery led to a median maximum reduction of body weight of -21.5 kg (IQR, -36.3 to -2.9 kg), median percent excess weight loss (%EWL) of -47.5 %EWL (IQR, -57.6 to -28.9 %EWL). This body weight reduction was followed by median weight regain of 24.1 kg (IQR: 10.0 to 42.0 kg), leading to a final weight change of -24.2 % EWL (IQR: -37.6 to -5.4 %EWL) after a maximum duration of 19 years post surgery. In one patient, bariatric surgery was accompanied by significant complications, including vitamin deficiencies and hernia development.

Conclusion: The indication for bariatric surgery in patients with monogenic obesity based on bi-allelic gene mutations and its benefit/risk balance has to be evaluated very cautiously by specialized centers. Furthermore, to avoid an unsuccessful operation, preoperative genetic testing of patients with a history of early onset obesity might be essential, even more since novel pharmacological treatment options are expected.
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http://dx.doi.org/10.1016/j.soard.2021.04.020DOI Listing
August 2021

Examination of the Igls Criteria for Defining Functional Outcomes of β-Cell Replacement Therapy: IPITA symposium report.

J Clin Endocrinol Metab 2021 Jun 1. Epub 2021 Jun 1.

Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, and Institute for Diabetes, Obesity & Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Context: The Igls criteria were developed to provide a consensus definition for outcomes of β-cell replacement therapy in the treatment of diabetes during a January 2017 workshop sponsored by the International Pancreas & Islet Transplant Association (IPITA) and the European Pancreas & Islet Transplant Association (EPITA). In July 2019, a symposium at the 17 th IPITA World Congress was held to examine the Igls criteria after two years in clinical practice, including validation against continuous glucose monitoring (CGM)-derived glucose targets, and to propose future refinements that would allow for comparison of outcomes with artificial pancreas system approaches.

Evidence Acquisition: Utilization of the criteria in various clinical and research settings were illustrated by population as well as individual outcome data of four islet and/or pancreas transplant centers. Validation against CGM metrics was conducted in 55 islet transplant recipients followed-up to 10 years from a fifth center.

Evidence Synthesis: The Igls criteria provided meaningful clinical assessment on an individual patient and treatment group level, allowing for comparison both within and between different β-cell replacement modalities. Important limitations include the need to account for changes in insulin requirements and C-peptide levels relative to baseline. In islet transplant recipients, CGM glucose time-in-range improved with each category of increasing β-cell graft function.

Conclusions: Future Igls 2.0 criteria should consider absolute rather than relative levels of insulin use and C-peptide as qualifiers with treatment success based on glucose assessment using CGM-metrics on par with assessment of HbA1c and severe hypoglycemia events.
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http://dx.doi.org/10.1210/clinem/dgab386DOI Listing
June 2021

US food and drug administration (FDA) panel endorses islet cell treatment for type 1 diabetes: A pyrrhic victory?

Transpl Int 2021 Jul 11;34(7):1182-1186. Epub 2021 Jun 11.

Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.

Allogeneic islet transplantation is a standard of care treatment for patients with labile type 1 diabetes in many countries around the world, including Japan, the United Kingdom, Australia, much of continental Europe, and parts of Canada. The United States is now endorsing islet cell treatment for type 1 diabetes, but the FDA has chosen to consider islets as a biologic that requires licensure, making the universal implementation of the procedure in the clinic very challenging and opening the manufacture of islet grafts to private companies. The commercialization of human tissues raises significant legal and ethical issues and ironically leads to a situation where treatments developed as a result of the scientific and economic efforts of academia over several decades become exploited exclusively by for-profit entities.
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http://dx.doi.org/10.1111/tri.13930DOI Listing
July 2021

BMI and pneumonia outcomes in critically ill COVID-19 patients: an international multicenter study.

Obesity (Silver Spring) 2021 May 9. Epub 2021 May 9.

Intensive Care Unit, Centre hospitalier de Dunkerque, 59240, Dunkerque.

Background: Previous studies unveiled a relation between the severity of COVID-19 pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, current smoking) in critically ill patients with COVID-19.

Methods: This multicenter retrospective cohort study enrolled patients admitted in intensive care for COVID-19, in 21 centers (Europe, Israel, USA) between 02/19/2020 and 05/19/2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV), and 28-day mortality.

Results: A total of 1,461 patients were enrolled, median(IQR) age was 64 years (40.9-72.0); 73.2% males; BMI 28.1 kg/m (25.4-32.3); 1,080 patients (73.9%) required IMV; the 28-day mortality estimate was 36.1% (95%CI, 33.0-39.5). Adjusted mixed logistic regression model showed a significant linear relation between BMI and IMV: OR 1.27 (95%CI, 1.12-1.45) per 5 kg/m . Adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was only increased in obesity class III (≥40 kg/m ) (HR 1.68 (95%CI 1.06-2.64).

Conclusion: In critically ill COVID-19 patients, we observed a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a non-linear association between BMI and mortality risk. (NCT04391738).
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http://dx.doi.org/10.1002/oby.23223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242742PMC
May 2021

IFNγ-producing NK cells in adipose tissue are associated with hyperglycemia and insulin resistance in obese women.

Int J Obes (Lond) 2021 Jul 1;45(7):1607-1617. Epub 2021 May 1.

Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France.

Background/objectives: Innate lymphoid cells (ILCs) play an important role in the maintenance of immune and metabolic homeostasis in adipose tissue (AT). The crosstalk between AT ILCs and adipocytes and other immune cells coordinates adipocyte differentiation, beiging, glucose metabolism and inflammation. Although the metabolic and homeostatic functions of mouse ILCs have been extensively investigated, little is known about human adipose ILCs and their roles in obesity and insulin resistance (IR).

Subjects/methods: Here we characterized T and NK cell populations in omental AT (OAT) from women (n = 18) with morbid obesity and varying levels of IR and performed an integrated analysis of metabolic parameters and adipose tissue transcriptomics.

Results: In OAT, we found a distinct population of CD56NKp46EOMES NK cells characterized by expression of cytotoxic molecules, pro-inflammatory cytokines, and markers of cell activation. AT IFNγ NK cells, but not CD4, CD8 or γδ T cells, were positively associated with glucose levels, glycated hemoglobin (HbA1c) and IR. AT NK cells were linked to a pro-inflammatory gene expression profile in AT and developed an effector phenotype in response to IL-12 and IL-15. Moreover, integrated transcriptomic analysis revealed a potential implication of AT IFNγ NK cells in controlling adipose tissue inflammation, remodeling, and lipid metabolism.

Conclusions: Our results suggest that a distinct IFNγ-producing NK cell subset is involved in metabolic homeostasis in visceral AT in humans with obesity and may be a potential target for therapy of IR.
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http://dx.doi.org/10.1038/s41366-021-00826-1DOI Listing
July 2021

Effects of proprotein convertase subtilisin kexin type 9 modulation in human pancreatic beta cells function.

Atherosclerosis 2021 06 20;326:47-55. Epub 2021 Apr 20.

Université de La Réunion, Inserm UMR 1188 DéTROI, Sainte Clotilde, France. Electronic address:

Background And Aims: Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) is an endogenous inhibitor of the LDL receptor (LDLR). Mendelian randomization studies suggest that PCSK9 deficiency increases diabetes risk, but the underlying mechanisms remain unknown. The aim of our study was to investigate whether PCSK9 or its inhibition may modulate beta cell function.

Methods: We assessed PCSK9 and insulin colocalization in human pancreatic sections by epifluorescent and confocal microscopy. We also investigated the expression and the function of PCSK9 in the human EndoC-βH1 beta cell line, by ELISA and flow cytometry, respectively. PCSK9 was inhibited with Alirocumab or siRNA. LDLR expression and LDL uptake were assessed by flow cytometry.

Results: PCSK9 was expressed and secreted from beta cells isolated from human pancreas as well as from EndoC-βH1 cells. PCSK9 secretion was enhanced by statin treatment. Recombinant PCSK9 decreased LDLR abundance at the surface of these cells, an effect abrogated by Alirocumab. Alirocumab as well as PCSK9 silencing increased LDLR expression at the surface of EndoC-βH1 cells. Neither exogenous PCSK9, nor Alirocumab, nor PCSK9 silencing significantly altered glucose-stimulated insulin secretion (GSIS) from these cells. High-low density lipoproteins (LDL) concentrations decreased GSIS, but the addition of PCSK9 or its inhibition did not modulate this phenomenon.

Conclusions: While PCSK9 regulates LDLR abundance in beta cells, inhibition of exogenous or endogenous PCSK9 does not appear to significantly impact insulin secretion. This is reassuring for the safety of PCSK9 inhibitors in terms of beta cell function.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.044DOI Listing
June 2021

Neuromedin U uses Gαi2 and Gαo to suppress glucose-stimulated Ca2+ signaling and insulin secretion in pancreatic β cells.

PLoS One 2021 15;16(4):e0250232. Epub 2021 Apr 15.

Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Neuromedin U (NMU), a highly conserved peptide in mammals, is involved in a wide variety of physiological processes, including impairment of pancreatic β-cell function via induction of mitochondrial dysfunction and endoplasmic reticulum (ER) stress, ultimately suppressing insulin secretion. NMU has two receptors, NMU receptor 1 (NMUR1) and NMUR2, both of which are G-protein-coupled receptors (GPCRs). Only NMUR1 is expressed in mouse islets and β cell-derived MIN6-K8 cells. The molecular mechanisms underlying the insulinostatic action mediated by NMUR1 in β cells have yet to be elucidated. In this study, we explored the molecular mechanism driving impairment of insulin secretion in β cells by the NMU-NMUR1 axis. Pretreatment with the Gαi/o inhibitor Bordetella pertussis toxin (PTX), but not the Gαq inhibitor YM254890, abolished NMU-induced suppression of glucose-stimulated insulin secretion and calcium response in β cells. Knockdown of Gαi2 and Gαo in β cells counteracted NMU-induced suppression of insulin secretion and gene alterations related to mitochondrial fusion (Mfn1, Mfn2), fission (Fis1, Drp1), mitophagy (Pink1, Park2), mitochondrial dynamics (Pgc-1α, Nrf1, and Tfam), ER stress (Chop, Atp2a3, Ryr2, and Itpr2), intracellular ATP level, and mitochondrial membrane potential. NMU decreased forskolin-stimulated intracellular cAMP in both mouse and human islets. We concluded that NMUR1 coupled to PTX-sensitive Gαi2 and Gαo proteins in β cells reduced intracellular Ca2+ influx and cAMP level, thereby causing β-cell dysfunction and impairment. These results highlight a novel signaling mechanism of NMU and provide valuable insights into the further investigation of NMU functions in β-cell biology.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250232PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049253PMC
April 2021

Evolution of Non-alcoholic Fatty Liver Disease (NAFLD) Biomarkers in Response to Weight Loss 1 Year After Bariatric Surgery-a Post Hoc Analysis of the FibroTest Prospective Study.

Obes Surg 2021 08 12;31(8):3548-3556. Epub 2021 Apr 12.

Department of Digestive Surgery, Rouen University Hospital, 1 rue de Germont, 76000, Rouen, France.

Background: Bariatric surgery is among the therapeutic options for non-alcoholic fatty liver disease (NAFLD), affecting 90% of patients with obesity. The aim of this study was to evaluate the evolution of NAFLD lesions 1 year after surgery using noninvasive markers.

Methods: From November 2011 to November 2012, 253 patients with obesity undergoing bariatric surgery in three French University Hospitals were included. Histological data regarding intraoperative liver biopsy were collected at baseline, clinical, and biological data, including FibroTest®, SteatoTest®, and NASHTest®, before and after surgery.

Results: Fibrosis' prevalence was 74.2% with a positive predictive value (PPV) for FibroTest® of 78.6% and 43.4% for significant fibrosis (Kleiner ≥ F2) with a negative predictive value (NPV) of 56.1%. NAFLD's prevalence was 84% with a PPV for SteatoTest® of 85.9% and 7.7% for NASH with an NPV for NASHTest® of 93.8%. One year after bariatric surgery, mean BMI had significantly decreased from 46.5 to 31.7 kg/m (p < 0.001). Fibrosis assessed by the FibroTest® showed that 82.5% of patients were F0 after surgery compared to 90.9% before. Using SteatoTest®, the percent of patient without steatosis (S0) increased from 1.6 to 49.6% after surgery, and rate of severe steatosis (S3) improved from 43.3 to 3.9%. NASHTest® revealed that the percent of patients without NASH increased from 12.8 to 73.6% and rates of NASH improved from 12 to 0.8%.

Conclusions: Validated noninvasive biomarkers SteatoTest® and NASHTest® suggested NAFLD and steatohepatitis improvement after bariatric surgery and might be useful tools for patient follow-up. Regarding fibrosis, FibroTest® was not accurate in patients with extreme obesity.
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http://dx.doi.org/10.1007/s11695-021-05402-0DOI Listing
August 2021

1921-2021: From insulin discovery to islet transplantation in type 1 diabetes.

Ann Endocrinol (Paris) 2021 Apr 8;82(2):74-77. Epub 2021 Apr 8.

INSERM U1190, 59000 Lille, France; University of Lille, 59000 Lille, France; CHU Lille, Endocrinology, Diabetology, Metabolism, and Nutrition, 59000 Lille, France. Electronic address:

One century after the discovery of insulin, the French Health regulations have just authorized the reimbursement for islet transplantation. Intraportal islet allotransplantation from a pancreatic donor is indicated in patients with type 1 diabetes (T1D) complicated with lability or hypoglycemia unawareness, or in case of a functioning kidney graft; islet auto-transplantation may be indicated after pancreatic surgery.Compared with insulin even administered in closed-loop pumps, the specificity of islet allotransplantation is the restoration of C-peptide secretion. Long-term insulin-independence is observed when the engrafted islet mass is sufficient, at the cost of immunosuppression. Fewer low-glucose events and less glucose variability, are observed even with minimal functional islet graft, after islet transplantation as at onset of T1D, when a residual C-peptide secretion is maintained, an objective currently approached with less aggressive immuno-modulating therapies than in the past. Therefore, restoration or preservation of endogen insulin secretion is an important goal, allowing to maintain a long-term glucose balance with more than 70% of time in range 3.9-10mmol/L and less than 3% of time <3.9mmol/L, thus reducing the occurrence of diabetic complications. In the clinical setting, - the preservation of C-peptide at early stage of T1D, - the use of technological ressources (multi-injections, sensors, insulin pump, closed-loop systems) at later stages, - and islet transplantation when hypoglycemia awareness becomes impaired are complementary for a personalized care all along the life of T1D patients.
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http://dx.doi.org/10.1016/j.ando.2021.03.006DOI Listing
April 2021

Pancreatic islet transplantation under the kidney capsule of mice: model of refinement for molecular and graft analysis.

Lab Anim 2021 Apr 8:236772211004051. Epub 2021 Apr 8.

Translational Research for Diabetes, Inserm, University of Lille, France.

Diabetes cell therapy by human islet transplantation can restore an endogenous insulin secretion and normal glycaemic control in type 1 diabetic patients for as long as 10 years post transplantation. Before transplantation, each clinical islet preparation undergoes extensive and quality controls. The quality control assay consists of transplanting human islets under the kidney capsule of immunocompromised mice. Currently, it is considered the best predictive factor to qualify clinical transplant efficiency. This chimeric model offers a wide area of study since it combines the possibility of producing not only quantitative but also a maximum of qualitative data. Today's technological advances allow us to obtain more accurate and stronger data from the animals used in research while ensuring their comfort and well-being throughout the protocol, including cage enrichment and pain treatment during and after surgery. As demonstrated in this valuable model, we are able to generate more usable results (Refine), while reducing the number of animals used (Reduce), by focusing on the development of analysis techniques (Replace), which clearly highlights the Burch and Russell 3Rs concept.
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http://dx.doi.org/10.1177/00236772211004051DOI Listing
April 2021

Comparison of Morbidity After Total Thyroidectomy Among Adult Patients With and Without Preoperative Hyperthyroidism.

JAMA Otolaryngol Head Neck Surg 2021 Jun;147(6):573-575

Chirurgie Cancérologique, Digestive et Endocrinienne, Hôtel Dieu, Centre Hospitalier Universitaire Nantes, Nantes, France.

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http://dx.doi.org/10.1001/jamaoto.2021.0080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974829PMC
June 2021

Quantitative dual isotope iodine/Tc-MIBI scintigraphy: A new approach to rule out malignancy in thyroid nodules.

Ann Endocrinol (Paris) 2021 Apr 13;82(2):83-91. Epub 2021 Mar 13.

Department of Endocrinology, Diabetology, and Metabolism, Lille University Hospital, Lille, France; Department of Endocrinology, Valenciennes General Hospital, Valenciennes, France.

Background: The aim of this study was to evaluate the role of dual isotope Iodine/Tc-MIBI thyroid scintigraphy (IMS) in discriminating between malignant and benign lesions in indeterminate nodules using quantitative analysis methods.

Methods: Thirty-five consecutive patients with thyroid nodules of indeterminate or non-diagnostic cytology and cold on Iodine scintigraphy (10 Bethesda I, 24 Bethesda III-IV, 1 in which cytology was impossible) underwent IMS between 2017 and 2019 with uptake quantification at two time points ahead of thyroidectomy: early and late. Images were analyzed by two blinded physicians.

Results: Twelve nodules were malignant and 23 benign on histopathology. Mean uptake values were lower in benign than in malignant nodules at both time points: early, 8.7±4.1 versus 12.9±3.5 (P=0.005); and late, 5.3±2.7 versus 7.7±1.1 (P=0.008). Interobserver reproducibility was excellent. The intraclass correlation coefficient was 0.86 in benign and 0.92 in malignant lesions for early uptake result (ER) and 0.94 and 0.85 respectively for late uptake result (LR). The optimal LR cut-off  to exclude a diagnosis of malignancy was set at 5.9 . The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off were, respectively, 100%, 65.2%, 60%, 100% and 77.1%.

Conclusion: Despite some study limitations, quantitative analysis of Tc-MIBI thyroid scintigraphy had a good reproducibility, which could help to rule out malignancy in non-diagnostic or indeterminate thyroid nodules and thereby reducing the number of patients undergoing unnecessary surgery when LR is below 5.9.
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http://dx.doi.org/10.1016/j.ando.2021.03.003DOI Listing
April 2021

Pancreatoduodenectomy for Neuroendocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1: An AFCE (Association Francophone de Chirurgie Endocrinienne) and GTE (Groupe d'étude des Tumeurs Endocrines) Study.

World J Surg 2021 06 1;45(6):1794-1802. Epub 2021 Mar 1.

Department of Digestive and Endocrine Surgery, Dijon University Hospital, University of Burgundy, Dijon, France.

Aim: To assess postoperative complications and control of hormone secretions following pancreatoduodenectomy (PD) performed on multiple endocrine neoplasia type 1 (MEN1) patients with duodenopancreatic neuroendocrine tumors (DP-NETs).

Background: The use of PD to treat MEN1 remains controversial, and evaluating the right place of PD in MEN1 disease makes sense.

Methods: Thirty-one MEN1 patients from the Groupe d'étude des Tumeurs Endocrines MEN1 cohort who underwent PD for DP-NETs between 1971 and 2013 were included. Early and late postoperative complications, secretory control and overall survival were analyzed.

Results: Indication for surgery was: Zollinger-Ellison syndrome (n = 18; 58%), nonfunctioning tumor (n = 9; 29%), insulinoma (n = 2; 7%), VIPoma (n = 1; 3%) and glucagonoma (n = 1; 3%). Mean follow-up was 141 months (range 0-433). Pancreatic fistulas occurred in 5 patients (16.1%), distant metastases in 6 (mean onset of 43 months; range 13-110 months), postoperative diabetes mellitus in 7 (22%), and pancreatic exocrine insufficiency in 6 (19%). Five-year overall survival was 93.3% [CI 75.8-98.3] and ten-year overall survival was 89.1% [CI 69.6-96.4]. After a mean follow-up of 151 months (range 0-433), the biochemical cure rate for MEN-1 related gastrinomas was 61%.

Conclusion: In MEN1 patients, pancreatoduodenectomy can be used to control hormone secretions (gastrin, glucagon, VIP) and to remove large NETs. PD was found to control gastrin secretions in about 60% of cases.
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http://dx.doi.org/10.1007/s00268-021-06005-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093175PMC
June 2021

Bariatric-Metabolic Surgery Utilisation in Patients With and Without Diabetes: Data from the IFSO Global Registry 2015-2018.

Obes Surg 2021 06 27;31(6):2391-2400. Epub 2021 Feb 27.

College of Medicine and Public Health, Flinders University, Adelaide, Australia.

Background: Comparative international practice of patients undergoing bariatric-metabolic surgery for type 2 diabetes mellitus (T2DM) is unknown. We aimed to ascertain baseline age, sex, body mass index (BMI) and types of operations performed for patients with T2DM submitted to the IFSO Global Registry.

Materials And Methods: Cross-sectional analysis of patients having primary surgery in 2015-2018 for countries with ≥90% T2DM data completion and ≥ 1000 submitted records.

Results: Fifteen countries including 11 national registries met the inclusion criteria. The rate of T2DM was 24.2% (99,537 of 411,581 patients, country range 12.0-55.1%) and 77.1% of all patients were women. In every country, patients with T2DM were older than those without T2DM (overall mean age 49.2 [SD 11.4] years vs 41.8 [11.9] years, all p < 0.001). Men were more likely to have T2DM than women, odds ratio (OR) 1.68 (95% CI 1.65-1.71), p < 0.001. Men showed higher rates of T2DM for BMI <35 kg/m compared to BMI ≥35.0 kg/m, OR 2.76 (2.52-3.03), p < 0.001. This was not seen in women, OR 0.78 (0.73-0.83), p < 0.001. Sleeve gastrectomy was the commonest operation overall, but less frequent for patients with T2DM, patients with T2DM 54.9% vs without T2DM 65.8%, OR 0.63 (0.63-0.64), p < 0.001. Twelve out of 15 countries had higher proportions of gastric bypass compared to non-bypass operations for T2DM, OR 1.70 (1.67-1.72), p < 0.001.

Conclusion: Patients with T2DM had different characteristics to those without T2DM. Older men were more likely to have T2DM, with higher rates of BMI <35 kg/m and increased likelihood of food rerouting operations.
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http://dx.doi.org/10.1007/s11695-021-05280-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113173PMC
June 2021

NASH-related increases in plasma bile acid levels depend on insulin resistance.

JHEP Rep 2021 Apr 16;3(2):100222. Epub 2020 Dec 16.

Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France.

Background & Aims: Plasma bile acids (BAs) have been extensively studied as pathophysiological actors in non-alcoholic steatohepatitis (NASH). However, results from clinical studies are often complicated by the association of NASH with type 2 diabetes (T2D), obesity, and insulin resistance (IR). Here, we sought to dissect the relationship between NASH, T2D, and plasma BA levels in a large patient cohort.

Methods: Four groups of patients from the Biological Atlas of Severe Obesity (ABOS) cohort (Clinical Trials number NCT01129297) were included based on the presence or absence of histologically evaluated NASH with or without coincident T2D. Patients were matched for BMI, homeostatic model assessment 2 (HOMA2)-assessed IR, glycated haemoglobin, age, and gender. To study the effect of IR and BMI on the association of plasma BA and NASH, patients from the HEPADIP study were included. In both cohorts, fasting plasma BA concentrations were measured.

Results: Plasma BA concentrations were higher in NASH compared with No-NASH patients both in T2D and NoT2D patients from the ABOS cohort. As we previously reported that plasma BA levels were unaltered in NASH patients of the HEPADIP cohort, we assessed the impact of BMI and IR on the association of NASH and BA on the combined BA datasets. Our results revealed that NASH-associated increases in plasma total cholic acid (CA) concentrations depend on the degree of HOMA2-assessed systemic IR, but not on β-cell function nor on BMI.

Conclusions: Plasma BA concentrations are elevated only in those NASH patients exhibiting pronounced IR.

Lay Summary: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease that frequently occurs in patients with obesity and type 2 diabetes. Reliable markers for the diagnosis of NASH are needed. Plasma bile acids have been proposed as NASH biomarkers. Herein, we found that plasma bile acids are only elevated in patients with NASH when significant insulin resistance is present, limiting their utility as NASH markers.
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http://dx.doi.org/10.1016/j.jhepr.2020.100222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878982PMC
April 2021

Salvage Robotic Roux-en-Y Fistulojejunostomy for Chronic Gastro-Colic Fistula After Laparoscopic Sleeve Gastrectomy.

Obes Surg 2021 Apr 15;31(4):1899-1900. Epub 2021 Feb 15.

General Endocrine Surgery Department, Lille University Hospital CHU Lille, Lille, France.

Roux-en-Y fistulojejunostomy (RYFJ) has been proposed as a surgical option for the treatment of a chronic fistula after sleeve gastrectomy but can be technically challenging. The robotic approach in bariatric surgery has emerged as a new rapidly evolving technology and allows performing more complex surgical procedures. Here we present the case of a 42-year-old man referred to our university tertiary center for a chronic gastro-colic fistula after laparoscopic SG who underwent a salvage robotic RYFJ. The aim of this video is to present our management of a chronic gastro-colic fistula after laparoscopic SG demonstrating the technical advantages of a robotic approach to a RYFJ.
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http://dx.doi.org/10.1007/s11695-021-05242-yDOI Listing
April 2021

Characterization of one anastomosis gastric bypass and impact of biliary and common limbs on bile acid and postprandial glucose metabolism in a minipig model.

Am J Physiol Endocrinol Metab 2021 04 25;320(4):E772-E783. Epub 2021 Jan 25.

U1190, Institut Pasteur de Lille, University of Lille, Inserm, Lille, France.

The alimentary limb has been proposed to be a key driver of the weight-loss-independent metabolic improvements that occur upon bariatric surgery. However, the one anastomosis gastric bypass (OAGB) procedure, consisting of one long biliary limb and a short common limb, induces similar beneficial metabolic effects compared to Roux-en-Y Gastric Bypass (RYGB) in humans, despite the lack of an alimentary limb. The aim of this study was to assess the role of the length of biliary and common limbs in the weight loss and metabolic effects that occur upon OAGB. OAGB and sham surgery, with or without modifications of the length of either the biliary limb or the common limb, were performed in Gottingen minipigs. Weight loss, metabolic changes, and the effects on plasma and intestinal bile acids (BAs) were assessed 15 days after surgery. OAGB significantly decreased body weight, improved glucose homeostasis, increased postprandial GLP-1 and fasting plasma BAs, and qualitatively changed the intestinal BA species composition. Resection of the biliary limb prevented the body weight loss effects of OAGB and attenuated the postprandial GLP-1 increase. Improvements in glucose homeostasis along with changes in plasma and intestinal BAs occurred after OAGB regardless of the biliary limb length. Resection of only the common limb reproduced the glucose homeostasis effects and the changes in intestinal BAs. Our results suggest that the changes in glucose metabolism and BAs after OAGB are mainly mediated by the length of the common limb, whereas the length of the biliary limb contributes to body weight loss. Common limb mediates postprandial glucose metabolism change after gastric bypass whereas biliary limb contributes to weight loss.
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http://dx.doi.org/10.1152/ajpendo.00356.2020DOI Listing
April 2021

Exome-Wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated With Fatty Liver Disease.

Gastroenterology 2021 Apr 6;160(5):1634-1646.e7. Epub 2021 Feb 6.

Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden; Clinical Nutrition Unit, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy; Cardiology Department, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address:

Background & Aims: Fatty liver disease (FLD) is a growing epidemic that is expected to be the leading cause of end-stage liver disease within the next decade. Both environmental and genetic factors contribute to the susceptibility of FLD. Several genetic variants contributing to FLD have been identified in exome-wide association studies. However, there is still a missing hereditability indicating that other genetic variants are yet to be discovered.

Methods: To find genes involved in FLD, we first examined the association of missense and nonsense variants with alanine aminotransferase at an exome-wide level in 425,671 participants from the UK Biobank. We then validated genetic variants with liver fat content in 8930 participants in whom liver fat measurement was available, and replicated 2 genetic variants in 3 independent cohorts comprising 2621 individuals with available liver biopsy.

Results: We identified 190 genetic variants independently associated with alanine aminotransferase after correcting for multiple testing with Bonferroni method. The majority of these variants were not previously associated with this trait. Among those associated, there was a striking enrichment of genetic variants influencing lipid metabolism. We identified the variants rs2792751 in GPAM/GPAT1, the gene encoding glycerol-3-phosphate acyltransferase, mitochondrial, and rs429358 in APOE, the gene encoding apolipoprotein E, as robustly associated with liver fat content and liver disease after adjusting for multiple testing. Both genes affect lipid metabolism in the liver.

Conclusions: We identified 2 novel genetic variants in GPAM and APOE that are robustly associated with steatosis and liver damage. These findings may help to better elucidate the genetic susceptibility to FLD onset and progression.
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http://dx.doi.org/10.1053/j.gastro.2020.12.023DOI Listing
April 2021

Proglucagon-Derived Peptides Expression and Secretion in Rat Insulinoma INS-1 Cells.

Front Cell Dev Biol 2020 10;8:590763. Epub 2020 Nov 10.

INSERM, U1190, Lille, France.

Rat insulinoma INS-1 cells are widely used to study insulin secretory mechanisms. Studies have shown that a population of INS-1 cells are bi-hormonal, co-expressing insulin, and proglucagon proteins. They coined this population as immature cells since they co-secrete proglucagon-derived peptides from the same secretory vesicles similar to that of insulin. Since proglucagon encodes multiple peptides including glucagon, glucagon-like-peptide-1 (GLP-1), GLP-2, oxyntomodulin, and glicentin, their specific expression and secretion are technically challenging. In this study, we aimed to focus on glucagon expression which shares the same amino acid sequence with glicentin and proglucagon. Validation of the anti-glucagon antibody (Abcam) by Western blotting techniques revealed that the antibody detects proglucagon (≈ 20 kDa), glicentin (≈ 9 kDa), and glucagon (≈ 3 kDa) in INS-1 cells and primary islets, all of which were absent in the kidney cell line (HEK293). Using the validated anti-glucagon antibody, we showed by immunofluorescence imaging that a population of INS-1 cells co-express insulin and proglucagon-derived proteins. Furthermore, we found that chronic treatment of INS-1 cells with high-glucose decreases insulin and glucagon content, and also reduces the percentage of bi-hormonal cells. In line with insulin secretion, we found glucagon and glicentin secretion to be induced in a glucose-dependent manner. We conclude that INS-1 cells are a useful model to study glucose-stimulated insulin secretion, but not that of glucagon or glicentin. Our study suggests Western blotting technique as an important tool for researchers to study proglucagon-derived peptides expression and regulation in primary islets in response to various metabolic stimuli.
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http://dx.doi.org/10.3389/fcell.2020.590763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683504PMC
November 2020

CDKN2A/p16INK4a suppresses hepatic fatty acid oxidation through the AMPKα2-SIRT1-PPARα signaling pathway.

J Biol Chem 2020 12 9;295(50):17310-17322. Epub 2020 Oct 9.

Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France. Electronic address:

In addition to their well-known role in the control of cellular proliferation and cancer, cell cycle regulators are increasingly identified as important metabolic modulators. Several GWAS have identified SNPs near , the locus encoding for p16INK4a (p16), associated with elevated risk for cardiovascular diseases and type-2 diabetes development, two pathologies associated with impaired hepatic lipid metabolism. Although p16 was recently shown to control hepatic glucose homeostasis, it is unknown whether p16 also controls hepatic lipid metabolism. Using a combination of and approaches, we found that p16 modulates fasting-induced hepatic fatty acid oxidation (FAO) and lipid droplet accumulation. In primary hepatocytes, p16-deficiency was associated with elevated expression of genes involved in fatty acid catabolism. These transcriptional changes led to increased FAO and were associated with enhanced activation of PPARα through a mechanism requiring the catalytic AMPKα2 subunit and SIRT1, two known activators of PPARα. By contrast, overexpression was associated with triglyceride accumulation and increased lipid droplet numbers , and decreased ketogenesis and hepatic mitochondrial activity Finally, gene expression analysis of liver samples from obese patients revealed a negative correlation between expression and and its target genes. Our findings demonstrate that p16 represses hepatic lipid catabolism during fasting and may thus participate in the preservation of metabolic flexibility.
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http://dx.doi.org/10.1074/jbc.RA120.012543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863903PMC
December 2020

Risk stratification of adrenal masses by [ F]FDG PET/CT: Changing tactics.

Clin Endocrinol (Oxf) 2021 02 26;94(2):133-140. Epub 2020 Nov 26.

Service de Médecine Nucléaire, Centre Hospitalo-Universitaire de la Timone, APHM, Centre Européen de Recherche en Imagerie Médicale, Aix Marseille Univ, Marseille, France.

Context: [ F]FDG PET/CT improves adrenal tumour characterization. However, there is still no consensus regarding the optimal imaging biomarkers of malignancy.

Objectives: To assess the performance of Tumour standardized uptake value (SUV) :Liver SUV for malignancy-risk and to build and evaluate a prediction model.

Design/methods: The cohort consisted of consecutive patients with adrenal masses evaluated by [ F]FDG PET/CT. The gold standard for malignancy was based on histology or a multidisciplinary consensus in nonoperated cases. The performance of the previously reported cut-off for Tumour SUV :Liver SUV (>1.5) was evaluated in this independent cohort. Additionally, a predictive model of malignancy was built from the training cohort (previous study) and evaluated in the validation cohort (current study).

Results: Sixty-four patients were evaluated; 28% of them had a Cushing's syndrome. Fifty-four adrenal masses were classified as benign and 10 as malignant (including 7 adrenocortical carcinomas). Compared to benign masses, malignant lesions were larger in size, had higher unenhanced densities and higher [ F]FDG uptake. CT-derived anthropometric parameters did not differ between benign and malignant masses. A tumour SUV :Liver SUV  > 1.5 showed a good diagnostic performance: Se = 90.0%/Sp = 92.6%/PPV = 69.2%/NPV = 98.0% and accuracy = 92.2%. A predictive model based on tumour size and tumour-to-liver uptake SUV ratio for malignancy-risk was validated and provides a complementary approach to the ratio.

Conclusions: Tumour SUV :Liver SUV uptake ratio is a useful biomarker for diagnosis of adrenal masses. Another tactic would be to calculate with the model an individual risk of malignancy and integrate this information into a shared decision-making process.
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http://dx.doi.org/10.1111/cen.14338DOI Listing
February 2021

Efficacy and Safety of the Duodeno-Jejunal Bypass Liner in Patients With Metabolic Syndrome: A Multicenter Randomized Controlled Trial (ENDOMETAB).

Ann Surg 2020 11;272(5):696-702

University Lille, Inserm, CHU Lille, Institut Pasteur Lille U1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, Integrated Center of Obesity, Lille, France.

Objective: The aim of this study was to compare the efficacy and safety of 12-month implantation of a duodeno-jejunal bypass liner (DJBL) with conventional medical care in patients with metabolic syndrome (MS).

Summary Background Data: DJBL is an endoscopic device for treating obesity and related disorders. The persistence of favorable results after 6 months has not been tested in a controlled study.

Methods: We conducted a multicenter randomized controlled trial, stratified by center and diabetes status. The primary endpoint was the remission of MS at 12 months. The secondary endpoints included body mass index (BMI), glucose control, blood pressure, and lipids, assessed at 12 months after implantation, and again, at 12 months after the removal of the DJBL. Up to 174 subjects were planned to be randomized into either the DJBL or the control arm at a 2:1 ratio, respectively. Study enrollment was discontinued by the Scientific Monitoring Committee due to the early termination of the ENDO trial (NCT01728116) by the US Food and Drug Administration. The study was terminated after withdrawal of the device's European Conformity marking by the European Medicines Agency, and an interim analysis was performed.

Results: A total of 82 patients were enrolled (67.5% female, 48.8% with diabetes). At 12 months after randomization, the primary endpoint was met in 6 (12%) DJBL patients and 3 (10%) controls (P = 0.72). Patients in the DJBL group experienced greater BMI loss [mean adjusted difference (95% confidence interval, CI) -3.1 kg/m (-4.4 to -1.9) kg/m, P < 0.001] and HbA1c change [mean adjusted difference -0.5% (95% CI -0.9 to -0.2); P < 0.001] than those in the control group. No difference remained statistically significant at 12 months after the removal of the DJBL. In the DJBL group, 39% of patients experienced at least one device-related serious adverse event, which was classified as Grade III Dindo-Clavien in 22%, and required premature device explantation in 16%.

Conclusions: The present study showed a transient clinical benefit of DJBL, which was only apparent at 1 year, when the device was still in situ, and was obtained at the risk of serious device-related adverse events in 39% of patients. These results do not support the routine use of DJBL for weight loss and glucose control in patients with MS.
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http://dx.doi.org/10.1097/SLA.0000000000004339DOI Listing
November 2020

Coxsackievirus-B4 Infection Can Induce the Expression of Human Endogenous Retrovirus W in Primary Cells.

Microorganisms 2020 Sep 1;8(9). Epub 2020 Sep 1.

Laboratoire de Virologie ULR3610 Univ Lille, CHU Lille, 59000 Lille, France.

Human Endogenous Retrovirus W Envelope (HERV-W ENV) mRNA or protein can be found in peripheral blood mononuclear cells (PBMCs) and exocrine pancreas of patients with type 1 diabetes (T1D). Further, previous observations have shown an association between enteroviral infection and development of T1D; specifically, coxsackievirus-B (CV-B) has been detected in the blood and pancreas of patients with T1D. Notably, viruses can activate HERV-W expression. Hence, we evaluated the effect of CV-B4 infection on HERV-W mRNA expression. Primary human pancreatic ductal cells were obtained from five brain-dead donors. In the pancreatic cells of three donors, the HERV-W mRNA level measured using RT-qPCR was upregulated upon CV-B4 infection. The HERV-W ENV protein was detected in the infected cells using the immunoblot assay. In human PBMCs inoculated with CV-B4 or when CV-B4 was incubated with an enhancing serum, the HERV-W mRNA level was higher than the background RNA level. In monocyte-derived macrophages obtained from 5 of 13 donors, the HERV-W mRNA level was higher in cultures inoculated with CV-B4 than in the control. Therefore, CV-B4 can upregulate or induce the transcription of a certain HERV-W copy (or copies) in primary cell cultures, such as monocytes, macrophages, and pancreatic cells.
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http://dx.doi.org/10.3390/microorganisms8091335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563422PMC
September 2020

A tool to predict progression of non-alcoholic fatty liver disease in severely obese patients.

Liver Int 2021 01;41(1):91-100

Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.

Background & Aims: Severely obese patients are a growing population at risk of non-alcoholic fatty liver disease (NAFLD). Considering the increasing burden, a predictive tool of NAFLD progression would be of interest. Our objective was to provide a tool allowing general practitioners to identify and refer the patients most at risk, and specialists to estimate disease progression and adapt the therapeutic strategy.

Methods: This predictive tool is based on a Markov model simulating steatosis, fibrosis and non-alcoholic steatohepatitis (NASH) evolution. This model was developped from data of 1801 severely obese, bariatric surgery candidates, with histological assessment, integrating duration of exposure to risk factors. It is then able to predict current disease severity in the absence of assessment, and future cirrhosis risk based on current stage.

Results: The model quantifies the impact of sex, body-mass index at 20, diabetes, age of overweight onset, on progression. For example, for 40-year-old severely obese patients seen by the general practitioners: (a) non-diabetic woman overweight at 20, and (b) diabetic man overweight at 10, without disease assessment, the model predicts their current risk to have NASH or F3-F4: for (a) 5.7% and 0.6%, for (b) 16.1% and 10.0% respectively. If those patients have been diagnosed F2 by the specialist, the model predicts the 5-year cirrhosis risk: 1.8% in the absence of NASH and 6.0% in its presence for (a), 10.3% and 26.7% respectively, for (b).

Conclusions: This model provides a decision-making tool to predict the risk of liver disease that could help manage severely obese patients.
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http://dx.doi.org/10.1111/liv.14650DOI Listing
January 2021

Risk Factors of Redo Surgery After Unilateral Focused Parathyroidectomy: Conclusions From a Comprehensive Nationwide Database of 13,247 Interventions Over 6 Years.

Ann Surg 2020 11;272(5):801-806

General and Endocrine Surgery Department, Lille University Hospital CHU Lille, Lille, France.

Background: Surgical removal of hyperfunctional parathyroid gland is the definitive treatment for primary hyperparathyroidism (pHPT). Postoperative follow-up shows variability in persistent/recurrent disease rate throughout different centers.

Objective: To evaluate the incidence of redo surgery after targeted parathyroidectomy for pHPT.

Methods: We performed a nationwide retrospective cohort study on the "Programme de Medicalisation des Systemes d'Information," the French administrative database that collects information on all healthcare facilities' discharges. We extracted data from 2009 to 2018 for all patients who underwent parathyroidectomy for pHPT between January 2011 to December 2016. The primary outcome was the reoperation rate within 2 years since first surgery. Patients who had a first attempt of surgery within the previous 24 months, familial hyperparathyroidism, multiglandular disease, and renal failure were excluded. Results were adjusted according to sex and the Elixhauser Comorbidity Index. Operative volume thresholds to define high-volume centers were achieved by the Chi-Squared Automatic Interaction Detector method.

Results: In the study period, 13,247 patients (median age 63, F/M=3.6) had a focused parathyroidectomy by open (88.7%) or endoscopic approach. Need of remedial surgery was 2.8% at 2 years. In multivariate analysis, factors predicting redo surgery were: cardiac history (P=0.008), obesity (P=0.048), endoscopic approach (P=0.005), and low-volume center (P<0.001). We evaluated that an annual caseload of 31 parathyroidectomies was the best threshold to discriminate high-volume centers and carries the lowest morbidity/failure rate.

Conclusion: Although focused parathyroidectomy represents a standardized operation, cure rate is strongly associated with annual hospital caseload, type of procedure (endoscopic), and patients' features (obesity, cardiac history). Patients with risk factors for redo surgery should be considered for an open surgery in a high-volume center.
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http://dx.doi.org/10.1097/SLA.0000000000004269DOI Listing
November 2020
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