Grenoble University Research Articles

Effects of SLC34A3 or SLC34A1 variants on calcium and phosphorus homeostasis.

Variants in SLC34A1 and SLC34A2 genes, which encode co-transporters NaPi2a and NaPi2c, respectively, can lead to hypophosphatemia due to renal phosphate loss. This condition results in hypercalcitriolemia and hypercalciuria, leading to formation of kidney stones and nephrocalcinosis. Phenotype is highly variable. Management includes hyperhydration, dietary modifications, and/or phosphate supplementation. Thiazides and azoles may be used, but randomized studies are needed to confirm their clinical efficacy. We conducted a retrospective study in the pediatric nephrology unit at Grenoble University Hospital from January 2010 to December 2023. The study aimed to describe clinical and biological symptoms of patients with confirmed SLC34A1 and SLC34A3 gene variants and their outcomes. A total of 11 patients (9 females) from 6 different families had variants in the SLC34A1 (5 patients) and SLC34A3 (6 patients) genes. Median age at diagnosis was 72 [1-108] months. Average follow-up duration was 8.1 ± 4.5years. Presenting symptom was nephrocalcinosis (4 cases), followed by renal colic (3 cases). At diagnosis, 90% of patients had hypercalciuria and 45% had hypercalcitriolemia. Management included hyperhydration and dietary advice. All patients showed favorable outcomes with normal growth and school attendance. One patient with an SLC34A3 variant showed regression of nephrocalcinosis. Kidney function remained normal. Clinical and biological manifestations of SLC34 gene variants are highly variable, even among siblings; therefore, management must be personalized. Hygienic and dietary measures (such as hyperhydration, a low sodium diet, and age-appropriate calcium intake) result in favorable outcomes in most cases. Use of azoles (e.g., fluconazole) appears to be a promising therapeutic option.

Unraveling complexity: morbidity factors in elderly kidney transplant recipients.

The rising prevalence of end-stage renal failure in the elderly has led to an increased number of kidney transplantations in older individuals. While age does not solely determine transplant eligibility, frailty in elderly recipients significantly impacts post-transplant outcomes, particularly within the first year. The RETRAITE (REnal TRAnsplantIon ouTcome in Elderly recipients) study, a single-center retrospective cohort study at Grenoble Alpes University Hospital (France), examined kidney transplant recipients aged 70years and above transplanted between 2015 and 2020. The composite primary endpoint was defined as either of any hospital stay exceeding 40days, death and/or return to dialysis within the first post-transplant year. The study explored risk factors for recipient and graft survival, rejection, hospitalizations over 40days, and severe infections during the initial post-transplant year. Over six years, 149 patients aged 70years or older received transplants. Eleven patients died, and seven returned to dialysis within the first year, corresponding to a 1-year graft survival rate of 87.9%. At 1year, 49 patients (33%) met the composite endpoint. There was a significant association between the composite endpoint and curative anticoagulation [odds ratio (OR) 5.20; P<.001], peripheral arteriopathy (OR 3.14; P<.001) and delayed graft function (OR8.24; P<.001). This cohort then was merged with a cohort of 150 younger kidney transplanted patients and we confirmed these results. Time on dialysis, prolonged cold ischemia and donor age contributed to higher morbidity and mortality. Conversely, preemptive and living donor transplants were associated with lower morbidity and mortality. In this cohort aged over 70years, age alone did not statistically correlate with increased morbidity and mortality. Variables related to grafts and donors, especially curative anticoagulation, were linked to poorer outcomes, emphasizing the favorable impact of preemptive and living donor transplants on morbidity and mortality in elderly patients.

Development and validation of a code-based algorithm using in-hospital medical records to identify patients with pulmonary arterial hypertension in a French healthcare database.

Pulmonary arterial hypertension (PAH) is a rare and severe disease for which most of the evidence about prognostic factors, evolution and treatment efficacy comes from cohorts, registries and clinical trials. We therefore aimed to develop and validate a new PAH identification algorithm that can be used in the French healthcare database "Système National des Données de Santé (SNDS)". We developed and validated the algorithm using the Grenoble Alpes University Hospital medical charts. We first identified PAH patients following a previously validated algorithm, using in-hospital ICD-10 (10th revision of the International Statistical Classification of Diseases) codes, right heart catheterisation procedure and PAH-specific treatment dispensing. Then, we refined the latter with the exclusion of chronic thromboembolic pulmonary hypertension procedures and treatment, the main misclassification factor. Second, we validated this algorithm using a gold standard review of in-hospital medical charts and calculated sensitivity, specificity, positive and negative predictive value (PPV and NPV) and accuracy. Finally, we applied this algorithm in the French healthcare database and described the characteristics of the identified patients. In the Grenoble University Hospital, we identified 252 unique patients meeting all the algorithm's criteria between 1 January 2010 and 30 June 2022, and reviewed all medical records. The sensitivity, specificity, PPV, NPV and accuracy were 91.0%, 74.3%, 67.9%, 93.3% and 80.6%, respectively. Application of this algorithm to the SNDS yielded the identification of 9931 patients with consistent characteristics compared to PAH registries. Overall, we propose a new PAH identification algorithm developed and adapted to the French specificities that can be used in future studies using the French healthcare database.

Management of SAH

Every year, the neurosurgical intensive care unit at Grenoble's university hospital (CHU) receives a large number of cerebrovascular patients. Data collected in the department during 2023 show that subarachnoid hemorrhage (SAH) is one of the most frequent causes of the pathologies treated. In this article, we focus on the appropriate course of action.

Sociological determinants of adherence to continuous positive airway pressure in the management of sleep apnoea syndrome: protocol for a transdisciplinary, prospective observational study

IntroductionObstructive sleep apnoea syndrome (OSAS) is a chronic multiorgan pathology that has a negative impact on quality of life. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS....

Treatment of non-systemic Sjögren's syndrome: Potential prevention of systematization with immunosuppressant agent/biotherapy

BackgroundSjögren's syndrome (SS) is a systemic autoimmune pathology manifested mainly by a dry syndrome, intense asthenia and arthromyalgia. Systemic manifestations may also occur. Since 2019, immunosuppressant agents (IS) or biotherapies are recommended only for patients with systemic involvement. However, before 2019, in some cases, paucisymptomatic patients had been treated with IS/biotherapies, often off-label. Objective: We propose to evaluate the benefit and safety of using IS/biotherapy in patients with SS without systemic involvement. Methods: We retrospectively collected the clinical records of all patients with SS diagnosed according to ACR/EULAR diagnostic criteria followed up between January 1980 and October 2023 at Grenoble University Hospital (France). Results: Eighty-three patients were included: 64 with an initially non-systemic form. Of these patients with an initially non-systemic form, 24 were treated with IS/biotherapy. None of them developed secondary systematization, whereas 11 out of 40 patients in the untreated group did (p < 0.05). On the other hand, IS/biotherapy did not appear to improve dry syndrome. There were no serious adverse events. Conclusion: Early introduction of an IS/biotherapy treatment appears to provide a benefit for the patient without side effects.

Pilot Study: Safety and Performance Validation of an Ingestible Medical Device for Collecting Small Intestinal Liquid in Healthy Volunteers.

The connection between imbalances in the human gut microbiota, known as dysbiosis, and various diseases has been well established. Current techniques for sampling the small intestine are both invasive for patients and costly for healthcare facilities. Most studies on human gut microbiome are conducted using faecal samples, which do not accurately represent the microbiome in the upper intestinal tract. A pilot clinical investigation, registered as NCT05477069 and sponsored by the Grenoble Alpes University Hospital, is currently underway to evaluate a novel ingestible medical device (MD) designed for collecting small intestinal liquids by Pelican Health. This study is interventional and monocentric, involving 15 healthy volunteers. The primary objective of the study is to establish the safety and the performance of the MD when used on healthy volunteers. Secondary objectives include assessing the device's performance and demonstrating the difference between the retrieved sample from the MD and the corresponding faecal sample. Multi-omics analysis will be performed, including metagenomics, metabolomics, and culturomics. We anticipate that the MD will prove to be safe without any reported adverse effects, and we collected samples suitable for the proposed omics analyses in order to demonstrate the functionality of the MD and the clinical potential of the intestinal content.

Analysis of screening for neonatal hypoglycemia in "large-for-gestational-age" newborns without risk factors, and proposed changes in practice at Grenoble University Hospital

Analysis of screening for neonatal hypoglycemia in "large-for-gestational-age" newborns without risk factors, and proposed changes in practice at Grenoble University Hospital

Decreasing hospitalizations through geriatric hotlines: a prospective French multicenter study of people aged 75 and above

BackgroundThe Emergency unit of the hospital (Department) (ED) is the fastest and most common way for most French general practitioners (GPs) to respond to the complexity of managing older adults patients with multiple chronic diseases. In 2013, French regional health authorities proposed to set up telephone hotlines to promote interactions between GP clinics and hospitals. The main objective of our study was to analyze whether the hotlines and solutions proposed by the responding geriatrician reduced the number of hospital admissions, and more specifically the number of emergency room admissions.MethodsWe conducted a multicenter observational study from April 2018 to April 2020 at seven French investigative sites. A questionnaire was completed by all hotline physicians after each call.ResultsThe study population consisted of 4,137 individuals who met the inclusion and exclusion criteria. Of the 4,137 phone calls received by the participants, 64.2% (n = 2 657) were requests for advice, and 35.8% (n = 1,480) were requests for emergency hospitalization. Of the 1,480 phone calls for emergency hospitalization, 285 calls resulted in hospital admission in the emergency room (19.3%), and 658 calls in the geriatric short stay (44.5%). Of the 2,657 calls for advice/consultation/delayed hospitalization, 9.7% were also duplicated by emergency hospital admission.ConclusionThis study revealed the value of hotlines in guiding the care of older adults. The results showed the potential effectiveness of hotlines in preventing unnecessary hospital admissions or in identifying cases requiring hospital admission in the emergency room. Hotlines can help improve the care pathway for older adults and pave the way for future progress.Trial registrationRegistered under Clinical Trial Number NCT03959475. This study was approved and peer-reviewed by the Ethics Committee for the Protection of Persons of Sud Est V of Grenoble University Hospital Center (registered under 18-CETA-01 No.ID RCB 2018-A00609-46).

Cell scientist to watch – Charlotte Aumeier

ABSTRACT Charlotte Aumeier is an Assistant Professor of Biochemistry at the University of Geneva, Switzerland. After completing her PhD at the University of Bonn, Germany, studying the cytoskeleton of diatoms, Charlotte moved to the University of Grenoble, France, for a postdoc, where she became hooked on microtubules. In 2018, she established her own lab in Geneva, where she and her team work to uncover the dynamics and regulatory mechanisms of microtubule networks using a variety of approaches, including synthetic biology and non-standard model organisms. We spoke with Charlotte over Zoom to learn more about her work, her love of diatoms and how she views some of the biggest challenges of her career as her biggest advantages as a scientist.

Rapid and automated screening of carbapenemase- and ESBL-producing Gram-negative bacteria from rectal swabs using chromogenic agar media and the ScanStation device.

The ScanSation 100 device (Interscience, France) is an incubator allowing real-time detection of bacterial colony growth by frequently imaging agar plates over time, counting CFU, and detecting colony color. This study evaluated its performance for the early detection of carbapenemase-producing bacteria (CPB) and extended-spectrum β-Lactamase-producing bacteria (ESBL-PB) from rectal swabs inoculated on CHROMagar mSuperCARBA and ESBL media, respectively. Rectal screening ESwabs collected from patients admitted to Grenoble University Hospital between January and June 2021 were analyzed. After inoculation, chromogenic media were incubated for 24 h in the automaton, with image acquisition every 30 min. ScanStation results were compared to visual observations of the plates after 24 h of incubation. In total, 501 rectal swabs were tested. ScanStation showed 100% positive percent agreement (PPA) for the detection of CPB and ESBL-PB, whereas the PPA of color categorization ranged between 45% and 100%. Negative percent agreement (NPA) ranged between 70% and 98%. Negative predictive values (NPVs) were 100% for both bacterial groups, whereas positive predictive values (PPVs) were 70.3% for CPB and 81.0% for ESBL-PB. Importantly, real-time screening allowed detection of the first suspected colony within 10-14 h of growth, on average, whereas visual observation is usually only performed once a day after 18-24 h of incubation. Our study demonstrates the potential use of early images to accelerate the detection of CPB and ESBL-PB and implement effective and timely infection control measures. IMPORTANCE The ScanStation 100 device is an incubator able to follow the real-time growth of bacterial colonies on agar plates through digital imaging, allowing users to sort plates according to the presence or absence of colonies, and to distinguish their color using four numeric color filters. Real-time screening shows that first colony detection is possible much earlier (after 10-14 h of growth, on average), whereas visual observation is usually performed only once a day after 18-24 h of incubation. The ScanStation device, combined with chromogenic agar media, is an efficient automated screening method to accelerate the detection of Gram-negative multidrug-resistant bacteria in laboratories that do not have access to larger laboratory automation systems. Our study shows that setting the image acquisition to one or two early images may allow for the detection of positive samples that were inoculated in the morning, by the end of the working day.

Trends in drivers testing positive for drugs of abuse in oral fluid from 2018 to 2021 in France

BackgroundDriving under the influence of drugs (DUID) is a risk factor for traffic accidents. The testing of oral fluid by roadside immunochromatography and laboratory-confirmed chromatography coupled to mass spectrometry (LC-MS/MS) analysis to detect drug abuse has increased in France. The aim of this study was to describe the trends observed in drivers testing positive for illicit drugs in oral fluid and to investigate the concordance between the two analytical methods used. MethodsWe received for confirmation 3051 oral fluid samples from drivers who had tested positive at the roadside with a Drugwipe-5S® device between 2018 and 2021 around Grenoble, France. Samples were collected with FLOQSwab® and analyzed by LC-MS/MS (THC, amphetamine, methamphetamine, MDMA and MDA, MDEA, cocaine and benzoylecgonine, morphine and 6-monoacetylmorphine) at Grenoble Alpes University Hospital, France. Binomial logistic regression was performed to evaluate consumption trends. ResultsMost of the drivers were men (93.2%), with a median age of 26 years (range: 14–66 years). Cannabis (94.6%) cocaine (17.5%) and MDMA (2.5%) were the drugs most frequently detected. Poly-drug use was observed in 17.3% of drivers and involved cannabis and cocaine in 85.3% of these drivers. Poly-drug use was more frequent among drivers over the age of 32 years (OR, 3.48; 95% CI, 2.59–4.68; p ≤ .001), as was cocaine use (OR, 5.15; 95% CI, 3.75–7.08; p ≤ .001). The frequency of positive tests for amphetamines was higher in women than in men (OR, 2.53; 95% CI, 1.50–4.27; p ≤ .001). The positive predictive value of Drugwipe-5S was 98.2% for cannabis, 22.6% for amphetamines, 75.4% for cocaine and 17.3% for opiates. At least one discrepancy between Drugwipe-5S® and LC-MS/MS results was observed for 22.3% of the samples tested. ConclusionWe report recent trends for drivers testing positive for illicit drugs in oral fluid in France. Cannabis was the most prevalent drug of abuse identified, suggesting that a general prevention program might be useful. Our results also highlight the need for LC-MS/MS confirmation when screening oral fluid for drugs of abuse.

Cohort profile for development of machine learning models to predict healthcare-related adverse events (Demeter): clinical objectives, data requirements for modelling and overview of data set for 2016–2018

PurposeIn-hospital health-related adverse events (HAEs) are a major concern for hospitals worldwide. In high-income countries, approximately 1 in 10 patients experience HAEs associated with their hospital stay. Estimating the risk...

Role and interest of hepcidin in iron homeostasis

Iron is an essential element to the well functionning of the organism and requires careful maintenance of its homeostasis. This is mainly due to hepcidin, a hormone secreted by the liver that controls the flow of iron within the body. It has a hyposideremic action by reducing the expression of ferroportin, the only protein known to this day, which can export iron into the extracellular environment. This has the effect of decreasing intestinal absorption and increasing intracellular retention, especially in macrophages. Hepcidin is stimulated by elevation of iron and inflammation while activation of erythropoiesis inhibits it. Understanding its regulation allows a better understanding of the pathophysiological mechanisms of overload diseases and iron deficiency. Therefore, hepcidin analysis is interesting for the exploration of iron homeostasis. In combination with other biological parameters of iron status, it is possible to find better instructions for therapeutic managements of iron metabolism diseases. Thus, an assaying method by coupling liquid chromatography and tandem mass spectrometry has been implemented at Grenoble University Hospital and the analytical performances of this assay met the laboratory requirements in terms of reliability of the analysis.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Synthetic Mid-urethral Sling for the Treatment of Urinary Incontinence in Women with Neurogenic Lower Urinary Tract Dysfunction: A Multicentric Retrospective Study.

To assess the efficacy, safety, and predictive factors for failure of synthetic mid-urethral slings for the treatment of urinary incontinence in a large cohort of women with neurogenic lower urinary tract dysfunction. Women aged 18 years or older who received a synthetic mid-urethral sling for stress urinary incontinence or mixed urinary incontinence in 3 centres between 2004 and 2019 and who had a neurological disorder were included. Exclusion criteria were less than 1 year of follow-up, concomitant pelvic organ prolapse repair, previous synthetic sling implantation, and no baseline urodynamics. The primary outcome was surgical failure, defined as recurrence of stress urinary incontinence during follow-up. Kaplan-Meier analysis was used to estimate the 5-year failure rate. Adjusted Cox proportional hazard model was used to identify factors associated with surgical failure. Complications and reoperations during the follow-up have also been reported. A total of 115 women with a median age of 53 years were included. The median follow-up duration was 75 months. The 5-year failure rate was 48% (95 CI 46-57%). Age above 50 years, negative TVT test and transobturator route were associated with surgical failure. 36 patients (31.3%) underwent at least 1 reoperation for complications or failure, and 2 required definitive intermittent catheterization. Synthetic mid-urethral slings may be an acceptable alternative to autologous slings or artificial urinary sphincters for the treatment of stress urinary incontinence in a selected group of patients with neurogenic lower urinary tract dysfunction.

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

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

When pediatric resuscitation and anesthesia teams simulate together

At the Grenoble-Alpes University Hospital Center, a high-fidelity simulation training project was born from the collaboration of the intensive care and pediatric anesthesia teams. The objective of these sessions was to improve practices by developing the technical and non-technical skills of the teams. Fifteen days were organized from 2018 to 2022, training 170 healthcare professionals. The results highlighted excellent satisfaction and helped improve professional practices.

Towards real-time monitoring of COVID-19 nosocomial clusters using SARS-CoV-2 genomes in a university hospital of the French Alps

ObjectivesExperience of Nextstrain [1,2] and its approach adapted to the local context encouraged us to carry out real-time monitoring of COVID-19 nosocomial clusters in our establishment, the Grenoble Alpes University Hospital. Patients and methods, ResultsThrough identification from electronic health records of nosocomial pathways and clusters and calculation of genetic distances from sequenced samples of COVID-19 patients, we were able to identify potential nosocomial clusters in very close to real time with a significant time saving compared to classical epidemiological surveillance, and to better understand and characterize nosocomial clusters. ConclusionThrough early detection and characterization of clusters, we may prevent infection of our patients by further implementing the appropriate measures.

Profils des myosites auto-immunes avec ou sans atteinte pulmonaire : une étude monocentrique rétrospective de 40 patients

IntroductionIdiopathic inflammatory myopathies (IMM) are rare diseases with clinico-biological heterogeneity. Pulmonary involvement is frequent and associated with some distinctive manifestations. The aim of this study was to describe the clinico-biological profile of patients with autoimmune myositis with and without pulmonary involvement. MethodsThis retrospective descriptive study included patients with idiopathic inflammatory myopathies and a positive antibody test performed at Grenoble Alpes University Hospital between 2010 and 2020. ResultsForty patients were included, the majority were women. The anti-Jo1 autoantibody was the most frequently found (37.5%). The prevalence of pulmonary involvement was 70%. Mechanics’ hands and Raynaud's syndrome were the extra-respiratory signs significantly more present in the group with lung involvement (P <0.05), in contrast to creatine kinase levels which were lower in this group (P <0.05). Glucocorticoids and rituximab were significantly more often used in the group with lung involvement (P <0.05). The 5-year survival rate was 76.2% in patients with lung involvement and 100% in patients without lung involvement (P=0.50). ConclusionWe report a high prevalence of lung involvement probably explained by the presence of many patients with anti-synthetase syndrome. Our study highlights a lower severity of muscle involvement in myositis patients with lung disease, which deserves to be confirmed in a larger study.