Reform of the first year of medical studies and diversification of student profiles in France: an unmet need?

OBJECTIVES: To determine whether the reform of the first year of medical studies implemented in September 2020 in France met its objective of diversifying the profiles of students admitted to second year at the faculty of medicine at the University of Tours. METHODS: Single-centered, retrospective study, covering students who passed the first year of medical studies between 2018 and 2022. Student profiles originating from three different entry gateways (PACES, PASS and L.AS) to the second year of medical studies were compared. RESULTS: One thousand four hundred and seventy-nine students over five promotions were included (806 in PACES, 329 in PASS, 198 in L.AS). The ratio of students who had obtained a baccalaureate with high or highest honors was significantly higher in PACES (85%) and PASS (96%) compared to L.AS (66%; p < 0.001). These differences were related to increased student intake via a standard pass in L.AS (21% compared to 3.2% in PACES and 0.9% in PASS) (p < 0.001). In terms of geographical origin, the proportion of students residing in regions outside the University City area increased significantly in L.AS (11%) compared to PACES (1.7%) and PASS (3.3%) (p < 0.001). The mean number of parents from the white-collar and knowledge professional category was significantly higher in PACES (0.91) and PASS (1.06) compared to L.AS (0.80; p < 0.001). CONCLUSION: Students with a scientific background and who obtained highest honors in their high school diploma, remain the standard in PACES and PASS. Diversification of student profiles was achieved only within the L.AS gateway, which represented 42% of total second year admissions during the post-reform year. Student profile diversification was therefore a partially achieved objective and follow up studies of future promotions is needed to assess the medium and long-term impact of the reform. Particular attention should be paid to the future of these students who have different profiles between L.AS and PASS to determine whether these changes will have any impact in the quality of healthcare for the French population.

The clinical course of interstitial lung disease in an adult patient with an ABCA3 homozygous complex allele under hydroxychloroquine and a review of the literature.

OBJECTIVE: The gene mutations responsible for ABCA3 protein deficiency are involved in respiratory distress of the newborn and much more rarely in adult interstitial lung diseases (ILD). An adult patient homozygous for a complex allele encompassing the p.Ala1027Pro likely pathogenic mutation and the p.Gly974Asp variation was followed for a late-onset and fibrotic ILD. The evolution was marked by progressive clinical and functional degradation despite corticosteroid pulses. The patient, who was first registered on the list for lung transplantation, was improved quickly and persistently for at least 6.5 years with hydroxychloroquine treatment, allowing removal from the transplant list.

Desquamative interstitial pneumonia induced by metal exposure. A case report and literature review.

BACKGROUND: Forms of interstitial pneumonia secondary to exposure to an air-contaminant are varied and so far, insufficiently described. OBJECTIVES/METHODS: We report here a case of a 57-year-old patient managed in our department for the exploration of MRC grade 2 dyspnoea and interstitial pneumonia. He mentioned multiple occupational and domestic exposures such as hens' excrements, asbestos and metal particles; he also had a previous history of smoking. RESULTS: High-resolution computed tomography showed ground glass opacities predominating in posterior territories and surrounding cystic lesions or emphysematous destruction. The entire etiological assessment revealed only macrophagic alveolitis with giant multinucleated cells on the bronchoalveolar lavage. A surgical lung biopsy allowed us to refine the diagnosis with evidence of desquamative interstitial pneumonia and pulmonary granulomatosis. Finally, the analysis of the mineral particles in the biopsy revealed abnormally high rates of Zirconium and Aluminium. We were therefore able to conclude to a desquamative interstitial pneumonia associated with pulmonary granulomatosis linked to metal exposure (Aluminium and Zirconium). The clinical, functional and radiological evolution was favorable after a systemic corticosteroid treatment with progressive decay over one year. CONCLUSION: This presentation reports the first case to our knowledge of desquamative interstitial pneumonitis related to exposure to Zirconium and the third one in the context of Aluminium exposure. The detailed analysis of the mineral particles present on the surgical lung biopsy allows for the identification of the relevant particle to refine the etiological diagnosis, to guide the therapeutic management and to give access to recognition as an occupational disease. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 79-84).

Pharmacokinetics of colistin after nebulization or intravenous administration of colistin methanesulphonate (Colimycin®) to cystic fibrosis patients.

OBJECTIVES: Colistin, administered as the prodrug colistin methanesulphonate (CMS), is an antibiotic frequently administered as aerosol in cystic fibrosis (CF) patient. Our aim was to assess the plasma PK of colistin in CF patients treated with CMS administered intravenously or as aerosol and to compare these results with those previously reported in healthy volunteers. METHODS: Six CF patients were included, CMS and colistin concentrations were measured in plasma, urine and sputum. Either after single intravenous administration of 2 Million International Unit (MIU) or after repeated nebulizations of 2 MIU of CMS. PK of CMS and colistin were assessed by a mixed effect modeling approach. RESULTS: Renal clearance of CMS was lower in CF patients compared to that previously reported in healthy volunteers (64.3 mL/min (RSE = 15%) vs. 103 mL/min (RSE = 8%)). However, apparent clearance of colistin was higher in CF patients compared to healthy volunteers (124 mL/min (RSE = 13%) vs. 48.7 mL/min (RSE = 15%)), resulting in reduced systemic exposure to colistin (dose normalized AUC (2 MIU) of 7.4 h.mg/L/MIU vs. 11.2 h.mg/L/MIU). After repeated nebulizations, colistin concentrations were very low in plasma (<0.21 mg/L). CONCLUSIONS: Although our study suggests a lower median dose normalized colistin plasma concentrations in CF patients compared with healthy controls, this difference was not significant and a larger study is needed to substantiate this.

Démographie des chirurgiens-dentistes en région Centre-Val de Loire : opportunités et perspectives.

The Center Val de Loire region is particularly affected by the shortage of health professionals. The demographics of dentists are not immune to this situation and the retirement of a practitioner has become a real public health issue. For this purpose, bridges were created between the faculties of odontology of Nantes, Clermont-Ferrand and the Faculty of Medicine of Tours, to welcome short cycle students in Center Val de Loire region, to create a link with the liberal practitioners and to allow the students to confront the health issues of this territory.

[Dentistry demographics of Center Val de Loire region: Opportunities and prospects]. / Démographie des chirurgiens-dentistes en région Centre-Val de Loire : opportunités et perspectives.

The Center Val de Loire region is particularly affected by the shortage of health professionals. The demographics of dentists are not immune to this situation and the retirement of a practitioner has become a real public health issue. For this purpose, bridges were created between the faculties of odontology of Nantes, Clermont-Ferrand and the Faculty of Medicine of Tours, to welcome short cycle students in Center Val de Loire region, to create a link with the liberal practitioners and to allow the students to confront the health issues of this territory.

Nebulized antibiotics in mechanically ventilated patients: a challenge for translational research from technology to clinical care.

Nebulized antibiotic therapy directly targets airways and lung parenchyma resulting in high local concentrations and potentially lower systemic toxicities. Experimental and clinical studies have provided evidence for elevated lung concentrations and rapid bacterial killing following the administration of nebulized antibiotics during mechanical ventilation. Delivery of high concentrations of antibiotics to infected lung regions is the key to achieving efficient nebulized antibiotic therapy. However, current non-standardized clinical practice, the difficulties with implementing optimal nebulization techniques and the lack of robust clinical data have limited its widespread adoption. The present review summarizes the techniques and clinical constraints for optimal delivery of nebulized antibiotics to lung parenchyma during invasive mechanical ventilation. Pulmonary pharmacokinetics and pharmacodynamics of nebulized antibiotic therapy to treat ventilator-associated pneumonia are discussed and put into perspective. Experimental and clinical pharmacokinetics and pharmacodynamics support the use of nebulized antibiotics. However, its clinical benefits compared to intravenous therapy remain to be proved. Future investigations should focus on continuous improvement of nebulization practices and techniques. Before expanding its clinical use, careful design of large phase III randomized trials implementing adequate therapeutic strategies in targeted populations is required to demonstrate the clinical effectiveness of nebulized antibiotics in terms of patient outcomes and reduction in the emergence of antibiotic resistance.

Therapeutic monoclonal antibodies for respiratory diseases: Current challenges and perspectives, March 31 - April 1, 2016, Tours, France.

Monoclonal antibody (mAb) therapeutics have tremendous potential to benefit patients with lung diseases, for which there remains substantial unmet medical need. To capture the current state of mAb research and development in the area of respiratory diseases, the Research Center of Respiratory Diseases (CEPR-INSERM U1100), the Laboratory of Excellence "MAbImprove," the GDR 3260 "Antibodies and therapeutic targeting," and the Grant Research program ARD2020 "Biotherapeutics" invited speakers from industry, academic and government organizations to present their recent research results at the Therapeutic Monoclonal Antibodies for Respiratory Diseases: Current challenges and perspectives congress held March 31 - April 1, 2016 in Tours, France.

Hiatal hernia on thoracic computed tomography in pulmonary fibrosis.

Gastro-oesophageal reflux has long been suspected of implication in the genesis and progression of idiopathic pulmonary fibrosis (IPF). We hypothesised that hiatal hernia may be more frequent in IPF than in other interstitial lung disease (ILD), and that hiatal hernia may be associated with more severe clinical characteristics in IPF.We retrospectively compared the prevalence of hiatal hernia on computed tomographic (CT) scans in 79 patients with IPF and 103 patients with other ILD (17 scleroderma, 54 other connective tissue diseases and 32 chronic hypersensitivity pneumonitis). In the IPF group, we compared the clinical, biological, functional, CT scan characteristics and mortality of patients with hiatal hernia (n=42) and without hiatal hernia (n=37).The prevalence of hiatal hernia on CT scan at IPF diagnosis was 53%, similar to ILD associated with scleroderma, but significantly higher than in the two other ILD groups. The size of the hiatal hernia was not linked to either fibrosis CT scan scores, or reduction in lung function in any group. Mortality from respiratory causes was significantly higher among IPF patients with hiatal hernia than among those without hiatal hernia (p=0.009).Hiatal hernia might have a specific role in IPF genesis, possibly due to pathological gastro-oesophageal reflux.

Aerosol Therapy in Adults Receiving High Flow Nasal Cannula Oxygen Therapy.

BACKGROUND: High flow nasal cannula oxygen therapy (HFT) is increasingly used in intensive and emergency care departments. Patients suffering from respiratory failure, who are likely to benefit from HFT, may require aerosolized bronchodilators; therefore, combining nebulization with HFT may be relevant. This study aimed to identify the optimal settings for the implementation of nebulization within an adult HFT circuit. METHODS: We assessed the mass and the particle size distribution of the aerosol emitted from the nasal cannula (inhalable mass) using mesh- and jet-nebulizers placed at various positions in the HFT circuit. Thereafter, the most relevant combination was used to evaluate the mass of salbutamol delivered downstream of an anatomical model reproducing aerosol deposition and leakage at the nasal and pharyngeal levels (respirable mass). The influence of HFT flow rate (30, 45, and 60 L/min), of breathing pattern (quiet and respiratory distress pattern) as well as of opened and closed mouth breathing was assessed. RESULTS: The most efficient position was that of a nebulizer placed upstream from the humidification chamber (inhalable mass ranging from 26% to 32% of the nebulizer charge). Using a mesh nebulizer, we observed a respirable mass ranging from 2% to 10% of the nebulizer charge. Higher HFT flow rates and open mouth breathing were associated with a lower efficiency. Simulating respiratory distress (i.e., increasing the simulated patient inspiratory flow) did not hamper drug delivery as compared to a quiet breathing pattern. CONCLUSIONS: Placing nebulizers within a HFT circuit upstream from the humidification chamber may enable to deliver clinically relevant masses of aerosol at the cannula outlet, but more importantly downstream of the nose and pharynx, even in case of high patients' inspiratory flow. This method of aerosol therapy is expected to produce a bronchodilatatory effect to be evaluated in the clinical settings.

Neutrophil proteases alter the interleukin-22-receptor-dependent lung antimicrobial defence.

Chronic obstructive pulmonary disease (COPD) is punctuated by episodes of infection-driven acute exacerbations. Despite the life-threatening nature of these exacerbations, the underlying mechanisms remain unclear, although a high number of neutrophils in the lungs of COPD patients is known to correlate with poor prognosis. Interleukin (IL)-22 is a cytokine that plays a pivotal role in lung antimicrobial defence and tissue protection. We hypothesised that neutrophils secrete proteases that may have adverse effects in COPD, by altering the IL-22 receptor (IL-22R)-dependent signalling.Using in vitro and in vivo approaches as well as reverse transcriptase quantitative PCR, flow cytometry and/or Western blotting techniques, we first showed that pathogens such as the influenza virus promote IL-22R expression in human bronchial epithelial cells, whereas Pseudomonas aeruginosa, bacterial lipopolysaccharide or cigarette smoke do not. Most importantly, neutrophil proteases cleave IL-22R and impair IL-22-dependent immune signalling and expression of antimicrobial effectors such as ß-defensin-2. This proteolysis resulted in the release of a soluble fragment of IL-22R, which was detectable both in cellular and animal models as well as in sputa from COPD patients with acute exacerbations.Hence, our study reveals an unsuspected regulation by the proteolytic action of neutrophil enzymes of IL-22-dependent lung host response. This process probably enhances pathogen replication, and ultimately COPD exacerbations.

Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys.

PURPOSE: The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. METHODS: Three baboons received CMS by IV infusion and by 2 types of aerosols generators and colistin by subcutaneous infusion. Gamma imaging was performed after nebulisation to determine colistin distribution in lungs. Blood samples were collected during 9 h and colistin and CMS plasma concentrations were measured by LC-MS/MS. A population pharmacokinetic analysis was conducted and simulations were performed to predict lung concentrations after nebulization. RESULTS: Higher aerosol distribution into lungs was observed by scintigraphy, when CMS was nebulized with Pari LC® star than with Eflow Rapid® nebulizer. This observation was confirmed by the fraction of CMS deposited into the lung (respectively 3.5% versus 1.3%).CMS and colistin simulated concentrations in epithelial lining fluid were higher after using the Pari LC star® than the Eflow rapid® system. CONCLUSIONS: A limited fraction of CMS reaches lungs after nebulization, but higher colistin plasma concentrations were measured and higher intrapulmonary colistin concentrations were simulated with the Pari LC Star® than with the Eflow Rapid® system.

Gastroesophageal reflux disease is a risk factor for severity of organizing pneumonia.

BACKGROUND: The link between organizing pneumonia (OP) and gastroesophageal reflux disease (GERD) is not well known. There is little evidence in the literature to establish a causal link between GERD and OP. OBJECTIVES: The aim of the study was to assess the hypothesis that OP is more severe when it is associated with GERD and that it leads to more frequent relapses. METHODS: In a retrospective study on 44 patients suffering from OP, we compared the clinical, radiological and histological characteristics of 2 groups, 1 composed of patients with GERD (n = 20) and the other of patients without GERD (n = 24). RESULTS: The GERD group was distinguished by a higher number of patients with migratory alveolar opacities on chest radiography and thoracic computerized tomography (14/20 vs. 9/24; p = 0.03 and 18/20 vs. 13/24; p = 0.01), greater hypoxemia [60 (42-80) vs. 70 (51-112) mm Hg; p = 0.03], greater bronchoalveolar lavage cellularity [0.255 (0.1-1.8) vs. 0.150 (0.05-0.4) g/l; p = 0.035] and more frequent relapses (14/20 vs. 9/24; p = 0.03). CONCLUSIONS: OP associated with GERD is more severe and results in more frequent relapses. Microinhalation of gastric secretions might induce lung inflammation leading to OP and relapse. We suggest that typical symptoms of GERD such as pyrosis should be investigated in OP.