Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

Perception of endoscopic endonasal surgery training by French otolaryngology residents: A STROBE analysis of expectations.

OBJECTIVES: To analyze the perception of endoscopic endonasal surgery training by French otolaryngology residents. MATERIAL AND METHODS: A multicenter retrospective observational study was conducted from March to April 2023. Otolaryngology residents from 7 French regions filled out a 27-item questionnaire on their training in endoscopic endonasal surgery. RESULTS: Out of 283 residents contacted, 126 (45%) filled out the questionnaire. Seventy-four (59%) had already partially or completely performed the surgeries specified in their diploma course. The level of mastery of the main steps of endonasal surgery and the level of autonomy were higher in the consolidation stage group than in the basic and advanced stages. Seventy residents (56%) felt they had gaps in their level of training. To improve training, 94 (75%) wished for more dissection sessions, surgical skills assessments each semester and simulation sessions. Eighty-nine (71%) felt they needed to find their own teaching aids and other methods to complete their training. One hundred and thirteen (90%) felt that the lack of funding available for congresses and training courses was detrimental. CONCLUSION: This study highlighted the overall satisfaction of residents with their training in endoscopic endonasal surgery. They expressed a desire for more dissection, simulation and evaluation.

Comparison of Three ß-Glucan Tests for the Diagnosis of Invasive Candidiasis in Intensive Care Units.

The (1→3)-ß-d-glucan (BDG) is a marker of invasive fungal infection that can be detected in serum by different commercial kits. In this study, we compared the performance of the Fungitell assay (FA), the Fungitell STAT assay (STAT), and the Wako ß-glucan test (WA) for the diagnosis of invasive candidiasis (IC) in the intensive care unit (ICU). Patients for whom at least one BDG testing was required for a clinical suspicion of IC were retrospectively enrolled. A total of 85 serum samples from 56 patients were tested by the three BDG tests. The rate of IC was 23% (13/56) with a predominance of noncandidemic (intra-abdominal) IC. STAT and WA results exhibited overall good correlation with those obtained by FA (Spearman's coefficient R = 0.90 and R = 0.89, respectively). For the recommended cutoffs of positivity, sensitivity and specificity for IC diagnosis were 77%/51% (FA, 80 pg/mL), 69%/53% (STAT, ratio 1.2), and 54%/65% (WA, 7 pg/mL), respectively. Optimal performance was obtained at 50 pg/mL (FA), ratio 1.3 (STAT), and 3.3 pg/mL (WA) with sensitivity/specificity of 85%/51%, 69%/57%, and 77%/58%, respectively. Overall, the three BDG tests showed comparable but limited performance in this setting with positive and negative predictive values for an estimated IC prevalence of 20% that were in the range of 30 to 35% and 85 to 95%, respectively.

Deterioration experienced by French otolaryngology residents in their training during the COVID-19 pandemic: A STROBE analysis.

OBJECTIVE: To evaluate the impact of the first three waves of COVID-19 on the academic and surgical training of ENT and Head and Neck Surgery residents in France. MATERIAL AND METHODS: Observational, retrospective study. A 55-item survey of academic education and surgical training was sent to ENT residents in five major French regions (Île-de-France, Rhône-Alpes Auvergne, Occitanie, Grand Est, Grand Ouest) from August to October 2021. RESULTS: Eighty-nine out of 135 residents (66%) responded. Two-thirds considered that surgical training was more affected than academic education, with reductions evaluated of 50-75%, 25-50% and 0-25% for the first three waves, respectively. Residents in Île-de-France, Rhône-Alpes Auvergne and Grand Est were the most affected by the first wave (75-100% reduction in surgical activity, in parallel to increased admissions). Otology, rhinology and functional exploration were the most affected, whereas pediatrics and oncology were spared. Seventy-one of the 89 residents (79.7%) felt that the first wave impacted their career, while this proportion decreased to 39.3% and 44.9% for the second and third waves, respectively. CONCLUSION: The first wave of COVID-19, compared to the following two waves, severely impacted the surgical training of French ENT residents, especially in regions severely impacted by the pandemic, while academic education was relatively safeguarded by the implementation of e-learning alternatives.

[Morbidity of extended pelvic lymphadenectomy during robot-assisted laparoscopic prostatectomy for localized cancer prostate]. / Morbidité du curage ganglionnaire pelvien étendu au cours de la prostatectomie totale laparoscopique robot assistée.

OBJECTIVES: To assess the morbidity specific of extended pelvic lymphadenectomy during robot-assisted laparoscopic radical prostatectomy in a 8 year retrospective study. MATERIAL: We carried out a single-center, single-surgeon retrospective study on 342 consecutive patients who underwent a robot-assisted laparoscopic radical prostatectomy and extended pelvic lymphadenectomy, from July 2010 to March 2018. Postoperative complications were recorded up to 3 months after the operation. RESULTS: Thirty (8.8%) patients had at least one complication related to lymphadenectomy including 1 vascular injury (0.3%), 7 injuries of the obturator nerve (2%), 5 venous thromboembolic complications (1.5%) including 4 pulmonary embolisms, 10 symptomatic lymphoceles (2.9%) and 8 lymphoedemas (2.3%). Of these complications, 13 were classified Clavien 1 (43.3%), 8 Clavien 2 (26.7%), 7 Clavien 3a (23.3%) and 2 Clavien 3b (6.7%). In univariate analysis a high age (P=0.04), high BMI (P<0.01) and pT stage (P=0.02) were significantly associated with complication whereas in multivariate analysis, only age (P=0.02) and BMI (P<0.01) lived were. In univariate analysis high BMI (P=0.04) and lymph node involvement (P=0.04) were associated with lymphatic complication. We did not find any other specific risk factor for the other complications. CONCLUSION: With 8.8% of overall complications related to lymphadenectomy and 5% of complication classified Clavien grade 2 or higher, extended pelvic lymphadenectomy was not very morbid. Age and BMI were risk factors for a overall complication. BMI and lymph node involvement were risk factors for lymphatic complications. LEVEL OF PROOF: 4.

Juvenile idiopathic arthritis-associated uveitis in the era of biological therapy: how the disease changed in more than 20 years of observation in a tertiary referral center in Rome (Italy).

OBJECTIVES: To describe the ophthalmological characteristics in a Juvenile idiopathic arthritis (JIA) cohort and to evaluate how therapeutic advances have changed the course of the uveitis. METHODS: Analysis of a retrospective cohort study of consecutive JIA pediatric patients including JIA-associated uveitis (JIA-U) and comparison with a previous study in the same uveitis center assessed before the wide-spread of biological therapy. RESULTS: The total of 49 JIA patients were analyzed, of whom 18 JIA-U, compared with a JIA-U past cohort of 66 patients. Systemic corticosteroids were used significantly less in the current JIA-U group (p = 0.008) than in the past one. JIA-U present cohort was on therapy more frequently with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) than the past group (p = 0.039), mostly treated with methotrexate (93.3%). Furthermore, a larger use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) was described in the current JIA-U group (p = 0.005) also associated with csDMARDs (p = 0.003). Adalimumab was used more (72.7%) in the present JIA-U cohort compared to a larger treatment with infliximab (61.5%) in the past (p = 0.005). Higher number of uveitis recurrences was observed in the previous cohort compared to the current one (p = 0.005). Fewer complications were described in this study than in the previous: posterior synechiae (p = 0.007), cataract (p < 0.001), band keratopathy (p < 0.001), and elevated intraocular pressure (IOP) (p = 0.047). CONCLUSION: Current therapies reduced the uveitis recurrences and ocular complications including cataract due also to the lower use of corticosteroids. The new close collaboration with the pediatric rheumatologic center in the same University has contributed to the care improvement and decrease of uveitis complications.

Impact of COVID-19 on surgical emergencies: nationwide analysis.

BACKGROUND: The COVID-19 pandemic has had a major impact on healthcare in many countries. This study assessed the effect of a nationwide lockdown in France on admissions for acute surgical conditions and the subsequent impact on postoperative mortality. METHODS: This was an observational analytical study, evaluating data from a national discharge database that collected all discharge reports from any hospital in France. All adult patients admitted through the emergency department and requiring a surgical treatment between 17 March and 11 May 2020, and the equivalent period in 2019 were included. The primary outcome was the change in number of hospital admissions for acute surgical conditions. Mortality was assessed in the matched population, and stratified by region. RESULTS: During the lockdown period, 57 589 consecutive patients were admitted for acute surgical conditions, representing a decrease of 20.9 per cent compared with the 2019 cohort. Significant differences between regions were observed: the decrease was 15.6, 17.2, and 26.8 per cent for low-, intermediate- and high-prevalence regions respectively. The mortality rate was 1.92 per cent during the lockdown period and 1.81 per cent in 2019. In high-prevalence zones, mortality was significantly increased (odds ratio 1.22, 95 per cent c.i. 1.06 to 1.40). CONCLUSION: A marked decrease in hospital admissions for surgical emergencies was observed during the lockdown period, with increased mortality in regions with a higher prevalence of COVID-19 infection. Health authorities should use these findings to preserve quality of care and deliver appropriate messages to the population.

Tracheostomies after SARS-CoV-2 intubation, performed by academic otorhinolaryngologists in the Paris area of France: Preliminary results.

OBJECTIVE: To analyse tracheostomies after intubation for SARS-Cov-2 infection performed by otorhinolaryngologists in 7 university hospitals in the Paris area of France during the month March 24 to April 23, 2020. MATERIAL AND METHODS: A multicentre retrospective observational study included 59 consecutive patients. The main goals were to evaluate the number, characteristics and practical conditions of tracheostomies, and the COVID-19 status of the otorhinolaryngologists. Secondary goals were to analyse tracheostomy time, decannulation rate, immediate postoperative complications and laryngotracheal axis status. RESULTS: Tracheostomy indications were for ventilatory weaning and extubation failure in 86% and 14% of cases, respectively. The technique was surgical, percutaneous or hybrid in 91.5%, 3.4% and 5.1% of cases, respectively. None of the operators developed symptoms consistent with COVID-19. Postoperative complications occurred in 15% of cases, with no significant difference between surgical and percutaneous/hybrid techniques (P=0.33), although no complications occurred after percutaneous or hybrid tracheostomies. No procedures or complications resulted in death. The decannulation rate was 74.5% with a mean tracheostomy time of 20±12 days. In 55% of the patients evaluated by flexible endoscopy after decannulation, a laryngeal abnormality was found. On univariate analysis, no clinical features had a significant influence on tracheostomy time, decannulation rate or occurrence of laryngeal lesions. CONCLUSION: The main findings of the present retrospective study were: absence of contamination of the surgeons, heterogeneity of practices between centres, a high rate of complications and laryngeal lesions whatever the technique, and the specificities of the patients.

Nutritional factors in sport-related concussion.

BACKGROUND: Sports concussion is a major problem that affects thousands of people every year. Concussion-related neurometabolic changes are thought to underlie neurophysiological alterations and post-concussion symptoms, such as headaches and sensitivity to light and noise, disabilities of concentration and tiredness. The injury triggers a complex neurometabolic cascade involving multiple mechanisms. There are pharmaceutical treatments that target one mechanism, but specific nutrients have been found to impact several pathways, thus offering a broader approach. This has prompted intensive research into the use of nutrient supplements as a concussion prevention and treatment strategy. METHOD: We realised a bibliographic state of art providing a contemporary clinical and preclinical studies dealing with nutritional factors in sport-related concussion. RESULTS: Numerous supplements, including n-3 polyunsaturated fatty acids, sulfur amino acids, antioxidants and minerals, have shown promising results as aids to concussion recovery or prevention in animal studies, most of which use a fluid percussion technique to cause brain injury, and in a few human studies of severe or moderate traumatic brain injury. Current ongoing human trials can hopefully provide us with more information, in particular, on new options, i.e. probiotics, lactate or amino acids, for the use of nutritional supplements for concussed athletes. CONCLUSION: Nutritional supplementation has emerged as a potential strategy to prevent and/or reduce the deleterious effects of sports-related concussion and subconcussive impacts.

[Management strategies for chronic rhinosinusitis with nasal polyps in adults]. / Stratégies de prise en charge de la polypose naso-sinusienne primitive de l'adulte.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the categories of chronic rhinosinusitis and is defined by the presence of bilateral polyps. It is frequently associated with other conditions (asthma, atopy, aspirin intolerance), which worsen its prognosis. STATE OF ART: The pathophysiology of CRSwNP is still poorly understood. The genesis of polyps is thought to be based on an initial epithelial lesion caused by environmental factors in the context of self-maintained chronic local inflammation. Multiple local and general factors can be involved in this inflammation, which is mainly of Th2 type in Europe. Abnormalities of the epithelial barrier and the immune system (eosinophilia, cytokines, T and B lymphocytes), genetic factors and pathogens, including Staphylococcus aureus, have been incriminated. The treatment of CRSwNP is mainly based on the application of local corticosteroids. Surgery remains an important part of patient management where CRSwNP becomes resistant to topical therapy. The management of CRSwNP may be at a turning point thanks to the arrival of biological therapies (anti-IgE, anti-IL-5, anti-IL-4/IL-13) the initial results of which are promising. PERSPECTIVES/CONCLUSIONS: With the new concept of endotypes, current avenues of research are moving towards a better understanding of the inflammatory mechanisms of CRSwNP. Immunotherapy appears to be a promising future for the treatment of CRSwNP.

Blood biomarkers of mild traumatic brain injury: State of art.

BACKGROUND: Mild traumatic brain injury (mTBI) is one of the most common causes of emergency department visits around the world. Up to 90% of injuries are classified as mTBI. Cranial computed tomography (CCT) is a standard diagnosis tool to identify intracranial complications in adults with mTBI. Alternatively, children can be admitted for inpatient observation with CCT scans performed only on those with clinical deterioration. The use of blood biomarkers is a supplementary tool for identifying patients at risk of intracerebral lesions who may need imaging. METHOD: We realised a bibliographic state of art providing a contemporary clinical and laboratory framework for blood biomarker testing in mTBI management. RESULTS: The S100B protein is the only biomarker that can be used today in the clinical routine for management of mTBI with appropriate evidence-based medicine. Due to its excellent negative predictive value, S100B protein is an alternative choice to CCT scanning for mTBI management with considered, consensual and pragmatic use. In this state of art, we propose points to help clinicians and clinical pathologists use serum S100B protein in the clinical routine. A state of art on the different biomarkers (GFAP, UCH-L1, NF [H or L], tau, H-FABP, SNTF, NSE, miRNAs, MBP) is also conducted. Some of these other biomarkers, used alone (GFAP, UCH-L1) or in combination (GFAP+H-FABP±S100B±IL10) can improve the specificity of S100B. CONCLUSION: Using a bibliographic state of art, we highlighted the added values of the blood biomarkers for the clinical management of mTBI.

Biotherapy and treatment of adult primary chronic rhinosinusitis with nasal polyps: Cellular and molecular bases.

The present article reviews the molecular and cellular mechanisms involved in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwCRSwNP) and underlying the action mechanisms of biotherapies. Biotherapy uses substances naturally produced by the organism or their specific antagonists targeting a proinflammatory mechanism. CRSwCRSwNP is a form of chronic rhinosinusitis (CRS), which is classically subdivided in to 2 types according to the presence of polyps. In recent years, the concept of endotypes emerged, with a more exhaustive definition of the types of CRS according to inflammatory mechanism, with a view to developing personalized treatments. CRSwNP pathophysiology is poorly understood. Polyps arise from a primary epithelial lesion in a context of chronic local inflammation, mainly type 2 in Europe, implicating eosinophils, IgE, Th2 cytokines (IL-4/IL-13, IL-5) and T and B cells. Biotherapy seems promising in CRSwNP. The present review details the various pathophysiological pathways underlying the action mechanisms of biotherapies, and the various published studies, assessing efficacy and mode of action in the treatment of CRSwNP.

Conidiobolus pachyzygosporus invasive pulmonary infection in a patient with acute myeloid leukemia: case report and review of the literature.

BACKGROUND: Conidiobolus spp. (mainly C. coronatus) are the causal agents of rhino-facial conidiobolomycosis, a limited soft tissue infection, which is essentially observed in immunocompetent individuals from tropical areas. Rare cases of invasive conidiobolomycosis due to C. coronatus or other species (C.incongruus, C.lamprauges) have been reported in immunocompromised patients. We report here the first case of invasive pulmonary fungal infection due to Conidiobolus pachyzygosporus in a Swiss patient with onco-haematologic malignancy. CASE PRESENTATION: A 71 year-old female was admitted in a Swiss hospital for induction chemotherapy of acute myeloid leukemia. A chest CT performed during the neutropenic phase identified three well-circumscribed lung lesions consistent with invasive fungal infection, along with a positive 1,3-beta-d-glucan assay in serum. A transbronchial biopsy of the lung lesions revealed large occasionally septate hyphae. A Conidiobolus spp. was detected by direct 18S rDNA in the tissue biopsy and subsequently identified at species level as C. pachyzygosporus by 28S rDNA sequencing. The infection was cured after isavuconazole therapy, recovery of the immune system and surgical resection of lung lesions. CONCLUSIONS: This is the first description of C. pachyzygosporus as human pathogen and second case report of invasive conidiobolomycosis from a European country.

Emerging echinocandin-resistant Candida albicans and glabrata in Switzerland.

Echinocandins represent the first-line therapy of candidemia. Echinocandin resistance among Candida spp. is mainly due to acquired FKS mutations. In this study, we report the emergence of FKS-mutant Candida albicans/glabrata in Switzerland and provide the microbiological and clinical characteristics of 9 candidemic episodes. All patients were previously exposed to echinocandins (median 26 days; range 15-77). Five patients received initial echinocandin therapy with persistent candidemia in 4 of them. Overall mortality was 33%.