Polymyalgia rheumatica and giant cell arteritis following COVID-19 vaccination: Results from a nationwide survey.

We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.

Proton pump inhibitors and risk of severe COVID-19 in older people.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 is a viral respiratory infection that can cause systemic disorders and lead to death, particularly in older people. Proton pump inhibitors (PPIs) increase the risk of enteric and lung infections. Considering the broad use of PPIs in older people, the potential role of PPIs in COVID-19 could be of dramatic significance. The objective of our study was to evaluate the link between PPIs and severe COVID-19 in older people. METHOD: We performed a retrospective cohort study, including all patients aged ≥65, hospitalised for a diagnosis of COVID-19. Epidemiological, clinical and biological data were extracted and we performed an Inverse Probability of Treatment Weighing method based on a propensity score. RESULTS: From March 2020 to February 2021, a total of 834 patients were included, with a median age of 83 and 52.8% were male. A total of 410 patients had a PPIs prescription, 358 (87.3%) were long-term PPIs-users and 52 (12.7%) were recent PPIs-users. Among PPIs-users, 163 (39.8%) patients developed severe COVID-19 versus 113 (26.7%) in PPIs-non users (odds ratio (OR) = 1.59 [1.18-2.14]; P < 0.05). Moreover, the double dose PPI-users had a higher risk of developing severe COVID-19 (OR = 3.36 [1.17-9.66]; P < 0.05) than the full dose PPI-users (OR = 2.15 [1.22-3.76]; P < 0.05) and the half dose PPI-users (OR = 1.64 [1.13-2.37]; P < 0.05). CONCLUSION: Our study reports evidence that the use of PPIs was associated with an increased risk of severe COVID-19 in older people.

Prediction of hospital readmission of multimorbid patients using machine learning models.

OBJECTIVE: The objective of this study is twofold. First, we seek to understand the characteristics of the multimorbid population that needs hospital care by using all diagnoses information (ICD-10 codes) and two aggregated multimorbidity and frailty scores. Second, we use machine learning prediction models on these multimorbid patients characteristics to predict rehospitalization within 30 and 365 days and their length of stay. METHODS: This study was conducted on 8 882 anonymized patients hospitalized at the University Hospital of Saint-Étienne. A descriptive statistical analysis was performed to better understand the characteristics of the patient population. Multimorbidity was measured using raw diagnoses information and two specific scores based on clusters of diagnoses: the Hospital Frailty Risk Score and the Calderon-Larrañaga index. Based on these variables different machine learning models (Decision Tree, Random forest and k-nearest Neighbors) were used to predict near future rehospitalization and length of stay (LoS). RESULTS: The use of random forest algorithms yielded better performance to predict both 365 and 30 days rehospitalization and using the diagnoses ICD-10 codes directly was significantly more efficient. However, using the Calderon-Larrañaga's clusters of diagnoses can be used as an efficient substitute for diagnoses information for predicting readmission. The predictive power of the algorithms is quite low on length of stay indicator. CONCLUSION: Using machine learning techniques using patients' diagnoses information and Calderon-Larrañaga's score yielded efficient results to predict hospital readmission of multimorbid patients. These methods could help improve the management of care of multimorbid patients in hospitals.

Ocular Inflammation Induced by Immune Checkpoint Inhibitors.

Ocular immunotherapy-related adverse events (IRAEs), although rare, can be sight-threatening. Our objective was to analyze ocular IRAEs diagnosed in France from the marketing of immune checkpoint inhibitors (ICPIs) until June 2021 and to review the literature. We collected the cases of 28 patients (36 ocular IRAEs), occurring after an average of 17 weeks (±19). Forty-six percent of patients were treated for metastatic melanoma. Anti-PD1 agents were responsible for 57% of the IRAEs. Anterior uveitis was the most common (44%), followed by panuveitis (28%). Of 25 uveitis cases, 80% were bilateral and 60% were granulomatous. We found one case with complete Vogt-Koyanagi-Harada syndrome and one case of birdshot retinochoroidopathy. The other IRAEs were eight ocular surface disorders, one optic neuropathy, and one inflammatory orbitopathy. Seventy percent of the IRAEs were grade 3 according to the common terminology of AEs. ICPIs were discontinued in 60% of patients and 50% received local corticosteroids alone. The literature review included 230 uveitis cases, of which 7% were granulomatous. The distributions of ICPIs, cancer, and type of uveitis were similar to our cohort. Ocular IRAEs appeared to be easily controlled by local or systemic corticosteroids and did not require routine discontinuation of ICPIs. Further work is still warranted to define the optimal management of ocular IRAEs.

TAFRO syndrome: A severe manifestation of Sjogren's syndrome? A systematic review.

BACKGROUND: Sjögren's syndrome (SjS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and lacrimal glands associated with sicca syndrome. TAFRO syndrome is a systemic inflammatory disease of unknown cause, characterized by Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis, Renal dysfunction and Organomegaly, first reported in 2010 in Japanese patients. Despite their rarity, both conditions have been concurrently reported in several patients during the recent years, hence questioning the existence of shared or related features. METHODS: A systematic review of the literature regarding SjS associated with TAFRO syndrome (SjS-TAFRO) was performed. The 2019 updated Masaki diagnostic criteria were used for TAFRO syndrome and SjS was considered when the diagnosis was mentioned by the authors, necessarily with either anti-Sjogren's Syndrome A (SSA) ± anti-Sjogren's Syndrome B (SSB) antibodies and/or histological evidence of focal lymphocytic sialadenitis. RESULTS: Ten cases of SjS-TAFRO have been reported in the literature to date. Compared to SjS patients without TAFRO syndrome, these 10 SjS-TAFRO had a lower female predominance (2.3:1 vs 9:1 women to man ratio) and a higher frequency of anti-SSA antibodies (90% vs 70%). All fulfilled the three major Masaki criteria i.e., anasarca, thrombocytopenia, and systemic inflammation. Seven of them (70%) had megakaryocyte hyperplasia or reticulin fibrosis in the bone marrow. Lymph node biopsy was performed in 8 out of 10 cases (80%) and results were consistent with Castleman disease in 6 (75%). Eight of them had developed renal failure (80%) within six months. Nine of them (90%) had organomegaly, with hepatosplenomegaly in 8 cases and splenomegaly alone in 1. CONCLUSION: This review brings new insights regarding TAFRO syndrome and suggests it could be a severe manifestation of SjS. The identification of shared abnormal signaling pathways could help in the therapeutic management of both diseases, which face an unmet therapeutic need.

Therapeutic Fasting: Are Patients Aged 65 and Over Ready?

While being the main potential beneficiaries of therapeutic fasting's health benefits, the elderly are frequently thought of as being too fragile to fast. The main objective of our survey was to review the knowledge, practices, and acceptability of therapeutic fasting in subjects aged 65 years and over. From September 2020 to March 2021, an online questionnaire was sent to subjects aged 65 and over, using the mailing list of local organizations working in the field of aging. The mean age of the 290 respondents was 73.8 ± 6.5 years, 75.2% were women and 54.1% had higher education. Among the respondents, 51.7% had already fasted and 80.7% deemed therapeutic fasting interesting, 83.1% would be willing to fast if it was proven beneficial for their health, and 77.2% if it was proven to decrease the burden of chronic diseases. Subjects aged 65 to 74 years considered themselves as having the greatest physical and motivational abilities to perform therapeutic fasting. People aged 65 years, or more, are interested in therapeutic fasting and a large majority would be ready to fast if such practice was proven beneficial. These results pave the way for future clinical trials evaluating therapeutic fasting in elderly subjects.

Fc receptors gone wrong: A comprehensive review of their roles in autoimmune and inflammatory diseases.

Systemic autoimmune and inflammatory diseases have a complex and only partially known pathophysiology with various abnormalities involving all the components of the immune system. Among these components, antibodies, and especially autoantibodies are key elements contributing to autoimmunity. The interaction of antibody fragment crystallisable (Fc) and several distinct receptors, namely Fc receptors (FcRs), have gained much attention during the recent years, with possible major therapeutic perspectives for the future. The aim of this review is to comprehensively describe the known roles for FcRs (activating and inhibitory FcγRs, neonatal FcR [FcRn], FcαRI, FcεRs, Ro52/tripartite motif containing 21 [Ro52/TRIM21], FcδR, and the novel Fc receptor-like [FcRL] family) in systemic autoimmune and inflammatory disorders, namely rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, Crohn's disease, ulcerative colitis, immunoglobulin (Ig) A vasculitis, Behçet's disease, Kawasaki disease, IgG4-related disease, immune thrombocytopenia, autoimmune hemolytic anemia, antiphospholipid syndrome and heparin-induced thrombocytopenia.

Pulmonary Involvement Responsive to Enzyme Replacement Therapy in an Elderly Patient with Gaucher Disease.

Type 1 Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder caused by deficient activity of beta-glucocerebrosidase, leading to accumulation of its substrate (glucosylceramide) in macrophages of the reticuloendothelial system, which are then referred to as Gaucher cells. The most frequent symptoms are asthenia, spleen and liver enlargement, bone abnormalities and cytopenia due to bone marrow infiltration. Lung involvement in GD is a rare finding, and it is unclear whether it may regress under enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Here we report a case of type 1 GD recently diagnosed in an elderly patient complicated by infiltrative lung disease, which responded to ERT. LEARNING POINTS: Type 1 Gaucher disease (GD) is the most common type of GD diagnosed in adulthood, and is characterized by great clinical heterogeneity.Pulmonary involvement is rare, mostly characterized by infiltrative lung disease and pulmonary hypertension, and typically unresponsive to enzyme replacement therapy (ERT).Type 1 GD should be included in the differential diagnosis of infiltrative lung disease of unclear origin in patients with cytopenia and/or splenomegaly.Infiltrative lung disease due to type 1 GD may respond to ERT even in elderly patients.

Systemic sarcoidosis revealed by venepunctures: a very rare but rewarding cutaneous manifestation.

A 67-year-old man was referred to our department for the onset of cutaneous lesions following venepunctures. His recent medical history included brief flu-like syndrome, persistent cough, dyspnoea, dry mouth, blurred vision and weight loss. The extensive clinical, biological and radiological check-up showed signs consistent with systemic sarcoidosis: right uveitis, hypercalcemia, renal failure, inflammatory syndrome, elevated levels of ACE, alveolitis with elevated CD4+/CD8+ T cell ratio, hilar and mediastinal lymphadenopathy, bilateral pulmonary infiltrates, mild bronchial obstruction and lowered diffusing capacity of the lungs for carbon monoxide. Multiple biopsy samples (bronchus, accessory salivary glands and one of the skin lesions) eventually confirmed the diagnosis. Corticosteroids resulted in skin lesions resolution in a few days and overall clinical, biological and lung function improvement. The infiltration of scars by granulomatous tissue is well recognised in sarcoidosis but its onset in venepuncture sites is a very rare but easily recognisable condition, which can be helpful for quick diagnosis purpose.

[Use and management of proton pump inhibitors: An observational study]. / Utilisation et gestion des inhibiteurs de la pompe à protons : une étude observationnelle.

INTRODUCTION: Proton pump inhibitors (PPIs) have improved the management and prevention of digestive diseases, leading to a heavy prescription of this therapy. In 2015, nearly one quarter of the French population had consumed a PPI and half of them were long-term users. The main objective of this study was to analyze, in patients hospitalized in several medical departments, the adequacy of long-term PPI prescriptions to recommendations. METHOD: The Use and management of proton pump inhibitors: an observational study project (UTOPPIA) is a longitudinal observational study conducted at the University Hospital of Saint-Étienne in the departments of hepato-gastroenterology, infectious and tropical diseases, internal medicine, vascular medicine and nephrology. All patients with PPI treatment on their usual outpatient prescription were interviewed. RESULTS: Over a 3-month period, 334 of hospitalized patients (30.7%) had received a long-term PPI prescription and 181 patients (54.2%) could be included in the study for a total of 274 indications. Ninety-nine patients (54.7%) had a long-term PPI prescription in accordance with the recommendations. The most frequent indication (70 prescriptions) was the prescription of an antiplatelet drug or anticoagulant for subjects at high risk of bleeding in 70 prescriptions. Fifty-three PPI treatments were amended during the hospital stay, including 9 discontinuations. The justification for the change was documented in the patients' chart in only 17% of cases. Individual interviews of patients revealed that 75.1% of them were in favour of discontinuing their PPI treatment. CONCLUSIONS: About one-third of hospitalized patients in medical wards in France have long-term PPI treatment and half of these prescriptions do not comply with good practice recommendations. A majority of patients report being willing to try to stop PPI therapy.

Graduated compression stockings in prevention of venous thromboembolism among acutely ill medical patients aged over 75 years: a French national survey.

Background: The thromboprophylactic efficacy of graduated compression stockings (GCS) has not yet been demonstrated in acutely ill medical patients, and guidelines vary considerably. Older acutely ill medical patients appear to constitute a distinctive population presenting high risks of both thrombosis and bleeding. Objective: To evaluate the practices and beliefs of a panel of French geriatricians regarding GCS management in acutely ill medical patients aged over 75 years. Methods: A survey was designed to study French geriatric practice concerning GCS use for thromboprophylaxis. Results: A total of 111 geriatricians answered the questionnaire. Among the responders, 46% declared frequent or very frequent prescription of GCS for preventing venous thromboembolism (VTE) in acutely ill, hospitalized medical patients, 54% declaring that they frequently re-evaluated GCS prescription during the patient's hospitalization. The main reason reported for discontinuing GCS use was patient request. Regarding complications of GCS, 87% of responders declared having already noted adverse effects with the use of GCS, although 80% estimated the risk of complications to be low or very low. In the context considered, the efficacy of wearing GCS was believed to be high or very high for 73% of responders. GCS prescription was judged to be in accordance with evidence-based medicine for 69%. Conclusion: There is a gap between the frequent use of GCS to prevent VTE in older patients presenting an acute medical illness and the availability of data concerning their efficacy, safety, and management by nurses. Prospective trials including clinical and cost effectiveness are needed.

The French Society of Internal Medicine's Top-5 List of Recommendations: a National Web-Based Survey.

BACKGROUND: The international project "Choosing Wisely" aims to target unnecessary and potentially harmful examinations and treatments. OBJECTIVE: To define the French Internal Medicine Top-5 list. DESIGN: Based on a review of existing Top-5 lists and personal experience, a working group of the French National Society of Internal Medicine selected 27 diagnostic and therapeutic procedures. They were submitted through a national web-based survey to French internists who rated from 1 to 5 the perceived frequency, uselessness, and risk of each procedure. A composite score was calculated as the unweighted addition of the three scores. PARTICIPANTS: Four hundred thirty internists answered the web-based survey (14% of all French internists including residents). All the French regions and status of the profession were represented. KEY RESULTS: For the 27 submitted procedures, the mean score (± SD) was 3.25 (± 0.48) for frequency, 3.10 (± 0.43) for uselessness, and 2.63 (± 0.84) for risk. The Top-5 list obtained with the composite score was as follows: 1. Do not prescribe long-term treatment with proton pump inhibitors without regular reevaluation of the indication 2. Do not administer preventive treatments (e.g., for dyslipidemia, hypertension…) in elderly people with dementia when potential risks outweigh the benefits 3. Do not administer hypnotic medications as first-line treatment for insomnia 4. Do not treat with an anticoagulant for more than 3 months a patient with a first venous thromboembolism occurring in the setting of a major transient risk factor 5. Do not screen for Lyme disease without an exposure history or related clinical examination findings We found that the composite score was strongly correlated to the risk score (rs = 0.88, p < 10-5) and not to the frequency (rs = 0.06, p = 0.75) or uselessness score (rs = 0.17, p = 0.38). CONCLUSIONS: This Top-5 list provides an opportunity to discuss appropriate use of health care practices in internal medicine.