To rapidly communicate information on the global clinical effort against Covid-19, the Journal has initiated a series of case reports that offer important teaching points or novel findings. The case reports should be viewed as observations rather than as recommendations for evaluation or treatment. In the interest of timeliness, these reports are evaluated by in-house editors, with peer review reserved for key points as needed.

Introduction: Idiosyncratic drug-induced neutropenia and agranulocytosis is seldom discussed in the literature, especially for new drugs such as biotherapies outside the context of oncology. In the present paper, we report and discuss the clinical data and management of this relatively rare disorder, with a focus on biotherapies used in autoimmune and auto-inflammatory diseases. Materials and methods: A review of the literature was carried out using the PubMed database of the US National Library of Medicine. We searched for articles published between January 2010 and May 2019 using the following key words or associations: “drug-induced neutropenia”, “drug-induced agranulocytosis”, and “idiosyncratic agranulocytosis”. We included specific searches on several biotherapies used outside the context of oncology, including: tumor necrosis factor (TNF)-alpha inhibitors, anti-CD20 agents, anti-C52 agents, interleukin (IL) 6 inhibitors, IL 1 inhibitors, and B-cell activating factor inhibitor. Results: Idiosyncratic neutropenia remains a potentially serious adverse event due to the frequency of severe sepsis with severe deep tissue infections (e.g., pneumonia), septicemia, and septic shock in approximately two-thirds of all hospitalized patients with grade 3 or 4 neutropenia (neutrophil count (NC) ≤ 0.5 × 109/L and ≤ 0.1 × 109/L, respectively). Over the last 20 years, several drugs have been strongly associated with the occurrence of idiosyncratic neutropenia, including antithyroid drugs, ticlopidine, clozapine, sulfasalazine, antibiotics such as trimethoprim-sulfamethoxazole, and deferiprone. Transient grade 1–2 neutropenia (absolute blood NC between 1.5 and 0.5 × 109/L) related to biotherapy is relatively common with these drugs. An approximate 10% prevalence of such neutropenia has been reported with several of these biotherapies (e.g., TNF-alpha inhibitors, IL6 inhibitors, and anti-CD52 agents). Grade 3–4 neutropenia or agranulocytosis and clinical manifestations related to sepsis are less common, with only a few case reports to date for most biotherapies. Special mention should be made of late onset and potentially severe neutropenia, especially following anti-CD52 agent therapy. During drug therapy, several prognostic factors have been identified that may be helpful when identifying ‘susceptible’ patients. Older age (>65 years), septicemia or shock, renal failure, and a neutrophil count ≤0.1 × 109/L have been identified as poor prognostic factors. Idiosyncratic neutropenia should be managed depending on clinical severity, with permanent/transient discontinuation or a lower dose of the drug, switching from one drug to another of the same or another class, broad-spectrum antibiotics in cases of sepsis, and hematopoietic growth factors (particularly G-CSF). Conclusion: Significant progress has been made in recent years in the field of idiosyncratic drug-induced neutropenia, leading to an improvement in their prognosis (currently, mortality rate between 5 and 10%). Clinicians must continue their efforts to improve their knowledge of these adverse events with new drugs as biotherapies.

Agranulocytosis is a rare, but serious and life-threatening hematologic disorder in elderly patients. Idiosyncratic drug-induced agranulocytosis (IDIA) has been classically defined by a neutrophil count below 0.5 × 10⁹/L. The annual incidence of IDIA in Europe is about 1.6–9.2 cases per million inhabitants. Increasing age and female sex have been considered as risk factors for the development of this condition. Besides, it is well known that older people take on average more drugs than younger people. This condition is most often associated with the intake of antibacterial agents, antiplatelets, antithyroids, antipsychotics, antiepileptics and nonsteroidal anti-inflammatory drugs (NSAIDs). Initially, agranulocytosis may present without symptoms, but may quickly progress to a severe infection and sepsis. The causative drug should be immediately stopped. In febrile patients, blood cultures and where indicated, site-specific cultures should be obtained and early treatment with empirical broad-spectrum antibiotics started. Even with adequate treatment, the mortality rate is higher in elderly patients reaching up to 20%. Hematopoietic growth factors have proven to be useful as they shorten the duration of neutropenia. However, data on neutropenia and agranulocytosis in the elderly meeting the criteria of evidence-based medicine are still poor in the literature. This review analyzes the results of our experience as well as other published studies of the universal literature.

Background: This is a narrative review of both the literature and Internet pertaining to telemedicine projects within the field of heart failure, with special attention placed on remote monitoring of second-generation projects and trials, particularly in France. Results: Since the beginning of the 2000’s, several telemedicine projects and trials focused on chronic heart failure have been developed. The first telemedicine projects (e.g., TEN-HMS, BEAT-HF, Tele-HF, and TIM-HF) primarily investigated telemonitoring or for the older ones, telephone follow-up. Numerous second-generation telemedicine projects have emerged in Europe over the last ten years or are still under development for computer science heart failure, especially in Europe, such as SCAD, OSICAT, E-care, PRADO-INCADO, and TIM-HF2. The E-care telemonitoring project fits within the telemedicine 2.0 framework, based on connected objects, new information and communication technologies (ICT) and Web 2.0 technologies. E-care is the first telemedicine project including artificial intelligence (AI). TIM-HF2 is the first positive prospective randomized study with regards to EBM with positive significant clinical benefit, in terms of unplanned cardiovascular hospital admissions and all-cause deaths. The potential contribution of second-generation telemedicine projects in terms of mortality, morbidity, and number of hospitalizations avoided is currently under study. Their impact in terms of health economics is likewise being investigated, taking into account that the economic and social benefits brought up by telemedicine solutions were previously validated by the original telemedicine projects.

Telemedicine is now in vogue, allowing computer and communication tools to be deployed in different fields of health, such as Cardiology, Dermatology, areas in which it has received interest, and in international studies. As the population ages, older people are increasingly concerned about this innovative practice. This is a narrative review of both the literature and Internet pertaining to telemedicine projects within the field of geriatric subjects in France. Since the beginning of the 2000’s, several telemedicine projects and trials focused on chronic heart failure have been developed in the elderly, and also in the field of dermatology. The potential contribution of second-generation telemedicine projects in terms of mortality, morbidity, and the number of hospitalizations avoided is currently under study. Their impact in terms of health economics is likewise being investigated, taking into account that the economic and social benefits brought up by telemedicine solutions were previously validated by the original telemedicine projects. We take a look at telemedicine projects in France concerning the elderly.

The objective of this review is to provide an update on the effectiveness of oral and nasal vitamin B12 (cobalamin) treatment in gastrointestinal (GI) disorders. Relevant articles were identified by PubMed and Google Scholar systematic search, from January 2010 and June 2018, and through hand search of relevant reference articles. Additional studies were obtained from references of identified studies, the Cochrane Library and the ISI Web of Knowledge. Data gleaned from reference textbooks and international meetings were also used, as was information gleaned from commercial sites on the web and data from CARE B12 research group. For oral vitamin B12 treatment, 4 randomized controlled trials (vs. intramuscular), 4 narrative and 4 systematic reviews, and 13 prospective studies fulfilled our inclusion criteria. These studies concerned patients with vitamin B12 deficiency related to: food-cobalamin malabsorption (n = 6), Biermer’s disease (n = 3), veganism or vegetarianism (n = 1), total gastrectomy after Roux-en-Y gastric bypass (n = 2) and Crohn’s disease (n = 1). Four prospective studies include patients with vitamin B12 deficiency related to the aforementioned etiologies, except veganism or vegetarianism. The systematic present review documents that oral vitamin B12 replacement, at a daily dose of 1000 μg (1 mg), was adequate to normalize serum vitamin B12 levels and cure main clinical manifestations related to vitamin B12 deficiency, in GI disorders, and thus, with safety profile. For nasal vitamin B12 treatment, only one preliminary study was available. We conclude that oral vitamin B12 is an effective alternative to intramuscular vitamin B12 (except in patients presenting with severe neurological manifestations). Oral vitamin B12 treatment avoids the discomfort, contraindication (in patients with anticoagulation), and cost of monthly injections.