Fat-soluble vitamins, including vitamins A, D, E, and K, are energy-free molecules that are essential to the body’s functioning and life. Their intake is almost exclusively exogenous, i.e., dietary. As a result, fat-soluble vitamin deficiencies are rarer in industrialized countries than in countries with limited resources. Certain groups of people are particularly affected, such as newborns or growing children, pregnant or breastfeeding women, and elderly or isolated individuals. Deficiencies in vitamins A, D, E, and K are also relatively frequent in subjects with digestive tract disorders, liver diseases, chronic pathologies, or in intensive care patients. Deficiencies or excesses of fat-soluble vitamins are responsible for a variety of more or less specific clinical pictures. Certain syndromes are typical of fat-soluble vitamin deficiency, such as the combination of ophthalmological and immunity impairments in the case of vitamin A deficiency or hemorrhagic syndrome and osteopenia in the case of vitamin E deficiency. This is also the case for osteomalacia, muscular weakness, even falls, and rickets in the case of vitamin D deficiency. Diagnosis of a deficiency in one of the fat-soluble vitamins relies on blood tests, which are not always essential for routine use. In this context, a therapeutic test may be proposed. Treatment of deficiencies requires vitamin supplementation, a well-balanced diet, and treatment of the cause.

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.

An observational and descriptive study including patients discharged for COVID-19 was carried out by the COVID-19 Working Group of the Hospital Clínico San Carlos (HCSC). We aimed to identify the main symptoms after 90 days of hospital discharged. A structured interview was conducted, through a “checklist” that included symptoms within the 90 days post-discharge. A total of 134 patients were enrolled. The most frequently referred symptoms were asthenia, dyspnea and weight loss. Anxiety was the most frequent psychological symptom found through the GAD-7 scale.

Background: Pulmonary congestion (PC) is associated with an increased risk of hospitalization and death in patients with heart failure (HF). Lung ultrasound is highly sensitive for detecting PC. The aim of this study is to evaluate whether lung ultrasound-guided therapy improves 6-month outcomes in patients with HF. Methods: A randomized, multicenter, single-blind clinical trial in patients discharged after hospitalization for decompensated HF. Participants were assigned 1:1 to receive treatment guided according to the presence of lung ultrasound signs of congestion (semi-quantitative evaluation of B lines and the presence of pleural effusion) versus standard of care (SOC). The primary endpoint was the combination of cardiovascular death, readmission, or emergency department or day hospital visit due to worsening HF at 6 months. In September 2020, after an interim analysis, patient recruitment was stopped. Results: A total of 79 patients were randomized (mean age 81.2 +/− 9 years) and 41 patients (51.8%) showed a left ventricular ejection fraction >50%. The primary endpoint occurred in 11 patients (29.7%) in the SOC group and in 11 patients (26.1%) in the LUS group (log-rank = 0.83). Regarding nonserious adverse events, no significant differences were found. Conclusions: LUS-guided diuretic therapy after hospital discharge due to ADHF did not show any benefit in survival or a need for intravenous diuretics compared with SOC.

Introduction: Inflammation is a fundamental phenomenon in heart failure, but the prognostic or therapeutic role of markers such as interleukin-6 (IL-6) has not yet been clarified. The objective of this study is to describe the clinical profile of patients with elevated IL-6 and determine if they have worse clinical outcomes. Methods: A retrospective c.ohort observational study including 78 patients with heart failure followed up at the Heart Failure Outpatient Clinic of the Internal Medicine Department. IL-6 was determined in all patients, who were then assigned into two groups according to IL-6 level (normal or high). Clinical and prognostic data were collected to determine the differences in both groups. Results: The average age was 79 years, 60% female. A total of 53.8% of the patients had elevated IL-6 (group 2). Patients with elevated IL-6 presented more frequently with anemia mellitus (64.3% vs. 41.7%; p = 0.046), atrial fibrillation (83.3% vs. 61.9% p = 0.036), dyslipidemia (76.2% vs. 58.2%; p = 0.03), higher creatinine levels (1.35 mg/dL vs. 1.08 mg/dL; p = 0.024), lower glomerular filtration rate (43.6 mL/min/m² vs. 59.9 mL/min/m²; p = 0.007), and anemia 25% vs. 52.4% p = 0.014. The factors independently associated with the increase in IL-6 were anemia 3.513 (1.163–10.607) and renal failure 0.963 (0.936–0.991), p < 0.05. Mortality was higher in the group with elevated IL-6 levels (16% vs. 2%; p = 0.044) with a log-rank p = 0.027 in the Kaplan–Meier curve. Conclusion: Patients with heart failure and elevated IL-6 most often have atrial fibrillation, diabetes mellitus, dyslipidemia, anemia, and renal failure. In addition, mortality was higher and a tendency of higher hospital admission was observed in stable HF patients with elevated IL-6.