Autoinflammatory Manifestations In Adult Patients.

Autoinflammatory diseases represent a family of immune-mediated conditions characterized by the unchecked activation of innate immunity. These conditions share common clinical features such as recurrent fever, inflammatory arthritis and elevation of acute phase reactants, in the absence of an identified infectious etiology, generally without detectable serum autoantibodies, with variable response to glucocorticoids and in some cases colchicine, which represented the mainstay of treatment until cytokine blockade therapies became available. The first autoinflammatory diseases to be described were monogenic disorders caused by missense mutations in inflammasome components and were recognized predominantly during childhood or early adulthood. However, the progress of genetic analyses and a more detailed immunological phenotyping capacity led to the discovery a wide spectrum of diseases, often becoming manifest or being diagnosed in the adult population. The beneficial role of targeting hyperinflammation via interleukin 1 in complex non-immune mediated diseases is a field of growing clinical interest. We provide an overview of the autoinflammatory diseases of interest to physicians treating adult patients and to analyze the contribution of hyperinflammation in non-immune-mediated diseases; the result is intended to provide a roadmap to orient scientists and clinicians in this broad area.

Eosinophils as Major Player in Type 2 Inflammation: Autoimmunity and Beyond.

Eosinophils are a subset of differentiated granulocytes which circulate in peripheral blood and home in several body tissues. Along with their traditional relevance in helminth immunity and allergy, eosinophils have been progressively attributed important roles in a number of homeostatic and pathologic situations. This review aims at summarizing available evidence about eosinophils functions in homeostasis, infections, allergic and autoimmune disorders, and solid and hematological cancers.Their structural and biological features have been described, along with their physiological behavior. This includes their chemokines, cytokines, granular contents, and extracellular traps. Besides, pathogenic- and eosinophilic-mediated disorders have also been addressed, with the aim of highlighting their role in Th2-driven inflammation. In allergy, eosinophils are implicated in the pathogenesis of atopic dermatitis, allergic rhinitis, and asthma. They are also fundamentally involved in autoimmune disorders such as eosinophilic esophagitis, eosinophilic gastroenteritis, acute and chronic eosinophilic pneumonia, and eosinophilic granulomatosis with polyangiitis. In infections, eosinophils are involved in protection not only from parasites but also from fungi, viruses, and bacteria. In solid cancers, local eosinophilic infiltration is variably associated with an improved or worsened prognosis, depending on the histotype. In hematologic neoplasms, eosinophilia can be the consequence of a dysregulated cytokine production or the result of mutations affecting the myeloid lineage.Recent experimental evidence was thoroughly reviewed, with findings which elicit a complex role for eosinophils, in a tight balance between host defense and tissue damage. Eventually, emerging evidence about eosinophils in COVID-19 infection was also discussed.

A Natural Language Processing-Based Virtual Patient Simulator and Intelligent Tutoring System for the Clinical Diagnostic Process: Simulator Development and Case Study.

BACKGROUND: Shortage of human resources, increasing educational costs, and the need to keep social distances in response to the COVID-19 worldwide outbreak have prompted the necessity of clinical training methods designed for distance learning. Virtual patient simulators (VPSs) may partially meet these needs. Natural language processing (NLP) and intelligent tutoring systems (ITSs) may further enhance the educational impact of these simulators. OBJECTIVE: The goal of this study was to develop a VPS for clinical diagnostic reasoning that integrates interaction in natural language and an ITS. We also aimed to provide preliminary results of a short-term learning test administered on undergraduate students after use of the simulator. METHODS: We trained a Siamese long short-term memory network for anamnesis and NLP algorithms combined with Systematized Nomenclature of Medicine (SNOMED) ontology for diagnostic hypothesis generation. The ITS was structured on the concepts of knowledge, assessment, and learner models. To assess short-term learning changes, 15 undergraduate medical students underwent two identical tests, composed of multiple-choice questions, before and after performing a simulation by the virtual simulator. The test was made up of 22 questions; 11 of these were core questions that were specifically designed to evaluate clinical knowledge related to the simulated case. RESULTS: We developed a VPS called Hepius that allows students to gather clinical information from the patient's medical history, physical exam, and investigations and allows them to formulate a differential diagnosis by using natural language. Hepius is also an ITS that provides real-time step-by-step feedback to the student and suggests specific topics the student has to review to fill in potential knowledge gaps. Results from the short-term learning test showed an increase in both mean test score (P<.001) and mean score for core questions (P<.001) when comparing presimulation and postsimulation performance. CONCLUSIONS: By combining ITS and NLP technologies, Hepius may provide medical undergraduate students with a learning tool for training them in diagnostic reasoning. This may be particularly useful in a setting where students have restricted access to clinical wards, as is happening during the COVID-19 pandemic in many countries worldwide.

Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19.

Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1-3. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)4-7. RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.

Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients.

In cases of COVID-19 acute respiratory distress syndrome, an excessive host inflammatory response has been reported, with elevated serum interleukin-6 levels. In this multicenter retrospective cohort study we included adult patients with COVID-19, need of respiratory support, and elevated C-reactive protein who received intravenous tocilizumab in addition to standard of care. Control patients not receiving tocilizumab were matched for sex, age and respiratory support. We selected survival as the primary endpoint, along with need for invasive ventilation, thrombosis, hemorrhage, and infections as secondary endpoints at 30 days. We included 64 patients with COVID-19 in the tocilizumab group and 64 matched controls. At baseline the tocilizumab group had longer symptom duration (13 ± 5 vs. 9 ± 5 days) and received hydroxychloroquine more often than controls (100% vs. 81%). The mortality rate was similar between groups (27% with tocilizumab vs. 38%) and at multivariable analysis risk of death was not significantly influenced by tocilizumab (hazard ratio 0.61, 95% confidence interval 0.33-1.15), while being associated with the use at baseline of non invasive mechanical or invasive ventilation, and the presence of comorbidities. Among secondary outcomes, tocilizumab was associated with a lower probability of requiring invasive ventilation (hazard ratio 0.36, 95% confidence interval 0.16-0.83; P = 0.017) but not with the risk of thrombosis, bleeding, or infections. The use of intravenous tocilizumab was not associated with changes in 30-day mortality in patients with COVID-19 severe respiratory impairment. Among the secondary outcomes there was less use of invasive ventilation in the tocilizumab group.

COVID-19 Digestive System Involvement and Clinical Outcomes in a Large Academic Hospital in Milan, Italy.

Since February 2020, the COVID-19 pandemic has spread to Italy affecting more than 100,000 people. Several studies have reported a high prevalence of gastrointestinal (GI) symptoms, and investigated their potential association with clinical outcomes.1 The timing, clinical significance, and possible impact on viral spread of GI symptoms presentation have not been fully elucidated. Elevation of liver function tests and other laboratory values has also been reported; however, their prognostic significance has not been clearly established.2.

Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy.

We described features of hospitalized Covid-19 patients and identified predictors of clinical deterioration. We included patients consecutively admitted at Humanitas Research Hospital (Rozzano, Milan, Italy); retrospectively extracted demographic; clinical; laboratory and imaging findings at admission; used survival methods to identify factors associated with clinical deterioration (defined as intensive care unit (ICU) transfer or death), and developed a prognostic index. Overall; we analyzed 239 patients (29.3% females) with a mean age of 63.9 (standard deviation [SD]; 14.0) years. Clinical deterioration occurred in 70 patients (29.3%), including 41 (17.2%) ICU transfers and 36 (15.1%) deaths. The most common symptoms and signs at admission were cough (77.8%) and elevated respiratory rate (34.1%), while 66.5% of patients had at least one coexisting medical condition. Imaging frequently revealed ground-glass opacity (68.9%) and consolidation (23.8%). Age; increased respiratory rate; abnormal blood gas parameters and imaging findings; coexisting coronary heart disease; leukocytosis; lymphocytopenia; and several laboratory parameters (elevated procalcitonin; interleukin-6; serum ferritin; C-reactive protein; aspartate aminotransferase; lactate dehydrogenase; creatinine; fibrinogen; troponin-I; and D-dimer) were significant predictors of clinical deterioration. We suggested a prognostic index to assist risk-stratification (C-statistic; 0.845; 95% CI; 0.802‒0.887). These results could aid early identification and management of patients at risk, who should therefore receive additional monitoring and aggressive supportive care.