Immune dysregulation is an important factor in the underlying complications in Influenza infection. ApoH, IL-8 and IL-15 as markers of prognosis.

Introduction: Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression. Methods: We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission. Results: Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71). Discussion: Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.

Nosocomial COVID-19: A Nationwide Spanish Study.

INTRODUCTION: SARS-CoV-2 is a highly contagious virus, and despite professionals' best efforts, nosocomial COVID-19 (NC) infections have been reported. This work aimed to describe differences in symptoms and outcomes between patients with NC and community-acquired COVID-19 (CAC) and to identify risk factors for severe outcomes among NC patients. METHODS: This is a nationwide, retrospective, multicenter, observational study that analyzed patients hospitalized with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from March 1, 2020, to April 30, 2021. NC was defined as patients admitted for non-COVID-19 diseases with a positive SARS-CoV-2 test on the fifth day of hospitalization or later. The primary outcome was 30-day in-hospital mortality (IHM). The secondary outcome was other COVID-19-related complications. A multivariable logistic regression analysis was performed. RESULTS: Of the 23,219 patients hospitalized with COVID-19, 1,104 (4.8%) were NC. Compared to CAC patients, NC patients were older (median 76 vs. 69 years; p < 0.001), had more comorbidities (median Charlson Comorbidity Index 5 vs. 3; p < 0.001), were less symptomatic (p < 0.001), and had normal chest X-rays more frequently (30.8% vs. 12.5%, p < 0.001). After adjusting for sex, age, dependence, COVID-19 wave, and comorbidities, NC was associated with lower risk of moderate/severe acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR]: 0.72; 95% confidence interval [CI]: 0.59-0.87; p < 0.001) and higher risk of acute heart failure (aOR: 1.40; 1.12-1.72; p = 0.003), sepsis (aOR: 1.73; 1.33-2.54; p < 0.001), and readmission (aOR: 1.35; 1.03-1.83; p = 0.028). NC was associated with a higher case fatality rate (39.1% vs. 19.2%) in all age groups. IHM was significantly higher among NC patients (aOR: 2.07; 1.81-2.68; p < 0.001). Risk factors for increased IHM in NC patients were age, moderate/severe dependence, malignancy, dyspnea, moderate/severe ARDS, multiple organ dysfunction syndrome, and shock; odynophagia was associated with lower IHM. CONCLUSIONS: NC is associated with greater mortality and complications compared to CAC. Hospital strategies to prevent NC must be strengthened.

Sporadic, non-functional, gastrin-producing duodenal neuroendocrine tumors: A retrospective study of an infrequent disease.

OBJECTIVES: Non-functioning gastrin-producing neuroendocrine neoplasms (NEN) of the duodenum are rare gastrointestinal tumors without a clinical syndrome due to gastrin production. Their incidence has significantly increased as an incidental finding during endoscopic studies. The aim of this study was to describe the characteristics and prognostic factors of this emergent and infrequent neoplasm. METHODS: We performed a retrospective observational study based on the duodenal NENs samples with positive staining for gastrin at the Department of Pathology, University Hospital 12-de-Octubre (Madrid, Spain) between 2000 and 2017. Patients with clinically functional tumors ([Zollinger-Ellison syndrome] or gastrin >1000 pg/mL), with previously diagnosed multiple endocrine neoplasia (MEN) syndrome or synchronous neoplasia were excluded. Clinicopathological and therapeutic variables, follow-up, recurrence, and mortality data were collected. RESULTS: In all, 21 patients were included. Most of the tumors were diagnosed incidentally as a single small polypoid lesion limited to mucosa/submucosa and with a low histological grade. Four (19.0%) patients presented with metastatic involvement at diagnosis (lymphatic and/or hepatic). These four patients also had a high or intermediate mitotic grade and infiltration further than submucosa. Local resection was applied in most cases as curative treatment. There were two cases of tumor recurrence and two tumor-related deaths with a 5-year disease-free survival of 81.0%. CONCLUSIONS: The majority of these tumors were diagnosed at a localized stage and had a good prognosis with treatment. Nevertheless, given the potential metastatic risk, a close follow-up is necessary, especially in those with aggressive pathological factors such as deep infiltration or high histological grade.

Presence of Extra-Criteria Antiphospholipid Antibodies Is an Independent Risk Factor for Ischemic Stroke.

Background: Ischemic stroke is the most common and severe arterial thrombotic event in Antiphospholipid syndrome (APS). APS is an autoimmune disease characterized by the presence of thrombosis and antiphospholipid antibodies (aPL), which provide a pro-coagulant state. The aPL included in the classification criteria are lupus anticoagulant, anti-cardiolipin (aCL) and anti-ß2-glycoprotein-I antibodies (aB2GPI) of IgG and IgM isotypes. Extra-criteria aPL, especially IgA aB2GPI and IgG/IgM anti-phosphatidylserine/prothrombin antibodies (aPS/PT), have been strongly associated with thrombosis. However, their role in the general population suffering from stroke is unknown. We aim (1) to evaluate the aPL prevalence in ischemic stroke patients, (2) to determine the role of aPL as a risk factor for stroke, and (3) to create an easy-to-use tool to stratify the risk of ischemic stroke occurrence considering the presence of aPL and other risk factors. Materials and Methods: A cohort of 245 consecutive ischemic stroke patients was evaluated in the first 24 h after the acute event for the presence of classic aPL, extra-criteria aPL (IgA aB2GPI, IgG, and IgM aPS/PT) and conventional cardiovascular risk factors. These patients were followed-up for 2-years. A group of 121 healthy volunteers of the same age range and representative of the general population was used as reference population. The study was approved by the Ethics Committee for Clinical Research (Reference numbers CEIC-14/354 and CEIC-18/182). Results: The overall aPL prevalence in stroke patients was 28% and IgA aB2GPI were the most prevalent (20%). In the multivariant analysis, the presence of IgA aB2GPI (OR 2.40, 95% CI: 1.03-5.53), dyslipidemia (OR 1.70, 95% CI: 1.01-2.84), arterial hypertension (OR 1.82, 95% CI: 1.03-3.22), atrial fibrillation (OR 4.31, 95% CI: 1.90-9.78), and active smoking (OR 3.47, 95% CI: 1.72-6.99) were identified as independent risk factors for ischemic stroke. A risk stratification tool for stroke was created based on these factors (AUC: 0.75). Conclusions: IgA aB2GPI are an important independent risk factor for ischemic stroke. Evaluation of aPL (including extra-criteria) in cardiovascular risk factor assessment for stroke can potentially increase the identification of patients at risk of thrombotic event, facilitating a decision on preventive treatments.

Case Report: Resetting the Humoral Immune Response by Targeting Plasma Cells With Daratumumab in Anti-Phospholipid Syndrome.

Introduction: Monoclonal antibodies (mAb) targeting plasma cells are malignant gammopathy designed and approved therapies. In recent years, these antibodies have also been increasingly introduced for non-malignant conditions such as autoimmune-mediated diseases. The Anti-Phospholipid Syndrome (APS) is an immune-mediated disorder in which autoantibodies against phospholipid associated proteins could elicit the activation of the coagulation cascade in specific situations. Therefore, the mainstream treatment for APS patients is the use of anticoagulant therapy. However, there are refractory patients who would benefit from targeting the antibodies rather than their effects. Rituximab, a B-cell depleting mAb, and intravenous immunoglobulins (IVIG) have been used in APS patients without showing a clear beneficial effect or a significant drop in anti-phospholipid antibody (aPL) levels. Clinical case: We present our first APS case treated with daratumumab, an anti-CD38 mAb, in a 21-year-old patient with APS who presented with recurrent venous thromboembolic events despite adequate anticoagulant therapy. She tested positive for lupus anticoagulant, anti-cardiolipin IgG, anti-beta-2-glycoprotein-I IgG and anti-phosphatidylserine/prothrombin IgG and IgM. She was administered one dose weekly of daratumumab for 4 weeks. The treatment showed an adequate safety profile and was well tolerated. The patient was discharged after undergoing a clinically significant improvement. After the therapy, her levels of positive aPL declined significantly and most continued to decrease during the next three months. The patient experienced a new thrombotic episode two years after the therapy associated with poor adherence to antithrombotic therapy. Conclusions: The treatment with daratumumab showed an adequate safety profile, was well tolerated and led to a significant clinical improvement. Levels of aPL lowered on therapy and the next three months and then rose again during follow-up. Further investigation is needed to better elucidate the role and optimal timing and doses of daratumumab in treatment of refractory APS.

Impact of functional status on 6-month mortality in elderly patients with acute venous thromboembolism: results from a prospective cohort.

Functional status linked to a poor outcome in a broad spectrum of medical disorders. Barthel Activities of Daily Life Index (BADLI) is one of the most extended tools to quantify functional dependence. Whether BADLI can help to predict outcomes in elderly patients with acute venous thromboembolism (VTE) is unknown. The current study aimed to ascertain the influence of BADLI on 6-month all-cause mortality in aged patients with VTE. This is a prospective observational study. We included consecutive patients older than 75-year-old with an acute VTE between April 2015 and April 2017. We analyzed several variables as mortality predictors, including BADLI-measured functional status. Afterward, we performed a multivariate analysis, using logistic regression, to identify all-cause mortality independent predictive factors. Two hundred and two subjects were included. Thirty-five (17%) patients died in the first 6 months. The leading cause of death was cancer (59%). After multivariable logistic regression, we identified BADLI and Charlson index as independent predictors for 6-months mortality [BADLI (every decrease of 10 points) OR 1.21 95% CI (1.03-1.42) and Charlson index OR 1.71 95% CI (1.21-2.43)]. Body mass index (BMI) values were inversely related to mortality [OR 0.85 95% CI (0.75-0.95)]. In conclusion, BADLI, BMI, and Charlson index scores are independent predictive factors for 6-month all-cause mortality in old patients with VTE.