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The ideal duration of anticoagulation therapy in patients with autoimmune disorders and venous thromboembolism (VTE) is controversial. We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) database to compare the incidence rate of major bleeding during anticoagulation versus the incidence rate of VTE recurrences after its discontinuation. We included 1061 patients with autoimmune disorders and VTE followed-up after discontinuing anticoagulant therapy: rheumatoid arthritis, 321; polymyalgia rheumatica, 159; ulcerative colitis, 134; Crohn’s disease, 111; systemic lupus erythematosus (SLE), 82; giant cell arteritis, 58; ankylosing spondylitis, 39; Behcet disease, 17; other vasculitides, 140. During anticoagulation (median, 183 days), 64 patients had major bleeding. After discontinuing anticoagulation (median, 190 days), 112 patients developed symptomatic VTE recurrences. In most subgroups, the incidence rate of major bleeding during therapy was similar to the incidence rate of VTE recurrences after its discontinuation. However, in patients with SLE (10.0 major bleeds, 95% confidence interval [CI] 4.07-20.9) per 100 patient-years vs. 3.62 VTE recurrences, 95% CI 1.15-8.74) or ankylosing spondylitis (10.9 major bleeds [95% CI 3.47-26.3] vs. 4.69 VTE recurrences, 95% CI 1.19-12.8) the incidence rates of major bleeding during anticoagulation were over twofold higher than the incidence rates of VTE recurrences after its discontinuation.

Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been reported to increase the risk of pulmonary thromboembolism (PTE). The aim of this study is to elucidate whether Coronavirus disease COVID-19-associated PTE has a different clinical expression than non-COVID-19 PTE due to a different pathophysiology. (2) Methods: retrospective study of PTE episodes conducted at our hospital between January 2019 and December 2020, comparing the group of COVID-19-associated PTE patients with a control group of non-COVID-19 PTE patients. (3) Results: A total of 229 patients with PTE were registered, 79 of whom had COVID-19. Cancer (15.2% vs. 39.3%; p < 0.001), previous surgery (0% vs. 8%; p = 0.01), previous VTE (2.5% vs. 15.3%; p = 0.003), signs and/or symptoms of deep venous thrombosis (DVT) (7.6% vs. 22.7%; p = 0.004) and syncope (1.3% vs. 8.1%; p = 0.035) were less frequent in the COVID-19 group. Central thrombosis was more frequent in the control group (35.3% vs. 13.9%; p = 0.001). No VTE recurrent episodes were observed in the COVID-19 group, whereas four (2.7%) episodes were recorded for the control group. One-month bleeding rate was higher in the COVID-19 group (10.1% vs. 1.3%; p = 0.004). (4) Conclusion: COVID-19-associated PTE has clinical characteristics that differ from those of PTE without COVID-19, including inferior severity and a lower rate of VTE recurrence. Physicians should be aware of the high risk of bleeding in the first month of COVID-19-associated PTE.

An increased risk of venous thromboembolism (VTE) in hospitalized patients with COVID-19 has been reported. We aimed to describe the incidence rate of VTE on patients with non-hematological cancer who required hospitalization due to COVID-19 at our center. In this prospective study, non-hematological cancer patients hospitalized for confirmed COVID-19 at our institution from 1st March to 30th April 2020, were evaluated daily for VTE complications during their hospital stay, and after discharge until 30th June 2020. Furthermore, Doppler ultrasound of lower limbs was routinely performed in asymptomatic patients based on D-dimer levels and current active cancer therapy. The primary outcome of this study was the cumulative incidence of VTE. Secondary outcomes were the cumulative incidence of bleeding and mortality. A total of 58 hospitalized non-hematological cancer patients and confirmed COVID-19 were identified. Median follow-up since initial symptoms of COVID-19 was 91 days (IQR 19–104). Pulmonary embolism was diagnosed in three (5%) patients. Symptomatic catheter-related deep vein thrombosis (DVT) was observed in one patient. Doppler ultrasound of lower limbs was done in 11 asymptomatic patients, showing distal DVT in two of them (18%). The cumulative incidence of VTE on day 14 after admission was 10%, without new VTE events after hospital discharge and up to 90 days follow-up. No bleeding complication was observed. Seventeen patients (29%) died in the first 14 days after COVID-19 diagnosis. Four patients died after discharge due to malignancy progression. The cumulative incidence of VTE in non-hematological cancer patients under active treatment was 10% at day 14 after admission, with no further new events in the following 12 weeks. Supplementary Information The online version contains supplementary material available at 10.1007/s11239-021-02448-w.

Introduction In patients receiving anticoagulation for deep vein thrombosis (DVT), a variety of reasons (including active bleeding or high-risk for bleeding) may lead into premature discontinuation of therapy (prior to completing 90 days). The relative frequency and clinical consequences of premature discontinuation in contemporary patients remain unknown. Methods We used the data from RIETE, an international registry of patients with venous thromboembolism (VTE), to identify patients with proximal (above knee) lower limb DVT who prematurely discontinued anticoagulation. We assessed the incidence of the composite outcome: pulmonary embolism (PE)-related death, sudden death, or recurrent VTE within the subsequent 30 days after discontinuation and compared the risk of these events vs. the risk in patients without premature discontinuation, once adjusted for demographics and clinical factors. Results Of 26,335 patients with proximal DVT recruited from 2001 to 2018, 1322 (5.02%) prematurely discontinued anticoagulation. Thirty days after discontinuation, 12 (0.91%) patients suffered fatal PE (n = 8) or sudden death (n = 4) and 33 (2.50%) had non-fatal recurrent VTE (PE = 15; recurrent DVT = 18). In patients with premature discontinuation, the 30-day incidence of the composite outcome was 1.62 per 1000 patient-days (95%CI: 0.00–3.80). During the first week after discontinuation, the incidence rate was 4.09 per 1000 patient-days (95%CI: 0.65–7.52). The adjusted odds of the composite outcome was 7.88 times (95%CI: 6.39–9.72) higher in patients who discontinued prematurely than in those without premature discontinuation. Conclusion Premature discontinuation of anticoagulation occurred in 5% of patients with proximal DVT, and was associated an 8-fold increased odds for the composite outcome.

An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had normalized in post-COVID-19 patients 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patient stratification and for designing innate immunity-focused therapies.

Patients with cirrhosis are not only at an increased risk of bleeding but also at risk of venous thromboembolism (VTE). We sought to determine the clinical characteristics, management, and outcomes after VTE in patients with cirrhosis. We used the data from RIETE (Registro Informatizado de la Enfermedad TromboEmbolica), an international registry of patients with VTE, to compare the outcomes in patients with and without cirrhosis. Main outcomes included all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent VTE, and bleeding. Among 43,611 patients with acute VTE, 187 (0.4%) had cirrhosis. Of these, 184 (98.4%) received anticoagulation for a median of 109 days (interquartile range [IQR]: 43–201 days), most commonly with enoxaparin (median dose: 1.77 [IQR: 1.38–2.00] mg/kg/day). Compared with patients without cirrhosis, those with cirrhosis had a higher rate of all-cause mortality (10.7 vs. 3.4%; odds ratio [OR]: 3.41; 95% confidence interval [CI]: 2.03–5.46) and fatal bleeding (2.1 vs. 0.2%; OR: 13.94; 95% CI: 3.65–37.90) but similar rates of fatal PE (0.5 vs. 0.5%; OR: 1.17; 95% CI: 0.03–6.70). Patients with cirrhosis had a higher rate of all-cause mortality per 100 patient-years of follow-up (58.9 vs. 16.0; hazard ratio [HR]: 3.70; 95% CI: 2.69–4.91). One-year hazard ratio of clinically relevant bleeding (HR: 2.86; 95% CI: 1.91–4.27), fatal bleeding (HR: 8.51; 95% CI: 3.5–20.7), or recurrent VTE (HR: 2.08; 95% CI: 1.00–4.36) was higher in patients with cirrhosis. Cirrhosis is a challenging comorbidity in patients with VTE. Most patients were treated with anticoagulation and had an elevated risk of recurrence, similar risk of fatal PE, and a very high risk of bleeding including fatal bleeds.

To the EditorA recent report in the present journal drew attention to lymphopenia in influenza infection [1]. Besides the authors’ main observation that a high rate of complications occurred in neu...

The role of viral load in the outcome of patients requiring hospital admission due to influenza is not well established. We aim to assess if there is an association between the viral load and the outcome in hospitalized patients with a confirmed influenza virus infection. A retrospective observational study including all adult patients who were hospitalized in our center with a confirmed influenza virus infection from January to May 2016. Viral load was measured by real-time reverse-transcriptase–polymerase chain reaction (rRT-PCR) cycle threshold (Ct) value on upper respiratory tract samples. Its value was categorized into three groups (low Ct, ≤ 20; intermediate Ct, > 20–30; and high Ct, > 30). Two hundred thirty-nine patients were included. Influenza A/H1N1pdm09 was isolated in 207 cases (86.6%). The mean Ct value was 26.69 ± 5.81. The viral load was higher in the unvaccinated group when compared with the vaccinated patients (Ct 25.17 ± 5.55 vs. 27.58 ± 4.97, p = 0.004). Only 27 patients (11.29%) presented a high viral load. Patients with a high viral load more often showed abnormal findings on chest X-ray (p = 0.015) and lymphopenia (p = 0.097). By contrast, there were no differences between the three groups (according to viral load), in associated pneumonia, respiratory failure, need for mechanical ventilation, sepsis, or in-hospital mortality. Our findings suggest that in patients admitted to the hospital with confirmed influenza virus infection (mostly A/H1N1pdm09), a high viral load is associated with a higher presence of abnormal findings on chest X-ray but not with a significant worse prognosis. In these cases, standardized quantitative PCR could be useful.

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/2072-6694/14/17/4127 Este artículo de investigación pertenece al número especial "Venous Thromboembolism and Cancer". En este artículo de investigación también participan: Carmen Díaz Pedroche, José Luis Lobo, Luciano López Jiménez, Raquel López Reyes, Luis Jara Palomares, José María Pedrajas, Isabelle Mahé, Manuel Monreal and The RIETE Investigators. Background: In patients with lung cancer and venous thromboembolism (VTE), the influence of cancer histology on outcome has not been consistently evaluated. Methods: We used the RIETE registry (Registro Informatizado Enfermedad TromboEmbólica) to compare the clinical characteristics and outcomes during anticoagulation in patients with lung cancer and VTE, according to the histology of lung cancer. Results: As of April 2022, there were 482 patients with lung cancer and VTE: adenocarcinoma 293 (61%), squamous 98 (20%), small-cell 44 (9.1%), other 47 (9.8%). The index VTE was diagnosed later in patients with squamous cancer than in those with adenocarcinoma (median, 5 vs. 2 months). In 50% of patients with adenocarcinoma, the VTE appeared within the first 90 days since cancer diagnosis. During anticoagulation (median 106 days, IQR: 45–214), 14 patients developed VTE recurrences, 15 suffered major bleeding, and 218 died: fatal pulmonary embolism 10, fatal bleeding 2. The rate of VTE recurrences was higher than the rate of major bleeding in patients with adenocarcinoma (11 vs. 6 events), and lower in those with other cancer types (3 vs. 9 events). On multivariable analysis, patients with adenocarcinoma had a non-significantly higher risk for VTE recurrences (hazard ratio [HR]: 3.79; 95%CI: 0.76–18.8), a lower risk of major bleeding (HR: 0.29; 95%CI: 0.09–0.95), and a similar risk of mortality (HR: 1.02; 95%CI: 0.76–1.36) than patients with other types of lung cancer. Conclusions: In patients with lung adenocarcinoma, the rate of VTE recurrences outweighed the rate of major bleeding. In patients with other lung cancers, it was the opposite.

Background Hospitalized patients with COVID-19 and raised D-dimer levels have high rates of venous thromboembolism (VTE). Methods We used data from hospitalized patients with COVID-19 that were tested for pulmonary embolism (PE) or deep vein thrombosis (DVT) because of raised D-dimer levels. We aimed to identify patients at increased risk for VTE. Results From March 25 to July 5th, 2020, 1,306 hospitalized patients with COVID-19 and raised D-dimer levels underwent testing for VTE in 12 centers. In all, 171 of 714 (24%) had PE, and 161 of 810 (20%) had DVT. The median time elapsed from admission to VTE testing was 12 days, and the median time from D-dimer measurement to testing 2 days. Most patients with VTE were men (62%), mean age was 62 ​± ​15 years, 45% were in an intensive care unit. Overall, 681 patients (52%) received VTE prophylaxis with standard doses, 241 (18%) with intermediate doses and 100 (7.7%) with therapeutic doses of anticoagulants. On multivariable analysis, patients with D-dimer levels >20 times the upper normal range (19% of the whole cohort) were at increased risk for VTE (odds ratio [OR]: 3.24; 95%CI: 2.18–4.83), as were those with a platelet count 20 times the upper normal range were at an increased risk for VTE. This may help to identify what patients could likely benefit from the use of higher than recommended doses of anticoagulants for VTE prophylaxis., Highlights • Hospitalized patients with COVID-19 and raised D-dimer levels have high rates of venous thromboembolism (VTE). • We used data from hospitalized patients with COVID-19 that were tested for venous thromboembolism (VTE) because of raised D-dimer levels, aimed to identify those at increased risk for VTE. • Patients with D-dimer levels >20 times the upper normal range (19% of the whole cohort) were at a 3-fold higher risk for VTE. • Our data support the identification of individuals with higher thrombotic risk.

AIM Previous studies have suggested a more frequent and severe course of novel coronavirus Sars-coV-2 infection in cancer patients undergoing active oncologic treatment. Our aim was to describe the characteristics of the disease in this population and to determine predictive factors for poor outcome in terms of severe respiratory distress (ARDS) or death. PATIENTS AND METHODS Patients consecutively admitted for SARS-CoV-2 infection were prospectively collected and retrospective statistical analysis was performed. Univariate and multivariate analyses were performed to assess potential factors for poor outcomes defined as ARDS or death. RESULTS 63 patients were analyzed, 34 of them developed respiratory failure (70% as ARDS). Lymphocytes/mm3 (412 vs. 686; p=0.001), serum albumin (2.84 vs. 3.1); LDH (670vs. 359; p, Highlights • Cancer patients are supposed to be specially vulnerable for Sars-CoV-2 infection. • Active cancer treatment could be deleterious in case of simultaneous SARS-CoV-2 infection. • Outcomes of patients under treatment and admitted for SARS-CoV-2 infection are described. • Hospitalized SARS-CoV-2 cancer patients show similar death rate to non-cancer patients.

Background: The choice of the imaging modality for diagnosis of pulmonary embolism (PE) could be influenced by provider, patient or hospital characteristics, or over time. However, little is known about the choice of the diagnostic modalities in practice. The aim of this study was to evaluate the variations in the use of imaging modalities for patients with acute PE. Methods: Using the data from Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective international registry of patients with venous thromboembolism (March 2001–January 2019), we explored the imaging modalities used in patients with acute PE. The imaging modalities included computed tomography pulmonary angiography, ventilation/perfusion scanning, pulmonary angiography, a combination of these tests, or PE signs and symptoms plus imaging-confirmed proximal deep vein thrombosis but no chest imaging. Results: Among 38 025 patients with confirmed PE (53.1% female, age: 67.3±17 years), computed tomography pulmonary angiography was the dominant modality of diagnosis in all RIETE enrollees (78.2% [99% CI, 77.6–78.7]); including pregnant patients (58.9% [99% CI, 47.7%–69.4%]) and patients with severe renal insufficiency (62.5% [99% CI, 59.9–65.0]). A greater proportion of patients underwent ventilation/perfusion scanning in larger hospitals compared with smaller hospitals (13.1% versus 7.3%, P P Conclusions: In a large multinational PE registry, variations were observed in the use of imaging modalities according to patient or institutional factors and over time. However, computed tomography pulmonary angiography was the dominant modality of diagnosis, even in pregnancy and severe renal insufficiency. The safety, costs, and downstream effects of these tests on PE-related and non-PE-related outcomes warrant further investigation.

Registro Informatizado de Enfermedad Tromboembólica Investigators., [Objective] Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE., [Methods] We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboembólica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel >6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the χ2 test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of, [Results] We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE., [Conclusions] Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events.

GAMES Investigators., [Background] Enterococcal endocarditis (EE) is a growing entity in Western countries. However, quality data from large studies is lacking., [Objectives] The purpose of this study was to describe the characteristics and analyze the prognostic factors of EE in the GAMES cohort., [Methods] This was a post hoc analysis of a prospectively collected cohort of patients from 35 Spanish centers from 2008 to 2016. Characteristics and outcomes of 516 cases of EE were compared with those of 3,308 cases of nonenterococcal endocarditis (NEE). Logistic regression and Cox proportional hazards regression analysis were performed to investigate risk factors for in-hospital and 1-year mortality, as well as relapses., [Results] Patients with EE were significantly older; more frequently presented chronic lung disease, chronic heart failure, prior endocarditis, and degenerative valve disease; and had higher median age-adjusted Charlson score. EE more frequently involved the aortic valve and prosthesis (64.3% vs. 46.7%; p < 0.001; and 35.9% vs. 28.9%; p = 0.002, respectively) but less frequently pacemakers/defibrillators (1.5% vs. 10.5%; p < 0.001), and showed higher rates of acute heart failure (45% vs. 38.3%; p = 0.005). Cardiac surgery was less frequently performed in EE (40.7% vs. 45.9%; p = 0.024). No differences in in-hospital and 1-year mortality were found, whereas relapses were significantly higher in EE (3.5% vs. 1.7%; p = 0.035). Increasing Charlson score, LogEuroSCORE, acute heart failure, septic shock, and paravalvular complications were risk factors for mortality, whereas prior endocarditis was protective and persistent bacteremia constituted the sole risk factor for relapse., [Conclusions] Besides other baseline and clinical differences, EE more frequently affects prosthetic valves and less frequently pacemakers/defibrillators. EE presents higher rates of relapse than NEE.

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). However, limited data exist on patient characteristics, treatments, and outcomes. To describe the clinical characteristics, treatment patterns, and short-term outcomes of patients diagnosed with VTE during hospitalization for COVID-19. This is a prospective multinational study of patients with incident VTE during the course of hospitalization for COVID-19. Data were obtained from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. All-cause mortality, VTE recurrences, and major bleeding during the first 10 days were separately investigated for patients in hospital wards versus those in intensive care units (ICUs). As of May 03, 2020, a total number of 455 patients were diagnosed with VTE (83% pulmonary embolism, 17% isolated deep vein thrombosis) during their hospital stay; 71% were male, the median age was 65 (interquartile range, 55–74) years. Most patients (68%) were hospitalized in medical wards, and 145 in ICUs. Three hundred and seventeen (88%; 95% confidence interval [CI]: 84–91%) patients were receiving thromboprophylaxis at the time of VTE diagnosis. Most patients (88%) received therapeutic low-molecular-weight heparin, and 15 (3.6%) received reperfusion therapies. Among 420 patients with complete 10-day follow-up, 51 (12%; 95% CI: 9.3–15%) died, no patient recurred, and 12 (2.9%; 95% CI: 1.6–4.8%) experienced major bleeding. The 10-day mortality rate was 9.1% (95% CI: 6.1–13%) among patients in hospital wards and 19% (95% CI: 13–26%) among those in ICUs. This study provides characteristics and early outcomes of patients diagnosed with acute VTE during hospitalization for COVID-19. Additional studies are needed to identify the optimal strategies to prevent VTE and to mitigate adverse outcomes associated.

Background Immunotherapy treatment with immune-checkpoint blockade has become a new paradigm in cancer treatment. Despite its efficacy, it has also given rise to a new class of adverse events, immune-related adverse events, which may affect any organ, including the thyroid and the pituitary. Case presentation We present a case of a 77-year-old Caucasian man with metastatic renal cell carcinoma on immunotherapy treatment who was admitted to our hospital with a severe persistent headache of sudden onset. He had been on corticosteroid therapy for 10 days for suspected immune-related thyroiditis. The patient had tachycardia and mild diarrhea, and his thyroid function tests were compatible with subclinical hyperthyroidism with a suppressed thyroid-stimulating hormone level of 0.01 μIU/ml (0.4–4.5), a raised free T4 level of 2.17 ng/dl (0.7–1.9), and a free T3 level of 4.66 pg/ml (2.27–5). Computed tomography and magnetic resonance imaging revealed an enlargement of the pituitary gland compatible with macroadenoma. In the face of a probable immune-related hypophysitis, high-dose corticosteroid treatment was started. A posterior hormonal evaluation revealed secondary hypothyroidism with a suppressed thyroid-stimulating hormone level of 0.11 μIU/ml (0.4–4.5) and low thyroid hormones, a normal free T4 level of 1.02 ng/dl (0.7–1.9), and a low free T3 level of 1.53 pg/ml (2.27–5). These new findings suggested central hypothyroidism possibly due to pituitary apoplexy as a complication of the macroadenoma. Therefore, levothyroxine substitution was started along with the previously started corticosteroid therapy. The patient’s headache and asthenia gradually resolved, and after a few days, he was released from the hospital with levothyroxine substitution and corticosteroid tapering. Conclusions This case emphasizes the importance of the differential diagnosis when dealing with patients on immune checkpoint inhibitors because other non-immune-related events may present. Our patient was finally diagnosed with immune-related hyperthyroidism and a concurrent pituitary macroadenoma. This case also highlights the importance of a prompt start of corticosteroid therapy once immune-related adverse events such as hypophysitis are suspected, because otherwise the outcome would be fatal.

Although hematological abnormalities have been described among patients with influenza virus infection, little is known about their impact on the outcome of the patients. The aim of this study was to assess the frequency and clinical impact of severe hematological abnormalities in patients with confirmed influenza virus infection. This was an observational retrospective study including all adult patients with diagnosis of influenza virus infection hospitalized from January to May 2016 in our institution. Influenza virus infection was diagnosed by means of rRT-PCR assay performed on respiratory samples. Poor outcome was defined as a composite endpoint in which at least one of the following criteria had to be fulfilled: (a) respiratory failure, (b) SOFA ≥2, or (c) death. Two hundred thirty-nine patients were included. Applying the HLH-04 criteria for the diagnosis of hemophagocytic syndrome, cytopenias (hemoglobin ≤9 g/dl, platelets 225 U/l (OR:4.45; CI:1–19.71, p=0.049). Hematological abnormalities are not uncommon among hospitalized patients with influenza virus infection, and they are associated with a poorer outcome.

Resumen Antecedentes y objetivo La hemophagocytic lymphohistiocytosis (HLH, «linfohistiocitosis hemofagocitica») es una entidad grave, producida por una incorrecta regulacion de la respuesta inmunologica frente a diversos estimulos del sistema inmunitario. Su diagnostico y tratamiento precoz suponen un reto para el clinico. Pacientes y metodo Hemos realizado un estudio descriptivo retrospectivo de los pacientes adultos diagnosticados de HLH, segun los criterios de la Histiocyte Society, entre los anos 2010 y 2015 en nuestra institucion, analizando sus caracteristicas clinicas, el estudio diagnostico-etiologico y su evolucion. Resultados Se analizaron 18 pacientes. La mediana de tiempo al diagnostico fue de 24 dias. La etiologia fue neoplasica en 8 casos (hematologica en 7), infecciosa en 6 (leishmaniasis visceral en 4), inflamatoria en uno, y en los 3 restantes, idiopatica. Se realizo tratamiento en 16 pacientes con corticoides, asociando ciclosporina en 2, inmunoglobulinas en uno, y etoposido con tacrolimus en otro. Conclusiones Destacamos la escasa utilizacion de etoposido en el tratamiento dirigido, el actualmente recomendado. La mortalidad global fue del 44%, asociada a la etiologia neoplasica principalmente (67 frente a 16,6% de mortalidad en la etiologia infecciosa, p

There is increasing evidence that ferritin is a key marker of macrophage activation, but its potential role in influenza infection remains unexplored. Our aim was to assess whether hyperferritinaemia (ferritin ≥500 ng/mL) could be a marker of poor prognosis in hospitalized patients with confirmed influenza A infection.We prospectively recruited all hospitalized adult patients who tested positive for the influenza A rRT-PCR assay performed on respiratory samples in two consecutive influenza periods (2016-17 and 2017-18). Poor outcome was defined as the presence of at least one of the following: respiratory failure, admission to the intensive care unit, or in-hospital mortality.Among 494 patients, 68 (14%) developed poor outcomes; 112 patients (23%) had hyperferritinaemia (39/68, 57% in the poor-outcome group versus 73/426, 17% in the remaining patients, p 0.0001). Median serum ferritin levels were significantly higher in the subgroup of patients with poor outcomes (609 ng/mL, range 231-967 versus 217 ng/mL, range 140-394, p 0.0001). In multivariate analysis, hyperferritinaemia was associated with a five-fold increase in the odds ratio of developing poor outcome. After adjusting for classic influenza risk factors, ferritin remained as a significant predictive factor in all exploratory models. Ferritin levels had a good discriminative capacity with an area under the ROC curve of 0.72 (95% confidence interval (CI) 0.65-0.8, p 0.001) and an overall diagnostic accuracy for predicting poor outcome of 79.3% (95%CI 75.4-82.7%).Serum ferritin may discriminate a subgroup of patients with influenza infection who have a higher risk of developing a poor outcome.

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.

Objective: To characterize the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically guided multivariable model. Patients and Methods: The Spanish Group of Autoimmune Diseases HLH Study Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed in internal medicine departments between January 3, 2013, and October 28, 2017. Results: The cohort consisted of 151 patients (91 men; mean age, 51.4 years). After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (P

Objectives To characterise the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically-guided multivariate model. Methods The HLH Study Group of the Spanish Group of Autoimmune Diseases (GEAS) was formed in 2013 with the aim of collecting a large series of Spanish adult patients with HLH with substantial experience in the management of patients with systemic diseases. By October 2017, the database included 151 consecutive patients who fulfilled at least 5 of the 8 criteria proposed by the Histiocytosis Society in 2004. Results The cohort consisted of 151 patients (91 male, mean age 51.4 years). After a mean follow-up of 17 months, 80 (53%) patients died. With respect to the HLH-dependent variables, adenopathies (HR 0.63, p=0.040), low platelets (HR 3.39, p=0.008), leukopenia (HR 1.81, p=0.047), severe hyponatremia (HR 1.61, p=0.042), disseminated intravascular coagulation (HR 1.87, p=0.034), bacterial infection (HR 1.99, p=0.025), mixed microbiological infections (HR 3.42, p=0.008) and >1 infectious trigger (HR 2.95, p=0.003) were associated with death. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (p 1 (p=0.011) infections and glucocorticoid monotherapy (p=0.021). After adjusting for confounding variables, platelets 1 infectious trigger (HR 3.43) and mixed microbiological infection (HR 2.96) remained significant. Multivariate Cox proportional hazards regression analysis identified >1 infectious trigger (HR 2.60, 95% CI 1.16 to 5.84) as the only variable independently associated with death. Conclusions The mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with >1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation and therapeutic management. Disclosure of Interest None declared

Background The natural history of patients with lung cancer and venous thromboembolism (VTE) has not been consistently evaluated. Methods We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics, time course, and outcomes during anticoagulation of lung cancer patients with acute, symptomatic VTE. Results As of May 2017, a total of 1,725 patients were recruited: 1,208 (70%) presented with pulmonary embolism (PE) and 517 with deep vein thrombosis (DVT). Overall, 865 patients (50%) were diagnosed with cancer Conclusion Active surveillance on early signs and/or symptoms of VTE in patients with recently diagnosed lung cancer and prescription of prophylaxis in those undergoing surgery or during periods of immobilization might likely help prevent VTE better, detect it earlier, and treat it more efficiently.

We sought to determine the risk factors for subsequent bleeding and recurrent venous thromboembolism (VTE) events following isolated noncatheter-associated upper extremity deep venous thrombosis (non-CA-UEDVT) to better inform future treatment decisions for this group of patients.The RIETE registry (Registro Informatizado de Enfermedad TromboEmbólica [Computerized Registry of Patients with Venous Thromboembolism]) is a prospective international registry of patients with objectively confirmed symptomatic VTE. Patients with a symptomatic, isolated, proximal UEDVT from March 2001 through March 2015 were analyzed. Any patient with an indwelling catheter or pacemaker lead at the DVT site and at the time of thrombosis was considered to have a CA-UEDVT and was excluded. Patient and treatment characteristics such as age, gender, comorbidities, VTE risk factors, treatment drug, and duration were collected. Outcomes examined included recurrent DVT, subsequent pulmonary embolism (PE), and hemorrhage. Multivariate analysis was performed using stepwise logistic regression.Of the 1100 patients who met the study criteria, 580 (53%) were male. The mean age of the patients was 50 ± 20 years, and overall patient survival at 1 year was 85%. Recurrent VTE occurred in 59 patients (5.4%). Of these, 46 patients (4%) had recurrent DVT, 10 (0.9%) had a PE following UEDVT diagnosis, and 3 (0.3%) had both. PE was fatal in three patients (0.3%). Bleeding occurred in 50 patients (4.5%), major bleeding in 19 patients (1.7%), and fatal bleeding in 6 patients (0.5%). On multivariate analysis, malignant disease was associated with VTE recurrence (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.04-3.45; P .04), whereas hemorrhage was associated with age (OR, 1.03; 95% CI, 1.01-1.05; P = .002) and malignant disease (OR, 2.53; 95% CI, 1.34-4.76; P .005). Hemorrhage and recurrent VTE were also significantly associated (OR, 2.79; 95% CI, 1.16-6.76; P .03).PE following non-CA-UEDVT is rare. Malignant disease was associated with VTE recurrence. Age and malignant disease were associated with hemorrhage, and VTE recurrence was associated with hemorrhage. Further prospective studies should be undertaken to best determine length of anticoagulation treatment for the varied populations of patients with UEDVT.

Background Social exclusion, experienced by vulnerable people at the margins of society, causes severe health inequity with dramatically increased risks of chronic disease and reductions in life-expectancy. Health services are not designed to meet the complex needs of socially excluded people (SEP). SEP are frequently unintentionally excluded from large observational studies such as household surveys and surveys requiring active participation (Levitas et al, 2007). This lack of data deepens inequity. Social exclusion in Ireland is strongly associated with injecting drug use, a strong risk factor for venous thromboembolism (VTE) (O'Reilly et al, 2015). Although an increased prevalence of VTE in lower socioeconomic groups has been described (Zoller et al, 2012), the impact of social exclusion and marginalisation on VTE has never been characterised in detail. The Registro Informatizado de Enfermedad TromboEmbólica (RIETE Registry) is the world's largest database on patients with VTE. It was commenced in 2001 and continues to collect prospective data on consecutive patients presenting to hospital with acute VTE events. Patients are followed longitudinally, for a minimum of three months (Bikdeli et al, 2018). One objective of the registry is to provide information on the natural history of VTE - particularly in subgroups of patients who would not usually be recruited to randomised clinical trials. Methods Our group has generated preliminary data (submitted separately to ASH 2019) which demonstrate that people with social exclusion can be identified from large national and international datasets using surrogate identifiers. The RIETE registry already collects several of these data elements that can be used to identify people who are socially excluded: HIV infection (which is strongly associated with injecting drug use), liver disease, chronic alcoholism and chronic psychiatric illness. We adapted the methodology developed in the Irish dataset and interrogated the RIETE registry utilising the available surrogate identifiers. We aimed to estimate the prevalence of social exclusion amongst patients with VTE, and to determine their clinical characteristics, treatment details and outcomes, with the ultimate goal of informing future service-planning and care-provision to this vulnerable group. Results At the time of interrogation of the RIETE registry, 79735 patients with VTE had been enrolled in 24 countries worldwide. Of these, 9211 (12%) met our criteria for SEP due to the presence of one or more of our surrogate identifiers. Of these, 60% presented with pulmonary embolism vs 52% in the non-SEP group (P Major bleeding was more frequent in the SEP group (5.36 vs 3.55 events per 100 patient-years; HR 1.51 (1.35-1.69)), particularly in those with liver disease (8.70 events per 100 patient years) or psychiatric disorders (5.31 per 100 patient years). Death occurred more frequently in the SEP group (17.9 vs 12.0 events per 100 patient years; HR 1.49 (1.40-1.58)), and recurrent VTE occurred most frequently in those with HIV infection (4.31 events per 100 patient-years) and liver disease (4.46 events per 100 patient years, compared with 3.46 in the non-SEP group). Although Vitamin K Antagonists were used for longer term therapy in the majority of both patient groups (50% SEP, 63% non-SEP), the proportion who received low molecular weight heparin was higher in the SEP group (36% vs 26%). This was highest in the HIV infected subgroup, our identifier that best correlates with injecting drug use. Conclusions Social exclusion, as determined by the use of surrogate markers from a large prospective VTE registry, was associated with a higher overall incidence of death and major bleeding in patients treated for VTE. These data highlight the inequities experienced by this vulnerable patient group, demonstrating the need for increased funding for service planning and care provision to better prevent and manage VTE. This can lead to reductions in hospital admissions and costs, but ultimately to the provision of equitable healthcare for SEP. Disclosures Ewins: Bayer: Other: Conference Fees & Travel Expenses; Amgen: Other: Conference Fees & Travel Expenses. Ni Ainle:Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Leo Pharma: Research Funding; Boehringer: Membership on an entity's Board of Directors or advisory committees; Actelion: Research Funding. Ni Cheallaigh:MSD: Other: Travel Expenses; Pfizer: Research Funding.

Patients with liver cirrhosis are not only at increased risk of bleeding, but also may suffer from complications such as venous thromboembolism (VTE). Data are limited about the relative frequency, clinical course, management, and outcomes of VTE in these patients. We used the data from RIETE, a

Background and objective Hemophagocytic lymphohistiocytosis (HLH) is a serious condition, caused by an improper regulation of the immune response to different stimuli of the immune system. Early diagnosis and treatment are a challenge for the clinician. Patients and method We conducted a retrospective study at our institution between 2010 and 2015, of adult patients diagnosed with HLH, in accordance with the criteria of the Histiocyte Society, analysing their clinical characteristics, diagnostic and etiological studies and the outcome. Results Eighteen patients were analysed. Median time to diagnosis was 24 days. We found neoplastic aetiology in 8 cases (7 hematologic), while it was infection-related in 6 (4 visceral leishmaniasis), and an inflammatory disease in one. In the remaining 3, an underlying cause for the HLH was not found. Course of treatment was corticosteroids in 16 patients, associated with cyclosporine in 2 of them, one received immunoglobulins, while another received etoposide with tacrolimus. Conclusions We emphasize the scarce use of etoposide therapy, the currently recommended treatment. Overall mortality was 44%, mainly associated with neoplastic aetiology (67 compared to 16.6% mortality in infection-related aetiology, P

A study was designed to assess the reliability of the serial detection of Aspergillus sp. DNA to diagnose invasive aspergillosis (IA) in patients with febrile neutropenia. Two blood and two serum samples were taken weekly from 83 patients. A total of 2,244 samples were analyzed by real-time quantitative PCR. Twelve (14.4%) patients were diagnosed with IA. Taking two consecutive positive results as the diagnostic criterion, PCR detected 11 cases, with 4 false positives, giving sensitivity, specificity, positive, and negative predictive values of 91.6%, 94.4%, 73.3%, and 98.5%, respectively. On analyzing in conjunction with high-resolution chest tomography (HRCT) and galactomannan (GM) testing, the combination of serial PCR and GM detected 100% of aspergillosis cases, with a positive predictive value of 75.1%. This diagnostic strategy presented, according to CART analysis, a receiver-operator curve with an area under the curve of 0.97 (95% confidence interval, 0.895 to 1.032; P < 0.01), with a relative risk of IA 6.92 times higher than the control population and with predictive success of 95.2%. As regards early diagnosis, the serial detection of Aspergillus DNA took on average 21 days less than HRCT and 68 days less than GM. The serial detection of Aspergillus DNA using real-time quantitative PCR has great diagnostic applicability, which increases when combined with GM quantification.

Introduccion En este estudio se describe un brote nosocomial de gripe en pacientes hematologicos de alto riesgo y su control mediante medidas preventivas y uso de zanamivir. Metodos Se evaluaron 15 pacientes que habian estado en contacto con un paciente con Influenza A. Se realizo cultivo viral del exudado nasofaringeo y se analizaron sus datos epidemiologicos, factores de riesgo y evolucion clinica. Se evaluo la eficacia de las medidas preventivas y del uso de zanamivir para profilaxis y tratamiento precoz de la infeccion gripal. Resultados Incluyendo el caso indice, 7 de 15 pacientes (46,6%) desarrollaron sintomas y en 5 de 7 (71,4%) se aislo el virus Influenza A. Los 8 pacientes restantes permanecieron asintomaticos y no se aislo virus Influenza del exudado nasofaringeo. Se realizo aislamiento de contacto y respiratorio y tratamiento precoz con zanamivir (10 mg/12 h por via inhalada, durante 5 dias) de los pacientes sintomaticos. Solo 1 de 7 pacientes sintomaticos desarrollo insuficiencia respiratoria; el resto tuvo un sindrome gripal de vias respiratorias superiores. No hubo mortalidad asociada. Se uso profilaxis con zanamivir en las mismas dosis en 3 pacientes asintomaticos de alto riesgo. La tolerancia al zanamivir fue buena en todos los pacientes. Desde que se iniciaron las medidas preventivas y el uso de zanamivir no se detectaron nuevos casos de gripe. Conclusion La tasa de ataque en un brote nosocomial de gripe en pacientes inmunodeprimidos puede ser muy elevada. La instauracion precoz de medidas de control junto con la profilaxis y tratamiento precoces con zanamivir permiten el control de estos brotes.

broncoscopia para lavado broncoalveolar (LBA) con fines diagnosticos. Entre las pruebas microbiologicas que se solicitaron destacamos: dos hemocultivos que fueron esteriles; tincion de Gram y cultivo de esputo no valorable por mala calidad de la muestra; antigeno de Legionella pneumophila serogrupo 1 en orina que fue negativo, y antigenemia de citomegalovirus negativa. Se realizo durante el ingreso test de la tuberculina; fue negativo y se procesaron tambien baciloscopias en esputo en tres muestras consecutivas sin evidencia de micobacterias en la tincion Ziehl-Neelsen y con cultivo en medio de Lowenstein-Jensen negativo a las 6 semanas en las mismas. La tincion de Gram en el LBA no detecto la presencia de microorganismos y el cultivo bacteriano fue negativo. Se realizo tambien en el LBA una tincion de plata para Pneumocystis jiroveci, cultivo de virus (adenovirus, influenza, virus respiratorio sincitial y citomegalovirus), baciloscopia y cultivo de micobacterias, asi como examen directo y cultivo de hongos. Todos los resultados fueron negativos. En el tercer dia de ingreso se nos informo de que el cultivo viral del exudado nasofaringeo procesado el primer dia del ingreso, confirma la presencia de virus respiratorio sincitial (VRS). Desde el ingreso y ante los hallazgos en TCAR se inicio tratamiento empirico con cotrimoxazol, cefepima y levofloxacino, todos por via intravenosa. Asi mismo, se anadio Caso clinico

The symptomatic presentation of cerebral schistosomiasis is uncommon. The case of a 25-year-old woman from Equatorial Guinea with headache and seizures secondary to cerebral neuroschistosomiasis, as confirmed by histopathological examination and microbiological study, is presented. A review of the literature on this subject is also provided.

Background There is limited information about clinical consequences of respiratory virus infections (RVI) in solid organ transplant recipients. No prospective epidemiological study has been published previously. Methods We selected a cohort of 152 transplant recipients (cardiac, hepatic and renal transplant recipients). Median time from transplantation was 17 months (range 1-50). They were prospectively followed-up for RVI during 7 months (October to April). Clinical and microbiological evaluation (cell culture, shell vial and polymerase chain reaction technique) of each RVI episode was made. Results We detected 81 RVI (0.91 episodes/patient/year). Complications were detected in 15/81 episodes (18.5%): acute bronchitis (10 cases), pneumonia (three cases; 3.7% of RVI episodes) and bacterial sinusitis (2 cases). In 4 of 81 episodes (5%), patients needed hospitalization. A respiratory virus was isolated in 17 of 68 nasopharyngeal samples (six respiratory syncytial virus, six influenza, four picornavirus, one adenovirus). Fever presented an 83% positive predictive value for the diagnosis of influenza virus infection among those with a positive microbiological isolation. There were no episodes of acute rejection coincidentally with RVI. Only 54% of the subjects had been previously vaccinated against influenza. Conclusions Incidence of RVI among solid organ transplant recipients is similar to general population but complications are higher. A relationship between RVI and rejection was not detected. The rate of influenza vaccination was lower than expected. The presence of fever in a transplant recipient with RVI strongly suggests influenza infection.

Information describing the incidence and clinical characteristics of late infection (LI) in solid organ transplantation (SOT) is scarce. The aim of this study was to define the incidence, clinical characteristics and risk factors for LI (>6 months) as compared with infection in the early period (