SARS-CoV-2-reactive interferon-γ-producing CD8+ T cells in patients hospitalized with coronavirus disease 2019.

There is limited information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell immune responses in patients with coronavirus disease 2019 (COVID-19). Both CD4+ and CD8+ T cells may be instrumental in resolution of and protection from SARS-CoV-2 infection. Here, we tested 25 hospitalized patients either with microbiologically documented COVID-19 (n = 19) or highly suspected of having the disease (n = 6) for presence of SARS-CoV-2-reactive CD69+ expressing interferon-γ (IFN-γ) producing CD8+ T cells using flow-cytometry for intracellular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS-CoV-2 Spike glycoprotein N-terminal 1 to 643 amino acid sequence and the entire sequence of SARS-CoV-2 M protein were used simultaneously as antigenic stimulus. Ten patients (40%) had detectable responses, displaying frequencies ranging from 0.15 to 2.7% (median of 0.57 cells/µL; range, 0.43-9.98 cells/µL). The detection rate of SARS-CoV-2-reactive IFN-γ CD8+ T cells in patients admitted to intensive care was comparable (P = .28) to the rate in patients hospitalized in other medical wards. No correlation was found between SARS-CoV-2-reactive IFN-γ CD8+ T-cell counts and SARS-CoV-2 S-specific antibody levels. Likewise, no correlation was observed between either SARS-CoV-2-reactive IFN-γ CD8+ T cells or S-specific immunoglobulin G-antibody titers and blood cell count or levels of inflammatory biomarkers. In summary, in this descriptive, preliminary study we showed that SARS-CoV-2-reactive IFN-γ CD8+ T cells can be detected in a non-negligible percentage of patients with moderate to severe forms of COVID-19. Further studies are warranted to determine whether quantitation of these T-cell subsets may provide prognostic information on the clinical course of COVID-19.

Prognostic value of diagnostic scales in community-acquired sepsis mortality at an emergency service. Prognosis in community-adquired sepsis.

OBJECTIVES: To asses the prognostic value of diagnostic scales in mortality of community-adquired sepsis and added value of additional parameters. METHODS: Prospective observational study of patients with community-adquired sepsis in the Emergency Room of University Hospital. The study population were patients presented in the Emergency Room with confirmed infection and practicians sepsis diagnosis. Demographics, triage vital signs, inhaled oxygen fraction, inflammatory markers, biochemistry, all-cause mortality during hospitalization and three months after were recorded. Prognostic value of qSOFA, NEWS, SOFA, SIRS, and amplified scales were calculated by using logistic regression and ROC curves. RESULTS: 201 patients, 54% male, average age 77±11,2 years were included. Sixty-three (31.5%) died during hospitalization and 24 (12%) three months after discharge. At the time of admission vital signs related with in-hospital mortality were Glasgow Coma Scale <13, respiratory rate ≥22 bpm, temperature, oxygen desaturation, high flow oxygen therapy and heart rate. Patients dead in-hospital had lower PaCO2, higher lactate, glucose and creatinine. Greater predictive capacity of the scales, from higher to lower, was: qSOFA, NEWS2, SOFA and SIRS. Amplified scales with lactate >2mg/dl, glucose, blood level >190mg/dl and PaCO2 <35mmHg improved predictive value. CONCLUSION: Amplified-qSOFA and amplified-NEWS2 scales at Emergency Department may offer a better prognostic of septic patients mortality.

Should we look for silent pulmonary embolism in patients with deep venous thrombosis?

BACKGROUND: Asymptomatic or silent pulmonary embolism (S-PE) in patients with deep vein thrombosis has been the focus of numerous publications with the objective of determining the incidence of S-PE and assessing whether its existence has any clinical or therapeutic consequences that outweigh the risks associated with the diagnostic tests performed and the increased healthcare costs. The objectives were to assess the incidence of S-PE using computed tomography angiogram (CTA), to understand the epidemiological factors that might trigger embolism, and to assess whether D-dimer (DD) predicts the existence of S-PE's. METHODS: A prospective and consecutive assessment of 103 hospitalized patients with lower limb DVT in the absence of PE symptoms, using CT scan. DD was quantified before anticoagulation. The risk factors and characteristics of the DVT were studied. A three-year follow-up assessing risk recurrence and clinical outcome was performed. RESULTS: The incidence of S-PE was 66%. In 77% of these cases, the main and lobar pulmonary arteries were affected. Iliac and femoral DVTs most often produced S-PE. ROC curve with a DD value higher than 578 ng/ml provided good sensitivity but low specificity to identify patients with S-PE. Diagnosis entailed higher hospitalization expenses. No significant recurrence rate of thrombotic events was observed in the S-PE group during the follow-up. CONCLUSIONS: The incidence of S-PE in lower-limb DVT is high, but in the absence of symptoms, diagnosis does not appear to be necessary, as there are no short- or long-term clinical or therapeutic consequences.

High miR-126-3p levels associated with cardiovascular events in a general population.

BACKGROUND: Endothelial dysfunction is a forerunner of atherosclerosis, leading to cardiovascular disease, and albuminuria is a marker of endothelial dysfunction. Circulating levels of microRNAs are emerging as potential biomarkers for cardiovascular disease. Here we estimate the predictive value of a plasma microRNAs signature associated with albuminuria in the incidence of cardiovascular events. METHODS: Plasma microRNAs quantified in hypertensive patients by next generation sequencing were validated in a cohort of patients and controls by real-time quantitative PCR. The microRNAs found to be associated with albuminuria were analysed for their prognostic value in predicting cardiovascular events incidence on a retrospective, population-based study (Hortega Study), using Cox proportional hazard models. RESULTS: A plasma microRNA profile was identified in the discovery cohort (n = 48) associated with albuminuria and three microRNAs (miR-126-3p, miR-1260b and miR-374a-5p) were confirmed in the validation cohort (n = 98). The microRNA signature discriminates urinary albumin excretion at baseline (n = 1025), and predicts the incidence of cardiovascular events and coronary heart disease and stroke in a general population retrospective study within a 14-year follow-up (n = 926). High miR-126-3p levels were associated with a shorter time free of both cardiovascular events (HR=1.48, (1.36-1.62), p < 0.0001), as well as coronary artery disease and stroke combined (HR=2.49, (2.19-2.83), p < 0.0001). CONCLUSIONS: An increased plasma microRNAs profile was identified in hypertensive patients with albuminuria. Increased miR-126-3p suggest it may serve as a prognostic marker for cardiovascular events in a long-term general population. Further studies will assess the potential role of miR-126-3p as a guide for the status of endothelial dysfunction.

Real world data of anticoagulant treatment in non-valvular atrial fibrillation across renal function status.

The objective is to assess the impact of anticoagulant treatment in non-valvular atrial fibrillation (AF) and different categories of renal dysfunction in real world. Electronic Health recordings of patients with diagnosis of AF and renal function collected throughout 5 years and classified according to KDIGO categories. Stroke, transitory ischemic attack (TIA), intracranial hemorrhage and all-cause mortality were identified. Anticoagulant treatments during the study period were classified in untreated (never received therapy), VKA, NOAC and Aspirin. The risk of events was calculated by Cox-proportional hazard models adjusted by confounders. A total of 65,734 patients with AF, mean age 73.3 ± 10.49 years old and 47% females and follow-up of 3.2 years were included. KDIGO classification were: G1 33,903 (51.6%), G2 17,456 (26.6%), G3 8024 (12.2%) and G4 6351 (9.7%). There were 8592 cases of stroke and TIA, 437 intracranial hemorrhage, and 9603 all-cause deaths (incidence 36, 2 and 38 per 103 person/year, respectively). 4.1% of patients with CHA2DS2-VASc Score 2 or higher did not receive anticoagulant therapy. Risk of stroke, TIA, and all-cause mortality increased from G1 to G4 groups. Anticoagulant treatments reduced the risk of events in the four categories, but NOAC seemed to offer significantly better protection. Renal dysfunction increases the risk of events in AF and anticoagulant treatments reduced the risk of stroke and all-cause mortality, although NOAC were better than VKA. Efforts should be done to reduce the variability in the use of anticoagulants even in this high risk group.

Incidence and impact of atrial fibrillation in heart failure patients: real-world data in a large community.

AIMS: The objective of the present study is to assess the bidirectional association between heart failure (HF) and atrial fibrillation (AF) using real-world data. METHODS AND RESULTS: From an electronic health recording with a population of 3 799 885 adult subjects, those with prevalent or incident HF were selected and followed throughout a study period of 5 years. Prevalence and incidence of AF, and their impact in the risk for acute HF hospitalization, worsening renal function, ischaemic and haemorrhagic stroke, and all-cause mortality were identified. We analysed all incident and prevalent patients with HF and AF, 128 086 patients (S1), and subsequently analysed a subset of patients with incident HF and AF, 57 354 patients (S2). We analysed all incident and prevalent patients with HF and AF, 128 086 patients (S1), and subsequently a subset of patients with incident HF and AF, 57 354 patients (S2). The prevalence of AF was 59 906 (46.7%) of the HF patients, while incidence in the S2 was 231/1000 patients/year. In both cohorts, S1 and S2, AF significantly increases the risk of acute heart failure hospitalization [incidence 79.1/1000 and 97.5/1000 patients/year; HR 1.53 (1.48-1.59 95% CI) and HR 1.32 (1.24-1.41 95% CI), respectively], risk of decreased renal function (eGFR reduced by >20%) [66.2/1000 and 94.0/1000 patients/year; HR 1.13 (1.09-1.18 95% CI) and HR 1.22 (1.14-1.31 95% CI), respectively] and all-cause mortality [203/1000 and 294/1000 patients/year; HR 1.62 (1.58-1.65 95% CI) and HR 1.65 (1.59-1.70 95% CI), respectively]. The number of episodes of hospitalization for acute heart failure was also significantly higher in the AF patients (27 623 vs. 10 036, P < 0.001). However, the risk for ischaemic stroke was reduced in the AF subjects [HR 0.66 (0.63-0.74 95% CI)], probably due to the anticoagulant treatment. CONCLUSIONS: AF is associated with an increment in the risk of episodes of acute heart failure as well as decline of renal function and increment of all-cause mortality.

Infective Endocarditis in the Elderly: Challenges and Strategies.

The specific management of infective endocarditis (IE) in elderly patients is not specifically addressed in recent guidelines despite its increasing incidence and high mortality in this population. The term "elderly" corresponds to different ages in the literature, but it is defined by considerable comorbidity and heterogeneity. Cancer incidence, specifically colorectal cancer, is increased in older patients with IE and impacts its outcome. Diagnosis of IE in elderly patients is challenging due to the atypical presentation of the disease and the lower performance of imaging studies. Enterococcal etiology is more frequent than in younger patients. Antibiotic treatment should prioritize diminishing adverse effects and drug interactions while maintaining the best efficacy, as surgical treatment is less commonly performed in this population due to the high surgical risk. The global assessment of elderly patients with IE, with particular attention to frailty and geriatric profiles, should be performed by multidisciplinary teams to improve disease management in this population.

Immunoglobulin G4-Related Aortitis and Severe Aortic Valve Stenosis Treated With Transcatheter Aortic Valve Replacement and Immunosuppression.

IgG4-related disease is an immune-mediated fibro-inflammatory disorder with multisystemic involvement. Aortitis and peri-aortitis are the most common cardiovascular manifestations of the disease. We present the case of a 65-year-old man with symptomatic severe aortic stenosis and concomitant IgG4 aortitis. The diagnosis was confirmed by IgG4 serum levels, positive positron emission computed tomography (PET-CT) scans, and pathology from mediastinal dissection. Surgical aortic valve replacement (SAVR) was unfeasible owing to extensive mediastinal fibrosis, and transcatheter aortic valve replacement (TAVR) was successfully performed. As ascending aorta access for SAVR in IgG4 aortitis with long-run fibrosis entails a high risk of mortality, TAVR could be considered in certain suitable patients.

Real-World Data of Anticoagulant Treatment in Non-valvular Atrial Fibrillation.

AIMS: To assess the impact of anticoagulant treatment on risk for stroke and all-cause mortality of patients with atrial fibrillation using real-world data (RWD). METHODS: Patients with prevalent or incident atrial fibrillation were selected throughout a study period of 5 years. Stroke, transitory ischemic attack, hemorrhagic stroke, and all-cause mortality were identified in the claims of the electronic health records (EHRs). Subjects were classified according to the anticoagulant treatment in four groups: untreated, vitamin K antagonists (VKAs), New Oral Anticoagulants (NOACs), and antiplatelet (AP). Risk of events and protection with anticoagulant therapy were calculated by Cox proportional hazard models adjusted by potential confounders. RESULTS: From a total population of 3,799,884 patients older than 18,123,227 patients with incident or prevalent atrial fibrillation (AF) were identified (mean age 75.2 ± 11.5 years old; 51.9% women). In a follow-up average of 3.2 years, 17,113 patients suffered from an ischemic stroke and transitory ischemic attack (TIA), 780 hemorrhagic stroke, and 42,558 all-cause death (incidence of 46, 8, 2, and 120 per 1,000 patients/year, respectively). Among CHA2DS2, VASc Score equal or >2, 11.7% of patients did not receive any anticoagulant therapy, and a large proportion of patients, 47%, shifted from one treatment to another. Although all kinds of anticoagulant treatments were significantly protective against the events and mortality, NOAC treatment offered significantly better protection compared to the other groups. CONCLUSION: In the real world, the use of anticoagulant treatments is far from guidelines recommendations and is characterized by variability in their use. NOACs offered better protection compared with VKAs.

Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome: Etiopathogenically Driven Analysis.

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<.001), mixed microbiological infections (P=.02), and more than 1 infection (P=.01) and glucocorticoid monotherapy (P=.02). According to univariate analyses, platelets of less than 100,000/mm3 (hazard ratio [HR], 3.39; 95% CI, 1.37-8.40), leukopenia (HR, 1.81; 95% CI, 1.01-3.23), severe hyponatremia (HR, 1.61; 95% CI, 1.02-2.54), disseminated intravascular coagulation (HR, 1.87; 95% CI, 1.05-3.34), bacterial infection (HR, 1.99; 95% CI, 1.09-3.63), mixed microbiological infections (HR, 3.42; 95% CI, 1.38-8.46), and 2 or more infectious triggers (HR, 2.95; 95% CI, 1.43-6.08) were significantly associated with death. In contrast, peripheral adenopathies (HR, 0.63; 95% CI, 0.40-0.98) and the immunosuppressive drug/intravenous immunoglobulin/biological therapies (HR, 0.44; 95% CI, 0.20-0.96) were protective against all-cause mortality. Multivariable Cox proportional hazards regression analysis identified 2 or more infectious triggers (HR, 3.14; 95% CI, 1.28-7.68) as the only variable independently associated with death. CONCLUSION: The mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with more than 1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation, and therapeutic management.

[Factors related to the risk of thrombosis in patients with lupus and antiphospholipid antibodies]. / Factores relacionados con el riesgo de trombosis en pacientes con lupus y positividad para anticuerpos antifosfolipídicos.

BACKGROUND AND OBJECTIVE: Antiphospholipid antibodies (aPL) are frequently associated with eritematosus systemic lupus (SLE) and increases the risk of thrombosis. The aim of the study was to analize risk factors of thrombosis and its temporal profile in subjects with SLE. PATIENTS AND METHOD: One hundred and two SLE patients -mean age: 37.5 years (range: 8-85); 90 women; mean of follow-up: 72 months (range: 9-324); 41 (40.2%) with aPL positive- were included in the study. Actuarial Kaplan-Meier curves were used to assess the thrombosis risk and Cox proportional hazard model was used to evaluate factors associated with the risk. RESULTS: 13 thrombotic events occurred in the group with aPL positive (mean of follow up: 83.5 months) and 5 events in aPL negative group (mean of follow up: 72 months). The event-rates were 3.93 and 0.96/100 patients/year for each group, respectively. Survival curves showed a significantly higher risk of thrombotic events in the patients with positive aPL as compared to the aPL negative group, and the risk still present throughout the observational time. Activated partial thromboplastine time up to 37 s was significantly associated with thrombosis risk (p = 0.003). Furthermore, positivity of lupus anticoagulant and proteinuria > 2.5 g/day tended to increase thrombotic risk, although they did not achieve statistical significance. CONCLUSIONS: In patients with SLE and aPL, risk of first thrombosis remains over the years, and a large activated partial thromboplastine time was the most important risk factor.

[Factors related to the differences in blood pressure values assessed by auscultatory or oscillometric methods]. / Factores que influyen en la diferencia de medida de presión arterial entre el método auscultatorio y el oscilométrico.

BACKGROUND AND OBJECTIVE: Measurement of blood pressure by using the auscultatory method coupled with mercury sphygmomanometer is rapidly being replaced for monitor using the oscillometric one. Discrepancies between the two methods and the factors related to them were analyzed in a large subset of adults. MATERIAL AND METHOD: Blood pressure values were obtained sequentially in the same arm by using a mercury sphygmomanometer and a Spacelabs monitor devices. The relationship between both kinds of measurements was assessed by the Pearson's correlation coefficients and the concordance by using the Bland and Altman method. Differences between the two methods were calculated and the factors related to the differences were sought by multiple regression models. RESULTS: A total of 1,742 adult subjects were analyzed. Pearson's correlation coefficients were 0.927, 0.922, 0.886, 0.962 for SBP, DBP, MBP and PR, respectively. Oscillometric method overestimate and infraestimate SBP values in the two extreme of SBP values, the lowest SBP the highest the values and vice versa. A similar trend was observed for DBP although the differences were minor. Pulse wave amplitude explains the 24% of the variance observed for SBP and arm circumference the 8% for DBP. CONCLUSIONS: Blood pressure values measured by oscillometric methods are influenced for pulse wave amplitude and by the arm circumference. These need to be taken in account when blood pressure assessment is obtained by using this method.

Reversible posterior leukoencephalopathy secondary to indinavir-induced hypertensive crisis: a case report.

Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon entity related to multiple and different pathologies, the most common being hypertensive crisis. It is believed to be secondary to the breakdown on the blood-brain barrier. At the beginning, it is undistinguishable from other leukoencephalopathies. However, the disappearance of brain lesions after removal of the potential cause, establish the differential diagnosis with other leukoencephalopathies. We present the case of an HIV-infected patient with a RPLS related to a hypertensive crisis short after the initiation of indinavir-containing highly active antiretroviral therapy. Once blood pressure was controlled and indinavir replaced by nelfinavir, white matter lesions at magnetic resonance imaging disappeared. The clinical and radiologic evolution excludes other diagnosis as progressive multifocal leukoencephalopathy and points indinavir as a potential hypertension-inducing agent in HIV-infected predisposed subjects.

[Risk factors and clinical characteristics of thromboembolic venous disease in young patients: a prospective study]. / Estudio prospectivo de los factores de riesgo y las características clínicas de la enfermedad tromboembólica en pacientes jóvenes.

BACKGROUND AND OBJECTIVE: We aimed to determine the risk factors of thromboembolic disease in young patients and to study the clinical characteristics according to the etiology. PATIENTS AND METHOD: A prospective study of 100 patients under 50 years who were not affected by neoplasias or chronic diseases and who required hospitalization due to thromboembolic disease. The morphological diagnosis was performed by eco-Doppler, flebography, lung gammagraphy or CT scan. Risk factors assessed were antithrombin, protein C and S deficiency, presence of factor V Leiden, prothrombin G20210A, hyperhomocisteinemia, increased PAI-I, increased factor VIII, and presence of antiphospholipid antibodies (APAs). Acquired factors were also evaluated. RESULTS: In 87% of patients, a venous thrombosis was observed in lower limbs. 37% of patients had congenital risk factors and 19% had APAs, whereas in the remaining patients only acquired factors were demonstrated. Most frequent congenital factors were factor V Leiden, pothrombin G20210A, and protein C and S deficiency. Most patients presented several risk factors. A family thrombotic history was significantly more frequent in the group with congenital risk factors. CONCLUSIONS: In 56% of young patients with thromboembolic disease, a congenital etiology or APAs are identified. In these patients the number of acquired factors needed to trigger thrombosis is fewer than in patients in whom a cause is not identified.

[Renal involvement in the human immunodeficiency virus infection]. / Alteración renal en la infección por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: Although renal pathologies are becoming an emergent problem in the population infected by the human immunodeficiency virus (HIV), there is very scarce information about the natural course of this problem. The objective of the present study is to describe renal lesions in an autopsy series of HIV-infected patients never treated with antiretroviral therapies. PATIENTS AND METHOD: Autopsy information has been retrospectively retrieved from 61 HIV-infected subjects (mean age, 36,9 [8,4] years; 58,6% drug abusers, 84% males) died in our hospital between 1984 and 1997. None of the patients received antiretroviral therapy. All autopsy and clinical reports were considered, as well as basic analytical parameters about renal function. Renal autopsy samples were specifically reviewed. RESULTS: At the time of the last admission, 9.8% of patients had renal insufficiency, who made up 44.3% of patients having renal insufficiency anytime. Infections were the main cause of death (76%). The majority of patients (93.4%) showed histopathological renal abnormalities, which were highly heterogeneous. Renal lesions were mainly located on the tubules (96.7%) and the interstitium (60.7%). Moreover, glomeruli were affected in 55.7% of patients. Most frequent histopathological diagnosis was acute tubular necrosis (16.4%) and septic nephritic abscesses (16.4%), followed by tubulointerstitial nephritis (9%). HIV-associated nephropathy was present in two patients (3.3%). There were no significant differences when considering the existent of renal failure. CONCLUSIONS: Renal histological abnormalities are frequent in the natural evolution of HIV infection. There is an important heterogeneity of lesions, mainly involving tubules, interstitium and mesangium. The cause of renal lesions is predominantly septic, according to the chief systemic process. It does not exist any relationship between renal analytical parameters and the presence of renal damage.

Long-term prospective study of recurrent venous thromboembolism in patients younger than 50 years.

Long-term incidence of recurrent venous thromboembolism (VTE) in patients younger than 50 years, not affected by a malignancy or chronic diseases, are poorly characterized. After the initial episode of VTE and cessation of oral anticoagulation, 98 patients, mean age 32.2+/-9.2 years were followed for a median of 117 months (range 6-165). Congenital risk factors for VTE were present in 36% of patients, acquired persistent (positive antiphospholipid antibodies during the whole follow-up) in 19%, and acquired transitory in 44%. Thirty episodes of recurrent VTE were documented. The cumulative incidence of VTE after 1 year of follow-up was 5.1%, 9.8% after 2 years, 14% after 4 years, and 34.2% after 8 years. In the univariate analysis, the relative risk of recurrent VTE was 2.66 [95% confidence interval (CI) 1.03-6.90] for congenital risk factors, 4.97 (95% CI 1.75-14.0) for persistent acquired (antiphospholipid antibodies), 2.64 (95% CI 1.23-5.66) for male gender and 2.27(1.00-5.15) for body mass index>30 kg/m2. In the multivariate analysis, male gender [hazard ratio (HR) 4.23, 95% CI 1.88-9.77) the presence of congenital factors (HR 3.28, 95% CI 1.25-8.63) and acquired persistent factors (HR 8.50, 95% CI 2.84-25.50) were independent risk factors for recurrent VTE. In patients under 50 years of age without malignancy or underlying chronic disease, hospitalized for an acute thromboembolic event, the presence of antiphospholipid antibodies, congenital defects of coagulation, male sex, and obesity were risk factors for recurrent VTE. These data raise the possibility that selected patients with VTE may require prolonged anticoagulation to prevent recurrent disease.