One-year cardiovascular outcomes after coronavirus disease 2019: The cardiovascular COVID-19 registry.

BACKGROUND: The long-term cardiovascular (CV) outcomes of COVID-19 have not been fully explored. METHODS: This was an international, multicenter, retrospective cohort study conducted between February and December 2020. Consecutive patients ≥18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 were included. Patients were classified into two cohorts depending on the nasopharyngeal swab result and clinical status: confirmed COVID-19 (positive RT-PCR) and control (without suggestive symptoms and negative RT-PCR). Data were obtained from electronic records, and clinical follow-up was performed at 1-year. The primary outcome was CV death at 1-year. Secondary outcomes included arterial thrombotic events (ATE), venous thromboembolism (VTE), and serious cardiac arrhythmias. An independent clinical event committee adjudicated events. A Cox proportional hazards model adjusted for all baseline characteristics was used for comparing outcomes between groups. A prespecified landmark analysis was performed to assess events during the post-acute phase (31-365 days). RESULTS: A total of 4,427 patients were included: 3,578 (80.8%) in the COVID-19 and 849 (19.2%) control cohorts. At one year, there were no significant differences in the primary endpoint of CV death between the COVID-19 and control cohorts (1.4% vs. 0.8%; HRadj 1.28 [0.56-2.91]; p = 0.555), but there was a higher risk of all-cause death (17.8% vs. 4.0%; HRadj 2.82 [1.99-4.0]; p = 0.001). COVID-19 cohort had higher rates of ATE (2.5% vs. 0.8%, HRadj 2.26 [1.02-4.99]; p = 0.044), VTE (3.7% vs. 0.4%, HRadj 9.33 [2.93-29.70]; p = 0.001), and serious cardiac arrhythmias (2.5% vs. 0.6%, HRadj 3.37 [1.35-8.46]; p = 0.010). During the post-acute phase, there were no significant differences in CV death (0.6% vs. 0.7%; HRadj 0.67 [0.25-1.80]; p = 0.425), but there was a higher risk of deep vein thrombosis (0.6% vs. 0.0%; p = 0.028). Re-hospitalization rate was lower in the COVID-19 cohort compared to the control cohort (13.9% vs. 20.6%; p = 0.001). CONCLUSIONS: At 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death. STUDY REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04359927.

Genetic and phenotypic attributes of splenic marginal zone lymphoma.

Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their underlying genomic abnormalities, pathway signatures, and microenvironment compositions to uncover biomarkers and therapeutic vulnerabilities. We studied 303 SMZL spleen samples collected through the IELSG46 multicenter international study (NCT02945319) by using a multiplatform approach. We carried out genetic and phenotypic analyses, defined self-organized signatures, validated the findings in independent primary tumor metadata and in genetically modified mouse models, and determined correlations with outcome data. We identified 2 prominent genetic clusters in SMZL, termed NNK (58% of cases, harboring NF-κB, NOTCH, and KLF2 modules) and DMT (32% of cases, with DNA-damage response, MAPK, and TLR modules). Genetic aberrations in multiple genes as well as cytogenetic and immunogenetic features distinguished NNK- from DMT-SMZLs. These genetic clusters not only have distinct underpinning biology, as judged by differences in gene-expression signatures, but also different outcomes, with inferior survival in NNK-SMZLs. Digital cytometry and in situ profiling segregated 2 basic types of SMZL immune microenvironments termed immune-suppressive SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and immune-silent SMZL (50% of cases, associated with an immune-excluded phenotype) with distinct mutational and clinical connotations. In summary, we propose a nosology of SMZL that can implement its classification and also aid in the development of rationally targeted treatments.

Severe infections in patients with lymphoproliferative diseases treated with new targeted drugs: A multicentric real-world study.

BACKGROUND: Lymphoid neoplasms treatment has recently been renewed to increase antitumor efficacy and conventional chemotherapies toxicities. Limited data have been published about the infection risk associated with these new drugs, therefore this study analyzes the infectious complications in patients with lymphoproliferative diseases (LPD) treated with monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab, or pembrolizumab), BTK inhibitors (ibrutinib and acalabrutinib), PI3K inhibitors (idelalisib) and BCL2 inhibitors (venetoclax). METHODS: Multicenter retrospective study of 458 LPD patients treated with targeted therapies in real-life setting, in 18 Spanish institutions, from the time of their commercial availability to August 2020. RESULTS: Severe infections incidence was 23% during 17-month median follow-up; cumulative incidence was higher in the first 3-6 months of targeted drug treatment and then decreased. The most frequent etiology was bacterial (54%). Nine (6%) Invasive fungal infections (IFI) were observed, in its majority in chronic lymphocytic leukemia (CLL) patients treated predominantly with ibrutinib. Significant risk factors for severe infection were: severe lymphopenia (p = 0.009, OR 4.7, range 1.3-1.7), combined targeted treatment vs single agent treatment (p = 0.014 OR 2.2 range 1.1-4.2) and previous rituximab (p = 0.03 OR 1.8, range 1.05-3.3). Infection-related mortality was 6%. In 22% of patients with severe infections, definitive discontinuation of the targeted drug was observed. CONCLUSION: A high proportion of patients presented severe infections during follow-up, with non-negligible attributable mortality, but infection incidence is not superior to the one observed during the chemotherapy era. In selected cases with specific risk factors for infection, antimicrobial prophylaxis should be considered.

Clinicobiological Characteristics and Outcomes of Patients with T-Cell Large Granular Lymphocytic Leukemia and Chronic Lymphoproliferative Disorder of Natural Killer Cells from a Single Institution.

T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorder of natural killer (NK) cells are two infrequent diseases characterized by clonal expansions of cytotoxic T lymphocytes and NK cells, respectively. Somatic mutations of STAT3 are involved in the pathogenesis of these entities. We describe the clinicobiological features, mutational status of STAT3/STAT5B, treatment and outcome of 131 patients. Neutropenia was the most frequent finding at diagnosis, followed by anemia. Concurrent hematological disorders were diagnosed in 37% of patients and autoimmune conditions and solid tumors in 17% and 15%, respectively. All patients who needed treatment belonged to the CD8+CD57+ group. Remarkably, patients included in the CD4+ group had a higher association with solid tumors (p = 0.037). STAT3 mutations were found in 17% of patients, mainly Y640F and D661Y mutations. Patients carrying STAT3 mutations more frequently presented with anemia, neutropenia, high LDH, high large granular lymphocyte counts and need for treatment (p = 0.0037). Methotrexate was the most frequently used agent (72% of cases). The overall response rate to all treatments was 50%. The 10-year overall survival of this series was 78%, with no differences according to the mutational status of STAT3. We compared the survival of these patients with the general Spanish population and no differences were found, confirming the indolent nature of these hematological malignancies. Our study further extends findings documented by others on the clinical behavior of the disease and the impact of STAT3, and for the first time analyzes survival compared to a matched general Spanish population.

Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol.

BACKGROUND: Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes. STUDY AND DESIGN: This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee. CONCLUSION: The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19.

Cuidados de Enfermería al inicio de Ventilación Mecánica Invasiva en la Unidad de Cuidados Intensivos / Nursing Care at the beginning of Invasive Mechanical Ventilation in the Intensive Care Unit

La ventilación mecánica es la alternativa terapéutica que sustituye la función ven-tilatoria total o parcial mientras se man-tienen niveles apropiados de PO2 y PCO2 en sangre arterial, con el fin de disminuir el trabajo respiratorio en los pacientes crí-ticos; principalmente los que presentan insuficiencia respiratoria aguda, por lo que se debe conocer cuándo está indicado este medio de soporte vital avanzado; así como los diferentes modos disponibles, los parámetros y alarmas ventilatorios ge-nerales acoplados a una estrategia de ven-tilación protectora para reducir las com-plicaciones que se puedan producir. De esta manera favorecemos la recuperación del paciente. La Gestión de Enfermería es la disciplina de la ciencia del cuidado que aplica el juicio profesional, la planificación, orga-nización, motivación y control de la pro-visión de procesos oportunos, seguros, humanos e integrales que aseguran la continuidad de la atención. El cuidado enfermero en la UAACI, se realiza de manera autónoma y en colaboración con el equipo de salud, se ajusta a las necesi-dades del paciente crítico, brindando ca-lidad y seguridad, en base a instrumentos que nos permiten monitorizar y evaluar la atención.Según la base de datos de la Unidad de Adultos Área de Cuidados Intensivos año 2018 el 51,4% de los pacientes in-gresados necesitaron apoyo ventilatorio invasivo, de los cuales el 72,0% co-rresponden a insuficiencia respiratoria aguda, el porcentaje restante a procedi-mientos programados. El objetivo de esta ruta es la estandari-zación de los Cuidados de Enfermería al inicio de la ventilación mecánica así como describir las fases de interven-ción de la enfermera y las actividades que debe cumplir en cada una de ellas, estableciendo un plan de cuidados para constatar que los objetivos planteados se consigan.

Mechanical ventilation is the thera-peutic alternative that replaces total or partial ventilatory function while maintaining appropriate levels of PO2 and PCO2 in arterial blood, in order to reduce respiratory work in critical pa-tients; mainly those with acute respi-ratory failure, so it should be known when this means of advanced life su-pport is indicated; as well as the diffe-rent modes available, general venti-lation parameters and alarms coupled to a protective ventilation strategy to reduce the complications that may occur. In this way we favor patient re-covery. Nursing Management is the disci-pline of care science that applies pro-fessional judgment, planning, organi-zation, motivation and control of the provision of timely, safe, human and comprehensive processes that ensure continuity of care. The nursing care in the UAACI is carried out autono-mously and in collaboration with the health team, adjusts to the needs of the critical patient, providing quality and safety, based on instruments that allow us to monitor and evaluate the care.According to the database of the Adult Unit Intensive Care Area year 2018, 51.4% of the admitted patients needed invasive ventilatory support, of which 72.0% correspond to acute respiratory failure, the remaining percentage to scheduled procedures.The objective of this route is the stan-dardization of Nursing Care at the be-ginning of mechanical ventilation as well as describing the phases of in-tervention of the nurse and the acti-vities that must be carried out in each of them, establishing a plan of care to verify that the set goals are achieved.