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Hospitalized patients with COVID-19 are at increased risk of thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. The aim was to evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. PROTHROMCOVID is a randomized, unblinded, controlled, multicenter trial enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) groups. All tinzaparin doses were administered once daily during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days. Of the 311 subjects randomized, 300 were included in the prespecified interim analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]). The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (p = 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences. Due to these results and the futility analysis, the trial was stopped. In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to affect the risk of thrombotic event, non-invasive ventilation, or mechanical ventilation or death. Trial RegistrationClinicalTrials.gov Identifier (NCT04730856). Edura-CT registration number: 2020-004279-42.

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90‐day and 1‐year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90‐day all‐cause (odds ratio [OR], 2.81; 95% CI, 2.33–3.38) and PE‐related mortality (OR, 2.38; 95% CI, 1.37–4.14) and increased 1‐year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10–9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all‐cause mortality (OR, 1.91; 95% CI, 1.57–2.32) but not PE‐related mortality (OR, 1.50; 95% CI, 0.85–2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90‐day all‐cause (OR, 2.28; 95% CI, 1.75–2.97) and PE‐related (OR, 3.64; 95% CI, 2.01–6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.

Objetivo: evaluar la incidencia de eventos trombóticos, sangrado y mortalidad comparando diferentes regímenes de anticoagulación en pacientes ingresados en unidades de cuidados intensivos (UCI) por COVID-19. Diseño: Estudio de cohortes retrospectivo observacional y analítico. Ámbito: pacientes con COVID-19 ingresados en una UCI de un hospital terciario entre marzo y abril de 2020. Pacientes: se incluyeron un total de 201 pacientes de UCI ingresados por COVID-19. Los pacientes se categorizaron en 3 grupos en función de la dosis de anticoagulación más alta recibida durante el ingreso: profiláctica, intermedia y terapéutica. Intervenciones: se comparó la incidencia de eventos trombóticos, hemorragia y mortalidad entre los grupos. Se realizaron dos regresiones logísticas multivariables para comprobar la asociación entre los eventos trombóticos y el sangrado con el régimen anticoagulante. Principales variables de interés: eventos trombóticos, sangrado y mortalidad. Resultados: de los pacientes incluidos, 78 recibieron dosis profilácticas, 94 intermedias y 29 terapéuticas. No se encontraron diferencias en los eventos trombóticos y la mortalidad entre grupos, mientras que los sangrados fueron más frecuentes en el grupo de dosis terapéutica (31%) e intermedia (15%) que en el grupo de dosis profiláctica (5%) (p

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.

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Despite well established clinical guidelines, performance of long-term oxygen therapy (LTOT) programs shows marked variability among territories. The current study assessed the LTOT program and the health status of patients on LTOT prior to the deployment of community-based integrated care in an urban health district of Barcelona (Spain).To assess: i) the LTOT program and health status of the patients on LTOT in the health district; ii) their frailty profile; and, iii) the requirements for effective deployment of integrated care services for these patients.Cross-sectional observational study design including all patients (n = 406) on LTOT living in the health district. Health status, frailty, arterial blood gases, forced spirometry and hand-grip muscle strength were measured. Network analysis of frailty was carried out.Adequacy of LTOT prescription (n = 362): 47% and 31% of the patients had PaO2 ≤ 60 mmHg and ≤55 mmHg, respectively. Adherence to LTOT: 31% of all patients used LTOT ≥15 h/d; this figure increased to 67% in those with PaO2≤60 mmHg. Assessment of frailty: Overall, LTOT patients presented moderate to severe frailty. Care complexity was observed in 42% of the patients.Adequacy and adherence to LTOT was poor and many patients were frail and complex. The outcomes of the network analysis may contribute to enhance assessment of frailty in LTOT patients. These observations suggest that an integrated care strategy has the potential to improve the health outcomes of these patients.

Gene polymorphisms, giving rise to low serum levels of mannose-binding lectin (MBL) or MBL-associated protease 2 (MASP2), have been associated with an increased risk of infections. The objective of this study was to assess the outcome of intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS) regarding the existence of functionally relevant MBL2 and MASP2 gene polymorphisms. The study included 243 ICU patients with SIRS admitted to our hospital, as well as 104 healthy control subjects. MBL2 and MASP2 single nucleotide polymorphisms were genotyped using a sequence-based typing technique. No differences were observed regarding the frequencies of low-MBL genotypes (O/O and XA/O) and MASP2 polymorphisms between patients with SIRS and healthy controls. Interestingly, ICU patients with a noninfectious SIRS had a lower frequency for low-MBL genotypes and a higher frequency for high-MBL genotypes (A/A and A/XA) than either ICU patients with an infectious SIRS or healthy controls. The existence of low- or / high-MBL genotypes or a MASP2 polymorphism had no impact on the mortality rates of the included patients. The presence of high-MBL-producing genotypes in patients with a noninfectious insult is a risk factor for SIRS and ICU admission. Sepsis is the main cause of death in intensive care units (ICU), with mortality rates above 50% in patients with septic shock (54). Increasing evidence suggests that variations in genes encoding different components of the immune system influence an individual’s capacity to respond adequately to infections. Genetic polymorphisms of several molecules of the innate immune system, such as tumor necrosis factor alpha (TNF-) (35), interleukin-1 receptor antagonist (IL-1RA) (2), and more recently plasminogen activator inhibitor 1 (PAI-1) (12), have been associated with increased mortality in patients with severe sepsis and septic shock. The mannose-binding lectin (MBL) is an important element of the innate immune defense system. The MBL is a circulating C-type plasma lectin, mainly produced by the liver, which binds to the specific carbohydrates present on the surface of different microorganisms (21, 38). In serum, MBL is present as oligomers (mainly trimers and tetramers) bound to the MBL-associated serine proteases (MASPs, which are also produced in the liver), mainly MASP2. Once bound to the carbohydrate residues, the MBL/MASP2 complex acts as an opsonin for phagocytosis for numerous pathogens and activates comple

Severe imported malaria is an important problem in many countries in which this disease is not endemic. This retrospective study describes the characteristics of 20 adults with severe imported malaria admitted to our intensive care unit from 1991 through 2007. All episodes were caused by Plasmodium falciparum and all patients had returned from sub-Saharan Africa, except for one transfusion recipient. All persons were considered non-immune, and none had taken appropriate chemoprophylaxis. The median time between the initiation of symptoms and the diagnosis was seven days. Five patients died (mortality rate = 25%). A higher frequency of unrousable coma and acidosis and a higher median Apache II score at admission was noted in the persons who died. Mortality by severe malaria remains high despite high quality management, which highlights the importance of chemoprophylaxis and early diagnosis and treatment.

Purpose Decreased ADAMTS-13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) seems to be associated with a poor prognosis in sepsis. However, its role in different septic syndromes and other causes of systemic inflammatory response syndrome (SIRS) remains unclear. The aims of this study were to assess ADAMTS-13 levels in patients with septic syndromes or noninfectious SIRS and to determine their association with morbidity and mortality. Methods The study population consisted of 178 patients admitted to the medical intensive care unit presenting either septic syndromes or noninfectious SIRS. ADAMTS-13 levels were analyzed. Results Patients with septic syndromes showed significantly lower levels of ADAMTS-13 compared with those with noninfectious SIRS (P = 0.014). Patients with severe sepsis or septic shock presented lower levels than those of patients with sepsis (P = 0.086). A significant negative correlation was found between ADAMTS-13 levels and delta Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores at admission in the septic patients. Patients who died had significantly lower levels of ADAMTS-13 compared with survivors, both in the whole population and among the septic patients (P = 0.002 and P = 0.009, respectively). Logistic regression analysis showed that decreased ADAMTS-13 levels were associated with an increased risk of in-intensive care unit mortality (odds ratio, 0.985; 95% confidence interval, 0.973-0.998; P = 0.023). Conclusions Septic patients have lower levels of ADAMTS-13 than do patients with noninfectious SIRS. Levels of ADAMTS-13 are correlated with illness severity in patients with septic syndromes. ADAMTS-13 levels were associated with an increased risk of mortality in critically ill patients with SIRS especially those with septic syndromes.