Factors associated with pulmonary infection in kidney and kidney-pancreas transplant recipients: a case-control study.

OBJECTIVE: To evaluate the etiology of and factors associated with pulmonary infection in kidney and kidney-pancreas transplant recipients. METHODS: This was a single-center case-control study conducted between December of 2017 and March of 2020 at a referral center for kidney transplantation in the city of Belo Horizonte, Brazil. The case:control ratio was 1:1.8. Cases included kidney or kidney-pancreas transplant recipients hospitalized with pulmonary infection. Controls included kidney or kidney-pancreas transplant recipients without pulmonary infection and matched to cases for sex, age group, and donor type (living or deceased). RESULTS: A total of 197 patients were included in the study. Of those, 70 were cases and 127 were controls. The mean age was 55 years (for cases) and 53 years (for controls), with a predominance of males. Corticosteroid use, bronchiectasis, and being overweight were associated with pulmonary infection risk in the multivariate logistic regression model. The most common etiologic agent of infection was cytomegalovirus (in 14.3% of the cases), followed by Mycobacterium tuberculosis (in 10%), Histoplasma capsulatum (in 7.1%), and Pseudomonas aeruginosa (in 7.1%). CONCLUSIONS: Corticosteroid use, bronchiectasis, and being overweight appear to be risk factors for pulmonary infection in kidney/kidney-pancreas transplant recipients, endemic mycoses being prevalent in this population. Appropriate planning and follow-up play an important role in identifying kidney and kidney-pancreas transplant recipients at risk of pulmonary infection.

Factors associated with pulmonary infection in kidney and kidney-pancreas transplant recipients: a case-control study / Fatores associados a infecção pulmonar em pacientes que receberam transplante de rim ou rim-pâncreas: estudo de caso-controle

ABSTRACT Objective: To evaluate the etiology of and factors associated with pulmonary infection in kidney and kidney-pancreas transplant recipients. Methods: This was a single-center case-control study conducted between December of 2017 and March of 2020 at a referral center for kidney transplantation in the city of Belo Horizonte, Brazil. The case:control ratio was 1:1.8. Cases included kidney or kidney-pancreas transplant recipients hospitalized with pulmonary infection. Controls included kidney or kidney-pancreas transplant recipients without pulmonary infection and matched to cases for sex, age group, and donor type (living or deceased). Results: A total of 197 patients were included in the study. Of those, 70 were cases and 127 were controls. The mean age was 55 years (for cases) and 53 years (for controls), with a predominance of males. Corticosteroid use, bronchiectasis, and being overweight were associated with pulmonary infection risk in the multivariate logistic regression model. The most common etiologic agent of infection was cytomegalovirus (in 14.3% of the cases), followed by Mycobacterium tuberculosis (in 10%), Histoplasma capsulatum (in 7.1%), and Pseudomonas aeruginosa (in 7.1%). Conclusions: Corticosteroid use, bronchiectasis, and being overweight appear to be risk factors for pulmonary infection in kidney/kidney-pancreas transplant recipients, endemic mycoses being prevalent in this population. Appropriate planning and follow-up play an important role in identifying kidney and kidney-pancreas transplant recipients at risk of pulmonary infection.

RESUMO Objetivo: Avaliar a etiologia da infecção pulmonar e os fatores a ela associados em pacientes que receberam transplante de rim ou rim-pâncreas. Métodos: Estudo unicêntrico de caso-controle realizado entre dezembro de 2017 e março de 2020 em um centro de referência em transplantes de rim em Belo Horizonte (MG). A proporção caso:controle foi de 1:1,8. Os casos foram pacientes que haviam recebido transplante de rim ou rim-pâncreas e que foram hospitalizados em virtude de infecção pulmonar. Os controles foram pacientes que haviam recebido transplante de rim ou rim-pâncreas e que não apresentaram infecção pulmonar, emparelhados com os casos pelo sexo, faixa etária e tipo de doador (vivo ou falecido). Resultados: Foram incluídos no estudo 197 pacientes. Destes, 70 eram casos e 127 eram controles. A média de idade foi de 55 anos (casos) e 53 anos (controles), com predomínio de pacientes do sexo masculino. O uso de corticosteroides, bronquiectasias e sobrepeso relacionaram-se com risco de infecção pulmonar no modelo de regressão logística multivariada. O agente etiológico de infecção mais comum foi o citomegalovírus (em 14,3% dos casos), seguido de Mycobacterium tuberculosis (em 10%), Histoplasma capsulatum (em 7,1%) e Pseudomonas aeruginosa (em 7,1%). Conclusões: O uso de corticosteroides, bronquiectasias e sobrepeso parecem ser fatores de risco de infecção pulmonar em pacientes que receberam transplante de rim ou rim-pâncreas, e as micoses endêmicas são prevalentes nessa população. O planejamento e acompanhamento adequados desempenham um papel importante na identificação de pacientes transplantados de rim/rim-pâncreas nos quais haja risco de infecção pulmonar.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial

BACKGROUND: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population. METHODS: We did a pragmatic, open-label (with blinded adjudication), multicentre, randomised, controlled trial, at 31 sites in Brazil. Patients (aged ≥18 years) hospitalised with COVID-19 and elevated D-dimer concentration, and who had COVID-19 symptoms for up to 14 days before randomisation, were randomly assigned (1:1) to receive either therapeutic or prophylactic anticoagulation. Therapeutic anticoagulation was in-hospital oral rivaroxaban (20 mg or 15 mg daily) for stable patients, or initial subcutaneous enoxaparin (1 mg/kg twice per day) or intravenous unfractionated heparin (to achieve a 0·3­0·7 IU/mL anti-Xa concentration) for clinically unstable patients, followed by rivaroxaban to day 30. Prophylactic anticoagulation was standard in-hospital enoxaparin or unfractionated heparin. The primary efficacy outcome was a hierarchical analysis of time to death, duration of hospitalisation, or duration of supplemental oxygen to day 30, analysed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding through 30 days. This study is registered with ClinicalTrials.gov (NCT04394377) and is completed. FINDINGS: From June 24, 2020, to Feb 26, 2021, 3331 patients were screened and 615 were randomly allocated (311 [50%] to the therapeutic anticoagulation group and 304 [50%] to the prophylactic anticoagulation group). 576 (94%) were clinically stable and 39 (6%) clinically unstable. One patient, in the therapeutic group, was lost to follow-up because of withdrawal of consent and was not included in the primary analysis. The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation, with 28 899 (34·8%) wins in the therapeutic group and 34 288 (41·3%) in the prophylactic group (win ratio 0·86 [95% CI 0·59­1·22], p=0·40). Consistent results were seen in clinically stable and clinically unstable patients. The primary safety outcome of major or clinically relevant non-major bleeding occurred in 26 (8%) patients assigned therapeutic anticoagulation and seven (2%) assigned prophylactic anticoagulation (relative risk 3·64 [95% CI 1·61­8·27], p=0·0010). Allergic reaction to the study medication occurred in two (1%) patients in the therapeutic anticoagulation group and three (1%) in the prophylactic anticoagulation group. INTERPRETATION: In patients hospitalised with COVID-19 and elevated D-dimer concentration, in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban to day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation. Therefore, use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in these patients in the absence of an evidence-based indication for oral anticoagulation.