Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19: A multicentre case series of 98 patients.

AIMS: To determine the safety and efficacy-potential of inhaled nebulised unfractionated heparin (UFH) in the treatment of hospitalised patients with COVID-19. METHODS: Retrospective, uncontrolled multicentre single-arm case series of hospitalised patients with laboratory-confirmed COVID-19, treated with inhaled nebulised UFH (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO2 ) and FiO2 , and the World Health Organisation modified ordinal clinical scale. RESULTS: There were 98 patients included. In patients on stable prophylactic or therapeutic systemic anticoagulant therapy but not receiving therapeutic UFH infusion, APTT levels increased from baseline of 34 ± 10 seconds to a peak of 38 ± 11 seconds (P < .0001). In 3 patients on therapeutic UFH infusion, APTT levels did not significantly increase from baseline of 72 ± 20 to a peak of 84 ± 28 seconds (P = .17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation. The oxygen saturation/FiO2 ratio and the FiO2 worsened before and improved after commencement of inhaled UFH (change in slope, P < .001). CONCLUSION: Inhaled nebulised UFH in hospitalised patients with COVID-19 was safe. Although statistically significant, inhaled nebulised UFH did not produce a clinically relevant increase in APTT (peak values in the normal range). Urgent randomised evaluation of nebulised UFH in patients with COVID-19 is warranted and several studies are currently underway.

INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies.

AIMS: Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus' entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. METHODS: The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) metatrial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes. ANALYSIS: We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. TRIAL REGISTRATION, ETHICS AND DISSEMINATION: The metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.

Enfermedad por arañazo de gato en paciente con artritis reumatoidea tratado con etanercept / Cat scratch disease during etanercept therapy in a rheumatoid arthritis patient

La enfermedad por arañazo de gato (EAG) es una enfermedad infecciosa causada por la proteobacteria Bartonella henselae, caracterizada por fiebre y linfadenopatía granulomatosa. La inmunosupresión es un factor de riesgo para el desarrollo de formas atípicas de la enfermedad. Presentamos el caso de una mujer de 52 años de edad que presentó fiebre y adenomegalias inguinales bilaterales. No tenía contacto aparente con animales. La paciente estaba recibiendo tratamiento con etanercept por artritis reumatoidea. La biopsia del ganglio linfático informó de una adenopatía granulomatosa. Evolucionó favorablemente con la interrupción de etanercept y el tratamiento con minociclina. Presentó remisión clínica y la seroconversión típica. La infección por Bartonella debería ser considerada como un diagnóstico diferencial en pacientes con artritis reumatoidea, con linfadenopatía de origen desconocido

Cat scratch disease (CSD) is an infectious disorder caused by Bartonella henselae and characterized by fever and granulomatous lymphadenopathy. Immunosuppression is a risk factor for the development of atypical forms of the disease. We report the case of a 52-year-old woman who presented with fever and bilateral inguinal lymph node enlargement. She did not have apparent contact with animals. The patient was receiving etanercept therapy for rheumatoid arthritis. Lymph node biopsy demonstrated granulomatous lymphadenitis. She was successfully managed by discontinuing etanercept and by treatment with minocycline. She developed clinical remission and typical seroconversion. Infection with Bartonella should be considered in the differential diagnosis in rheumatoid arthritis patients with lymphadenopathy of unknown origin

Cat scratch disease during etanercept therapy in a rheumatoid arthritis patient. / Enfermedad por arañazo de gato en paciente con artritis reumatoidea tratado con etanercept.

Cat scratch disease (CSD) is an infectious disorder caused by Bartonella henselae and characterized by fever and granulomatous lymphadenopathy. Immunosuppression is a risk factor for the development of atypical forms of the disease. We report the case of a 52-year-old woman who presented with fever and bilateral inguinal lymph node enlargement. She did not have apparent contact with animals. The patient was receiving etanercept therapy for rheumatoid arthritis. Lymph node biopsy demonstrated granulomatous lymphadenitis. She was successfully managed by discontinuing etanercept and by treatment with minocycline. She developed clinical remission and typical seroconversion. Infection with Bartonella should be considered in the differential diagnosis in rheumatoid arthritis patients with lymphadenopathy of unknown origin.

Risk of venous thromboembolic disease and adequacy of prophylaxis in hospitalized patients in Argentina: a multicentric cross-sectional study.

BACKGROUND: Venous thromboembolic disease (VTE) is associated with high morbi-mortality. Adherence rate to the recommendations of antithrombotic prophylaxis guidelines (ATPG) is suboptimal. The aim of this study was to describe the adequacy of antithrombotic prophylaxis (ATP) in hospitalized patients as the initial stage of a program designed to improve physician adherence to -ATP recommendations in Argentina. METHODS: This study was a multicenter, cross-sectional study that included 28 Institutions throughout 5 provinces in Argentina. RESULTS: 1315 patients were included, 729 (55.4%) were hospitalized for medical (clinical) reasons, and 586 (44.6%) for surgical reasons. Adequate ATP was provided to 66.9% of the patients and was more frequent in surgical (71%) compared to clinical (63.6%) subjects (p < 0.001). Inadequate ATP resulted from underuse in 76.6% of the patients. Among clinical, 203 (16%) had increased bleeding risk and mechanical ATP was used infrequently. CONCLUSIONS: The adequacy of ATP was better in low VTE risk clinical and surgical patients and high VTE risk in orthopedic patients. There was worse adequacy in high risk patients (with active neoplasm) and in those with pharmacological ATP contraindications, in which the use of mechanical methods was scarce. The adequacy of ATP was greater at institutions with < 150 beds compared with larger institutions. This is the first multicentric study reporting ATP in Argentina. Understanding local characteristics of medical performance within our territory is the first step in order to develop measures for improving ATP in our environment.

[Venous thromboembolic prophylaxis. Guidelines for adults in Argentina]. / Guía de recomendaciones para la profilaxis de la enfermedad tromboembólica venosa en adultos en la Argentina.

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).

Guía de recomendaciones para la profilaxis de la enfermedad tromboembólica venosa en adultos en la Argentina / Venous thromboembolic prophylaxis: Guidelines for adults in Argentina

La enfermedad tromboembólica venosa (ETV) en adultos posee elevada morbimortalidad y puede asociarse a complicaciones crónicas invalidantes. Sin embargo, la adherencia a estándares de cuidado no es óptima. Se analizó la evidencia disponible en tromboprofilaxis y se generaron recomendaciones (1) o sugerencias (2) con diferentes grados de evidencia (A, B o C) para diferentes escenarios y métodos de tromboprofilaxis. En cirugías ortopédicas mayores se recomienda la profilaxis farmacológica con heparinas de bajo peso molecular, HBPM (1B), fondaparinux, dabigatrán y rivaroxaban (1B) que deben iniciarse durante la internación y mantenerse hasta 35 días después de la cirugía de cadera y hasta 10 días posteriores a la artroplastia de rodilla. La artroscopia de rodilla y la cirugía de columna programada no requieren profilaxis farmacológica (2B) salvo que posean factores de riesgo adicionales, en cuyo caso se recomiendan las HBPM. En pacientes con internación clínica y movilidad reducida esperable mayor a tres días, que posean factores de riesgo adicionales, se recomienda tromboprofilaxis con HBPM, HNF o fondaparinux (1B) hasta el alta. Aquellos pacientes neuroquirúrgicos o con HIC deberán recibir inicialmente tromboprofilaxis mecánica (2C) y dependiendo del caso, iniciar HBPM o HNF entre las 24-72 horas posteriores (2C). Estas últimas dos drogas son recomendadas para pacientes críticos. Los pacientes sometidos a cirugías no ortopédicas con bajo riesgo de ETV deberán realizar deambulación precoz (2C) y tromboprofilaxis mecánica (2C), mientras que aquellos en los que el riesgo de ETV sea elevado deberán recibir HBPM y HNF (1B o 2C según su riesgo de sangrado).(AU)

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).(AU)

Guía de recomendaciones para la profilaxis de la enfermedad tromboembólica venosa en adultos en la Argentina / Venous thromboembolic prophylaxis: Guidelines for adults in Argentina

La enfermedad tromboembólica venosa (ETV) en adultos posee elevada morbimortalidad y puede asociarse a complicaciones crónicas invalidantes. Sin embargo, la adherencia a estándares de cuidado no es óptima. Se analizó la evidencia disponible en tromboprofilaxis y se generaron recomendaciones (1) o sugerencias (2) con diferentes grados de evidencia (A, B o C) para diferentes escenarios y métodos de tromboprofilaxis. En cirugías ortopédicas mayores se recomienda la profilaxis farmacológica con heparinas de bajo peso molecular, HBPM (1B), fondaparinux, dabigatrán y rivaroxaban (1B) que deben iniciarse durante la internación y mantenerse hasta 35 días después de la cirugía de cadera y hasta 10 días posteriores a la artroplastia de rodilla. La artroscopia de rodilla y la cirugía de columna programada no requieren profilaxis farmacológica (2B) salvo que posean factores de riesgo adicionales, en cuyo caso se recomiendan las HBPM. En pacientes con internación clínica y movilidad reducida esperable mayor a tres días, que posean factores de riesgo adicionales, se recomienda tromboprofilaxis con HBPM, HNF o fondaparinux (1B) hasta el alta. Aquellos pacientes neuroquirúrgicos o con HIC deberán recibir inicialmente tromboprofilaxis mecánica (2C) y dependiendo del caso, iniciar HBPM o HNF entre las 24-72 horas posteriores (2C). Estas últimas dos drogas son recomendadas para pacientes críticos. Los pacientes sometidos a cirugías no ortopédicas con bajo riesgo de ETV deberán realizar deambulación precoz (2C) y tromboprofilaxis mecánica (2C), mientras que aquellos en los que el riesgo de ETV sea elevado deberán recibir HBPM y HNF (1B o 2C según su riesgo de sangrado).

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).

Guía de recomendaciones para la profilaxis de la enfermedad tromboembólica venosa en adultos en la Argentina. / [Venous thromboembolic prophylaxis. Guidelines for adults in Argentina].

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).

Guía de recomendaciones para la profilaxis de la enfermedad tromboembólica venosa en adultos en la Argentina / [Venous thromboembolic prophylaxis. Guidelines for adults in Argentina].

The venous thromboembolic disease (VTD) in adults has a high morbidity and mortality. It can be also associated to disabling chronic conditions. In spite of this, prophylaxis in healthcare assistance is still underused. In this article, the available evidence in thromboprophylaxis was analyzed to offer recommendations (1) or suggestions (2) classified according to different levels of evidence (A, B or C). Different medical scenarios and types of thromboprophylaxis were analyzed. In major orthopedic surgeries low molecular weight heparins, LMWH, inhibitors of the Xa and IIa factors are recommended (1B) to be started during hospitalization and continued for 35 days in hip replacement surgery and for 10 days in total knee replacement surgery. Knee arthroscopy and spine surgery do not require pharmacologic treatment (2B) unless the patient has other risks factors for thrombosis. In such cases, LMWH are recommended. Non-surgical patients who have at least one risk factor should receive LMWH, NFH or fondaparinux (1B) if they are to be bedridden or unable to walk for three or more days. Patients undergoing neurosurgery or with intracranial hemorrhage should receive mechanic prophylaxis (2C), and accordingly they should start LMWH or NFH 24 to 72 hours afterwards (2C). The latter two drugs are recommended for critically ill patients. Patients with low risk for VTD undergoing other type of surgeries should be prescribed with mechanical prophylaxis (2C) and encouraged to walk promptly (2C), while those with high risk should be prescribed with LMWH or NFH (1B or 2C according to bleeding risk factors).

Frecuencia de los grupos sanguíneos y análisis de la progresiva disminución del factor Rh negativo en la población Argentina / Frequency of blood groups and analysis of the progressive decrease of Rh negative factor in the Argentinian population

Se analizaron los grupos sanguíneos de 73875 dadores de sangre que concurrieron al Banco de Sangre del Policlínico Ferroviario Central, en relación a la provincia o país de nacimiento. Se estudiaron los grupos ABO, el genotipi cde y los fenotipos Cde, cdE y CdE. Se confeccionaron mapas de la Republica Argentina en los que se describe la frecuencia relativa de los grupos sanguíneos estudiados. En base a estos resultados y a los datos del último censo, se estimó la prevalencia probable de los grupos sanguíneos en la población total de la Republica Argentina. Los porcentajes obtenidos para los distintos grupos son: O = 53,8%; A = 34,7%; B = 8,8%; AB = 2,7%; cde = 8,4%; Cde = 0,44%; cdE = 0,21%; CdE = 0,06% y total Rh negativo = 9,11%. Se observó a lo largo del período de estudio, la disminución progresiva en la prevalencia del grupo cde/cde (p+0,047). Se calculó la proporción de los componentes génicos europeo y aborigen de la población argentina, usando como marcadores al grupo 0 y al factor Rh negativo. Los porcentajes encontrados en la población nativa fueron: componente europeo 81,77% y 81,47% y componente aborigen 18,23% y 18,57%

Frecuencia de los grupos sanguíneos y análisis de la progresiva disminución del factor Rh negativo en la población Argentina / Frequency of blood groups and analysis of the progressive decrease of Rh negative factor in the Argentinian population

Se analizaron los grupos sanguíneos de 73875 dadores de sangre que concurrieron al Banco de Sangre del Policlínico Ferroviario Central, en relación a la provincia o país de nacimiento. Se estudiaron los grupos ABO, el genotipi cde y los fenotipos Cde, cdE y CdE. Se confeccionaron mapas de la Republica Argentina en los que se describe la frecuencia relativa de los grupos sanguíneos estudiados. En base a estos resultados y a los datos del último censo, se estimó la prevalencia probable de los grupos sanguíneos en la población total de la Republica Argentina. Los porcentajes obtenidos para los distintos grupos son: O = 53,8%; A = 34,7%; B = 8,8%; AB = 2,7%; cde = 8,4%; Cde = 0,44%; cdE = 0,21%; CdE = 0,06% y total Rh negativo = 9,11%. Se observó a lo largo del período de estudio, la disminución progresiva en la prevalencia del grupo cde/cde (p+0,047). Se calculó la proporción de los componentes génicos europeo y aborigen de la población argentina, usando como marcadores al grupo 0 y al factor Rh negativo. Los porcentajes encontrados en la población nativa fueron: componente europeo 81,77% y 81,47% y componente aborigen 18,23% y 18,57% (AU)