Letermovir Primary Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: Real-Life Data from a University Hospital in Argentina.

Background: Cytomegalovirus (CMV) infection remains the most common clinically significant infection after allogeneic hematopoietic stem cell transplantation (allo-HCT) and is associated with considerable morbidity and mortality. Objectives: The present study was designed to describe and compare the incidence of untreated CMV reactivation (uCMVr), clinically significant infection (cs-CMVi) and disease (CMVd), as well as CMV-related hospitalization and outcome of allo-HCT patients, either treated with letermovir (LET) primary prophylaxis or managed with preemptive therapy (PET). Methods: This is a prospective observational cohort study of adult CMV seropositive allo-HCT patients who either received primary prophylaxis with LET within the first 100 days after HCT or were managed with PET. Results: The study population comprised 105 patients (28 in the LET group and 77 in the PET group). Compared to the PET group, patients in the LET group received more allo-HCT from alternative donors (54.5% vs. 82.14%, P=0.012). More than half of the patients in both groups were classified as high risk for CMVd. In the LET vs. PET group, cs-CMVi and CMVd developed respectively in 0 vs. 50 (64.94%), P=<0.0001, and 0 vs. 6 (7.79%), P=0.18. In the LET group, uCMVr occurred in 5 (17.8%) and were all considered blips. Hospital admissions related to cs-CMVi or CMVd in the PET group vs. LET group were 47 (61.04%) vs. 0, respectively, P=<0.0001. No differences were observed in 100-day mortality. Conclusions: LET primary prophylaxis proved effective in preventing cs-CMVi and CMVd and reducing hospitalizations in allo-HCT adults. Blips can occur during prophylaxis and do not require LET discontinuation.

Letermovir para prevención de la infección por citomegalovirus en receptores de trasplante alogénico de progenitores hematopoyéticos / Letermovir for prevention of cytomegalovirus infection in allogeneic stem cell transplant receivers

INTRODUCCIÓN: La infección por citomegalovirus (CMV) sigue siendo la infección con relevancia clínica más frecuente luego del trasplante alogénico de progenitores hematopoyéticos (TPHa), presentando alta morbilidad y mortalidad. Por este motivo, es importante implementar estrategias de prevención para reducir la frecuencia de la infección por CMV. OBJETIVO: Describir la frecuencia de infección, infección clínicamente significativa (ICS) y enfermedad por CMV en pacientes seropositivos que recibieron un TPHa y profilaxis primaria con letermovir. PACIENTES Y MÉTODOS: Estudio descriptivo de cohorte longitudinal, en pacientes con TPHa seropositivos para CMV que recibieron profilaxis primaria con letermovir hasta el día 100 posTPH. RESULTADOS: Se incluyeron 25 pacientes adultos con una mediana de edad de 41 años, el 44% fue de donante no relacionado y 36% de donante haploidéntico. Ochenta por ciento tenía tres o más factores de riesgo para infección por CMV y a 52% se le estratificó como de alto riesgo para enfermedad por CMV. La profilaxis con letermovir tuvo una mediana de duración de 97 días. Durante los 100 días pos-TPH, 20% de los pacientes presentaron infección por CMV, con carga viral plasmática detectable no cuantificable, que se negativizó en el siguiente control semanal sin discontinuación del letermovir. Ningún paciente presentó ICS ni enfermedad por CMV durante este período. CONCLUSIÓN: La profilaxis con letermovir fue efectiva para prevenir la ICS y la enfermedad por CMV.

BACKGROUND: Cytomegalovirus (CMV) infection remains the most common clinically significant infection after allogeneic stem cell transplantation (aSCT), with a high morbidity and mortality rate. In order to reduce its frequency, prevention strategies should be implemented. AIM: To describe the frequency of infection, clinically significant infection (CSI) and CMV disease in seropositive patients who received aSCT and primary prophylaxis with letermovir. METHODS: Longitudinal descriptive cohort study in seropositive patients who received aSCT and primary prophylaxis with letermovir until day 100 post-SCT. RESULTS: Twenty-five adult patients with a median age of 41 years were included; 44% were unrelated donors, and 36% were haploidentical donors. Eighty percent had three or more risk factors for CMV infection, and 52% were stratified as high risk for CMV disease. Letermovir prophylaxis had a median duration of 97 days. Twenty percent of the patients developed CMV infection through day 100 post-SCT, with detectable non-quantifiable CMV viral load in plasma. This became negative in the following weekly control without discontinuation of letermovir. No patient developed CSI or CMV organ disease during this period. CONCLUSION: Letermovir prophylaxis proved to be effective in preventing CSI and CMV disease.

Coagulopatía y Covid-19. Recomendaciones para una realidad cambiante / Coagulopathy and COVID-19. Recommendations for a changing reality

La pandemia COVID-19 provocada por el betacoronavirus SARS-CoV-2 exige rápidas respuestas desde el campo de la medicina. El riesgo de tromboembolismo venoso y arterial está aumentado durante la infección, especialmente en pacientes críticos. En ese contexto se destaca una coagulopatía caracterizada por niveles elevados de dímero D, con tendencia a la falla multiorgánica, y aumento de la mortalidad. Esas anormalidades de la hemostasia responden a varios mecanismos que deben tenerse en cuenta para la toma de decisiones terapéuticas. Analizamos la evidencia científica disponible en la que se fundamenta el enfoque terapéutico de la coagulopatía descripta y sus complicaciones, con el objetivo de diseñar recomendaciones terapéuticas realistas tendientes a disminuir la morbilidad y la mortalidad en pacientes con COVID-19

The coronavirus disease 2019 (COVID-19) pandemic requires rapid medical responses. The risk of venous and arterial thromboembolism increases in critically ill patients with SARS-CoV-2 infection. There is a hypercoagulable state that includes elevated levels of D-dimer, with an increased risk of organ failure and increased mortality. The abnormalities described in hemostasis should be considered for therapeutic decision making. We analyzed the available scientific evidence for the therapeutic approach of coagulopathy in the course of the disease with the objective of designing realistic therapeutic recommendations aimed at reducing morbidity and mortality in patients with COVID-19

[Coagulopathy and COVID-19. Recommendations for a changing reality]. / Coagulopatía y COVID-19. Recomendaciones para una realidad cambiante.

The coronavirus disease 2019 (COVID-19) pandemic requires rapid medical responses. The risk of venous and arterial thromboembolism increases in critically ill patients with SARS-CoV-2 infection. There is a hypercoagulable state that includes elevated levels of D-dimer, with an increased risk of organ failure and increased mortality. The abnormalities described in hemostasis should be considered for therapeutic decision making. We analyzed the available scientific evidence for the therapeutic approach of coagulopathy in the course of the disease with the objective of designing realistic therapeutic recommendations aimed at reducing morbidity and mortality in patients with COVID-19.

La pandemia COVID-19 provocada por el betacoronavirus SARS-CoV-2 exige rápidas respuestas desde el campo de la medicina. El riesgo de tromboembolismo venoso y arterial está aumentado durante la infección, especialmente en pacientes críticos. En ese contexto se destaca una coagulopatía caracterizada por niveles elevados de dímero D, con tendencia a la falla multiorgánica, y aumento de la mortalidad. Esas anormalidades de la hemostasia responden a varios mecanismos que deben tenerse en cuenta para la toma de decisiones terapéuticas. Analizamos la evidencia científica disponible en la que se fundamenta el enfoque terapéutico de la coagulopatía descripta y sus complicaciones, con el objetivo de diseñar recomendaciones terapéuticas realistas tendientes a disminuir la morbilidad y la mortalidad en pacientes con COVID-19.

Coagulopatía y covid-19. recomendaciones para una realidad cambiante / Coagulopathy and COVID-19. Recommendations for a changing reality

Resumen La pandemia COVID-19 provocada por el betacoronavirus SARS-CoV-2 exige rápidas respuestas desde el campo de la medicina. El riesgo de tromboembolismo venoso y arterial está aumentado durante la infección, especialmente en pacientes críticos. En ese contexto se destaca una coagulopatía caracterizada por niveles elevados de dímero D, con tendencia a la falla multiorgánica, y aumento de la mortalidad. Esas anormalidades de la hemostasia responden a varios mecanismos que deben tenerse en cuenta para la toma de decisiones terapéuticas. Analizamos la evidencia científica disponible en la que se fundamenta el enfoque terapéutico de la coagulopatía descripta y sus complicaciones, con el objetivo de diseñar recomendaciones terapéuticas realistas tendientes a disminuir la morbilidad y la mortalidad en pacientes con COVID-19.

Abstract The coronavirus disease 2019 (COVID-19) pandemic requires rapid medical responses. The risk of venous and arterial thromboembolism increases in critically ill patients with SARS-CoV-2 infection. There is a hypercoagulable state that includes elevated levels of D-dimer, with an increased risk of organ failure and increased mortality. The abnormalities described in hemostasis should be considered for therapeutic decision making. We analyzed the available scientific evidence for the therapeutic approach of coagulopathy in the course of the disease with the objective of designing realistic therapeutic recommendations aimed at reducing morbidity and mortality in patients with COVID-19.

Allogeneic stem cell transplantation improves survival in relapsed Hodgkin lymphoma patients achieving complete remission after salvage treatment.

Allogeneic stem cell transplant (alloSCT) is a current treatment option for patients with refractory/relapsed classic Hodgkin lymphoma (CHL), including those who have failed an autologous transplantation. We performed a retrospective multicenter analysis of 113 patients (median age 28 years; range 14-56; 54% males) with refractory/relapsed (R/R) CHL who had undergone alloSCT in Argentina. Kaplan-Meier was used to estimate overall (OS) and progression-free survival (PFS). Relapse rate (RR) and non-relapse mortality (NRM) were estimated with cumulative incidence analysis. Disease status at transplant was complete remission (CR) in 39%, partial remission (PR) in 44%, and stable/progressed disease (S/PD) in 17% of the patients. Donor type was matched related (MRD) in 60%, unrelated (URD) in 19%, and haploidentical (HID) in 21% of the patients. OS and PFS at 2 years were 43% and 27%, respectively, for all the cohort. In the univariate analysis, patients in CR showed better OS (p ≤ 0.001) and PFS (p ≤ 0.001), and lower NRM (p = 0.04). HID had better PFS (p = 0.04) and lower RR (p = 0.02). In the multivariate analysis, CR showed a significant impact on OS and PFS, and HID on PFS. AlloSCT is a feasible procedure in patients with CHL. Those in CR at the time of the transplant had better outcomes. Haploidentical transplantation is associated with better PFS in these patients with poor prognosis.

[Percutaneous balloon angioplasty for treatment of chronic thromboembolic pulmonary hypertension]. / Angioplastia percutánea con balón en hipertensión pulmonar tromboembólica crónica.

Chronic thromboembolic pulmonary hypertension is characterized by the presence of organized thrombotic material in the pulmonary arteries which causes elevation of the pulmonary vascular resistance, right heart failure, and death if not treated. Pulmonary thromboendarterectomy is the treatment of choice and can be curative when the obstruction is proximal. There are cases in which this therapy is not possible, and pulmonary angioplasty is a therapeutic alternative of growing interest. We present our experience with three patients diagnosed with chronic thromboembolic pulmonary hypertension in whom pulmonary endarterectomy was not possible and pulmonary angioplasty was performed. All patients showed improvement of functional class, six-minute walk distance, and hemodynamic as well as angiographic parameters.

Angioplastia percutánea con balón en hipertensión pulmonar tromboembólica crónica / Percutaneous balloon angioplasty for treatment of chronic thromboembolic pulmonary hypertension

La hipertensión pulmonar tromboembólica crónica se caracteriza por la presencia de material trombótico organizado dentro de las arterias pulmonares que genera elevación de la resistencia vascular pulmonar, insuficiencia cardíaca derecha y, eventualmente, la muerte. El tratamiento de elección es la tromboendarterectomía pulmonar, que suele ser curativa si la obstrucción es proximal. En algunos casos este tratamiento no es posible y surge como alternativa la angioplastia pulmonar con balón (APB), que está generando creciente interés. Se presentan tres casos de pacientes con hipertensión pulmonar tromboembólica a los que por diferentes circunstancias no pudo tratarse con tromboendarterectomía y se realizó APB comprobándose, en los tres casos, mejoría de la clase funcional, prueba de la caminata de seis minutos, además de parámetros hemodinámicos y angiográficos.

Chronic thromboembolic pulmonary hypertension is characterized by the presence of organized thrombotic material in the pulmonary arteries which causes elevation of the pulmonary vascular resistance, right heart failure, and death if not treated. Pulmonary thromboendarterectomy is the treatment of choice and can be curative when the obstruction is proximal. There are cases in which this therapy is not possible, and pulmonary angioplasty is a therapeutic alternative of growing interest. We present our experience with three patients diagnosed with chronic thromboembolic pulmonary hypertension in whom pulmonary endarterectomy was not possible and pulmonary angioplasty was performed. All patients showed improvement of functional class, six-minute walk distance, and hemodynamic as well as angiographic parameters.

Safety and feasibility of balloon-expandable stent implantation for the treatment of type I endoleaks following endovascular aortic abdominal aneurysm repair.

AIMS: The occurrence of type I endoleaks represent an ominous sign after endovascular aneurysms repair (EVAR). We report our experience using balloon-expandable stents (BES) for the treatment of proximal Type I endoleaks at five high-volume hospitals in Argentina. METHODS AND RESULTS: Of 1,395 patients who underwent EVAR, we retrospectively collected data of 29 (2%) consecutive patients who underwent additional BES to repair proximal type I endoleaks. The mean age was 75.8 years old (range 63-87) and 93% were male. A hostile anatomy was found in 89.6% of the cases. BES oversize (balloon/neck diameter ration ≥ 30%) was frequent (69%); whereas, BES/prosthesis diameter ratio was less than 1 in 79% of the cases. Complete and partial sealing was obtained 72 and 28% of the cases, respectively. There were no immediate or late surgical conversion or major complications related with stent implantation. At a median time follow-up of 14.9 months (25-75% interquartiles: 4.5-17.5 months), there were no cardiovascular deaths, evidence of aneurysm sac enlargement or need for re-intervention. CONCLUSIONS: Our preliminary results suggest that BES implantation for the treatment of proximal type I endoleaks is feasible and safe with favourable mid-term results and may preclude the need for surgical conversion.

Isolation of Chlamydophila pneumoniae from atheromas of the carotid artery and their antibiotics susceptibility profile.

BACKGROUND: Atherosclerosis is pathogenically similar to a chronic inflammatory response. Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis. Chlamydophila pneumoniae has been suggested to play a role in the origin of PAD. OBJECTIVE: To determine whether C. pneumoniae is present in atherosclerosis lesions of the carotid artery wall in patients with PAD through several diagnostic methods and to characterize C. pneumoniae susceptibility profiles. METHODS: The presence of C. pneumoniae in 9 tissue samples from atherosclerotic lesions obtained by carotid endarterectomy was investigated by 3 methods. Karnofsky-fixed specimens were examined by transmission electron microscopy (TEM), isolation of C. pneumoniae was attempted in LLCMK2 cell structure (ICC), and the presence of chlamydial DNA was investigated by polymerase chain reaction (PCR). The in vitro activities of azithromycin, roxithromycin and penicillin were tested in 4 isolations and the reference strain of C. pneumoniae (AR39). RESULTS: C. pneumoniae was detected in atherosclerotic plaques from 4 patients with PAD. The pathogen was identified by TEM, PCR and ICC. We report data of the in vitro susceptibility of 4 strains. These strains did not differ from respiratory AR39 strain in their susceptibility patterns to azithromycin, roxithromycin and penicillin. CONCLUSIONS: C. pneumoniae is frequently found in the advanced carotid atherosclerotic lesions of patients undergoing endarterectomy. Although these findings do not establish causality in carotid artery atherosclerosis, they should stimulate investigation of the possible causal or pathogenic role of C. pneumoniae. Notably, the profiles of antibiotic susceptibility of C. pneumoniae isolated from 4 of the patients did not differ from those of the reference strain.

Isolation of Chlamydophila pneumoniae from atheromas of the carotid artery and their antibiotics susceptibility profile

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Infusiones de linfocitos de dador como imunoterapia adoptiva en pacientes con neoplasias hamatologicas recaidos post transplante alogenico de celulas progenitoras hematopoyeticas / Donor lymphocyte infusions for the treatment of relapse after allogeneic hematopoietic stem cell transplantation

Un número creciente de publicaciones ha demostrado claramente que la infusión de infusión de linfocitos provenientes del dador original es capaz de reinducir remisiones en pacientes con recaídas luego de un trasplante alogénico de células precursoras hematopoyéticas. También se ha comunicado que la efectividad de la misma varía en las distintas patologías en la que se ha utilizado. Los mejores resultados se obtuvieron en leucemia mieloide crónica, con un rango de remisiones entre 60 y 80 por ciento, mientras que los pacientes con leucemia aguda mieloblástica o síndromes melodisplásicos mostraron porcentajes de remisiones del orden del 20 a 40 por ciento y y pacientes con mieloma múltiple un nível de respuestas próximo a 40 por ciento. En cambio en leucemia aguda linfoblástica los resultados han sido por lo general desalentadores, con un rango de respuestas de apenas 10-20 por ciento y aun inferiores en algunas series. Dada la eficacia de las ILD en ciertas recaidas hematológicas post trasplante alogénico como se expondrá en detalle en esta revisión, es justificado anticipar la extensión de su indicación a pacientes recaídos no trasplantados y como terapia de mantenimiento de la remision obtenida por quimioterapia convencional o a altas dosis.

Infusiones de linfocitos de dador como imunoterapia adoptiva en pacientes con neoplasias hamatologicas recaidos post transplante alogenico de celulas progenitoras hematopoyeticas / Donor lymphocyte infusions for the treatment of relapse after allogeneic hematopoietic stem cell transplantation

Un número creciente de publicaciones ha demostrado claramente que la infusión de infusión de linfocitos provenientes del dador original es capaz de reinducir remisiones en pacientes con recaídas luego de un trasplante alogénico de células precursoras hematopoyéticas. También se ha comunicado que la efectividad de la misma varía en las distintas patologías en la que se ha utilizado. Los mejores resultados se obtuvieron en leucemia mieloide crónica, con un rango de remisiones entre 60 y 80 por ciento, mientras que los pacientes con leucemia aguda mieloblástica o síndromes melodisplásicos mostraron porcentajes de remisiones del orden del 20 a 40 por ciento y y pacientes con mieloma múltiple un nível de respuestas próximo a 40 por ciento. En cambio en leucemia aguda linfoblástica los resultados han sido por lo general desalentadores, con un rango de respuestas de apenas 10-20 por ciento y aun inferiores en algunas series. Dada la eficacia de las ILD en ciertas recaidas hematológicas post trasplante alogénico como se expondrá en detalle en esta revisión, es justificado anticipar la extensión de su indicación a pacientes recaídos no trasplantados y como terapia de mantenimiento de la remision obtenida por quimioterapia convencional o a altas dosis. (AU)