[Assessing Convalescent Plasma Efficacy in Moderate COVID-19 Hospitalizations: A Bicentric Retrospective Study]. / Uso de plasma de convalecientes de COVID-19 en pacientes hospitalizados por SARS-CoV-2 de moderada grave-dad en la Región de Los Ríos, Chile.

INTRODUCTION: COVID-19 claimed millions of lives, mainly in the pre-vaccine era. Preliminary studies showed promising efficacy of convalescent plasma against SARS-CoV-2 (CP). OBJECTIVE: To evaluate the efficacy of CP in patients hospitalized for COVID-19 with moderate severity. METHODS: Retrospective, bicentric study including adults hospitalized for moderate (non-critical) COVID-19 who required oxygen therapy. CP donated by survivors of mild cases (600 cc) were searched for IgG anti-SARS-CoV-2. Its impact on mortality, hospital stay (days), and need for mechanical ventilation (IMV) was evaluated. RESULTS: Of the 119 patients included, 58% were men (median age 60 years), 88% had comorbidity, and 43% had a high-risk CALL score. Forty-three patients (36%) received CP, only 15 (12.6%) early (< 7 days). Twenty-two patients had to be transferred to the intensive care unit; 18 received IMV, and 15 died (12.6%). The use of CP was not associated with changes in mortality (p = 0.16), need for IMV (p = 0.79), or hospital stay (p = 0.24). Its early administration (< 7 days of symptoms) did not show a significant association either. The presence of heart disease and subsequently requiring IMV were independent factors of mortality. CONCLUSIONS: The use of CP in patients hospitalized for moderately severe COVID-19 was not associated with lower mortality, hospital stay, or the need for IMV.

[Search for mutations in patients with Philadelphia negative myeloproliferative neoplasms in a public hospital in Chile]. / Estudio de mutaciones en neoplasias mieloproliferativas Philadelphia negativas en un hospital público chileno.

BACKGROUND: Philadelphia negative myeloproliferative neoplasms (Ph-MPN) are clonal disorders whose pathogenesis has been elucidated in recent years, creating diagnostic and prognostic algorithms. AIM: To study JAK2, CALR y MPL gene mutations in patients with Ph-MPN. MATERIALS AND METHODS: Descriptive cross-sectional observational study of patients with MPN (2015-2019), reviewing clinical, demographic and laboratory data. JAK2, CALR and MPL gene mutations were analyzed by RT-PCR. RESULTS: We studied 72 patients. Fifty percent had essential thrombocythemia (ET), 26.4% had polycythemia vera (PV) and 23.6% had primary myelofibrosis (PM). Bone marrow biopsy was available in 76.5%. At diagnosis, the mean age was 65.5 years and 61% were symptomatic. A thrombotic event was the most frequent problem in 20% and 25% had splenomegaly. There were statistically significant differences in hematological parameters between the different MPNs. JAK2 V617F mutation was detected in 61.1%. Only 19 JAK2 V617F negative patients were available for CALR and MPL mutation studies, identifying 10 triple negative cases. Kaplan Meier curves showed a median survival of 88 months, being similar in the three MPNs. Causes of death in 20 patients were thrombotic complications in 30%, disease progression in 25%, infection in 20%, other neoplasms in 15% and other causes in 10%. CONCLUSIONS: The presentation and frequency of JAK2 V617F, CALR and MPL mutations in our cohort was similar to those reported in other studies for ET and PM. JAK2 V617F mutation was lower for PV. No significant differences between the three MPNs were observed for overall survival. We could not assess the prognostic value of the mutations.

[Clinical and epidemiological characteristics of the Philadelphia negative myeloproliferative neoplasms in Chile]. / Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). AIM: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. MATERIAL AND METHODS: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. RESULTS: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. CONCLUSIONS: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

[Clinical and epidemiological characteristics of the Philadelphia negative myeloproliferative neoplasms in Chile]. / Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). AIM: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. MATERIAL AND METHODS: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. RESULTS: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. CONCLUSIONS: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

[Treatment of Hodgkin lymphoma. Analysis of 915 patients]. / Evaluación del tratamiento de linfoma de Hodgkin con esquema ABVD en Chile.

BACKGROUND: Hodgkin lymphoma has a high rate of curability, even in advanced stages. AIM: To assess the results of Hodgkin lymphoma treatment using the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy regimen. MATERIAL AND METHODS: Analysis of a database held by the Chilean Ministry of Health, including all patients treated at accredited cancer treatment centers. RESULTS: Data for 915 patients, median age 35 years (range 15-86 years) and followed for a median of 97 months (range 1-347 months) were analyzed. Forty-one percent had localized disease. Overall survival at five years for localized and advanced stages was 92% and 74%, respectively. The figures for progression free survival were 87% and 64%, respectively. Patients with relapse who received autologous stem cell transplantation (ASCT) had a five year overall survival of 92%, compared to 64% among those who did not undergo this procedure (p < 0.01). The Guarantees in Health Program set up by the Ministry of Health, was associated with earlier stage disease at diagnosis. CONCLUSIONS: The ABVD regimen achieves high rates of cure in localized stages of the disease but the results in advanced stages are not optimal. ASCT significantly improves survival in patients with relapse. The Guarantees in Health Program is associated with earlier diagnosis of the disease.

Sustained Antibody-Dependent NK Cell Functions in Mild COVID-19 Outpatients During Convalescence.

The coronavirus disease 2019 (COVID19) pandemic has left researchers scrambling to identify the humoral immune correlates of protection from COVID-19. To date, the antibody mediated correlates of virus neutralization have been extensively studied. However, the extent that non-neutralizing functions contribute to anti-viral responses are ill defined. In this study, we profiled the anti-spike antibody subtype/subclass responses, along with neutralization and antibody-dependent natural killer cell functions in 83 blood samples collected between 4 and 201 days post-symptoms onset from a cohort of COVID-19 outpatients. We observed heterogeneous humoral responses against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Overall, anti-spike profiles were characterized by a rapid rise of IgA and sustained IgG titers. In addition, strong antibody-mediated natural killer effector responses correlated with milder disease and being female. While higher neutralization profiles were observed in males along with increased severity. These results give an insight into the underlying function of antibodies beyond neutralization and suggest that antibody-mediated natural killer cell activity is a key function of the humoral response against the SARS-CoV-2 spike protein.

Different outcomes for transplant-eligible newly diagnosed multiple myeloma patients in Latin America according to the public versus private management: a GELAMM study.

The aim of this study was to describe clinical and survival characteristics of transplant-eligible multiple myeloma (MM) patients in Latin America (LA), with a special focus on differences between public and private healthcare facilities. We included 1293 patients diagnosed between 2010 and 2018. A great disparity in outcomes and survival between both groups was observed. Late diagnosis and low access to adequate frontline therapy and ASCT in public institutions probably explain these differences. Patients treated with novel drug induction protocols, followed by autologous stem cell transplantation (ASCT) and maintenance, have similar overall survival compared to that published internationally.

Uso de plasma de convalecientes de COVID-19 en pacientes hospitalizados por SARS-CoV-2 de moderada grave-dad en la Región de Los Ríos, Chile

Introducción: COVID-19 cobró millones de vidas especialmente en la era pre-vacunas. Estudios preliminares mostraban eficacia promisoria del plasma de personas convalecientes anti SARS-CoV-2 (PPC). Objetivo: evaluar la eficacia del PPC en hospitalizados por COVID-19 de moderada gravedad. Material y Métodos: Estudio retrospectivo, bicéntrico, en adultos hospitalizados por COVID-19 moderado (no crítico) que requirieron oxigenoterapia. Al plasma donado por sobrevivientes de cuadros leves (600 cc) se les realizó búsqueda de IgG anti SARS-CoV-2. Se evaluó su impacto en mortalidad, estadía hospitalaria (días) y necesidad de ventilación mecánica (VMI). Resultados: De los 119 pacientes incluidos, 58% eran hombres (edad mediana 60 años), 88% poseía comorbilidad y 43% tenía "CALL score" de alto riesgo. 43 pacientes (36%) recibieron PPC, sólo 15 (12,6%) precozmente (< 7 días). 22 pacientes debieron trasladarse a unidad intensiva, 18 recibieron VMI y 15 fallecieron (12,6%). El uso de PPC no se asoció a cambios en la mortalidad (p = 0,16), necesidad de VMI (p = 0,79) ni en la estadía hospitalaria (p = 0,24). Su administración en forma precoz (< 7 días de síntomas) tampoco demostró asociación significativa. La presencia de cardiopatía y el requerir posteriormente VMI fueron factores independientes asociados a mortalidad. Conclusiones: El uso de PPC en pacientes hospitalizados por COVID-19 de moderada gravedad no se asoció a menor mortalidad, estadía hospitalaria ni necesidad de VMI.

Introduction: COVID-19 claimed millions of lives, mainly in the pre-vaccine era. Preliminary studies showed promising efficacy of convalescent plasma against SARS-CoV-2 (CP). Objective: To evaluate the efficacy of CP in patients hospitalized for COVID-19 with moderate severity. Methods: Retrospective, bicentric study including adults hospitalized for moderate (non-critical) COVID-19 who required oxygen therapy. CP donated by survivors of mild cases (600 cc) were searched for IgG anti-SARS-CoV-2. Its impact on mortality, hospital stay (days), and need for mechanical ventilation (IMV) was evaluated. Results: Of the 119 patients included, 58% were men (median age 60 years), 88% had comorbidity, and 43% had a high-risk CALL score. Forty-three patients (36%) received CP, only 15 (12.6%) early (< 7 days). Twenty-two patients had to be transferred to the intensive care unit; 18 received IMV, and 15 died (12.6%). The use of CP was not associated with changes in mortality (p = 0.16), need for IMV (p = 0.79), or hospital stay (p = 0.24). Its early administration (< 7 days of symptoms) did not show a significant association either. The presence of heart disease and subsequently requiring IMV were independent factors of mortality. Conclusions: The use of CP in patients hospitalized for moderately severe COVID-19 was not associated with lower mortality, hospital stay, or the need for IMV.

Estudio de mutaciones en neoplasias mieloproliferativas Philadelphia negativas en un hospital público chileno / Search for mutations in patients with Philadelphia negative myeloproliferative neoplasms in a public hospital in Chile

BACKGROUND: Philadelphia negative myeloproliferative neoplasms (Ph-MPN) are clonal disorders whose pathogenesis has been elucidated in recent years, creating diagnostic and prognostic algorithms. AIM: To study JAK2, CALR y MPL gene mutations in patients with Ph-MPN. MATERIALS AND METHODS: Descriptive cross-sectional observational study of patients with MPN (2015-2019), reviewing clinical, demographic and laboratory data. JAK2, CALR and MPL gene mutations were analyzed by RT-PCR. Results: We studied 72 patients. Fifty percent had essential thrombocythemia (ET), 26.4% had polycythemia vera (PV) and 23.6% had primary myelofibrosis (PM). Bone marrow biopsy was available in 76.5%. At diagnosis, the mean age was 65.5 years and 61% were symptomatic. A thrombotic event was the most frequent problem in 20% and 25% had splenomegaly. There were statistically significant differences in hematological parameters between the different MPNs. JAK2 V617F mutation was detected in 61.1%. Only 19 JAK2 V617F negative patients were available for CALR and MPL mutation studies, identifying 10 triple negative cases. Kaplan Meier curves showed a median survival of 88 months, being similar in the three MPNs. Causes of death in 20 patients were thrombotic complications in 30%, disease progression in 25%, infection in 20%, other neoplasms in 15% and other causes in 10%. CONCLUSIONS: The presentation and frequency of JAK2 V617F, CALR and MPL mutations in our cohort was similar to those reported in other studies for ET and PM. JAK2 V617F mutation was lower for PV. No significant differences between the three MPNs were observed for overall survival. We could not assess the prognostic value of the mutations.

Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile

Background: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). Aim: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. Material and Methods: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. Results: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. Conclusions: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

Evaluación del tratamiento de linfoma de Hodgkin con esquema ABVD en Chile / Treatment of Hodgkin lymphoma: analysis of 915 patients

Background: Hodgkin lymphoma has a high rate of curability, even in advanced stages. Aim: To assess the results of Hodgkin lymphoma treatment using the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy regimen. Material and Methods: Analysis of a database held by the Chilean Ministry of Health, including all patients treated at accredited cancer treatment centers. Results: Data for 915 patients, median age 35 years (range 15-86 years) and followed for a median of 97 months (range 1-347 months) were analyzed. Forty-one percent had localized disease. Overall survival at five years for localized and advanced stages was 92% and 74%, respectively. The figures for progression free survival were 87% and 64%, respectively. Patients with relapse who received autologous stem cell transplantation (ASCT) had a five year overall survival of 92%, compared to 64% among those who did not undergo this procedure (p < 0.01). The Guarantees in Health Program set up by the Ministry of Health, was associated with earlier stage disease at diagnosis. Conclusions: The ABVD regimen achieves high rates of cure in localized stages of the disease but the results in advanced stages are not optimal. ASCT significantly improves survival in patients with relapse. The Guarantees in Health Program is associated with earlier diagnosis of the disease.

Limitación crónica al flujo aéreo en pacientes con secuelas de tuberculosis pulmonar: Caracterización y comparación con EPOC / Chronic airways obstruction in patients with tuberculosis sequelae: a comparison with EPOC

Chronic airway obstruction (CAO) resulting from tuberculosis (TB) sequelae (CAO-TB) is a frequent condition in our population. However the information in the medical literature is scarce. The management of these patients usually follows guidelines for other illnesses such as chronic obstructive pulmonary disease (COPD) or asthma. To better characterize CAO-TB, 25 patients with this condition that never smoked nor were diagnosed having asthma, were studied by means of spirometry, arterial blood gases and 6-minute walk test. Furthermore, they were compared with 12 COPD patients with similar FEV1 values. CAO-TB patients had history of tuberculosis 35 ± 11 years earlier, and all of them presented with lung scarring in one or both upper lobes. They were younger than COPD (58 ± 11 vs 69 ± 6 y.o.; p = 0.001) and females predominated over males (20/5 vs 2/10; p = 0.001). The FEV1/FVC ratio pre- and post-bronchodilator were higher in CAO-TB than in COPD patients (67 percent ± 12 vs 54 percent ± 9 pre; p = 0.001; 65 percent ± 14 vs 51 percent ± 7; p = 0.003 post, respectively). There were no differences in the remaining spirometric indices nor in arterial blood gases. The 6-min distance walked was comparable in both groups: 343 m (69 percent) in CAO-TB and 361 m (76 percent) in COPD. There were no differences in the oxygen saturation nor in heart rate neither at the beginning nor at the end of the 6-min walk test. However, CAO-TB patients had a higher respiratory rate at the beginning (22.7 ± 4.7 vs 19.8 ± 3.1 breath/min; p = 0.05) and at the end of the walk test (27.3 ± 6.7 vs 21.9 ± 3.3; p = 0.01) than COPD patients; although the Borg dyspnoea score was not different (1 ± 0,7 vs 1 ± 0.5 initial, 3 ± 1.5 vs 2.5 ± 0.8 final). Furthermore, a significant linear correlation between respiratory rate and Borg score was found both at the beginning (r = 0.747; p < 0.001) and at the end (r = 0.507; p = 0.01) of the walk test. In conclusion, CAO-TB patients are functionally comparable to COPD patients, although they have higher respiratory rate and develop more dyspnoea because of their added restrictive impairment. In addition to spirometry, tests for assessment of dyspnoea such as 6-minute walk test must be considered, to evaluate the response to treatment in CAO-TB patients.

La limitación crónica al flujo aéreo (LCFA) secundaria a secuelas de tuberculosis (LCFA-TB) es relativamente frecuente en nuestro medio, pero la información sobre esta condición en la literatura es escasa. El manejo terapéutico de estos enfermos suele seguir las guías de otras entidades como la Enfermedad Pulmonar Obstructiva Crónica (EPOC) y el Asma Bronquial. Con el objetivo de caracterizar la LCFA-TB, 25 enfermos con esta condición, que nunca fumaron ni tuvieron asma, fueron estudiados mediante espirometría, gasometría arterial y prueba de caminata de 6 minutos. Los pacientes LCFA-TB fueron comparados con 12 pacientes EPOC que tenían un grado similar de obstrucción. Los enfermos con LCFA-TB habían presentado tuberculosis 35 ± 11 años antes y tenían lesiones fibrosas con retracción en uno o ambos lóbulos superiores. Eran más jóvenes que los pacientes con EPOC (58 ± 11 vs 69 ± 6 años; p = 0,001) y predominaban las mujeres sobre los hombres (20/5 vs 2/10; p = 0,001). La relación VEF1/CVF basal fue más elevada en los pacientes con LCFA-TB que en los con EPOC (67 por ciento ± 12 vs 54 por ciento ± 9; p = 0,001) al igual que la relación VEF1/CVF posterior a broncodilatador (65 por ciento ± 14 vs 51 por ciento ± 7; p = 0,003). No hubo diferencias en los demás índices espirométricos ni en los gases arteriales. La distancia recorrida en 6 minutos fue similar en ambos grupos de pacientes: 343 m (69 por ciento) en LCFA-TB y 361 m (76 por ciento) en EPOC. No hubo diferencias en la oximetría ni en la frecuencia cardíaca inicial ni final. En cambio, los pacientes con LCFA-TB presentaron una frecuencia respiratoria (FR) más elevada que los pacientes con EPOC, tanto al comienzo (22,7 ± 4,7 vs 19,8 ± 3,1; p = 0,05) como al final de la prueba (27,3 ± 6,7 vs 21,9 ± 3,3; p = 0,01). Aunque no hubo diferencias en el grado de disnea (escala de Borg: 1 ±0,7 vs 1 ± 0,5 inicial, 3 ± 1,5 vs 2,5 ± 0,8 final). Además, existió una correlación significativa entre la FR y los puntos de la escala de Borg al inicio de la prueba (r = 0,747; p < 0,001) y al final de ésta (r = 0,507; p = 0,01). En conclusión, los pacientes con LCFA-TB tienen un comportamiento funcional parecido a los pacientes con EPOC, aunque por el componente restrictivo de su limitación ventilatoria presentan más polipnea y tienden a desarrollar más disnea con el ejercicio. La valoración de la respuesta al tratamiento en estos enfermos debiera considerar, además de la espirometría, pruebas de evaluación de disnea como la distancia recorrida en seis minutos.