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 / Assessing Convalescent Plasma Efficacy in Moderate COVID-19 Hospitalizations: A Bicentric Retrospective Study

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.

Admissions by tuberculosis in a regional reference Center. A complex and worrying scenario / Ingresos por tuberculosis en un hospital regional. Un escenario complejo y preocupante

OBJECTIVES: To characterize clinical aspects, evaluate the diagnostic opportunity, and identify factors associated with mortality in patients hospitalized for tuberculosis (TB). METHODS: Retrospective study of patients admitted for TB to a Regional Hospital in Chile between 2011 and 2019. RESULTS: 142 TB events required hospitalization in this period (38.2% of total cases). All risk groups were identified, with a significant increase in patients with diabetes mellitus. The pulmonary location was the most frequent (71.1%), followed by disseminated forms (16.2%). The sensitivity of microscopy smear in cases of pulmonary TB (isolated or combined) was 78.8% and lower in cases of bronchoalveolar lavage (58.3%). PCR was only occasionally applied (< 10%) with a sensitivity of 100% in sputum samples. Its use increased progressively and reached a positivity of 33% (6 out of 18 cases) in cases with negative sputum staining. The median time between symptom onset and diagnosis was prolonged (9 weeks), and 32.5% of all regional events were diagnosed at the hospital. Dose adjustments (22.1%), corticosteroid use (25%), and treatment interruptions were frequent (11%). Lethality reached 19%, and by multivariate analysis, only shock was associated with a fatal outcome. CONCLUSIONS: In this case series, the diagnosis of TB cases was delayed, scarcely diagnosed by molecular methods, highly concentrated at the hospital level, required admission in a large percentage of cases, and had a high case-fatality rate.

OBJETIVOS: Caracterizar aspectos clínicos, evaluar la oportunidad diagnóstica e identificar factores asociados a mortalidad en pacientes ingresados por tuberculosis (TB). MÉTODOS: Estudio retrospectivo de pacientes ingresados por TB a un Hospital Regional en Chile entre el 2011 y 2019. RESULTADOS: Un total de 142 eventos de TB requirieron hospitalización en el período (38,2% del total). Todos los grupos de riesgo fueron identificados con un aumento significativo de los pacientes con diabetes mellitus. La localización pulmonar fue la más frecuente (71,1%), seguida de la forma diseminada (2 o más sitios; 16,2%). La sensibilidad de la tinción de expectoración en casos de TB pulmonar (aislada o combinada) fue de 78,8% y más baja en casos de lavado broncoalveolar (58,3%). La PCR fue sólo ocasionalmente aplicada (< 10%) con una sensibilidad del 100% en muestras de expectoración. Su uso aumentó progresivamente en el período y el incremento diagnóstico de TB en casos con tinción negativa de expectoración estudiados con PCR fue de 33% (6 de 18 casos). La mediana entre inicio de síntomas y el diagnóstico fue prolongada (9 semanas) y el 32,5% de los eventos regionales fueron diagnosticados en el hospital. Los ajustes de dosis (22,1%), uso de corticoides (25%) e interrupciones del tratamiento fueron hechos frecuentes (11%). La letalidad alcanzó 19% y en el análisis multivariado sólo la aparición de shock se asoció a un desenlace fatal. CONCLUSIONES: En esta serie de casos, el diagnóstico de casos de TB fue tardío, infrecuentemente diagnosticado por métodos moleculares, concentrado en la atención terciaria, requirió hospitalización en un gran porcentaje de casos y tuvo una elevada letalidad.

Severe acute respiratory infections (SARI) from influenza in adult patients in Chile: the experience of a sentinel hospital / La infección respiratoria aguda grave asociada a la gripe en pacientes adultos en Chile: experiencia de un hospital centinela / Infecção respiratória aguda grave (SARI) decorrente da influenza em pacientes adultos no Chile: experiência de um hospital-sentinela

ABSTRACT Objective To 1) describe clinical characteristics of adult patients in Chile with severe acute respiratory infections (SARI) associated with influenza viruses, and 2) analyze virus subtypes identified in specimens collected from those patients, hospital resources used in clinical management, clinical evolution, and risk factors associated with a fatal outcome, using observational data from the SARI surveillance network (SARInet). Methods Adults hospitalized from 1 July 2011 to 31 December 2015 with influenza-associated SARI at a SARI sentinel surveillance hospital in Santiago were identified and the presence of influenza in all cases confirmed by reverse transcription polymerase chain reaction (RT-PCR), using respiratory samples. Results A total of 221 patients (mean age: 74.1 years) were hospitalized with influenza-associated SARI during the study period. Of this study cohort, 91.4% had risk factors for complications and 34.3% had been vaccinated during the most recent campaign. Pneumonia was the most frequent clinical manifestation, occurring in 57.0% of the cohort; other manifestations included influenza-like illness, exacerbated chronic bronchitis, decompensated heart failure, and asthmatic crisis. Cases occurred year-round, with an epidemic peak during autumn-winter. Both influenza A (H1N1pdm09 and H3N2) and B virus co-circulated. Critical care beds were required for 26.7% of the cohort, and 19.5% needed ventilatory assistance. Multivariate analysis identified four significant factors associated with in-hospital mortality: 1) being bedridden (adjusted odds ratio (aOR): 22.3; 95% confidence interval (CI): 3.0-164); 2) admission to critical care unit (aOR: 8.9; CI: 1.44-55); 3) Pa02/Fi02 ratio < 250 (aOR: 5.8; CI: 1.02-33); and 4) increased serum creatinine concentration (> 1 mg/dL) (aOR: 5.47; CI: 1.20-24). Seasonal influenza vaccine was identified as a significant protective factor (aOR: 0.14; CI: 0.021-0.90). Conclusions Influenza-associated SARI affected mainly elderly patients with underlying conditions. Most patients evolved to respiratory failure and more than one-quarter required critical care beds. Clinical presentation was variable. Death was associated with host characteristics and disease-associated conditions, and vaccine was protective. Virus type did not influence outcome.

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RESUMO Objetivo Descrever as características clínicas de pacientes adultos com infecção respiratória aguda grave (SARI) associada ao vírus da influenza e analisar os subtipos virais identificados em amostras coletadas destes pacientes, os recursos hospitalares empregados no tratamento clínico, a evolução clínica e os fatores de risco clínicos associados a um desfecho fatal, a partir de dados observacionais da rede de vigilância de SARI (SARInet) no Chile. Métodos Foram identificados os adultos hospitalizados com SARI associada a influenza em um hospital-sentinela de vigilância de SARI, em Santiago, de 1o de julho de 2011 a 31 de dezembro de 2015. A ocorrência de influenza foi confirmada em amostras respiratórias em todos os casos com a reação em cadeia da polimerase via transcriptase reversa (RT-RCP). Resultados Ao todo, 221 pacientes (idade média de 74,1 anos) foram hospitalizados com SARI associada a influenza no período de estudo. Nesta coorte, 91,4% apresentavam fatores de risco para complicação e 34,3% haviam sido vacinados na última campanha de vacinação. Pneumonia foi a manifestação clínica mais frequente, ocorrendo em 57,0% da coorte. Outras manifestações foram doença gripal, bronquite crônica exacerbada, insuficiência cardíaca descompensada e crise asmática. Os casos estiveram distribuídos ao longo do ano, com pico epidêmico no outono-inverno. Houve circulação simultânea dos vírus da influenza A (H1N1pdm09 e H3N2) e B. Leitos de terapia intensiva foram necessários em 26,7% da coorte e suporte ventilatório, em 19,5%. Na análise multivariada, quatro fatores importantes associados à mortalidade hospitalar foram identificados: estar restrito ao leito (odds ratio ajustado [ORaj] 22.3; intervalo de confiança de 95% [IC 95%] 3.0-164); ser admitido na unidade de terapia intensiva (ORaj 8.9, IC 95% 1.4 4-55); relação Pa02/Fi02 <250 (ORaj 5.8; IC 95% 1.02-33) e aumento da creatinina sérica (>1 mg/dl) (ORaj 5.47; IC 95% 1.20-24). A vacinação sazonal contra influenza foi identificada como importante fator de proteção (ORaj 0.14; IC 95% 0.021-0.90). Conclusões A SARI associada a influenza acometeu sobretudo pacientes idosos com doenças preexistentes. A maioria dos pacientes evoluiu com insuficiência respiratória e mais de um quarto precisou de cuidados intensivos. O quadro clínico foi variável. Morte foi associada às características do hospedeiro e problemas relacionados à doença. A vacinação teve efeito protetor e o tipo viral não influiu no desfecho.

Espondilodiscitis: experiencia clínica en un hospital general de Chile / Spondylodiscitis: clinical experience in a Chilean general hospital

Introducción: La espondilodiscitis (ED) implica prolongados períodos de hospitalización, de latencia diagnóstica y riesgo de complicaciones a largo plazo. No existen publicaciones recientes en Chile al respecto. Objetivos: Caracterizar un grupo de pacientes con ED. Pacientes y Métodos: Serie clínica, que incluyó pacientes en un período de ocho años. Resultados: 37 pacientes, 37,8% mujeres y 62,2% hombres, con promedio etario 66,8 años; 64,9% adultos mayores, 35,1% diabéticos y 21,6% con co-morbilidad urológica. Los principales síntomas fueron dolor y fiebre. 89,2% tuvo elevación de VHS. 86,5% contó con resonancia magnética, que siempre fue confirmatoria, siendo la columna lumbar la localización más frecuente (43,2%). Se identificó etiología en 28/37 pacientes: en 71,4% cocáceas grampositivas (Staphylococcus aureus predominantemente), sólo en 10,7% M. tuberculosis. Staphylococcus aureus estuvo asociado a co-morbilidades médicas en forma significativa (p < 0,05) y el grupo de bacilos gramnegativos a historia hepatobiliar y/o intestinal (p < 0,05). El método de mayor rendimiento fue el cultivo obtenido por punción quirúrgica. El tratamiento antimicrobiano fue indicado en promedio por 63,8 días (IQR 53-72), con reacciones adversas en 18,9%. La estadía hospitalaria fue 38,9 días promedio, no existiendo fallecidos durante este período. 18,9% presentó secuelas motoras. Discusión: La mayoría de pacientes con ED correspondió a adultos mayores, siendo S. aureus la principal etiología. Hubo una baja frecuencia de M. tuberculosis. Resultó considerable la magnitud de efectos adversos asociados a la terapia antimicrobiana y las complicaciones neurológicas.

Background: Spondylodiscitis (SD) involves long periods of hospitalization, diagnostic latency and risk of long-term complications. No updated series are available in Chile and a change in demographic features and etiology is suspected. Aim: To characterize a group of patients with SD. Patients and Methods: Clinical series including patients over an 8 year period. Results: We identified 37 patients; 37.8% women and 62.2% men (mean age 66.8 years); 64.9% were elderly; 35.1% had diabetes and 21.6% urological comorbidity. Main symptoms were pain and fever. Erythrocyte sedimentation rate was elevated in 89.2%, and 86.5% patients had MRI, which was always confirmatory. Lumbar spine was the most common site of infection (43.2%). Etiology was identified in 28/37 patients: 71.4% yielded grampositive cocci (Staphylococcus aureus predominantly), Mycobacterium tuberculosis was identified in only 10.7%. Staphylococcus aureus was associated to medical comorbidities (p < 0,05) and gramnegative bacilli to hepatobiliar or intestinal symptoms (p < 0,05). Culture obtained by a surgical procedure had the highest yield. The average duration of antibiotic therapy was 63.8 days (IQR 53-72). Treatment-related side effects were detected in 18.9% of patients. The average hospital stay was 38.9 days. No deaths occurred during hospitalization. Motor sequelae were present in 18.9% of this series. Discussion: Most patients with SD were older adults. Staphylococcus aureus was predominant and M. tuberculosis was uncommon. Antibiotic side effects were relevant as well as the neurological complications.

Cotrimoxazol en infecciones óseas: toxicidad e impacto clínico y económico / Cotrimoxazole in bone-related infections: toxicity and clinical and economic impact

Background: Cotrimoxazole is a therapeutic option for bone-related infections but is associated to hyperkalemia and renal failure. Tolerance to this drug may reduce length of stay (LOS) and hospital charges. Aims: To evaluate renal, potassium toxicity, clinical outcome, and use of hospital resources in patients treated with cotrimoxazole for bone-related infections. Methods: Retrospective analysis of adult patients with bone-related infections confirmed by culture and treated with this drug. Serum potassium and creatinine levels were analyzed during follow-up and risk factors for hyperkalemia were searched. Length of stay (LOS) and hospital charges were compared. Clinical outcome was evaluated as a secondary endpoint. Results: From 2011 to 2014, 23 patients were identified (mean age 64.7 years). Diabetes mellitus, peripheral vascular disease, and previous amputations prevalence were high (82.6%, 47.8%, and 43.5%, respectively). Median serum potassium concentration increased significantly at first control (4.35 mEq/L to 4.9 mEq/L; p < 0.001), and also creatinine serum concentration (0.9 to 1.1 mg/dL; p < 0.05). Seven patients developed hyperkalemia. Cotrimoxazole was discontinued in 10 patients (43.5%), and in 6, discharge was postponed. Drugs active against the renin-angiotensin system (DAARAS) were associated with kyperkalemia (OR 10.8 IC95 1.37-85; p < 0.05). LOS was higher among patients with cotrimoxazole toxicity (median LOS 56 versus 30 days, p < 0.05). Patients with no cotrimoxazole interruption had less drug-related hospital charges (median values of 563 versus 2820 USD, respectively; p < 0.01). Conclusions: Cotrimoxazole use must be monitored in order to detect hyperkalemia or renal toxicity and suspend its prescription. Patients that use DAARAS have a higher risk of kyperkalemia. LOS and drug-related hospital charges are reduced when patients can tolerate cotrimoxazole.

Antecedentes: Cotrimoxazol es una alternativa en infecciones óseas pero se ha asociado al desarrollo de falla renal e hiperkalemia. Objetivo: Evaluar toxicidad renal, hiperkalemia, estadía y gastos hospitalarios y evolución clínica en un grupo de pacientes con infecciones óseas tratados con este compuesto. Pacientes y Métodos: Estudio retrospectivo-descriptivo de pacientes adultos con infecciones óseas confirmadas con cultivos y tratados con este compuesto. Seguimiento de creatinina y kalemia y búsqueda de factores de riesgo para hiperkalemia, comparación de gastos y estadía hospitalaria y análisis de eficacia clínica. Resultados: Desde el año 2011 al 2014 se identificaron 23 pacientes (promedio de edad 64,7 años). La prevalencia de diabetes mellitus tipo 2 (82,6%), enfermedad vascular periférica (47,8%) y amputaciones previas (43,5%) fue elevada. La mediana de la kalemia basal aumentó significativamente al primer control (4,35 a 4,9 mEq/L) al igual que la creatinina plasmática (0,9 a 1,1 mg/dL). Siete pacientes desarrollaron hiperkalemia (30,4%). Se suspendió cotrimoxazol en 10 casos (43,5%) y en 6 casos se postergó el alta. El uso de fármacos activos contra el sistema renina-angiotensina (FASRA) se asoció a hiperkalemia (OR 10,8 IC95 1,37-85; p < 0,05). La estadía hospitalaria fue mayor en el grupo con toxicidad a cotrimoxazol (mediana de 56 versus 30 días; p < 0,05) y los pacientes sin suspensión de terapia tuvieron menos gastos por fármacos (medianas de 563 vs 2.820 USD, p < 0,01). Conclusiones: El uso de cotrimoxazol debe ser monitorizado para detectar hiperkalemia o toxicidad renal y suspender su prescripción. Los pacientes que usan FASRA tienen mayor riesgo de hiperkalemia. La estadía y gastos hospitalarios por fármacos son menores en pacientes que toleran el cotrimoxazol.

Morbilidad y mortalidad asociada a hospitalizaciones por influenza pandémica A (H1N1) 2009 en dos hospitales de la Región Metropolitana y evaluación de su impacto económico / Morbidity and mortality associated to influenza A (H1N1) 2009 admissions in two hospitals of the Metropolitan area and analysis of its economic impact

Influenza A (H1N1) 2009 infection was an important cause of morbidity and mortality in Chile. Aim: To characterize the clinical pattern of hospitalized patients, identify risk factors associated with ICU admission or death, and evaluate its economic impact. Patients and Methods: Twenty five adult patients admitted to 2 hospitals in the Metropolitan Area from May 2009 to December 2010 with PCR confirmed H1N1 infection were analyzed. Total hospital charges were obtained and, using data of registered cases, expenses for the whole country during the first epidemic wave were estimated. Results: Aill cases presented a risk factor: age over 60 years old (n = 13, 52%), co-morbid conditions (n = 24, 96%) or pregnancy (n = 1, 4%). Pneumonia was present in 64% (n = 16) and 16% (n = 4) had hypotension. Only 6 patients (24%) had a CURB-65 score ≥ 2 and 36% (n = 9) requiring ICU admission. Case fatality rate was 16% (n = 4). By multivariate analysis, diabetes mellitus type 2 was independently associated with ICU admission or death (OR 8.12; IC95 1.11-59.2, p < 0.05). Hospital charges for those admitted to ICU or the intermediate care unit reached US$ 20,304, and US$ 1,262 for those admitted in general wards. We estimated US$ 20 million in hospital charges for influenza related hospitalizations during the first wave for the whole country. Conclusions: A high proportion of patients affected by influenza A (H1N1) 2009 infection required ICU admission during 2009-2010. Case fatality rate associated to this infection was high, and diabetes mellitus type 2 was a risk factor for ICU admission or death. Hospital charges were higher for those admitted in critical care units and represented an important expenditure for Chile during the first wave. The CURB-65 score was inappropriate to recognize patients at risk of hospitalization or ICU admission.

Introducción: La infección por influenza A (H1N1) pandémica representó una importante carga de morbilidad y mortalidad en Chile. Objetivo: Caracterización clínica de pacientes hospitalizados durante los años 2009 y 2010, identificar factores de riesgo asociados con ingreso a UCI o muerte y determinar el impacto económico de esta enfermedad. Pacientes y Métodos: Análisis de las características clínicas y evolución en un grupo de 25 pacientes adultos ingresados a dos hospitales institucionales en la Región Metropolitana confirmados por RPC desde mayo de 2009 a diciembre de 2010. Estudio de gastos hospitalarios y estimación de gasto nacional según registro de casos atendidos desde mayo a agosto de 2009. Resultados. Todos los pacientes presentaron una condición de riesgo: edad > 60 años (n: 13, 52%), co-morbilidad (n: 24, 96%) o embarazo ((n: 1, 4%). El 64% (n: 16) presentó neumonía y 16% tuvieron hipotensión arterial (n: 4). Sólo 6 pacientes (24%) tuvieron puntuación CURB-65 ≥ 2. Un 36% (n: 9) requirió manejo en Unidad de Cuidados Intensivos (UCI) y 4 pacientes fallecieron (16%). Por análisis multivariado, el antecedente de diabetes mellitus tipo 2 se asoció en forma significativa e independiente al ingreso a UCI o a un desenlace fatal (OR 8,12; IC95 1,11-59,2, p < 0,05). El gasto por paciente en aquellos que ingresaron a la UCI o Intermedio alcanzó los US$ 20.304 y US$ 1.262, para los que no ingresaron a estas unidades. Para Chile, se estimó un gasto mínimo de 20 millones de dólares por concepto de hospitalización para los primeros cuatro meses de la pandemia el 2009, asumiendo que 60% ingresó a UCI o Unidades Intermedias. Conclusiones: Una alta proporción de los pacientes afectados por influenza A (H1N1) 2009 requirió ingreso a UCI durante los años 2009-2010. La letalidad de esta infección fue elevada y la diabetes mellitus tipo 2 fue un factor de riesgo para ingreso a UCI o muerte. Los gastos hospitalarios fueron elevados, especialmente en los que ingresaron a unidades críticas. El sistema CURB-65 tiene una baja capacidad para reconocer riesgo de hospitalización o muerte en estos pacientes.