Assessing the influence of the COVID-19 pandemic on the incidence, clinical presentation, and clindamycin resistance rates of Streptococcus pyogenes infections.

Objectives: Streptococcus pyogenes (group A Streptococcus [GAS]) is a prevalent cause of community-acquired bacterial infections, with invasive GAS (iGAS) infections presenting severe morbimortality. Clindamycin is generally used based on its antitoxin effect. This study investigates changes in iGAS incidence, clinical presentation, outcomes, and clindamycin resistance in an adult cohort. Methods: This is a retrospective analysis of S. pyogenes episodes from a tertiary adult hospital in Barcelona (Spain) between 2015 and 2023. The pre-pandemic period includes data from 2015-2019. The pandemic period, from 2020-2021, and post-pandemic period comprised 2022 to the first semester of 2023. Results: The global incidence of GAS infections in the pre-pandemic and post-pandemic periods were 2.62 and 2.92 cases per 10.000 hospital admissions, whereas for iGAS cases, they were 1.85 and 2.34. However, a transient decrease was observed during the pandemic period: 1.07 and 0.78 per 10.000 hospital admissions. There was a significant decrease in GAS and iGAS infections during the pandemic period compared with the pre-pandemic incidence (P <0.001 for GAS infections and P = 0.001 for iGAS cases) and the post-pandemic incidence (P = 0.032 for GAS infections and P = 0.037 for iGAS cases). The most common source of infection was skin and soft tissue infections with 264 (54%) cases. Skin and soft tissue infections and cases of necrotizing fasciitis increased during the pandemic. Clindamycin resistance occurred in 13.5% of isolations during the pre-pandemic and 17.5% in post-pandemic period (P = 0.05). Conclusions: Our study revealed a temporary reduction in iGAS infections, followed by resurgence in the post-pandemic period. The observed rise in clindamycin resistance emphasizes the importance of monitoring local resistance patterns for tailored treatment.

Diagnosis of Bone Marrow Necrosis following Severe Vaso-Occlusive Crisis in Patient with Compound Heterozygous Sickle Cell Disease.

Introduction: Bone marrow necrosis is a rare entity that can develop in context of a sickle cell disease vaso-occlusive crisis. Its physiopathology is related to an endothelial dysfunction taking place in bone marrow microvasculature. Case Presentation: A 30-year-old patient with history of compound heterozygous sickle cell disease was admitted following SARS-CoV-2 infection with fever and diarrhea. After initial favorable evolution, he developed a severe vaso-occlusive crisis with intense hemolysis and multi-organ ischemic complications. Patient then developed high fever and hypoxemia. With the suspicion of acute thoracic syndrome, a red blood cell exchange was performed. Respiratory symptoms ceased but patient persisted febrile with very high levels of acute phase reactants, persistent pancytopenia, and leucoerythroblastic reaction. An infectious cause was ruled out. Afterward, bone marrow aspiration and bone marrow biopsy showed a picture of bone marrow necrosis, which is an extremely rare complication of vaso-occlusive crisis but, paradoxically, more frequent in milder heterozygote cases of sickle cell disease. Ultimately, large deposits of complement membrane attack complex (particles C5b-9) were demonstrated after incubation of laboratory endothelial cells with activated plasma from the patient. Discussion: The clinical presentation and findings are consistent with a case of bone marrow necrosis. In this setting, the demonstration of complement as a potential cause of the endothelial dysfunction mimics the pattern of atypical hemolytic uremic syndrome and other microangiopathic anemias. This dysregulation may be a potential therapeutic target for new complement activation blockers.

Mortality risk model validation in a prospective cohort of patients from the sixth wave of the COVID-19 pandemic in a hospital emergency department. / Validación del modelo de riesgo de mortalidad en una cohorte prospectiva de pacientes de la sexta ola epidémica de la COVID-19 en un servicio de urgencias hospitalario.

OBJECTIVES: To validate risk factors for mortality in patients treated for COVID-19 in a hospital emergency department during the sixth wave of the pandemic. MATERIAL AND METHODS: Prospective observational noninterventional study. We included patients over the age of 18 years with a confirmed diagnosis of COVID-19 between December 1, 2021, and February 28, 2022. For each patient we calculated a risk score based on age 50 years or older (2 points) plus 1 point each for the presence of the following predictors: Barthel index less than 90 points, altered level of consciousness, ratio of arterial oxygen saturation to fraction of inspired oxygen less than 400, abnormal breath sounds, platelet concentration less than 100 × 109/L, C-reactive protein level of 5 mg/dL or more, and glomerular filtration rate less than 45 mL/min. The model was assessed with the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 1156 patients included, 790 (68%) had received at least 2 vaccine doses. The probability of 30-day survival was 96%. A risk score was calculated for 609 patients. Four hundred seventeen patients were at low risk of death, 180 were at intermediate risk, and 10 were at high risk. The probability of death within 30 days was 1%, 13%, and 50% for patients in the 3 risk groups, respectively. The sensitivity, specificity, and positive and negative predictive values of a risk score of 3 points or less were 88%, 72%, 19%, 99%, respectively.The AUC for the model was 0.87. CONCLUSION: The risk model identified low risk of mortality and allowed us to safely discharge patients treated for COVID-19 in our tertiary-care hospital emergency department.

OBJETIVO: Validación de un indicador de mortalidad derivado durante los primeros meses de la pandemia de la COVID-19 en pacientes con COVID-19 atendidos durante la sexta ola epidémica en un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional prospectivo no intervencionista. Se incluyeron pacientes > 18 años diagnosticados de casos confirmados de COVID-19 (1 diciembre 2021-28 febrero 2022). Se calculó el indicador para cada paciente: edad $ 50 años (2 puntos), índice de Barthel 90 puntos (1 punto), alteración de consciencia (1 punto), índice de SaO2/FIO2 400 (1 punto), auscultación respiratoria patológica (1 punto), plaquetas 100 x 109/L (1 punto), proteína C reactiva $ 5 mg/dL (1 punto) y filtrado glomerular 45 mL/min (1 punto). El rendimiento del indicador se valoró con el análisis del área bajo la curva de la característica operativa del receptor (ABC-COR). RESULTADOS: De los 1.156 pacientes incluidos en el estudio, 790 (68%) habían recibido como mínimo una dosis de vacuna. La probabilidad de supervivencia a los 30 días de la serie fue del 96%. El indicador de riesgo se pudo calcular en 609 pacientes. Cuatrocientos diecisiete pacientes se clasificaron como de riesgo bajo, 182 de riesgo intermedio y 10 de riesgo alto. La probabilidad de mortalidad a los 30 días fue de 1%, 13% y 50%, respectivamente. La sensibilidad, especificidad y valores predictivos positivo y negativo para un punto de corte menor o igual a 3 puntos fue 88%, 72%, 19%, 99%, respectivamente. El ABC-COR para el indicador fue de 0,87. CONCLUSIONES: Un valor del indicador de bajo riesgo permite dar de alta con seguridad a los pacientes con COVID-19 que se atienden en un SUH de un centro de tercer nivel.

Validación del modelo de riesgo de mortalidad en una cohorte prospectiva de pacientes de la sexta ola epidémica de la COVID-19 en un servicio de urgencias hospitalario / Mortality risk model validation in a prospective cohort of patients from the sixth wave of the COVID-19 pandemic in a hospital emergency department

Objetivo. Validación de un indicador de mortalidad derivado durante los primeros meses de la pandemia de la COVID-19 en pacientes con COVID-19 atendidos durante la sexta ola epidémica en un servicio de urgencias hospitalario (SUH). Método. Estudio observacional prospectivo no intervencionista. Se incluyeron pacientes > 18 años diagnosticados de casos confirmados de COVID-19 (1 diciembre 2021-28 febrero 2022). Se calculó el indicador para cada paciente: edad $ 50 años (2 puntos), índice de Barthel < 90 puntos (1 punto), alteración de consciencia (1 punto), índice de SaO2/FIO2 < 400 (1 punto), auscultación respiratoria patológica (1 punto), plaquetas < 100 x 109/L (1 punto), proteína C reactiva $ 5 mg/dL (1 punto) y filtrado glomerular < 45 mL/min (1 punto). El rendimiento del indicador se valoró con el análisis del área bajo la curva de la característica operativa del receptor (ABC-COR). Resultados. De los 1.156 pacientes incluidos en el estudio, 790 (68%) habían recibido como mínimo una dosis de vacuna. La probabilidad de supervivencia a los 30 días de la serie fue del 96%. El indicador de riesgo se pudo calcular en 609 pacientes. Cuatrocientos diecisiete pacientes se clasificaron como de riesgo bajo, 182 de riesgo intermedio y 10 de riesgo alto. La probabilidad de mortalidad a los 30 días fue de 1%, 13% y 50%, respectivamente. La sensibilidad, especificidad y valores predictivos positivo y negativo para un punto de corte menor o igual a 3 puntos fue 88%, 72%, 19%, 99%, respectivamente. El ABC-COR para el indicador fue de 0,87. Conclusión. Un valor del indicador de bajo riesgo permite dar de alta con seguridad a los pacientes con COVID-19 que se atienden en un SUH de un centro de tercer nivel. (AU)

Objective. To validate risk factors for mortality in patients treated for COVID-19 in a hospital emergency department during the sixth wave of the pandemic. Method. Prospective observational noninterventional study. We included patients over the age of 18 years with a confirmed diagnosis of COVID-19 between December 1, 2021, and February 28, 2022. For each patient we calculated a risk score based on age 50 years or older (2 points) plus 1 point each for the presence of the following predictors: Barthel index less than 90 points, altered level of consciousness, ratio of arterial oxygen saturation to fraction of inspired oxygen less than 400, abnormal breath sounds, platelet concentration less than 100 × 109 /L, C-reactive protein level of 5 mg/dL or more, and glomerular filtration rate less than 45 mL/min. The model was assessed with the area under the receiver operating characteristic curve (AUC). Results. Of the 1156 patients included, 790 (68%) had received at least 2 vaccine doses. The probability of 30-day survival was 96%. A risk score was calculated for 609 patients. Four hundred seventeen patients were at low risk of death, 180 were at intermediate risk, and 10 were at high risk. The probability of death within 30 days was 1%, 13%, and 50% for patients in the 3 risk groups, respectively. The sensitivity, specificity, and positive and negative predictive values of a risk score of 3 points or less were 88%, 72%, 19%, 99%, respectively.The AUC for the model was 0.87. Conclusion. The risk model identified low risk of mortality and allowed us to safely discharge patients treated for COVID-19 in our tertiary-care hospital emergency department. (AU)

Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide.

Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-transplant cyclophosphamide (PTCy) and the effects of Tac IPV on the occurrence of acute GVHD (aGVHD) were analyzed. Tac IPV was calculated from pre-dose concentrations (C0) measured during the first month after Tac initiation. The cumulative rates of grades II-IV and grades III-IV aGVHD at day +100 were 22.7% and 7%, respectively. Higher Tac IPV was associated with a greater risk of developing GVHD, with patients having IPV > 50th percentile having significantly higher rates of grades II-IV (34.9% vs. 10.8%; hazard ratio [HR] 3.858, p < 0.001) and grades III-IV (12.7% vs. 1.5%; HR 9.69, p = 0.033) aGVHD than patients having IPV ≤ 50th percentile. Similarly, patients with IPV > 75th percentile had higher rates of grades II-IV (41.9% vs. 16.5%; HR 3.30, p < 0.001) and grades III-IV (16.1% vs. 4.1%; HR 4.99, p = 0.012) aGVHD than patients with IPV ≤ 75th percentile. Multivariate analyses showed that high Tac IPV (>50th percentile) was an independent risk factor for grades II-IV (HR 2.99, p = 0.018) and grades III-IV (HR 9.12, p = 0.047) aGVHD. Determination of Tac IPV soon after alloHSCT could be useful in identifying patients at greater risk of aGVHD.

Risk score for mortality due to COVID-19: a prospective temporal validation cohort study in the emergency department of a tertiary care hospital. / Validación temporal de un modelo de riesgo de mortalidad por COVID-19 en una cohorte prospectiva en un servicio de urgencias de un hospital de tercer nivel.

OBJECTIVES: To validate a previously described hospital emergency department risk model to predict mortality in patients with COVID-19. MATERIAL AND METHODS: Prospective observational noninterventional study. Patients aged over 18 years diagnosed with COVID-19 were included between December 1, 2020, and February 28, 2021. We calculated a risk score for each patient based on age 50 years (2 points) plus 1 point each for the presence of the following predictors: Barthel index 90 points, altered level of consciousness, ratio of arterial oxygen saturation to fraction of inspired oxygen 400, abnormal breath sounds, platelet concentration 100 × 109/L, C reactive protein level 5 mg/dL, and glomerular filtration rate 45 mL/min. The dependent variable was 30-day mortality. We assessed the score's performance with the area under the receiver operating characteristic curve (AUC). RESULTS: The validation cohort included 1223 patients. After a median follow-up of 80 days, 143 patients had died; 901 patients were classified as having low risk (score, 4 points), 270 as intermediate risk (5-6 points), and 52 as high risk ( 7 points). Thirty-day mortality rates at each risk level were 2.8%, 22.5%, and 65.4%, respectively. The AUC for the score was 0.883; for risk categorization, the AUC was 0.818. CONCLUSION: The risk score described is useful for stratifying risk for mortality in patients with COVID-19 who come to a tertiary-care hospital emergency department.

OBJETIVO: Validación de un indicador de mortalidad previamente descrito en pacientes con COVID-19 en un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional prospectivo no intervencionista. Se incluyeron pacientes 18 años diagnosticados de COVID-19 (1 de diciembre de 2020 hasta 28 de febrero de 2021). Se calculó el indicador para cada paciente: edad 50 años (2 puntos), índice de Barthel 90 puntos (1 punto), alteración de consciencia (1 punto), índice de SaO2/ FIO2 400 (1 punto), auscultación respiratoria patológica (1 punto), plaquetas 100 x 109/L (1 punto), proteína C reactiva 5 mg/dL (1 punto) y filtrado glomerular 45 mL/min (1 punto). La variable dependiente fue la mortalidad observada a 30 días. El rendimiento del indicador se valoró con el análisis del área bajo la curva de la característica operativa del receptor (ABC-COR). RESULTADOS: La validación del indicador se realizó sobre una cohorte de 1.223 pacientes. Tras una mediana de seguimiento de 80 días, 143 pacientes habían fallecido. Un total de 901 pacientes fueron catalogados como riesgo bajo (indicador 4 puntos), 270 lo fueron como riesgo intermedio (5-6 puntos) y 52 como riesgo alto ( 7 puntos). La mortalidad a 30 días observada en cada categoría fue de 2,8%, 22,5% y 65,4%, respectivamente. El ABC-COR fue de 0,883 para el indicador utilizado cuantitativamente y de 0,818 cuando se usó cualitativamente en forma de categorías de riesgo. CONCLUSIONES: El indicador descrito es una herramienta útil para estratificar el riesgo de mortalidad de los pacientes con COVID-19 que consultan a un SUH de un centro de tercer nivel.

Validación temporal de un modelo de riesgo de mortalidad por COVID-19 en una cohorte prospectiva en un servicio de urgencias de un hospital de tercer nivel / Risk score for mortality due to COVID-19: a prospective temporal validation cohort study in the emergency department of a tertiary care hospital

Objetivo. Validación de un indicador de mortalidad previamente descrito en pacientes con COVID-19 en un servicio de urgencias hospitalario (SUH). Método. Estudio observacional prospectivo no intervencionista. Se incluyeron pacientes $ 18 años diagnosticados de COVID-19 (1 de diciembre de 2020 hasta 28 de febrero de 2021). Se calculó el indicador para cada paciente: edad $ 50 años (2 puntos), índice de Barthel < 90 puntos (1 punto), alteración de consciencia (1 punto), índice de SaO2/ FIO2 < 400 (1 punto), auscultación respiratoria patológica (1 punto), plaquetas < 100 x 109/L (1 punto), proteína C reactiva $ 5 mg/dL (1 punto) y filtrado glomerular < 45 mL/min (1 punto). La variable dependiente fue la mortalidad observada a 30 días. El rendimiento del indicador se valoró con el análisis del área bajo la curva de la característica operativa del receptor (ABC-COR). Resultados. La validación del indicador se realizó sobre una cohorte de 1.223 pacientes. Tras una mediana de seguimiento de 80 días, 143 pacientes habían fallecido. Un total de 901 pacientes fueron catalogados como riesgo bajo (indicador # 4 puntos), 270 lo fueron como riesgo intermedio (5-6 puntos) y 52 como riesgo alto ($ 7 puntos). La mortalidad a 30 días observada en cada categoría fue de 2,8%, 22,5% y 65,4%, respectivamente. El ABC-COR fue de 0,883 para el indicador utilizado cuantitativamente y de 0,818 cuando se usó cualitativamente en forma de categorías de riesgo. Conclusión. El indicador descrito es una herramienta útil para estratificar el riesgo de mortalidad de los pacientes con COVID-19 que consultan a un SUH de un centro de tercer nivel.

Objective. To validate a previously described hospital emergency department risk model to predict mortality in patients with COVID-19. Methods. Prospective observational noninterventional study. Patients aged over 18 years diagnosed with COVID-19 were included between December 1, 2020, and February 28, 2021. We calculated a risk score for each patient based on age $50 years (2 points) plus 1 point each for the presence of the following predictors: Barthel index <90 points, altered level of consciousness, ratio of arterial oxygen saturation to fraction of inspired oxygen <400, abnormal breath sounds, platelet concentration <100 × 109/L, C reactive protein level $5 mg/dL, and glomerular filtration rate <45 mL/min. The dependent variable was 30-day mortality. We assessed the score’s performance with the area under the receiver operating characteristic curve (AUC). Results. The validation cohort included 1223 patients. After a median follow-up of 80 days, 143 patients had died; 901 patients were classified as having low risk (score, #4 points), 270 as intermediate risk (5-6 points), and 52 as high risk ($7 points). Thirty-day mortality rates at each risk level were 2.8%, 22.5%, and 65.4%, respectively. The AUC for the score was 0.883; for risk categorization, the AUC was 0.818. Conclusion. The risk score described is useful for stratifying risk for mortality in patients with COVID-19 who come to a tertiary-care hospital emergency department.