Eficácia da ivermectina e atazanavir no tempo de recuperação dos sintomas de covid-19: uma coorte prospectiva / Effectiveness of ivermectin and atazanavir on time to resolution from covid-19 symptoms: a prospective cohort / Eficacia de ivermectina y atazanavir en el tiempo hasta lá resolución de los síntomas de covid-19: una cohorte prospectiva

Objetivo: avaliar a eficácia da Ivermectina e do Atazanavir em comparação com placebo no tempo de resolução dos sintomas e no tempo de duração da doença por COVID-19. Método: estudo observacional, de coorte prospectivo, longitudinal, descritivo e analítico com pacientes sintomáticos ambulatoriais, acompanhados por 06 meses em duas Unidades Básicas de Saúde para atendimento de COVID-19 em Teresina- Piauí, Brasil, no período de novembro a abril de 2021 identificados por amostragem aleatória 1:1:1. Foram realizados exames Reverse transcription polymerase chain reaction (RT-PCR) para confirmação laboratorial da suspeita de infecção pelo novo coronavírus e avaliação sociodemográfica e clínica. Resultados: dos 87 pacientes randomizados, 62,1% (n=54) eram do sexo masculino, com média de idade de 35,1 anos, possuíam companheira (53,9%), baixa renda (50,6%), eutróficos (40,7%) e sem comorbidades de saúde (78,2%). Não houve diferença entre o tempo médio para resolução dos sintomas, que foi de 21 dias (IQR, 8-30) no grupo atazanavir, 30 dias (IQR, 5-90) no grupo ivermectina em comparação com 14 dias (IQR, 9-21) no grupo controle. No dia 180, houve resolução dos sintomas em 100% no grupo placebo, 93,9% no grupo atazanavir e 95% no grupo ivermectina. A duração mediana da doença foi de 08 dias em todos os braços do estudo. Conclusão: o tratamento com atazanavir (6 dias) e ivermectina (3 dias) não reduziu o tempo de resolução dos sintomas e nem o tempo de duração da doença entre os pacientes ambulatoriais com COVID-19 leve em comparação com o grupo placebo. Os resultados não suportam o uso de ivermectina e atazanavir para tratamento de COVID-19 leve a moderado.

Objective: to evaluate the effectiveness of Ivermectin and Atazanavir compared to placebo in the time to resolution of symptoms and duration of illness due to COVID-19. Method: observational, prospective, longitudinal, descriptive and analytical cohort study with symptomatic outpatients, followed for 06 months in two Basic Health Units for COVID-19 care in Teresina-Piauí, Brazil, from November to April 2021 identified by 1:1:1 random sampling. Reverse transcription polymerase chain reaction (RT-PCR) tests were performed for laboratory confirmation of suspected infection with the new coronavirus and sociodemographic and clinical evaluation. Results: of the 87 randomized patients, 62.1% (n=54) were male, with a mean age of 35.1 years, had a partner (53.9%), low income (50.6%), eutrophic (40.7%) and without health comorbidities (78.2%). There was no difference between the median time to resolution of symptoms, which was 21 days (IQR, 8-30) in the atazanavir group, 30 days (IQR, 5- 90) in the ivermectin group compared with 14 days (IQR, 9- 21) in the control group. At day 180, there was resolution of symptoms in 100% in the placebo group, 93.9% in the atazanavir group, and 95% in the ivermectin group. The median duration of illness was 8 days in all study arms. Conclusion: Treatment with atazanavir (6 days) and ivermectin (3 days) did not reduce the time to symptom resolution or the duration of illness among outpatients with mild COVID-19 compared to the placebo group. The results do not support the use of ivermectin and atazanavir for the treatment of mild to moderate COVID-19.

Objetivo: evaluar la efectividad de Ivermectina y Atazanavir en comparación con placebo en el tiempo de resolución de los síntomas y duración de la enfermedad por COVID-19. Método: estudio de cohorte observacional, prospectivo, longitudinal, descriptivo y analítico con pacientes ambulatorios sintomáticos, seguidos durante 06 meses en dos Unidades Básicas de Salud para atención de COVID-19 en Teresina-Piauí, Brasil, de noviembre a abril de 2021 identificados por 1:1:1 muestreo aleatorio. Se realizaron pruebas de reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) para confirmación de laboratorio de sospecha de infección por el nuevo coronavirus y evaluación sociodemográfica y clínica. Resultados: de los 87 pacientes aleatorizados, 62,1% (n=54) eran del sexo masculino, con una edad media de 35,1 años, tenían pareja (53,9%), bajos ingresos (50,6%), eutróficos (40,7%) y sin comorbilidades de salud (78,2%). No hubo diferencia entre la mediana de tiempo hasta la resolución de los síntomas, que fue de 21 días (RIC, 8-30) en el grupo de atazanavir, 30 días (RIC, 5- 90) en el grupo de ivermectina en comparación con 14 días (RIC, 9 - 21) en el grupo control. En el día 180, hubo una resolución de los síntomas del 100 % en el grupo de placebo, del 93,9 % en el grupo de atazanavir y del 95 % en el grupo de ivermectina. La mediana de duración de la enfermedad fue de 8 días en todos los brazos del estudio. Conclusión: El tratamiento con atazanavir (6 días) e ivermectina (3 días) no redujo el tiempo de resolución de los síntomas ni la duración de la enfermedad entre los pacientes ambulatorios con COVID-19 leve en comparación con el grupo placebo. Los resultados no respaldan el uso de ivermectina y atazanavir para el tratamiento de la COVID-19 de leve a moderada.

Cefalea atribuida a ictus isquémico. Actualización semiológica y diagnóstica / Headache attributed to ischaemic stroke. An update on its semiology and diagnosis

Introducción: La cefalea es un síntoma frecuente tras el ictus isquémico agudo. Su identificación y diagnóstico constituyen un reto por el perfil de paciente y los criterios diagnósticos actuales de esta entidad. Los objetivos del estudio fueron determinar la prevalencia de cefalea atribuida a ictus isquémico y su forma persistente, y analizar las variables clinicodemográficas y el grado de cumplimiento de los criterios de la Clasificación Internacional de Cefaleas (ICHD-III). Pacientes y métodos: Es un estudio observacional analítico de cohortes prospectivo de pacientes ingresados con ictus isquémico agudo en la unidad de ictus de un hospital de tercer nivel en un período de 12 meses. Resultados: Se incluyó a 244 pacientes con ictus isquémico agudo (el 59,8%, varones; edad media: 71 ± 12,8 años). El 23,2% presentó cefalea en el momento del ingreso o bien en las primeras 72 horas y el 12,5% de ellos presentó cefalea persistente atribuida a ictus isquémico. El 62,5% cumplió los criterios diagnósticos de acuerdo con la ICHD-III. Conclusión: La cefalea tras el ictus isquémico es un síntoma frecuente. Su aparición se asoció al sexo femenino, al ictus de territorio vertebrobasilar y a puntuaciones bajas en la National Institutes of Health Stroke Scale. Sería recomendable revisar los criterios diagnósticos actuales.(AU)

Introduction: Headache is a common symptom in acute ischemic stroke which is often overlooked and undertreated because of focus in neurologic function, communication difficulties in stroke patients and the current diagnostic criteria of this type of headache. The present study aimed to determine the prevalence of Acute and Persistent Headache Attributed to Ischemic Stroke and to analyze the fulfillment of the criteria of the International Classification of Headaches (ICHD-IID). Patients and methods: Prospective observational analytical cohort study. The study population consisted of patients with acute ischemic stroke admitted to the Stroke Unit of a tertiary care hospital over a period of 12 months. Results: Two hundred and forty-four patients with acute ischemic stroke (59.8% males, mean age 71+12.8 years) were included. Headache at onset or at the first 72 hours was present in 23.2% and 12.5% of them presented persistent headache attributed to ischemic stroke. Only 62.5% of the headaches at stroke onset fulfilled the diagnostic criteria of ICHD-III. Conclusion: Headache after ischemic stroke is a common symptom. It was associated with female sex, posterior circulation stroke and low scores on the National Institutes of Health Stroke Scale (NIHSS). The current diagnostic criteria should be reviewed.

Intradural extramedullary tumors. Retrospective cohort study assessing prognostic factors for functional outcome in adult patients / Tumores intradurales-extramedulares. Estudio retrospectivo de cohorte valorando factores predictores de «outcome» en pacientes adultos

Objective The purpose of this study is to analyze a series of patients with intradural extramedullary tumors (IDEM) and assess factors that may modify or determine the final long term outcome and management. Materials and methods Single Center, retrospective study of a series of surgical patients with IDEM lesions from our Institution operated between 2010 and 2021. Patients with less than 6 months of follow up were excluded. Several preoperative demographics, clinical, imaging and surgical features, as well as histopathology, recurrence and adjuvancy were assessed. Patients’ final clinical outcome was categorized using the McCormick scale. Results A total of 203 patients with a mean follow-up of 30.50 months (range 6–130) were included. 57.64% of the analyzed population was female and the mean age was 50.51 years. The most frequent location of the tumors was dorsal (34.98%) followed by the lumbar region (32.02%). Total resection was achieved in 84.24% of cases, and the most frequent histopathology was Schwannoma (36.45%), followed by Meningioma (30.05%). Pain was the most usual initial symptom (63.05%). In our analysis, functional outcome after surgery was associated with statistical significance with preoperative McCormick grade, tumor type, EOR and postoperative complications such as hematoma and sphincter involvement. Conclusion The management of these lesions depends on many factors. It is worthy of mention that clinical presentation, EOR, histopathology and postoperative complications have shown significant prognostic value for the final outcome. Early treatment with the intention of achieving GTR when possible, using carefully tailored approaches, should be considered before the onset of significant symptoms (AU)

Objetivo Analizar una serie de pacientes con tumores intradurales extramedulares y evaluar factores que pueden modificar o determinar el resultado final y el manejo a largo plazo. Materiales y métodos Estudio monocéntrico, retrospectivo de una cohorte de pacientes quirúrgicos con lesiones intradurales extramedulares (IDEM) operados entre 2010 y 2021 y un mínimo de seis meses de seguimiento. Se evaluaron características clínicas, de imagen y quirúrgicas, histopatología, recurrencia y adyuvancia. El resultado clínico final de los pacientes se categorizó utilizando la escala de McCormick. Resultados Se incluyeron un total de 203 pacientes con un seguimiento medio de 30,50 meses (rango 6-130). De la población analizada, 57,64% era del sexo femenino y la edad media fue de 50,51 años. La localización más frecuente de los tumores fue dorsal (34,98%) seguida de la región lumbar (32,02%). La resección total se logró en 84,24% de los casos, y la histopatología más frecuente fue el schwannoma (36,45%), seguido del meningioma (30,05%). El dolor fue el síntoma inicial más habitual (63,05%). En nuestro análisis, el resultado funcional posoperatorio se asoció con significancia estadística con el grado de McCormick preoperatorio, la histopatología, el grado de resección y las complicaciones posoperatorias como el hematoma y la afectación esfinteriana. Conclusión El manejo de estas lesiones depende de muchos factores. Cabe mencionar que la presentación clínica, el grado de resección, la histopatología y las complicaciones posoperatorias han mostrado un importante valor pronóstico para el desenlace. Se debe considerar el tratamiento temprano con la intención de lograr resección total cuando sea posible, mediante abordajes cuidadosamente adaptados, antes de la aparición de síntomas significativos (AU)

Ipsilateral proximal and shaft femoral fractures: Results of two treatment strategies / Fracturas ipsilaterales proximales y diafisarias del fémur: resultados de 2 estrategias de tratamiento

Introduction: Ipsilateral proximal and shaft femoral fractures typically occur in young adults after high-energy trauma. No consensus exists regarding the optimal internal fixation device or surgical strategy for these complex fractures. Our main objective is to identify differences on outcomes and complications between patients treated with one or combined implants. Material and method: This is a single-center retrospective cohort study in patients with associated fractures of the proximal (31 AO) and shaft femur (32 AO). We divided the patients into two groups according to the use of single (Group I) or combined implants (Group II). Demographic, clinical, radiological, surgical data and development of complications were collected.Results: We identified 28 patients (19 men and 9 women) with an average age of 43 years. We used an anterograde femoral nail in group I (17 patients) and a retrograde femoral nail or a plate associated with hip lag screws or sliding hip screw in Group II (11 patients). Patients were followed up for 26.28 (9.12–62.88) months. Osteonecrosis of the femoral head, osteoarthritis, infection or nonunion was found in 9 patients (32%). No significant differences (p 0.70) were found in complications between two groups or between definitive surgical fixation before or after the first 24h. Conclusions: No differences in the development of complications or timing of definitive fixation were found between the use of one or combined implants in ipsilateral proximal femur and shaft fractures. Regardless of the implant chosen, an appropriate osteosynthesis technique is crucial, even so high complication rates are expected.

Introducción: Las fracturas ipsilaterales proximales y diafisarias del fémur suelen ocurrir en adultos jóvenes después de un traumatismo de alta energía. No existe consenso sobre el dispositivo de fijación interna óptimo o la estrategia quirúrgica para estas fracturas complejas. Nuestro principal objetivo es identificar las diferencias en los resultados y complicaciones entre los pacientes tratados con un implante o combinados. Material y método: Este es un estudio de cohorte retrospectivo unicéntrico en pacientes con fracturas asociadas del fémur proximal (31 AO) y diafisarias (32 AO). Dividimos a los pacientes en 2 grupos según el uso de implantes únicos (grupo i) o combinados (grupo ii). Se recogieron datos demográficos, clínicos, radiológicos, quirúrgicos y complicaciones. Resultados: Se identificaron 28 pacientes (19 hombres y 9 mujeres) con una edad promedio de 43 años. Utilizamos un clavo femoral anterógrado en el grupo i (17 pacientes) y un clavo femoral retrógrado o una placa con tornillos a compresión o tornillo deslizante de cadera en el grupo ii (11 pacientes). Los pacientes fueron seguidos durante 26,28 (9,12-62,88) meses. Se encontró osteonecrosis de la cabeza femoral, osteoartritis, infección o seudoartrosis en 9 pacientes (32%). No se encontraron diferencias significativas (p=0,70) en las complicaciones entre los 2 grupos o entre la fijación quirúrgica definitiva antes o después de las primeras 24h. Conclusiones: No se encontraron diferencias en el desarrollo de complicaciones o el momento de la fijación definitiva entre el uso de un implante o combinado en fracturas ipsilaterales de fémur proximal y diafisario. Independientemente del implante elegido, una técnica de osteosíntesis adecuada es crucial; aun así son esperables altas tasas de complicaciones.(AU)

[Artículo traducido] Fracturas ipsilaterales proximales y diafisarias del fémur: resultados de dos estrategias de tratamiento / Ipsilateral proximal and shaft femoral fractures: Results of two treatment strategies

Introduction: Ipsilateral proximal and shaft femoral fractures typically occur in young adults after high-energy trauma. No consensus exists regarding the optimal internal fixation device or surgical strategy for these complex fractures. Our main objective is to identify differences on outcomes and complications between patients treated with one or combined implants. Material and method: This is a single-center retrospective cohort study in patients with associated fractures of the proximal (31 AO) and shaft femur (32 AO). We divided the patients into two groups according to the use of single (Group I) or combined implants (Group II). Demographic, clinical, radiological, surgical data and development of complications were collected.Results: We identified 28 patients (19 men and 9 women) with an average age of 43 years. We used an anterograde femoral nail in group I (17 patients) and a retrograde femoral nail or a plate associated with hip lag screws or sliding hip screw in Group II (11 patients). Patients were followed up for 26.28 (9.12–62.88) months. Osteonecrosis of the femoral head, osteoarthritis, infection or nonunion was found in 9 patients (32%). No significant differences (p 0.70) were found in complications between two groups or between definitive surgical fixation before or after the first 24h. Conclusions: No differences in the development of complications or timing of definitive fixation were found between the use of one or combined implants in ipsilateral proximal femur and shaft fractures. Regardless of the implant chosen, an appropriate osteosynthesis technique is crucial, even so high complication rates are expected.

Introducción: Las fracturas ipsilaterales proximales y diafisarias del fémur suelen ocurrir en adultos jóvenes después de un traumatismo de alta energía. No existe consenso sobre el dispositivo de fijación interna óptimo o la estrategia quirúrgica para estas fracturas complejas. Nuestro principal objetivo es identificar las diferencias en los resultados y complicaciones entre los pacientes tratados con un implante o combinados. Material y método: Este es un estudio de cohorte retrospectivo unicéntrico en pacientes con fracturas asociadas del fémur proximal (31 AO) y diafisarias (32 AO). Dividimos a los pacientes en 2 grupos según el uso de implantes únicos (grupo i) o combinados (grupo ii). Se recogieron datos demográficos, clínicos, radiológicos, quirúrgicos y complicaciones. Resultados: Se identificaron 28 pacientes (19 hombres y 9 mujeres) con una edad promedio de 43 años. Utilizamos un clavo femoral anterógrado en el grupo i (17 pacientes) y un clavo femoral retrógrado o una placa con tornillos a compresión o tornillo deslizante de cadera en el grupo ii (11 pacientes). Los pacientes fueron seguidos durante 26,28 (9,12-62,88) meses. Se encontró osteonecrosis de la cabeza femoral, osteoartritis, infección o seudoartrosis en 9 pacientes (32%). No se encontraron diferencias significativas (p=0,70) en las complicaciones entre los 2 grupos o entre la fijación quirúrgica definitiva antes o después de las primeras 24h. Conclusiones: No se encontraron diferencias en el desarrollo de complicaciones o el momento de la fijación definitiva entre el uso de un implante o combinado en fracturas ipsilaterales de fémur proximal y diafisario. Independientemente del implante elegido, una técnica de osteosíntesis adecuada es crucial; aun así son esperables altas tasas de complicaciones.(AU)

Predictores radiológicos del volumen final del infarto cerebral en pacientes con obstrucción vascular proximal / Radiological predictors of final infarct volume in patients with proximal vascular occlusion

Introducción: Múltiples variables clínicas y radiológicas están involucradas en el pronóstico neurológico de los pacientes con accidente cerebrovascular (ACV) isquémico. Alrededor del 30% de los ACV isquémicos son causados por la obstrucción vascular proximal del circuito anterior; en estos casos, la utilidad de la trombólisis sistémica es limitada. La angiotomografía está indicada en los pacientes que pueden ser candidatos a tratamiento endovascular. Diferentes factores radiológicos como el grado de colaterales leptomeníngeas, o el largo, la densidad o la extensión del trombo, fueron descritos como predictores del pronóstico neurológico tras un ACV isquémico con compromiso vascular proximal. El volumen final del infarto cerebral se correlaciona con la mortalidad y el grado funcional a largo plazo de estos pacientes. El propósito de este estudio es determinar los mejores predictores radiológicos del volumen final del infarto cerebral en pacientes con ACV isquémico con compromiso proximal, utilizando angiotomografía. Materiales y métodos: Realizamos un estudio observacional retrospectivo. Incluimos pacientes adultos con ACV isquémico causado por la obstrucción de un vaso proximal, diagnosticados mediante angiotomografía en el período de junio de 2009 a diciembre de 2019. Medimos la densidad y el largo del trombo en la adquisición sin contraste, registramos el grado de colaterales leptomeníngeas y la extensión del trombo utilizando el clot burden score. Luego medimos el volumen final del infarto en una tomografía de control y analizamos el grado de correlación entre estos factores radiológicos en el volumen infartado. Resultados: Incluimos 54 pacientes con ACV isquémico por compromiso vascular proximal; 41 (75%) fueron mujeres. La mediana de edad fue de 82 años. Alrededor del 60% de los ACV comprometieron el hemisferio derecho y el vaso más afectado fue el segmento M1 de la arteria cerebral media (40,7%)...(AU)

Introduction: Various clinical and radiologic variables impact the neurologic prognosis of patients with ischemic cerebrovascular accidents. About 30% of ischemic cerebrovascular accidents are caused by proximal obstruction of the anterior circulation; in these cases, systemic thrombolysis is of limited usefulness. CT angiography is indicated in candidates for endovascular treatment. Various radiologic factors, including the grade of leptomeningeal collateral circulation, as well as the length, density, and extension of the thrombus, have been identified as predictors of neurologic prognosis after anterior ischemic cerebrovascular accidents due to proximal vascular obstruction. Final infarct volume correlations with mortality and long-term functional outcome in these patients. This study aimed to determine the best predictors of final infarct volume on CT angiography in patients with ischemic cerebral accidents due to proximal occlusion. Materials and methods: This retrospective observational study included adults with ischemic cerebrovascular accidents due to obstruction of the anterior circulation diagnosed by CT angiography in the period comprising June 2009 through December 2019. We measured the length and density of the thrombus in unenhanced CT images, and we used the clot burden score to record the grade of leptomeningeal collateral circulation and the extension of the thrombus. Then we measured the final infarct volume on follow-up CT and analyzed the correlations among these radiologic factors in the infarct volume. Results: We included 54 patients [mean age, 82 y; 41 (75%) women] with ischemic cerebrovascular accidents due to proximal occlusion. About 60% of the cerebrovascular accidents affected the right cerebral hemisphere, and the most commonly affected vessel was the M1 segment of the medial cerebral artery (40.7%)...(AU)

Efecto de la N-acetilcisteína en la mortalidad de pacientes ingresados por COVID-19: estudio de cohorte retrospectivo / Impact of N-Acetylcysteine in the mortality of patients hospitalized with COVID-19: a retrospective cohort study

Introducción y objetivo La N-acetilcisteína se ha propuesto para el tratamiento de COVID-19 gracias a sus efectos mucolítico, antioxidante y antiinflamatorio. El presente estudio tiene como objetivo evaluar su efecto en pacientes ingresados con COVID-19, en términos de mortalidad. Material y métodos Estudio de cohorte retrospectivo unicéntrico. Se incluyeron todos los pacientes ingresados por COVD-19 entre marzo y abril de 2020 en nuestro hospital. Resultados Un total de 378 pacientes fueron incluidos; de ellos, 196 (51,9%) fueron hombres, la edad media fue de 73,3±14,5 años. Un total de 199 (52,6%) pacientes recibieron tratamiento con N-acetilcisteína. Más del 70% tuvieron tos, fiebre y/o disnea. La mortalidad hospitalaria global fue del 26,7%. Un análisis multivariante mediante regresión logística identificó la edad de los pacientes [mayores de 80 años; OR: 8,4 (IC95%: 3-23,4)], una afectación radiológica moderada o grave medida por la escala RALE [OR: 7,3 (IC95%: 3,2-16,9)], el consumo de tabaco [OR: 2,8 (IC95%: 1,3-6,1)] y arritmia previa [OR: 2,8 (IC95%: 1,3-6,2)] como factores de riesgo que se asociaron independientemente con la mortalidad durante el ingreso. El tratamiento con N-acetilcisteína fue identificado como factor protector [OR: 0,57 (IC95%: 0,31-0,99)]. El asma podría representar asimismo un factor protector de mortalidad, aunque en el presente estudio no alcanza significación estadística [OR: 0,19 (IC95%: 0,03-1,06)]. Conclusiones Los pacientes con COVID-19 tratados con N-acetilcisteína presentaron una menor mortalidad y mejor evolución en nuestro estudio. Futuros estudios prospectivos o ensayos clínicos aleatorizados deben confirmar el papel de la N-acetilcisteína en pacientes con COVID-19 (AU)

Introduction and aim N-acetylcysteine has been proposed for the treatment of COVID-19 thanks to its mucolytic, antioxidant and anti-inflammatory effects. Our aim is to evaluate its effect on patients admitted with COVID-19 in mortality terms. Material and methods Retrospective single-center cohort study. All patients admitted to our hospital for COVID-19 from March to April 2020 have been considered. Results A total of 378 patients were included, being 196 (51.9%) men, with an average age of 73.3±14.5 years. The 52.6% (199) received treatment with N-acetylcysteine. More than 70% presented coughs, fever, and/or dyspnea. The global hospital mortality was 26.7%. A multivariate analysis through logistic regression identified the age of patients [older than 80; OR: 8.4 (95% CI: 3–23.4)], a moderate or severe radiologic affectation measured by the RALE score [OR: 7.3 (95% CI: 3.2–16.9)], the tobacco consumption [OR: 2.8 (95% CI: 1.3–6.1)] and previous arrhythmia [OR 2.8 (95% CI: 1.3–6.2)] as risk factor that were independently associated with mortality during the admission. The treatment with N-acetylcysteine was identified as a protective factor [OR: 0.57 (95% CI: 0.31–0.99)]. Asthma also seems to have a certain protective factor although it was not statistically significant in our study [OR: 0.19 (95% CI: 0.03–1.06)]. Conclusions Patients with COVID-19 treated with N-acetylcysteine have presented a lower mortality and a better evolution in this study. Future prospective studies or randomized clinical trials must confirm the impact of N-acetylcysteine on COVID-19 patients (AU)

Association between sex steroid hormones and subsequent hyperglycemia during pregnancy.

Objective: Sex steroid hormones may play a role in insulin resistance and glucose dysregulation. However, evidence regarding associations between early-pregnancy sex steroid hormones and hyperglycemia during pregnancy is limited. The primary objective of this study was to assess the relationships between first trimester sex steroid hormones and the subsequent development of hyperglycemia during pregnancy; with secondary evaluation of sex steroid hormones levels in mid-late pregnancy, concurrent with and subsequent to diagnosis of gestational diabetes. Methods: Retrospective analysis of a prospective pregnancy cohort study was conducted. Medically low-risk participants with no known major endocrine disorders were recruited in the first trimester of pregnancy (n=319). Sex steroid hormones in each trimester, including total testosterone, free testosterone, estrone, estradiol, and estriol, were assessed using high-performance liquid chromatography and tandem mass spectrometry. Glucose levels of the 1-hour oral glucose tolerance test and gestational diabetes diagnosis were abstracted from medical records. Multivariable linear regression models were fitted to assess the associations of individual first trimester sex steroids and glucose levels. Results: In adjusted models, first trimester total testosterone (ß=5.24, 95% CI: 0.01, 10.46, p=0.05) and free testosterone (ß=5.98, 95% CI: 0.97, 10.98, p=0.02) were positively associated with subsequent glucose concentrations and gestational diabetes diagnosis (total testosterone: OR=3.63, 95% CI: 1.50, 8.78; free testosterone: OR=3.69; 95% CI: 1.56, 8.73). First trimester estrone was also positively associated with gestational diabetes (OR=3.66, 95% CI: 1.56, 8.55). In mid-late pregnancy, pregnant people with gestational diabetes had lower total testosterone levels (ß=-0.19, 95% CI: -0.36, -0.02) after adjustment for first trimester total testosterone. Conclusion: Early-pregnancy sex steroid hormones, including total testosterone, free testosterone, and estrone, were positively associated with glucose levels and gestational diabetes in mid-late pregnancy. These hormones may serve as early predictors of gestational diabetes in combination with other risk factors.

Exposure to Neighborhood Walkability and Residential Greenness and Incident Fracture.

Importance: Emerging studies have suggested that environmental factors are associated with fracture. However, little is known about the association of neighborhood walkability and residential greenness with fracture. Objective: To investigate the association of long-term exposure to walkability and greenness with incident fracture and explore the potential interaction effect. Design, Setting, and Participants: This cohort study recruited participants aged 40 years or older in Ningbo, China from June 2015 to January 2018. Participants were observed for outcomes through February 2023, with data analysis conducted in March 2023. Exposures: Neighborhood walkability was measured by a modified walkability calculation method according to a walk score tool. Residential greenness was assessed by satellite-derived normalized difference vegetation index (NDVI) within a 1000-m buffer. Main Outcomes and Measures: Incident fracture was ascertained according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes via the Yinzhou Health Information System. Cox proportional hazards models were fit, with age as time scale to estimate the associations of walkability and greenness with fracture. Potential effect modification was explored by covariates, as well as the interactive effect of walkability and greenness. Results: A total of 23 940 participants were included in this study with 13 735 being female (57.4%). The mean (SD) age at baseline was 63.4 (9.4) years. During a follow-up period of 134 638 person-years, 3322 incident fractures were documented. In the full adjusted model, every IQR increment in neighborhood walkability and residential greenness was associated with a hazard ratio (HR) of 0.88 (95% CI, 0.83-0.92) and 0.84 (95% CI, 0.80-0.89), respectively, for fracture. Furthermore, the association of greenness and fracture was greater with an increase in walkability. The HR (Q4 vs Q1) for greenness was 0.62 (95% CI, 0.46-0.82) in neighborhoods with the highest quartile of walkability. Conclusions and Relevance: This population cohort study suggested that long-term exposure to neighborhood walkability and residential greenness were both associated with lower risk of incident fracture. The benefits of greenness increased in more walkable areas.

Rate of Correction and All-Cause Mortality in Patients With Severe Hypernatremia.

Importance: Hypernatremia is common among hospitalized patients and is associated with high mortality rates. Current guidelines suggest avoiding fast correction rates but are not supported by robust data. Objective: To investigate whether there is an association between hypernatremia correction rate and patient survival. Design, Setting, and Participants: This retrospective cohort study examined data from all patients admitted to the Tel Aviv Medical Center between 2007 and 2021 who were diagnosed with severe hypernatremia (serum sodium ≥155 mmol/L) at admission or during hospitalization. Statistical analysis was performed from April 2022 to August 2023. Exposure: Patients were grouped as having fast correction rates (>0.5 mmol/L/h) and slow correction rates (≤0.5 mmol/L/h) in accordance with current guidelines. Main Outcomes and Measures: All-cause 30-day mortality. Results: A total of 4265 patients were included in this cohort, of which 2621 (61.5%) were men and 343 (8.0%) had fast correction rates; the median (IQR) age at diagnosis was 78 (64-87) years. Slow correction was associated with higher 30-day mortality compared with fast correction (50.7% [1990 of 3922] vs 31.8% [109 of 343]; P < .001). These results remained significant after adjusting for demographics (age, gender), Charlson comorbidity index, initial sodium, potassium, and creatinine levels, hospitalization in an ICU, and severe hyperglycemia (adjusted odds ratio [aOR], 2.02 [95% CI, 1.55-2.62]), regardless of whether hypernatremia was hospital acquired (aOR, 2.19 [95% CI, 1.57-3.05]) or documented on admission (aOR, 1.64 [95% CI, 1.06-2.55]). There was a strong negative correlation between absolute sodium correction during the first 24 hours following the initial documentation of severe hypernatremia and 30-day mortality (Pearson correlation coefficient, -0.80 [95% CI, -0.93 to -0.50]; P < .001). Median (IQR) hospitalization length was shorter for fast correction vs slow correction rates (5.0 [2.1-14.9] days vs 7.2 [3.5-16.1] days; P < .001). Prevalence of neurological complications was comparable for both groups, and none were attributed to fast correction rates of hypernatremia. Conclusions and Relevance: This cohort study of patients with severe hypernatremia found that rapid correction of hypernatremia was associated with shorter hospitalizations and significantly lower patient mortality without any signs of neurologic complications. These results suggest that physicians should consider the totality of evidence when considering the optimal rates of correction for patients with severe hypernatremia.

Different types of milk consumption and the risk of dementia: Analysis from a large-scale cohort study.

BACKGROUND & AIMS: Previous studies have investigated whether milk consumption has a role in preventing the development of cognitive impairment, but the results were inconsistent. Importantly, most of them have disregarded the role of different types of milk. This study aimed to examine the associations between different types of milk consumption and the risk of dementia. METHODS: In this large-scale cohort study, participants without cognitive impairment at baseline were included from the UK Biobank. The type of milk mainly used was self-reported at baseline, including full-cream milk, skimmed-milk, soy milk, other milk, and no milk. The primary outcome was all-cause dementia. Secondary outcomes included Alzheimer's disease and vascular dementia. RESULTS: Of the 307,271 participants included in the study (mean age 56.3 [SD 8.1] years), 3789 (1.2%) incident all-cause dementia cases were observed over a median follow-up of 12.3 years. After adjustment for potential confounders, only soy milk consumers had a statistically significantly lower risk of all-cause dementia compared with no milk consumers (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.54 to 0.90). When compared with soy milk non-consumers consisting of full-cream milk, skimmed-milk, and other milk consumers, soy milk consumers still showed a lower risk of all-cause dementia (HR, 0.76; 95% CI, 0.63 to 0.92), and there was no significant interaction with genetic risk for dementia (P for interaction = 0.15). Soy milk consumers showed a lower risk of Alzheimer's disease (HR, 0.70; 95% CI, 0.51 to 0.94; P = 0.02), while the association was not significant for vascular dementia (HR, 0.72; 95% CI, 0.47 to 1.12; P = 0.14). CONCLUSIONS: The main consumption of soy milk was associated with a lower risk of dementia, particularly non-vascular dementia. Additional studies are needed to investigate how this association varies with the dose or frequency of the consumption of soy milk and to examine the generalizability of these findings in different populations.

Immunoadsorption-Based HLA Desensitization in Patients Awaiting Deceased Donor Kidney Transplantation: An Interventional, Non-Randomised, Single Cohort Study.

Whether immunoadsorption (IADS) as part of desensitization protocols could facilitate deceased donor kidney transplantation (KT) in highly sensitized (HS) patients remains to be proven. We retrospectively analyzed our IADS based desensitization protocol for deceased donor KTs between 2013 and 2018. Fifteen HS patients (age 52 years [40-56]) were included. Waiting time before IADS was 6 years [5-10] and the interval between IADS initiation and KT was 5 months [1-12] for the 14 transplanted patients. Nine patients had prior KT. Calculated panel reactive antibody decreased significantly during the protocol (99.3% [92.5-99.9] vs. 79.4% [56.7-81.9]; p = 0.004). Death-censored graft survival was 85.7% at 1 and 2 years post-transplantation. One-year median plasma creatinine level was 135 µmol/L [111-202]. Six developed active antibody mediated rejection (ABMR) at 1 year, with a median delay of 13 days [11-26]. Eight patients developed severe infections, including two fatal outcomes. Finally, compared to 93% of patients who received desensitization receiving a KT, only 43% of a control with similar characteristics underwent transplantation. However, no difference was found in overall probability of being alive with a functioning graft at the end of follow-up. The results indicate that our IADS-based desensitization strategy was not effective due to a high rate of ABMR and severe infectious complications which pose a challenge to its universalization.

Causes and consequences of child growth faltering in low-resource settings.

Growth faltering in children (low length for age or low weight for length) during the first 1,000 days of life (from conception to 2 years of age) influences short-term and long-term health and survival1,2. Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. Identification of age windows and population subgroups on which to focus will benefit future preventive efforts. Here we use a population intervention effects analysis of 33 longitudinal cohorts (83,671 children, 662,763 measurements) and 30 separate exposures to show that improving maternal anthropometry and child condition at birth accounted for population increases in length-for-age z-scores of up to 0.40 and weight-for-length z-scores of up to 0.15 by 24 months of age. Boys had consistently higher risk of all forms of growth faltering than girls. Early postnatal growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits exhibited higher mortality rates from birth to 2 years of age than children without growth deficits (hazard ratios 1.9 to 8.7). The importance of prenatal causes and severe consequences for children who experienced early growth faltering support a focus on pre-conception and pregnancy as a key opportunity for new preventive interventions.

Patient-reported reactogenicity and safety of COVID-19 vaccinations vs. comparator vaccinations: a comparative observational cohort study.

BACKGROUND: In the course of the SARS-CoV-2 pandemic, multiple vaccines were developed. Little was known about reactogenicity and safety in comparison to established vaccines, e.g. influenza, pneumococcus, or herpes zoster. Therefore, the present study aimed to compare self-reported side effects in persons vaccinated against SARS-CoV-2 with the incidence of side effects in persons receiving one of the established vaccines. METHODS: A longitudinal observational study was conducted over a total of 124 days using web-based surveys. Persons receiving either a vaccination against SARS-CoV-2 or one of the established vaccines (comparator group) were included. In the first questionnaire (short-term survey), 2 weeks after vaccination, mainly local and systemic complaints were evaluated. The long-term survey (42 days after vaccination) and follow-up survey (124 weeks after vaccination) focused on medical consultations for any reason. Multivariate analyses were conducted to determine the influence of the vaccine type (SARS-CoV-2 vs. comparator) and demographic factors. RESULTS: In total, data from 16,636 participants were included. Self-reported reactogenicity was lowest in the comparator group (53.2%) and highest in the ChAdOx1 group (85.3%). Local reactions were reported most frequently after mRNA-1273 (73.9%) and systemic reactions mainly after vector-based vaccines (79.8%). Almost all SARS-CoV-2 vaccines showed increased odds of reporting local or systemic reactions. Approximately equal proportions of participants reported medical consultations. None in the comparator group suspected a link to vaccination, while this was true for just over one in 10 in the mRNA-1273 group. The multivariate analysis showed that people with SARS-CoV-2 vaccination were not more likely to report medical consultations; patients who had received a regimen with at least one ChAdOx1 were even less likely to report medical consultations. Younger age, female gender and higher comorbidity were mostly associated with higher odds of medical consultations. CONCLUSION: The rate of adverse reactions after established vaccinations was roughly comparable to previous studies. Two weeks after vaccination, participants in the SARS-CoV-2 vaccination group reported more local and systemic local reactions than participants in the comparator group. In the further course, however, there were no higher odds of medical consultations in either of the two groups. Thus, altogether, we assume comparable safety. TRIAL REGISTRATION: DRKS-ID DRKS00025881 and DRKS-ID DRKS00025373.

Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care.

BACKGROUND: Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs). METHODS: Matched cohort study using primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS-CoV-2 infection and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults with no diagnosis of confirmed or suspected SARS-CoV-2 infection. The primary outcome was a composite of any of the following IMIDs: autoimmune thyroiditis, coeliac disease, inflammatory bowel disease (IBD), myasthenia gravis, pernicious anaemia, psoriasis, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo. The secondary outcomes were each of these conditions separately. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes, adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications. RESULTS: Six hundred and nighty six (0.15%) and 2230 (0.12%) patients in the exposed and unexposed cohort developed an IMID during the follow-up period over 0.29 person-years, giving a crude incidence rate of 4.59 and 3.65 per 1000 person-years, respectively. Patients in the exposed cohort had a 22% increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.12 to 1.33). The incidence of three IMIDs was significantly associated with SARS-CoV-2 infection. These were T1DM (aHR 1.56, 1.09 to 2.23), IBD (aHR 1.36, 1.18 to 1.56), and psoriasis (1.23, 1.05 to 1.42). CONCLUSIONS: SARS-CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. However, these findings could be potentially due to ascertainment bias. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19.

Beyond the Concepts of Elder and Marginal in DCD Liver Transplantation: A Prospective Observational Matched-Cohort Study in the Italian Clinical Setting.

Donation after circulatory determination of death (DCD) is a valuable strategy to increase the availability of grafts for liver transplantation (LT). As the average age of populations rises, the donor pool is likely to be affected by a potential increase in DCD donor age in the near future. We conducted a prospective cohort study to evaluate post-transplantation outcomes in recipients of grafts from elderly DCD donors compared with younger DCD donors, and elderly donors after brainstem determination of death (DBD). From August 2020 to May 2022, consecutive recipients of deceased donor liver-only transplants were enrolled in the study. DCD recipients were propensity score matched 1:3 to DBD recipients. One-hundred fifty-seven patients were included, 26 of whom (16.6%) were transplanted with a DCD liver graft. After propensity score matching and stratification, three groups were obtained: 15 recipients of DCD donors ≥75 years, 11 recipients of DCD donors <75 years, and 28 recipients of DBD donors ≥75 years. Short-term outcomes, as well as 12 months graft survival rates (93.3%, 100%, and 89.3% respectively), were comparable among the groups. LT involving grafts retrieved from very elderly DCD donors was feasible and safe in an experienced high-volume center, with outcomes comparable to LTs from younger DCD donors and age-matched DBD donors.

Impact of red blood cell distribution width-albumin ratio on prognosis of patients with CKD.

The red blood cell distribution width-albumin ratio (RAR) is a prognostic factor for adverse outcomes in various populations. However, whether RAR is associated with renal outcomes remains unclear. Therefore, we aimed to investigate the impact of RAR on the prognosis in patients with chronic kidney disease (CKD). We conducted a retrospective cohort study using 997 CKD patients who were enrolled in the Fukushima Cohort Study. Patients were categorized into tertiles (T1-3) according to the baseline RAR. The associations of RAR with end-stage kidney disease (ESKD) were assessed using Kaplan-Meier curves and multivariable cox regression analyses. Receiver operating characteristic (ROC) curves were performed to test whether significant differences were present between red cell distribution width (RDW) and RAR. The median age was 66, 57% were men, the median eGFR was 47.8 ml/min/1.73 m2, and the median value of RAR was 3.5. The higher RAR group showed an increased risk for ESKD in the Kaplan-Meier curve analysis. Compared to the lowest RAR group, higher RAR groups had a higher risk of ESKD (hazard ratio [HR] 1.37, 95% CI 0.68-2.78 and 2.92, 95% CI 1.44-5.94) for T2 and T3 groups, respectively. ROC curve analysis proved that the discriminating ability of RAR for ESKD was superior to RDW. A higher RAR value was associated with worse renal outcomes in patients with CKD. RAR could be a convenient and useful prognostic marker for renal prognosis.

Neonatal outcomes of elective labor induction in low-risk term pregnancies.

The rate of labor induction has increased in recent years. The results of previously conducted studies examining associations between elective induction of labor (IOL) and neonatal outcomes have been contradictory. The aim of this study was to examine the intrinsic neonatal risks following IOL. We conducted a population-based cohort study, including all women with recorded low-risk singleton pregnancies at a gestational age between 37 + 0 and 41 + 6 weeks in Sweden from 1999 to 2017. Data were collected from the Swedish Medical Birth register. Two study groups were compared-the elective induction group with the spontaneous labor onset group. The results showed that the rate of elective IOL increased from 7.2% in 1999 to 16.4% in 2017. Elective IOL was associated with a higher OR for chorioamnionitis, bacterial sepsis, intracranial hemorrhage, assisted ventilation, hyperbilirubinemia, APGAR < 7 at 5 min, and neonatal seizures compared to deliveries with spontaneous labor onset. Regarding mortality outcomes, no significant differences were shown between the groups for either early term or full-term deliveries. We conclude that IOL is associated with neonatal complications, although causality could not be established in this observational study. It is important to be aware of the increased risk and perform IOL with caution.

Clinical, epidemiological and laboratory characteristics of cases of Covid-19-related maternal near miss and death at referral units in northeastern Brazil: a cohort study.

Objective: Covid-19 poses a major risk during pregnancy and postpartum, resulting in an increase in maternal mortality worldwide, including in Brazil; however, little research has been conducted into cases of a near miss. This study aimed to describe the frequency of COVID-19-related near miss and deaths during pregnancy or in the postpartum in referral centers in northeastern Brazil, as well as the clinical, epidemiological, and laboratory characteristics of the women who experienced a severe maternal outcome.Methods: A retrospective and prospective cohort study was performed between April 2020 and June 2021 with hospitalized pregnant and postpartum women with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction (RT-PCR). Data from five tertiary hospitals in northeastern Brazil were evaluated. Descriptive statistical analysis was performed using Epi Info, version 7.2.5.0.Results: A total of 463 patients were included. Of these, 64 (14% of the sample) had a severe maternal outcome, with 42 cases of near miss (9%) and 22 maternal deaths (5%). Patients who had a severe maternal outcome were predominantly young (median age 30 years) and 65.6% were black or brown-skinned. The women had between 6 and 16 years of schooling; 45.3% had a stable partner; 81.3% were pregnant at the time of admission to the study; and 76.6% required a Cesarean section. The great majority (82.8%) had severe acute respiratory syndrome (SARS). Other complications included hypertensive syndromes (40.6%), pneumonia (37.5%), urinary tract infections (29.7%), acute renal failure (25.0%) and postpartum hemorrhage (21.9%). Sepsis developed in 18.8% of cases, neurological dysfunction in 15.6%, and hepatic dysfunction and septic shock in 14.1% of cases each. The relative frequency of admission to an intensive care unit was 87.5%, while 67.2% of the patients required assisted mechanical ventilation, and 54.7% required noninvasive ventilation. Antibiotics were prescribed in 93.8% of cases and corticosteroids in 71.9%, while blood transfusion was required in 25.0% of cases and renal replacement therapy in 15.6%. Therapeutic anticoagulants were administered to 12.5% of the patients. Of the patients who had a severe maternal outcome, the frequency of respiratory dysfunction was 93.8%, with 50.0% developing neurological dysfunction and 37.5% cardiovascular dysfunction. Hematological dysfunction was found in 29.7%, renal dysfunction in 18.8%, and uterine dysfunction in 14.1%. Hepatic dysfunction occurred in 7.8% of the sample. The near-miss ratio for Covid-19 was 1.6/1000 live births and the maternal mortality ratio for Covid-19 was 84.8/100,000 live births, with a mortality index of 34.4% in the sample.Conclusion: This study revealed a low Covid-19-related maternal near miss (MNM) ratio of 1.6/1000 live births and a high Covid-19-related maternal mortality ratio (MMR) of 84.81/100,000 live births. The mortality index was also high. Most of the patients were admitted while pregnant, were young, married and black or brown-skinned, and none had completed university education. The majority had SARS and required admission to an intensive care unit and mechanical ventilation. Most were submitted to a Cesarean section.