COVID-19 Computed tomography patterns in renal replacement therapy patients / Padrões de tomografia computadorizada da COVID-19 em pacientes em terapia renal substitutiva

ABSTRACT Introduction: Lung diseases are common in patients with end stage kidney disease (ESKD), making differential diagnosis with COVID-19 a challenge. This study describes pulmonary chest tomography (CT) findings in hospitalized ESKD patients on renal replacement therapy (RRT) with clinical suspicion of COVID-19. Methods: ESKD individuals referred to emergency department older than 18 years with clinical suspicion of COVID-19 were recruited. Epidemiological baseline clinical information was extracted from electronic health records. Pulmonary CT was classified as typical, indeterminate, atypical or negative. We then compared the CT findings of positive and negative COVID-19 patients. Results: We recruited 109 patients (62.3% COVID-19-positive) between March and December 2020, mean age 60 ± 12.5 years, 43% female. The most common etiology of ESKD was diabetes. Median time on dialysis was 36 months, interquartile range = 12-84. The most common pulmonary lesion on CT was ground glass opacities. Typical CT pattern was more common in COVID-19 patients (40 (61%) vs 0 (0%) in non-COVID-19 patients, p < 0.001). Sensitivity was 60.61% (40/66) and specificity was 100% (40/40). Positive predictive value and negative predictive value were 100% and 62.3%, respectively. Atypical CT pattern was more frequent in COVID-19-negative patients (9 (14%) vs 24 (56%) in COVID-19-positive, p < 0.001), while the indeterminate pattern was similar in both groups (13 (20%) vs 6 (14%), p = 0.606), and negative pattern was more common in COVID-19-negative patients (4 (6%) vs 12 (28%), p = 0.002). Conclusions: In hospitalized ESKD patients on RRT, atypical chest CT pattern cannot adequately rule out the diagnosis of COVID-19.

RESUMO Introdução: Doenças pulmonares são comuns em pacientes com doença renal em estágio terminal (DRET), dificultando o diagnóstico diferencial com COVID-19. Este estudo descreve achados de tomografia computadorizada de tórax (TC) em pacientes com DRET em terapia renal substitutiva (TRS) hospitalizados com suspeita de COVID-19. Métodos: Indivíduos maiores de 18 anos com DRET, encaminhados ao pronto-socorro com suspeita de COVID-19 foram incluídos. Dados clínicos e epidemiológicos foram extraídos de registros eletrônicos de saúde. A TC foi classificada como típica, indeterminada, atípica, negativa. Comparamos achados tomográficos de pacientes com COVID-19 positivos e negativos. Resultados: Recrutamos 109 pacientes (62,3% COVID-19-positivos) entre março e dezembro de 2020, idade média de 60 ± 12,5 anos, 43% mulheres. A etiologia mais comum da DRET foi diabetes. Tempo médio em diálise foi 36 meses, intervalo interquartil = 12-84. A lesão pulmonar mais comum foi opacidades em vidro fosco. O padrão típico de TC foi mais comum em pacientes com COVID-19 (40 (61%) vs. 0 (0%) em pacientes sem COVID-19, p < 0,001). Sensibilidade 60,61% (40/66), especificidade 100% (40/40). Valores preditivos positivos e negativos foram 100% e 62,3%, respectivamente. Padrão atípico de TC foi mais frequente em pacientes COVID-19-negativos (9 (14%) vs. 24 (56%) em COVID-19-positivos, p < 0,001), enquanto padrão indeterminado foi semelhante em ambos os grupos (13 (20%) vs. 6 (14%), p = 0,606), e padrão negativo foi mais comum em pacientes COVID-19-negativos (4 (6%) vs. 12 (28%), p = 0,002). Conclusões: Em pacientes com DRET em TRS hospitalizados, um padrão atípico de TC de tórax não pode excluir adequadamente o diagnóstico de COVID-19.

Prevalence of dry eye disease in the low vision population at the University of Colorado

Purpose: To evaluate the prevalence of diagnosed dry eye syndrome, meibomian gland dysfunction, and blepharitis amongst the low vision population. Methods: A retrospective analysis was conducted on patients seen in the University of Colorado Low Vision Rehabilitation Service between the dates of 12/1/2017 and 12/1/2022. 74 ICD-10 codes were used to identify patients as having dry eye syndrome or not having dry eye syndrome. Data was further analyzed to determine the prevalence of blepharitis and meibomian gland dysfunction using 29 blepharitis and 9 meibomian gland dysfunction ICD-10 codes. Data were also analyzed to determine the age and sex of the patients with diagnosed dry eye syndrome. Results: The percentage of patients with a diagnosis of dry eye syndrome by an eyecare provider was 38.02 %. The prevalence of dry eye syndrome by age group was 3.57 % for 0–19 years, 14.35 % for 20–39 years, 29.07 % for 40–59 years, 43.79 % for 60–79 years, and 46.21 % for 80 and above. The prevalence of meibomian gland dysfunction and blepharitis was 11.90 % and 9.1 % respectively. Dry eye syndrome prevalence amongst males was 31.59 % and 42.47 % for females. Conclusion: This study demonstrates that dry eye syndrome in the low vision population is a significant co-morbidity occurring in over a third of patients in the University of Colorado Low Vision Rehabilitation Service. These findings are meaningful as ocular comfort should not be overlooked while managing complex visual needs. (AU)

Type 2 diabetes patients requiring empagliflozin in Southeast of Iran: Frequency and guideline adherence (2022–2023) / Pacientes con diabetes tipo 2 que requieren empagliflozina en el sureste de Irán: frecuencia y cumplimiento de las directrices (2022-2023)

Introduction: Empagliflozin plays a beneficial role in individuals with type 2 diabetes at high risk of cardiovascular complications. This study aimed to assess the prevalence of individuals with type 2 diabetes who required empagliflozin based on clinical guidelines between the years 2022 and 2023. Material and methods: This study was a descriptive-analytical cross-sectional study conducted on a target population of patients with type 2 diabetes. Patient data, including demographic characteristics, smoking status, hypertension, hyperlipidemia, renal insufficiency, retinopathy, and proteinuria, were collected. The indication for prescribing empagliflozin was determined based on the risk of cardiovascular complications. Results: A total of 398 individuals with type 2 diabetes with a mean age of 58.4 years were examined. Overall, 87.4% of the patients had an indication for empagliflozin prescription. The indication for empagliflozin prescription was significantly higher in men, individuals with hyperlipidemia, those over 55 years of age, obese individuals, and smokers. The mean age, body mass index, and triglyceride levels were higher in candidates for empagliflozin prescription. Male candidates for empagliflozin had significantly higher rates of smoking and systolic blood pressure compared to females. Conclusions: The findings of this study demonstrated that a significant percentage of individuals with type 2 diabetes had an indication for empagliflozin prescription based on clinical and laboratory criteria. (AU)

Introducción: La empagliflozina tiene un papel beneficioso en las personas con diabetes tipo 2 con alto riesgo de complicaciones cardiovasculares. Este estudio tuvo como objetivo evaluar la prevalencia de pacientes con este padecimiento que requerían empagliflozina según las guías clínicas entre los años 2022 y 2023. Material y métodos: Se trata de un estudio transversal descriptivo-analítico realizado en una población objetivo de personas con diabetes tipo 2. Se recogieron los datos de los pacientes, incluyendo las características demográficas, el hábito tabáquico, la hipertensión, la hiperlipidemia, la insuficiencia renal, la retinopatía y la proteinuria. La indicación para prescribir empagliflozina se determinó en función del riesgo de complicaciones cardiovasculares. Resultados: Se examinaron un total de 398 individuos con diabetes tipo 2 con una edad media de 58,4 años. En general, 87,4% de estos tenía una indicación para la prescripción de empagliflozina, la cual fue significativamente mayor en los hombres, aquellos con hiperlipidemia, obesidad, los mayores de 55 años y los fumadores. La edad media, el índice de masa corporal y los niveles de triglicéridos fueron mayores en los candidatos a la prescripción de este medicamento. Los candidatos masculinos a este fármaco tenían tasas significativamente más altas de tabaquismo y presión arterial sistólica, en comparación con las mujeres. Conclusiones: Los resultados de este estudio demostraron que un porcentaje significativo de personas con diabetes tipo 2 tenía una indicación para la prescripción de empagliflozina según los criterios clínicos y de laboratorio. (AU)

Renin–angiotensin–aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial / Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de enfermedad renal crónica en pacientes hipertensos añosos sin proteinuria: ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos

Introduction: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. Materials and methods: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3–4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. Results: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was −4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. Conclusions: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023). (AU)

Introducción: Actualmente no existe suficiente evidencia sobre el efecto nefroprotector de los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) en pacientes añosos con enfermedad renal crónica (ERC) sin proteinuria y sin cardiopatía. El objetivo es evaluar el efecto de los BSRAA en la progresión de la ERC en este grupo poblacional. Métodos: Se trata de un estudio prospectivo, aleatorizado, que compara la eficacia de los BSRAA vs. otros tratamientos antihipertensivos en la progresión renal en personas mayores de 65 años con ERC estadios 3 y 4 e índice albúmina/creatinina<30mg/g. Aleatorización 1:1 BSRAA o tratamiento antihipertensivo estándar. Se recogieron cifras tensionales y parámetros analíticos de un año previo a la aleatorización y durante el seguimiento. Resultados: Se incluyeron 88 pacientes seguidos durante tres años con edad media de 77,9±6,1 años. De estos, se aleatorizaron 40 al grupo BSRAA y 48 al estándar. La etiología de ERC fue: 53 vascular, 16 intersticial y 19 no filiada. En el primer grupo se observó una progresión de la ERC con una caída del filtrado glomerular estimado (FGe) de -4,3±1,1mL/min, mientras que en el grupo estándar un aumento del FGe durante el seguimiento de 4,6±0,4mL/min, p=0,024. No se apreciaron diferencias entre ambos en el control tensional, el número de antihipertensivos, la albuminuria, los niveles de potasio, la incidencia de eventos cardiovasculares ni la mortalidad durante el seguimiento. Conclusiones: En pacientes añosos no diabéticos con ERC no proteinúrica y sin cardiopatía el uso de BSRAA no añade beneficio en la progresión de la ERC. Ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos (PROERCAN) (NCT03195023). (AU)

Efectos sobre los procesos cognitivos del entrenamiento basado en doble tarea en personas con enfermedad de Parkinson: una revisión sistemática / Effects on cognitive processes of dual-task training in people with Parkinson’s disease: a systematic review

Introducción: La doble tarea es una intervención no farmacológica en personas con condiciones neurodegenerativas, utilizada en la enfermedad de Parkinson (EP), principalmente para favorecer el desempeño motor. El objetivo de esta revisión es reunir la evidencia actual sobre cómo el entrenamiento de doble tarea afecta a los procesos cognitivos en personas que presenten EP. Material y métodos. Se desarrolló una revisión sistemática, aplicando las directrices de PRISMA, incluyendo artículos obtenidos en las bases de datos de PubMed, Web of Science, Science Direct y Springer Link. La calidad metodológica se evaluó mediante PEDro y ROBINS-I. Resultados: Doce artículos cumplieron con los criterios de inclusión y exclusión: nueve de ellos corresponden a ensayos controlados aleatorizados y los tres restantes fueron estudios no aleatorizados. Se identificaron mejoras en la atención y las funciones ejecutivas, aunque la diversidad en enfoques y duración dificulta llegar a conclusiones definitivas. Conclusiones: Es crucial expandir la investigación, estandarizando los programas de intervención. Del mismo modo, es importante llevar a cabo estudios longitudinales y controlados aleatorizados en muestras representativas que permitan llegar a conclusiones aplicables a otros contextos.(AU)

Introduction: Dual-tasking is a non-pharmacological intervention in people with neurodegenerative conditions, and is used in Parkinson’s disease (PD), primarily to enhance motor performance. The aim of this review is to compile the current evidence on how dual-task training affects cognitive processes in people with PD. Material and methods: A systematic review was undertaken, applying PRISMA guidelines, which included articles obtained from the PubMed, Web of Science, Science Direct and Springer Link databases. Methodological quality was assessed using PEDro and ROBINS-I. Results: Twelve articles met the inclusion and exclusion criteria: nine of them were randomized controlled trials, and the remaining three were non-randomized studies. Improvements in attention and executive functions were identified, although the diversity of approaches and duration means that reaching definitive conclusions is difficult. Conclusions: Increased research and standardized intervention programmes are essential. Longitudinal and randomized controlled studies in representative samples which provide conclusions that are applicable to other contexts are also important.(AU)

Renal osteodystrophy and clinical outcomes: a prospective cohort study / Osteodistrofia renal e desfechos clínicos: um estudo de coorte prospectivo

Abstract Introduction: Renal osteodystrophy (ROD) refers to a group of bone morphological patterns that derive from distinct pathophysiological mechanisms. Whether the ROD subtypes influence long-term outcomes is unknown. Our objective was to explore the relationship between ROD and clinical outcomes. Methods: This study is a subanalysis of the Brazilian Registry of Bone Biopsies (REBRABO). Samples from individual patients were classified as having osteitis fibrosa (OF), mixed uremic osteodystrophy (MUO), adynamic bone disease (ABD), osteomalacia (OM), normal/minor alterations, and according to turnover/mineralization/volume (TMV) system. Patients were followed for 3.4 yrs. Clinical outcomes were: bone fractures, hospitalization, major adverse cardiovascular events (MACE), and death. Results: We enrolled 275 participants, of which 248 (90%) were on dialysis. At follow-up, 28 bone fractures, 97 hospitalizations, 44 MACE, and 70 deaths were recorded. ROD subtypes were not related to outcomes. Conclusion: The incidence of clinical outcomes did not differ between the types of ROD.

Resumo Introdução: Osteodistrofia renal (OR) refere-se a um grupo de padrões morfológicos ósseos que decorrem de mecanismos fisiopatológicos distintos. É desconhecido se os subtipos de OR influenciam desfechos em longo prazo. Nosso objetivo foi explorar as relações entre OR e desfechos. Métodos: Este estudo é uma subanálise do Registro Brasileiro de Biópsias Ósseas (REBRABO). As amostras de cada paciente foram classificadas em osteíte fibrosa (OF), osteodistrofia urêmica mista (MUO), doença óssea adinâmica (ABD), osteomalácia (OM), alterações normais/menores, e pelo sistema Remodelação / Mineralização / Volume (RMV). Os pacientes foram acompanhados por 3,4 anos. Os eventos clínicos foram: fraturas ósseas, hospitalizações, eventos cardiovasculares adversos maiores (MACE), e óbito. Resultados: Analisamos 275 indivíduos, 248 (90%) deles estavam em diálise. No acompanhamento, 28 fraturas ósseas, 97 hospitalizações, 44 MACE e 70 óbitos foram registrados. Os subtipos de OR não foram relacionados aos desfechos clínicos. Conclusão: A incidência de desfechos clínicos não diferiu entre os tipos de OR.

Consideraciones bioéticas en el manejo de la esclerosis lateral amiotrófica: Una aproximación al quehacer fonoaudiológico

Introducción: La esclerosis lateral amiotrófica (ELA) es la forma más común de enfermedad degenerativa de motoneurona en la edad adulta y es considerada una enfermedad terminal. Por lo mismo, el accionar del fonoaudiólogo debe considerar el respeto a los principios bioéticos básicos para garantizar una asistencia adecuada. Objetivo: Conocer aquellas consideraciones bioéticas relacionadas al manejo y estudio de personas con ELA para luego brindar una aproximación hacia el quehacer fonoaudiológico. Método: Se efectuó una búsqueda bibliográfica en las bases de datos PubMed, Scopus y SciELO. Se filtraron artículos publicados desde 2000 hasta junio de 2023 y fueron seleccionados aquellos que abordaban algún componente bioético en población con ELA. Resultados: Aspectos relacionados al uso del consentimiento informado y a la toma de decisiones compartidas destacaron como elementos esenciales para apoyar la autonomía de las personas. Conclusión: Una correcta comunicación y una toma de decisiones compartida son claves para respetar la autonomía de las personas. A su vez, la estandarización de procedimientos mediante la investigación clínica permitirá aportar al cumplimiento de los principios bioéticos de beneficencia y no maleficencia, indispensables para la práctica profesional.

Introduction: Amyotrophic lateral sclerosis (ALS) is the most common form of degenerative motor neuron disease in adulthood and is considered a terminal disease. For this reason, the actions of the speech therapist must consider respect for basic bioethical principles to guarantee adequate assistance. Objective: To know those bioethical considerations related to the management and study of people with ALS to then provide an approach to speech therapy. Methodology: A bibliographic search was carried out in the PubMed, Scopus, and SciELO databases. Articles published from 2000 to June 2023 were filtered and those that addressed a bioethical component in the population with ALS were selected. Results: Aspects related to the use of informed consent and shared decision-making stood out as essential elements to support people's autonomy. Conclusion: Proper communication and shared decision-making are key to respecting people's autonomy. In turn, the standardization of procedures through clinical research will contribute to compliance with the bioethical principles of beneficence and non-maleficence, essential for professional practice.

Concomitant treatment with safinamide and antidepressant drugs: Safety data from real clinical practice / Tratamiento concomitante de safinamida y antidepresivos: Datos de seguridad sobre la práctica en la vida real

Background and purpose: The aim of this study was to assess the possible pharmacological interactions between safinamide and antidepressants, and in particular the appearance of serotonin syndrome with data from real life. Methods: We conducted a retrospective observational study of patients with Parkinson's disease from our Movement Disorders Unit, who were under treatment with any antidepressant drug and safinamide. Specifically, symptoms suggestive of serotonin syndrome were screened for. Also, we collected time of simultaneous use, doses of levodopa and other antiparkinsonian drugs. Results: Clinical records were reviewed for the study period of September 2018 to September 2019. Seventy-eight PD patients who were treated with safinamide of which 25 (32.05%) had a concomitant treatment with an antidepressant drug, being sertraline and escitalopram the most frequent. Mean age was 80 years ± 8.43 and H&Y stage was 3 [2–4]. Mean dose of levodopa used was 703.75 mg ± 233.15. Median duration of concomitant treatment with safinamide and antidepressant drug was 6 months (IQR 20.5), and over eighteen months in 5 cases. No case of serotonin syndrome was recorded, neither was any of its typical manifestations combined or in isolation. Conclusions: Our real clinical practice study suggests that concomitant use of safinamide with antidepressant drugs in PD patients seemed to be safe and well tolerated, even in the long term. However, caution is warranted, individualizing treatment regimens and monitoring the potential appearance of adverse effects.(AU)

Objetivos: El objetivo de este estudio ha sido evaluar las posibles interacciones farmacológicas entre safinamida y antidepresivos; en particular la aparición del síndrome serotoninérgico mediante datos obtenidos en la vida real. Material y métodos: Realizamos un estudio observacional retrospectivo de pacientes con enfermedad de Parkinson (EP) de nuestra unidad de trastornos del movimiento, que estaban en tratamiento con algún fármaco antidepresivo y safinamida. Específicamente, se examinaron los síntomas sugestivos de síndrome serotoninérgico. Además, se recogieron tiempos de uso simultáneo, dosis de levodopa y otros fármacos antiparkinsonianos concomitantes. Resultados: Se revisaron las historias clínicas correspondientes al período de estudio de septiembre de 2018 a septiembre de 2019. Setenta y ocho pacientes con EP se encontraban en tratamiento con safinamida, de los cuales 25 (32,05%) se encontraban recibiendo además un fármaco antidepresivo, siendo sertralina y escitalopram los más frecuentes. La edad media fue de 80 años ± 8,43 y el estadio H&Y fue de 3 [2-4]. La dosis media de levodopa utilizada fue de 703,75 mg ± 233,15. La mediana de duración del tratamiento concomitante con safinamida y un fármaco antidepresivo fue de 6 meses (IQR: 20,5), y más de 18 meses en 5 casos. No se registró ningún caso de síndrome serotoninérgico, ni tampoco ninguno de sus síntomas de forma aislada. Conclusión: Nuestro estudio de práctica clínica real sugiere que el uso concomitante de safinamida con fármacos antidepresivos en pacientes con EP parece ser seguro y bien tolerado, incluso a largo plazo. Sin embargo, es necesaria precaución, individualizando los regímenes de tratamiento, y controlando la posible aparición de efectos adversos.(AU)

Intra and inter-rater remote assessment of bradykinesia in Parkinson's disease / Evaluación remota de la bradicinesia en la enfermedad de Parkinson mediante análisis intra e inter evaluadores

Introduction: Reliable assessment of individuals with Parkinson's disease (PD) is essential for providing adequate treatment. Clinical assessment is a complex and time-consuming task, especially for bradykinesia, since its evaluation can be influenced by the degree of experience of the examiner, patient collaboration and individual bias. Improvement of the clinical evaluation can be obtained by considering assessments from several professionals. However, this is only true when inter and intra-rater agreement are high. Recently, the Movement Disorder Society highlighted, during the COVID-19 pandemic, the need to develop and validate technologies for remote assessment of the motor status of people with PD. Thus, this study introduces an objective strategy for the remote evaluation of bradykinesia using multi-specialist analysis. Methods: Twelve volunteers with PD participated and these were asked to execute finger tapping, hand opening/closing and pronation/supination movements. Each task was recorded and rated by fourteen PD health experts for each patient. The scores were assessed on an individual basis. Intra and inter-rater agreement and correlation were estimated. Results: The results showed that agreements and correlations between experienced examiners were high with low variability. In addition, group analysis was noted as possessing the potential to solve individual inconsistency bias. Conclusion: Furthermore, this study demonstrated the need for a group with prior training and experience, along with indicating the importance for the development of a clinical protocol that can use telemedicine for the evaluation of individuals with PD, as well as the inclusion of a specialized mediating group. In Addition, this research helps to the development of a valid remote assessment of bradykinesia.(AU)

Introducción: La evaluación confiable de las personas con la enfermedad de Parkinson (EP) es esencial para lograr con un tratamiento adecuado. La evaluación clínica es una tarea compleja y que requiere mucho tiempo, especialmente para la bradicinesia, ya que su evaluación puede verse influenciada por el grado de experiencia del examinador, la colaboración del paciente y el sesgo individual. La mejora de la evaluación clínica se puede obtener considerando las evaluaciones de varios profesionales. Sin embargo, esto solo es más preciso cuando el convenio intra e inter evaluadores es alto. Recientemente, la Sociedad de Trastornos del Movimiento destacó, durante la pandemia COVID-19, la necesidad de desarrollar y validar tecnologías para la evaluación remota del estado motor de las personas con EP. Por lo tanto, este estudio presenta una estrategia objetiva para la evaluación remota de la bradicinesia mediante un análisis multi evaluadores. Métodos: Participaron 12 voluntarios con EP y se les pidió que ejecutaran movimientos de golpeteo de dedos de las manos, movimientos con las manos y pronación-supinación de las manos. Cada ejecución del movimiento fue registrado y calificado por 14 expertos en salud. Las puntuaciones se evaluaron de forma individual. Se estimó el convenio y la correlación intra e inter evaluadores. Resultados: Los resultados mostraron que los convenios y las correlaciones inter evaluadores experimentados son altos con baja variabilidad. Además, se observó que el análisis de grupo posee el potencial de resolver el sesgo de inconsistencia individual. Conclusiones: De esta forma, este estudio demostró la necesidad de un grupo con formación y experiencia previa, señalando la importancia para el desarrollo de un protocolo clínico que utiliza la telemedicina para la evaluación de personas con EP y como la inclusión de un grupo mediador especializado. En realidad, esta investigación propone una evaluación remota eficaz de la bradicinesia.(AU)

Natural course of hemodynamically stable hemispheres contralateral to operated hemispheres in adult patients with ischemic moyamoya diseases.

The necessity of bilateral bypass in adult moyamoya disease (MMD) remains unclear despite its recommendation for pediatric and hemorrhagic cases. We aimed to investigate the natural course of hemodynamically stable unoperated hemispheres after bypass surgery for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD. Among 288 patients, the mean age at the first operation of the unstable hemispheres was 40.8 ± 12.2 years. The mean follow-up period was 62.9 ± 46.5 months. 45 patients (15.6%) experienced stroke events in the unoperated hemisphere, consisting of hemorrhagic stroke in 8 (2.8%) and ischemic stroke in 37 (12.8%), including progressive transient ischemic attack in 25 (8.7%) and infarction in 12 (4.2%). Among them, 39 patients (13.5%) underwent bypass surgery. The annual risk of total stroke is 3.0%/patient-year, with 2.5% for ischemic stroke and 0.5% for hemorrhagic stroke. The 5- and 10-year cumulative risks of ischemic stroke were 13.4% and 18.3%, respectively, and those of hemorrhagic stroke were each 3.2%. The natural course of hemodynamically stable hemispheres contralateral to the operated ones appeared fairly good. Additional bypass surgery on the unoperated hemispheres should be considered for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD during the follow-up.

Global, regional, and national burden of incidence, prevalence, and years lived with disability for facial fractures from 1990 to 2019: a systematic analysis for the Global Burden of Disease study 2019.

BACKGROUND: Facial fractures are common injuries causing cosmetic, functional, and psychological damage. The purpose of this study was to assess the incidence, prevalence, and years lived with disability (YLDs) of facial fractures from 1990 to 2019 using the Global Burden of Disease (GBD). METHODS: Detailed data for the disease burden of facial fractures were obtained from online available public data (Global Health Data Exchange) derived from the GBD study. The incidence, prevalence, and YLDs of facial fractures from 1990 to 2019 were analyzed by country, region, age, gender, sociodemographic index (SDI), and cause. The age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized YLDs rate (ASYR), and estimated annual percentage change (EAPC) were calculated to evaluate the disease burden and quantify the trends over time. The main causes of facial fractures in different years and ages were assessed. RESULTS: Globally, there were 8.9 million incident cases, 1.5 million cases prevalent cases, and 98.1 thousand years YLDs in 2019. Compared with 1990, the number of incident cases, prevalent cases, and YLDs increased, while ASIR (EAPC, - 0.47; 95% uncertainty interval [UI], - 0.57 to - 0.37), ASPR (EAPC, - 0.39; 95% UI, - 0.46 to - 0.31), ASYR (EAPC, - 0.39; 95% UI, - 0.47 to - 0.32) showed a downward trend. The high SDI region held the highest ASIR, ASPR, and ASYR both in 1990 and 2019, such as New Zealand, Slovenia, and Australia. The burden was higher in men than in women from 1990 to 2019, while the ASRs in women exceeded that of men in the elderly. The ASIR peaked in the young adult group, however, the ASPR and ASYR increased with age. Falls and road injuries were the leading causes of facial fractures. CONCLUSIONS: Facial fractures continue to cause a heavy burden on public health worldwide. More targeted strategies need to be established to control the burden of facial fractures.

The discovery of regional neurotoxicity-associated metabolic alterations induced by carbon quantum dots in brain of mice using a spatial metabolomics analysis.

BACKGROUND: Recently, carbon quantum dots (CQDs) have been widely used in various fields, especially in the diagnosis and therapy of neurological disorders, due to their excellent prospects. However, the associated inevitable exposure of CQDs to the environment and the public could have serious severe consequences limiting their safe application and sustainable development. RESULTS: In this study, we found that intranasal treatment of 5 mg/kg BW (20 µL/nose of 0.5 mg/mL) CQDs affected the distribution of multiple metabolites and associated pathways in the brain of mice through the airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique, which proved effective in discovery has proven to be significantly alerted and research into tissue-specific toxic biomarkers and molecular toxicity analysis. The neurotoxic biomarkers of CQDs identified by MSI analysis mainly contained aminos, lipids and lipid-like molecules which are involved in arginine and proline metabolism, biosynthesis of unsaturated fatty acids, and glutamine and glutamate metabolism, etc. as well as related metabolic enzymes. The levels or expressions of these metabolites and enzymes changed by CQDs in different brain regions would induce neuroinflammation, organelle damage, oxidative stress and multiple programmed cell deaths (PCDs), leading to neurodegeneration, such as Parkinson's disease-like symptoms. This study enlightened risk assessments and interventions of QD-type or carbon-based nanoparticles on the nervous system based on toxic biomarkers regarding region-specific profiling of altered metabolic signatures. CONCLUSION: These findings provide information to advance knowledge of neurotoxic effects of CQDs and guide their further safety evaluation.

Amino-7,8-dihydro-4H-chromenone derivatives as potential inhibitors of acetylcholinesterase and butyrylcholinesterase for Alzheimer's disease management; in vitro and in silico study.

In this article, we present the design and synthesis of amino-7,8-dihydro-4H-chromenone derivatives as possible inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) for the management of Alzheimer's disease (AD). The target compounds were evaluated against AChE and BChE in vitro, and 4k exhibited good potency against BChE (IC50 = 0.65 ± 0.13 µM) compared with donepezil used as a positive control. Kinetic studies revealed that compound 4k exhibited a competitive-type inhibition with a Ki value of 0.55 µM. Molecular docking and molecular dynamics simulations further supported the rationality of our design strategy, as 4k showed promising binding interactions with the active sites of BChE. Overall, our findings highlight the potential of amino-7,8-dihydro-4H-chromenone derivatives as promising candidates for developing novel therapeutics targeting cholinesterase in managing AD.

Effectiveness of immunoglobulin replacement therapy in preventing infections in patients with chronic obstructive pulmonary disease: a systematic review.

PURPOSE: Immunoglobulin replacement therapy is a standard treatment for patients with antibody production deficiencies, which is of interest in patients with chronic obstructive pulmonary disease (COPD). This systematic review, registered with PROSPERO (CRD42021281118), assessed the current literature regarding immunoglobulin replacement therapy on COPD clinical outcomes in patients with low immunoglobulin G (IgG) serum concentrations. METHODS: Literature searches conducted from inception to August 23, 2021, in databases including MEDLINE, EMBASE, and CINAHL. Population (sex, age, comorbidities), baseline clinical characteristics (pulmonary function testing results, IgG levels), and outcome (hospitalizations, emergency department visits) were extracted after title/abstract and full text screening. The Cochrane risk of bias assessment form was used for risk of bias assessment of randomized controlled trials and the National Heart, Lung, and Blood Institute (NHLBI) assessment was used for pre and post studies. RESULTS: A total of 1381 studies were identified in the preliminary search, and 874 records were screened after duplicates were removed. Screening 77 full texts yielded four studies that were included in the review. CONCLUSION: It is unclear whether immune globulin replacement therapy reduces acute exacerbation frequency and severity in COPD. Current evidence suggests that it is worth considering, but better developed protocols for administration of immune globulin supplementation is required for future randomized controlled trials.

Factors influencing hospitalization or emergency department visits and mortality in type 2 diabetes following the onset of new cardiovascular diagnoses in a population-based study.

BACKGROUND: Individuals with type 2 diabetes (T2D) are at increased risk of developing cardiovascular disease (CVD) which necessitates monitoring of risk factors and appropriate pharmacotherapy. This study aimed to identify factors predicting emergency department visits, hospitalizations, and mortality among T2D patients after being newly diagnosed with CVD. METHODS: In a retrospective observational study conducted in Region Halland, individuals aged > 40 years with T2D diagnosed between 2011 and 2019, and a new diagnosis of CVD between 2016 and 2019, were followed for one year from the date of CVD diagnosis. The first encounter for CVD diagnosis was categorized as inpatient-, outpatient-, primary-, or emergency department care. Follow-up included laboratory tests, blood pressure, pharmacotherapies, and healthcare utilization. Hazard ratios (HR) in two Cox regression analyses determined relative risks for emergency visits/hospitalization and mortality, adjusting for age, sex, glucose regulation, lipid levels, kidney function, blood pressure, pharmacotherapy, and healthcare utilization. RESULTS: The study included a total of 1759 T2D individuals who received a new CVD diagnosis, with 67% diagnosed during inpatient care. The average hospitalization stay was 6.5 days, and primary care follow-up averaged 10.1 visits. Patients with CVD diagnosed in primary care had a HR 0.52 (confidence interval [CI] 0.35-0.77) for emergency department visits/hospitalization, but age had a HR 1.02 (CI 1.00-1.03). Pharmacotherapy with insulin, DPP4-inhibitors, aldosterone antagonists, and beta-blockers had a raised HR. Highest mortality risk was observed when CVD was diagnosed inpatient care, systolic blood pressure < 100 mm Hg and elevated HbA1c. Age had a HR 1.05 (CI 1.03-1.08), eGFR < 30 ml/min HR 1.46 (CI 1.01-2.11), and LDL-Cholesterol > 2,5 h 1.46 (CI 1.01-2.11) and associated with increased mortality risk. Pharmacotherapy with metformin had a HR 0.41 (CI 0.28-0.62), statins a HR 0.39 (CI 0.27-0.57), and a primary care follow-up < 30 days a HR 0.53 (CI 0.37-0.77) and associated with lower mortality risk. CONCLUSIONS: T2D individuals who had a new diagnosis of CVD were predominantly diagnosed when hospitalized, while follow-up typically occurred in primary care. Identifying factors that predict risks of mortality and hospitalization should be a focus of follow-up care, underscoring the critical role of primary care in the effective management of T2D and CVD.

Characteristics associated with occurrence of stroke in patients with infective endocarditis - a retrospective cohort study.

BACKGROUND: Stroke is a severe complication of infective endocarditis (IE), associated with high rates of mortality. Data on how IE patients with and without stroke differ may help to improve understanding contributing mechanisms. METHODS: All patients treated for IE between 2019 and 2021 with and without associated stroke were identified from the medical records of three academic tertiary care hospitals in Germany, all part of Charité - Universitätsmedizin Berlin, Germany. Multivariable logistic regression analyses were performed to identify variables associated with the occurrence of stroke. RESULTS: The study population consisted of 353 patients diagnosed with IE. Concomitant stroke occurred in 96/353 (27.2%) patients. Acute stroke was independently associated with co-occurring extracerebral arterial embolism [adjusted Odds ratio (aOR = 2.52; 95% confidence interval (CI) 1.35-4.71)], acute liver failure (aOR = 2.62; 95% CI 1.06-6.50), dental focus of infection (aOR = 3.14; 95% CI 1.21-8.12) and left-sided IE (aOR = 28.26; 95% CI 3.59-222.19). Stroke was found less often in IE patients with congenital heart disease (aOR = 0.20; 95% CI 0.04-0.99) and atypical pathogens isolated from blood culture (aOR = 0.31; 95% CI 0.14-0.72). CONCLUSIONS: Stroke is more likely to occur in individuals with systemic complications affecting other organs, too. Special attention should be addressed to dental status. The low incidence of stroke in patients with congenital heart disease may reflect awareness and prophylactic measures.

Neuroinflammation increases oxygen extraction in a mouse model of Alzheimer's disease.

BACKGROUND: Neuroinflammation, impaired metabolism, and hypoperfusion are fundamental pathological hallmarks of early Alzheimer's disease (AD). Numerous studies have asserted a close association between neuroinflammation and disrupted cerebral energetics. During AD progression and other neurodegenerative disorders, a persistent state of chronic neuroinflammation reportedly exacerbates cytotoxicity and potentiates neuronal death. Here, we assessed the impact of a neuroinflammatory challenge on metabolic demand and microvascular hemodynamics in the somatosensory cortex of an AD mouse model. METHODS: We utilized in vivo 2-photon microscopy and the phosphorescent oxygen sensor Oxyphor 2P to measure partial pressure of oxygen (pO2) and capillary red blood cell flux in cortical microvessels of awake mice. Intravascular pO2 and capillary RBC flux measurements were performed in 8-month-old APPswe/PS1dE9 mice and wildtype littermates on days 0, 7, and 14 of a 14-day period of lipopolysaccharide-induced neuroinflammation. RESULTS: Before the induced inflammatory challenge, AD mice demonstrated reduced metabolic demand but similar capillary red blood cell flux as their wild type counterparts. Neuroinflammation provoked significant reductions in cerebral intravascular oxygen levels and elevated oxygen extraction in both animal groups, without significantly altering red blood cell flux in capillaries. CONCLUSIONS: This study provides evidence that neuroinflammation alters cerebral oxygen demand at the early stages of AD without substantially altering vascular oxygen supply. The results will guide our understanding of neuroinflammation's influence on neuroimaging biomarkers for early AD diagnosis.

Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals.

BACKGROUND: Individuals on the preclinical Alzheimer's continuum, particularly those with both amyloid and tau positivity (A + T +), display a rapid cognitive decline and elevated disease progression risk. However, limited studies exist on brain atrophy trajectories within this continuum over extended periods. METHODS: This study involved 367 ADNI participants grouped based on combinations of amyloid and tau statuses determined through cerebrospinal fluid tests. Using longitudinal MRI scans, brain atrophy was determined according to the whole brain, lateral ventricle, and hippocampal volumes and cortical thickness in AD-signature regions. Cognitive performance was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). A generalized linear mixed-effects model was used to examine group × time interactions for these measures. In addition, progression risks to mild cognitive impairment (MCI) or dementia were compared among the groups using Cox proportional hazards models. RESULTS: A total of 367 participants (48 A + T + , 86 A + T - , 63 A - T + , and 170 A - T - ; mean age 73.8 years, mean follow-up 5.1 years, and 47.4% men) were included. For the lateral ventricle and PACC score, the A + T - and A + T + groups demonstrated statistically significantly greater volume expansion and cognitive decline over time than the A - T - group (lateral ventricle: ß = 0.757 cm3/year [95% confidence interval 0.463 to 1.050], P < .001 for A + T - , and ß = 0.889 cm3/year [0.523 to 1.255], P < .001 for A + T + ; PACC: ß = - 0.19 /year [- 0.36 to - 0.02], P = .029 for A + T - , and ß = - 0.59 /year [- 0.80 to - 0.37], P < .001 for A + T +). Notably, the A + T + group exhibited additional brain atrophy including the whole brain (ß = - 2.782 cm3/year [- 4.060 to - 1.504], P < .001), hippocampus (ß = - 0.057 cm3/year [- 0.085 to - 0.029], P < .001), and AD-signature regions (ß = - 0.02 mm/year [- 0.03 to - 0.01], P < .001). Cox proportional hazards models suggested an increased risk of progressing to MCI or dementia in the A + T + group versus the A - T - group (adjusted hazard ratio = 3.35 [1.76 to 6.39]). CONCLUSIONS: In cognitively normal individuals, A + T + compounds brain atrophy and cognitive deterioration, amplifying the likelihood of disease progression. Therapeutic interventions targeting A + T + individuals could be pivotal in curbing brain atrophy, cognitive decline, and disease progression.

Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease.

BACKGROUND: Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs. STUDY DESIGN AND METHODS: A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry. RESULTS: Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005). CONCLUSIONS: Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.

Structural and functional characterization of FabG4 from Mycolicibacterium smegmatis.

The rise in antimicrobial resistance is a global health crisis and necessitates the development of novel strategies to treat infections. For example, in 2022 tuberculosis (TB) was the second leading infectious killer after COVID-19, with multi-drug-resistant strains of TB having an ∼40% fatality rate. Targeting essential biosynthetic pathways in pathogens has proven to be successful for the development of novel antimicrobial treatments. Fatty-acid synthesis (FAS) in bacteria proceeds via the type II pathway, which is substantially different from the type I pathway utilized in animals. This makes bacterial fatty-acid biosynthesis (Fab) enzymes appealing as drug targets. FabG is an essential FASII enzyme, and some bacteria, such as Mycobacterium tuberculosis, the causative agent of TB, harbor multiple homologs. FabG4 is a conserved, high-molecular-weight FabG (HMwFabG) that was first identified in M. tuberculosis and is distinct from the canonical low-molecular-weight FabG. Here, structural and functional analyses of Mycolicibacterium smegmatis FabG4, the third HMwFabG studied to date, are reported. Crystal structures of NAD+ and apo MsFabG4, along with kinetic analyses, show that MsFabG4 preferentially binds and uses NADH when reducing CoA substrates. As M. smegmatis is often used as a model organism for M. tuberculosis, these studies may aid the development of drugs to treat TB and add to the growing body of research that distinguish HMwFabGs from the archetypal low-molecular-weight FabG.