Long-term Natural History of Pediatric Dominant and Recessive RYR1-Related Myopathy.

BACKGROUND AND OBJECTIVES: RYR1-related myopathies are the most common congenital myopathies, but long-term natural history data are still scarce. We aim to describe the natural history of dominant and recessive RYR1-related myopathies. METHODS: A cross-sectional and longitudinal retrospective data analysis of pediatric cases with RYR1-related myopathies seen between 1992-2019 in 2 large UK centers. Patients were identified, and data were collected from individual medical records. RESULTS: Sixty-nine patients were included in the study, 63 in both cross-sectional and longitudinal studies and 6 in the cross-sectional analysis only. Onset ranged from birth to 7 years. Twenty-nine patients had an autosomal dominant RYR1-related myopathy, 31 recessive, 6 de novo dominant, and 3 uncertain inheritance. Median age at the first and last appointment was 4.0 and 10.8 years, respectively. Fifteen% of patients older than 2 years never walked (5 recessive, 4 de novo dominant, and 1 dominant patient) and 7% lost ambulation during follow-up. Scoliosis and spinal rigidity were present in 30% and 17% of patients, respectively. Respiratory involvement was observed in 22% of patients, and 12% needed ventilatory support from a median age of 7 years. Feeding difficulties were present in 30% of patients, and 57% of those needed gastrostomy or tube feeding. There were no anesthetic-induced malignant hyperthermia episodes reported in this cohort. We observed a higher prevalence of prenatal/neonatal features in recessive patients, in particular hypotonia and respiratory difficulties. Clinical presentation, respiratory outcomes, and feeding outcomes were consistently more severe at presentation and in the recessive group. Conversely, longitudinal analysis suggested a less progressive course for motor and respiratory function in recessive patients. Annual change in forced vital capacity was -0.2%/year in recessive vs -1.4%/year in dominant patients. DISCUSSION: This clinical study provides long-term data on disease progression in RYR1-related myopathies that may inform management and provide essential milestones for future therapeutic interventions.

Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad / Therapeutic agents tested in 238 COVID-19 hospitalized patients and their relationship with mortality

ANTECEDENTES Y OBJETIVO: En los últimos meses se han realizado grandes esfuerzos para evaluar las terapias más eficaces en el manejo de pacientes con COVID-19. Actualmente ninguna combinación ha demostrado de manera consistente una relación clara con la mortalidad. Nuestro objetivo fue valorar el patrón de asociaciones observado entre los distintos tratamientos intrahospitalarios administrados a 238 pacientes ingresados por COVID-19 y la mortalidad. MATERIALES Y MÉTODOS: Se analizaron las historias clínicas electrónicas de aquellos pacientes dados de alta o que fallecieron por COVID-19 entre el 16 de marzo y el 10 de abril de 2020 en el Hospital Universitario San Cecilio (Granada, España). Se obtuvo información sobre sexo, edad, comorbilidades al ingreso, parámetros clínicos, analíticos, pruebas de imagen y tratamientos empíricos empleados. La variable de desenlace fue la mortalidad intrahospitalaria. Para estimar las asociaciones entre los diferentes tratamientos y el riesgo de mortalidad se estimaron, mediante modelos de regresión de Cox, hazard ratio ajustadas por edad, sexo, patologías previas y gravedad al ingreso. RESULTADOS: La combinación de fármacos más frecuentemente empleada fue la formada por heparina de bajo peso molecular (HBPM), hidroxicloroquina y ritonavir/lopinavir. Ninguno de los tratamientos utilizados mostró una asociación independiente con la mortalidad. Los fármacos que mostraron una asociación inversa de mayor magnitud fueron el tocilizumab y los corticoides. CONCLUSIONES: El patrón se asociaciones obtenido es consistente con lo reportado en la bibliografía. Parece oportuno diseñar ensayos aleatorizados que valoren el posible efecto protector de los corticoides y el tocilizumab sobre el riesgo de muerte en algunos subgrupos de pacientes hospitalizados por COVID-19

BACKGROUND AND OBJECTIVES: In the last months great efforts have been developed to evaluate the more efficient therapeutic agents in the management of patients with COVID-19. Currently, no specific drug combination has consistently demonstrated an association with mortality. The aim of this study was to assess the pattern of associations observed between the different in-hospital treatments administered to a series of 238 patients admitted for COVID-19 and their relationship with mortality. METHODS: The electronic medical records of patients that discharged or died from COVID-19 in the Hospital Universitario San Cecilio (Granada, Spain) between March 16 and April 10, 2020 were analysed. From these records, information was obtained on sex, age, comorbidities at admission, clinical information, analytical parameters, imaging tests and empirical treatments used. The outcome variable was the in-hospital mortality. To estimate the associations between the different therapeutic alternatives and the risk of mortality, hazard ratios adjusted for age, sex, previous pathologies and severity at discharge were estimated using Cox regression models. RESULTS: The most frequently used combination of drugs was low molecular weight heparins, hydroxychloroquine, and ritonavir/lopinavir. None of the analysed treatments showed independent association with mortality. The drugs that showed a greater inverse association with mortality were tocilizumab and corticoids. CONCLUSIONS: The observed association patterns are consistent with previous literature. It seems necessary to design randomized controlled clinical trials that evaluate the possible protector effect of tocilizumab and corticoids in the risk of mortality for some subgroups of COVID-19 hospitalized patients

Therapeutic agents tested in 238 COVID-19 hospitalized patients and their relationship with mortality.

BACKGROUND AND OBJECTIVES: In the last months great efforts have been developed to evaluate the more efficient therapeutic agents in the management of patients with COVID-19. Currently, no specific drug combination has consistently demonstrated an association with mortality. The aim of this study was to assess the pattern of associations observed between the different in-hospital treatments administered to a series of 238 patients admitted for COVID-19 and their relationship with mortality. METHODS: The electronic medical records of patients that discharged or died from COVID-19 in the Hospital Universitario San Cecilio (Granada, Spain) between March 16 and April 10, 2020 were analysed. From these records, information was obtained on sex, age, comorbidities at admission, clinical information, analytical parameters, imaging tests and empirical treatments used. The outcome variable was the in-hospital mortality. To estimate the associations between the different therapeutic alternatives and the risk of mortality, Hazard Ratios adjusted for age, sex, previous pathologies and severity at discharge were estimated using Cox Regression models. RESULTS: The most frequently used combination of drugs was low molecular weight heparins, hydroxychloroquine, and ritonavir/lopinavir. None of the analysed treatments showed independent association with mortality. The drugs that showed a greater inverse association with mortality were tocilizumab and corticoids. CONCLUSIONS: The observed association patterns are consistent with previous literature. It seems necessary to design randomized controlled clinical trials that evaluate the possible protector effect of tocilizumab and corticoids in the risk of mortality for some subgroups of COVID-19 hospitalized patients.

ANTECEDENTES Y OBJETIVO: En los últimos meses se han realizado grandes esfuerzos para evaluar las terapias más eficaces en el manejo de pacientes con COVID-19. Actualmente ninguna combinación ha demostrado de manera consistente una relación clara con la mortalidad. Nuestro objetivo fue valorar el patrón de asociaciones observado entre los distintos tratamientos intrahospitalarios administrados a 238 pacientes ingresados por COVID-19 y la mortalidad. MATERIALES Y MÉTODOS: Se analizaron las historias clínicas electrónicas de aquellos pacientes dados de alta o que fallecieron por COVID-19 entre el 16 de marzo y el 10 de abril de 2020 en el Hospital Universitario San Cecilio (Granada, España). Se obtuvo información sobre sexo, edad, comorbilidades al ingreso, parámetros clínicos, analíticos, pruebas de imagen y tratamientos empíricos empleados. La variable de desenlace fue la mortalidad intrahospitalaria. Para estimar las asociaciones entre los diferentes tratamientos y el riesgo de mortalidad se estimaron, mediante modelos de regresión de Cox, hazard ratio ajustadas por edad, sexo, patologías previas y gravedad al ingreso. RESULTADOS: La combinación de fármacos más frecuentemente empleada fue la formada por heparinade bajo peso molecular (HBPM), hidroxicloroquina y ritonavir/lopinavir. Ninguno de los tratamientos utilizados mostró una asociación independiente con la mortalidad. Los fármacos que mostraron una asociación inversa de mayor magnitud fueron el tocilizumab y los corticoides. CONCLUSIONES: El patrón se asociaciones obtenido es consistente con lo reportado en la bibliografía. Parece oportuno diseñar ensayos aleatorizados que valoren el posible efecto protector de los corticoides y el tocilizumab sobre el riesgo de muerte en algunos subgrupos de pacientes hospitalizados por COVID-19.

[Therapeutic agents tested in 238 COVID-19 hospitalized patients and their relationship with mortality]. / Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad.

BACKGROUND AND OBJECTIVES: In the last months great efforts have been developed to evaluate the more efficient therapeutic agents in the management of patients with COVID-19. Currently, no specific drug combination has consistently demonstrated an association with mortality. The aim of this study was to assess the pattern of associations observed between the different in-hospital treatments administered to a series of 238 patients admitted for COVID-19 and their relationship with mortality. METHODS: The electronic medical records of patients that discharged or died from COVID-19 in the Hospital Universitario San Cecilio (Granada, Spain) between March 16 and April 10, 2020 were analysed. From these records, information was obtained on sex, age, comorbidities at admission, clinical information, analytical parameters, imaging tests and empirical treatments used. The outcome variable was the in-hospital mortality. To estimate the associations between the different therapeutic alternatives and the risk of mortality, hazard ratios adjusted for age, sex, previous pathologies and severity at discharge were estimated using Cox regression models. RESULTS: The most frequently used combination of drugs was low molecular weight heparins, hydroxychloroquine, and ritonavir/lopinavir. None of the analysed treatments showed independent association with mortality. The drugs that showed a greater inverse association with mortality were tocilizumab and corticoids. CONCLUSIONS: The observed association patterns are consistent with previous literature. It seems necessary to design randomized controlled clinical trials that evaluate the possible protector effect of tocilizumab and corticoids in the risk of mortality for some subgroups of COVID-19 hospitalized patients.

Clinical Factors, Preventive Behaviours and Temporal Outcomes Associated with COVID-19 Infection in Health Professionals at a Spanish Hospital.

The novel coronavirus disease (COVID-19) outbreak has quickly spread around the world, with Spain being one of the most severely affected countries. Healthcare professionals are an important risk group given their exposure. The aims of this study were to determine the prevalence of symptoms, main concerns as patients, preventive behaviours of healthcare professionals, and the different temporal outcomes associated with the negativization of PCR results. A total of 238 professionals were analysed and follow-up was conducted from 11 March to 21 April 2020 through clinical records, in-depth surveys, and telephone interviews. Symptoms, concerns, and preventive measures were documented, and temporal outcomes (start and end of symptoms, first positive PCR, and negativization of PCR) were analysed through survival analyses. A high prevalence of gastrointestinal symptoms (especially in women and older professionals), fever, cough, and fatigue were reported. The main concern was contagion in the work and home environment. Professionals (especially men) reported low use of face masks before the pandemic. Our analysis indicates that the median times for the negativization of PCR testing to confirm the resolution of infection is 15 days after the end of symptoms, or 25 days after the first positive PCR test. Our results suggest that these times are longer for women and for professionals aged ≥55 years, therefore follow-up strategies should be optimized in light of both variables. This is the first study we are aware of to report factors associated with the time to negativization of PCR results. We present the first rigorous estimates of time outcomes and hope that these data can be valuable to continue feeding the prediction models that are currently being developed. Similar studies are required to corroborate our results.

Sociodemographic, clinical and laboratory factors on admission associated with COVID-19 mortality in hospitalized patients: A retrospective observational study.

BACKGROUND: To identify and quantify associations between baseline characteristics on hospital admission and mortality in patients with COVID-19 at a tertiary hospital in Spain. METHODS AND FINDINGS: This retrospective case series included 238 patients hospitalized for COVID-19 at Hospital Universitario Clínico San Cecilio (Granada, Spain) who were discharged or who died. Electronic medical records were reviewed to obtain information on sex, age, personal antecedents, clinical features, findings on physical examination, and laboratory results for each patient. Associations between mortality and baseline characteristics were estimated as hazard ratios (HR) calculated with Cox regression models. Series mortality was 25.6%. Among patients with dependence for basic activities of daily living, 78.7% died, and among patients residing in retirement homes, 80.8% died. The variables most clearly associated with a greater hazard of death were age (3% HR increase per 1-year increase in age; 95%CI 1-6), diabetes mellitus (HR 2.42, 95%CI 1.43-4.09), SatO2/FiO2 ratio (43% HR reduction per 1-point increase; 95%CI 23-57), SOFA score (19% HR increase per 1-point increase, 95%CI 5-34) and CURB-65 score (76% HR increase per 1-point increase, 95%CI 23-143). CONCLUSIONS: The patients residing in retirement homes showed great vulnerability. The main baseline factors that were independently associated with mortality in patients hospitalized for COVID-19 were older age, diabetes mellitus, low SatO2/FiO2 ratio, and high SOFA and CURB-65 scores.

Norovirus: ¿un huésped más en residencias de la tercera edad? / Norovirus: One more guest in residential homes for the elderly?

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Mitochondrial Disease in Children: The Nephrologist's Perspective.

Mitochondrial diseases (MD) are a heterogeneous group of clinical syndromes characterized by the involvement of different organ systems. They constitute the most prevalent hereditary metabolic disease group. OBJECTIVE: To review the importance of the kidney in MD from the nephrologist's perspective within the setting of a pediatric tertiary reference center. STUDY DESIGN: Retrospective study of children (<18 years) with MD followed between 2000 and 2016 at a tertiary Spanish center. RESULTS: 52 patients were included. The mean age at the time of the study was 10 years (SD ± 5.1). The mean follow-up time was 6.1 years (SD ± 4.7). The median age at diagnosis was 2.5 years (0.3-13.5).The median number of affected systems was two (range 1-6). The nervous system was the most affected system, with 51 patients (~98%) presenting with neurological involvement. 20 patients (~40%) presented with endocrinological manifestations, 18 (~35%) with vision problems, 16 (~30%) with gastrointestinal symptoms, 5 (~10%) patients developed hearing impairment, and 6 (~10%) cardiac disease.We detected renal involvement in 13 patients (25%). Eight patients had tubular disease, most frequently hypercalciuria with hypouricemia and five patients had glomerular involvement, with proteinuria and/or decreased glomerular filtration rate as the most frequent symptoms. Only 21 patients (~40%) had been seen by a pediatric nephrologist. CONCLUSIONS: Renal disease was a common occurrence in patients with mitochondrial disease, present in our study in 25% of patients. A regular screening of renal function parameters and the involvement of a nephrologist as part of the multidisciplinary approach to mitochondrial disease appears warranted.

Secondary Intracranial Hypertension in Pediatric Patients With Leukemia.

BACKGROUND: We investigated the clinical characteristics of a pediatric population with hemato-oncological disease and intracranial hypertension, analyze the therapeutic response and outcome, and compare its characteristics with respect to a control group with idiopathic intracranial hypertension. METHODS: We retrospectively analyzed patients with hemato-oncological disease and secondary intracranial hypertension in our center during the past five years. We compared these individuals with a historical cohort with idiopathic intracranial hypertension from our institution (control group). RESULTS: We identified eight patients, all with leukemia, and 21 controls. Mean age at diagnosis was 10.6 years, and 62% of individuals were female. Most of them were under treatment with drugs (62% corticosteroids, 75% active chemotherapy). Mean opening pressure of cerebrospinal fluid was 35 cm H2O. All had headache, but only 28% complained of visual symptoms. Only 12.5% exhibited papilledema at the time of diagnosis (versus 71% in controls). All of them were treated with acetazolamide, with average therapy duration of nine months, and all had a favorable outcome (versus 57% of controls who needed second-line treatment). None of them showed long-term visual complications (versus 20% of controls). CONCLUSIONS: Patients with hemato-oncological disease and secondary intracranial hypertension may not develop typical symptomatology. Thus, diagnosis and recognition of this entity among this cohort may be difficult. Associated factors are diverse and do not show an obvious causal relationship. A high index of suspicion must be maintained for diagnosis, because a favorable outcome is expected with prompt treatment. Acetazolamide is effective as a first-line therapy and caused few side effects.

Utilización de bromuros en cinco pacientes epilépticos / Use of bromides in five epileptic patients

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