The impact of clinical genome sequencing in a global population with suspected rare genetic disease.

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities.

Diagnostic approach and monitoring of chronic kidney disease in the primary care pediatric population.

Chronic kidney disease (CKD) has severe consequences on the quality and expectancy of life and is considered a major health problem worldwide. This is, especially relevant in pediatric patients, as they have unique characteristics and a mortality rate 30 times higher (in advanced stages) than healthy people. This review aims to define the minimum components for the diagnostic approach and monitoring of CKD in the pediatric population from primary health care to promote comprehensive care and adequate risk management. For this purpose, we performed a systematic review of the literature with a panel of experts. Based on the evidence, to optimize the definition, diagnosis, and timely treatment of CKD in the pediatric population, we formulated 21 recommendations. These were approved by the research team and peer-reviewed by clinical experts. They will facilitate the definition of the diagnostic approach for CKD in the pediatric population in primary health-care settings, allowing for timely treatment intervention, comprehensive care, and monitoring of this disease.

La enfermedad renal crónica (ERC) tiene graves consecuencias en la calidad y la esperanza de vida, y se considera un importante problema de salud a nivel mundial. Esto es especialmente relevante en pacientes pediátricos, ya que presenta características únicas y una tasa de mortalidad en etapas avanzadas que es 30 veces mayor que en personas sanas. El objetivo de esta revisión fue definir los componentes mínimos para el abordaje diagnóstico y para el seguimiento de la ERC en la población pediátrica desde la atención primaria en salud, con el fin de promover la atención integral y una adecuada gestión del riesgo. Para esto, se realizó una revisión sistemática de la literatura con panel de discusión de expertos. Basándonos en la evidencia, y con el objetivo de optimizar la definición, diagnóstico y tratamiento oportuno de la ERC en la población pediátrica, se formularon 21 recomendaciones. Estas fueron aprobadas por el equipo desarrollador y los pares expertos clínicos evaluadores, y permitirán definir de manera oportuna el abordaje diagnóstico de la ERC en la población pediátrica desde la atención primaria en salud, facilitando la intervención temprana, una atención integral y el seguimiento de esta patología.

Differential psychophysiological responses associated with decision-making in children from different socioeconomic backgrounds.

This study examined how socioeconomic status (SES) influences on decision-making processing. The roles of anticipatory/outcome-related cardiac activity and awareness of task contingencies were also assessed. One hundred twelve children (Mage = 5.83, SDage = 0.32; 52.7% female, 51.8% low-SES; data collected October-December 2018 and April-December 2019) performed the Children's Gambling Task, while heart rate activity was recorded. Awareness of gain/loss contingencies was assessed after completing the task. Distinct decision-making strategies emerged among low and middle/high-SES children. Despite similar awareness levels between SES groups, future-oriented decision-making was linked solely to the middle/high-SES group. Somatic markers did not manifest unequivocally. However, contrasting cardiac patterns were evident concerning feedback processing and the association between anticipatory activity and awareness (low: acceleration vs. middle/high: deceleration). Results are interpreted from an evolutionary-developmental perspective.

Guiding Principles to Address the Impact of Algorithm Bias on Racial and Ethnic Disparities in Health and Health Care.

Importance: Health care algorithms are used for diagnosis, treatment, prognosis, risk stratification, and allocation of resources. Bias in the development and use of algorithms can lead to worse outcomes for racial and ethnic minoritized groups and other historically marginalized populations such as individuals with lower income. Objective: To provide a conceptual framework and guiding principles for mitigating and preventing bias in health care algorithms to promote health and health care equity. Evidence Review: The Agency for Healthcare Research and Quality and the National Institute for Minority Health and Health Disparities convened a diverse panel of experts to review evidence, hear from stakeholders, and receive community feedback. Findings: The panel developed a conceptual framework to apply guiding principles across an algorithm's life cycle, centering health and health care equity for patients and communities as the goal, within the wider context of structural racism and discrimination. Multiple stakeholders can mitigate and prevent bias at each phase of the algorithm life cycle, including problem formulation (phase 1); data selection, assessment, and management (phase 2); algorithm development, training, and validation (phase 3); deployment and integration of algorithms in intended settings (phase 4); and algorithm monitoring, maintenance, updating, or deimplementation (phase 5). Five principles should guide these efforts: (1) promote health and health care equity during all phases of the health care algorithm life cycle; (2) ensure health care algorithms and their use are transparent and explainable; (3) authentically engage patients and communities during all phases of the health care algorithm life cycle and earn trustworthiness; (4) explicitly identify health care algorithmic fairness issues and trade-offs; and (5) establish accountability for equity and fairness in outcomes from health care algorithms. Conclusions and Relevance: Multiple stakeholders must partner to create systems, processes, regulations, incentives, standards, and policies to mitigate and prevent algorithmic bias. Reforms should implement guiding principles that support promotion of health and health care equity in all phases of the algorithm life cycle as well as transparency and explainability, authentic community engagement and ethical partnerships, explicit identification of fairness issues and trade-offs, and accountability for equity and fairness.

Consenso de expertos sobre recomendaciones basadas en evidencia para el diagnóstico, tratamiento y seguimiento de enfermedad de Fabry en pediatría / Expert Consensus on Evidence-Based Recommendations for the Diagnosis, Treatment, and Follow-Up of Fabry Disease in Pediatric Patients / Consenso de especialistas colombianos sobre recomendações baseadas em evidências para o diagnóstico, tratamento e acompanhamento da doença de Fabry em pediatria

Antecedentes: la enfermedad de Fabry (Ef) es una enfermedad rara ligada a X secundaria al depósito lisosomal de glicoesfingolípidos, debido a la deficiencia de la enzima alfa galactosidasa A (α-Gal A). A pesar de su baja frecuencia, es una condición que afecta la calidad de vida de los pacientes y disminuye su esperanza de vida. Objetivo: generar recomendaciones informadas para el diagnóstico y tratamiento de pacientes pediátricos (menores de 18 años) con Ef. Material y Métodos: revisión de literatura en bases de datos y literatura gris a partir de 2010, incluyendo guías de práctica clínica, revisiones sistemáticas y estudios primarios. La calidad de evidencia se evaluó de acuerdo con el tipo. Las recomendaciones se sometieron a consenso de expertos a través de metodología Delphi modificada. El acuerdo se definió a partir del 80 %. Resultados: A partir del análisis de la evidencia recolectada se formularon un total de 45 recomendaciones para tamización, diagnóstico y tratamiento de paciente pediátrico con Ef. El panel revisor estuvo conformado por once expertos en el tema. Las recomendaciones fueron aprobadas con puntuaciones entre 82.3 % y 100 %. Conclusiones: las recomendaciones resultantes del consenso de expertos permitirán la toma de decisiones clínicas y estandarización de la práctica en la atención de pacientes pediátricos con Ef en el país y la región. El diagnóstico temprano y oportuno garantiza una disminución del impacto en la calidad de vida de los pacientes y sus familiares

Background: Fabry disease (fD) is a rare X-linked disease characterized by the accumulation of glyco- sphingolipids in lysosomes due to the deficiency in the production of alpha-galactosidase A (α-Gal A) enzyme. Despite its low frequency, this disease has a serious impact on the life expectancy and quality. Objective: To make evidence-based recommendations for the diagnosis and treatment of fD in pediatric patients (<18 years of age). Materials and Methods: A study of databases and gray literature was conducted in 2010, including clinical practice guidelines, systematic reviews, and primary research. The type of evidence was used to determine the quality of evidence. The recommendations were submitted to an expert consensus using the modified Delphi process. The agreement was set at 80%. Conclusions: The recommendations emerging from this expert consensus will enable the standardization of care provision for pediatric patients with fD in Colombia and Latin America and clinical decision-making for disease management. Notably, making an early diagnosis ensures a reduction in the impact of this disease on the quality of life of patients and their families

Fundamento: a doença de Fabry (Df) é uma rara doença ligada ao cromossomo X secundária à deposi- ção lisossômica de glicoesfingolipídeos devido à deficiência da enzima alfa galactosidase A (α-Gal A). Apesar de sua baixa frequência, é uma condição que afeta a qualidade de vida dos pacientes e diminui sua expectativa de vida. Objetivo: gerar recomendações baseadas em evidências para o diagnóstico e tratamento de pacientes pediátricos (com menos de 8 anos de idade) com Df. Materais e Métodos: foi realizada uma revisão da literatura em bases de dados e literatura cinza a partir de 2010, incluindo diretrizes de prática clínica, revisões sistemáticas e estudos primários. A qualidade da evidência foi avaliada de acordo com o tipo de evidência. As recomendações foram submetidas ao consenso de especialistas usando a metodologia Delphi modificada. A concordância foi definida a partir de 80%. Resultados: com base na análise das evidências coletadas, foram formuladas um total de 45 recomendações para triagem, diagnóstico e tratamento de pacientes pediátricos com doença de Fabry. O painel de revisão foi composto por onze especialistas no assunto. As recomendações foram aprovadas com pontuações entre 82,3% e 100%. Conclusões: as recomendações resultantes do consenso de especialistas permitirão a tomada de decisão clínica e a padronização da prática no cuidado de pacientes pediátricos com Df em nível nacional e regional; o diagnóstico precoce e oportuno garante a redução do impacto na qualidade de vida dos pacientes e seus familiares.

Recomendaciones sobre la vacunación contra SARS-CoV-2 en pacientes en diálisis y lista de espera de trasplante renal

Contexto las personas con diálisis se consideran una población de alto riesgo de infección por SARS-CoV-2, complicaciones y muerte. En Colombia, cerca del 44 % de la población en diálisis es menor de 60 años, adicionalmente, por los mismos retos que ha impuesto la pandemia a los programas de trasplantes, se ha incrementado notoriamente la población joven que debe seguir en diálisis al no tener opción a corto plazo de un trasplante renal, por lo tanto, las limitaciones en el acceso temprano a la vacunación contra SARS-CoV-2 agudizarían los problemas de esta población, provocando pérdidas considerables en años de vida que la vacuna podría salvar. Objetivo el objetivo del presente documento es sintetizar los principales motivos por los que se recomienda la priorización de la vacunación de los pacientes en diálisis crónica y lista de espera para trasplante renal. Metodología se realizó una búsqueda rápida de información sobre la vacunación en pacientes con ERC en diálisis o en espera de trasplante renal. La información resultante fue analizada críticamente por expertos en nefrología para la formulación de recomendaciones. Los resultados de la búsqueda se presentan a manera de síntesis narrativa. Resultados a partir de la información revisada y discutida por los expertos en nefrología se proponen 4 recomendaciones para la vacunación contra el virus SARS-Cov-2. Conclusiones la Asociación Colombiana de Nefrología e Hipertensión Arterial, la Asociación Colombiana de Nefrología Pediátrica y la Asociación Colombiana de Trasplante de Órganos, comprometidos con la salud de los pacientes con enfermedad renal en diálisis y listas de espera de trasplantes en Colombia, se unen a la solicitud mundial de generar recomendaciones para la vacunación contra SARS-CoV-2.

Background People on dialysis are considered a high-risk population for SARS-CoV-2 infection, complications, and death. In Colombia, about 44% of the population on dialysis is under 60 years of age. In addition, due to the same challenges that the pandemic has imposed on transplant programs, the young population that must continue on dialysis has increased markedly, as they have no option in the short term of a kidney transplant, therefore, the limitations in early access to vaccination against SARS-CoV-2 would exacerbate the problems of this population, causing considerable losses in years of life that the vaccine could save. Purpose The objective of this document is to summarize the main reasons why the prioritization of vaccination of patients on chronic dialysis and on the kidney transplant waiting list is recommended. Methodology A rapid search for information on vaccination in patients with CKD on dialysis or awaiting kidney transplantation was performed. The resulting information was critically analyzed by experts in nephrology for the formulation of recommendations. The search results are presented as a narrative synthesis. Results Based on the information reviewed and discussed by nephrology experts, 4 recommendations are proposed for vaccination against the SARS-Cov-2 virus. Conclusions The Colombian Association of Nephrology and Arterial Hypertension (ASOCOLNEF), the Colombian Association of Pediatric Nephrology (ACONEPE) and the Colombian Association of Organ Transplantation (ACTO), committed to the health of patients with kidney disease on dialysis and transplant waiting lists in Colombia, join to generate recommendations for prioritization and vaccination against SARS-CoV-2.

Simulation-based education improves military trainees' skill performance and self-confidence in tourniquet placement: A randomized controlled trial.

BACKGROUND: Tactical Combat Casualty Care (TCCC) is the standard of care for stabilization and treatment of military trauma patients. The Department of Defense has mandated that all service members receive role-based TCCC training and certification. Simulation education can increase procedural skills by providing opportunities for deliberate practice in safe, controlled environments. We developed and evaluated the effectiveness of a simulation-based TCCC training intervention to improve participants' skill performance and self-confidence in tourniquet placement. METHODS: This study was a single-blinded, randomized trial with waitlist controls. Army Reserve Officers Training Corp cadets from a single training battalion comprised the study population. After randomization and baseline assessment of all participants, group A alone received focused, simulation-based TCCC tourniquet application training. Three months later, all participants underwent repeat testing, and after crossover, the waitlist group B received the same intervention. Two months later, all cadets underwent a third/final assessment. The primary outcome was tourniquet placement proficiency assessed by total score achieved on a standardized eight-item skill checklist. A secondary outcome was self-confidence in tourniquet application skill as judged by participants' Likert scale ratings. RESULTS: Forty-three Army Reserve Officers Training Corp cadets completed the study protocol. Participants in both group A (n = 25) and group B (n = 18) demonstrated significantly higher performance from baseline to final assessment at 5 months and 2 months, respectively, following the intervention. Mean total checklist score of the entire study cohort increased significantly from 5.53 (SD = 2.00) at baseline to 7.56 (SD = 1.08) at time 3, a gain of 36.7% ( p < 0.001). Both groups rated their self-confidence in tourniquet placement significantly higher following the training. CONCLUSION: A simulation-based TCCC curriculum resulted in significant, consistent, and sustained improvement in participants' skill proficiency and self-confidence in tourniquet placement. Participants maintained these gains 2 months to 5 months after initial training. LEVEL OF EVIDENCE: Therapeutic/care management; Level II.

Socioeconomic status differences in children's affective decision-making: The role of awareness in the Children's Gambling Task.

Future-oriented decision-making is an important adaptive behavior. In the present study, we examined whether decision-making varies as a function of socioeconomic status (SES) using the Children's Gambling task (CGT). We administered the CGT to 227 children (49% female, 48% low SES) between the ages of 5 and 7 years. After completing the CGT, we assessed children's knowledge of the reward/loss contingencies. Data analysis was conducted through multilevel modeling. Fluid intelligence, as measured by the Test of Nonverbal Intelligence, was included as a covariate in the analysis. Overall performance differed between SES groups. Children from middle/high-SES backgrounds learned to choose more from the deck with higher future reward. In contrast, children in the low-SES group did not act in a full future-oriented manner. No differences were found in the level of explicit understanding of the task reached by the two SES groups. Whereas middle/high-SES children with higher knowledge of the game performed better on the last blocks of the task in comparison with their same-SES peers with no understanding, low-SES children with higher explicit knowledge did not exhibit an improvement in their decision-making strategy in comparison with their same-SES low-awareness counterparts. Fluid intelligence did not predict CGT performance, suggesting that SES differences were not mediated by reasoning capabilities. The finding that children from low-SES families continued exhibiting an immediate reward-oriented strategy despite being aware of deck contingencies fits with (although speculatively) the evolutionary-developmental framework. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Does urban climate follow urban form? Analysing intraurban LST trajectories versus urban form trends in 3 cities with different background climates.

The current climate change trend urges the application of efficient spatial planning to mitigate the effects of urbanization on local urban warming. Nevertheless, how urban temperatures respond to urban form changes inside cities is still insufficiently understood. In this paper, we explored the relationship between urban form and diurnal space-time land surface temperature (LST) trends (2003-2019) in Beijing (continental climate), Cairo (arid) and Santiago (temperate). We analysed changes in land cover, white sky albedo (WSA), night-time lights (NL) and the enhanced vegetation index (EVI) inside areas representing clustered thermal performance (steady cold and hot spots and warming cold and hot spots). The structure of local climate zones (LCZs) was assessed for each LST trend. To test the relevance of other urban form dimensions, we analysed the hierarchical influence of the employed 2D metrics (i.e., built-up cover, WSA, NL and EVI) and additional 3D indicators (i.e., height and volume) on LST, applying machine learning classification and regression trees (CARTs) to Beijing's data. Despite diverse patterns of urban form change, cities in our sample present common LST trends, with thermal differences as a consequence of local climate. LCZs are composed of highly heterogeneous built-up areas inside LST trend categories. In the case of Beijing, LST is hierarchically driven by footprint, WSA and EVI. Moreover, by adding height and volume, urban form differences between LST trend classes that are not evident with 2D data were found. Our findings suggest that a compact green urban tissue is necessary to cope with the current trends of urban warming, taking into account city-specific measures based on the local background climate.

Intraurban heterogeneity of space-time land surface temperature trends in six climate-diverse cities.

Surface urban heat islands (SUHIs) are present in all cities, derived from their thermal properties. While looking at the spatiotemporal variability of land surface temperature (LST), there is still a gap in understanding patterns of change. In this paper, we analysed diurnal and nocturnal annual mean LST trends in continental (Beijing), temperate (Mexico City and Santiago), and arid (Cairo, Hyderabad, and Riyadh) cities employing 1 km MODIS data (2003-2019). Each time-series was assessed with the structure of a space-time cube. Hot and cold spots were detected for each year and the LST trends were analysed. Each pixel was classified into different space-time LST trends and their SUHIs were estimated. Cities exhibit trends of increasing temperatures in cold and hot spots for diurnal and nocturnal data. Temperatures are increasing faster in hot spots for diurnal and in cold spots for nocturnal scenes. Steady hot spots and warming hot spots exhibit the highest SUHIs for day and night. Our approach provides a framework to empirically delineate the spatial intraurban heterogeneity of LST patterns over time. This spatially explicit information provides insights into urban areas requiring heat mitigation strategies and can be used to monitor the performance of measures already implemented for climate adaptation.

Novel Compound Heterozygous Mutation c.3955_3958dup and c.5825C>T in the ATM Gene: Clinical Evidence of Ataxia-Telangiectasia and Cancer in a Peruvian Family.

Pathogenic and likely pathogenic variants in the ATM gene are associated both with Ataxia-telangiectasia disease or ATM syndrome and an increased cancer risk for heterozygous carriers. We identified a novel compound heterozygous mutation c.3955_3958dup (p.Asp1320delinsValTer) and c.5825C>T (p.Ala1942Val) in the ATM gene in a Peruvian patient with progressive ataxia combined with other movement disorders, mild conjunctival telangiectasia and increased alpha-fetoprotein, without history of recurrent infection or immunodeficiency. We also determined the carrier status of the family members, and we were able to detect gastric and breast cancer at an early stage during the cancer risk assessment in the mother (c.3955_3958dup). Here, we describe clinical evidence for the novel compound heterozygous mutation and c.3955_3958dup not previously reported.

Consenso colombiano de expertos sobre recomendaciones informadas en la evidencia para la prevención, diagnóstico y manejo de la infección por SARS-CoV-2/COVID-19 en paciente pediátrico con enfermedad renal crónica o lesión renal aguda asociada a COVID-19 / Colombian consensus of experts on evidence-informed recommendations for the prevention, diagnosis, and management of SARS-CoV-2 / COVID-19 infection in pediatric patients with chronic kidney disease or acute kidney injury associated with COVID-19

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Abstract Introduction: The numbers of SARS-CoV-2 infection in the pediatric population are low so far. There is limited information about the behavior of SARS-CoV-2 in a pediatric patient with chronic kidney disease. Objective: To formulate informed recommendations to the prevention, diagnosis, and management of SARS-CoV-2 infection in pediatric patients with kidney disease or acute kidney injury associated with COVID-19 in Colombia. Methodology: A rapid systematic review was performed in Embase and Pubmed databases and scientific societies, to answer questions prioritized by clinical experts in pediatric nephrology. The quality of the evidence was evaluated with validated tools according to the type of study. The preliminary recommendations were consulted by an expert group. The agreement was defined when approval was obtained from at least 70% of the experts consulted. Results: A response was obtained from ' 9 experts in pediatric nephrology in Colombia, who declared the conflict of interest before the consultation. The range of agreement for the recommendations ranged from 78.9% to '00%. The recommendations did not require a second consultation. Conclusion: The evidence-based recommendations for the management of a patient with kidney disease and COVID-19 in the Colombian context are presented.

Urban form datasets of 194 cities delineated based on the contiguous urban fabric for 1990 and 2015.

The present research datasets were processed for the article "The global homogenization of urban form. An assessment of 194 cities across time" [1]. They consist of land cover spatial layers, longitude and latitude point data and tabulated data with computed landscape metrics and the characterization of urban form of 194 cities for 1990 and 2015. Contiguous urban fabric at 30 m spatial resolution was derived from the Atlas of Urban Expansion database for 1990 and 2015 [2]. Landscape metrics were computed as quantitative measures of composition and spatial arrangement of each city and dimensions of the database were reduced employing correlation and principal components analysis. Hierarchical clustering was employed to group cities according to the similarity of their urban form and analysis of variance was applied to test for significant differences between them. The spatial layers contained in this article can be complemented with past and future land cover data to model urban form change at broader temporal scales. The landscape metrics are useful for cross-city comparisons at regional, national and global levels in combination with other complementary indicators. The datasets are valuable for urban planners, urban ecologists, NGO's, decision makers and other with interest on local and global landscape change in urban areas, particularly urban expansion and its impacts.

Effect of 90-Min Bikram Yoga on Basic Psychological Needs Among Practitioners in the Southwestern United States.

BACKGROUND: In our modern society, physical activity is a lifestyle choice. Bikram Yoga is a low impact; moderate exercise and the understanding of motivation and adherence to the practice is unknown. This study aimed to evaluate the effect of 90 min Bikram Yoga practice on basic psychological needs of competence (the sense of skill mastery), autonomy (volitionally performing a task), and relatedness (a connection with others) as postulated in self-determination theory for motivation. METHODS: The sample included Bikram Yoga practitioners in the Southwestern United States (n = 126) averaged between the age group of 35 and 64, predominately female, and highly educated. Responses to the Psychological Need Satisfaction in Exercise Scale were analyzed using multivariate analysis of variance. RESULTS: Results showed a statistically significant effect of frequency of Yoga attendance on the satisfaction of basic psychological needs (i.e., competence, autonomy, and relatedness); (P = 0.025); specifically, Yoga practitioners who attended four or more classes per week had higher satisfaction levels of Basic Psychological Need for competence (P = 0.013) and relatedness (P = 0.034). A statistically significant effect of the level of experience on the satisfaction of basic psychological needs (i.e., competence, autonomy, and relatedness) (P = 0.014) found in experienced Bikram Yoga practitioners, specifically for competence (P = 0.013) and relatedness (P = 0.023) compared to novice counterparts. CONCLUSION: The study provides some evidence of an individual's motivation for a 90 min Bikram Yoga practice and possible adherence. Future investigation of Bikram Yoga practice adopting self-determination theory appears worthwhile.

Ampliación del tamizaje de errores innatos del metabolismo en Perú: reporte de caso con trastorno del metabolismo de cobalamina / Widened screening for innate metabolism disorders in Peru: report of a case with cobalamin metabolism disorder

RESUMEN El tamizaje neonatal de los errores innatos del metabolismo se instauró hace más de 50 años en el mundo. En Latinoamérica, Uruguay, Costa Rica, Chile, Brasil y Colombia han implementado esta política de salud pública de manera sostenida. La tecnología para detectar estas enfermedades ha ido progresando con un mejor costo/efectividad, haciendo que sea de acceso casi universal. Los trastornos del metabolismo intracelular de la cobalamina es un grupo heterogéneo clasificados en tres fenotipos bioquímicos. Reportamos al primer paciente en Perú con diagnóstico tardío de una variante homocigota c.394 C>T en el gen MMACHC, el cual pertenece al grupo de complementación cblC el cual produce aciduria metilmalónica y homocistinuria, caracterizado por talla baja, hipotonía, retraso del desarrollo psicomotor, convulsiones, anemia megaloblástica, trombocitopenia y neutropenia ondulantes; con homocisteína elevada, acidemia metilmalónica, y contradictoriamente aumento de vitamina B12 en sangre. Es importante el diagnóstico oportuno de enfermedades potencialmente tratables, evitando o disminuyendo la severidad del fenotipo, a través de la implementación de nuevas tecnologías en nuestro país.

ABSTRACT Neonatal screening for innate metabolism disorders was instituted more than 50 years ago. In Latin America, countries like Uruguay, Costa Rica, Chile, Brazil, and Colombia have implemented this public health measurement in a sustained fashion. Technology for detecting these conditions has been steadily progressing, achieving a good cost/effectiveness ratio, so access for such test is practically universal. Intracellular cobalamin metabolism disorders constitute a heterogeneous group that is subdivided in three biochemical phenotypes. We report the first patient in Peru with a late diagnosis of a homozygous c.394 C>T variant in the MMACHC gene, which belongs to the cbIC complementation group, which leads to methyl-malonic aciduria and homocystinuria, characterized by low height, retardation of psychomotor development, seizures, megaloblastic anemia, and variable thrombocytopenia and neutropenia. Also, homocysteine levels are high, there is methyl-malonic academia, and there is a paradoxical vitamin B12 increase in peripheral blood. This paper emphasizes the importance of making a timely diagnosis of potentially treatable conditions, avoiding or reducing the severity of the implied phenotype, with the implementation of new technologies in our country.

Recomendaciones para el uso racional de la prueba 25-hidroxivitamina D Resumen de política

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The exponential increase in the request for laboratory tests of 25-Hydroxyvitamin D or [25 (OH) D has ignited the alarms and generated a strong call for attention, since it may reflect deficiencies in the standardization of clinical practice and in the use non-systematic scientific evidence for decision-making in real life, which allows to analyze the indications of the test, its frequency, interpretation and even to assess the impact for health systems, especially when contrasted with the minimum or almost. No effects of the strategy of screening or supplying indiscriminately to the general population, without considering a comprehensive clinical assessment of risks and needs of people. From a purely public health impact point of view, the consequence of massive and unspecified requests is affecting most of the health systems and institutions at the global level. The primary studies that determined average population intake values have been widely used in the formulation of recommendations in Clinical Practice Guidelines, but unfortunately misinterpreted as cut points to diagnose disease and allow the exaggerated prescription of nutritional substitution. The coefficient of variation in routine tests to measure blood levels of 25 (OH) D is high (28%), decreasing the overall accuracy of the test and simultaneously, increasing both the falsely high and falsely low values. The most recent scientific evidence analyzes and seriously questions the usefulness and the real effect of the massive and indiscriminate practice of prescribing vitamin D without an exhaustive risk analysis. The available evidence is insufficient to recommend a general substitution of vitamin D to prevent fractures, falls, changes in bone mineral density, incidence of cardiovascular diseases, cerebrovascular disease, neoplasms and also to modify the growth curve of mothers' children. They received vitamin D as a substitute during pregnancy. The recommendations presented in the document are based on the critical analysis of current evidence and the principles of good clinical practice and invite to consider a rational use of 25 (OH) D tests in the context of a clinical practice focused on people and a comprehensive assessment of needs and risks. The principles of good practice suggest that clinicians may be able to justify that the results of the 25 (OH) D test strongly influence and define clinical practice and modify the outcomes that interest people and impact their health and wellness. Currently there is no clarity on how to interpret the results, and the relationship between symptoms and 25 (OH) D levels, which may not be consistent with the high prevalence of vitamin D deficiency reported. For this reason, it is suggested to review the rationale of the request for tests for systematic monitoring of levels of 25 (OH) D or in all cases where substitution is performed. Consider the use of 25 (OH) D tests within the comprehensive evaluation of people with suspicion or confirmation of the following conditions: rickets, osteomalacia, osteoporosis, hyper or hypoparathyroidism, malabsorption syndromes, sarcopenia, metabolic bone disease.

Síndrome de cascanueces en combinación con nefropatía IgA: causa de hematuria y proteinuria persistentes. Reporte de un caso y revisión de la literatura / Nutcracker syndrome combined with IgA Nephropathy: a cause of recurrent hematuria and proteinuria. Case report

RESUMEN El síndrome de cascanueces se produce por la obstrucción de la vena renal izquierda, debido al atrapamiento entre la aorta y la arteria mesentérica superior. Se manifiesta por dolor, hematuria, varicocele o síntomas urinarios bajos o pelvianos. La prevalencia de este síndrome es desconocida, pero se ha incrementado con el advenimiento de estudios no invasivos para su diagnóstico. Por su parte, la nefropatía IgA es la glomerulopatía más común en el mundo y representa cerca del 15 % de las causas de hematuria en niños. La combinación de nefropatía IgA y el síndrome de cascanueces es inusual, con pocos casos descritos en la literatura. Describimos el caso de un escolar de 9 años con hematuria y proteinuria persistente en el curso de una púrpura de Henoch-Schönlein, en quien se realiza una biopsia renal documentando nefropatía IgA. Sin embargo, durante el seguimiento, por la persistencia de hematuria y proteinuria aunadas a otros síntomas, se realizan estudios adicionales que confirman un síndrome de cascanueces. Es clave en los pacientes con la persistencia de estos síntomas descartar la asociación de estas dos enfermedades para evitar intervenciones innecesarias.

SUMMARY The nutcracker syndrome is caused by the obstruction of the left renal vein secondary to its compression between the superior mesenteric artery and the aorta. Clinically, this syndrome manifests with pain, hematuria, varicocele or lower urinary tract symptoms. The prevalence of this syndrome is currently unknown; however, the diagnosis of this condition has increased thanks to the availability of non-invasive studies that allow its recognition. On the other hand, IgA nephropathy is the most common type of glomerular disease worldwide. Almost 15% of the causes of hematuria in children are secondary to this condition. The combination of IgA nephropathy and the nutcracker syndrome is rare. In the current literature, few cases have been described. We described the case of a 9-year-old scholar with hematuria and persistent proteinuria in the course of a purpura of Henoch-Schonlein in whom renal biopsy documented IgA nephropathy. However, during follow-up, due to the persistence of hematuria and proteinuria, in addition to other symptoms, additional studies are carried out confirming a Nutcracker syndrome. It is key in patients with persistent symptoms to rule out the association of these two diseases to avoid unnecessary interventions.

Pielonefritis xantogranulomatosa en pediatría / Pediatric Xanthogranulomatous Pyelonephritis

Resumen La pielonefritis xantogranulomatosa es una variante atípica, severa y poco frecuente de una forma crónica de pielonefritis, que puede ocurrir a cualquier edad. En niños está generalmente asociada a malformaciones urológicas congénitas como obstrucción de las vías urinarias. Se describe el caso de un paciente de un año con episodios febriles recurrentes en quien, tras el tratamiento fallido de una pionefrosis y después de descartar múltiples diagnósticos diferenciales, se decide realizar nefreureterectomía izquierda, considerando clínicamente una pielonefritis xantogranulomatosa, la cual fue confirmada por estudio histopatológico.

Abstract Xanthogranulomatous pyelonephritis is an atypical, severe and infrequent variant of a chronic form of pyelonephritis, which can occur at any age. In children it is generally associated with congenital urological malformations as obstruction of the urinary tract. Next, we describe the case of a 1-year-old patient, with recurrent febrile episodes, where after the failed treatment of pionefrosis and after ruling out multiple differential diagnoses, it was decided to perform a left nephrectomy clinically considering a xanthogranulomatous pyelonephritis, a diagnosis confirmed by study histopathological.