Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

Coexistence of Thyrolipomatosis and Tongue Squamous Cell Carcinoma: A Case Report.

Thyrolipomatosis, a diffuse non-neoplastic infiltration of fatty tissue in the thyroid gland, is an extremely rare condition with only about 30 cases reported worldwide. A few of these cases report the concurrency of thyrolipomatosis and malignant neoplasms in the thyroid or colon, but never with tongue cancer. A 44-year-old female patient with an infiltrative tongue mass suggestive of carcinoma presented for an outpatient consultation. Cervical imaging revealed multiple lymphadenopathies and a multinodular goitre with diffuse fatty infiltration, suggestive of thyrolipomatosis. Surgical intervention included partial resection of the tongue and thyroid (left hemiglossectomy and right hemithyroidectomy, respectively) and lymphadenectomy. The thyroid specimen showed diffuse fat metaplasia of the stromal thyroid tissue, confirming incidental thyrolipomatosis. During post-operative follow-up, the patient presented with recurrence of squamous cell carcinoma as indicated by new right-sided thyroid nodules, left-sided lymphadenopathies with confirmatory biopsy, and a growing neck mass that became infected. The patient developed septic shock and later died. Thyrolipomatosis causes thyroid swelling and can be clinically detected as goitres or as an incidental finding. Diagnosis is suggested by cervical imaging (ultrasonography, computed tomography or magnetic resonance), but confirmation is histological after thyroidectomy. Although thyrolipomatosis is benign, it could develop concurrently with neoplastic diseases, especially on embryologically related tissues (e.g. thyroid and tongue). This case report is the first in the literature describing the coexistence between thyrolipomatosis and tongue cancer in an adult Peruvian patient.

Scoping review of measures of treatment burden in patients with multimorbidity: advancements and current gaps.

OBJECTIVES: To identify, assess, and summarize the measures to assess burden of treatment in patients with multimorbidity (BoT-MMs) and their measurement properties. STUDY DESIGN AND SETTING: MEDLINE via PubMed was searched from inception until May 2021. Independent reviewers extracted data from studies in which BoT-MMs were developed, validated, or reported as used, including an assessment of their measurement properties (e.g., validity and reliability) using the COnsensus-based Standards for the selection of health Measurement INstruments. RESULTS: Eight BoT-MMs were identified across 72 studies. Most studies were performed in English (68%), in high-income countries (90%), without noting urban-rural settings (90%). No BoT-MMs had both sufficient content validity and internal consistency; some measurement properties were either insufficient or uncertain (e.g., responsiveness). Other frequent limitations of BoT-MMs included absent recall time, presence of floor effects, and unclear rationale for categorizing and interpreting raw scores. CONCLUSION: The evidence needed for use of extant BoT-MMs in patients with multimorbidity remains insufficiently developed, including that of suitability for their development, measurement properties, interpretability of scores, and use in low-resource settings. This review summarizes this evidence and identifies issues needing attention for using BoT-MMs in research and clinical practice.

Hypertension prevalence by degrees of urbanization and altitude in Peru: pooled analysis of 186 906 participants.

OBJECTIVE: Few studies, using countrywide data, examined how hypertension prevalence varies at diverse degrees of urbanization and altitude. This study examined the association between urbanization and altitude, including the potential interaction between those variables, with hypertension prevalence in Peru. METHODS: Cross-sectional analysis of the Peruvian Demographic and Health Survey (2014-2019). Hypertension (SBP ≥140 mmHg or DBP ≥90 mmHg or self-reported diagnosis) was the outcome. Exposures were altitude levels, and urbanization assessed with four indicators (urban/rural; type of place of residence; population density level; and population size level). RESULTS: Among 186 906 participants (mean age ± standard deviation: 40.6 ± 17.9; 51.1% women), pooled hypertension prevalence was 19% [95% confidence interval (CI) 18.7-19.3], which was higher in urban compared with rural areas (prevalence ratio: 1.09; 95% CI 1.05-1.15). Compared with countryside, hypertension was higher in towns (prevalence ratio: 1.09; 95% CI 1.04-1.15), small cities (prevalence ratio: 1.07; 95% CI 1.02-1.13) and large cities (prevalence ratio: 1.19; 95% CI 1.12-1.27). Compared with least density settings (1-500 inhabitants/km 2 ), hypertension was higher in the highest density (≥10 001 inhabitants/km 2 ) settings (prevalence ratio: 1.12; 95% CI 1.07-1.18). Population size was not associated with hypertension. Compared with low altitude, hypertension was lower above 2500 m (prevalence ratio 0.91; 95% CI 0.87-0.94) and above 3500 m (prevalence ratio 0.89; 95% CI 0.84-0.95). Interaction between exposures had varying patterning. CONCLUSION: Hypertension in Peru is more prevalent at urban than rural areas, especially in large cities and in more densely populated areas above 10 001 inhabitants/km 2 , and less prevalent at altitudes above 2500 m.

Quantifying the childhood and adolescent overnutrition attributable to specific risk factors: The Young Lives Study in Peru.

OBJECTIVE: Launching priority actions demand a comprehensive appraisal of the size effect that risk factors have on the burden of overweight and obesity. This study aimed to estimate the incidence of overweight and obesity among children and adolescents, with special emphasis on the role of specific risk factors. MATERIALS AND METHODS: Secondary analysis of data from the younger cohort of the Young Lives Study in Peru (2002-2017). The outcomes were: overweight and obesity, defined by the World Health Organization standards; whereas the exposures included caesarean birth, physical activity levels, sodas and sugar-sweetened beverages consumption, snacks consumption, and maternal body mass index (BMI). We used multilevel Poisson regression models, considering the repetitive nature of data, to estimate incidence rate ratios (IRRs) and population attributable fractions (PAFs). RESULTS: A total of 2052 children, mean age 1 (SD 0.4) year, and 50% girls, were enrolled at baseline. After 14 (SD 0.5) years of follow-up, the incidence of overweight and obesity were 7.9 (95% CI 7.6-8.2) and 2.2 (95% CI 2.0-2.4) per 100 person-year, respectively. Maternal BMI (IRRs 3.51; PAF 31.8%), low physical activity (IRR 1.64; PAF 27.4%), caesarean birth (IRR 1.63; PAF 11.4%), almost daily snack consumption (IRR 1.60; PAF 32.1%), and almost daily consumption of sweetened beverages (IRR 1.47; PAF 26.0%) increased the risk of developing obesity. CONCLUSIONS: This study provides evidence on the risk of overweight and obesity attributable to diet habits, physical activity and the obesogenic niche among children and adolescents in Peru, which may guide the implementation of evidence-based interventions.

Urbanization in Peru is inversely associated with double burden of malnutrition: Pooled analysis of 92,841 mother-child pairs.

OBJECTIVE: This study assessed the relationship between urbanization and the double burden of malnutrition (DBM) in Peru. METHODS: A cross-sectional analysis of the Demographic and Health Survey (2009 to 2016) was conducted. A DBM "case" comprised a child with undernutrition and a mother with overweight/obesity. For urbanization, three indicators were used: an eight-category variable based on district-level population density (inhabitants/km2 ), a dichotomous urban/rural variable, and place of residence (countryside, towns, small cities, or capital/large cities). RESULTS: The prevalence of DBM was lower in urban than in rural areas (prevalence ratio [PR] 0.70; 95% CI: 0.65-0.75), and compared with the countryside, DBM was less prevalent in towns (PR 0.75; 95% CI: 0.69-0.82), small cities (PR 0.73; 95% CI: 0.67-0.79), and capital/large cities (PR 0.53; 95% CI: 0.46-0.61). Using population density, the adjusted prevalence of DBM was 9.7% (95% CI: 9.4%-10.1%) in low-density settings (1 to 500 inhabitants/km2 ), 5.9% (95% CI: 4.9%-6.8%) in mid-urbanized settings (1,001 to 2,500 inhabitants/km2 ), 5.8% (95% CI: 4.5%-7.1%) in more densely populated settings (7,501 to 10,000 inhabitants/km2 ), and 5.5% (95% CI: 4.1%-7.0%) in high-density settings (>15,000 inhabitants/km2 ). CONCLUSIONS: The prevalence of DBM is higher in the least-urbanized settings such as rural and peri-urban areas, particularly those under 2,500 inhabitants/km2 .

Trends and patterns of the double burden of malnutrition (DBM) in Peru: a pooled analysis of 129,159 mother-child dyads.

BACKGROUND: This study aims to evaluate trends of DBM in Peru over the last 20 years. METHODS: Using individual-level data collected in nationally representative household surveys from Peru between 1996 and 2017, we analysed trends in the prevalence and patterning of the DBM. We classified the nutritional status of children and their mothers as undernourished (either underweight, stunted or wasted for children), normal, overweight or obese. Children classified as experiencing the DBM were those undernourished and living with an overweight or obese mother. We also fitted logistic regression models to evaluate the probability of children having an overweight/obese mother across subgroups of socioeconomic status, place of residence and education. RESULTS: The overall percentage of children experiencing the DBM in 2016 was 7%, and constitutes ~203,600 children (90% of whom were stunted). Between 1996 and 2016, undernourished children have seen the largest relative increase in the risk of having an overweight mother (31% vs. 37%) or obese mother (6% vs. 17%); however, due to the substantial decrease in the absolute number of undernourished children, the DBM has not grown. Moreover, all children, irrespective of their own nutritional status, are now more likely to live with an overweight or obese mother, a consistent pattern across wealth, location and education subgroups, and all regions of Peru. CONCLUSIONS: DBM prevalence in Peru has decreased, although the number of DBM cases is estimated to be above 200,000. In addition, all children are now more likely to live with overweight or obese mothers. The basic pattern has shifted from one of undernourished children whose mothers have a 'normal' BMI, to one where now most children have a 'normal' or healthy anthropometric status, but whose mothers are overweight or obese. This suggest that Peru is on the cusp of a major public health challenge requiring significant action.

Dysregulated actin dynamics in activated PI3Kδ syndrome.

Activated PI3Kδ syndrome (APDS) Type I results from gain-of-function mutations in PIK3CD, which encodes the p110δ subunit of PI3Kδ. Abnormal actin dynamics have been hypothesized to contribute to the lymphopenia associated with this disease but have not been studied in patients with APDS. We report a patient with APDS who had widespread necrotic skin lesions that were responsive specifically to immunosuppressive therapy. EBV-transformed lymphoblastoid cells (EBV-LCLs) from patients with APDS exhibit increased polymerized actin and increased apoptosis, suggesting a contribution of impaired actin dynamics to this disease.

[Lymphocyte population count as a first approach to the diagnosis of primary immunodeficiencies]. / Recuento poblacional linfocitario como primera aproximación al diagnóstico de inmunodeficiencias primarias.

Primary immunodeficiencies (PID) are characterized by alterations in the components of the immune system. The lymphocyte population count by flow cytometry is an approach to molecular diagnosis and is expressed by immunophenotypes. The objective of the study was to describe the lymphocyte population count and immunophenotyping compatible with PID in patients with suspected PID in a Peruvian national reference hospital. Records of 261 cases meeting the Jeffrey Modell Foundation's PID clinical suspicion criteria were reviewed between April and December of 2016. Of the 261 suspected cases of PID, 54.8% were males. We found 93 patients (35.6%) with PID-compatible immunophenotyping. The common variable immunodeficiency immunophenotype was the most frequent (36.6%), followed by agammaglobulinemias (18.3%). Antibody deficiencies were the most common PID. Other molecular tests are needed for a specific genetic diagnosis.

Las inmunodeficiencias primarias (IDP) se caracterizan por alteraciones de los componentes del sistema inmunitario. El recuento poblacional linfocitario por citometría de flujo es una aproximación al diagnóstico molecular y se expresa por inmunofenotipos. El objetivo del estudio fue describir el recuento poblacional linfocitario y los inmunofenotipos compatibles con IDP en pacientes con sospecha de IDP en un hospital de referencia nacional peruano. Se revisaron los registros de 261 casos que cumplían con los criterios de sospecha clínica para IDP de la Jeffrey Modell Foundation entre abril y diciembre de 2016. De los 261 casos con sospecha de IDP se hallaron 54,8% de varones. Se encontró 93 pacientes (35,6%) con inmunofenotipos compatibles con alguna IDP. El inmunofenotipo de inmunodeficiencia común variable fue más frecuente (36,6%), seguido de agammaglobulinemias (18,3%). Las deficiencias de anticuerpos fueron las IDP más frecuentes. Es necesario realizar otras pruebas moleculares para el diagnóstico genético específico.

Recuento poblacional linfocitario como primera aproximación al diagnóstico de inmunodeficiencias primarias / Lymphocyte population count as a first approach to the diagnosis of primary immunodeficiencies

RESUMEN Las inmunodeficiencias primarias (IDP) se caracterizan por alteraciones de los componentes del sistema inmunitario. El recuento poblacional linfocitario por citometría de flujo es una aproximación al diagnóstico molecular y se expresa por inmunofenotipos. El objetivo del estudio fue describir el recuento poblacional linfocitario y los inmunofenotipos compatibles con IDP en pacientes con sospecha de IDP en un hospital de referencia nacional peruano. Se revisaron los registros de 261 casos que cumplían con los criterios de sospecha clínica para IDP de la Jeffrey Modell Foundation entre abril y diciembre de 2016. De los 261 casos con sospecha de IDP se hallaron 54,8% de varones. Se encontró 93 pacientes (35,6%) con inmunofenotipos compatibles con alguna IDP. El inmunofenotipo de inmunodeficiencia común variable fue más frecuente (36,6%), seguido de agammaglobulinemias (18,3%). Las deficiencias de anticuerpos fueron las IDP más frecuentes. Es necesario realizar otras pruebas moleculares para el diagnóstico genético específico.

ABSTRACT Primary immunodeficiencies (PID) are characterized by alterations in the components of the immune system. The lymphocyte population count by flow cytometry is an approach to molecular diagnosis and is expressed by immunophenotypes. The objective of the study was to describe the lymphocyte population count and immunophenotyping compatible with PID in patients with suspected PID in a Peruvian national reference hospital. Records of 261 cases meeting the Jeffrey Modell Foundation's PID clinical suspicion criteria were reviewed between April and December of 2016. Of the 261 suspected cases of PID, 54.8% were males. We found 93 patients (35.6%) with PID-compatible immunophenotyping. The common variable immunodeficiency immunophenotype was the most frequent (36.6%), followed by agammaglobulinemias (18.3%). Antibody deficiencies were the most common PID. Other molecular tests are needed for a specific genetic diagnosis.

Manejo quirúrgico de pseudotumor hemofílico retroperitoneal: Reporte de caso / Surgical management of a retroperitoneal hemophilic pseudotumor: Report of a case

El pseudotumor hemofílico es una complicación muy rara vista en pacientes con hemofilia severa, y que cuyo manejo aún no se encuentra estandarizado. Se presenta el caso de un paciente varón de 33 años de edad admitido en el servicio de cirugía del Hospital Nacional Dos de Mayo por presentar una tumoración localizada en fosa iliaca izquierda, dolorosa a la palpación, asociada a alteración de la marcha. Realizada la exéresis, se identificó un pseudotumor hemofílico gigante ubicado en retroperitoneo. Este caso expone el primer reporte de manejo de pseudotumor hemofílico en nuestro país, con resultados satisfactorios a los 12 meses del posoperatorio.

The hemophilic pseudotumor is a very rare complication occurring in patients with severe hemophilia, and its management has not been standardized yet. We present the case of a 33-year old male patient who was admitted to the surgery ward in Dos de Mayo Hospital in Lima, Peru, who presented with a tumoral mass located in the left iliac fossa, which was painful when palpated, and it was associated with gait alterations. When the mass was excised, a giant hemophilic pseudotumor located in the retroperitoneum was identified. This is the first case describing the management of a hemophilic pseudotumor in our country, with satisfactory results at 12 months after surgery.

[Neurotoxic effect of aqueous extract of boldo (Peumus boldus) in an animal model]. / Efecto neurotóxico del extracto acuoso de boldo (Peumus boldus) en un modelo animal.

OBJECTIVES: To assess the neurotoxic effect of the aqueous extract of boldo (Peumus boldus) in an experimental model. MATERIALS AND METHODS: 20 male Holtzman rats of 250 ± 15 g were randomized into four groups: the negative control received saline solution (SS) orally (PO), the positive control received 6-hydroxydopamine intracranially (IC) and SS by PO. Experimental group 1 received aqueous extract of boldo (AEB) by PO, and experimental group 2 received 6-hydroxydopamine intracranially and AEB by PO. The experiment lasted 21 days. A neurological assessment was performed which had three components: a) clinical, evaluated with the rotarod test, b) biochemical, by measuring serum levels of uric acid, and c) histopathology, by immunohistochemistry for substantia nigra dopaminergic neurons. The Kruskal Wallis test and the Dunn test were used to assess differences between groups. RESULTS: A significant decrease was found in the latency time of the rotarod test between the negative and positive control group (p<0.01), negative control and experimental 1 (p=0.09), negative control and experimental 2 (p<0.01), positive control and experimental 1 (p=0.04), and experimental 1 and 2 (p=0.09). There was no significant intergroup difference in the identification of uric acid. There was a depletion of the total dopaminergic neurons in the neuronal count, without intergroup difference. CONCLUSIONS: A neurotoxic effect of aqueous extract of boldo was recognized at a clinical level in Holtzman male rats.

Efecto neurotóxico del extracto acuoso de boldo (Peumus boldus) en un modelo animal / Neurotoxic effect of aqueous extract of boldo (Peumus boldus) in an animal model

Objetivos : Evaluar el efecto neurotóxico del extracto acuoso de boldo (Peumus boldus) en un modelo experimental. Materiales y métodos. Se diseñó un experimento, que incluyó 20 ratas macho Holtzman de 250 ± 15 gr, distribuidas aleatoriamente en cuatro grupos: el control negativo recibió solución salina (SS) por vía oral (VO), el control positivo que recibió 6-hidroxidopamina por vía intracraneal (VIC) y SS por VO, el grupo experimental 1 recibió extracto acuoso de boldo (EAB) por VO y el grupo experimental 2 recibió 6-hidroxidopamina por VIC y EAB por VO, en todos los casos durante 21 días. Se realizó una evaluación neurológica, la cual tuvo tres componentes: a) clínico, evaluado con el test de rotarod, b) bioquímico, mediante la determinación de niveles séricos de ácido úrico, y c) histopatológico, por inmunohistoquímica para neuronas dopaminérgicas de sustancia negra. Se empleó la prueba de Kruskal Wallis y el test de Dunn para evaluar las diferencias entre los grupos. Resultados. Se encontró disminución significativa en el tiempo de latencia del test de rotarod entre los grupos control negativo y control positivo (p<0,01), control negativo y experimental 1 (p=0,09), control negativo y experimental 2 (p<0,01), control positivo y experimental 1 (p=0,04), y experimental 1 y 2 (p=0,09). En la determinación de ácido úrico no hubo diferencia significativa intergrupal. En el conteo neuronal hubo depleción de neuronas dopaminérgicas totales, pero sin diferencia intergrupal. Conclusiones. Se evidencio un efecto neurotóxico del extracto acuoso de boldo en ratas macho de la cepa Holtzman a nivel clínico.

Objectives. To assess the neurotoxic effect of the aqueous extract of boldo (Peumus boldus) in an experimental model. Materials and methods. 20 male Holtzman rats of 250 ± 15 g were randomized into four groups: the negative control received saline solution (SS) orally (PO), the positive control received 6-hydroxydopamine intracranially (IC) and SS by PO. Experimental group 1 received aqueous extract of boldo (AEB) by PO, and experimental group 2 received 6-hydroxydopamine intracranially and AEB by PO. The experiment lasted 21 days. A neurological assessment was performed which had three components: a) clinical, evaluated with the rotarod test, b) biochemical, by measuring serum levels of uric acid, and c) histopathology, by immunohistochemistry for substantia nigra dopaminergic neurons. The Kruskal Wallis test and the Dunn test were used to assess differences between groups. Results. A significant decrease was found in the latency time of the rotarod test between the negative and positive control group (p<0.01), negative control and experimental 1 (p=0.09), negative control and experimental 2 (p<0.01), positive control and experimental 1 (p=0.04), and experimental 1 and 2 (p=0.09). There was no significant intergroup difference in the identification of uric acid. There was a depletion of the total dopaminergic neurons in the neuronal count, without intergroup difference. Conclusions. A neurotoxic effect of aqueous extract of boldo was recognized at a clinical level in Holtzman male rats.