Giant cavernous malformation of the posterior fossa with lymphangiomatous phenotype, associated with orbital venolymphatic anomaly in an 11-month-old patient: case report and literature review.

The synchronous presentation of venolymphatic anomalies of the orbit and noncontiguous intracranial cavernous malformations is uncommon. Herein, we present a case of an 11-month-old female patient diagnosed with orbital venolymphatic anomaly associated with a large cavernous malformation in the posterior fossa, who underwent complete surgical resection of the latter. The immunohistochemical analysis was positive for podoplanin, a marker expressed by lymphatic endothelial cells, but not vascular endothelium. This exceptional finding suggests lymphatic involvement in the etiology of the lesion. In our review of the literature, we did not find similar cases in patients under 1 year of age.

Response to comment on "genetic variants and source of introduction of SARS-CoV-2 in South America".

During a pandemic, science needs data to generate helpful evidence, and researchers assume this responsibility despite the risk of potential bias. This is the response to the comment made by Pedro Romero, who argued that our manuscript did not use reassembling and mapping strategies for corroborating mutations, and lacked bootstrap support in the phylogenetic analysis.

Genetic variants and source of introduction of SARS-CoV-2 in South America.

After more than 4 months of the COVID-19 pandemics with genomic information of SARS-CoV-2 around the globe, there are more than 1000 complete genomes of this virus. We used 691 genomes from the GISAID database. Several studies have been reporting mutations and hotspots according to viral evolution. Our work intends to show and compare positions that have variants in 30 complete viral genomes from South American countries. We classified strains according to point alterations and portray the source where strains came into this region. Most viruses entered South America from Europe, followed by Oceania. Only Chilean isolates demonstrated a relationship with Asian isolates. Some changes in South American genomes are near to specific domains related to viral replication or the S protein. Our work contributes to the global understanding of which sort of strains are spreading throughout South America, and the differences among them according to the first isolates introduced to this region.

The effect of early-stage public health policies in the transmission of COVID-19 for South American countries.

OBJECTIVES: The analysis of transmission dynamics is crucial to determine whether mitigation or suppression measures reduce the spread of coronavirus disease 2019 (COVID-19). This study sought to estimate the basic (R0 ) and time-varying (Rt ) reproduction number of COVID-19 and contrast the public health measures for ten South American countries. METHODS: Data was obtained from the European Centre for Disease Prevention and Control. Country-specific R0 values during the first two weeks of the outbreak and Rt values after 90 days were estimated. RESULTS: Countries used a combination of isolation, physical distancing, quarantine, and community-wide containment measures to staunch the spread of COVID-19 at different points in time. R0 ranged from 1.52 (95% confidence interval: 1.13-1.99) in Venezuela to 3.83 (3.04-4.75) in Chile, whereas Rt after 90 days ranged from 0.71 (95% credible interval: 0.39-1.05) in Uruguay to 1.20 (1.19-1.20) in Brazil. Different R0 and Rt values may be related to the testing capacity of each country. CONCLUSION: R0 in the early phase of the outbreak varied across the South American countries. The public health measures adopted in the initial period of the pandemic appear to have reduced Rt over time in each country, albeit to different levels.

OBJETIVOS: Estimar el número de reproducción básico (R0 ) y el número de reproducción efectivo (Rt ) de la COVID-19 y contrastarlos con las medidas de salud pública implementadas en diez países de América del Sur. MÉTODOS: Los datos se obtuvieron del Centro Europeo para la Prevención y el Control de las Enfermedades. Se estimó el R0 de cada país durante las dos primeras semanas del brote y el Rt después de 90 días. RESULTADOS: Los países utilizaron una combinación de aislamiento, distanciamiento físico, cuarentena y medidas de contención en toda la comunidad para detener la propagación de la COVID-19 en diferentes momentos. El R0 osciló entre 1,52 (IC95%: 1,13-1,99) en Venezuela y 3,83 (IC95%: 3,04-4,75) en Chile, mientras que el Rt después de 90 días varió entre 0,71 (intervalo de credibilidad 95%: 0,39-1,05) en Uruguay y 1,20 (intervalo de credibilidad 95%: 1,19-1,20) en Brasil. Los diferentes valores de R0 y Rt pueden estar relacionados con la capacidad de llevar a cabo pruebas de detección viral de cada país. CONCLUSIÓN: Los valores del R0 en la fase inicial del brote variaron entre los países sudamericanos. Las medidas de salud pública adoptadas en el período inicial de la pandemia parecen haber reducido el Rt con el tiempo en cada país, aunque en niveles diferentes.

Parity and Overweight/Obesity in Peruvian Women.

INTRODUCTION: The rise in noncommunicable diseases and their risk factors in developing countries may have changed or intensified the effect of parity on obesity. We aimed to assess this association in Peruvian women using data from a nationally representative survey. METHODS: We used data from Peru's Demographic and Health Survey, 2012. Parity was defined as the number of children ever born to a woman. We defined overweight as having a body mass index (BMI, kg/m2) of 25.0 to 29.9 and obesity as a BMI ≥30.0. Generalized linear models were used to evaluate the association between parity and BMI and BMI categories, by area of residence and age, adjusting for confounders. RESULTS: Data from 16,082 women were analyzed. Mean parity was 2.25 (95% confidence interval [CI], 2.17-2.33) among rural women and 1.40 (95% CI, 1.36-1.43) among urban women. Mean BMI was 26.0 (standard deviation, 4.6). We found evidence of an association between parity and BMI, particularly in younger women; BMI was up to 4 units higher in rural areas and 2 units higher in urban areas. An association between parity and BMI categories was observed in rural areas as a gradient, being highest in younger women. CONCLUSION: We found a positive association between parity and overweight/obesity. This relationship was stronger in rural areas and among younger mothers.

Pharmacogenetic variability of tuberculosis biomarkers in native and mestizo Peruvian populations.

In Peru, 29 292 people were diagnosed with tuberculosis in 2022. Although tuberculosis treatments are effective, 3.4%-13% are associated with significant adverse drug reactions, with drug-induced liver injury (DILI) considered the most predominant. Among the first-line antituberculosis drugs, isoniazid is the main drug responsible for the appearance of DILI. In liver, isoniazid (INH) is metabolized by N-acetyltransferase-2 (NAT2) and cytochrome P450 2E1 (CYP2E1). Limited information exists on genetic risk factors associated with the presence of DILI to antituberculosis drugs in Latin America, and even less is known about these factors in the native and mestizo Peruvian population. The aim of this study was to determine the prevalence of NAT2 and CYP2E1 genotypes in native and mestizo population. An analytical cross-sectional analysis was performed using genetic data from mestizo population in Lima and native participants from south of Peru. NAT2 metabolizer was determined as fast, intermediate and slow, and CYP2E1 genotypes were classified as c1/c1, c1/c2 and c2/c2, from molecular tests and bioinformatic analyses. Of the 472 participants, 36 and 6 NAT2 haplotypes were identified in the mestizo and native population, respectively. In mestizo population, the most frequent NAT2*5B and NAT2*7B haplotypes were associated with DILI risk; while in natives, NAT2*5G and NAT2*13A haplotypes were associated with decreased risk of DILI. For CYP2E1, c1/c1 and c1/c2 genotypes are the most frequent in natives and mestizos, respectively. The linkage disequilibrium of NAT2 single nucleotide polymorphisms (SNPs) was estimated, detecting a block between all SNPs natives. In addition, a block between rs1801280 and rs1799929 for NAT2 was detected in mestizos. Despite the limitations of a secondary study, it was possible to report associations between NAT2 and CYP2E alleles with Peruvian native and mestizo by prevalence ratios. The results of this study will help the development of new therapeutic strategies for a Tuberculosis efficient control between populations.

Antigen-Induced IL-1RA Production Discriminates Active and Latent Tuberculosis Infection.

The IGRA (Interferon Gamma Release Assays) test is currently the standard specific test for Mycobacterium tuberculosis infection status. However, a positive test cannot distinguish between active tuberculosis disease (ATBD) and latent tuberculosis infection (LTBI). Developing a test with this characteristic is needed. We conducted longitudinal studies to identify a combination of antigen peptides and cytokines to discriminate between ATBD and LTBI. We studied 54 patients with ATBD disease and 51 with LTBI infection. Cell culture supernatant from cells stimulated with overlapping Mycobacterium tuberculosis novel peptides and 40 cytokines/chemokines were analyzed using the Luminex technology. To summarize longitudinal measurements of analyte levels, we calculated the area under the curve (AUC). Our results indicate that in vitro cell stimulation with a novel combination of peptides (Rv0849-12, Rv2031c-14, Rv2031c-5, and Rv2693-06) and IL-1RA detection in culture supernatants can discriminate between LTBI and ATBD.

Guillain-Barre syndrome outbreak in Peru: Association with polymorphisms in IL-17, ICAM1, and CD1.

BACKGROUND: Guillain-Barre Syndrome (GBS) is considered a complex disorder with significant environmental effect and genetic susceptibility. Genetic polymorphisms in CD1E, CD1A, IL-17, and/or ICAM1 had been proposed as susceptibility genetic variants for GBS mainly in Caucasian population. This study explores the association between selected polymorphisms in these genes and GBS susceptibility in confirmed GBS cases reported in mestizo population from northern Peru during the most recent GBS outbreak of May 2018. METHODS: A total of nine nonrelated cases and 11 controls were sequenced for the polymorphic regions of CD1A, CD1E, IL-17, and ICAM1. RESULTS: We found a significant protective association between heterozygous GA genotype in ICAM1 (241Gly/Arg) and GBS (p < .047). IL-17 was monomorphic in both controls and patients. No significant differences were found in the frequency of SNPs in CD1A and CD1E between the group with GBS patients and healthy controls. CONCLUSION: ICAM1 polymorphisms might be considered as potential genetic markers of GBS susceptibility. Further studies with larger sample size will be required to validate these findings.

Genetics and genomics in Peru: Clinical and research perspective.

Peruvians currently preserve in their DNA the history of 2.5 million years of human evolution and 150,000 years of migration from Africa to Peru or the Americas. The development of Genetics and Genomics in the clinical and academic field is shown in this review.

[Nevoid basal-cell carcinoma syndrome (Gorlin Syndrome): report of two cases and review of the literature]. / Síndrome de carcinoma de células basales nevoides (Síndrome Gorlin): reporte de dos casos y revisión de la literatura.

Gorlin syndrome (GS) is a genetic disorder with an autosomal dominant inheritance pattern, with complete penetrance and variable expressivity. GS is caused by germline mutations in the genes PTCH1 or SUFU, which are components of the Sonic hedgehog molecular pathway. GS is characterized by the presence of multiple nevoid basal cell carcinomas, odontogenic cysts, calcification of the brain sickle, and lesions in the palms and soles. This study is the first to report cases in Peru of patients with GS who underwent genetic evaluation and counseling. We present two GS cases that meet the clinical criteria for the syndrome and review the literature.

El síndrome Gorlin (SG) es una condición genética, con patrón de herencia autosómico dominante, con penetrancia completa y expresividad variable, debida a mutaciones germinales en los genes PTCH1 o SUFU, los cuales son componentes de la vía molecular Sonic hedgehog. El SG se caracteriza por la presencia de múltiples carcinomas de células basales nevoides, quistes odontogénicos, calcificación de la hoz del cerebro y lesiones en sacabocado en palmas y plantas. Este es el primer reporte de casos en el Perú sobre pacientes con SG, que cuentan con evaluación y asesoría genética. Presentamos dos casos de SG que cumplen criterios clínicos del síndrome y una revisión de la literatura.

A Peruvian Child with 18p-/18q+ Syndrome and Persistent Microscopic Hematuria.

Chromosome 18 pericentric inversion carriers could have offspring with recombinant chromosomes, leading to patients with clinical variable manifestations. Patients with 18p-/18q+ rearrangements share some clinical characteristics, while other characteristics differ. Factors for such divergence include the length of the inverted segment, among others. Here, we describe a Peruvian child with dysmorphic features, intellectual disability persistent microscopic hematuria, aortic pseudocoarctation, and descending aorta arteritis, among others. Karyotype analysis of family members determined the mother as the carrier of a pericentric inversion: 18[inv(18)(p11.2q21.3)]. This child carries a recombinant chromosome 18, with chromosomal microarray analysis detecting two genomic imbalances in patient's chromosome 18: one duplicated region and one deleted segment in the large and the short arms, respectively. Persistent microscopic hematuria has not been reported among 18p-/18q+ phenotypes. Our patient elucidates that other factors play significant and yet unknown roles for not fulfilling the proposed genotype-phenotype correlation associated with hemizygosity in this type of recombinant chromosome 18 or presenting these features as the patient ages.

Distribution of Short-Term and Lifetime Predicted Risks of Cardiovascular Diseases in Peruvian Adults.

BACKGROUND: Short-term risk assessment tools for prediction of cardiovascular disease events are widely recommended in clinical practice and are used largely for single time-point estimations; however, persons with low predicted short-term risk may have higher risks across longer time horizons. METHODS AND RESULTS: We estimated short-term and lifetime cardiovascular disease risk in a pooled population from 2 studies of Peruvian populations. Short-term risk was estimated using the atherosclerotic cardiovascular disease Pooled Cohort Risk Equations. Lifetime risk was evaluated using the algorithm derived from the Framingham Heart Study cohort. Using previously published thresholds, participants were classified into 3 categories: low short-term and low lifetime risk, low short-term and high lifetime risk, and high short-term predicted risk. We also compared the distribution of these risk profiles across educational level, wealth index, and place of residence. We included 2844 participants (50% men, mean age 55.9 years [SD 10.2 years]) in the analysis. Approximately 1 of every 3 participants (34% [95% CI 33 to 36]) had a high short-term estimated cardiovascular disease risk. Among those with a low short-term predicted risk, more than half (54% [95% CI 52 to 56]) had a high lifetime predicted risk. Short-term and lifetime predicted risks were higher for participants with lower versus higher wealth indexes and educational levels and for those living in urban versus rural areas (P<0.01). These results were consistent by sex. CONCLUSIONS: These findings highlight potential shortcomings of using short-term risk tools for primary prevention strategies because a substantial proportion of Peruvian adults were classified as low short-term risk but high lifetime risk. Vulnerable adults, such as those from low socioeconomic status and those living in urban areas, may need greater attention regarding cardiovascular preventive strategies.

Agreement Between Cardiovascular Disease Risk Scores in Resource-Limited Settings: Evidence from 5 Peruvian Sites.

It is unclear how well currently available risk scores predict cardiovascular disease (CVD) risk in low-income and middle-income countries. We aim to compare the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort risk equations (ACC/AHA model) with 6 other CVD risk tools to assess the concordance of predicted CVD risk in a random sample from 5 geographically diverse Peruvian populations. We used data from 2 Peruvian, age and sex-matched, population-based studies across 5 geographical sites. The ACC/AHA model were compared with 6 other CVD risk prediction tools: laboratory Framingham risk score for CVD, non-laboratory Framingham risk score for CVD, Reynolds risk score, systematic coronary risk evaluation, World Health Organization risk charts, and the Lancet chronic diseases risk charts. Main outcome was in agreement with predicted CVD risk using Lin's concordance correlation coefficient. Two thousand one hundred and eighty-three subjects, mean age 54.3 (SD ± 5.6) years, were included in the analysis. Overall, we found poor agreement between different scores when compared with ACC/AHA model. When each of the risk scores was used with cut-offs specified in guidelines, ACC/AHA model depicted the highest proportion of people at high CVD risk predicted at 10 years, with a prevalence of 29.0% (95% confidence interval, 26.9-31.0%), whereas prevalence with World Health Organization risk charts was 0.6% (95% confidence interval, 0.2-8.6%). In conclusion, poor concordance between current CVD risk scores demonstrates the uncertainty of choosing any of them for public health and clinical interventions in Latin American populations. There is a need to improve the evidence base of risk scores for CVD in low-income and middle-income countries.

Nutritional transition in children under five years and women of reproductive age: a 15-years trend analysis in Peru.

BACKGROUND: Rapid urbanization, increase in food availability, and changes in diet and lifestyle patterns have been changing nutritional profiles in developing nations. We aimed to describe nutritional changes in children under 5 years and women of reproductive age in Peru, during a 15-year period of rapid economic development and social policy enhancement. MATERIALS AND METHODS: Trend analyses of anthropometric measures in children of preschool age and women between 15-49 years, using the Peruvian National Demographic and Family Health Surveys (DHS) from 1996 to 2011. WHO growth curves were used to define stunting, underweight, wasting and overweight in children <5 y. We employed the WHO BMI-age standardized curves for teenagers between 15-19 y. In women >19 years, body mass index (BMI) was analyzed both categorically and as a continuous variable. To statistically analyze the trends, we used regression models: Linear and Poisson for continuous and binary outcomes, respectively. RESULTS: We analyzed data from 123 642 women and 64 135 children, from 1996 to 2011. Decreases over time were evidenced for underweight (p<0.001), wasting (p<0.001), and stunting (p<0.001) in children under 5 y. This effect was particularly noted in urban settings. Overweight levels in children reduced (p<0.001), however this reduction stopped, in urban settings, since 2005 (∼12%). Anemia decreased in children and women (p<0.001); with higher reduction in urban (↓43%) than in rural children (↓24%). BMI in women aged 15-19 years increased (p<0.001) across time, with noticeable BMI-curve shift in women older than 30 years. Moreover, obesity doubled during this period in women more than 19 y. CONCLUSION: Nutrition transition in Peru shows different patterns for urban and rural populations. Public policies should emphasize targeting both malnutrition conditions--undernutrition/stunting, overweight/obesity and anemia--considering age and place of residence in rapid developing societies like Peru.

[Mandatory requirement of social health service in Peru: discriminatory and unconstitutional]. / El requisito obligatorio del servicio social en salud del Perú: discriminatorio e inconstitucional.

The rural and urban-edge health service (SERUMS) is an activity that only health professionals perform for the Peruvian government, as it is a mandatory requirement to qualify for a second specialty or to work in public hospitals and public health care facilities, and obtain government scholarships for future training. The few legal changes in the rules of this social program and the focus of “service” restricted to health professionals lead to a perception of this policy as discriminatory and unconstitutional because it violates the right to education and work. There is no scientific evidence that supports the usefulness and effectiveness of this program in terms of quality of service and health indicator improvement, as well as in adequate distribution and retention of health professionals. We suggest to abolish the compulsory requirement and to reformulate a political strategy to help attract and retain health professionals in vulnerable areas of Peru.

Factores de riesgo en las enfermedades genéticas / Risk factors in genetic diseases

Existen más de 10 000 enfermedades genéticas descritas en el mundo y afectan alrededor del 7% de la población mundial, causando alta morbimortalidad y costos para los sistemas de salud pública. Representan un reto diagnóstico por la variabilidad clínica y la necesidad de pruebas diagnósticas moleculares. En el Perú, son escasas las investigaciones respecto a estas condiciones y, aunque se ha promulgado la Ley de Enfermedades Huérfanas o Raras (Ley Nº 29698), no se han implementado estrategias sanitarias nacionales para el diagnóstico, manejo y prevención. La presente publicación tiene como objetivo describir los factores de riesgo más frecuentes, los cuales están relacionados a enfermedades o síndromes de etiología genética

More than 10,000 genetic diseases have been described, which affect approximately 7% of the whole world population, leading to high morbidity and mortality rates, as well as to elevated healthcare costs. The diagnosis of these conditions is a tough challenge, because of their clinical variability and the low availability of molecular diagnostic tests. There is little research performed in Peru dealing with these diseases, and although a 'Bill for Orphan or Rare Diseases' (Law N° 29698) has been recently issued, no national healthcare strategies have been implemented for the diagnosis, management, and prevention of genetic diseases. This paper aims to describe the risk factors that are more frequently related to diseases or syndromes with a genetic origin

[Association between television viewing and obesity in Peruvian women]. / Asociación entre ver televisión y obesidad en mujeres peruanas.

OBJECTIVE: To assess the association between frequency of television viewing, overweight and obesity in a nationally representative sample of Peruvian women. METHODS: Secondary analysis of the Demographic and Health Survey 2008 including women aged from 15 to 49 years old. The outcome variables were obesity (body mass index >30 kg/m²) and overweight (body mass index >25 but <30 kg/m²) whereas the exposure variable was frequency of television viewing (never, occasionally, almost every day). Logistic regression taking into account the multistage study design and adjusting for potential confounders was used. Results were presented as adjusted odds ratios (aOR) with 95% confidence intervals (95%CI). RESULTS: A total of 21,712 women were included in the analysis. The prevalence of overweight was 34.7% (95%CI 33.8%;35.7%), and obesity prevalence was 14.3% (95%CI 13.6%;15.1%). Compared to women who never watched television, those who reported watching television occasionally and almost daily were more likely to be obese: aOR 1.7 (95%CI 1.3;-2.3) and aOR 2.6 (95%CI 2.0;3.5), respectively. The magnitude of this association was lower for overweight: aOR 1.2 (95CI 1.3;2.3) and aOR 1.6 (95%CI 1.1;1.4), respectively. The strength of the association was greater in urban areas. CONCLUSIONS: Frequency of television viewing was associated with overweight and obesity in Peruvian women and the strength of this association varied by area of residence. These findings can provide input to strategies for obesity prevention in the Peruvian context.

The association between socioeconomic status and obesity in Peruvian women.

Historically in developing countries, the prevalence of obesity has been greater in more advantaged socioeconomic groups. However, in recent years the association between socioeconomic status (SES) and obesity has changed and varies depending on the country's development stage. This study examines the relationship between SES and obesity using two indicators of SES: education or possession assets. Using the cross-sectional 2008 National Demographic and Family Health Survey of Peru (ENDES 2008), we investigated this relationship in women aged 15-49 years living in rural and urban settings. Descriptive, linear and logistic regressions analyses were conducted accounting for the multistage nature of the sampling design. The overall prevalence of obesity in this study was 14.1% (95% confidence interval (CI): 13.3-14.8); 8.4% (95% CI: 7.5-9.3) in rural areas and 16.2% (95% CI: 15.2-17.2) in urban areas. Wealthier women were more likely to be obese, and this association was stronger in rural areas. Conversely, more educated women were less likely to be obese, especially in urban areas. The distribution of obesity in Peruvian women is strongly related to socioeconomic position, and differs whether measured as possession assets or by level of education. These findings could have important implications for policy development in Peru.

Síndrome de carcinoma de células basales nevoides (Síndrome Gorlin): reporte de dos casos y revisión de la literatura / Nevoid basal-cell carcinoma syndrome (Gorlin Syndrome): report of two cases and review of the literature

RESUMEN El síndrome Gorlin (SG) es una condición genética, con patrón de herencia autosómico dominante, con penetrancia completa y expresividad variable, debida a mutaciones germinales en los genes PTCH1 o SUFU, los cuales son componentes de la vía molecular Sonic hedgehog. El SG se caracteriza por la presencia de múltiples carcinomas de células basales nevoides, quistes odontogénicos, calcificación de la hoz del cerebro y lesiones en sacabocado en palmas y plantas. Este es el primer reporte de casos en el Perú sobre pacientes con SG, que cuentan con evaluación y asesoría genética. Presentamos dos casos de SG que cumplen criterios clínicos del síndrome y una revisión de la literatura.

ABSTRACT Gorlin syndrome (GS) is a genetic disorder with an autosomal dominant inheritance pattern, with complete penetrance and variable expressivity. GS is caused by germline mutations in the genes PTCH1 or SUFU, which are components of the Sonic hedgehog molecular pathway. GS is characterized by the presence of multiple nevoid basal cell carcinomas, odontogenic cysts, calcification of the brain sickle, and lesions in the palms and soles. This study is the first to report cases in Peru of patients with GS who underwent genetic evaluation and counseling. We present two GS cases that meet the clinical criteria for the syndrome and review the literature