Costa Rican Patients Research Articles

Clinical, immunological and genetic characterization of patients with X‐linked agammaglobulinemia in Costa Rica

AbstractX‐linked agammaglobulinemia is caused by mutations in the gene encoding Bruton tyrosine kinase. It produces an arrest in the maturation and differentiation of B cells with very low levels of all immunoglobulins isotypes. The aim of the study was to characterize the clinical, immunological and genetic defects in patients with XLA in Costa Rica. Sixteen cases were identified over a period of 30 years, a case every 2 years, approximately. Three patients were asymptomatic and diagnosis was made on family history. The average age of onset of symptoms was 1.46 years‐old (0.08–6.1). Six patients (44%) had onset of symptoms before 1 year of age and 12 (81%) patients before 5 years of age. The average age of diagnosis was 3.63 years‐old (0.17–13, SD 3.51 years‐old the average time between the onset of symptoms and the diagnosis was 2.5 years (2.5 months to 12 years, SD 3 years). The initial reason to study the patients was a recurrent infection, family history of XLA, arthritis and neutropenia. Four patients had pneumonia and two had suppurative lung disease. Nine patients had recurrent infections: acute otitis media, sinusitis, mastoiditis and recurrent diarrhoea. Three patients presented with arthritis. Neutropenia as an isolated event was not identified in any case. All patients receive monthly IVIG and no deaths were reported. Three new likely pathogenic/pathogenic variants in BTK gene have been described in our population. This is the first report of XLA Costa Rican patients and their BTK mutations.

Colorectal cancer vaccines: in silico identification of tumor-specific antigens associated with frequent HLA-I alleles in the costa rican Central Valley population

Colorectal cancer is a complex disease in which uncontrolled growth of abnormal cells occurs in the large intestine (colon or rectum). The study of tumor-specific antigens (neoantigens), molecules that interact with the immune system, has been extensively explored as a possible therapy called in silico cancer vaccine. Cancer vaccine studies have been triggered by the current high-throughput DNA sequencing technologies. However, there is no universal bioinformatic protocol to study tumor-antigens with DNA sequencing data.
 We propose a bioinformatic protocol to detect tumor-specific antigens associated with single nucleotide variants (SNVs) or “mutations” in colorectal cancer and their interaction with frequent HLA alleles (complex that present antigens to immune cells) in the Costa Rican Central Valley population. We used public data of human exome (DNA regions that produce functional products, including proteins). A variant calling analysis was implemented to detect tumorspecific SNVs, in comparison to healthy tissue. We then predicted and analyzed the peptides (protein fragments, the tumor specific antigens) derived from these variants, in the context of its affinity with frequent alleles of HLA type I of the Costa Rican population.
 We found 28 non-silent SNVs, present in 26 genes. The protocol yielded 23 strong binders peptides derived from the SNVs for frequent alleles (greater than 8%) for the Costa Rican population at the HLA-A, B and C loci. It is concluded that the standardized protocol was able to identify neoantigens and this can be considered a first step for the eventual design of a colorectal cancer vaccine for Costa Rican patients. To our knowledge, this is the first study of an in silico cancer vaccine using DNA sequencing data in the context of the Costa Rican HLA alleles.

Thrombolysis Experience in Costa Rica Compared Against Individual Patient Data from two Randomized Controlled Trials

ObjectivesWe sought to compare thrombolysis outcomes from the Costa Rican Stroke Registry Program (CRSRP) with published individual patient data from NINDS and CLOTBUST-ER trials using matching and outcome modeling from randomized clinical trials (RCTs). Materials and methodsA retrospective observational study matching subjects on baseline characteristics, from the CRSRP, the control arm of CLOTBUST-ER, and the interventional arm of NINDS trials. Day 7-10/discharge modified Rankin Score (mRS), and early mortality was compared between matched subjects. A mortality model derived from RCTs was developed, and outcomes were compared at similar baseline NIHSS scores. CRSRP symptomatic hemorrhage (SICH) rate was compared with an Ibero-American cohort (IAC). ResultsOf 540 CRSRP patients, 351 received rt-PA under 3 hours and were matched with NINDS subjects yielding 292 pairs; 161 CRSRP subjects treated within 4.5 hours were matched with CLOTBUST-ER subjects resulting in 151 pairs. The proportion of patients achieving excellent outcomes (mRS 0-1) did not differ between CRSRP and either NINDS or CLOTBUST-ER (CRSRP vs NINDS: 36.6% vs 32.9%, p=0.3; CRSRP vs CLOTBUST-ER: 26.5% vs 24.5%, p=0.8). Mortality was higher for CRSRP vs CLOTBUST-ER (7.3% vs 0.7%, p=0.006), but not vs NINDS (6.5% vs 4.5%, p=0.4). A pooled mortality model derived from 15 RCTs representing 4410 patients (R2=0.39) showed CRSRP and NINDS within expected mortality, while CLOTBUST-ER showed lower than expected mortality. CRSRP SICH rate equaled IAC (5.7% vs 5.7%; p=0.9). ConclusionsFunctional outcomes and SICH of thrombolysed Costa Rican patients compared favorably with published datasets, with a potential increase in early mortality.

Clinical and Genetic Analysis of Costa Rican Patients With Parkinson's Disease.

Background: Most research in genomics of Parkinson's disease (PD) has been done in subjects of European ancestry, leading to sampling bias and leaving Latin American populations underrepresented. We sought to clinically characterize PD patients of Costa Rican origin and to sequence familial PD and atypical parkinsonism-associated genes in cases and controls.Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, and motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes including GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, and ATP13A2.Results: Mean age of PD probands was 62.12 ± 13.51 years; 57.6% were male. The frequency of risk and protective factors averaged ~45%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders, and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants in LRRK2 were nominally associated with PD; six were located between amino acids p.1620 and 1623 in the C-terminal-of-ROC (COR) domain of Lrrk2. Non-synonymous GBA variants (p.T369M, p.N370S, and p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R.Discussion: This is the first study that describes sociodemographics, risk factors, clinical presentation, and genetics of Costa Rican patients with PD, adding information to genomics research in a Latino population.

Effectiveness of intravenous tocilizumab in routine clinical practice in a cohort of Costa Rican patients with rheumatoid arthritis

ObjectiveTo determine the effectiveness and the incidence of severe adverse events in a cohort of Costa Rican patients with Rheumatoid Arthritis (RA) treated with intravenous (IV) tocilizumab (TCZ). Patients and methodsA retrospective analysis was carried out in 45 patients that were unresponsive to disease-modifying antirheumatic drugs (DMARDs). The study included patients who received IV TCZ every 4 weeks (4 mg/kg) along with methotrexate or leflunomide. Effectiveness was measured through the incidence of clinical remission according to a disease activity score – erythrocyte sedimentation rate (DAS28-ESR) less than 2.6. Safety was assessed by the incidence rate of serious adverse events. An univariate and multivariate logistic regression analysis was performed to assess the association of potential variables with the probability of achieving remission during the first 3 months of TCZ therapy. ResultsDuring the 3rd month of TCZ therapy, a total of 22 patients (48.9%; 95% Confidence Interval (CI) 34.3%–63.5%) achieved remission. The cumulative incidence of patients with remission at month 12 was 75.0% (n = 34) (95% CI: 62.3%–87.6%). A total of 18 patients (40%; 95% CI: 25.7%–54.3%) were switched to a 8 mg/kg dose due to the absence of remission. The incidence rate of serious adverse events was .98 per 100 patients/year, all of them due to infectious diseases with no fatal events reported. Only basal DAS28-ESR was associated with the probability of achieving remission at month 3. ConclusionsIV TCZ (4 mg/kg) is an effective and safe treatment for RA patients in a clinical setting in Costa Rica.

Abstract P17: Outcomes After Thrombolysis for Ischemic Stroke in Costa Rica Compare Favorably With International Cohorts

Background: More than 70% of strokes occur in resource-poor countries. Outcomes are often not well documented. rt-PA for acute ischemic stroke was approved in 2012 for use in Costa Rica (CR). A hub and spoke model was initiated and a dataset established, the CR Stroke Registry Program (CRSRP) for conditional- and post-approval monitoring. Here, we compared CRSRP rt-PA outcomes to similarly treated subjects from the 1995 NINDS rt-PA trial and the 2019 CLOTBUST-ER control arm. Methods: Subjects were matched using a published pairing methodology and day 7-10/discharge modified Rankin Score (mRS), symptomatic intracerebral hemorrhages (SICH) and early mortality compared. A mortality model was generated from 15 randomized controlled trials (RCTs) and outcomes compared at similar baselines. SICH rates were compared with other cohorts: Get With The Guidelines (GWTG), a combined international IV thrombolysis trial pool, and 2 Ibero-American populations. Results: Of 424 CRSRP patients, 284 receiving rt-PA under 3 hrs were matched with 308 NINDS subjects. 131 non-diabetic CRSRP subjects, treated within 4.5 hrs, NIHSS 10 - 24 and Alberta Stroke Program Early CT Score (ASPECTS)>7, were matched with 300 CLOTBUST-ER subjects. Percent achieving either mRS 0-1 or 0-2 did not differ between CRSRP and either NINDS or CLOTBUST-ER (mRS 0-1: CRSRP:33.9% vs NINDS:33.6%; CRSRP:23.8% vs CLOTBUST-ER:27.0%, all p>=.05 / mRS 0-2: CRSRP:40.0% vs NINDS:41.4%; CRSRP:31.1% vs CLOTBUST-ER:36.1%, all p=>.05). Mortality was higher for CRSRP vs CLOTBUST-ER (6.6% vs 0.8%; p=0.05) but not vs NINDS (6.8% vs 4.3%; p=0.3). A predictive model (R 2 =0.39) showed neither cohort exceeded expected pooled mortality, with CLOTBUST-ER the lowest mortality. SICH rate was higher in CRSRP vs CLOTBUST-ER (7.3% vs 0.0% p=0.008) but not vs NINDS (5.7% vs 6.8% p=0.7)). SICH rates were not higher when compared with 4 international cohorts. Conclusion: Functional outcomes of Costa Rican patients receiving rt-PA compared favorably with 2 RCTs (NINDS and CLOTBUST-ER). SICH and mortality were higher than CLOTBUST-ER, although both were within expected range compared to other international cohorts. Systems of care development in order to further lower SICH and participate in the endovascular era are underway.

CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica

Steroid 21-hydroxylase deficiency accounts for 95% of congenital adrenal hyperplasia (CAH) cases. Newborn screening has allowed for early detection of the disease, and currently, molecular analysis can identify the genotypes of these patients. Phenotype-genotype correlation has been well described in previous studies. In Costa Rica, there is no data about the genetic background of these patients, nor their phenotypic correlation. DesignObservational, retrospective, descriptive study based on the review of patient records who had a diagnosis of CAH and were performed molecular analysis using gene sequencing or MLPA during the period from 2006 to 2018 (N = 58). ObjectiveTo describe the clinical and genetic characteristics of CAH patients due to 21-hydroxylase deficiency at the National Children's Hospital “Dr. Carlos Sáenz Herrera”, Caja Costarricense de Seguro Social (CCSS) in Costa Rica. Results53% (31/58) of the patients were male and 80% (37/46) were born full term; 72% (42/58) had salt wasting phenotype, 9% (5/58) simple virilizing phenotype and 19% (11/58) non-classic phenotype. The most frequent variants were c.292+5G>A in 26% (15/58) of patients and Del/Del in 21% (12/58) of them. ConclusionsThe most frequent mutation in our study population was the c.292+5G>A, which was found in 15/58 patients. This rare variant has only been reported in three other studies so far but as an infrequent mutation in CAH patients. The genetic characteristics of Costa Rican patients differ from what has been documented worldwide and could respond to a founder effect.

IKZF1 Deletions as a Prognostic Factor in Costa Rican Patients With Pediatric B-Cell Acute Lymphoblastic Leukemia.

The IKZF1 gene encodes for Ikaros, a transcriptional factor in B-cell development. Deletions in this gene have been associated with a worse prognosis in B-cell acute lymphoblastic leukemia (B-ALL). We evaluated the presence of these alterations in all Costa Rican pediatric patients diagnosed with B-ALL between 2011 and 2014, treated with a modified Berlin-Frankfurt-Münster therapeutic protocol. Multiplex polymerase chain reaction with 2 detection methods (agarose gel and gene scanning) was used to detect intragenic deletions and multiplex ligation-dependent probe amplification for whole-gene deletions. Differences between groups (normal vs. deleted IKZF1) were analyzed by the χ test, the Kaplan-Meier test was used to calculate relapse-free survival and overall survival, and Cox regression was performed for multivariant analysis. Minimum follow-up was 4.5 years. Incidence of IKZF1 deletions was 12.9% (n=20), with an equal amount of intragenic and complete gene deletions. Adverse karyotype (P=0.048), high-risk category (P=0.030), occurrence of relapse (P=0.021), and medullar relapse (P=0.011) were statistically associated with the presence of deletions in IKZF1. Relapse-free survival at 54 months was lower in patients harboring an IKZF1 deletion than that in patients with IKZF1-wt (40.0% vs. 66.7%; P=0.014). Patients with B-ALL and IKZF1 deletions, showed a poorer relapse-free survival, in comparison with patients with IKZF1-wt, suggesting that IKZF1 status is an independent prognostic factor for pediatric patients with B-ALL.

Efectividad del tocilizumab intravenoso en la práctica clínica usual de una cohorte de pacientes costarricenses con artritis reumatoide

To determine the effectiveness and the incidence of severe adverse events in a cohort of Costa Rican patients with Rheumatoid Arthritis (RA) treated with intravenous (IV) tocilizumab (TCZ). A retrospective analysis was carried out in 45 patients that were unresponsive to disease-modifying antirheumatic drugs (DMARDs). The study included patients who received IV TCZ every 4 weeks (4mg/kg) along with methotrexate or leflunomide. Effectiveness was measured through the incidence of clinical remission according to a disease activity score - erythrocyte sedimentation rate (DAS28-ESR) less than 2.6. Safety was assessed by the incidence rate of serious adverse events. An univariate and multivariate logistic regression analysis was performed to assess the association of potential variables with the probability of achieving remission during the first 3 months of TCZ therapy. During the 3rd month of TCZ therapy, a total of 22 patients (48.9%; 95% Confidence Interval (CI) 34.3-63.5%) achieved remission. The cumulative incidence of patients with remission at month 12 was 75.0% (n=34) (95% CI: 62.3-87.6%). A total of 18 patients (40%; 95% CI: 25.7-54.3%) were switched to a 8mg/kg dose due to the absence of remission. The incidence rate of serious adverse events was .98 per 100 patients/year, all of them due to infectious diseases with no fatal events reported. Only basal DAS28-ESR was associated with the probability of achieving remission at month 3. IV TCZ (4mg/kg) is an effective and safe treatment for RA patients in a clinical setting in Costa Rica.

Microsatellite instability in Costa Rican patients with colorectal adenocarcinoma and its association with overall survival and response to fluoropyrimidine-based chemotherapy

BackgroundMicrosatellite instability (MSI) is a prognostic and predictive factor in colorectal cancer (CRC). Previous trials have acknowledged that MSI prevalence varies according to ethnicity. The aim of this study was to determine the prevalence of MSI among CRC patients from Costa Rica and to analyze its influence on overall survival (OS) and response to fluoropyrimidine-based chemotherapy. MethodsWe conducted a retrospective cohort study with all diagnosed CRC cases from 2010 to 2015 in a referral center in San José, Costa Rica. MSI was determined by immunohistochemical analysis. Clinical and epidemiological variables were retrieved from medical records. An univariate and multivariate COX regression analysis was performed to evaluate the association between MSI and mortality in the overall population and in those patients treated or not with fluoropyrimidine-based chemotherapy. Results553 CRC patients were identified during the study timeframe, and 165 of them were diagnosed with MSI (29.84 %; 95 % Confidence Interval CI: 26.02–33.65%). MSI was associated with M1 disease, and right-sided tumor location. After adjusting for potential confounders, MSI was an independent prognostic factor for OS (Hazard Ratio (HR): 0.56; 95 %CI: 0.43-0.67; Log-rankp = 0.03). MSI status did not modify the response to fluoropyrimidine-based chemotherapy (HR: 0.56; 95 %CI: 0.18–1.80; Log-rank: p = 0.33). ConclusionsMSI was detected in a higher proportion of CRC patients than previously reported for other non-Hispanic populations. MSI was an independent prognostic factor for OS, but did not predict the efficacy of cytotoxic treatment with Fluoropyrimidine-based chemotherapy.

Underlying domains of anxiety trait in a Costa Rican sample: Preliminary results

BackgroundImprecision of the psychiatric phenotype might partially explain the failure of genetic research to identify genes that contribute to susceptibility of anxiety disorders. Previous research concluded two underlying constructs, worry and rumination, might explain anxiety sub-syndromic symptoms in Costa Rican patients with history of mania. The goal of the current study is to explore the presence of latent constructs for quantitative anxiety in a group of subjects with a wide diagnostic phenotype and non-affected individuals. MethodsWe conducted an exploratory factor analysis of anxiety trait in 709 subjects. Our sample was comprised by 419 subjects with psychiatric disorders and 290 non-affected individuals. We used principal factors extraction method with squared multiple correlations of the STAI (trait subscale). ResultsWe found the following preliminary results: a three-factor solution with a good simple structure and statistical adequacy was obtained with a KMO of 0.92 (>0.6) and Bartlett's Test of Sphericity of 5644,44 (p < 0.05). The STAI items were grouped into three factors: anxiety-absent, worry and rumination based on the characteristics of the symptoms. ConclusionTwo underlying constructs, worry and rumination may explain anxiety sub-syndromic symptoms in Costa Rican subjects. Our proposed underlying structure of subsyndromal anxiety in individuals should be considered as an important factor in defining better phenotypic characterizations on a broader diagnostic concept. Worry and rumination as a phenotypic characterization may assist in genotyping; however, its predictive value on actual illness outcome still requires more research. The Genome-Wide QTL analysis for anxiety trait in the same sample is ongoing.

SAT-LB049 Identification of a Rare Mutation in Congenital Adrenal Hyperplasia Patients in Costa Rica

: Congenital adrenal hyperplasia (CAH) is a group of enzymatic defects in cortisol biosynthesis. Steroid 21-hydroxylase deficiency accounts for greater than 90% of cases. Newborn screening has allowed for early detection of cases and currently, molecular analysis can identify the genotypes of these patients. Phenotype-genotype correlation has been well described in previous studies. In Costa Rica, there is no data about the genetic background of these patients, nor their phenotypic correlation. Design: observational, retrospective, descriptive study based on review of patient files who had a diagnosis of CAH and were performed molecular analysis using gene sequencing or MLPA during the period from 2006 to 2018 (N=58). Objective: to describe the clinical and genetic characteristics of CAH patients due to 21-hydroxylase deficiency in Costa Rica. Results: 53.4% (31/58) of the patients were males and 80.4% (37/46) were born full term; 72.4% (42/58) had salt wasting phenotype, 8.6% (5/58) simple virilizing phenotype and 19.0% (11/58) non-classic phenotype. The most frequent genotypes were c.292+5G>A homo in 22.4% (13/58) of patients and Del/Del in 20.7% (12/58). Conclusions: The most frequent mutation in our study population was the c.292+5G>A, which was found in 13/58 patients. This rare variant has only been reported in other three studies so far but as an infrequent mutation in CAH patients (1,2,3). The genetic characteristics of Costa Rican patients differ from what has been documented worldwide and could respond to a founder effect. Reference: (1) Friaes et al., Molecular Genetics and Metabolism. 2006;88:58-65. (2) Ezquieta et al., Prenat Diagn. 2010;30:758-763. (3) Marino et al., Clinical Endocrinology. 2011;75:427-435. Disclosure: All authors have nothing to disclose. Sources of Research Support: no financial support was used for this study, it was financed entirely by the authors. A donation for the statistical work was granted by the National Association for the Study of Diabetes, Endocrinology and Metabolism of Costa Rica (ANPEDEM). Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SA12 - UNDERLYING DOMAINS OF ANXIETY TRAIT IN A COSTA RICAN SAMPLE

Imprecision of the psychiatric phenotype might partially explain the failure of genetic research to identify genes that contribute to susceptibility of anxiety disorders. It has been suggested that using a broad anxiety phenotype instead of a DSM-IV anxiety disorder diagnosis might enhance the chance of finding candidate genes for this complex group of symptoms. Previous research concluded that two underlying constructs, worry and rumination may explain anxiety subsyndromic symptoms in Costa Rican patients with history of mania or hypomania. Therefore, the goal of the current study is to explore the presence of latent constructs for quantitative anxiety in a group of subjects with a wide diagnostic phenotype (schizophrenia, schizoaffective disorder, bipolar disorder and major depressive disorder) and non-affected individuals. We conducted an exploratory factor analysis of anxiety trait in 709 subjects originally recruited for a Costa Rican study of Bipolar Disorder. Our sample was comprised by 419 (59%) subjects with psychiatric disorders and 290 (41%) non-affected individuals. The most frequent diagnoses were bipolar disorder 167 (23%) followed by major depressive disorder 144 (20%). The sample was 57% female and had a mean age of 41.2 (SD 14.90). We used principal factors extraction method with squared multiple correlations (SPSS v.20) of the STAI (trait subscale). A three-factor solution with a good simple structure and statistical adequacy was obtained with a KMO of 0.92 (>0.6) and Bartlett's Test of Sphericity of 5644,44 (p<0.05). The STAI items were grouped into three factors: 1) anxiety-absent, 2) worry and 3) rumination based on the characteristics of the symptoms. Two underlying constructs, worry and rumination may explain anxiety subsyndromic symptoms in Costa Rican subjects. Responses to items associated with factor 1 describe people with emotional stability, meaning no anxiety. The items associated to the factor 2 indicate anxiety about actual and future events and stressful situations, meaning worry. On the other hand, the factor 3 cluster components associated with thoughts about past events and recurrent situations, namely rumination. How the type of symptoms affects the clinical presentation and prognosis of the mania/hypomania raise an important line of research. Our proposed underlying structure of subsyndromal anxiety in individuals should be considered as an important factor in defining better phenotypic characterizations on a broader diagnostic concept. Worry and rumination as a phenotypic characterization may assist in genotyping; however, its predictive value on actual illness outcome still requires more research. The Genome-Wide QTL analysis for anxiety trait in the same sample is ongoing.

Identification and Functional Characterization of CLCN1 Mutations Found in Nondystrophic Myotonia Patients.

Mutations in the gene coding for the skeletal muscle Cl(-) channel (CLCN1) lead to dominant or recessive myotonia. Here, we identified and characterized CLCN1 mutations in Costa Rican patients, who had been clinically diagnosed with myotonic dystrophy type 1 but who were negative for DM1 mutations. CLCN1 mutations c.501C>G, p.F167L and c.1235A>C, p.Q412P appeared to have recessive inheritance but patients had atypical clinical phenotypes; c.313C>T, p.R105C was found in combination with c.501C>G, p.F167L in an apparently recessive family and the c.461A>G, p.Q154R variant was associated with a less clear clinical picture. In Xenopus oocytes, none of the mutations exhibited alterations of fast or slow gating parameters or single channel conductance, and mutations p.R105C, p.Q154R, and p.F167L were indistinguishable from wild-type (WT). p.Q412P displayed a dramatically reduced current density, surface expression and exerted no dominant negative effect in the context of the homodimeric channel. Fluorescently tagged constructs revealed that p.Q412P is expressed inefficiently. Our study confirms p.F167L and p.R105C as myotonia mutations in the Costa Rican population, whereas p.Q154R may be a benign variant. p.Q412P most likely induces a severe folding defect, explaining the lack of dominance in patients and expression systems, but has WT properties once expressed in the plasma membrane.

Thrombophilic factors associated with Venous Sinus Thrombosis in Costa Rican Patients, First Report

Thrombophilic factors associated with Venous Sinus Thrombosis in Costa Rican Patients, First Report

The geographic origin of Helicobacter pylori isolated from Costa Rican patients

Helicobacter pylori infects a significant proportion of the world population and it is associated with pathologies which include chronic atrophic gastritis, peptic ulcer, and gastric neoplasias such as gastric adenocarcinoma and MALT lymphoma. Costa Rica has a high prevalence of the infection and an elevated incidence of gastric cancer and its associated mortality. The global population structure for H. pylori has been established using a MLST scheme. The population structure of the strains of H. pylori circulating in Costa Rica is currently unknown. We characterized the geographical origin of 24 H. pylori isolates from Costa Rican patients. We identified 142 new alleles for the genes included in the scheme and in eight of the 24 isolates from Costa Rican patients, all seven alleles sequenced were described for the first time. Twenty-one isolates from Costa Rican patients group with hpEurope strains and the remaining three isolates grouped with hspWAfrica isolates (Bayesian posterior probability values above 0.70, P = 0.05, after 2 000 000 generations). The obtained result in the MLST analysis was not unexpected and reflects the genetic composition of the Costa Rican population.

Principal domains of quantitative anxiety trait in subjects with lifetime history of mania

High comorbidity rates for anxiety have been documented in subjects with history of mania or hypomania. We explored the presence of latent constructs of quantitative anxiety in subjects who have a history of mania or hypomania. We conducted an exploratory factor analysis of anxiety trait in 212 subjects who have a lifetime history of at least one manic/hypomanic syndrome. Participants were originally recruited for a Costa Rican sibling pair genetic study of Bipolar Disorder. We used principal factors extraction method with squared multiple correlations (SAS/SAT Professional software) of the STAI (trait subscale). A three-factor solution with a good simple structure and statistical adequacy was obtained with a KMO of 0.84 (>0.6) and Bartlett's Test of Sphericity of 2.4668E-162 (p<0.05). Items were grouped into anxiety-absent factor and the anxiety-present symptoms in two additional factors based on the nature of the symptoms, worry and rumination. Comorbid disorders could affect the interaction of anxiety score with manic/hypomanic symptoms. Some statistical parameters (mood status independence, score distribution and correlation between trait score and quantitative mania/hypomania) were not taken into consideration to extract the factors. Because anxiety dimensions were explored on individuals with history of mania or hypomania and not in healthy subjects, comparison of our results with other studies can draw confusing conclusions. Two underlying constructs, worry and rumination may explain anxiety sub-syndromic symptoms in Costa Rican patients with history of mania or hypomania.

Epidemiology of Spondyloarthropathies in Central America

The authors reviewed retrospectively a cohort of 233 spondyloarthropathy patients observed in 2 centers in Guatemala City, Guatemala, and in hospitals in San Salvador, El Salvador, and San Jose, Costa Rica. Guatemalan patients were either from the clinic of Guatemalan Association against Rheumatic Diseases (n = 105) or from the private clinic of AGK (n = 78). El Salvador patients (n = 17) were from Hospital Instituto Salvadoreño del Seguro Social, and Costa Rican patients (n = 33) were from Hospital Calderon Guardia, San Jose, Costa Rica. Except for the Costa Rican data, which were published in 2007, the patients’ medical records were analyzed using standardized questionnaires. Prevalence of spondyloarthropathy was slightly higher in females than males (57% versus 43%, respectively). The median age was 47.5 years. Most of our patients were diagnosed with reactive arthritis or undifferentiated arthritis (47% and 33%, respectively); 10% of patients had ankylosing spondylitis and 9% psoriatic arthritis.

The lack of relationship between reported self-care, and the factors that influence blood hypertension, in Costa Rican patients

La hipertensión arterial es un problema de salud importante actualmente a nivel mundial, cuyo control depende de un buen nivel de autocuidado, tema que no ha sido estudiado en personal universitario de América Latina. Queríamos saber si los factores que se sabe favorecen la hipertensión arterial, tenían relación con el nivel de autocuidado en los pacientes. Entrevistamos para ello a 80 empleados universitarios hipertensos que consultaron el servicio médico de una universidad costarricense entre el 14 de enero de 2002 y el 15 de diciembre de 2008. Se les aplicó un Cuestionario de Evaluación de Adherencia Terapéutica en Pacientes Hipertensos, de elaboración propia a partir de la prueba de Morinsky y del cuestionario Martin-Bayarre-Grau. La edad, sexo,educación, historial médico, tratamiento y relación con el personal de salud no tuvieron asociación con el nivel de autocuidado informado por los pacientes. Dentro de una escala de 1 a 100, la mayoría de los pacientes obtuvo entre 75 y 90 puntos, lo que indica que reportan altos niveles de autocuidado. Nuestra experiencia con estos pacientes indica que el autocuidado que informan tener es coherente con los niveles de control de su hipertensión. Este tipo de estudio no es nuevo en países industrializados, pero llena un vacío importante en nuestro conocimiento de la salud en personal universitario latinoamericano.

Variability in HIV-1 partial genomic sequences in Costa Rican patients: analysis with different bioinformatics tools

To estimate subtype and genomic variability in the HIV pol gene of Costa Rican patients by using different bioinformatics tools and to use this information to establish new policies to better manage these patients. A total of 113 pol sequences available from Costa Rican patients under highly active antiretroviral therapy were analyzed by using the Genotyping, REGA, Stanford, and MEGA programs. The pol sequences came from 77 virologic failures (VF) and 36 basal samples (BS). Of the 77 VF, 22 also were sequenced in the env region. No major differences were found among the variables studied. However, there was a tendency for more variability in VF patients with a high baseline viral load. In the pol gene, 75%-83% of BS and 66%-75% of VF samples were pure B subtype by Genotyping and REGA, respectively. The other samples presented variations related mainly to circulating recombinant form CRF12 by genotyping or to CRF17 or -29 by phylogenetic analysis or a new possible BD recombinant with all programs. In the Stanford program, all variable samples showed a subtype B with high polymorphism. The variability in the env sequences was lower than that in the pol region. The B subtype is predominant in Costa Rican HIV-positive patients. There is high variability within sequences with potential recombination between B and F or D subtypes. The BD recombinant has not been previously reported. This high variability is likely the result of possible recombinant events, nonadherence to antiretroviral therapy, sexual intercourse without protection, and many sexual partners. Similar studies should be done in other countries in the Region, in particular in those places with extensive immigration, in order to decrease the possibility of virus variability as well as the cost of antiretroviral therapy.