Cohort Of Mexican Patients Research Articles

Role of Genetic Polymorphisms -238 G>A and -308 G>A, and Serum TNF-α Levels in a Cohort of Mexican Pediatric Neuroblastoma Patients: Preliminary Study.

The results of in vitro and in vivo studies have shown the pro-tumor effects of TNF-α, and this cytokine's increased expression is associated with poor prognosis in patients with some types of cancer. Our study objective was to evaluate the possible association of TNF-α genetic polymorphisms and serum levels with susceptibility and prognosis in a cohort of Mexican patients with NB. We performed PCR-RFLP and ELISA methods to analyze the genetics of these SNPs and determine serum concentrations, respectively. The distribution of the -308 G>A and -238 G>A polymorphisms TNFα genotypes was considerably different between patients with NB and the control group. The SNP rs1800629 GG/GA genotypes were associated with a decreased risk of NB (OR = 0.1, 95% CI = 0.03-0.393, p = 0.001) compared with the AA genotype, which was associated with susceptibility to NB (OR = 2.89, 95% CI = 1.45-5.76, p = 0.003) and related to unfavorable histology and high-risk NB. The rs361525 polymorphism GG genotype was associated with a lower risk of developing NB compared with the GA and AA genotypes (OR = 0.2, 95% CI = 0.068-0.63, p = 0.006). Circulating TNF-α serum concentrations were significantly different (p < 0.001) between patients with NB and healthy controls; however, we found no relationship between the analyzed TNF-α serum levels and SNP genotypes. We found associations between the rs1800629AA genotype and lower event-free survival (p = 0.026); SNP rs361525 and TNF-α levels were not associated with survival in patients with NB. Our results suggest the TNF-α SNP rs1800629 as a probable factor of NB susceptibility. The -308 G/A polymorphism AA genotype has a probable role in promoting NB development and poor prognosis associated with unfavorable histology, high-risk tumors, and lower EFS in Mexican patients with NB. It should be noted that it is important to conduct research on a larger scale, through inter-institutional studies, to further evaluate the contribution of TNF-α genetic polymorphisms to the risk and prognosis of NB.

Prevalence of Genetic Mutations in Patients with Metastatic Prostate Cancer in a Cohort of Mexican Patients

Background: Prostate cancer is a malignant neoplasm of the male genitourinary system with the highest incidence worldwide. Susceptibility genes related to aggressiveness and prognosis, such as BRCA1/2, ATM, PTEN, have been identified. Currently, reports related to germline mutations in patients with prostate cancer in Latin American populations are very limited or absent. In the Mexican population, reports are also limited, especially in the context of metastatic prostate cancer. Determining the prevalence of these mutations is relevant to predict the potential aggressiveness of tumors and allow the use of targeted therapies, such as PARPi inhibitors. Objective: Determine the prevalence of germline mutations in patients with metastatic prostate cancer and establish their clinical characteristics at diagnosis. Material and Methods: Sixty-nine patients with metastatic PCa underwent testing and genetic analysis using the Comprehensive Multi-Cancer Hereditary Cancer Panel. The prevalence of germline mutations was assessed, and the cohort was divided into two groups for the evaluation and analysis of clinical characteristics between the mutated and non-mutated populations. Results: We identified mutations in 15 out of 69 patients (21.73%), while 54 patients (78.26%) had no mutations. Pathogenic mutations were observed in 15.9% of patients, Variants of Uncertain Significance (VUS) in 34.78%, and 5.79% had both. The most frequent mutations included ATM (11.54%), BRCA1 (11.54%), BRCA2 (7.69%), FANCA (7.69%), and FANCM (7.69%). No statistically significant differences were found in PSA levels, age at diagnosis, and resistance to castration between the two groups. Conclusions: Our study unveiled a mutation rate of 21.73%, marked by a significant prevalence of ATM, FANCA, FANCM, and Variants of Uncertain Significance (VUS). This pattern deviates from findings in other series, underscoring the necessity for improved access to clinical genetic testing in our population.

The impact of vitamin D levels on the progression-free survival of women with hormone receptor-positive, HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors.

e13075 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) halt the transition from the G1 to the S phase, a process governed by the hyperphosphorylation of the retinoblastoma (Rb) protein. Similarly, vitamin D3 has been demonstrated to induce cell cycle arrest through the inhibition of various cyclin-dependent kinases, including those responsible for phosphorylating the Rb protein. Therefore, we hypothesized that suboptimal vitamin D levels may compromise the efficacy of CDK4/6i used to treat hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). Methods: We conducted a retrospective single-center study of women diagnosed with HR-positive, HER2-negative MBC and treated with any CDK4/6i between 2020 and 2023. Eligible patients were those who received at least one cycle of CDK4/6i, had a baseline 25-OH vitamin D measurement, and had a follow-up period of more than three months. Independent samples T-test, X2, and Fisher’s exact tests were used to evaluate associations between variables. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and compared according to vitamin D levels using the log-rank test. Results: Among 31 patients, the mean age at diagnosis was 53 years (SD 14), 24 (77%) received CDK4/6i in the first-line setting, and 9 (29%) had suboptimal vitamin D levels (&lt;20 ng/ml). Clinicopathological features based on vitamin D levels are shown (Table). The type of iCDK was different according to vitamin D levels (p = 0.036), with no other observed differences between groups. With a median follow-up of 26 months (95% CI 17-35) since iCDK initiation, median PFS was not reached for the entire cohort. A univariate analysis revealed that patients with suboptimal vitamin D levels had an inferior median PFS compared to patients with optimal levels (14 months [95%CI 4-24] vs. not reached [p=0.016]). Notably, no other parameter was associated with PFS in univariate analyses. Conclusions: In this cohort of Mexican patients with HR-positive, HER2-negativeMBC, suboptimal vitamin D levels adversely impacted PFS. Given the retrospective nature of this study and the limited number of patients, we emphasize the importance of studying these findings prospectively. [Table: see text]

The usefulness of the genetic panel in the classification and refinement of diagnostic accuracy of Mexican patients with Marfan syndrome and other connective tissue disorders.

Marfan syndrome (MFS) is a multisystem genetic disorder with over 3000 mutations described in the fibrillin 1 (FBN1) gene. Like MFS, other connective tissue disorders also require a deeper understanding of the phenotype-genotype relationship due to the complexity of the clinical presentation, where diagnostic criteria often overlap. Our objective was to identify mutations in patients with connective tissue disorders using a genetic multipanel and to analyze the genotype-phenotype associations in a cohort of Mexican patients. We recruited 136 patients with MFS and related syndromes from the National Institute of Cardiology. Mutations were identified using next-generation sequencing (NGS). To examine the correlation between mutation severity and severe cardiovascular conditions, we focused on patients who had undergone Bentall-de Bono surgery or aortic valve repair. The genetic data obtained allowed us to reclassify the initial clinical diagnosis across various types of connective tissue disorders. The transforming growth factor beta receptor 2 (TGFBR2) rs79375991 mutation was found in 10 out of 16 (63%) Loeys-Dietz patients. We observed a high prevalence (65%) of more severe mutations, such as frameshift indels and stop codons, among patients requiring invasive treatments like aortic valve-sparing surgery, Bentall and de Bono procedures, or aortic valve replacement due to severe cardiovascular injury. Although our study did not achieve precise phenotype-genotype correlations, it underscores the importance of a multigenetic panel evaluation. This could pave the way for a more comprehensive diagnostic approach and inform medical and surgical treatment decision-making.

The functional TNFAIP3 rs2230926T/G (Phe127Cys) variant confers risk to systemic lupus erythematosus in a Latin American population

TNFAIP3 is a classical systemic lupus erythematosus (SLE)-associated risk locus identified by genome-wide association studies (GWASs) and replicated by candidate gene association studies primarily in Caucasians and Asians. However, in Latin American populations, its role on SLE susceptibility is not known. We conducted a case-control study to evaluate whether the TNFAIP3 rs2230926T/G (Phe127Cys) variant is associated with risk of developing SLE in a cohort of Mexican patients. The TNFAIP3 rs2230926T/G variant was analyzed in 561 patients with SLE and 499 control subjects, using TaqMan probes. We found that the G allele was associated with susceptibility to SLE under the allelic (OR 2.09, p = 0.005) and genotypic (OR 2.14, p = 0.004) models. In conclusion, our results show that TNFAIP3 rs2230926T/G is a risk factor for the development of SLE in the Mexican population.

A Comparative Study of Hyper-CVAD and Modified CALGB-10403 Regimens in Adults with Philadelphia-Negative Acute Lymphoblastic Leukemia

Introduction: Induction with pediatric-inspired regimens (PIR) in young adults with acute lymphoblastic leukemia (ALL) is being increasingly used due to its demonstrated improvement in overall survival (OS) compared to historical adult regimens. However, in certain comparisons, PIR, specifically augmented BFM, did not exhibit an OS benefit when compared to the adult Hyper-CVAD regimen. Additionally, Hispanic patients with ALL often present with disease-related high-risk features and a high prevalence of comorbidities like obesity and metabolic syndrome, which may contribute to unfavorable outcomes and a particular adverse event profile. This study aimed to compare the OS and relapse-free survival (RFS) of patients treated with a PIR, a modified CALGB 10403 (mCALGB), and the Hyper-CVAD regimen. Methods: This observational retrospective cohort study was conducted at a single reference center in Mexico City. The study included adult patients aged 18-49 years with newly diagnosed Philadelphia (Ph)-negative ALL who received induction chemotherapy with either mCALGB or Hyper-CVAD between January 2015 and May 2023. High-risk karyotype was defined by hypodiploid, complex, or t(v;11q23), and hyperleukocytosis was characterized by &amp;gt; 30 x 10 3/µL white blood cells. Measurable residual disease (MRD) was assessed via flow cytometry. A comparative analysis of sociodemographic, clinical, and laboratory characteristics was performed between the two treatment groups using Student's t-test (parametric) or U Mann-Whitney (non-parametric) for continuous variables, and the Chi-square / exact Fisher tests for categorical variables. OS and RFS were estimated using Kaplan-Meier survival analysis, and the log-rank test was used to compare both survivals. A Cox regression analysis was performed to identify prognostic factors for OS and RFS. Results: The study included 100 patients: 36 treated with Hyper-CVAD and 64 with mCALGB. The median age at diagnosis was 26 years (IQR 20.5-38), with 56% being male, and 52% being overweight or obese. No statistically significant differences were observed in the clinical and laboratory features between the treatment groups (see Table 1). Regarding induction-related mortality, febrile neutropenia, or admission to an intensive care unit during induction, no differences were found between Hyper-CVAD and mCALGB (see Table 1). A non-significant trend towards a higher rate of grade 3 or 4 hepatotoxicity during induction was observed in patients receiving the modified CALGB 10403: 56.3% vs. 36.1% with an odds ratio (OR) of 2.275 (95% CI 0.982-5.272), p=0.063. The complete response (CR) rate was 87.6%. MRD was assessed in 83% of patients, with &amp;lt;0.1% detected in 62.7% of them. There were no differences between Hyper-CVAD and mCALGB regarding CR or MRD&amp;lt;0.1% (88.9% vs. 86.9%, p=1, and 53.8% vs. 66.7%, p=0.330, respectively). The relapse rate for the entire population was 41.8%, with Hyper-CVAD demonstrating a higher relapse rate compared to mCALGB: 64.7% vs. 28.1%, p=0.001. The median RFS was 54.1 months (95% CI NR-NR) for mCALGB and 12.7 months (95% CI 2.9-22.5) for Hyper-CVAD, with a 3-year RFS of 61.2% vs. 31.5%, p=0.008. In a multivariate analysis for RFS, significant prognostic factors included WBC &amp;gt;30 x 10 3/µL (HR 4.47, 95% CI 2.09-9.57, p&amp;lt;0.001), post-induction MRD &amp;gt;0.1% (HR 4.07, 95% CI 1.86-8.90, p&amp;lt;0.001), and mCALGB vs. Hyper-CVAD (HR 0.37, 95% CI 0.18-0.78, p=0.01). The median OS for the entire cohort was 32.3 months (95% CI 28.3-80.1), with mCALGB demonstrating a non-reached (NR) median OS (95% CI NR-NR), and Hyper-CVAD exhibiting a median OS of 22.4 months (95% CI 13.8-31) with a 3-year OS of 64.8% vs. 35.0%, p=0.037 (see Figure 1). In a multivariate analysis for OS, significant prognostic factors included WBC &amp;gt;30 x 10 3/µL (HR 3.57, 95% CI 1.58-8.09, p=0.002), post-induction MRD &amp;gt;0.1% (HR 2.58, 95% CI 1.17-5.69, p=0.002), and mCALGB vs. Hyper-CVAD (HR 0.29, 95% CI 0.13-0.66, p=0.003). Conclusion: Among a cohort of Mexican patients, treatment with mCALGB was independently associated with better RFS and OS compared to Hyper-CVAD.

A Review of Disparities and Unmet Newborn Screening Needs over 33 Years in a Cohort of Mexican Patients with Inborn Errors of Intermediary Metabolism.

Advances in an early diagnosis by expanded newborn screening (NBS) have been achieved mainly in developed countries, while populations of middle- and low-income countries have poor access, leading to disparities. Expanded NBS in Mexico is not mandatory. Herein, we present an overview of the differences and unmet NBS needs of a group of Mexican patients with inborn errors of intermediary metabolism (IEiM), emphasizing the odyssey experienced to reach a diagnosis. We conducted a retrospective observational study of a historical cohort of patients with IEiM from a national reference center. A total of 924 patients with IEiM were included. Although 72.5% of the diseases identified are detectable by expanded NBS, only 35.4% of the patients were screened. The mortality in the unscreened group was almost two-fold higher than that in the screened group. Patients experienced a median diagnostic delay of 4 months, which is unacceptably long considering that to prevent disability and death, these disorders must be treated in the first days of life. Patients had to travel long distances to our reference center, contributing to their unacceptable diagnostic odyssey. This study highlights the urgent need to have an updated, expanded NBS program with adequate follow up in Mexico and promote the creation of regional medical care centers. We also provide compelling evidence that could prove valuable to decision makers overseeing public health initiatives for individuals impacted by IEiM from middle- and low-income countries.

SAT603 A Heterogeneous Genetic Background Underlies Familial And Young-onset Pituitary Tumors

Abstract Disclosure: J.M. Zuarth-Vazquez: None. R.G. Rebollar-Vega: None. C. Ramírez-Rentería: None. W.E. Hernández-Núñez: None. M. Torres-Morán: None. A.L. Franco-Álvarez: None. J. Eseiza-Acevedo: None. M. Aguilar-Soto: None. D. Cuevas-Ramos: None. E. Sosa-Eroza: None. M. Mercado: None. A. Gamboa-Dominguez: None. L.C. Hernández-Ramírez: None. Introduction: Inherited pituitary neuroendocrine tumors (PitNETs) are considered rare and may present either as isolated lesions or in association with other endocrine tumors. Despite significant progress in the understanding of their molecular basis, the precise pathophysiological mechanisms in many patients with familial and sporadic pituitary tumors are unknown. Although the clinical presentation may point towards a specific genetic cause, a combination of careful clinical assessment and state-of-the-art genetic testing is required. Objective: To describe 4 cases of PitNETs with heterogeneous clinical presentations and genetic causes from a cohort of Mexican patients with neuroendocrine tumors. Methodology: Patients were recruited under informed consent from two different reference hospitals in Mexico City. Germline genetic testing was performed using either a custom-made or a commercial next-generation sequencing (NGS) panel. When available, relevant variants were confirmed in tissue samples. Genetic results were correlated with clinical, biochemical, and imaging characteristics. Results: Case 1 is an 18-year-old male with gigantism due to a 3-cm GH/prolactin-secreting PitNET, that was not cured after transsphenoidal surgery (TSS). Genetic testing showed a CDKN1B (NM_004064.5) c.356T&amp;gt;C, p.I119T variant of uncertain significance. No relevant family history was informed. Currently, the patient is treated with monthly octreotide LAR. Case 2 is a patient with young-onset acromegaly (15y) due to a GH-secreting PitNET. She was initially treated with bromocriptine and then underwent TSS without achieving remission. Radiotherapy was therefore indicated, resulting in panhypopituitarism. The likely pathogenic variant of AIP (NM_003977.4) c.872_877del, p.V291_L292del, was identified. Case 3 was diagnosed at the age of 15 with gigantism, treated with TSS and radiotherapy, subsequently demonstrating biochemical cure. Whole-exome sequencing showed the AIP pathogenic variant c.910C.T, p.R304*, indicative of familial isolated pituitary adenoma, confirmed by the history of two paternal first cousins with gigantism. Finally, a 54-year-old man (case 4), with a personal and family history of neurofibromatosis type 1, was incidentally diagnosed with a 16 mm, apparently non-functional PitNET, for which he is awaiting surgery. The pathogenic NF1 (NM_001042492.3) variant c.147C&amp;gt;A, p.Y49* was identified. Conclusions: Our data confirm that inherited PitNETs encompass a variety of clinical phenotypes. Modern NGS-based genetic testing is an effective method for identifying such cases. Precise molecular testing has an impact on the timely diagnosis of these lesions, as well as on their prognosis and the need for genetic counseling. Presentation: Saturday, June 17, 2023

Longitudinal clinical phenotyping of post COVID condition in Mexican adults recovering from severe COVID-19: a prospective cohort study.

Few studies have evaluated the presence of Post COVID-19 conditions (PCC) in people from Latin America, a region that has been heavily afflicted by the COVID-19 pandemic. In this study, we describe the frequency, co-occurrence, predictors, and duration of 23 symptoms in a cohort of Mexican patients with PCC. We prospectively enrolled and followed adult patients hospitalized for severe COVID-19 at a tertiary care centre in Mexico City. The incidence of PCC symptoms was determined using questionnaires. Unsupervised clustering of PCC symptom co-occurrence and Kaplan-Meier analyses of symptom persistence were performed. The effect of baseline clinical characteristics was evaluated using Cox regression models and reported with hazard ratios (HR). We found that amongst 192 patients with PCC, respiratory problems were the most prevalent and commonly co-occurred with functional activity impairment. 56% had ≥5 persistent symptoms. Symptom persistence probability at 360 days 0.78. Prior SARS-CoV-2 vaccination and infection during the Delta variant wave were associated with a shorter duration of PCC. Male sex was associated with a shorter duration of functional activity impairment and respiratory symptoms. Hypertension and diabetes were associated with a longer duration of functional impairment. Previous vaccination accelerated PCC recovery. In our cohort, PCC symptoms were frequent (particularly respiratory and neurocognitive ones) and persistent. Importantly, prior SARS-CoV-2 vaccination resulted in a shorter duration of PCC.

Prevalence and clinical correlations of Non-Motor Symptoms in patients with Ataxia: Study in a cohort of Mexican patients

Prevalence and clinical correlations of Non-Motor Symptoms in patients with Ataxia: Study in a cohort of Mexican patients

Clinical Characteristics and Outcomes of Mexican Patients With Behçet's Syndrome.

The aim of this study was to describe the clinical characteristics and outcomes of Mexican patients with Behçet syndrome (BS) from a single center. This medical records review study included patients with established BS diagnosis, followed up in a tertiary care center in Mexico City from 2000 to 2020. Demographics, clinical characteristics, laboratory and imaging studies, disease activity, damage, treatment, and outcomes were assessed and compared according to sex and with other international cohorts. Descriptive statistics were used, and differences between groups were evaluated using the χ2 or Mann-Whitney U tests. Thirty-eight patients were included, 23 (60%) women and 15 (40%) men; the median age at BS diagnosis was 33 years (range, 24-39 years). The most frequent manifestations at diagnosis were recurrent oral and genital ulcers in 34 (89%) and 29 (76%), respectively, musculoskeletal in 21 (55%), and cutaneous in 15 (39%). The most frequent phenotype was the joint involvement. Treatment comprised prednisone in all, colchicine (24 [63%]), pentoxifylline (12 [32%]), and thalidomide (10 [26%]). During a median follow-up time of 12.5 years (range, 7-23 years), relapses were frequent (97%), severe infections were present in 5 patients (13%), and 2 patients (5%) died due to sepsis and pneumonia. Men showed a higher frequency of arterial hypertension (47% vs. 13%, p = 0.03) and thrombosis (20% vs. 0, p = 0.05), and a lower frequency of genital ulcers (40% vs. 78%, p = 0.03) than women. This cohort of Mexican patients with BS showed a predominance of female sex, joint involvement phenotype, frequent relapses, and favorable outcomes. Differences in comorbidities and clinical manifestations were identified according to sex.

Acute heart failure in women: phenotypes and outcomes in Mexico. Gender differences?

Abstract Background Latin America has limited information about sex differences in acute heart failure and about hospital outcome. This study sought to examine clinical features and outcomes of patients with AHF in a coronary care unit of a single Mexican institution. Aims To examine the sex differences in clinical features, phenotype, etiologies and mortality of patients with acute heart failure in a single institution of Latin-America. Methods This was a retrospective study of consecutive patients hospitalized with AHF in a coronary care unit of a Mexican teaching hospital between January 2006 and December 2020. Results During the study period, 24,262 patients were hospitalized, 9,408 (38.8%) had AHF, of which 3,230 (34.3%) were women. Women with AHF, compared to men with AHF, were older (median, 64 vs. 61 years, P&amp;lt;0.0001) and more likely to have a history of hypertension, stroke, atrial fibrillation, and hypothyroidism. The ischemic heart disease was more frequent in men (67.8% vs 40.5%; p&amp;lt;0.0001), however, valvular heart disease and cardiomyopathies were more frequent in women (32.9% vs 16.9% and 16.0 vs 10.2%, respectively; p&amp;lt;0.0001) (figure 1). At presentation, women had a higher frequency of worsening chronic HF (59.8%), worse NYHA class, preserved left ventricular ejection fraction (LVEF) (median, 45% vs 38%; P&amp;lt;0.0001), and lower estimated glomerular filtration rates. Overall, unadjusted in-hospital mortality was higher in women (18.9 vs 16.1, p&amp;lt;0.0001), but only different in ischemic heart disease (18.2 vs 15.7, p&amp;lt;0.03) and valvular heart disease (21.8 vs 18.2%, p&amp;lt;0.03). In-hospital mortality adjusted for age and LVEF showed that women had a higher risk of death. (Odds ratio 1.34; 95% CI, 1.19–1.51, P&amp;lt;0.0001) (figure 2). Conclusions In this cohort of Mexican patients hospitalized with AHF, there were important differences in clinical characteristics and aetiologies between women and men. Women have a higher frequency of worsening chronic HF and as well as renal function. Nevertheless, despite having a preserved LVEF, in-hospital mortality was higher in women compared to men. Funding Acknowledgement Type of funding sources: None. Figure 1. Aetiology in acute heart failureFigure 2. Kaplan-Meier curves for mortality

Development of Zika NS1 ELISA methodology for seroprevalence detection in a cohort of Mexican patients in an endemic region

BackgroundZika (ZIKV) is a mosquito-borne virus that has caused multiple outbreaks in Americas. The early and accurate diagnosis of ZIKV is the key to minimize the health burden imposed on the infected patients. Many commercial ZIKV diagnosis kit are available based on ZIKV envelope antigen with varying sensitivity and specificity. ObjectiveThe aim of this study was to develop sensitive ELISA methodology based on recombinant ZIKV NS1 and NS1 β-ladder antigens for seroprevalence detection in a cohort of patients in an arbovirus endemic Mexican region in comparison to a commercial kit. Study designWe obtained serum samples from 60 patients presenting with febrile illness and from 10 healthy donors in Michoacán state in 2016–2017. These samples were screened for ZIKV by RT-PCR and used to develop NS1 based ELISA and compared to a commercial kit. ResultsOur results indicate that both ZIKV sNS1 and β-ladder-based ELISA can reliably detect anti-ZIKV NS1 antibodies in infected patients, relevant for the serodiagnosis of ZIKV. Determination of antibody titers showed that it offered higher sensitivity than a commercially available ZIKV ELISA. Over 90% seropositivity against ZIKV for the febrile patients was detected in Lázaro Cárdenas which is an arbovirus endemic region while lower seropositivity was observed in the healthy volunteers in Morelia (non-endemic area). ConclusionWe conclude that our simple and sensitive in-house NS1 based ELISA used in this study has excellent sensitivity, is easy to use and can provide fast results suitable for larger population-based seroprevalence studies in the future.

Molecular and Hematological Analysis of Alpha- and Beta-Thalassemia in a Cohort of Mexican Patients.

Introduction: Alpha- and beta-thalassemia are caused by reduced or absent synthesis of hemoglobin (Hb) subunits α and/or β. HBA2, HBA1, and HBB mutations are the main cause of thalassemias. The aim of this article is to analyze molecular and hematological features of α- and β-thal in a cohort of Mexican patients. Methods: One hundred forty-one thalassemia patients were studied. Peripheral blood was collected for blood cell count, electrophoresis, Hb quantification, and molecular testing. Molecular screening was performed by Gap-PCR, ARMS-PCR, Sanger sequencing, and MLPA. Results: Fifty-four patients had α-thal, 75 β-thal, and 12 patients were complex cases, we observed 13 α- and 18 β-thal alleles in 43 genotypes, -α3.7/αα and βCd39C>T/β were the most frequent. Four α-thal deletions (-Mex4 included HBA2 and HBA1, whereas (αα)Mex5, Mex6 and Mex7 involved MCS-R), a hereditary persistence of fetal hemoglobin-2 like (HPFH-2 like) deletion and six alleles not previously reported in Mexicans (α-59C>Tα, -α4.2, αPlasenciaα, β-32C>T, βInitCdA>C and βFSCd71/72+A) were identified. Conclusion: The observed alleles denote the high heterogeneity and multiple origin admixture of Mexican population. Hematological data are consistent with genotypes, variability in simple carriers, from asymptomatic forms to mild or moderate anemia, was ascertained. We emphasize the importance to consider hematological parameters to establish adequate molecular screening strategies.

Wallenberg syndrome and isolated lateral bulbar infarction: Clinical characteristics and prognosis in a cohort of Mexican patients

Wallenberg syndrome and isolated lateral bulbar infarction: Clinical characteristics and prognosis in a cohort of Mexican patients

Impact of Systemic Lupus Erythematosus on Pregnancy: Analysis of a Large 10-Year Longitudinal Mexican Cohort.

Pregnancy in patients with systemic lupus erythematosus is considered a high risk one since it is associated with a higher rate of maternal-fetal complications compared with the pregnancies in healthy women. The aim of this study was to describe the maternal-fetal outcomes in a cohort of Mexican patients with systemic lupus erythematosus and to identify risk factors associated with adverse maternal and fetal outcomes. A cohort of pregnant lupus patients was analyzed. Maternal-fetal complications were described, and clinical, biochemical, and immunological variables associated with obstetric adverse outcomes were studied. Descriptive statistics, comparison of variables using appropriate tests, and finally logistic regression analysis were performed to identify potential risk factors for adverse maternal and fetal outcomes. A total of 351 pregnancies were included in a 10-year period. The most frequently observed maternal adverse outcomes were lupus flare (35%) and preeclampsia (14.5%). Active lupus before pregnancy (hazards ratio [HR], 3.7; 95% confidence interval [CI], 1.1-12.5; p = 0.003) was a predictor for these complications, whereas the use of antimalarial drugs (HR, 0.4; 95% CI, 0.2-0.7; p = 0.007) was a protective factor. The most frequent fetal adverse outcomes were preterm birth (38.1%), miscarriages (10%), and low birth weight babies (28%), and very low birth weight newborns (11%). Proteinuria in early pregnancy (HR, 7.1; 95% CI, 1.01-50.3; p = 0.04) and preeclampsia (HR, 9.3; 95% CI, 1.7-49.7; p = 0.009) were risk factors associated with these complications. Variables related to systemic lupus erythematosus activity predict an adverse maternal outcome, whereas proteinuria in early pregnancy and preeclampsia are associated with an adverse fetal outcome.

Molecular genetic diagnosis by next-generation sequencing in a cohort of Mexican patients with haemophilia and report of novel variants

IntroductionMolecular analysis in haemophilia is currently used in the diagnosis, treatment and prognosis of this disease. Hispanic populations in Latin America have been of interest to researchers due to the reportedly high prevalence of inhibitors in these patients. AimTo perform next-generation sequencing (NGS) in a cohort of Mexican patients with HA and HB and correlate with clinical phenotypes. MethodsPatients with Haemophilia A (HA) or haemophilia B (HB), were evaluated using NGS with an Ion AmpliSeq Custom Panel. Odds ratios (ORs) for associations between F8 variants and inhibitors were obtained. ResultsA total of 85 patients (60 with HA and 25 with HB) were included. Pathogenic variants in F8 were found in 93.3% of HA patients and in F9 in 96% of HB patients. Twelve novel potentially pathogenic variants were found. Inhibitors were observed in 20% of patients with severe HA. Four patients clinically diagnosed with HA were negative for F8 variants. ConclusionOverall detection rate of pathogenic variants in F8 and F9 genes was 94.6%. We identified 12 non previously reported variants and pathogenic variants in other coagulation related genes. Molecular diagnosis of HA and HB permits better options for management, assessment and genetic counseling.

Biochemical relapse free survival rate in patients with prostate cancer treated with external radiotherapy: outcomes obtained at the CMN Siglo XXI Hospital de Oncología, CMN 20 de Noviembre and Hospital General de México of the México City.

Biochemical relapse-free survival (bRFS) rate is determined by a cohort of Mexican patients (n=595) with prostate cancer who received treatment with external radiotherapy. Patients with prostate cancer were collected from CMN Siglo XXI (IMSS), CMN 20 de Noviembre (ISSSTE), and Hospital General de México (HGM). For the IMSS, 173 patients that are treated with three-dimensional conformal radiation therapy (3D-CRT) and 250 with SBRT, for the ISSSTE 57 patients are treated with 3D-CRT and on the HGM 115 patients are managed with intensity modulated radiation therapy (IMRT). The percentage of patients by risk group is: low 11.1%, intermediate 35.1% and high 53.8%. The average follow-up is 39 months, and the Phoenix criterion was used to determine the bRFS. The Kaplan-Meier technique for the construction of the survival curves and, the Cox proportional hazards to model the cofactors. (a) The bRFS rates obtained are 95.9% for the SBRT (7Gy fx, IMSS), 94.6% for the 3D-CRT (1.8Gy fx, IMSS), 91.3% to the 3D-CRT (2.65Gy fx, IMSS), 89.1% for the SBRT (7.25Gy fx, IMSS), 88.7% for the IMRT (1.8Gy fx, HGM) %, and 87.7% for the 3D-CRT (1.8Gy fx, ISSSTE). (b) There is no statistically significant difference in the bRFS rates by fractionation scheme, c) Although the numerical difference in the bRFS rate per risk group is 95.5%, 93.8% and 89.1% for low, intermediate and high risk, respectively, these are not statistically significant. The RT techniques for the treatment of PCa are statistically equivalent with respect to the bRFS rate. This paper confirms that the bRFS rates of Mexican PCa patients who were treated with conventional vs. hypofractionated schemes do not differ significantly.

Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019. Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds. Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17months (range, 0-186months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations. The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.

Mutations identified in a cohort of Mexican patients with lysosomal acid lipase deficiency

Introduction and ObjectivesLysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disease caused by mutations in the LIPA gene, located on the long arm of chromosome 10 (10q23.31). Up until now, more than 59 mutations have been described and which are the cause of a very wide clinical spectrum. The goal of this study was to identify the mutations present in Mexican pediatric patients with a diagnosis of LAL-D. Materials and methodsA cross-sectional study was carried out which included all the pediatric patients with LAL-D treated in a tertiary hospital in Mexico from January 2000 to June 2017. ResultsSixteen patients with LAL-D were identified with a disease phenotype marked by the accumulation of cholesteryl esters. Eight distinct variants in the LIPA gene sequence were found, four pathogenic variants and four probably pathogenic. In six individuals, the variants were found in the homozygous state and ten were compound heterozygous. The eight variants were inverted, with five found on exon 4 and the others on exons 2, 8 and 10. The variant c.386A>G;p.His129Arg was the most common, being found in six of the 16 individuals (37.5%), making it much more frequent than what had previously been reported in the literature in proportion to the rest of the variants. The mutation known as E8SJM, which has been the mostly frequently found at the international level, was not the most common among this group of Mexican patients.In conclusion, Mexican patients present a different frequency of mutations associated with LAL-D in comparison to European populations.