Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure.

Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case-control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal-fetal KIR-HLA-C mismatch in patients.

Hiperplasia endometrial asociada al uso del tamoxifeno en pacientes con cáncer de mama en Barranquilla / Endometrial hyperplasia associated with use of tamoxifen in patients with breast cancer in Barranquilla

Resumen Introducción: el tamoxifeno ha sido el medicamento de primera línea para el tratamiento del cáncer de mama; sin embargo, se han evidenciado serios eventos adversos con su uso. El objetivo de este trabajo fue determinar la hiperplasia endometrial asociada al uso de tamoxifeno en mujeres con cáncer de mama en una institución oncológica de la ciudad de Barranquilla- Colombia. Metodología: estudio de casos y controles retrospectivo. Se incluyeron 202 pacientes con cáncer de mamá tratadas entre 2012 y 2017. Fueron evaluadas variables antropométricas, sociodemográficas, personales, clínicas y patológicas. Se estimaron los Odds Ratios (OR) crudos y ajustados. Resultados: 68 participantes fueron diagnosticadas con hiperplasia endometrial secundaria al tratamiento antineoplásico. De éstas, 59 (86,7 %) usaron tamoxifeno, la mayoría (37,2 %) por un lapso de 6-11 meses. El análisis bivariado mostró asociación entre la hiperplasia endometrial y uso del tamoxifeno con un OR de 3,9 (IC95 %: 1,8-8,5) y 2,9 (IC95 %: 1,18-7,5) en los análisis crudos y ajustados, respectivamente. Conclusión: el uso de tamoxifeno se asocia con la presencia de hiperplasia endometrial.

Abstract Introduction: tamoxifen has been the first line drug for the treatment of breast cancer; however, serious adverse events have been evidenced with its use. The aim of this study was to determine endometrial hyperplasia associated with the use of tamoxifen in women with breast cancer in an oncological institution in the city of Barranquilla, Colombia. Methodology: retrospective case-control study. A total of 202 patients with breast cancer treated between 2012 and 2017 were included. Anthropometric, sociodemographic, personal, clinical and pathological variables were evaluated. Crude and adjusted Odds ratios (OR) were estimated. Results: 68 participants were diagnosed with endometrial hyperplasia secondary to antineoplastic treatment. Of these, 59 (86.7 %) used tamoxifen, the most of them (37.2 %) for a period of 6-11 months. Bivariate analysis showed an association between endometrial hyperplasia and tamoxifen use with an OR of 3.9 (95%CI: 1.8-8.5) and 2.9 (95%CI: 1.18-7.5) in the crude and adjusted analyses, respectively. Conclusion: tamoxifen use is associated with the presence of endometrial hyperplasia.

Demographic and clinical characterization of multiple sclerosis in Mexico: The REMEMBer study.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system with high prevalence in young adults around the world. The vast majority of epidemiological studies and statistics are based on European and American data, so most clinical guidelines and medical consensus are based on this information. There is very limited evidence in Mexico regarding demographic and clinical aspects of MS. Therefore, this study comprehensively described the epidemiological and clinical features of MS in a large cohort of patients from eight tertiary-level centers in Mexico. METHODS: A cross-sectional multicenter study was conducted. A group of neurologists, the "Registro Mexicano de Esclerosis Multiple" (REMEMBer) group, compiled the information of MS patients (January to December 2019) from eight tertiary-level centers. Clinical and demographic data were extracted. RESULTS: A total of 1,185 patients were included. The mean age was 40.65 ± 11.43 years old. Women represented more than half of the whole cohort (64.9% vs. 35.1%). Of the whole cohort, forty-three percent of MS patients had a relative with at least one autoimmune disease (MS: 24%, other autoimmune disorders: 74.9%) or thyroid disease (28%). Furthermore, the mean age of clinical onset was 31.23 ± 9.71 (range: 16-68) years old, and the disease duration was 9.33 ± 7.25 (0.46-40.19) years. The most prevalent phenotype of MS was relapsing-remitting (87.76%). Primary (1.18%) and secondary (9.11%) progressive, as well as clinically isolated syndrome (CIS, 1.43%), were also found. Clinical phenotypes (facial, hearing, and speech disorders, and movement impairment and ataxia) and the frequency of thyroid disorders were different between genders. CONCLUSION: In Mexico, the frequency of MS seems to be higher in the female gender (2:1 women/men ratio) compared to other series. In addition, there was a predominance of facial, hearing and speech disorders, as well as movement impairment and ataxia. Thyroid diseases were more common in women with multiple sclerosis than men.

Experience in IVIg therapy for selected women with recurrent reproductive failure and NK cell expansion.

PROBLEM: Recurrent reproductive failure (RRF) has been associated with expansion of circulating NK cells, key cells for maternal tolerance, decidual vasculogenesis and embryo growth. This study reports our experience in intravenous immunoglobulin (IVIg) therapy of a large cohort of women with RRF with expanded circulating NK and/or NKT-like cells (blood NKT cells are a heterogeneous subset of T cells that share properties of both T cells and NK cells). METHOD OF STUDY: Observational study of RRF women with NK or NKT-like expansion (>12% or 10% cutoff levels of total lymphocytes, respectively), treated with IVIg for the next gestation. RESULTS: By multivariant logistic regression analysis after adjusting for age, NK cells subsets and other therapies, IVIg significantly improved the live birth rate to 96.3% in women with recurrent miscarriage (RM) compared with 30.6% in case not receiving IVIg (P < 0.0001). In women with recurrent implantation failure (RIF), in comparison with women not receiving IVIg, treatment increased the pregnancy rate from 26.2 to 93.8% (P ≤ 0.0001) and the live birth rate from 17.9 to 80.0% in RIF (P ≤ 0.0001). CONCLUSIONS: Immunomodulation with IVIg in our selected group of RRF patients with immunologic alterations enhanced clinical pregnancy and live birth rates. Our results may facilitate the design of future clinical trials of IVIg in this pathology.

New decision-tree model for defining the risk of reproductive failure.

PROBLEM: Natural killer (NK) cells play a key role in embryo implantation and pregnancy success, whereas blood and uterine NK expansions have been involved in the pathophysiology of reproductive failure (RF). Our main goal was to design in a large observational study a tree-model decision for interpretation of risk factors for RF. METHODS OF STUDY: A hierarchical multivariate decision model based on a classification and regression tree was developed. NK and NKT-like cell subsets were analyzed by flow cytometry. RESULTS: By multivariate analysis, blood NK cells expansion was an independent risk factor for RF (both recurrent miscarriages and implantation failures). We propose a new decision-tree model for the risk interpretation of women with RF based on a combination of main risk factors. CONCLUSIONS: Women with age above 35 years and >13% CD56⁺CD16⁺ NK cells showed the highest risk of further pregnancy loss (100%).