Survival Outcomes of Patients With Breast Cancer in a Mexican Population.

PURPOSE: The Instituto Mexicano del Seguro Social is a tripartite contribution providing care to more than 74 million beneficiaries, representing more than 50% of the country's general population. This study aims to describe the survival outcomes and clinicopathologic characteristics of patients with breast cancer at our Center. METHODS: A retrospective cohort of patients with breast cancer treated between January 2012 and December 2020 was conducted. Survival outcomes were assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using a Cox proportional hazards model. RESULTS: There were 5,264 patients included with a median follow-up of 54.9 months. Forty-three percent (n = 2,274) were diagnosed in stage I-IIA, 43.1% (n = 2,269) in stage IIB-III, and 7% (n = 383) in stage IV. At 5 years, disease-free survival was 74.9% (95% CI, 73.5 to 76.3) and overall survival (OS) 90.4% (95% CI, 89.4 to 91.3). For stage IV, it was 22.7% (95% CI, 17.3 to 28.5). High histologic grade (hazard ratio, 1.51 [95% CI, 1.34 to 1.7]; P < .001) and lymphovascular invasion (LVI; hazard ratio, 1.85 [95% CI, 1.62 to 2.1]; P < .001) were associated with a higher risk of recurrence. CONCLUSION: Histologic grade and LVI should be considered in the decision to treat with adjuvant chemotherapy in sites where genomic signatures are not available. Our OS data are comparable with other Mexican series; however, it is lower in stage IV. Much remains to be done at the national level, mainly regarding access to additional therapies for each breast cancer subtype. This work contributes to the evaluation of areas for improvement in outcomes in our population.

Single-cell immune landscape of human atherosclerotic plaques.

Atherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. However, specific characteristics of dysregulated immune cells within atherosclerotic lesions that lead to clinical events such as ischemic stroke or myocardial infarction are poorly understood. Here, using single-cell proteomic and transcriptomic analyses, we uncovered distinct features of both T cells and macrophages in carotid artery plaques of patients with clinically symptomatic disease (recent stroke or transient ischemic attack) compared to asymptomatic disease (no recent stroke). Plaques from symptomatic patients were characterized by a distinct subset of CD4+ T cells and by T cells that were activated and differentiated. Moreover, some T cell subsets in these plaques presented markers of T cell exhaustion. Additionally, macrophages from these plaques contained alternatively activated phenotypes, including subsets associated with plaque vulnerability. In plaques from asymptomatic patients, T cells and macrophages were activated and displayed evidence of interleukin-1ß signaling. The identification of specific features of innate and adaptive immune cells in plaques that are associated with cerebrovascular events may enable the design of more precisely tailored cardiovascular immunotherapies.

Tissue Changes in the Development of Fatty Liver by Chronic Ingestion of Sucrose Associated with Obesity and Dyslipidemia in Rats.

A diet high in sucrose, which is a common food constituent, induces obesity and non- alcoholic fatty liver (NFLD) caused by high caloric intake; however, it is important to investigate those sequential changes in the hepatic parenchyma related to sugar consumption which are associated to obesity and dyslipidemia. We analyzed the effects of long-term sucrose intake on fatty liver development, by the administration of 30% sucrose in drinking water in healthy Wistar rats during 30 weeks. Serum variables, body fat index, caloric intake and microscopic examination of liver tissue were monitored. In the first week, grade 1 steatosis was observed with ballooned hepatocytes, with a caloric intake of 125 ± 1.90 kcal / day / 100 g of body weight; together with a gain of 71% in abdominal fat with respect to the control group and dyslipidemia. During the 10 to 20 weeks period, steatosis grade 2 with noticeable inflammation (steatohepatitis), polymorphic cells and ballooned hepatocytes were evident. After 10 weeks, the caloric intake was 72.9 ± 5.99 kcal / day / 100 g of body weight with 199% of gain in abdominal fat in SUC groups with respect control group (p < 0.01) and moderate dyslipidemia; while after 20 weeks, the caloric intake was 61.6 ± 4.65 kcal / day / 100 g of body weight with 208% of gain in abdominal fat and also moderate dyslipidemia. After 30 weeks steatosis grade 3 with marked inflammation (steatohepatitis), periportal fibrosis, globose and fat-filled hepatocytes were observed, with a caloric intake of 52.3 ± 3.05 kcal / day / 100 g of body weight and 232% of gain in abdominal fat that was related to severe dyslipidemia. In conclusion, the sequential changes in the development of NAFLD were associated with the ingestion of sucrose and obesity since the first week of administration.

Neospora caninum in Axis Deer ( Axis axis ) and Fallow Deer ( Dama dama ) in Northern Mexico.

Serum samples from 18 axis deer ( Axis axis ) and 19 fallow deer ( Dama dama ) were analyzed with an enzyme-linked immunosorbent assay for Neospora caninum antibodies. Two axis (11%) and two fallow deer (11%) were positive for N. caninum antibodies.

The Amoebicidal Effect of Ergosterol Peroxide Isolated from Pleurotus ostreatus.

Dysentery is an inflammation of the intestine caused by the protozoan parasite Entamoeba histolytica and is a recurrent health problem affecting millions of people worldwide. Because of the magnitude of this disease, finding novel strategies for treatment that does not affect human cells is necessary. Ergosterol peroxide is a sterol particularly known as a major cytotoxic agent with a wide spectrum of biological activities produced by edible and medicinal mushrooms. The aim of this report is to evaluate the amoebicidal activity of ergosterol peroxide (5α, 8α-epidioxy-22E-ergosta-6,22-dien-3ß-ol isolated from 5α, 8α-epidioxy-22E-ergosta-6,22-dien-3ß-ol) (Jacq.) P. Kumm. f. sp. Florida. Our results show that ergosterol peroxide produced a strong cytotoxic effect against amoebic growth. The inhibitory concentration IC50 of ergosterol peroxide was evaluated. The interaction between E. histolytica and ergosterol peroxide in vitro resulted in strong amoebicidal activity (IC50 = 4.23 nM) that may be due to the oxidatory effect on the parasitic membrane. We also tested selective toxicity of ergosterol peroxide using a cell line CCL-241, a human epithelial cell line isolated from normal human fetal intestinal tissue. To the best of our knowledge, this is the first report on the cytotoxicity of ergosterol peroxide against E. histolytica, which uncovers a new biological property of the lipidic compound isolated from Pleurotus ostreatus (Jacq.) P. Kumm. f. sp. Florida.

Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy.

A 14-year-old female with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency underwent bilateral adrenalectomy at 6 years of age as a result of poor hormonal control. Because the patient was adrenalectomized, extra adrenal androgen production was suspected. Imaging studies including pelvic ultrasound and pelvic magnetic resonance imaging (MRI) were obtained to evaluate for adrenal rest tumors of the ovaries. Abdominal MRI was obtained to evaluate for residual adrenal tissue. A cystic lesion arising from her right ovary suspicious for ovarian neoplasm was noted on pelvic MRI. Right salpingo-oophorectomy was performed and histopathological examination revealed ovarian serous adenocarcinoma, low-grade, and well-differentiated. Tumor marker CA-125 was elevated and additional ovarian cancer staging workup confirmed stage IIIC due to one lymph node positive for carcinoma. The patient then developed a large left ovarian cyst, which led to a complete total abdominal hysterectomy and removal of the left ovary and fallopian tube. Pathology confirmed ovarian serous adenocarcinoma with microscopic focus of carcinoma in the left ovary. After numerous complications, the patient responded well to chemotherapy, CA-125 levels fell and no evidence of carcinoma was observed on subsequent imaging. To our knowledge, this is the first reported case of an ovarian serous adenocarcinoma in a patient with CAH. Although rare, we propose that the ovaries were the origin of androgen production and not residual adrenal tissue. The relationship between CAH and ovarian carcinomas has yet to be established, but further evaluation is needed given the poor survival rate of high-grade serous ovarian carcinoma.

Pitfalls in hormonal diagnosis of 17-beta hydroxysteroid dehydrogenase III deficiency.

Steroid 17ß-hydroxysteroid dehydrogenase III (17ß-HSD3) deficiency is a rare autosomal recessive disorder that usually presents in patients with a 46,XY karyotype with ambiguous genitalia at birth. The 17ß-HSD3 enzyme, which is encoded by the HSD17B3 gene, converts gonadal delta-4 androstenedione (Δ4) to testosterone (T). Such 17ß-HSD3 enzyme deficiency is expected to lead to an increased ratio of D4 to T when the patient undergoes a human chorionic gonadotropin stimulation (hCG) test. Two patients with 46,XY disorders of sexual differentiation were studied. Serum D4 and T levels were measured by HPLC tandem mass spectrometry. As one of the patients was born to consanguineous parents, we performed single nucleotide polymorphism (SNP) microarray to analyze regions of homozygosity (ROH). The HSD17B3 gene was sequenced using the Sanger method. Contrary to expectations, both patients demonstrated decreased D4/T ratio after hCG stimulation. Initial sequencing results for the androgen receptor or 5α-reductase were negative for mutations. ROH analysis identified HSD17B3 as a candidate gene that might cause the disease. Sanger sequencing of the HSD17B3 gene confirmed 17ß-HSD3 deficiency in both patients. Serum D4/T ratios are not reliable parameters for the diagnosis of 17ß-HSD3 deficiency. Molecular genetic analysis provides accurate diagnosis.

Noninvasive prenatal diagnosis of congenital adrenal hyperplasia using cell-free fetal DNA in maternal plasma.

CONTEXT: Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition that arises from mutations in CYP21A2 gene, which encodes for the steroidogenic enzyme 21-hydroxylase. To prevent genital ambiguity in affected female fetuses, prenatal treatment with dexamethasone must begin on or before gestational week 9. Currently used chorionic villus sampling and amniocentesis provide genetic results at approximately 14 weeks of gestation at the earliest. This means that mothers who want to undergo prenatal dexamethasone treatment will be unnecessarily treating seven of eight fetuses (males and three of four unaffected females), emphasizing the desirability of earlier genetic diagnosis in utero. OBJECTIVE: The objective of the study was to develop a noninvasive method for early prenatal diagnosis of fetuses at risk for CAH. PATIENTS: Fourteen families, each with a proband affected by phenotypically classical CAH, were recruited. DESIGN: Cell-free fetal DNA was obtained from 3.6 mL of maternal plasma. Using hybridization probes designed to capture a 6-Mb region flanking CYP21A2, targeted massively parallel sequencing (MPS) was performed to analyze genomic DNA samples from parents and proband to determine parental haplotypes. Plasma DNA from pregnant mothers also underwent targeted MPS to deduce fetal inheritance of parental haplotypes. RESULTS: In all 14 families, the fetal CAH status was correctly deduced by targeted MPS of DNA in maternal plasma, as early as 5 weeks 6 days of gestation. CONCLUSIONS: MPS on 3.6 mL plasma from pregnant mothers could potentially provide the diagnosis of CAH, noninvasively, before the ninth week of gestation. Only affected female fetuses will thus be treated. Our strategy represents a generic approach for noninvasive prenatal testing for an array of autosomal recessive disorders.