Terapia de Hemoadsorción de Citoquinas e Inmunoglobulina G enriquecida en Falla Orgánica Múltiple: Reporte de caso.

Introducción La obstrucción intestinal es la alteración del flujo del contenido luminal del tracto gastrointestinal debido a factores mecánicos. Los casos graves pueden evolucionar a shock séptico refractario con alta mortalidad. Para esta afección se han propuesto terapias innovadoras que pueden cambiar el pronóstico. Reporte: Un paciente masculino de 62 años presenta un cuadro de obstrucción intestinal acompañado de sepsis. La laparotomía exploratoria revela un tumor en el colon descendente y necrosis extensa del colon, requiriendo resección colónica e ileostomía. A pesar de la intervención, el paciente desarrolla choque séptico refractario y falla multiorgánica, con un pronóstico grave. Se implementa terapia de hemoadsorción de citoquinas e inmunoglobulina G enriquecida con inmunoglobulina M dentro de las primeras 32 horas. Se presenta posteriormente recuperación progresiva de parámetros clínicos y de laboratorio, asimismo como estado general. Conclusiones: La terapia hemoadsorción puede reducir la dosis de vasopresores, mejorar la hemodinamia y reducir los marcadores inflamatorios en pacientes con sepsis. La pentaglobina puede reducir el riesgo de mortalidad, disminuir la duración de la ventilación mecánica y mejorar la función renal en pacientes con sepsis. (provisto por Infomedic International)

Introduction Intestinal obstruction is the alteration of the flow of the luminal contents of the gastrointestinal tract due to mechanical factors. Severe cases may progress to refractory septic shock with high mortality. Innovative therapies have been proposed for this condition that may change the prognosis. Report: A 62-year-old male patient presents with intestinal obstruction accompanied by sepsis. Exploratory laparotomy reveals a tumor in the descending colon and extensive colon necrosis, requiring colonic resection and ileostomy. Despite the intervention, the patient develops refractory septic shock and multiorgan failure, with a severe prognosis. Cytokine hemoadsorption therapy and immunoglobulin G enriched with immunoglobulin M were implemented within the first 32 hours. Progressive recovery of clinical and laboratory parameters is subsequently presented, as well as general condition. Conclusions: Hemoadsorption therapy can reduce the dose of vasopressors, improve hemodynamics and reduce inflammatory markers in patients with sepsis. Pentaglobin can reduce the risk of mortality, decrease the duration of mechanical ventilation and improve renal function in patients with sepsis. (provided by Infomedic International)

A microRNA Profile Regulates Inflammation-Related Signaling Pathways in Young Women with Locally Advanced Cervical Cancer.

Cervical cancer (CC) remains among the most frequent cancers worldwide despite advances in screening and the development of vaccines against human papillomavirus (HPV), involved in virtually all cases of CC. In mid-income countries, a substantial proportion of the cases are diagnosed in advanced stages, and around 40% of them are diagnosed in women under 49 years, just below the global median age. This suggests that members of this age group share common risk factors, such as chronic inflammation. In this work, we studied samples from 46 patients below 45 years old, searching for a miRNA profile regulating cancer pathways. We found 615 differentially expressed miRNAs between tumor samples and healthy tissues. Through bioinformatic analysis, we found that several of them targeted elements of the JAK/STAT pathway and other inflammation-related pathways. We validated the interactions of miR-30a and miR-34c with JAK1 and STAT3, respectively, through dual-luciferase and expression assays in cervical carcinoma-derived cell lines. Finally, through knockdown experiments, we observed that these miRNAs decreased viability and promoted proliferation in HeLa cells. This work contributes to understanding the mechanisms through which HPV regulates inflammation, in addition to its canonical oncogenic function, and brings attention to the JAK/STAT signaling pathway as a possible diagnostic marker for CC patients younger than 45 years. To our knowledge to date, there has been no previous description of a panel of miRNAs or even ncRNAs in young women with locally advanced cervical cancer.

Predictors of Endocrine Resistance in a Cohort of Mexican Breast Cancer Patients.

Purpose: This study aimed to determine the prevalence of endocrine resistance in a cohort of Hispanic Mexican breast cancer (BC) patients receiving care at Instituto Nacional de Cancerología (INCan). Additionally, the clinical-pathological factors associated with endocrine resistance were identified, and their impact on patient survival was explored. Methods: A retrospective analysis of 200 BC patients who attended INCan between 2012 and 2016 with estrogen receptor (ER) and progesterone receptor (PR) positive tumors was made. Endocrine resistance was defined according to the International Consensus Guidelines for Advance Breast Cancer 2 definition. Their clinicopathological characteristics were analyzed to determine the association with endocrine resistance presence. We used sensitivity analyses and multivariate-adjusted logistic regressions, Kaplan-Meier curves, and multivariate-adjusted Cox regressions. P-value < 0.05 was considered as statistically significant. Results: Endocrine resistance was observed in 32.5% of patients included in this study. The distinction between hormone resistance and sensitivity was influenced by tumor size and node status. It had a mean diameter of 7.15 cm in endocrine resistance cases compared to 5.71 cm in non-endocrine, with N3 status present in 20% of endocrine resistance cases versus only 2.2% in non-endocrine (p-value < 0.001). The clinical stage exhibited a strong association with endocrine resistance (Risk Ratio [RR] 4.39, 95% confidence interval [95%CI] 1.50, 11.43). Furthermore, endocrine resistance significantly impacted mortality during the follow-up, with a Hazard Ratio [HR] of 23.7 (95%CI 5.20, 108.42) in multivariable-adjusted models. However, a complete pathological response reduced the endocrine resistance risk, as demonstrated by a Risk Ratio (RR) of 0.15 (95% CI 0.03, 0.75). Conclusions: Advanced clinical stage at diagnosis predicted endocrine resistance in Hispanic Mexican BC patients. Complete pathologic response in locally advanced disease patients was also a key predictor of endocrine resistance. These results indicated that endocrine resistance was a critical factor in BC during follow-up.

The every woman study™ low- and middle-income countries edition protocol: A multi-country observational study to assess opportunities and challenges to improving survival and quality of life for women with ovarian cancer.

BACKGROUND: Ovarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income countries highlighted common challenges and opportunities to improve survival and quality of life for women affected by ovarian cancer. However, no comparable data exist for low-and middle-income countries, where 70% of women with the disease live. This study aims to address this evidence gap. METHODS: This is an observational multi-country study set in low- and middle-income countries. We aim to recruit over 2000 women diagnosed with ovarian cancer across multiple hospitals in 24 countries in Asia, Africa and South America. Country sample sizes have been calculated (n = 70-96 participants /country), taking account of varying national five-year disease prevalence rates. Women within five years of their diagnosis, who are in contact with participating hospitals, are invited to take part in the study. A questionnaire has been adapted from a tool previously used in high-income countries. It comprises 57 multiple choice and two open-ended questions designed to collect information on demographics, women's knowledge of ovarian cancer, route to diagnosis, access to treatments, surgery and genetic testing, support needs, the impact of the disease on women and their families, and their priorities for action. The questionnaire has been designed in English, translated into local languages and tested according to local ethics requirements. Questionnaires will be administered by a trained member of the clinical team. CONCLUSION: This study will inform further research, advocacy, and action in low- and middle-income countries based on tailored approaches to the national, regional and global challenges and opportunities. In addition, participating countries can choose to repeat the study to track progress and the protocol can be adapted for other countries and other diseases.

Taxonomic distinctness and diversity patterns of a polychaete (Annelida) community on the continental shelf of the Southern Gulf of Mexico.

The spatial patterns of taxonomic diversity of annelid polychaete species from the continental shelf in the Southern Gulf of Mexico were examined in this study. We used taxonomic distinctness and its spatial variations to explore the diversity patterns and how they change between Southern Gulf of Mexico regions. In addition, using taxonomic distinctness as a dissimilarity measure and Ward's Clustering, we characterized three distinct faunal assemblages. We also investigated patterns of richness, taxonomic distinctness, and distance decay of similarity between sampling stations as a ß-diversity measure. Finally, we examined the spatial relationships between polychaete assemblages and environmental variables to test the relative importance of spatial and environmental components in annelid polychaete community structure from the Southern Gulf of Mexico. We used a combination of eigenvector-based multivariate analyses (dbMEMs) and distance-based redundancy analysis (dbRDA) to quantify the relative importance of these explanatory variables on the spatial variations of taxonomic distinctness. The significance level of spatial and environmental components to the distribution of polychaete species showed that the combined effect of spatial processes and sediment characteristics explained a higher percentage of the variance than those parameters could alone.

The structure-giving role of Rb+ ions for water-ice nanoislands supported on Cu(111).

We characterize the effect of rubidium ions on water-ice nanoislands in terms of area, fractal dimension, and apparent height by low-temperature scanning tunneling microscopy. Water nanoislands on the pristine Cu(111) surface are compared to those at similar coverage on a Rb+ pre-covered Cu(111) surface to reveal the structure-giving effect of Rb+. The presence of Rb+ induces changes in the island shape, and hence, the water network, without affecting the nanoisland volume. The broad area distribution shifts to larger values while the height decreases from three bilayers to one or two bilayers. The nanoislands on the Rb+ pre-covered surface are also more compact, reflected in a shift in the fractal dimension distribution. We relate the changes to a weakening of the hydrogen-bond network by Rb+.

Delivery of hereditary cancer genetics services to patients newly diagnosed with ovarian and endometrial cancers at three gynecologic oncology clinics in the USA, Brazil, and Mexico.

OBJECTIVE: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic. METHODS: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer (microsatellite instability/immunohistochemistry, MSI/IHC), referral to genetics services for patients with ovarian cancer, completed genetics consultations, and germline genetic testing for patients with ovarian and endometrial cancers. Timeliness was calculated as the average number of days between diagnosis and the relevant delivery metric. Descriptive statistics were used to analyze data. RESULTS: In total, 1195 patients (596 with ovarian cancer, 599 with endometrial cancer) were included in the analysis, and rates of genetics service delivery varied by clinic. For patients with ovarian cancer, referral rates ranged by clinic from 32.6% to 89.5%; 30.4-65.1% of patients completed genetics consultation and 32.6-68.7% completed genetic testing. The timeliness to genetic testing for patients with ovarian cancer ranged by clinic from 107 to 595 days. A smaller proportion of patients with endometrial cancer completed MSI/IHC testing (10.0-69.2%), with the average time to MSI/IHC ranging from 15 to 282 days. Rates of genetics consultation among patients with endometrial cancer ranged by clinic from 10.8% to 26.0% and 12.5-16.6% completed genetic testing. CONCLUSIONS: All clinics successfully established baseline rates and timeliness of delivering hereditary cancer genetics services to patients with ovarian and endometrial cancers. Lower rates of delivering genetics services to patients with endometrial cancer warrant additional research and quality improvement efforts.

Factors Associated with Parametrial Involvement in Endometrial Carcinoma in Patients Treated with Radical Hysterectomy.

INTRODUCTION: Describe factors associated with parametrial involvement, and how these factors modify the prognosis of patients with endometrial carcinoma treated with radical hysterectomy. METHODS: Observational study in which categorized patients according to those with and without parametrial involvement. A descriptive analysis and comparative analysis were performed for associations between parametrial spread and clinical, surgical, and pathology variables. RESULTS: We analyzed 85 patients, which 18 (21%) had parametrial involvement. Pathology factors associated with parametrial involvement were the endometrioid subtype, grade 3, and variants of poor prognosis (odds ratio (OR) 3.41, 95% CI 1.09-10.64; P = 0.035), myometrial invasion of over 50% (OR 7.76, 95% CI 1.65-36.44; P = 0.009), serosal involvement (OR 17.07, 95% CI 3.87-75.35; P < 0.001), ovarian metastasis (OR 5.15, 95% CI 1.36-19.46; P = 0.016), positive peritoneal cytology (OR 3.9, 95% CI 1.04-14.77; P = 0.044), and lymph node metastasis (OR 3.4; 95% CI 1.16-9.97; P = 0.026). Five-year disease-free survival was 74% (95% CI 57.4-85.4) for the group without parametrial spread and 50.8% (95% CI 22.7-73.4) for the group with parametrial spread (P = 0.001). Similarly, 5-year overall survival was 85.2% (95% CI 67.9-93.6) for the group without parametrial spread and 47.5% (95% CI 8.1-80.2) for the group with parametrial spread (P = 0.002). CONCLUSION: Factors associated with parametrial involvement were histologies of poor prognosis, tumors affecting uterine serosa, cervix, or spread beyond the uterus. Additionally, parametrial involvement directly affects prognosis by reducing overall survival, disease-free survival and increasing odds for recurrence.

Air Pollution and Lung Cancer: Contributions of Extracellular Vesicles as Pathogenic Mechanisms and Clinical Utility.

PURPOSE OF REVIEW: This review addresses the pressing issue of air pollution's threat to human health, focusing on its connection to non-small cell lung cancer (NSCLC) development. The aim is to explore the role of extracellular vesicles (EVs) as potential pathogenic mechanisms in lung cancer, including NSCLC, induced by air pollutants. RECENT FINDINGS: Recent research highlights EVs as vital mediators of intercellular communication and key contributors to cancer progression. Notably, this review emphasizes the cargo of EVs released by both cancerous and non-cancerous lung cells, shedding light on their potential role in promoting various aspects of tumor development. The review underscores the importance of comprehending the intricate interplay between air pollution, biological damage mechanisms, and EV-mediated communication during NSCLC development. Major takeaways emphasize the significance of this understanding in addressing air pollution-related lung cancer. Future research avenues are also highlighted, aiming to enhance the applicability of EVs for diagnosis and targeted therapies, ultimately mitigating the inevitable impact of air pollution on NSCLC development and treatment.

Percepciones sobre la importancia de las ciencias básicas en estudiantes de odontología y medicina / Perceptions of the importance of basic sciences in odontology and medical students

Introducción: El aprovechamiento de los cursos de ciencias básicas puede depender de las percepciones estudiantiles sobre la importancia de estos en su vida profesional, por lo que se hace necesario determinar el grado de importancia que los estudiantes le confieren a este tipo de cursos. Materiales y métodos: Se presentó un cuestionario con 9 declaraciones a 54 estudiantes de odontología y medicina. Las respuestas se pasaron a una escala numérica para su análisis. Se usó una prueba de U de Mann-Whitney con el fin de evaluar diferencias entre estudiantes de ambas facultades. Resultados: Los estudiantes en conjunto mostraron tener una buena opinión de la importancia de las ciencias básicas en la práctica clínica. Se observó también que es mayor la proporción de estudiantes de odontología que consideran que la investigación básica no es útil para su práctica clínica. Conclusión: Los estudiantes consideran las ciencias básicas necesarias para un buen desempeño profesional.

Introduction: The benefit of basic science courses may depend on students' perceptions of the importance of these courses in their professional life, therefore, it's necessary to determine the degree of importance that students give to this type of courses. Materials and methods: A questionnaire with 9 statements was presented to 54 dental and medical students. The responses were converted to a numerical scale for analysis. Using a Mann-Whitney U test, differences between students from both faculties were evaluated. Results: The students showed a good opinion of the importance of basic sciences in clinical practice. It was also observed that the proportion of dental students who consider that basic research is not useful for their clinical practice is higher. Conclusion: Students consider the basic sciences necessary for good professional performance.

Somatic Copy Number Alterations in Colorectal Cancer Lead to a Differentially Expressed ceRNA Network (ceRNet).

Colorectal cancer (CRC) represents the second deadliest malignancy worldwide. Around 75% of CRC patients exhibit high levels of chromosome instability that result in the accumulation of somatic copy number alterations. These alterations are associated with the amplification of oncogenes and deletion of tumor-ppressor genes and contribute to the tumoral phenotype in different malignancies. Even though this relationship is well known, much remains to be investigated regarding the effect of said alterations in long non-coding RNAs (lncRNAs) and, in turn, the impact these alterations have on the tumor phenotype. The present study aimed to evaluate the role of differentially expressed lncRNAs coded in regions with copy number alterations in colorectal cancer patient samples. We downloaded RNA-seq files of the Colorectal Adenocarcinoma Project from the The Cancer Genome Atlas (TCGA) repository (285 sequenced tumor tissues and 41 non-tumor tissues), evaluated differential expression, and mapped them over genome sequencing data with regions presenting copy number alterations. We obtained 78 differentially expressed (LFC > 1|< -1, padj < 0.05) lncRNAs, 410 miRNAs, and 5028 mRNAs and constructed a competing endogenous RNA (ceRNA) network, predicting significant lncRNA-miRNA-mRNA interactions. Said network consisted of 30 lncRNAs, 19 miRNAs, and 77 mRNAs. To understand the role that our ceRNA network played, we performed KEGG and GO analysis and found several oncogenic and anti-oncogenic processes enriched by the molecular players in our network. Finally, to evaluate the clinical relevance of the lncRNA expression, we performed survival analysis and found that C5orf64, HOTAIR, and RRN3P3 correlated with overall patient survival. Our results showed that lncRNAs coded in regions affected by SCNAs form a complex gene regulatory network in CCR.

Factors associated with emergency room readmission after elective surgery for ovarian carcinoma.

BACKGROUND: Hospital readmission is a quality metric of hospital care and has been studied in ovarian carcinoma, but its evaluation has several limitations. Also, emergency room (ER) readmission is considered an adverse effect because it represents patient costs. Therefore, our objective was to determine the rate of ER readmission, its causes, and associated factors. METHODS: A retrospective study of 592 patients with ovarian carcinoma who underwent upfront surgery, neoadjuvant therapy, or surgery for recurrent disease. An analysis of factors associated with ER readmission, hospital readmission, and surgical complications was performed, including multivariate analysis to assess for case-mix factors. RESULTS: Of 592 patients, the median age was 51 years, and the predominant type of treatment was the neoadjuvant approach (52.9%); 46% underwent upfront surgeries and six surgeries for recurrence. The ratio to ER readmission was 11.8% (70 patients), of whom 12 patients were admitted more than once. The factors associated with ER readmission were prolonged surgery, intraoperative bleeding, extended hospital stay, the time of the day when the surgery was performed, and post-surgical complications. The hospital readmissions were 4.2%, and the overall morbidity was 17.6%. In the multivariate analysis, the only factor associated with ER readmission was the presence of surgical complications (OR = 39.01). The factors independently associated with hospital readmission were the entrance to the intensive care unit (OR = 1.37), the presence of surgical complications (OR = 2.85), and ER readmission (OR = 1.45). CONCLUSION: ER readmission is an adverse event representing the presence of symptoms/complications in patients. Evaluating the ER readmission independently of the readmission to the hospital is critical because it will allow modifying medical care behaviors to prevent patients from unnecessarily returning to the hospital after a hospital discharge to manage preventable medical problems. TRIAL REGISTRATION: researchregistry7882.

Pathogenic variant profile in DNA damage response genes correlates with metastatic breast cancer progression-free survival in a Mexican-mestizo population.

Introduction: Metastatic breast cancer causes the most breast cancer-related deaths around the world, especially in countries where breast cancer is detected late into its development. Genetic testing for cancer susceptibility started with the BRCA 1 and 2 genes. Still, recent research has shown that variations in other members of the DNA damage response (DDR) are also associated with elevated cancer risk, opening new opportunities for enhanced genetic testing strategies. Methods: We sequenced BRCA1/2 and twelve other DDR genes from a Mexican-mestizo population of 40 metastatic breast cancer patients through semiconductor sequencing. Results: Overall, we found 22 variants -9 of them reported for the first time- and a strikingly high proportion of variations in ARID1A. The presence of at least one variant in the ARID1A, BRCA1, BRCA2, or FANCA genes was associated with worse progression-free survival and overall survival in our patient cohort. Discussion: Our results reflected the unique characteristics of the Mexican-mestizo population as the proportion of variants we found differed from that of other global populations. Based on these findings, we suggest routine screening for variants in ARID1A along with BRCA1/2 in breast cancer patients from the Mexican-mestizo population.

Influence of luminal and basal subtype in prognosis of high-grade non muscle invasive urothelial carcinoma.

BACKGROUND: Recent studies have shown that the classification of high-grade urothelial carcinoma non-muscle invasive (HGBCNMI) based on molecular subtypes might be a valuable strategy to identify patients with a worse clinical prognosis. OBJECTIVE: Determine the effect of the luminal and basal molecular subtype determined by immunistochemical on prognosis in patients with HGBC in Mexican population. METHODS: Phenotypes were evaluated by immunohistochemical staining of luminal (GATA3, FOXA1) and basal (CK5/6, CK14) markers in paraffin-embedded tissue samples from 45 patients with a diagnosis of HGBCNMI treated at Instituto Nacional de Cancerología-México (INCan) between 2009 and 2019. The association with prognosis was evaluated using Kaplan-Meier curves and multivariable-adjusted Cox models. RESULTS: HGBCNMI patients showed mean age of 58.77 years (SD: ±12.08 years). We identified expression of the luminal molecular subtype in 35 cases (77.78 %), and 10 cases (22.22 %) with "combined" expression of the molecular subtype (basal and luminal expression). The combined phenotype was statistically more frequent in metastatic cases (p-value = 0.028). In Kaplan-Meier curves, combined expression of luminal and basal molecular markers was associated with disease progression (p-value = 0.002, log-rank test). Cox regression models confirmed this association, which was not influenced by age (p-value = 0.007) or gender (p-value = 0.007). No association of phenotypes with overall survival (p-value = 0.860) or relapse (p-value = 0.5) was observed. CONCLUSION: The combined expression of immunohistochemical markers of the luminal and basal subtype might be considered as predictor for disease progression in patients with HGBCNMI in Mexican population.

Mutational Landscape of Bladder Cancer in Mexican Patients: KMT2D Mutations and chr11q15.5 Amplifications Are Associated with Muscle Invasion.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute-Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and exome sequenced. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

A Pathogenic Variant Reclassified to the Pseudogene PMS2P1 in a Patient with Suspected Hereditary Cancer.

The PMS2 gene is involved in DNA repair by the mismatch repair pathway. Deficiencies in this mechanism have been associated with Lynch Syndrome (LS), which is characterized by a high risk for colorectal, endometrial, ovarian, breast, and other cancers. Germinal pathogenic variants of PMS2 are associated with up to 5% of all cases of LS. The prevalence is overestimated for the existence of multiple homologous pseudogenes. We report the case of a 44-year-old woman diagnosed with breast cancer at 34 years without a relevant cancer family history. The presence of pathogenic variant NM_000535.7:c.1A > T, (p.Met1Leu) in PMS2 was determined by next-generation sequencing analysis with a panel of 322 cancer-associated genes and confirmed by capillary sequencing in the patient. The variant was determined in six family members (brothers, sisters, and a son) and seven non-cancerous unrelated individuals. Analysis of the amplified region showed high homology of PMS2 with five of its pseudogenes. We determined that the variant is associated with the PMS2P1 pseudogene following sequence alignment analysis. We propose considering the variant c.1A > T, (p.Met1Leu) in PMS2 for reclassification as not hereditary cancer-related, given the impact on the diagnosis and treatment of cancer patients and families carrying this variant.

Analysis of Mexican young women with primary ovarian insufficiency induced by gynaecological and haematological cancer management.

This was a retrospective study that included 114 women younger than 40 years with induced primary ovarian insufficiency. Patients who presented vasomotor symptoms had a higher proportion (26 [63.41%] versus 58 [79.45%], OR 2.23, 95% CI 0.95-5.23, p = .065) to initiate hormone replacement therapy. Vasomotor symptoms were present in patients with ovarian cancer (OR 0.27, 95% CI 0.09-0.8, p = .18), haematologic cancer (OR 0.11, 95% CI 0.2-0.65, p = .014), radiotherapy (OR 2.62, 95% CI 1.04-6.54, p = .039) and chemotherapy with radiotherapy (OR 2.72, 95% CI 1.01-7.35, p = .049). Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy, and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms.Impact StatementWhat is already known on this subject? In young women with cancer, induced primary ovarian insufficiency can result as an ovarian surgery or as an adverse effect of chemotherapy or radiotherapy. Regardless of aetiology, patients are going to manifest early climacteric symptoms with an increased risk for cardiovascular disease, metabolic syndrome and osteoporosis.What do the results of this study add? Patients who presented vasomotor symptoms had initially a higher proportion of hormone replacement therapy. Patients that were treated exclusively with radiotherapy or with chemotherapy and concomitant radiotherapy have a significantly increased risk to manifest vasomotor symptoms.What are the implications of these findings for clinical practice and/or future research? Having ovarian or haematological cancer, being managed with radiotherapy and/or chemotherapy and having follicle-stimulating hormone parameters higher than 35 mUI/mL are factors that significantly increase the risk of presenting vasomotor symptoms.

Expression of DNA Methyltransferase 3B Isoforms Is Associated with DNA Satellite 2 Hypomethylation and Clinical Prognosis in Advanced High-Grade Serous Ovarian Carcinoma.

Alterations in DNA methylation are critical for the carcinogenesis of ovarian tumors, especially ovarian carcinoma (OC). DNMT3B, a de novo DNA methyltransferase (DNMT), encodes for fifteen spliced protein products or isoforms. DNMT3B isoforms lack exons for the catalytic domain, with functional consequences on catalytic activity. Abnormal expression of DNMT3B isoforms is frequently observed in several types of cancer, such as breast, lung, kidney, gastric, liver, skin, leukemia, and sarcoma. However, the expression patterns and consequences of DNMT3B isoforms in OC are unknown. In this study, we analyzed each DNMT and DNMT3B isoforms expression by qPCR in 63 OC samples and their association with disease-free survival (DFS), overall survival (OS), and tumor progression. We included OC patients with the main histological subtypes of EOC and patients in all the disease stages and found that DNMTs were overexpressed in advanced stages (p-value < 0.05) and high-grade OC (p-value < 0.05). Remarkably, we found DNMT3B1 overexpression in advanced stages (p-value = 0.0251) and high-grade serous ovarian carcinoma (HGSOC) (p-value = 0.0313), and DNMT3B3 was overexpressed in advanced stages (p-value = 0.0098) and high-grade (p-value = 0.0004) serous ovarian carcinoma (SOC). Finally, we observed that overexpression of DNMT3B isoforms was associated with poor prognosis in OC and SOC. DNMT3B3 was also associated with FDS (p-value = 0.017) and OS (p-value = 0.038) in SOC patients. In addition, the ovarian carcinoma cell lines OVCAR3 and SKOV3 also overexpress DNMT3B3. Interestingly, exogenous overexpression of DNMT3B3 in OVCAR3 causes demethylation of satellite 2 sequences in the pericentromeric region. In summary, our results suggest that DNMT3B3 expression is altered in OC.