Design and Development of a Heterogeneous Active Assisted Living Solution for Monitoring and Following Up with Chronic Heart Failure Patients in Spain.

Heart failure is the most common disease among elderly people, and the risk increases with age. The use of smart Internet of Things (IoT) systems for monitoring patients with chronic heart failure (CHF) in a non-intrusive manner can result in better control of the disease, improving proactive healthcare through real-time and historical patient's data, promoting self-care in patients, reducing unneeded interaction between patients and doctors, reducing the number of hospitalizations and saving healthcare costs. This work presents an active assisted living (AAL) solution based on the IoT to provide a tele-assistance platform for CHF patients from the public health service of the region of Murcia in Spain, with formal and informal caregivers and health professionals also as key actors. In this article, we have detailed the methodology, results, and conclusions of the prevalidation phase for the set of IoT technologies to be integrated in the AAL platform, the first mandatory step before the deployment of a large-scale pilot that will lead to improving the innovation of the system from its current technology readiness level to the market. The work presented, in the framework of the H2020 Pharaon project, aims to serve as inspiration to the R&D community for the design, development, and deployment of AAL solutions based on heterogeneous IoT technologies, or similar approaches, for smart healthcare solutions in real healthcare institutions.

Gynecologic cancer surveillance in the era of SARS-CoV-2 (COVID-19).

The SARS-CoV-2 (COVID-19) pandemic has significantly impacted the management of patients with gynecologic cancers. Many centers have reduced access to routine visits to avoid crowded waiting areas and specially to reduce the infection risk for oncologic patients. The goal of this review is to propose a surveillance algorithm for patients with gynecologic cancers during the COVID-19 pandemic based on existing evidence and established guidelines. It is time to consider strategies based on telemedicine and to adapt protocols in this new era. We hereby propose a strategy for routine surveillance both during and beyond the pandemic.

Impact of a community contraceptive counselling intervention on adolescent fertility rates: a quasi-experimental study.

BACKGROUND: From 2000 to 2008, in urban areas in Spain, adolescent fertility and abortion rates underwent unprecedented increases, consecutive to intensive immigration from developing countries. To address unmet needs for contraception information and services, a community-based, gender-sensitive and culturally adapted brief counselling intervention (SIRIAN program) was launched in some deprived neighbourhoods with a high proportion of immigrants in Barcelona. Once a randomized controlled trial demonstrated its effectiveness in increasing the use of contraceptives, we aim to examine its population impact on adolescent fertility rates. METHODS: Quasi-experimental study with comparison group, using population data from 2005 to 2016. Five neighbourhoods in the lowest tercile of Disposable Household Income were intervened in 2011-13. The comparison group included the three neighbourhoods which were in the same municipal district and in the lowest Disposable Household Income tercile, and displayed the highest adolescent fertility rates. Generalized linear models were fitted to assess absolute adolescent fertility rates and adjusted by immigrant population between pre-intervention (2005-10) and post-intervention periods (2011-16); Difference in Differences and relative pre-post changes analysis were performed. RESULTS: In 2005-10 the intervention group adolescent fertility rate was 27.90 (per 1000 women 15-19) and 21.84 in the comparison group. In 2011-16 intervention areas experienced great declines (adolescent fertility rate change: - 12.30 (- 12.45 to - 12.21); p < 0.001), while comparison neighbourhoods remained unchanged (adolescent fertility rate change: 1.91 (- 2.25 to 6.07); p = 0.368). A reduction of - 10.97 points (- 13.91 to - 8.03); p < 0.001) is associated to the intervention. CONCLUSION: Adolescent fertility rate significantly declined in the intervention group but remained stable in the comparison group. This quasi-experimental study provide evidence that, in a country with universal health coverage, a community counselling intervention that increases access to contraception, knowledge and sexual health care in hard-to-reach segments of the population can contribute to substantially reduce adolescent fertility rates. Reducing adolescent fertility rates could become a feasible goal in cities with similar conditions.

Role of Chlamydia trachomatis serology in conservative management of cervical intraepithelial neoplasia grade 2.

OBJECTIVE: To evaluate the spontaneous progression of cervical intraepithelial neoplasia grade 2 (CIN2) in accordance with Chlamydia trachomatis (chlamydia) serology. METHODS: A prospective observational study included women diagnosed with CIN2 by cervical biopsy and managed conservatively for 24 months at Hospital del Mar, Barcelona, between December 2011 and October 2013. Serum anti-chlamydia immunoglobulin G (IgG), previous cytology, and high-risk human papillomavirus (HPV) genotyping were recorded at baseline. The outcome was regression, persistence, or progression of CIN2. RESULTS: Overall, 93 women aged 18-56 years were enrolled. Spontaneous regression was observed for 61 (66%) women, and 21 (23%) progressed to CIN3. Eight (9%) women had chlamydia seropositivity at baseline. Multivariate analysis showed that anti-chlamydia IgG seropositivity (odds ratio [OR], 19.1; 95% confidence interval [CI], 1.9-189.7), previous high-grade squamous intraepithelial lesion cytology (OR, 5.0; 95% CI, 1.7-14.6), and HPV16 (OR, 4.8; 95% CI, 1.7-13.7) increased the risk of CIN2 persistence or progression. CONCLUSION: Women with CIN2 and chlamydia IgG seropositivity had increased risk of progression to CIN2+ and immediate treatment may be recommended for these women. Larger clinical studies are needed to confirm the results, but chlamydia serology might be introduced into CIN2 management to better individualize treatment.

Circulating miRNAs, isomiRs and small RNA clusters in human plasma and breast milk.

Circulating small RNAs, including miRNAs but also isomiRs and other RNA species, have the potential to be used as non-invasive biomarkers for communicable and non-communicable diseases. This study aims to characterize and compare small RNA profiles in human biofluids. For this purpose, RNA was extracted from plasma and breast milk samples from 15 healthy postpartum mothers. Small RNA libraries were prepared with the NEBNext® small RNA library preparation kit and sequenced in an Illumina HiSeq2000 platform. miRNAs, isomiRs and clusters of small RNAs were annotated using seqBuster/seqCluster framework in 5 plasma and 10 milk samples that passed the initial quality control. The RNA yield was 81 ng/mL [standard deviation (SD): 41] and 3985 ng/mL (SD: 3767) for plasma and breast milk, respectively. Mean number of good quality reads was 4.04 million (M) (40.01% of the reads) in plasma and 12.5M (89.6%) in breast milk. One thousand one hundred eighty two miRNAs, 12,084 isomiRs and 1,053 small RNA clusters that included piwi-interfering RNAs (piRNAs), tRNAs, small nucleolar RNAs (snoRNA) and small nuclear RNAs (snRNAs) were detected. Samples grouped by biofluid, with 308 miRNAs, 1,790 isomiRs and 778 small RNA clusters differentially detected. In summary, plasma and milk showed a different small RNA profile. In both, miRNAs, piRNAs, tRNAs, snRNAs, and snoRNAs were identified, confirming the presence of non-miRNA species in plasma, and describing them for the first time in milk.

Effects of a counselling intervention to improve contraception in deprived neighbourhoods: a randomized controlled trial.

Background: This study aims to evaluate the effects of a community-based counselling intervention to improve contraception use among immigrant and native residents in deprived neighbourhoods. Methods: Randomized controlled trial. Women aged 14-49 years and men aged 14-39 years from two low-income neighbourhoods with high proportion of immigration in Barcelona (Catalonia, Spain) who had not undergone irreversible contraception and were not planning a pregnancy were recruited (2011-13). A culturally developed and theoretically based brief counselling intervention was delivered in community settings. The primary outcome was the consistent use of effective contraceptive methods (optimal use). Secondary outcomes were the incorrect use of effective methods and the use of less effective methods stratified by sex and migrant status. Differences within subgroups from baseline to the 3-month follow-up were analysed by intention to treat and per protocol. The effects were assessed with adjusted robust Poisson regressions. Results: The study enrolled and randomized 746 eligible participants. There were no differences between the intervention and control groups in demographic characteristics. Optimal use significantly increased in men, women, immigrants and natives in the intervention group, with no changes in the control group. In the intervention group, inconsistent use of effective methods decreased by 54.9% and that of less effective methods by 47.2%. The overall adjusted prevalence ratio of optimal use in the intervention group versus the control group was 1.138 (95% CI: 1.010-1.284). Conclusion: This brief counselling intervention increased the consistent use of effective contraception in low-income neighbourhoods with a high proportion of immigration.

Imaging and pathology features to predict axillary tumor load in breast cancer.

AIM: We investigated if imaging and pathology features could help to identify a high axillary tumor burden (ATB) in breast cancer patients, in order to individualize decisions on axillary lymph node (ALN) dissection (ALND). METHODS: We retrospectively analyzed patients primarily treated with surgery in our unit between 2011 and 2014. We divided the patients in two groups: low ATB (LATB) if ≤ 2 ALN were infiltrated and high ATB (HATB) if > 2 ALN were infiltrated. RESULTS: Data of 105 patients was included in the study. Axillary ultrasound (AUS) features associated with HATB were any sign of ALN infiltration (76 vs 24%, P = 0.027) and > 2 suspicious ALNs (73% vs 27%, P = 0.018); however, when AUS revealed ≤ 2 suspicious ALNs, 39% of these patients had HATB. Any sign of ALN infiltration on magnetic resonance imaging was associated with HATB (48% vs 52%, P = 0.031). Positive preoperative ALN cytology or biopsy was associated with HATB (53% vs 47%, P = 0.008), while p53 positivity (80% vs 20%) and high histological grade (68% vs. 32%) correlated with LATB (P = 0.05 and P = 0.02, respectively). In multivariate analysis, only positive preoperative ALN cytology or biopsy was associated with HATB (P = 0.038). CONCLUSIONS: AUS was useful for detecting HATB but was not as effective in patients with LATB. Proving axillary infiltration with AUS-directed cytology or biopsy is the most effective method to predict HATB.

Utility of Human Papillomavirus Genotyping in the Management of Low-Grade Squamous Intraepithelial Lesions.

OBJECTIVE: The aim of the study was to determine the usefulness of human papillomavirus (HPV) partial genotyping test in the triage of newly diagnosed low-grade squamous intraepithelial lesions (LSILs). MATERIALS AND METHODS: We analyzed 143 patients with LSIL diagnosed de novo. Lesions were classified as positive for HPV 16 or HPV 18, positive for HPV but not HPV 16 or HPV 18 (HPVno16no18) or no HPV detected (HPVneg). Patients were followed for a period of 2 years or until the lesion progressed. We calculated absolute and relative risks for progression and regression according to the HPV result. RESULTS: The mean (SD) age was 33.8 (11.1) years. A total of 19.6% were positive for HPV 16, 4.9% for HPV 18, and 63.6% for HPVno16no18. The absolute risk of HPV 16 for progression to cervical intraepithelial neoplasia grade 2 or more (CIN 2+) was 32.1%, 14.3% for HPV 18, and 5.8% for HPVno16no18. None of the HPVneg cases evolved to CIN 2+. The presence of HPV 16 conferred a 7.4 (95% CI = 2.7-20.3) times greater risk of developing CIN 2+ than its absence. The absolute risks for HPV 16, HPV 18, HPVno16no18, and HPVneg for regression were 53.6%, 57.1%, 75.4%, and 87.5%, respectively. Relative risks for regression were 0.7 (95% CI = 0.5-0.9) for HPV 16 and 1.3 (95% CI = 1.1-1.5) for HPVneg. CONCLUSIONS: The HPV 16 LSILs are more likely to progress to CIN 2+, so tight control and immediate colposcopy are crucial, whereas when HPV 16 is not present, follow-up could be less strict. Low-grade squamous intraepithelial lesions in which high-risk HPV is not detected do not progress to CIN 2+, so its control should be different from other LSIL, and conservative management could be an acceptable strategy.

Perinatal outcomes in children born after fresh or frozen embryo transfer: a Catalan cohort study based on 14,262 newborns.

OBJECTIVE: To ascertain whether perinatal outcomes are affected by vitrification and/or controlled ovarian hyperstimulation (COH). DESIGN: Register-based cohort study. SETTING: Not applicable. PATIENT(S): Women undergoing in vitro fertilization (IVF) between 2008 and 2012 using autologous or donated eggs who had a singleton pregnancy delivered from the 24th week onward. INTERVENTION(S): Fresh embryo transfer (ET) or frozen-thawed ET in women undergoing IVF. MAIN OUTCOME MEASURE(S): Primary outcome birthweight, and secondary outcomes gestational age at delivery, small for gestational age, mode of delivery, and perinatal mortality. RESULT(S): In the autologous egg population, newborns from the fresh ET group had lower birthweight than the frozen-thawed ET group (3,152.9 ± 545.5g and 3,343.2 ± 532.3g, respectively), and this difference persisted even after adjusting for confounding factors, and the newborns had a higher risk of being small for gestational age (SGA). In contrast, among egg-donor recipients undergoing ET, the mean birthweight did not differ between the groups (3,165 ± 604.15 g and 3,143.60 ± 604.21g in the fresh and frozen-thawed ET groups, respectively); however, in the adjusted regression model birthweight was statistically significantly higher in the fresh ET group than the frozen-thawed ET group. The risk of SGA remained comparable between the fresh versus frozen-thawed ET groups. We observed no statistically significant differences in perinatal mortality between groups either in the autologous egg population or in the donor recipient group. CONCLUSION(S): Perinatal outcomes are negatively affected by COH and not affected by the vitrification process.

The impact of endometriosis on the outcome of Assisted Reproductive Technology.

BACKGROUND: Endometriosis has been described to impair fertility through various mechanisms. However, studies evaluating the reproductive outcomes of women undergoing assisted reproductive technologies show controversial results. The aim of this study is to assess whether the reproductive outcome is impaired among women with endometriosis-associated infertility undergoing IVF. METHODS: A retrospective cohort study was performed, including women undergoing IVF reported by the Red Latinoamericana de Reproduccion Asistida (Redlara) registry, between January 2010 and December 2012. The study group included women with endometriosis-associated infertility, and the control group women with tubal factor, endocrine disorders or unexplained infertility. Women above 40 years, severe male factor and premature ovarian failure were excluded. The reproductive outcomes of between both groups were compared. The primary outcome was live birth. Secondary outcomes included clinical pregnancy, miscarriage, number of oocytes retrieved and number of fertilized oocytes. Outcomes were assessed after the first fresh IVF cycle, and were adjusted for age and number of embryos transferred. RESULTS: A total of 22.416 women were included (3.583 with endometriosis and 18.833 in the control group). Mean age of patients in the endometriosis group and control group was 34.86 (3.47) and 34.61 (3.91) respectively, p = 0.000. The mean number of oocytes retrieved were 8.89 (6.23) and 9.86 (7.02) respectively, p = 0.000. No significant differences were observed between groups in terms of live birth (odds ratio (OR) 1.032, p = 0.556), clinical pregnancy (OR 1.044, p = 0.428) and miscarriage rates (OR 1.049, p = 0.623). Women with endometriosis had significantly lower number of oocytes retrieved (incidence risk ratio (IRR) 0.917, 95% CI 0.895-0.940), however, the number of fertilized oocytes did not differ among the two groups when adjusting for the number of oocytes retrieved (IRR 1.003, p = 0.794). An age-stratified analysis was performed, and no differences were observed in the reproductive outcomes between groups for women aged under 35 and 35 to 40. CONCLUSIONS: Reproductive outcomes among women undergoing IVF and diagnosed with endometriosis-associated infertility do not differ significantly from women without the disease. Although women with endometriosis generate fewer oocytes, fertilization rate is not impaired and the likelihood of achieving a live birth is also not affected.

Usefulness of p16INK4a staining for managing histological high-grade squamous intraepithelial cervical lesions.

p16INK4a (p16) tumor-suppressor protein is a biomarker of human papillomavirus (HPV) oncogenic activity that has revealed a high rate of positivity in histological high-gade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 2 (HSIL/CIN2) lesions. However, there is a paucity of data regarding p16 status as a surrogate marker of HSIL/CIN2 evolution. The aim of this study was to evaluate the outcome of HSIL/CIN2 patients followed up without treatment for 12 months according to p16 immunohistochemical staining. Patients diagnosed with HSIL/CIN2 colposcopy-directed biopsy, were recruited prospectively between December 2011 and October 2013. p16 staining was performed in all HSIL/CIN2 diagnostic biopsies. Follow-up was conducted every 4 months by cytology, colposcopy and biopsy if suspicion of progression and once the 12 months of follow-up completed. Complete regression, partial regression, persistence, and progression rates of HSIL/CIN2 were defined as a final outcome. A total of 96 patients were included in the analysis. The rate of spontaneous regression was 64%, while 28% had persistent disease, and 8% progressed at 12 months of follow-up. p16 was positive in 81 (84%) initial HSIL/CIN2 biopsies. Regression was observed in all 15 p16 negative cases and in 46 of 81 (57%) p16 positive cases (P=0.001). In conclusion, patients with p16 negative HSIL/CIN2 biopsy had a high rate of regression during first 12 months of follow-up. Status of p16 staining could be considered for HSIL/CIN2 management.

Mammographic extent of microcalcifications and oestrogen receptor expression affect preoperative breast carcinoma in situ size estimation.

BACKGROUND: The aim of our study was to establish which clinical, radiologic and pathologic factors could predict the risk of under- and overestimation of the breast ductal carcinoma in situ (DCIS) size when preoperatively measuring the maximum mammographic extent of microcalcifications (MEM). METHODS: We made a retrospective review of patients with a DCIS treated in our Breast Unit between May 2005 and May 2012. Clinical, pathologic and radiologic data were evaluated as possible predictive factors for over- or underestimation of DCIS size when measuring MEM. RESULTS: We obtained precise measurements of MEM in 82 patients (84 DCIS lesions). Maximum MEM measurement correctly estimated maximum pathology size in 57 lesions (68.7 %). Patients with a correctly estimated DCIS, with an underestimated DCIS and with an overestimated DCIS significantly differed in DCIS ER expression (p = 0.022) and in maximum MEM measurement (p = 0.000). Constructing two ROC curves, we found that a maximum MEM measurement ≥25 mm and ER expression ≥90 % were both discrimination points for overestimation and ER ≤ 45 % was a discrimination point for underestimation. Using these cutoff points, we defined four groups of patients with different risks of over- and underestimation. CONCLUSIONS: Risk of over- or underestimation of DCIS size through MEM measurement depends on DCIS ER expression and MEM itself. Identifying which patients are at a significant risk of over- or underestimation could help the breast surgeon when discussing the surgical options with the patient.

Role of First-Trimester HbA1c as a Predictor of Adverse Obstetric Outcomes in a Multiethnic Cohort.

Context: Risk of obstetric complications increases linearly with rising maternal glycemia. Testing hemoglobin A1c (HbA1c) is an effective option to detect hyperglycemia, but its association with adverse pregnancy outcomes remains unclear. Emerging data sustain that an early HbA1c ≥5.9% could act as a pregnancy risk marker. Objective: To determine, in a multiethnic cohort, whether an early ≥5.9% HbA1c could be useful to identify women without diabetes mellitus at increased pregnancy risk. Design and Setting: A prospective study was conducted at Hospital del Mar, Barcelona, between April 2013 and September 2015. Patients and Intervention: A total of 1631 pregnant women had an HbA1c measurement added to their first antenatal blood tests and were screened for gestational diabetes mellitus at 24 to 28 weeks' gestation. Outcome Measures: Primary outcome was macrosomia. Secondary outcomes were preeclampsia, preterm birth, and cesarean section rate. Results: A total of 1228 pregnancies were included for outcome analysis. Women with HbA1c ≥5.9% (n = 48) showed a higher rate of macrosomia (16.7% vs 5.9%, P = 0.008) and a tendency toward a higher rate of preeclampsia (9.32% vs 3.9%, P = 0.092). There were no statistically significant differences in other pregnancy outcomes. After adjusting for potential confounders, an HbA1c ≥5.9% was independently associated with a 3-fold increased risk of macrosomia (95% confidence interval, 1.127 to 8.603, P = 0.028) and preeclampsia (95% confidence interval, 1.086 to 11.532, P = 0.036). Conclusions: In a multiethnic population, an early HbA1c ≥5.9% measurement identifies women at high risk for poorer pregnancy outcomes independently of gestational diabetes mellitus diagnosis later in pregnancy. Further studies are required to establish cutoff points adapted to each ethnic group and to assess whether early detection and treatment are of benefit.

Value of p16(INK4a) and Ki-67 Immunohistochemical Staining in Cervical Intraepithelial Neoplasia Grade 2 Biopsies as Biomarkers for Cervical Intraepithelial Neoplasia Grade 3 in Cone Results.

OBJECTIVE: To evaluate the usefulness of p16(INK4a) (p16) and Ki-67 staining in high-grade cervical intraepithelial neoplasia (CIN2) biopsies in order to predict CIN3 results in cone specimens, thereby sparing those not likely at risk for CIN3 from unnecessary cone excision. STUDY DESIGN: We retrospectively recruited patients with CIN2 colposcopy-directed biopsy treated by loop electrosurgical excision procedure. The expression of p16 and Ki-67 was qualitatively and quantitatively analyzed in all biopsies and cone specimens. RESULTS: A total of 123 patients from January 2009 to December 2010 were included in the study. CIN3 in cone specimens was observed in 35 patients (28.5%). Ki-67 positive immunostaining in > 50% of epithelial cells was related to CIN3 diagnoses in cone specimens (p = 0.043). However, p16+ and Ki-67+ evaluated by thirds of the epithelial thickness in CIN2 biopsies did not show a significant correlation with the cone results. In multivariate analysis, Ki-67 cell expression over 50% in CIN2 biopsies and high-grade squamous intraepithelial lesion (HSIL) in the previous cytology were statistically associated with CIN3 results in the cone (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.04-6.29; OR 2.68, 95% CI 1.07-6.72, respectively). CONCLUSION: Patients with HSIL in the previous cytology and Ki-67 cell expression over 50% in their CIN2 biopsies could be considered in need of treatment by cone for their higher risk of underlying CIN3 lesions.

[Relationship between lipid alterations during pregnancy and adverse pregnancy outcomes]. / Comportamiento de los lípidos durante la gestación y su relación con acontecimientos obstétricos desfavorables.

Lipids play an important role during pregnancy, and in this period major changes occur in lipoprotein metabolism. During the third trimester plasma cholesterol and triglyceride levels are substantially increased, returning to normal after delivery. Described associations between increased morbidity during pregnancy and excessive increases in plasma cholesterol and triglycerides. For this reason we have reviewed the relationship between lipid alterations, preeclampsia, gestational diabetes and preterm birth. The overall metabolic control can improve pregnancy outcomes, and the assessment of supraphysiological changes in lipid profile will classify pregnancy risk at a higher level, which would entail a stricter control.

Ultrasound-Guided Aspiration With and Without Ethanol Sclerotherapy in the Management of Simple Adnexal Cysts: A Single-Center Experience.

STUDY OBJECTIVES: To compare the efficacy of ultrasound-guided aspiration versus aspiration with ethanol sclerotherapy in the management of simple adnexal cysts measuring 3 to 10 cm, and to explore the risk factors for recurrence associated with each approach. DESIGN: A prospective follow-up of patients after cyst aspiration with and without ethanol sclerotherapy in simple adnexal cysts in a single-center trial (Canadian Task Force classification II-1). SETTING: Bellvitge Teaching Hospital, Barcelona, Spain. PATIENTS: Cyst aspiration and ethanol sclerotherapy were performed in 66 and 75 patients, respectively, between 2002 and 2014. Women enrolled before March 2009 underwent simple aspiration (group 1), and those enrolled after March 2009 underwent ethanol sclerotherapy (group 2). INTERVENTIONS: Ultrasound-guided fine-needle aspiration with and without ethanol sclerotherapy. MEASUREMENTS AND MAIN RESULTS: Potential risk factors for recurrence-age, menopausal status, symptoms, cyst diameter, laterality, aspirated volume, simple US-guided aspiration or alcohol sclerotherapy, and complications-were analyzed by logistic regression. The recurrence rates were analyzed by the Kaplan-Meier and Mantel-Haenszel methods. The overall recurrence rates were 72.7% (48 of 66) in group 1 and 22.7% (17 of 75) in group 2 (p < .0001). Risk factors significantly associated with recurrence were simple aspiration without ethanol sclerotherapy (odds ratio [OR], 19.7; 95% confidence interval [CI], 6.756-57.714), postmenopausal status (OR, 9.3; 95% CI, 1.720-50.956), and cyst size (OR, 1.04; 95% CI, 1.005-1.093). CONCLUSION: Based on the lower recurrence rate, ethanol sclerotherapy was more efficacious than simple aspiration in the management of simple adnexal cysts measuring <10 cm.

Nidogen 1 and Nuclear Protein 1: novel targets of ETV5 transcription factor involved in endometrial cancer invasion.

Endometrial cancer is the most frequent malignancy of the female genital tract in western countries. Our group has previously characterized the upregulation of the transcription factor ETV5 in endometrial cancer with a specific and significant increase in those tumor stages associated with myometrial invasion. We have shown that ETV5 overexpression in Hec1A endometrial cancer cells induces epithelial to mesenchymal transition resulting in the acquisition of migratory and invasive capabilities. In the present work, we have identified Nidogen 1 (NID1) and Nuclear Protein 1 (NUPR1) as direct transcriptional targets of ETV5 in endometrial cancer cells. Inhibition of NID1 and NUPR1 in ETV5 overexpressing cells reduced cell migration and invasion in vitro and reduced tumor growth and dissemination in an orthotopic endometrial cancer model. Importantly, we confirmed a significant increase of NUPR1 and NID1 protein expression in the invasion front of the tumor compared to their paired superficial zone, concomitant to ETV5 overexpression. Altogether, we conclude that NID1 and NUPR1 are novel targets of ETV5 and are actively cooperating with ETV5 at the invasion front of the tumor in the acquisition of an invasive phenotype to jointly drive endometrial cancer invasion.

p53 expression in breast cancer predicts tumors with low probability of non-sentinel nodes infiltration.

AIM: Several predictive tools of non-sentinel lymph nodes neoplastic involvement when a positive sentinel lymph node is found have been described. However, molecular factors have been rarely evaluated to build these tools. The aim of this study was to establish which factors predicted non-sentinel lymph nodes infiltration in our setting, including some molecular factors. MATERIAL AND METHODS: We carried out a retrospective review of 161 patients with breast cancer and a positive sentinel lymph node who had undergone axillary lymph node dissection, none of whom had received neoadjuvant treatment. Features evaluated as predictive factors for non-sentinel node positivity were: menopausal status, tumor size, histological subtype, histological grade, lymphovascular invasion, extracapsular invasion, Ki67 index, hormonal receptors, CerbB2 and p53 expression, size of sentinel lymph node metastases and number of sentinel lymph nodes affected. RESULTS: Tumor size (P = 0.001), size of sentinel lymph node metastases (P = 0.001), lobular invasive carcinoma (P = 0.05) and lymphovascular invasion (P = 0.006) were significantly associated with non-sentinel lymph node positivity. Tumor p53 positive expression was strongly associated with non-sentinel lymph node negativity (P = 0.000). In multivariate analysis, all these factors but tumor size maintained their significance. The discrimination power of the model calculated by the area under the receiver-operator curve was 0.811 (95% confidence interval, 0.741-0.880). CONCLUSION: p53 expression in breast cancer was highly predictive of non-sentinel lymph node negativity in our study. New studies should evaluate if it would be useful to add p53 expression to other existing predictive tools.

Human papillomavirus and breast cancer: no evidence of association in a Spanish set of cases.

BACKGROUND/AIM: Great controversy exists about the association between Human Papillomavirus (HPV) and breast tumors. The aim of this study was to explore the presence of HPV DNA in a large set of breast cancer cases. MATERIALS AND METHODS: Techniques used followed the standards for an international retrospective survey of HPV-DNA genotyping, coordinated by our own group and the DDL Laboratories in Rijswijk, the Netherlands. Paraffin-embedded samples were used. SPF-10 broad-spectrum primers were applied, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse-line probe assay. RESULTS: A total of 78 samples were included in the study, 2 of benign conditions and 76 carcinomas, including different histological subtypes. HPV was not present in any of the specimens studied irrespective of histology, hormonal status and stage of disease. CONCLUSION: Our data do not support the involvement of HPV in breast carcinogenesis as no evidence of its presence was found.