Effect of a Multi-Ingredient Coriolus-versicolor-Based Vaginal Gel in Women with HPV-Dependent Cervical Lesions: The Papilobs Real-Life Prospective Study.

Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. HPV infection and persistency may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. The objective was to prospectively evaluate the results of using a Coriolus-versicolor-based vaginal gel (Papilocare®) on HPV-dependent low-grade cervical lesion repair in a real-life scenario. HPV-positive women ≥ 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). A 6-month second treatment cycle was prescribed when needed. Repair of the cervical low-grade lesions through cytology and colposcopy, HPV clearance, and level of satisfaction, and tolerability were evaluated. In total, 192 and 201 patients accounted for the total and safety analyses, respectively, and 77.1% repaired cervical lesions at 6 or 12 months (76.0% for high-risk HPV). Additionally, 71.6% achieved HPV clearance throughout the study's duration (70.6% for high-risk HPV). Satisfaction level was rated 7.9 and 7.5 out of 10 at 6 and 12 months, respectively. Only three mild-moderate product-related adverse events were reported, and all of them were resolved by the end of the study. In our study, we observed higher regression rates of low-grade cervical lesions in women treated with Papilocare® vaginal gel than spontaneous regression rates reported in the literature.

Ovulation and extra-ovarian origin of ovarian cancer.

The mortality rate of ovarian cancer remains high due to late diagnosis and recurrence. A fundamental step toward improving detection and treatment of this lethal disease is to understand its origin. A growing number of studies have revealed that ovarian cancer can develop from multiple extra-ovarian origins, including fallopian tube, gastrointestinal tract, cervix and endometriosis. However, the mechanism leading to their ovarian localization is not understood. We utilized in vitro, ex vivo, and in vivo models to recapitulate the process of extra-ovarian malignant cells migrating to the ovaries and forming tumors. We provided experimental evidence to support that ovulation, by disrupting the ovarian surface epithelium and releasing chemokines/cytokines, promotes the migration and adhesion of malignant cells to the ovary. We identified the granulosa cell-secreted SDF-1 as a main chemoattractant that recruits malignant cells towards the ovary. Our findings revealed a potential molecular mechanism of how the extra-ovarian cells can be attracted by the ovary, migrate to and form tumors in the ovary. Our data also supports the association between increased ovulation and the risk of ovarian cancer. Understanding this association will lead us to the development of more specific markers for early detection and better prevention strategies.

TLR2 enhances ovarian cancer stem cell self-renewal and promotes tumor repair and recurrence.

Primary ovarian cancer is responsive to treatment, but chemoresistant recurrent disease ensues in majority of patients. Recent compelling evidence demonstrates that a specific population of cancer cells, the cancer stem cells, initiates and sustains tumors. It is therefore possible that this cell population is also responsible for recurrence. We have shown previously that CD44+/MyD88+ epithelial ovarian cancer stem cells (CD44+/MyD88+ EOC stem cells) are responsible for tumor initiation. In this study, we demonstrate that this population drives tumor repair following surgery- and chemotherapy-induced tumor injury. Using in vivo and in vitro models, we also demonstrate that during the process of tumor repair, CD44+/MyD88+ EOC stem cells undergo self-renewal as evidenced by upregulation of stemness-associated genes. More importantly, we show that a pro-inflammatory microenvironment created by the TLR2-MyD88-NFκB pathway supports EOC stem cell-driven repair and self-renewal. Overall, our findings point to a specific cancer cell population, the CD44+/MyD88+ EOC stem cells and a specific pro-inflammatory pathway, the TLR2-MyD88-NFκB pathway, as two of the required players promoting tumor repair, which is associated with enhanced cancer stem cell load. Identification of these key players is the first step in elucidating the steps necessary to prevent recurrence in EOC patients.

Near-miss o casi pérdida en un hospital de referencia / Near-miss in a referral hospital

Objetivos. Análisis de la salud materna a partir de la mortalidad directa y del concepto de casi-pérdida en el Hospital Universitario La Fe de Valencia desde 1991 hasta 2007. Material y método. Calculamos la ratio mortalidad materna directa (RMMD) entre 1971-2007 y la ratio morbilidad obstétrica severa-mortalidad entre 1991-2007 con sus causas. Resultados. Objetivamos una disminución significativa de la RMMD (rho=-1) con un descenso significativo de mortalidad por patología cardio-vascular. Cuando analizamos la morbilidad materna severa, observamos: un aumento significativo de riesgo por placenta previa (OR=1,79), abruptio (OR=1,35), rotura uterina (OR=2,48) y complicaciones anestésicas (OR=6,20) y un descenso significativo de hemorragia posparto (OR=0,63) e infección puerperal grave(OR=0,32), permaneciendo estable la prevalencia de trastornos hipertensivos del embarazo, fenómenos tromboembólicos y muerte fetal intraútero y la ratio morbilidad severa/mortalidad durante el periodo estudiado. Conclusión. Es difícil estimar la ratio morbilidad obstétrica severa-mortalidad por las diferentes definiciones de near-miss en la literatura. La RMMD disminuyó, permaneciendo estable la razón morbilidad / mortalidad (AU)

Objectives. To analyze maternal health from direct mortality and the concept of near-miss at La Fe University Hospital in Valencia (Spain) from 1991 to 2007. Material and methods. We calculated the direct maternal mortality ratio (DMMR) from 1971-2007 and the severe obstetric morbility-mortality ratio from 1991-2007, and analyzed their causes. Results. A significant DMMR decrease (rho=- 1), with a significant reduction in mortality due to cardiovascular disease was found. When analyzing severe maternal morbidity, we observed an increase of placenta previa (OR=1.79), abruptio placentae (OR=1.35), uterine rupture (OR=2.48) and anesthetic complications (OR=6.20), with a significant decrease of postpartum hemorrhage (OR=0.63) and severe puerperal infection (OR=0.32).The prevalence of hypertensive disorders of pregnancy, thromboembolic disease, intrauterine fetal death and severe morbidity/mortality ratio remained stable during the study period. Conclusions. Estimating the severe obstetric morbidity-mortality ratio due to different near-miss definitions in the literature is difficult. The DMMR decreased, while the morbidity/mortality ratio remained stable (AU)