Can miRNAs be useful biomarkers in improving prognostic stratification in endometrial cancer patients? An update review

Endometrial cancer (EC) is the most common gynecological cancer, with annual incidence rates in Western countries ranging between 15 and 25 per 100 000 women. About 15% to 20% of patients with EC have high-risk disease and follow an aggressive clinical course. Unfortunately, the assessment of histologic parameters is poorly reproducible and conventional clinicopathological and molecular features do not reliably predict either the patient's response to the available treatments or the definition of personalized therapeutic approaches. In this context, the identification of novel diagnostic and prognostic biomarkers, which can be integrated in the current classification schemes, represents an unmet clinical need and an important challenge. miRNAs are key players in cancer by regulating the expression of specific target genes. Their role in EC, in association with clinical and prognostic tumor biomarkers, has been investigated but, so far, with little consensus among the studies. The present review aims to describe the recent advances in miRNAs research in EC taking into consideration the current classification schemes and to highlight the most promising miRNAs. Finally, a perspective point of view sheds light on the challenges ahead in the landscape of EC

Role of circulating mirnas in therapeutic response in epithelial ovarian cancer: A systematic revision

Epithelial ovarian cancer (EOC) is one of the most lethal cancers worldwide, mostly due to nonspecific symptoms and a lack of screening tests, which, taken together, contribute to delayed diagnosis and treatment. The current clinical biomarker is serum CA-125, which allows the identification of most advanced primary and relapsed disease and correlates with disease burden; however, as well highlighted in the literature, CA-125 often lacks sensitivity and specificity, and is not helpful in monitoring chemotherapeutic response or in predicting the risk of relapse. Given that, the identification of novel biomarkers able to foster more precise medical approaches and the personalization of patient management represents an unmet clinical requirement. In this context, circulating miRNAs may represent an interesting opportunity as they can be easily detected in all biological fluids. This is particularly relevant when looking for non-invasive approaches that can be repeated over time, with no pain and stress for the oncological patient. Given that, the present review aims to describe the circulating miRNAs currently identified as associated with therapeutic treatments in OC and presents a complete overview of the available evidence

Predictive role of MRI and18F FDG PET response to concurrent chemoradiation in T2B cervical cancer on clinical outcome: A retrospective single center study

Tumor response in locally advanced cervical cancer (LACC) is generally evaluated with MRI and PET, but this strategy is not supported by the literature. Therefore, we compared the diagnostic performance of these two techniques in the response evaluation to concurrent chemoradiotherapy (CCRT) in LACC. Patients with cervical cancer (CC) stage T2b treated with CCRT and submitted to MRI and PET/CT before and after treatment were enrolled in the study. All clinical, pathological, therapeutic, radiologic and follow-up data were collected and examined. The radiological response was analyzed and compared to the follow-up data. Data of 40 patients with LACC were analyzed. Agreement between MRI and PET/CT in the evaluation response to therapy was observed in 31/40 (77.5%) of cases. The agreement between MRI, PET/CT and follow-up data showed a Cohen kappa coefficient of 0.59 (95% CI = 0.267\u20130.913) and of 0.84 (95% CI = 0.636\u20131.00), respectively. Considering the evaluation of primary tumor response, PET/CT was correct in 97.5% of cases, and MRI in 92.5% of cases; no false negative cases were observed. These results suggest the use of PET/CT as a unique diagnostic imaging tool after CCRT, to correctly assess residual and progression disease

Could kallikrein-related serine peptidase 3 be an early biomarker of environmental exposure in young women?

Bisphenols and phthalates affect androgen receptor-mediated signaling that directly reg-ulates Kallikrein-Related serine Peptidase 3 (KLK3) secretion, indicating that environmental factors may play a role in KLK3 secretion. With the aim of obtaining preliminary data on whether KLK3 could serve as an early marker of environmental pollution effects, in 61 and 58 healthy women living in a high environmental impact (HEI) and low environmental impact (LEI) area, respectively, serum KLK3 levels at different phases of menstrual cycle were measured. KLK3 values resulted in always being higher in the HEI group with respect to the LEI group. These differences were partic-ularly relevant in the ovulatory phase (cycle day 12°–13°) of the menstrual cycle. The differences in KLK3 values during the three phases of the menstrual cycle were significant in the LEI group dif-ferently from the HEI group. In addition, higher progesterone levels were observed in the LEI group with respect to the HEI group in the luteal phase, indicating an opposite trend of KLK3 and progesterone in this phase of the menstrual cycle. Although changes in KLK3 could also depend on other factors, these preliminary data could be an early indication of an expanding study of the role of biomarkers in assessing early environmental effects for female reproductive health

Large deviations for a damped telegraph process

In this paper we consider a slight generalization of the damped telegraph process in Di Crescenzo and Martinucci (2010). We prove a large deviation principle for this process and an asymptotic result for its level crossing probabilities (as the level goes to infinity). Finally we compare our results with the analogous well-known results for the standard telegraph process

Malignant Bowel Obstruction in Ovarian Cancer Recurrence: The Role of Palliative Surgery in a Decision-Making Process

Background: Malignant bowel obstruction (MBO) is often the latest stage in ovarian cancer (OC). The therapy of this condition ranges from medical waiting to surgery. The objective of this pilot study is to compare the two strategies so that we can provide a path forward for future studies. Methods: From 700 women diagnosed with OC in the database of the Division of Gynecologic Oncology we crossed the names of those admitted by the emergency services of the IRCSS Azienda Ospedaliero Universitaria of Bologna, Italy. We selected MBO patients with a history of OC as the only neoplastic condition and compared the results between medical conduct and surgery to restore intestinal transit. Results: Of the 700 women in our database, 36 were eligible for study according to the inclusion and exclusion criteria: 9 in surgery group and 27 in medical group. Surgical conduct (tumor biopsy and stoma) appears to be resolutory for the obstruction and have a better result than medical therapy regarding recurrence of MBO, despite the development of greater complications. Relapses of MBOs occurred in 11% of surgical patients and 44% of medical patients (p = 0.0714). Furthermore, after surgical treatment, five patients (55%) experienced postoperative complications; in four cases, severe anemia requiring blood transfusion, while one patient developed post-surgical sepsis, which evolved into multiple organ failure and death. Of the 9 patients treated surgically, 2 (22%) were given surgery as a first choice. In most cases (78%), surgery was decided upon when medical treatment failed. The only discriminative factor appears to be age. The length of hospitalization increased with the patient’s age (p = 0.0181) as statistically significant factors for a worse outcome in surgery. Conclusions: MBO requires complex and multidisciplinary management where different factors need to be considered before initiating surgical therapy. Future studies are needed to deal with this complex problem

Comparative efficacy and acceptability of psychological interventions for the treatment of adult outpatients with anorexia nervosa: a systematic review and network meta-analysis

Background: No consistent first-option psychological interventions for adult outpatients with anorexia nervosa emerges from guidelines. We aimed to compare stand-alone psychological interventions for adult outpatients with anorexia nervosa with a specific focus on body-mass index, eating disorder symptoms, and all-cause dropout rate. Methods: In this systematic review and network meta-analysis, we assessed randomised controlled trials about stand-alone pharmacological or non-pharmacological treatments of adult outpatients with anorexia nervosa, defined according to standardised criteria, with data for at least two timepoints relating to either body-mass index or global eating disorder psychopathology. We searched Cochrane CENTRAL, CINAHL, MEDLINE, and PsychINFO for published and unpublished literature from inception until March 20, 2020. The primary outcomes were the change in body mass index and clinical symptoms, and the secondary outcome was all-cause dropout rate, which were all assessed for treatment as usual, cognitive behavioural therapy (CBT), Maudsley anorexia treatment for adults, family-based treatment, psychodynamic-oriented psychotherapies, a form of CBT targeting compulsive exercise, and cognitive remediation therapy followed by CBT. Global and local inconsistencies for the network meta-analysis were measured, and CINeMA was used to assess the confidence in evidence for primary outcomes. The protocol is registered in PROSPERO (CRD42017064429). Findings: Of 14 003 studies assessed for their title and abstract, 16 (0·1%) randomised controlled trials for psychological treatments were included in the systematic review, of which 13 (0·1%) contributed to the network meta-analysis, with 1047 patients in total (of whom 1020 [97·4%] were female). None of the interventions outperformed treatment as usual in our primary outcomes, but the all-cause dropout rate was lower for CBT than for psychodynamic-oriented psychotherapies (OR 0·54, 95% CI 0·31–0·93). Heterogeneity or inconsistency emerged only for a few comparisons. Confidence in the evidence was low to very low. Interpretation: Compared with treatment as usual, specific psychological treatments for adult outpatients with anorexia nervosa can be associated with modest improvements in terms of clinical course and quality of life, but no reliable evidence supports clear superiority or inferiority of the specific treatments that are recommended by clinical guidelines internationally. Our analysis is based on the best data from existing clinical studies, but these findings should not be seen as definitive or universally applicable. There is an urgent need to fund new research to develop and improve therapies for adults with anorexia nervosa. Meanwhile, to better understand the effects of available treatments, participant-level data should be made freely accessible to researchers to eventually identify whether specific subgroups of patients are more likely to respond to specific treatments. Funding: Flinders University, National Institute for Health Research Oxford Health Biomedical Research Centre

Limits on decaying dark energy density models from the CMB temperature-redshift relation

The nature of the dark energy is still a mystery and several models have been proposed to explain it. Here we consider a phenomenological model for dark energy decay into photons and particles as proposed by Lima (J. Lima, Phys. Rev. D 54, 2571 (1996)). He studied the thermodynamic aspects of decaying dark energy models in particular in the case of a continuous photon creation and/or disruption. Following his approach, we derive a temperature redshift relation for the CMB which depends on the effective equation of state $w_{eff}$ and on the "adiabatic index" $\gamma$. Comparing our relation with the data on the CMB temperature as a function of the redshift obtained from Sunyaev-Zel'dovich observations and at higher redshift from quasar absorption line spectra, we find $w_{eff}=-0.97 \pm 0.034$, adopting for the adiabatic index $\gamma=4/3$, in good agreement with current estimates and still compatible with $w_{eff}=-1$, implying that the dark energy content being constant in time.Comment: 8 pages, 1 figur