Oral and depot progestin therapy for endometriosis : Towards a personalized medicine

Introduction: Endometriosis is an estrogen-dependent chronic inflammatory disorder that requires a life-long management plan. Long-term adherence to treatment is pivotal to ensure an effective clinical management. In this optic, one of the cornerstone of endometriosis medical treatment is represented by progestins. Areas covered: This narrative review examines the clinical efficacy, safety and tolerability of oral and depot progestins used in the treatment of endometriosis. The material included in the current manuscript was obtained with a MEDLINE search through PubMed from inception until February 2017. Expert opinion: Progestins are effective in controlling pain symptoms in the majority of women with endometriosis, and their effect seems not inferior to that achieved with other compounds used to treat the disease, such as gonadotropin-releasing hormone agonist. Available progestins include a broad range of both oral and depot compounds, and represent, in most cases, an inexpensive treatment option. In addition, progestins do not increase significantly thrombotic risk and could be adopted in those women with metabolic or cardiovascular contraindication to estrogen-progestins. The choice between the different available compounds should be tailored for every woman with preference to the most cost-effective treatment, depending on the most complained symptom and disease location

Psychosexual consequences of female genital mutilation and the impact of reconstructive surgery : a narrative review

Purpose: We aim to provide a comprehensive overview of the health consequences of female genital mutila- tion/cutting (FGM/C), with a particular focus on the psychosexual implications of this practice and the overall impact of reconstructive plastic surgery. Methods: A MEDLINE search through PubMed was performed to identify the best quality evidence published studies in English language on long-term health consequences of FGM/C. Results: Women with FGM/C are more likely to develop psychological disorders, such as post-traumatic stress disorder, anxiety, somatization, phobia, and low self-esteem, than those without FGM/C. Most studies showed impaired sexual function in women with FGM/C. In particular, women with FGM/C may be physiologically less capable of becoming sexually stimulated than uncut women. Reconstructive surgery could be beneficial, in terms of both enhanced sexual function and body image. However, prospective studies on the impact of re- constructive surgery are limited, and safety issues should be addressed. Conclusion: Although it is clear that FGM/C can cause devastating immediate and long-term health conse- quences for girls and women, high-quality data on these issues are limited. Psychosexual complications need to be further analyzed to provide evidence-based guidelines and to improve the health care of women and girls with FGM/C. The best treatment approach involves a multidisciplinary team to deal with the multifaceted FGM/C repercussions

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV

Corrosion of Mg alloy in the presence of ammonium ion : evidence of hydride sub-products

Corrosion of AZ31 Mg alloy was systematically investigated by different experimental approaches in the presence and in the absence of NH4+. Remarkable reactivity of Mg/NH4+ system was manifested by copious evolution of hydrogen over a dark corrosion film, associated to active deprotonation of complex Mg hydrides, more likely bridged Mg2+(AlH4-)2Mg2+(H-)2 complexes covered by a skin of MgO. Metastability of hydride phases is favored in the presence of species that alter the equilibrium dissociation of water, such as NH4+ and SO42-. Chemical recombination of hydrogen atoms of oxidic Mg hydrides is proposed as the kinetically determinant process

The risk of malignancy in uterine polyps : a systematic review and meta-analysis

BACKGROUND: Endometrial polyps are a common condition. The risk of malignancy has often led to an overtreatment with high health care costs and huge psychological distress. OBJECTIVE: We conducted a systematic review and a meta-analysis in order to estimate the prevalence of premalignant and malignant lesions in women undergoing hysteroscopic polypectomy. DATA SOURCE: We developed the search using PubMed/MEDLINE and EMBASE databases to identify papers published between 2000- January 2019. The research strategy used on Pubmed was: ("polyps" (MESH) OR "endometrial polyp*") AND ("malignancy" OR "cancer" OR "histopathology" OR "hysteroscopy" OR "ultrasound", OR "sonohysterography"). The same search was modified for EMBASE. STUDY ELIGIBILITY: We included all observational retrospective and prospective studies and studies were selected for the review if they met following inclusion criteria: pre-operative diagnosis of benign-looking endometrial polyps at ultrasound examination or at hysteroscopy, excision of endometrial polyps via surgical hysteroscopy, histopathological diagnosis of benign polyps, or hyperplasia without atypia, or premalignancy (atypical hyperplasia) or malignancy (endometrial cancer). Moreover, studies were included if number or percentage of subjects with and without malignancy was provided and if they reported data about menopausal and/or bleeding status. We excluded data presented exclusively as abstracts in national and international meetings, or case report or review articles that did not include original data and papers published in other than English language. Our primary outcome was the prevalence of endometrial premalignant or malignant polyps in the total series, among premenopausal and postmenopausal women and among women with or without abnormal bleeding and then in subgroup analysis according to study design, diagnostic method, study region and calendar year of publication. RESULTS: A total of 51 studies reporting data on 35,345 women were included in this review. The prevalence of malignant polyps was 2.73% (95% CI 2.57-2.91) with very high heterogeneity among studies. The rates were lower for premenopausal women (1.12%) than post-menopausal ones (4.93%) and the difference was statistically significant (chi-square\u2009=\u2009397.21. p\u2009<\u2009.0001). The risk of malignancy was higher among symptomatic (5.14%) than asymptomatic ones (1.89%) (chi-square\u2009=\u2009133.13 p\u2009<\u2009.001). We observed higher rate of malignant polyps in prospective studies. In the meta-analysis selecting 10 prospective studies the random pooled estimate was 5.88 (95% CI: 4.06-7.97) with heterogeneity among studies (heterogeneity chi square\u2009=\u200917.55 P\u2009=\u2009.025) whereas in retrospective studies the random pooled estimate was 2.94 (95% CI:2.24-3.71) with high heterogeneity among studies (P\u2009<\u2009.001). This finding can be due to more strict diagnostic criteria in prospective studies. CONCLUSION: Symptomatic vaginal bleeding and postmenopausal status in women with endometrial polyps increased the risk of malignancy. This finding could be an useful evidence to select patients who need to undergo hysteroscopic resection of endometrial polyps and women to whom, instead, an expectant management can be offer

Aggregation/fibrillogenesis of recombinant human prion protein and Gerstmann-Straussler-Scheinker disease peptides in the presence of metal ions.

In this study we investigated the role of Cu(2+), Mn(2+), Zn(2+), and Al(3+) in inducing defective conformational rearrangements of the recombinant human prion protein (hPrP), which trigger aggregation and fibrillogenesis. The research was extended to the fragment of hPrP spanning residues 82-146, which was identified as a major component of the amyloid deposits in the brain of patients affected by Gerstmann-Str\ue4ussler-Scheinker (GSS) disease. Variants of the 82-146 wild-type subunit [PrP-(82-146)(wt)] were also examined, including entirely, [PrP-(82-146)(scr)], and partially scrambled, [PrP-(82-146)(106)(-)(126scr)] and [PrP-(82-146)(127)(-)(146scr)], peptides. Al(3+) strongly stimulated the conversion of native hPrP into the altered conformation, and its potency in inducing aggregation was very high. Despite a lower rate and extent of prion protein conversion into altered isoforms, however, Zn(2+) was more efficient than Al(3+) in promoting organization of hPrP aggregates into well-structured, amyloid-like fibrillar filaments, whereas Mn(2+) delayed and Cu(2+) prevented the process. GSS peptides underwent the fibrillogenesis process much faster than the full-length protein. The intrinsic ability of PrP-(82-146)(wt) to form fibrillar aggregates was exalted in the presence of Zn(2+) and, to a lesser extent, of Al(3+), whereas Cu(2+) and Mn(2+) inhibited the conversion of the peptide into amyloid fibrils. Amino acid substitution in the neurotoxic core (sequence 106-126) of the 82-146 fragment reduced its amyloidogenic potential. In this case, the stimulatory effect of Zn(2+) was lower as compared to the wild-type peptide; on the contrary Al(3+) and Mn(2+) induced a higher propensity to fibrillation, which was ascribed to different binding modalities to GSS peptides. In all cases, alteration of the 127-146 sequence strongly inhibited the fibrillogenesis process, thus suggesting that integrity of the C-terminal region was essential both to confer amyloidogenic properties on GSS peptides and to activate the stimulatory potential of the metal ions

Stem cells commitment on graphene-based Scaffolds

In the last years, a rapid development in production, and functionalization of graphene give rise to several products that have shown great potentials in many fields, such as nanoelectronics, energy technology, sensors, and catalysis. In this context we should not forget the biomedical application of graphene that became a new area with outstanding potential. The first study on graphene for biomedical applications has been performed by Dai in 2008 that reported the use of graphene oxide as an efficient nanocarrier for drug delivery. This pioneristic study opened the doors for the use of graphene in widespread biomedical applications such as drug/gene delivery, biological sensing and imaging, antibacterial materials, but also as biocompatible scaffold for cell culture and tissue engineering. The application of graphene-based scaffolds for tissue engineering applications is confirmed by the many exciting and intriguing literature reports over the last few years, that clearly confirm that graphene and its related substrates are excellent platforms for adhesion, proliferation, and differentiation of various cells such as human Mesenchymal stem cells, human neuronal stem cells, and induced pluripotent stem cells. Since most of the papers on this fields are related to in vitro studies, several future in vivo investigations need to be conducted in order to lead to its utilization as implantable tissue engineering material

&apos;Money for nothing&apos; . The role of robotic assisted laparoscopy for the treatment of endometriosis

Despite higher costs for robotic assisted laparoscopy (RAL) than standard laparoscopy (SL), RAL treatment of endometriosis is performed without established indications. PubMed/MEDLINE was searched for 'robotic surgery' and 'endometriosis' or 'gynaecological benign disease' from January 2000 to December 2016. Full-length studies in English reporting original data were considered. Among 178 articles retrieved, 17 were eligible: 11 non-comparative (RAL only) and six comparative (RAL versus SL). Non-comparative studies included 445 patients. Mean operating time, blood loss and hospital stay were 226\u2009min, 168\u2009ml and 4 days. Major complications and laparotomy conversions were 3.1% and 1.3%. Eight studies reported pain improvement at 15-month follow-up. Comparative studies were all retrospective; 749 women underwent RAL and 705 SL. Operating time was longer for RAL in five studies. Major complications and laparotomy conversions for RAL and SL were 1.5% versus 0.3% and 0.3% versus 0.5%. One study reported pain reduction for RAL at 6-month follow-up. RAL treatment of endometriosis did not provide benefits over SL, overall and among subgroups of women with severe endometriosis, peritoneal endometriosis and obesity. Available evidence is low-quality, and data regarding long-term pain relief and pregnancy rates are lacking. RAL treatment of endometriosis should be performed only within controlled studies

Self-management and psychological-sexological interventions in patients with endometriosis: strategies, outcomes, and integration into clinical care

Endometriosis has a multifactorial etiology. The onset and progression of the disease are believed to be related to different pathogenic mechanisms. Among them, the environment and lifestyle may play significant roles. Diet, dietary supplements, physical exercise, osteopathy, massage, acupuncture, transcutaneous electrical nerve stimulation, and Chinese herbal medicine may represent a complementary and feasible approach in the treatment of symptoms related to the disease. In this narrative review, we aimed to examine the most updated evidence on these alternative approaches implicated in the self-management of the disease. In addition, several studies have demonstrated that endometriosis may negatively impact mental health and quality of life, suggesting that affected women may have an increased risk of developing psychological suffering as well as sexual problems due to the presence of pain. In light of these findings, we discuss the importance of integrating psychological interventions (including psychotherapy) and sexual therapy in endometriosis treatment