Ibrutinib is an orally available, small-molecule tyrosine kinase inhibitor. Its main purpose is to inhibit Bruton’s tyrosine kinase (BTK), an enzyme that is crucial in B cell development. It is FDA approved for the treatment of certain hematological malignancies. Several promising off-target drug effects have led to multiple, mostly preclinical investigations regarding its use in solid tumors. Unfortunately, data on its effectiveness in gynecological malignancies are limited, and (systematic) reviews are missing. The objective of this review was to summarize the existing literature and to analyze the evidence of ibrutinib as a treatment option in gynecological malignancies, including breast cancer. Studies were identified in MEDLINE and EMBASE using a defined search strategy, and preclinical or clinical research projects investigating ibrutinib in connection with these malignancies were considered eligible for inclusion. Our findings showed that preclinical studies generally confirm ibrutinib’s efficacy in cell lines and animal models of ovarian, breast, and endometrial cancer. Ibrutinib exerts multiple antineoplastic effects, such as on-target BTK inhibition, off-target kinase inhibition, and immunomodulation by interference with myeloid-derived suppressor cells (MDSCs), programmed death-ligand 1 (PD-L1), and T cell response. These mechanisms were elaborated and discussed in the context of the evidence available. Further research is needed in order to transfer the preclinical results to a broader clinical appliance.

Background There is a growing body of human, animal and in vitro studies on vitamin D (vit D) substitution in endometriosis. The aim of this systematic review is to critically appraise and qualitatively synthesize the results of the available studies that examine the supplementation of vit D for endometriosis treatment. Methods A systematic search of the literature was conducted in four electronic databases (Medline, Cochrane, Scopus, Embase) and grey literature for original research articles on humans, animals and in vitro models published in any language. Results Four human studies, four animal studies and four in vitro studies were included. Quantitative synthesis of human studies showed no significant effect of vit D intake for dysmenorrhea (2 studies, 44 vit D vs 44 placebo, mean -0.71, 95% CI -1.94, 0.51) and non-cyclic pelvic pain (2 studies, 42 vit D vs 38 placebo, mean 0.34, 95% CI -0.02, 0.71). Regarding reproductive outcomes in women with endometriosis after in vitro fertilization, the only available study showed no differences between women taking vit D and women taking placebo. Three of the four included animal studies showed regression of endometriotic implants when treated with vit D. The in vitro studies demonstrated that vit D decreases invasion and proliferation of endometriotic lesions without affecting apoptosis. Conclusions Although in vitro and animal studies suggest regression of the endometriotic implants and decrease of invasion and proliferation after vit D supplementation, this was not reflected in the results of the meta-analysis, which showed no benefit of vit D supplementation in patients with endometriosis and dysmenorrhea or non-cyclic pelvic pain as well as on the outcome of IVF treatment. However, given the heterogeneity and the diversity of the available studies, more research is required to shed light on the role of vit D supplementation in women with endometriosis.

Objectives: Endocrine drugs represent an important cornerstone of endometriosis therapy. Pharmaceutical alternatives with similar efficacy remain out of sight in the near future. Aim of this study is to investigate attitudes and perceptions concerning endocrine therapies among affected women. Study design: An online survey was distributed via social media in Austria, Germany, and Switzerland. Primary endpoints were satisfaction, attitudes and perceptions towards endocrine endometriosis drugs and secondary outcomes differences regarding demographic variables. Results: Of 1420 respondents, 63.5 % (n = 901) described their own attitude towards these drugs as rather negative. The most frequently reported unfavorable associations and experiences were sideeffects in general (85.5 %, n = 1181), change in libido (67.5 %, n = 932), hormone cycle disruptions (65.9 %, n = 910), and inefficiency at alleviating symptoms (38.2 %, n = 527). In total, 66.1 % (n = 935) were not satisfied with endocrine drugs for endometriosis. Age 30 years, living in a large city, and having an academic degree were significantly correlated to a more negative perception of these drugs and greater dissatisfaction with current endocrine endometriosis drugs. Conclusions: Among women with endometriosis -and particularly among those aged 30 years, being large-city residents, or holding an academic degree -there appears to be a relevant degree of rejection and wariness towards endocrine endometriosis drugs. Given the prevalence of endometriosis and the few pharmaceutical alternatives on the horizon, these data point a growing need for further research and development of non-hormonal drugs for the treatment of endometriosis.

Background Social media platforms, such as Facebook and Instagram, are increasingly being used to share health-related information by “influencers,” regular users, and institutions alike. While patients may benefit in various ways from these interactions, little is known about the types of endometriosis-related information published on social media. As digital opinion leaders influence the perceptions of their followers, physicians need to be aware about ideas and beliefs that are available online, in order to address possible misconceptions and provide optimal patient care. Objective The aim of this study was to identify and analyze frequent endometriosis-related discussion topics on social media in order to offer caregivers insight into commonly discussed subject matter and aspects. Methods We performed a systematic search using predefined parameters. Using the term “endometriosis” in Facebook’s search function and a social media search engine, a list of Facebook pages was generated. A list of Instagram accounts was generated using the terms “endometriosis” and “endo” in Instagram’s search function. Pages and accounts in English with 5000 or more followers or likes were included. Nonpublic, unrelated, or inactive pages and accounts were excluded. For each account, the most recent 10 posts were identified and categorized by two independent examiners using qualitative content analysis. User engagement was calculated using the numbers of interactions (ie, shares, likes, and comments) for each post, stratified by the number of followers. Results A total of 39 Facebook pages and 43 Instagram accounts with approximately 1.4 million followers were identified. Hospitals and medical centers made up 15% (6/39) of the Facebook pages and 5% (2/43) of the Instagram accounts. Top accounts had up to 111,600 (Facebook) and 41,400 (Instagram) followers. A total of 820 posts were analyzed. On Facebook, most posts were categorized as “awareness” (101/390, 25.9% of posts), “education and research” (71/390, 18.2%), and “promotion” (64/390, 16.4%). On Instagram, the top categories were “inspiration and support” (120/430, 27.9% of posts), “awareness” (72/430, 16.7%), and “personal story” (72/430, 16.7%). The frequency of most categories differed significantly between platforms. User engagement was higher on Instagram than on Facebook (3.20% vs 0.97% of followers per post). On Instagram, the highest percentage of users engaged with posts categorized as “humor” (mean 4.19%, SD 4.53%), “personal story” (mean 3.02%, SD 4.95%), and “inspiration and support” (mean 2.83%, SD 3.08%). On Facebook, posts in the categories “awareness” (mean 2.05%, SD 15.56%), “humor” (mean 0.91%, SD 1.07%), and “inspiration and support” (mean 0.56%, SD 1.37%) induced the most user engagement. Posts made by hospitals and medical centers generated higher user engagement than posts by regular accounts on Facebook (mean 1.44%, SD 1.11% vs mean 0.88%, SD 2.71% of followers per post) and Instagram (mean 3.33%, SD 1.21% vs mean 3.19%, SD 2.52% of followers per post). Conclusions Facebook and Instagram are widely used to share endometriosis-related information among a large number of users. Most posts offer inspiration or support, spread awareness about the disease, or cover personal issues. Followers mostly engage with posts with a humoristic, supportive, and awareness-generating nature. Health care providers should be aware about the topics discussed online, as this may lead to an increased understanding of the needs and demands of digitally proficient patients with endometriosis.

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Ibrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase, an enzyme central in B cell development. It is indicated as a therapy for certain hematological diseases such as chronic lymphocytic leukemia (CLL), but also exerts off-target effects on several receptors and kinases. In this paper, we hypothesize that ibrutinib may suppress the tumor marker CA-125 in ovarian cancer. The hypothesis is based on an observation of CA-125 normalization in a patient with low-grade serous ovarian cancer who received ibrutinib for concurrent CLL. We propose a mechanistic model explaining this possible drug effect as a foundation for further research.

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