Immune-Related Sclerosing Cholangitis and Subsequent Pyogenic Liver Abscesses in Two Patients With Melanoma Treated by Triplet Therapy: A Case Report.

Immune checkpoint inhibitors have improved the treatment of many cancers. However, immune-related (IR) adverse events can limit their use. A rare but potentially severe IR adverse event is IR-cholangitis, which is mostly induced by anti-programmed cell death 1 (PD1) antibodies and is often corticosteroid-resistant. Consequently, immunosuppressive therapy is increased, which interferes with the antitumor response and bears the risk of infection. We report on 2 patients with BRAF V600E mutant melanoma, who presented with IR-sclerosing cholangitis under triplet therapy with atezolizumab [anti-programmed cell death ligand 1 (PD-L1) antibody], vemurafenib (BRAF inhibitor), and cobimetinib (MEK inhibitor). In both cases, the administration of corticosteroids initially resulted in a marginal improvement but was followed by a rebound of biliary enzymes and the subsequent emergence of pyogenic liver abscesses with bacteremia. Liver abscesses developed without preceding invasive procedures, which implies that a more restrictive approach to immunosuppressive therapy for IR-cholangitis should be considered. To our knowledge, we report the first 2 cases of IR-cholangitis and subsequent liver abscesses without prior invasive intervention, the first cases of IR-cholangitis induced by triplet therapy, and 2 of the few anti-PD-L1 induced cases contributing to the evidence that both anti-PD1 and anti-PD-L1 antibodies induce IR-cholangitis. Treatment strategies for IR-cholangitis need to be improved to prevent life-threatening infectious complications.

Sexual attraction to visual sexual stimuli in association with steroid hormones across menstrual cycles and fertility treatment.

BACKGROUND: Steroid hormones (i.e., estradiol, progesterone, and testosterone) are considered to play a crucial role in the regulation of women's sexual desire and sexual attraction to sexual stimuli throughout the menstrual cycle. However, the literature is inconsistent, and methodologically sound studies on the relationship between steroid hormones and women's sexual attraction are rare. METHODS: This prospective longitudinal multisite study examined estradiol, progesterone, and testosterone serum levels in association with sexual attraction to visual sexual stimuli in naturally cycling women and in women undergoing fertility treatment (in vitro fertilization, IVF). Across ovarian stimulation of fertility treatment, estradiol reaches supraphysiological levels, while other ovarian hormones remain nearly stable. Ovarian stimulation hence offers a unique quasi-experimental model to study concentration-dependent effects of estradiol. Hormonal parameters and sexual attraction to visual sexual stimuli assessed with computerized visual analogue scales were collected at four time points per cycle, i.e., during the menstrual, preovulatory, mid-luteal, and premenstrual phases, across two consecutive menstrual cycles (n = 88 and n = 68 for the first and second cycle, respectively). Women undergoing fertility treatment (n = 44) were assessed twice, at the beginning and at the end of ovarian stimulation. Sexually explicit photographs served as visual sexual stimuli. RESULTS: In naturally cycling women, sexual attraction to visual sexual stimuli did not vary consistently across two consecutive menstrual cycles. While in the first menstrual cycle sexual attraction to male bodies, couples kissing, and at intercourse varied significantly with a peak in the preovulatory phase, (all p ≤ 0.001), there was no significant variability across the second cycle. Univariable and multivariable models evaluating repeated cross-sectional relationships and intraindividual change scores revealed no consistent associations between estradiol, progesterone, and testosterone and sexual attraction to visual sexual stimuli throughout both menstrual cycles. Also, no significant association with any hormone was found when the data from both menstrual cycles were combined. In women undergoing ovarian stimulation of IVF, sexual attraction to visual sexual stimuli did not vary over time and was not associated with estradiol levels despite intraindividual changes in estradiol levels from 122.0 to 11,746.0 pmol/l with a mean (SD) of 3553.9 (2472.4) pmol/l. CONCLUSIONS: These results imply that neither physiological levels of estradiol, progesterone, and testosterone in naturally cycling women nor supraphysiological levels of estradiol due to ovarian stimulation exert any relevant effect on women's sexual attraction to visual sexual stimuli.