Tumor lysis Syndrome in a Patient with Metastatic Breast Cancer Treated with Alpelisib.

PURPOSE: Tumor lysis syndrome (TLS) is a rare but life-threatening phenomenon that occurs mainly in patients with aggressive hematologic or highly chemotherapy sensitive solid tumors such as high-grade neuroendocrine carcinoma or testicular cancer. Tumor lysis syndrome is exceedingly rare in hormone receptor-positive, HER2-negative breast cancer. Furthermore, TLS following treatment with alpelisib, a novel phosphatidylinositol 3-kinase (PI3K) inhibitor used to treat PIK3CA-mutated (gene encoding p110α subunit of PI3K), hormone receptor positive advanced breast cancer, has never been described in patients with nonhematologic malignancies. METHODS: In the following case, we present a patient with hormone receptor-positive, HER2-negative, PIK3CA-mutated metastatic breast cancer who developed TLS 12 days after starting fulvestrant and alpelisib. RESULTS: Patient was promptly treated with improvement in her renal function to baseline without requiring renal replacement therapy. Alpelisib was resumed at a reduced dose with no further complications. CONCLUSION: Through this case, we discuss the potential complications of TLS and the importance of prompt recognition and treatment.

A Retrospective Chart Review of Contraceptive Use among Adolescents with Opioid Use Disorder.

STUDY OBJECTIVE: To describe contraceptive use among female adolescents initiating outpatient treatment for opioid use disorder. DESIGN: Retrospective chart review. SETTING: Outpatient clinic providing medication-assisted treatment for substance use disorders to adolescents and young adults. PARTICIPANTS: Nonpregnant female adolescents who presented for treatment from January 1, 2013 to January 31, 2016 (N = 123). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prescription contraceptive use at baseline and initiation of a new method within 90 days. RESULTS: Of 123 female adolescents who presented for treatment of opioid use disorder, 113 (91.9%) reported sexual activity and 80 (65.0%) were not using prescription contraception at intake. Previous pregnancy was reported by 43 (35.0%) and 20 (16.3%) were positive for a sexually transmitted infection. Contraceptive counseling was not documented for 73 (59.3%) patients. Among patients with no prescription contraception at baseline, 56 of 80 (70.0%) initiated a method within the study window. Significant predictors (odds ratio [OR]; 95% confidence interval) of contraceptive initiation included previous pregnancy (8.6; 1.39-52.99), education of less than a high school diploma/general equivalency diploma (7.4; 1.63-33.41), and return for follow-up visit (9.8; 2.18-43.69). CONCLUSION: Young women who presented for opioid use disorder treatment were at high risk of adverse reproductive health outcomes. Most were sexually active and not using prescription contraception. Findings underscore the need for contraceptive counseling in this patient population. Optimally, these services would be provided in conjunction with substance use treatment. Improved contraceptive counseling documentation will allow evaluation of effective contraceptive counseling strategies for adolescents with opioid use disorders and might serve to inform future interventions.

ROCK1 deficiency enhances protective effects of antioxidants against apoptosis and cell detachment.

We have recently reported that the homologous Rho kinases, ROCK1 and ROCK2, play different roles in regulating stress-induced stress fiber disassembly and cell detachment, and the ROCK1 deficiency in mouse embryonic fibroblasts (MEF) has remarkable anti-apoptotic, anti-detachment and pro-survival effects against doxorubicin, a chemotherapeutic drug. This study investigated the roles of ROCK isoforms in doxorubicin-induced reactive oxygen species (ROS) generation which is believed to be the major mechanism underlying its cytotoxicity to normal cells, and especially to cardiomyocytes. Different antioxidants have been shown to provide a protective role reported in numerous experimental studies, but clinical trials of antioxidant therapy showed insufficient benefit against the cardiac side effect. We found that both ROCK1-/- and ROCK2-/- MEFs exhibited reduced ROS production in response to doxorubicin treatment. Interestingly, only ROCK1 deficiency, but not ROCK2 deficiency, significantly enhanced the protective effects of antioxidants against doxorubicin-induced cytotoxicity. First, ROCK1 deficiency and N-acetylcysteine (an anti-oxidant) treatment synergistically reduced ROS levels, caspase activation and cell detachment. In addition, the reduction of ROS generation in ROCK1-/- MEFs in response to doxorubicin treatment was in part through inhibiting NADPH oxidase activity. Furthermore, ROCK1 deficiency enhanced the inhibitory effects of diphenyleneiodonium (an inhibitor of NADPH oxidase) on ROS generation and caspase 3 activation induced by doxorubicin. Finally, ROCK1 deficiency had greater protective effects than antioxidant treatment, especially on reducing actin cytoskeleton remodeling. ROCK1 deficiency not only reduced actomyosin contraction but also preserved central stress fiber stability, whereas antioxidant treatment only reduced actomyosin contraction without preserving central stress fibers. These results reveal a novel strategy to enhance the protective effect of antioxidant therapy by targeting the ROCK1 pathway to stabilize the actin cytoskeleton and boost the inhibitory effects on ROS production, apoptosis and cell detachment.