Targeting androgen biosynthesis in prostate cancer: implications on endocrine physiology.

PURPOSE OF REVIEW: Targeting specific steroidogenic enzymes is effective in decreasing testosterone synthesis, resulting in significant antitumor effects in prostate cancer. Such treatments result in disruptions of complicated and intertwining pathways with systemic physiologic consequences via effects on the adrenal gland and renin-angiotensin-aldosterone axis. This review highlights some of these aspects that need to be taken into consideration when treating patients with androgen biosynthesis inhibitors. RECENT FINDINGS: Targeting CYP17A1, a key enzyme involved in androgen biosynthesis, is a well established treatment in prostate cancer. More recently, efforts are underway to target a gatekeeper enzyme of steroidogenesis, CYP11A1. This enzyme mediates conversion of cholesterol to pregnenolone, the first step in steroid hormone biogenesis. Studies are beginning to demonstrate antitumor effects of ODM-208, a CYP11A1 inhibitor in prostate cancer. Although anticipated to have a therapeutic role in prostate cancer, there are potential downstream effects of CYP11A1 targeting arising from suppression of the entire adrenal cortex, including long-term adrenal insufficiency and possibly cardiovascular dysregulation. SUMMARY: Agents targeting androgen biosynthesis can have systemic implications. Balancing management of prostate cancer with better understanding of the mechanisms associated with potential side effects will allow for patients to obtain improved antitumor benefit while mitigating against treatment-associated adverse effects.

Amyl Nitrite-Induced Hemolytic Anemia: Acute Therapy and Prevention.

Inhaled nitrites have been a substance of recreational use for centuries, primarily among men who have sex with men (MSM). However, there is a lack of awareness of the use of inhaled nitrites in this population and the possible complications and health disparities it carries. In this case report, we present a 62-year-old man with a past medical history of glucose-6 phosphate dehydrogenase (G6PD) deficiency presenting with severe hemolytic anemia and methemoglobinemia after recreational use of inhaled nitrites. The case was complicated with the presence of methemoglobinemia in a patient with G6PD deficiency. This report also aims to increase awareness of the use of nitrites in the MSM population. The use of nitrites is a predictor for high-risk sexual behavior and is associated with positive human immunodeficiency virus (HIV) status.

The effect of anticoagulation on clinical outcomes in novel Coronavirus (COVID-19) pneumonia in a U.S. cohort.

BACKGROUND: COVID-19 infection is associated with D-dimer elevations, high rates of thrombus formation, and poor clinical outcomes. We sought to determine if empiric therapeutic anticoagulation (AC) affected survival in COVID-19 patients compared to standard prophylactic AC. METHODS: Retrospective analysis of 402 COVID-19 patients hospitalized between March 15 and May 31, 2020 was performed. Clinical outcomes were compared between 152 patients treated with therapeutic AC to 250 patients on prophylactic AC. An elastic net logistic regression was designed to first identify the important variables affecting mortality. These variables were then included as covariates to AC in standard multivariate logistic regression models studying the effect of AC on death. Nonparametric survival analysis was conducted, and Kaplan Meier curves were constructed. RESULTS: Increased mortality was associated with therapeutic AC [OR 3.42 (2.06, 5.67)]. The log-rank test was statistically significant at p = 0.001 showing higher mortality for patients treated with therapeutic AC compared to prophylactic AC. Subset analysis of critically ill and intubated patients had similar survival curves regardless of AC dose. The log-rank test was not significant even with Prentice modification. For non-ICU patients, the log rank test favoring prophylactic AC disappeared when the analysis was stratified by D-dimer level less or greater than 3 µg/mL. Approximately 9% of patients receiving therapeutic AC experienced clinically significant bleeding or thrombocytopenia, versus 3% in those receiving prophylactic AC. CONCLUSIONS: In our cohort, therapeutic anticoagulation provided no mortality benefit over thromboprophylaxis, independent of co-morbidities or disease severity. More adverse events were observed with therapeutic AC.

Filgrastim induced thrombocytopenia.

Drug-induced thrombocytopenia (DITP) is suggested by severe thrombocytopenia with subsequent recovery of platelet count after removal of the offending drug. The diagnosis is ascertained when there is reproducibility of thrombocytopenia with repeated exposure. Filgrastim is used during peripheral blood progenitor cell harvest during autologous stem cell transplantation in the setting of multiple myeloma to prolong event-free survival and overall mortality. The following case illustrates all of the suggestive features of DITP after filgrastim exposure during elective stem cell harvest. Due to the inability to tolerate filgrastim, autologous stem cell transplant was aborted in this patient and he was maintained on induction chemotherapy.