Publications

Approximately 20% of metastatic prostate cancers harbor mutations in genes required for DNA repair by homologous recombination repair (HRR) such as HRR defects confer synthetic lethality to PARP inhibitors (PARPi) such as olaparib and talazoparib. In ovarian or breast cancers, olaparib resistance has been associated with HRR restoration, including by mutation reversion. Whether similar mechanisms operate in prostate cancer, and could be detected in liquid biopsies, is unclear. Here, we identify reversion mutations associated with olaparib and talazoparib resistance in patients with prostate cancer. Analysis of circulating cell-free DNA (cfDNA) reveals reversion mutation heterogeneity not discernable from a single solid-tumor biopsy and potentially allows monitoring for the emergence of PARPi resistance. The mechanisms of clinical resistance to PARPi in DNA repair-deficient prostate cancer have not been described. Here, we show reversion mutations in patients with prostate cancer with metastatic disease who developed resistance to talazoparib and olaparib. Furthermore, we show that PARPi resistance is highly multiclonal and that cfDNA allows monitoring for PARPi resistance. .

PURPOSE

One of the unanswered questions in symptom clusters research is whether the number and types of symptom clusters vary based on the dimension of the symptom experience used to create the clusters. Given that patients with breast cancer receiving chemotherapy (CTX), report between 10 and 32 concurrent symptoms and studies of symptom clusters in these patients are limited, the purpose of this study, in breast cancer patients undergoing CTX (n = 515), was to identify whether the number and types of symptom clusters differed based on whether symptom occurrence rates or symptom severity ratings were used to create the clusters.

METHODS

A modified version of the Memorial Symptom Assessment Scale was used to assess for the occurrence and severity of 38 symptoms, one week after the administration of CTX. Exploratory factor analysis was used to extract the symptom clusters.

RESULTS

Both the number and types of symptom clusters were similar using symptom occurrence rates or symptom severity ratings. Five symptom clusters were identified using symptom occurrence rates (i.e., psychological, hormonal, nutritional, gastrointestinal, epithelial). Six symptom clusters (i.e., psychological, hormonal, nutritional, gastrointestinal, epithelial, chemotherapy neuropathy) were identified using symptom severity ratings. Across the two dimensions, the specific symptoms within each of the symptom clusters were similar.

CONCLUSIONS

Identification of symptom clusters in patients with breast cancer may be useful in guiding symptom management interventions. Future studies are warranted to determine if symptom clusters remain stable over a cycle of CTX in patients with breast cancer.

OBJECTIVE

Carbon monoxide (CO) is an odorless, colorless gas produced by fossil fuel combustion. On October 29, 2012, Hurricane Sandy moved ashore near Atlantic City, New Jersey, causing widespread morbidity and mortality, $30 to $50 billion in economic damage, and 8.5 million households to be without power. The combination of power outages and unusually low temperatures led people to use alternate power sources, placing many at risk for CO exposure.

METHODS

We examined Hurricane Sandy-related CO exposures from multiple perspectives to help identify risk factors and develop strategies to prevent future exposures. This report combined data from 3 separate sources (health departments, poison centers via the National Poison Data System, and state and local public information officers).

RESULTS

Results indicated that the number of CO exposures in the wake of Hurricane Sandy was significantly greater than in previous years. The persons affected were mostly females and those in younger age categories and, despite messaging, most CO exposures occurred from improper generator use.

CONCLUSIONS

Our findings emphasize the continued importance of CO-related communication and ongoing surveillance of CO exposures to support public health response and prevention during and after disasters. Additionally, regional poison centers can be a critical resource for potential on-site management, public health promotion, and disaster-related CO exposure surveillance. (Disaster Med Public Health Preparedness. 2017;11:562-567).