Effect of dermatological consultation on survival in patients with checkpoint inhibitor-associated cutaneous toxicity.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) are a common side-effect of immune checkpoint inhibitors (ICIs). However, prior work examining these toxicities in detail has considered only the fraction of events evaluated by dermatologists. Associations between dermatology referral, cirAE treatment and survival outcomes remain underexplored across care settings. OBJECTIVES: To comprehensively categorize cirAE patterns among all patients treated with immunotherapy at our institution, and to evaluate: (i) the effect of dermatology referral on cirAE treatment and (ii) the impact of cirAE treatment on survival. METHODS: This was a retrospective cohort analysis of patients with cancer who initiated ICI therapy between 1 January 2016 and 8 March 2019 and developed one or more cirAEs, as screened for using International Classification of Diseases 10th revision codes and confirmed via manual chart review (n = 358). All relevant information documented prior to 31 March 2020 was included. RESULTS: CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred (odds ratio 6·08, P < 0·001). Patients who received any cirAE treatment had improved progression-free survival [hazard ratio (HR) 0·59, P = 0·001] and overall survival (HR 0·58, P = 0·007) compared with those who did not. CONCLUSIONS: CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred, and patients who received any treatment for a cirAE had improved survival outcomes.

Association of sporadic and familial Barrett's esophagus with breast cancer.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Based on striking aggregation of breast cancer and BE/EAC within families as well as shared risk factors and molecular mechanisms of carcinogenesis, we hypothesized that BE may be associated with breast cancer. Pedigree analysis of families identified prospectively at multiple academic centers as part of the Familial Barrett's Esophagus Consortium (FBEC) was reviewed and families with aggregation of BE/EAC and breast cancer are reported. Additionally, using a matched case-control study design, we compared newly diagnosed BE cases in Caucasian females with breast cancer (cases) to Caucasian females without breast cancer (controls) who had undergone upper endoscopy (EGD). Two familial pedigrees, meeting a stringent inclusion criterion, manifested familial aggregation of BE/EAC and breast cancer in an autosomal dominant inheritance pattern with incomplete penetrance. From January 2008 to October 2016, 2812 breast cancer patient charts were identified, of which 213 were Caucasian females who underwent EGD. Six of 213 (2.82%) patients with breast cancer had pathology-confirmed BE, compared to 1 of 241 (0.41%) controls (P-value < 0.05). Selected families with BE/EAC show segregation of breast cancer. A breast cancer diagnosis is marginally associated with BE. We postulate a common susceptibility between BE/EAC and breast cancer.

Biogeochemical environments of streambed-sediment pore waters with and without arsenic enrichment in a sedimentary rock terrain, New Jersey Piedmont, USA.

Release of arsenic (As) from sedimentary rocks has resulted in contamination of groundwater in aquifers of the New Jersey Piedmont Physiographic Province, USA; the contamination also may affect the quality of the region's streamwater to which groundwater discharges. Biogeochemical mechanisms involved in the release process were investigated in the streambeds of Six Mile Run and Pike Run, tributaries to the Millstone River in the Piedmont. At Six Mile Run, streambed pore water and shallow groundwater were low or depleted in oxygen, and contained As at concentrations greater than 20 µg/L. At Pike Run, oxidizing conditions were present in the streambed, and the As concentration in pore water was 2.1 µg/L. The 16S rRNA gene and the As(V) respiratory reductase gene, arrA, were amplified from DNA extracted from streambed pore water at both sites and analyzed, revealing that distinct bacterial communities that corresponded to the redox conditions were present at each site. Anaerobic enrichment cultures were inoculated with pore water from gaining reaches of the streams with acetate and As(V). As(V) was reduced by microbes to As(III) in enrichments with Six Mile Run pore water and groundwater, whereas no reduction occurred in enrichments with Pike Run pore water. Cloning and sequencing of the arrA gene indicated 8 unique operational taxonomic units (OTUs) at Six Mile Run and 11 unique OTUs at Pike Run, which may be representative of the arsenite oxidase gene arxA. Low-oxygen conditions at Six Mile Run have favored microbial As reduction and release, whereas release was inhibited by oxidizing conditions at Pike Run.