Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients.

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease. Actionable alterations (MSI-H phenotype and HRR genes) were identified in approximately a fifth of all cases. These results help elucidate the landscape of genomic alterations across the clinical spectrum of prostate cancer.

Virological and cytological changes in tears and conjunctiva of patients with COVID-19.

Purpose: To analyze the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears/conjunctival epithelium and assess the cytomorphological changes in the conjunctival epithelium of coronavirus disease 2019 (COVID-19) patients. Methods: In this pilot study, patients with moderate to severe COVID-19 were recruited from the COVID ward/intensive care unit of the institute. Tears and conjunctival swabs were collected from COVID-19 patients and sent to the virology laboratory for reverse transcription polymerase chain reaction (RT-PCR) testing. Conjunctival swabs were used to prepare smears, which underwent cytological evaluation and immunocytochemistry for SARS-CoV-2 nucleocapsid protein. Results: Forty-two patients were included. The mean age of participants was 48.61 (range: 5-75) years. Seven (16.6%) patients tested positive for SARS-CoV-2 ribonucleic acid in tears samples, four (9.5%) of which were positive on conjunctival swab by RT-PCR in the first test. Cytomorphological changes were observed significantly more in smears from patients with positive RT-PCR on tear samples, including bi-/multi-nucleation (p = 0.01), chromatin clearing (p = 0.02), and intra-nuclear inclusions (p < 0.001). One case (3.2%) showed immunopositivity for SARS-CoV-2; this patient had severe disease and the lowest Ct values for tear and conjunctival samples among all positive cases. Conclusion: Conjunctival smears from patients with COVID-19 revealed cytomorphological alterations, even in the absence of clinically significant ocular infection. However, viral proteins were demonstrated within epithelial cells only rarely, suggesting that although the conjunctival epithelium may serve as a portal for entry, viral replication is possibly rare or short-lived.