Multifocal Unilateral Orange Fundus Tumors in a Young Man.

A 38-year-old man had an asymptomatic, orange, macular choroidal mass with macular choroidal folds and a retinal pigment epithelial detachment in the right eye and a second orange mass nasal to the optic disc also in the right eye. What would you do next?

Missed games, financial losses, and characteristics of eye injuries in the National Basketball Association during the 2010-2011 to 2017-2018 seasons.

PURPOSE: The purpose is to report financial loss, demographic metrics, and mechanisms of injury associated with eye injuries in the National Basketball Association (NBA) from the 2010-2011 to 2017-2018 seasons. METHODS: We performed a retrospective review of eye injuries in the NBA from the 2010-2011 to 2017-2018 seasons using publicly available information from Basketball Reference and the Pro Sports Transactions websites. Only injuries of the eye and adnexa that caused players to miss games in the regular season and playoffs were included in the study. Financial loss was calculated based on the regular season salary of the players and normalized for inflation with 2018 as the base year. RESULTS: There were 30 eye injuries causing a total of 106 missed games and $7,486,770 in financial losses across eight seasons. Linear regressions showed a moderately positive increase in eye injuries (Pearson's r = 0.68, P = 0.07, and 0.79 injuries per year/1000 game-days increase) and financial losses (Pearson's r = 0.67, P = 0.07, and $185.75 increase per year/1000 game-days) over time. There were significantly more games missed due to orbital fractures than games missed due to contusions/lacerations (11.5 vs. 2.8 missed games, P = 0.01). CONCLUSION: We demonstrate an increasing trend of eye injuries in the NBA, resulting in increased financial loss. Injuries may be varied in type and affect the number of games missed.

Immunization with a self-assembling nanoparticle vaccine displaying EBV gH/gL protects humanized mice against lethal viral challenge.

Epstein-Barr virus (EBV) is a cancer-associated pathogen responsible for 165,000 deaths annually. EBV is also the etiological agent of infectious mononucleosis and is linked to multiple sclerosis and rheumatoid arthritis. Thus, an EBV vaccine would have a significant global health impact. EBV is orally transmitted and has tropism for epithelial and B cells. Therefore, a vaccine would need to prevent infection of both in the oral cavity. Passive transfer of monoclonal antibodies against the gH/gL glycoprotein complex prevent experimental EBV infection in humanized mice and rhesus macaques, suggesting that gH/gL is an attractive vaccine candidate. Here, we evaluate the immunogenicity of several gH/gL nanoparticle vaccines. All display superior immunogenicity relative to monomeric gH/gL. A nanoparticle displaying 60 copies of gH/gL elicits antibodies that protect against lethal EBV challenge in humanized mice, whereas antibodies elicited by monomeric gH/gL do not. These data motivate further development of gH/gL nanoparticle vaccines for EBV.

Adequacy of samples obtained via percutaneous core-needle rebiopsy for EGFR T790M molecular analysis in patients with non-small cell lung cancer following acquired resistance to first-line therapy: A systematic review and meta-analysis.

MICRO ABSTRACT: Rebiopsies characterizing resistance mutations in patients with non-small cell lung cancer (NSCLC) can guide personalized medicine and improve overall survival rates. In this systematic review, we examine the suitability of percutaneous core-needle biopsy (PT-CNB) to obtain adequate samples for molecular characterization of the acquired resistance mutation T790M. This review provides evidence that PT-CNB can obtain samples with high adequacy, with a mutation detection rate that is in accordance with prior literature. BACKGROUND: Non-small cell lung cancer (NSCLC) comprises 85% of all lung cancers and has seen improved survival rates with the rise of personalized medicine. Resistance mutations to first-line therapies, such as T790M, however, render first-line therapies ineffective. Rebiopsies characterizing resistance mutations inform therapeutic decisions, which result in prolonged survival. Given the high efficacy of percutaneous core-needle biopsy (PT-CNB), we conducted the first systematic review to analyze the ability of PT-CNB to obtain samples of high adequacy in order to characterize the acquired resistance mutation T790M in patients with NSCLC. METHODS: We performed a comprehensive literature search across PubMed, Embase, and CENTRAL. Search terms related to "NSCLC," "rebiopsy," and "PT-CNB" were used to obtain results. We included all prospective and retrospective studies that satisfied our inclusion and exclusion criteria. A random effects model was utilized to pool adequacy and detection rates of the chosen articles. We performed a systematic review, meta-analysis, and meta-regression to investigate the adequacy and T790M detection rates of samples obtained via PT-CNB. RESULTS: Out of the 173 studies initially identified, 5 studies met the inclusion and exclusion criteria and were chosen for our final cohort of 436 patients for meta-analysis. The pooled adequacy rate of samples obtained via PT-CNB was 86.92% (95% CI: [79.31%, 92.0%]) and the pooled T790M detection rate was 46.0% (95% CI: [26.6%, 66.7%]). There was considerable heterogeneity among studies (I2 > 50%) in both adequacy and T790M detection rates. CONCLUSION: PT-CNB can obtain adequate samples for T790M molecular characterization in NSCLC lung cancer patients. Additional prospective studies are needed to corroborate the results in this review.

Eye injuries in the National Hockey League from 2010 to 2018: an analysis of injury rates, mechanisms, and the National Hockey League visor policy.

OBJECTIVE: We aim to assess the efficacy of widespread visor adoption by assessing eye injury rates during the 2010-2018 seasons. We also compare injury rates, missed games, and financial losses to previously reported data in order to track progress over time. Lastly, we characterize the mechanism and type of eye injuries sustained by National Hockey League (NHL) players to examine risk areas within NHL games. DESIGN: We performed a retrospective review of NHL player injuries using official NHL team reports, ProSportsTransactions, and TSN Sports. PARTICIPANTS: All NHL players who suffered an eye injury from 2010 to 2018 were included; 31 injuries matched this criterion. METHODS: Trends in injuries, missed games, and financial losses over time were analyzed using Pearson's correlation coefficients. Wilcoxon-Mann-Whitney tests were performed to compare our data with eye injury data. Fisher's exact test was performed to assess significance between mechanism and type of eye injury and outcome. RESULTS: There were 31 total eye injuries causing 233 missed games and a total of US$8 951 000 in financial losses across the 2010-2018 seasons. There was a strong decrease in the number of eye injuries (r = -0.83, p = 0.01) and a moderate decrease in number of missed games (r = -0.62, p = 0.09). Injuries due to direct puck strikes contributed to over US$6.5 million in financial losses and led to significantly more missed games compared with stick injuries (14.6 vs 4.3). CONCLUSION: We tangibly demonstrate the financial and physical effects of recent safety interventions and indicate areas for improved safety in the NHL.

A CD40 Agonist and PD-1 Antagonist Antibody Reprogram the Microenvironment of Nonimmunogenic Tumors to Allow T-cell-Mediated Anticancer Activity.

In cancers with tumor-infiltrating lymphocytes (TILs), monoclonal antibodies (mAbs) that block immune checkpoints such as CTLA-4 and PD-1/PD-L1 promote antitumor T-cell immunity. Unfortunately, most cancers fail to respond to single-agent immunotherapies. T regulatory cells, myeloid derived suppressor cells (MDSCs), and extensive stromal networks within the tumor microenvironment (TME) dampen antitumor immune responses by preventing T-cell infiltration and/or activation. Few studies have explored combinations of immune-checkpoint antibodies that target multiple suppressive cell populations within the TME, and fewer have studied the combinations of both agonist and antagonist mAbs on changes within the TME. Here, we test the hypothesis that combining a T-cell-inducing vaccine with both a PD-1 antagonist and CD40 agonist mAbs (triple therapy) will induce T-cell priming and TIL activation in mouse models of nonimmunogenic solid malignancies. In an orthotopic breast cancer model and both subcutaneous and metastatic pancreatic cancer mouse models, only triple therapy was able to eradicate most tumors. The survival benefit was accompanied by significant tumor infiltration of IFNγ-, Granzyme B-, and TNFα-secreting effector T cells. Further characterization of immune populations was carried out by high-dimensional flow-cytometric clustering analysis and visualized by t-distributed stochastic neighbor embedding (t-SNE). Triple therapy also resulted in increased infiltration of dendritic cells, maturation of antigen-presenting cells, and a significant decrease in granulocytic MDSCs. These studies reveal that combination CD40 agonist and PD-1 antagonist mAbs reprogram immune resistant tumors in favor of antitumor immunity.