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Reactive nitrogen species (RNS) is a subset of free oxygen radicals called reactive oxygen species (ROS). Physiological levels of ROS are necessary to maintain the reproductive functions such as cell signaling, tight junction regulation, production of hormones, capacitation, acrosomal reaction, sperm motility, and zona pellucida binding. However, an excess of RNS can adversely affect reproductive potential by causing testicular dysfunction, decreased gonadotropin secretion, and abnormal semen parameters. Because such levels of RNS have been demonstrated in males with fertility problems and routine semen analysis has not been able to accurately predict IVF outcomes, it is imperative that novel strategies be developed in order to both assess and treat oxidative stress. This article describes both physiological and pathological roles of this unique subset of ROS.

BackgroundWheat allergy is among the most common food allergy in children, but few publications are available assessing the risk of anaphylaxis due to wheat.MethodsIn this study, we report the case of near-fatal anaphylaxis to wheat in a patient undergoing an oral food challenge (OFC) after the ingestion of a low dose (256 mg) of wheat. Moreover, for the first time, we analyzed the risk of anaphylaxis during an OFC to wheat in 93 children, compared to other more commonly challenged foods such as milk, egg, peanuts, and soy in more than 1000 patients.ResultsThis study, which includes a large number of OFCs to wheat, shows that wheat is an independent risk factor that is associated with anaphylaxis requiring epinephrine administration (Odds Ratio [OR] = 2.4) and anaphylaxis requiring epinephrine administration to low dose antigen (OR = 8.02). Other risk factors for anaphylaxis, anaphylaxis requiring epinephrine administration, and anaphylaxis to low dose antigen was a history of a prior reaction not involving only the skin (OR = 1.8, 1.9 and 1.8 respectively). None of the clinical variables available prior to performing the OFC could predict which children among those undergoing OFCs to wheat would develop anaphylaxis or anaphylaxis for low dose antigen.ConclusionThis study shows that wheat is an independent risk factor that is associated with anaphylaxis requiring epinephrine administration and anaphylaxis requiring epinephrine administration to low dose antigen.

BackgroundImmune checkpoint inhibitors (ICIs) improve survival outcomes in metastatic melanoma and non-small cell lung cancer (NSCLC). Preclinical evidence suggests that overexpression of cyclo-oxygenase-2 (COX2) in tumors facilitates immune evasion through prostaglandin E2 production and that COX inhibition synergizes with ICIs to promote antitumor T-cell activation. This study investigates whether concurrent COX inhibitor (COXi) use during ICI treatment compared with ICI alone is associated with improved time-to-progression (TTP), objective response rate (ORR) and overall survival (OS) in patients with metastatic melanoma and NSCLC.MethodsWe retrospectively reviewed 90 metastatic melanoma and 37 metastatic NSCLC patients, treated with ICI between 2011 and 2019. Differences in TTP and OS by ICI+COXi versus ICI alone were compared using Kaplan-Meier and Cox regression. Interaction between ICI+COXi versus ICI alone and pretreatment neutrophil–lymphocyte ratio (NLR) was examined. Independent radiology review per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was performed.ResultsFor patients with melanoma, median TTP was significantly prolonged in ICI+COXi versus ICI alone (245 vs 100.5 days, p=0.002). On multivariate analysis, ICI+COXi associated with increased TTP (HR 0.36, 95% CI 0.2 to 0.66, p=0.001), adjusted for age, pretreatment NLR, and gender. For NSCLC patients, ICI+COXi also associated with increased TTP compared with ICI alone on multivariate analysis (HR 0.45; 95% CI 0.21 to 0.97; p=0.042) adjusted for age. ORR at 6 months was significantly higher in patients who received ICI+COXi compared with ICI alone in both melanoma (58.6% vs 19.2%, p=0.0005) and NSCLC (73.7% vs 33.3%, p=0.036) cohorts. In the melanoma cohort, high pretreatment NLR (>5) associated with decreased TTP (HR 3.21, 95% CI 1.64 to 6.3; p=0.0007); however, ICI+COXi significantly associated with increased TTP in high NLR (>5) patients (HR 0.08, 95% CI 0.03 to 0.25), but not in low NLR (≤5) patients (HR 0.65, 95% CI 0.32 to 1.32). Similar outcomes were found in an adjusted melanoma cohort after RECIST review.ConclusionsOur study suggests that COXi use concurrently with ICI significantly associated with longer TTP and improved ORR at 6 months in patients with metastatic melanoma and NSCLC compared with ICI alone. Furthermore, COXi use appears to reverse the negative prognostic effect of a high NLR by prolonging TTP in patients with melanoma.

The baseline volume of ABM and the fraction of ABM present in patients vary significantly. The ongoing NRG-GY006 trial and other efforts at bone marrow sparing use V10, V20, and mean dose to the ABM during planning optimization. This analysis suggests that the volume of ABM spared 40 Gy (> 738 cc) may be a stronger predictor of HT than conventional dosimetric parameters. This should be further evaluated for clinical use.

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Purpose/Objective(s) To establish the prevalence of SARS-CoV-2 in asymptomatic patients scheduled to receive radiation therapy and its impact on management decisions. Materials/Methods Between April 2020 and July 2020, patients without influenza-like-illness (ILI) symptoms at four radiation oncology departments (2 academic university hospitals and 2 community hospitals) underwent polymerase chain reaction (PCR) testing for SARS-CoV-2 prior to the initiation of treatment. Patients were tested either prior to radiotherapy simulation or after simulation but prior to treatment initiation. Patients tested for indications of ILI symptoms were excluded from this analysis. Management of SARS-CoV-2-positive patients was individualized based on disease site and acuity. Results Over a three-month period, a total of 385 tests were performed in 336 asymptomatic patients either prior to simulation (n=75), post-simulation, prior to treatment (n=230), or on-treatment (n=49). A total of 5 patients tested positive for SARS-CoV-2, for a pre-treatment prevalence of 1.3% (2.6% in North/Central NJ and 0.4% in Southern NJ/Southeast PA). The median age of positive patients was 58 years (range: 38-78 years). All positive patients were white and were relatively equally distributed with regard to gender (2 male, 3 female) and ethnicity (2 Hispanic and 3 non-Hispanic). The median Charlson comorbidity score among positive patients was 5. All 5 patients were treated for different primary tumor sites, the large majority had advanced disease (80%), and all were treated for curative intent. The majority of positive patients were being treated with either sequential or concurrent immunosuppressive systemic therapy (80%). Initiation of treatment was delayed for 14 days with the addition of re-testing for 4 patients, while one patient was treated without delay but with additional infectious-disease precautions. Conclusion Broad-based pre-treatment asymptomatic testing of radiation oncology patients for SARS-CoV-2 is of limited value, even in a high-incidence region. Future strategies may include focused risk-stratified asymptomatic testing.

NCT02427399; https://clinicaltrials.gov/ct2/show/NCT02427399 .