Rhinovirus persistence during the COVID-19 pandemic-Impact on pediatric acute wheezing presentations.

Rhinoviruses have persisted throughout the COVID-19 pandemic, despite other seasonal respiratory viruses (influenza, parainfluenza, respiratory syncytial virus, adenoviruses, human metapneumovirus) being mostly suppressed by pandemic restrictions, such as masking and other forms of social distancing, especially during the national lockdown periods. Rhinoviruses, as nonenveloped viruses, are known to transmit effectively via the airborne and fomite route, which has allowed infection among children and adults to continue despite pandemic restrictions. Rhinoviruses are also known to cause and exacerbate acute wheezing episodes in children predisposed to this condition. Noninfectious causes such as air pollutants (PM2.5 , PM10 ) can also play a role. In this retrospective ecological study, we demonstrate the correlation between UK national sentinel rhinovirus surveillance, the level of airborne particulates, and the changing patterns of pediatric emergency department presentations for acute wheezing, before and during the COVID-19 pandemic (2018-2021) in a large UK teaching hospital.

5-Hydroxymethylcytosine is an independent predictor of survival in malignant melanoma.

Outcomes for melanoma patients vary within cancer stage. Prognostic biomarkers are potential adjuncts to provide more precise prognostic information. Simple, low-cost biomarker assays, such as those based on immunohistochemistry, have strong translational potential. 5-hydroxymethylcytosine (5 hmC) shows prognostic potential in melanoma but prior studies were small. We, therefore, analysed 5 hmC in a retrospective cohort to provide external validation of its prognostic value. Two hundred primary melanomas were evaluated for 5 hmC expression using immunohistochemistry. The primary objective was to assess the effect on overall survival while controlling for important confounders. Univariable and multivariable analyses were performed. REMARK guidelines were followed. The 5 hmC immunohistochemistry scoring showed very strong inter-observer agreement (ICC 0.88) and expression was significantly related to age, site, Breslow thickness, ulceration, mitotic rate, and stage. Kaplan-Meier analysis showed 5 hmC was associated with metastasis-free, melanoma-specific, and overall survival, P<0.0001 for each. In univariable Cox proportional hazards models, 5 hmC hazard ratios were significant and remained so in a multivariable model. A two-step cox model was created using stage and 5 hmC, as stage is the gold standard for clinical practice. The addition of 5 hmC produced significant improvement in the model and 5 hmC and stage were independent significant predictors. This is the largest study of the prognostic value of 5 hmC immunohistochemistry in melanoma. The 5 hmC scoring was easily and reproducibly performed and it was an independent predictor of metastasis-free survival, melanoma-specific survival, and overall survival. This work supports further development of 5 hmC as a prognostic biomarker and suggests that it could add more precision to American Joint Committee on Cancer staging.

Breslow Density Is a Novel Prognostic Feature That Adds Value to Melanoma Staging.

Histomorphologic prognostic biomarkers that can be measured using only an hematoxylin and eosin stain are very attractive because they are simple and cheap. We conceived an entirely novel biomarker of this type, the Breslow density (BD), which measures invasive melanoma cell density at the site where Breslow thickness (BT) is measured. This study assessed BD's prognostic value. In this study, BD was measured in 1329 melanoma patients. Measurement accuracy and precision was assessed using intraclass correlation coefficient (ICC). Survival was assessed with a primary end-point of melanoma-specific survival (MSS) and also overall survival and metastasis-free survival. We found that BD measurement was accurate compared with gold standard image analysis (ICC, 0.84). Precision was excellent for 3 observers with different experience (ICC, 0.93) and for an observer using only written instructions (ICC, 0.93). BD was a highly significant predictor in multivariable analysis for overall survival, MSS, and metastasis-free survival (each, P<0.001) and it explained MSS better than BT, but BT and BD together had best explanatory capability. A BD cut point of ≥65% was trained in 970 melanomas and validated in 359. This cut point showed promise as a novel way to upstage melanoma from T stage "a" to "b." BD was combined with BT to create a targeted burden score. This was a validated as an adjunct to American Joint Committee on Cancer stage. In summary, BD can be measured accurately and precisely. It demonstrated independent prognostic value and explained MSS better than BT alone. Notably, we demonstrated ways that BD could be used with American Joint Committee on Cancer version 8 staging.

A Novel Numerical Scoring System for Melanoma Tumor-infiltrating Lymphocytes Has Better Prognostic Value Than Standard Scoring.

The purpose of this study was to evaluate the prognostic value of tumor-infiltrating lymphocytes (TILs) in melanoma and to determine whether a simpler numerical scoring system would be more effective. In total, 655 patients presenting to a UK teaching hospital with primary invasive melanoma were analyzed. TILs were rescored using the standard Clark's method and univariable and multivariable analyses of the effect of TILs on overall survival (OS), disease-specific survival (DSS), and metastasis-free survival (MFS) was assessed using Cox regression. In total, 30 (5%) melanomas showed absent, 464 (71%) nonbrisk, and 161 (24%) brisk TILs. There was a statistically significant relationship between TILs and Breslow thickness, age, melanoma type, mitotic rate, and histologic regression. TIL grade was a significant predictor of MFS in multivariable analysis (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.25-0.77) but was not significant for OS or DSS. By contrast, when a simple numerical TIL percentage score was used this was a strong predictor of OS (HR, 0.55; 95% CI, 0.38-0.78), DSS (HR, 0.25; 95% CI, 0.14-0.44), and MFS (HR, 0.32; 95% CI, 0.21-0.51) in multivariable analysis. The percentage TIL score was also significant when adjusted for the prognostic gold standard, American Joint Committee on Cancer stage: OS (HR, 0.66; 95% CI, 0.46-0.95), DSS (HR, 0.33; 95% CI, 0.19-0.60), and MFS (HR, 0.41; 95% CI, 0.26-0.65). The TIL percentage score was subsequently validated in new cases. In summary, this study strongly confirms that higher amounts of TILs are associated with better prognosis and in addition demonstrates the value of a simplified numerical TIL scoring system.