The purpose of this study was to determine the level of gross motor skills in ASD children during the COVID-19 Pandemic. Participants in this study were ASD children with a total of 25 children aged 8-12 years (M = 10.02;SD 1.27), who were selected by random sampling technique. This research instrument is the Test of Gross Motor Development-2 (TGMD-2). Data analysis in this study is descriptive analysis. The results of gross motor skills show that 20 ASD children are in the average standard score of 4-5 (gross motor question = 70-79) in the low assessment category (80.00%) and 5 ASD children are in the average standard score of 1-3 (gross motor question = <70) is included in the very low assessment category (20.00%). Therefore, the majority of the total gross motoric data for ASD children are in the low category, namely 20 children or 80.00%. This research is not without limitations in its implementation. This research contributes to the implementation of future research, namely the need for treatment to optimize Gross Motor skills in Children with Autism Spectrum Disorder during the COVID-19 Pandemic. The urgency for proper and measurable treatment and the limitations of this study are important things to pay attention to for further research. © 2021 by authors, all rights reserved.

Simple Summary Vulvar squamous cell carcinoma (VSCC) is the most common form of vulvar malignancy, and its incidence has increased in recent years. For better diagnosis and prognostication, and to expand available treatment options, molecular characterization of VSCC is crucial. We sought to identify aberrations in DNA methylation in VSCC, as this has been implicated in the development of several cancers. To this end, we performed genome-wide methylation sequencing on a set of VSCC and normal vulvar tissue using the Infinium MethylationEPIC BeadChip array. We detected 199 genes to be differentially methylated in VSCC compared to normal vulvar tissue. Of these, 194 genes were hyper-methylated, which leads to a loss of function of the genes. As most of these genes are involved in transcription regulator activity, our results suggest that disruption of this process plays an important role in VSCC development. Abstract DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (Δβ) of ±0.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.

Introduction Immune checkpoint inhibitors (CPIs) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce. Methods We conducted a multicenter (six cancer centers), cohort study of outcomes in patients treated with IFX for corticosteroid-refractory CPI-induced enterocolitis between 2007 and 2020. The primary outcome was corticosteroid-free clinical remission (CFCR) with Common Terminology Criteria for Adverse Events (CTCAE) grade 0 for diarrhea at 12 weeks after IFX initiation. We also assessed cancer outcomes at 1 year using RECIST V1.1 criteria. Results 127 patients (73 male; median age 59 years) were treated with IFX for corticosteroid-refractory CPI-induced enterocolitis. Ninety-six (75.6%) patients had diarrhea CTCAE grade >2 and 115 (90.6%) required hospitalization for colitis. CFCR was 41.2% at 12 weeks and 50.9% at 26 weeks. In multivariable logistic regression, IFX-resistant enterocolitis was associated with rectal bleeding (OR 0.19; 95% CI 0.04 to 0.80; p=0.03) and absence of colonic crypt abscesses (OR 2.16; 95% CI 1.13 to 8.05; p=0.03). Cancer non-progression was significantly more common in patients with IFX-resistant enterocolitis (64.4%) as compared with patients with IFX-responsive enterocolitis (37.5%; p=0.013). Conclusion This is the largest study to date reporting outcomes of IFX therapy in patients with corticosteroid-refractory CPI-induced enterocolitis. Using predefined robust endpoints, we have demonstrated that fewer than half of patients achieved CFCR. Our data also indicate that cancer outcomes may be better in patients developing prolonged and severe inflammatory side effects of CPI therapy.

The clinical and immunologic implications of the SARS-CoV-2 pandemic for patients with cancer receiving systemic anticancer therapy have introduced a multitude of clinical challenges and academic controversies. This review summarizes the current evidence, discussion points, and recommendations regarding the use of immune checkpoint inhibitors (ICIs) in patients with cancer during the SARS-CoV-2 pandemic, with a focus on patients with melanoma and renal cell carcinoma (RCC). More specifically, we summarize the theoretical concepts and available objective data regarding the relationships between ICIs and the antiviral immune response, along with recommended clinical approaches to the management of melanoma and RCC patient cohorts receiving ICIs throughout the course of the COVID-19 pandemic. Additional insights regarding the use of ICIs in the setting of current and upcoming COVID-19 vaccines and broader implications toward future pandemics are also discussed.

While our knowledge of the evolutionary features of primary tumors has grown exponentially over the last few years our understanding of evolution of metastases is more limited and many open questions remain, regarding the timing of metastatic dissemination, the acquisition of metastatic competence and the underpinning of the variety of metastatic phenotypes observed in the clinic from latent metastases to solitary and oligo-metastases to widespread metastases. We have leveraged unique translational protocols that allow interrogation of tumor evolution from the earliest stages of diseases to death to address some of these questions. In the context of renal cell cancers we show that the mode of evolution at the primary tumor site determines the tempo and distribution of systemic metastases; that the features that distinguish metastasis-competent clones included genome instability and aneuploidy; and that metastatic competence often emerges in the centre of the primary tumor. In the context of melanoma we observe a wide spectrum of metastatic seeding that includes organ-specific metastatic clones, monophyletic and polyphyletic seeding and polyclonal mixing at metastatic sites. We observe progressive increase in aneuploidy and occurrence of whole genome doubling as melanoma metastases progress and resist treatment suggesting this as a a mechanism of immune-evasion and treatment resistance. Citation Format: Samra Turajlic. Understanding evolution of metastatic disease in renal cancer and melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY02-02.