Hidradenitis suppurativa perspectives during the COVID-19 pandemic.

The COVID-19 pandemic created a new set of challenges regarding the care of patients with hidradenitis suppurativa (HS). Access to safe, timely medical care and the use of immunosuppressive therapy were central topics of concern for patients and providers. In addition, the incidence and severity of SARS-CoV-2 infection in patients with HS were critical to examine during the evolving pandemic and to provide recommendations for patients for makinginformed decisions about their disease and its management. Another consideration of the COVID-19 pandemic was the role of the internet to connect individuals with HS with each other and experts in the field. This is a unique contribution that collectively examines the perspectives of HS medical care and support during the COVID-19 pandemic.

PRMT-1 and p120-Catenin as EMT Mediators in Osimertinib Resistance in NSCLC.

Osimertinib, an irreversible tyrosine kinase inhibitor, is a first-line therapy in EGFR-mutant NSCLC patients. Prolonged treatment with Osimertinib leads to resistance due to an acquired C797S mutation in the EGFR domain and other mechanisms, such as epithelial-mesenchymal transition (EMT). In this study, we investigated the role of PRMT-1 and p120-catenin in mediating Osimertinib resistance (OR) through EMT. These studies found upregulation of gene and protein expression of PRMT-1, p120-catenin and Kaiso factor. Knockdown of p120-catenin using siRNA increased OR efficacy by 45% as compared to cells treated with mock siRNA and OR. After 24 h of transfection, the percentage wound closure in cells transfected with p120-catenin siRNA was 26.2%. However, in mock siRNA-treated cells the wound closure was 7.4%, showing its involvement in EMT. We also found high levels of p120-catenin expressed in 30% of smokers as compared to 5.5% and 0% of non-smokers and quit-smokers (respectively) suggesting that smoking may influence p120-catenin expression in NSCLC patients. These results suggest that biomarkers such as PRMT-1 may mediate EMT by methylating Twist-1 and increasing p120-catenin expression, which causes transcriptional activation of genes associated with Kaiso factor to promote EMT in Osimertinib-resistant cells.

Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies.

Melanoma possesses invasive metastatic growth patterns and is one of the most aggressive types of skin cancer. In 2021, it is estimated that 7180 deaths were attributed to melanoma in the United States alone. Once melanoma metastasizes, traditional therapies are no longer effective. Instead, immunotherapies, such as ipilimumab, pembrolizumab, and nivolumab, are the treatment options for malignant melanoma. Several biomarkers involved in tumorigenesis have been identified as potential targets for molecularly targeted melanoma therapy, such as tyrosine kinase inhibitors (TKIs). Unfortunately, melanoma quickly acquires resistance to these molecularly targeted therapies. To bypass resistance, combination treatment with immunotherapies and single or multiple TKIs have been employed and have been shown to improve the prognosis of melanoma patients compared to monotherapy. This review discusses several combination therapies that target melanoma biomarkers, such as BRAF, MEK, RAS, c-KIT, VEGFR, c-MET and PI3K. Several of these regimens are already FDA-approved for treating metastatic melanoma, while others are still in clinical trials. Continued research into the causes of resistance and factors influencing the efficacy of these combination treatments, such as specific mutations in oncogenic proteins, may further improve the effectiveness of combination therapies, providing a better prognosis for melanoma patients.

Outcomes of symptom screening and universal COVID-19 reverse transcriptase polymerase chain reaction testing before endoscopy in a community-based ambulatory surgery center.

BACKGROUND AND AIMS: Elective endoscopy resumed in our outpatient ambulatory center after instituting the preprocedure policy of a confirmed negative coronavirus disease 2019 (COVID-19) reverse transcriptase polymerase chain reaction (RT-PCR) status performed 72 hours before a scheduled procedure as mandated by the state of Illinois. In addition, all patients were required to contemporaneously complete the American Society for Gastrointestinal Endoscopy (ASGE) COVID-19 risk screening questionnaire published April 28, 2020 as outlined in the ASGE guidance document for reopening GI endoscopy during the COVID-19 pandemic. The aim of our study is to report the outcomes of 1000 patients who successfully completed the clinical aspects of the ASGE COVID-19 risk screening questionnaire and whose RT-PCR tests were valid for interpretation. METHODS: Data were retrospectively collected from patient medical records for demographics, symptom responses to the preprocedure ASGE COVID-19 risk screening questionnaire, and RT-PCR test results of patients scheduled to undergo an elective outpatient endoscopy at Rockford Gastroenterology Associates from May 22 through June 28, 2020. Descriptive statistics and standard calculation methods to determine both positive and negative predictive values were used for data analysis. RESULTS: Eight of 1000 patients included in the study tested positive for COVID-19. Three of 8 patients reported 1 or more symptoms on the ASGE COVID-19 risk screening questionnaire. One hundred nineteen additional patients reported symptoms on the ASGE COVID-19 risk screening questionnaire but tested negative for COVID-19. The positive and negative predictive values of the ASGE COVID-19 risk screening questionnaire were 2.46% and 99.43%, respectively. CONCLUSIONS: The low incidence of COVID-19 infection in a community-based ambulatory surgery center is supported by a positive RT-PCR test rate of .80%. Absence of symptoms on the ASGE COVID-19 risk screening questionnaire was highly predictive of a negative RT-PCR test (99.43% negative predictive value), whereas the positive predictive value was low (2.46%) in symptomatic patients. A positive RT-PCR test was invaluable in preventing 5 asymptomatic patients from undergoing endoscopy. Similarly, 119 symptomatic patients underwent endoscopic evaluation who would have otherwise been excluded without RT-PCR testing. Symptom-based screening alone should not be the primary preprocedural assessment tool in selecting patients for undergoing endoscopy during the COVID-19 pandemic.