N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.
Neurodegenerative disorders (NDD) are chronic neurological diseases characterized by loss and/or damage to neurons along with the myelin sheath, and patients are at higher risk of severe infection with the SARS‑CoV‑2. A comprehensive literature search was performed using relevant terms and inclusion‑exclusion criteria. Recent articles, subjects older than 50 years, and articles written in the English language were included, whereas letters to the editor and articles related to pregnant women were excluded from the review study. COVID‑19 appears to damage angiotensin‑II receptors which cause natural killer cells to lose the ability to clear virus‑infected cells, owing to worse outcomes in patients with NDD. COVID‑19 can worsen the symptoms of Alzheimer’s disease. In addition, COVID‑19 worsens drug‑responsive motor symptoms in Parkinson’s disease (PD) and other symptoms like fatigue and urinary complaints. Vitamin D is essential in decreasing pro‑inflammatory and increasing anti‑inflammatory cytokines in ongoing COVID‑19 infections and reducing angiotensin receptors and, hence, decreasing COVID‑19 infection severity. Telemedicine shows promise for patients with NDD but is yet to overcome legal issues and personal barriers. COVID‑19 has a significant effect on neurodegenerative conditions, which appears partly to the nature of the NDD and the neuro‑invasive capabilities of the SARS‑CoV‑2. The protective role of vitamin D in patients with NDD further supports this hypothesis. Modifications in current health care, like the telemedicine platform, are required to address the increased risk of serious infection in this population. Further studies will be required to clarify conflicting reports in many fields.
e21150 Background: Capmatinib is a selective inhibitor of MET receptor that got accelerated FDA approval in May 2020 to treat NSCLC with MET ex 14 mutation (METex14). Here, we proclaim the first review of capmatinib efficacy and safety profile in METex14 positive NSCLC patients. Methods: A systematic literature search was conducted using PubMed, Cochrane Library, Clinicaltrials.gov, and Google Scholar. We compiled and analyzed the original studies evaluating the clinical response of capmatinib in MET ex14 mutated advanced NSCLC. Results: The most recent results (as of January 6, 2020) of the GEOMETRY Mono-1 phase 2 study showed an overall response rate (ORR) of 41% (69/97; 95% CI, 29-53) with 41% partial response (PR), and 36% stable disease (SD) in patients who previously received 1-2 prior therapy lines (cohort 4). While the ORR, PR, and SD were 68% ( n = 29/97; 95% CI, 48-84), 64%, and 25%, respectively in treatment naïve patients (cohort 5b). Median progression-free survival (mPFS) and duration of response (DOR) were 5.4 months (mon) and 9.7 mon (95%CI, 5.6-13.0) in cohort 4 vs. 12.4 mon and 12.6 mon (CI, 5.6- not estimated), respectively in cohort 5b. Moreover, disease control was shown in n = 54/69 patients in cohort 4 (95% CI 78 (97-87) and n = 27/28 patients (95% CI 96 (82-100). A post-hoc analysis of 19 patients out of 69 who were pre-treated with immunotherapy demonstrated an ORR of 57.9% (n = 11/19; 95%CI 33.5-79.7) with capmatinib. In contrast, treatment-naive had an ORR of 34% (n = 17/50; 95%CI 21.2-48.8) as per the investigator. Median PFS was 3.29 mon noted on prior therapy. In the phase 1 retrospective analysis reported by Choi et al., ORR was 50% with a median duration of 16.1 (5.3-36.4) mon. Among 45 Japanese pts with MET ex 14 mutated or MET amplified status, the ORR was 36.4% (95% CI 10.9%-69.2%) with a PFS of 4.70 mon in the MET ex 14 mutated groups who had received a second or third line of therapy. Most commonly reported adverse events were peripheral edema, nausea, vomiting, and elevated creatinine across all studies and were mostly grade 1-2. Conclusions: Our results showed that capmatinib has promising anti-tumor activity in patients with NSCLC harboring MET exon 14 skipping mutation. The efficacy and tolerability profile of capmatinib is remarkable, particularly in treatment-naïve patients. Although the GEOMETRY Mono-1 trial is still ongoing, further clinical studies with long-term follow-up are needed.
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