Metformin: Activation of 5' AMP-activated protein kinase and its emerging potential beyond anti-hyperglycemic action.

Metformin is a plant-based drug belonging to the class of biguanides and is known to treat type-2 diabetes mellitus (T2DM). The drug, combined with controlling blood glucose levels, improves the body's response to insulin. In addition, trials have identified the cardioprotective potential of metformin in the diabetic population receiving the drug. Activation of 5' AMP-activated protein kinase (AMPK) is the major pathway for these potential beneficial effects of metformin. Historically, much emphasis has been placed on the potential indications of metformin beyond its anti-diabetic use. This review aims to appraise other potential uses of metformin primarily mediated by the activation of AMPK. We also discuss various mechanisms, other than AMPK activation, by which metformin could produce beneficial effects for different conditions. Databases including PubMed/MEDLINE and Embase were searched for literature relevant to the review's objective. Reports from both research and review articles were considered. We found that metformin has diverse effects on the human body systems. It has been shown to exert anti-inflammatory, antioxidant, cardioprotective, metabolic, neuroprotective, anti-cancer, and antimicrobial effects and has now even been identified as effective against SARS-CoV-2. Above all, the AMPK pathway has been recognized as responsible for metformin's efficiency and effectiveness. Owing to its extensive potential, it has the capability to become a part of treatment regimens for diseases apart from T2DM.

Prevalence and Assessment of Factors Associated with COVID-19 Vaccine Hesitancy in an Ethnic Minority Oncology Patient Population.

BACKGROUND: Complicating the COVID-19 pandemic are the healthcare disparities experienced by ethnic minorities, especially those with comorbidities including cancer. The introduction of COVID-19 vaccines has been instrumental in blunting the morbidity and mortality from the pandemic; however, vaccine hesitancy, particularly among ethnic minorities, has been a major concern. Thus, we sought to evaluate the knowledge and perspectives of COVID-19 and vaccines among our ethnic minority cancer patient population. METHODS: Following an IRB approved protocol, questionnaires were completed by patients in a predominantly ethnic minority population at a single institution between 1 February and 30 June 2021. Included were any adult cancer patients with either a solid or hematologic malignancy. RESULTS: Among the 84 patients that were offered the questionnaires, 52 patients responded, with a median age of 63.5 years. Overall, 36% were non-Hispanic Blacks and 30% were Hispanics; 65% were receiving active treatment for their cancer. Seventy-nine percent believed COVID-19 to be dangerous or harmful to them, 61% were concerned about the side effects, yet 65% considered COVID-19 vaccines as safe. Among the seven patients that refused the vaccine, (71%, n = 5) cited side effects and/or (57%, n = 4) believed that the vaccine was not needed. Overall, there was a significantly higher chance of being vaccinated if patients were receiving active cancer treatment, believed COVID-19 was harmful, or that the vaccine was safe, and knew COVID-19 was a virus. CONCLUSIONS: This exploratory study demonstrates that most ethnic minority cancer patients are receptive to vaccines, with a majority being vaccinated. However, we also discovered various reasons why this group of patients may not want be vaccinated, including concerns about side effects and perception that COVID-19 is not harmful. These findings can help us further understand the complex nature of vaccine hesitancy in ethnic minority cancer patients, and aid in developing future vaccine awareness strategies as the COVID-19 pandemic continues to evolve.

Increased Incidence of Thrombosis in a Cohort of Cancer Patients with COVID-19.

BACKGROUND: Increased rates of thromboembolism (TE) have been reported in patients with COVID-19, even without prior predisposition to thrombosis. Cancer patients are already predisposed to a hypercoagulable state. This study was designed to assess the TE incidence in COVID-19+ patients with active cancer and its impact on survival. METHODS: Data from cancer patients with documented COVID-19 during the dates March 15th-April 10th, 2020, were retrospectively reviewed. Active cancer was defined as disease treated within the past year. Diagnosis and evaluation of thrombosis were done at the clinicians' discretion. All imaging studies' reports within 30 days of the COVID-19 positive test were reviewed for identification of new arterial and/or venous TE. Patients were followed for 30 days from the date of COVID-19+ test for development of TE, hospital length of stay (LOS), and mortality. RESULTS: Of 90 patients, 11 (12.2%) were found to have 13 new TE within 30 days of COVID-19+ test: 8 (8.9%) arterial and 5 (5.6%) venous. Arterial TE was primarily new strokes and/or microvascular cerebral disease (7) with 1 splenic infarct. Venous TE was superficial (1) and deep (3) venous thromboses with 1 pulmonary embolism. Peak D-dimer (DD) values were numerically higher in the TE group versus those with no TE, median peak DD, 7.7 versus 3.2 µg/mL, p = 0.25. Kidney disease was more frequent among patients with TE (72.7%) versus those without TE (31.6%), p = 0.02. Prophylactic or therapeutic anticoagulation (AC) in the inpatient setting was more common among those without TE, any AC, TE versus no TE, 9.1% versus 79.0%, p < 0.0001. Only 1 patient on enoxaparin prophylaxis developed TE. Mortality was higher in the TE group than in those without TE (hazard ratio: 2.6; 95% CI [1.2-5.6], p = 0.009). Cancer type, presence of metastases, administration of prior chemotherapy, patient setting (inpatient, intensive care unit, outpatient, emergency department visit), LOS, and ventilation did not correlate with increased incidence of TE. CONCLUSION: Cancer patients with COVID-19 have high overall TE rates with a significant incidence of arterial events. TE was associated with worse survival outcomes.

Patterns of seroconversion for SARS-CoV2-IgG in patients with malignant disease and association with anticancer therapy.

Patients with cancer have been identified in several studies to be at high risk of developing severe COVID-19; however, rates of SARS-CoV-2 IgG seroconversion and its association with cancer types and anti-cancer therapy remain obscure. We conducted a retrospective cohort study in patients with cancer that underwent SARS-CoV-2 IgG testing. Two hundred and sixty-one patients with a cancer diagnosis underwent SARS-CoV-2 IgG testing and demonstrated a high rate of seroconversion (92%). However, significantly lower seroconversion was observed in patients with hematologic malignancies (82%), patients that received anti-CD-20 antibody therapy (59%) and stem cell transplant (60%). Interestingly, all 17 patients that received immunotherapy, including 16 that received anti-PD-1/PD-L1 monoclonal antibodies, developed SARS-Cov-2 IgG antibodies (100% seroconversion). These data show differential rates of seroconversion in specific patient groups and bear importance for clinical monitoring and vaccination strategies that are being developed to mitigate the COVID-19 pandemic.

Seroconversion rates following COVID-19 vaccination among patients with cancer.

As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. On comparison with solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematologic malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than with mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies.

Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. SIGNIFICANCE: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access.This article is highlighted in the In This Issue feature, p. 1426.

Case Fatality Rate of Cancer Patients with COVID-19 in a New York Hospital System.

Patients with cancer are presumed to be at increased risk from COVID-19 infection-related fatality due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. A total of 218 COVID-19-positive patients from March 18, 2020, to April 8, 2020, with a malignant diagnosis were identified. A total of 61 (28%) patients with cancer died from COVID-19 with a case fatality rate (CFR) of 37% (20/54) for hematologic malignancies and 25% (41/164) for solid malignancies. Six of 11 (55%) patients with lung cancer died from COVID-19 disease. Increased mortality was significantly associated with older age, multiple comorbidities, need for ICU support, and elevated levels of D-dimer, lactate dehydrogenase, and lactate in multivariate analysis. Age-adjusted CFRs in patients with cancer compared with noncancer patients at our institution and New York City reported a significant increase in case fatality for patients with cancer. These data suggest the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population. SIGNIFICANCE: COVID-19 in patients with cancer is associated with a significantly increased risk of case fatality, suggesting the need for proactive strategies to reduce likelihood of infection and improve early identification in this vulnerable patient population.This article is highlighted in the In This Issue feature, p. 890.