Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication in Infected Patients With Solid Tumors.

INTRODUCTION: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety. METHODS: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI. RESULTS: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men (41; 79%), White (31; 59%), without cirrhosis (34; 65%), and with HCV genotype 1 (40; 77%). Four patients (7.7%) experienced HCV inhibition while receiving ICI including 1 patient who developed undetectable viremia for 6 months in the absence of direct-acting antivirals (DAA). Two patients (4%) developed HCV reactivation, both while receiving immunosuppressive therapy for ICI-related toxic effects. Adverse events occurred in 36 patients (69%), and 39 of the 47 adverse events (83%) were grade 1-2. Grade 3-4 adverse events occurred in 8 patients (15%), and in all cases, they were related to ICI, not to HCV. No HCV-associated liver failure or death occurred. DISCUSSION: Inhibition of HCV replication with virologic cure can develop in patients receiving ICI without DAA. HCV reactivation occurs primarily in patients receiving immunosuppressants for ICI-related toxic effects. ICI are safe in HCV-infected patients with solid tumors. Chronic HCV infection should not be considered a contraindication for ICI therapy.

International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03). Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality. Funding: National Cancer Institute and National Institutes of Health.

The Impact of Artificial Sweeteners on Human Health and Cancer Association: A Comprehensive Clinical Review.

Artificial sweeteners are sugar substitutes that provide high sweetening power associated with low accompanied calories. In this study, we aim to review the data on the use, benefits, side effects, and cancer risks of artificial sweeteners. We reviewed data in the PubMed, MEDLINE, Google Scholar, Embase, and Scopus databases to search for studies about artificial sweeteners from the inception of the database to July 20, 2023, published in the English language. We discuss systematic reviews and meta-analyses, randomized clinical trials, and observational cohort studies that address the use of artificial sweeteners and their effect on health. In our review, we show that artificial sweeteners have been shown to impact various functions of the gastrointestinal system. Other studies have demonstrated an association with neurologic symptoms such as headache and taste alteration. Moreover, recent studies have established an association between artificial sweeteners and cardiovascular risk and diabetes. Importantly, the majority of research data show no link between the use of artificial sweeteners and cancer risk. Although most studies show that there is no established link between these products and cancer risk, artificial sweeteners are associated with multiple diseases. Hence, more studies are needed to better characterize the effect of artificial sweeteners on human health.

International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship.

Background: In this international multicenter study we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods: We retrospectively collected de-identified data on a cohort of cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, from 16 international centers. Results: We analyzed 3966 COVID-19 confirmed patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were more likely to be pancytopenic, and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding two weeks (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms (p≤0.01). By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who did not (5.9% vs 17.6%; p=0.03). Conclusions: Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality. Condensed Abstract: In this large multicenter worldwide study of 4015 patients with COVID-19 that included 1115 patients with cancer, we found that cancer is an independent risk factor for increased 30-day all-cause mortality. Remdesivir is a promising treatment modality to reduce 30-day all-cause mortality.

High sustained virologic response rate after 8 weeks of direct-acting antivirals in cancer patients with chronic hepatitis C virus.

OBJECTIVE: There is no prospective data on 8 weeks of direct-acting antivirals (DAA) therapy with glecaprevir/pibrentasvir (GLE/PIB) or ledipasvir/sofosbuvir (LDV/SOF) in hepatitis C virus (HCV)-infected patients with different types of malignancies. This study evaluated the efficacy and safety with 8 weeks of DAA therapy in cancer patients with chronic HCV infection. METHODS: Patients treated with DAAs at our center during 2014-2021 were included in a prospective observational study. Efficacy (sustained virologic response at 12 weeks; SVR12) and safety [adverse events and clinically significant drug-drug interactions (DDIs)] were assessed. RESULTS: We included 47 patients. Most were men (29; 62%), white (33; 70%), non-cirrhotic (45; 96%), and with HCV genotype 1 (38; 85%). None of the patients had HCC. The SVR12 rate was 96% (45/47; 95% CI: 86-99%) for the entire study cohort, 100% [17/17; 95% CI: 82-100%] for the patients treated with GLE/PIB and 93% [28/30; 95% CI: 79-98%] for the patients treated with LDV/SOF. Fisher's exact test showed no significant difference in SVR12 rates between the regimens (P = 0.53). No patients had serious adverse events (grade 3-4) or treatment discontinuation. Among the 17 patients who received concomitant cancer therapy, no DDIs occurred. CONCLUSION: Eight weeks of DAA therapy is highly effective and safe in HCV-infected patients with different types of malignancies and may grant access to investigational cancer therapy, broadening treatment options.

Serologic versus molecular testing for screening for hepatitis C virus infection in patients with hematologic malignancies.

Testing for antibody against hepatitis C virus (anti-HCV) is a low-cost diagnostic method worldwide; however, an optimal screening test for HCV in patients with cancer has not been established. We sought to identify an appropriate screening test for HCV infection in patients with hematologic malignancies and/or hematopoietic cell transplants (HCT). Patients in our center were simultaneously screened using serological (anti-HCV) and molecular (HCV RNA) assays (February 2019-November 2019). In total, 214 patients were enrolled in this study. Three patients (1.4%) were positive for anti-HCV, and 2 (0.9%) were positive for HCV RNA. The overall percentage agreement was 99.5% (95% CI: 97.4-99.9). There were no cases of seronegative HCV virus infection. The positive percentage agreement was 66.7% (95% CI: 20.8-93.9), and the negative percentage agreement was 100.0% (95% CI: 98.2-100.0). Cohen kappa coefficient was 0.80 (95% CI: 0.41-1.00, P < .0001). The diagnostic yield of screening for chronic HCV infection in patients with cancer is similar for serologic and molecular testing.

Overcoming Therapy Resistance in Colon Cancer by Drug Repurposing.

Colorectal cancer (CRC) is the third most common cancer in the world. Despite improvement in standardized screening methods and the development of promising therapies, the 5-year survival rates are as low as 10% in the metastatic setting. The increasing life expectancy of the general population, higher rates of obesity, poor diet, and comorbidities contribute to the increasing trends in incidence. Drug repurposing offers an affordable solution to achieve new indications for previously approved drugs that could play a protagonist or adjuvant role in the treatment of CRC with the advantage of treating underlying comorbidities and decreasing chemotherapy toxicity. This review elaborates on the current data that supports drug repurposing as a feasible option for patients with CRC with a focus on the evidence and mechanism of action promising repurposed candidates that are widely used, including but not limited to anti-malarial, anti-helminthic, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic agents.

Impact of CD4+ T-cell count on sustained virologic response to direct-acting antivirals in hepatitis C virus monoinfected cancer patients: a prospective observational study.

Limited data are available on the use of CD4+ T-cell count and percentage to predict response to direct-acting antiviral (DAA) treatment outside the hepatitis C virus (HCV)-HIV coinfected population. We sought to determine the impact of CD4+ T-cell count and percentage on response to DAAs in cancer patients with HCV monoinfection. Patients treated with DAAs were enrolled in a prospective observational study. CD4+ T-cell count and percentage was measured at baseline, end of treatment (EOT), and 12 weeks after the EOT (SVR12). A total of 174 patients were enrolled. Most patients (155/174, 89%) achieved an SVR12. A multivariate logistic regression model found that patients with hepatocellular carcinoma, HCV-3 and previous DAA treatment were more likely to develop treatment failure. Neither univariate analysis nor multivariate logistic regression analysis did show any association between CD4+ T-cell count or percentage and SVR12. CD4 T-cell count or percentage does not appear to impact SVR rates in cancer patients with HCV monoinfection receiving DAAs.

A Case of Dysembryoplastic Neuroepithelial Tumor in an Adolescent Male.

Dysembryoplastic neuroepithelial tumors (DNETs) are benign mixed glioneuronal neoplasms that frequently occur in children and young adults. We present the case of a 17-year-old male who arrived at the hospital following seizure-like activity. A magnetic resonance imaging (MRI) scan showed a 10 x 8 x 10 mm, oval-shaped, non-enhancing, well-defined mass within the right hippocampus. The patient underwent a transcortical approach via the middle temporal gyrus for resection of the mass; histopathological examination demonstrated the presence of round, uniform cells in an extensively myxoid background with diffuse reactivity to glial fibrillary acidic protein (GFAP). DNETs are considered benign, non-recurring lesions. Complete surgical resection is associated with a seizure-free outcome in 80% to 100% of cases.

Adverse Effects Associated with Proton Pump Inhibitor Use.

Proton pump inhibitors (PPIs) marked a before and after in the management of gastric acid-related disorders since their introduction to the market in 1989. Due to a novel, highly effective mechanism of action blocking the last converging step of gastric acid secretion by parietal cells and very few and mostly tolerable side effects, these drugs quickly displaced other pharmacological compounds such as H2 antagonists as the first treatment choice for peptic ulcer disease, gastroesophageal ulcers, Zollinger-Ellison syndrome, nonsteroidal anti-inflammatory drug-associated ulcers, and eradication of Helicobacter pylori, leading to an exponential increase in their prescription up to now. However, widespread PPI use has led to emerging evidence of long-term adverse effects not described previously, including increased risk of kidney, liver, and cardiovascular disease, dementia, enteroendocrine tumors of the gastrointestinal tract, susceptibility to respiratory and gastrointestinal infections, and impaired absorption of nutrients. Although the evidence published thus far has not established strong correlations, it has been relevant enough to raise new questions about PPIs' safety profile and reconsideration of their clinical indications. Hence, the aim of this review is to evaluate the association between PPI use and the risk of serious adverse effects given increasing concerns about the overuse of PPIs in the general population.

Cáncer de próstata y polimorfismos de la glutation s-transferasa en una población venezolana / Prostate cancer and polymorphisms of the glutathione s-transferase in a population Venezuelan

En vista de la alta prevalencia del cáncer de próstata en la población venezolana y la ausencia de un patrón genético conocido en relación a la expresión de las enzimas Glutatión S-transferasas, se estudió la relación entre la expresión de un polimorfismo nulo de estas enzimas y la presencia de cáncer de adenocarcinoma prostática Métodos: Se incluyen 100 individuos para el muestreo no probabilístico, 50 pacientes con diagnóstico de adenocarcinoma de próstata comprobado mediante biopsia y 50 controles con hiperplasia prostática benigna demostrada mediante tacto y corroborada por ultrasonido transrectal, provenientes de los principales hospitales del país, se procedió a tomar muestra de sangre y mediante reacción de cadena de polimerasa, se determinó la presencia o ausencia de los genes para las enzimas Glutatión S-transferasa Mu 1 (GST M) y glutatión S-transferasa theta 1 (GST T1). Resultados: se logró evidenciar que el genotipo nulo se encontró en 40 y 24% de los pacientes mientras que para los controles fue de 38% y 22% respectivamente, demostrando que en la población venezolana estudiada no existen diferencias significativas entre casos y controles. Conclusiones: No se pudo demostrar una diferencia significativa entre los dos grupos estudiados. Recomendaciones: A pesar de nuestros hallazgos, se necesitan estudios futuros con muestras de mayor tamaño para dilucidar la posible asociación entre este patrón enzimático con el riesgo de presentar cáncer de próstata(AU)

Prostate cancer presents with a high incidence in the Venezuelan population. there is no known genetic pattern related to the expression of drug metabolizing enzymes Glutathione S-transferases. Methods: We proceeded to study the possible correlation between null polymorphism for these enzymes and prostate adenocarcinoma. the sample included 100 patients recruited from the Urology Department of three University Hospitals in Caracas, Venezuela, 50 cancer patients and 50 cancer free controls. Blood samples were drawn from each patient and polymorphisms for Glutathione S-transferase Mu 1 (GST M1) and Glutathione-sS-transferase theta 1(GST T1) were determined by polymerase chain reaction from lymphocytes. Results: Null genotype was found in 40% and 24% of cancer patients whereas the percentage in controls was 38 and 22% respectively, showing no statistically significant differences between the two groups. Conclusions: It was not possible to show a significant difference between the two groups. Recommendations: Due to the small size of the sample, it would be necessary to explore further in a larger population sample to determine whether there is an association between the expression of these enzymes and prostate cancer(AU)