Nebulized glycyrrhizin/enoxolone drug modulates IL-17A in COVID-19 patients: a randomized clinical trial.

Introduction: Glycyrrhizin (GA) and its derivative Enoxolone (18ß), isolated from the Glycyrrhiza glabra plant, are two potential molecules for treating viral diseases. Both demonstrate to regulate immune system with antiviral and anti-inflammatory activities, with the latter mainly due to modulation of inflammatory cytokines. The aim of this clinical trial was to evaluate the safety and efficacy of a nebulized GA/18ß drug for treating COVID-19 patients. Methods: An open label, randomized, placebo-controlled clinical trial was conducted in Mexico City from January-August 2022 (Registration No. PROTAP-CLI-00). Clinical and biochemical parameters were recorded. Blood samples from patients were regularly collected to evaluate interleukins IL-4, IL-2, IL-1b, TNF-α, IL-17A, IL-6, IL-10,IFN-γ, IL-12, IL-8 and TGF-ß1, as well as IgM and IgG against SARS-CoV-2. Two doses of the drug were used - 30/2 mg (dose A) and 90/4 mg (dose B). Results and discussion: Both GA/18ß doses modulated inflammatory response by reducing mainly IL-17A expression, which in turn kept IL-1ß, IL-6, IL-8 and TNF-α interleukins unchanged, indicating significant modulation of key interleukin levels to prevent exacerbation of the immune response in COVID-19 patients. Early on, dose A increased IgM, while dose B induced expression of the antiviral IFN-γ. No severe side effects were seen with either dose, indicating nebulized GA/18ß is a safe treatment that could be used for COVID-19 and potentially other viral infections involving inflammatory response.

Acute Promyelocytic Leukemia: A Long-Term Retrospective Study in Mexico.

BACKGROUND: The present retrospective study reviewed acute promyelocytic leukemia (APL) cases recorded in Mexico between January 2007 and January 2017. The primary objective of the study was to evaluate overall survival (OS) in Mexican patients with APL. Secondary objective was to evaluate the impact of induction treatment with different anthracyclines on OS, event-free survival (EFS) and complications in this patient population. METHODS: The medical charts of patients referred to medical institutions in Mexico from January 2007 through January 2017 for the treatment of suspected APL were reviewed retrospectively. Patients aged 15 - 75 years, in whom the diagnosis of APL was confirmed, who had an Eastern Cooperative Group performance status of 0 - 2, and who were eligible for combined treatment with intensive chemotherapy and all-trans retinoic acid (ATRA), were included in the study. Study participants received induction and consolidation treatment with ATRA plus either daunorubicin or idarubicin, followed by 2 years of single-agent ATRA as maintenance therapy. Patients who were unable to pay for ATRA treatment received anthracycline-based induction and consolidation, with methotrexate plus mercaptopurine as maintenance therapy. RESULTS: A total of 360 patients from 21 public and private hospitals were included in the study. The median age of the population was 37 years, and 51% were male. Of the 360 patients, 205 (57%) vs. 155 (43%) received daunorubicin vs. idarubicin as induction treatment for APL. ATRA was administered to 201 (98%) patients in the daunorubicin group vs. 138 (89%) in the idarubicin group (P = 0.001), and was initiated at diagnosis in 92% vs. 73% of recipients, respectively (P = 0.0001). At 150 months, OS and EFS for the entire population were 84% and 79%, respectively. Both OS (90% vs. 76%, P = 0.003) and EFS (85% vs. 72%, P = 0.001) were significantly prolonged in daunorubicin vs. idarubicin recipients. Rates of complications were similar in the two groups. CONCLUSIONS: As arsenic trioxide (ATO) is not currently available in Mexico, anthracycline plus ATRA is the mainstay of treatment for APL here. Our results confirm the efficacy of this strategy, with high OS and EFS rates being observed 12.5 years after diagnosis.

Treatment-Related Mortality From Infectious Complications in an Acute Leukemia Clinic.

BACKGROUND: The main causes of mortality in patients with acute leukemia are the infectious complications. The author wanted to know the induction-related mortality and treatment-related mortality in the acute leukemia patients at the Instituto Nacional de Cancerologia (INCan), Mexico. Also the author is interested in finding out the micro-organism and the main site of infection to make some changes in the management of patients in these clinics. Primary objective was induction chemotherapy-related mortality and treatment-related mortality. Secondary objective was to determine the site of infection, micro-organism, type of chemotherapy related with more mortality and relapse mortality. METHODS: This was a retrospective case-series analysis of all patients who were admitted to the INCan Acute Leukemia Clinic between January 2012 and December 2015 with febrile neutropenic complications. We reviewed the case histories of all patients, including those with acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), acute biphenotypic leukemia and acute promyelocytic leukemia, regardless of disease status (newly diagnosed or relapsed) at the time of clinic attendance. Patients who died as the result of an infectious complication during the analysis window were identified, and their demographics, disease characteristics, treatment history (chemotherapy within 45 days of date of death) and details of the infectious complication resulting in death were collected. RESULTS: Of the 313 patients studied during that time period, 84 (27%) died as a result of infectious complications. Lung infections were the most common, accounting for 67% of all deaths from infectious complications. Escherichia coli producing extended-spectrum beta-lactamases was the most frequently isolated infectious organism (12 patients; 14%). The majority of deaths occurred during either induction therapy (27 patients; 32%) or treatment for a first relapse (25 patients; 30%). Hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (hyper-CVAD) was the chemotherapy regimen most commonly received within 45 days prior to death (17 patients; 20%). CONCLUSIONS: Our findings suggest a need for long-term management and supportive care to prevent infectious complication-associated fatalities during both initial chemotherapy and subsequent disease relapse in patients with acute leukemia. The use of prophylaxis will help patients to prevent complications.

Efficacy of hydralazine and valproate in cutaneous T-cell lymphoma, a phase II study.

OBJECTIVES: To evaluate the activity and safety of hydralazine and valproate (Transkrip) in cutaneous T-cell lymphoma (CTCL). METHODS: Previously untreated and progressive/refractory CTCL patients received hydralazine at 83 mg or 182 mg/day for slow and rapid acetylators respectively plus magnesium valproate at a total dose of 30 mg/Kg t.i.d daily in continuous 28-day cycles in this phase II study. The primary objective was overall response rate (ORR) measured by the modified severity weighted assessment tool (m-SWAT), secondary end-points were time to response (TTR), time to progression (TTP), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Fourteen patients were enrolled (7 untreated and 7 pretreated). ORR was 71% with 50% complete and 21% partial. Two had stable disease and two progressed. At a median follow-up of 36 months (5-52), median TTR was 2 months (1-4); median DOR was 28 months (5-45); median PFS 36 and not reached for OS. There were no differences in median TTR, DOR, and PFS between treated and pretreated patients. Pruritus relieve was complete in 13 out of 14 patients. No grade 3 or 4 toxicities were observed. CONCLUSION: The combination of hydralazine and valproate is safe, very well tolerated and effective in CTCL.