11-Azaartemisinin derivatives bearing halogenated aromatic moieties: Potent anticancer agents with high tumor selectivity.

While artemisinin and its derivatives, including 11-azaartemisinin-based compounds, have shown promising anticancer activity, the integration of halogens into aromatic structures can amplify drug potency, metabolic stability, and selectivity. Herein, we present the synthesis of new novel 11-azaartemisinin derivatives bearing halogenated aromatic moieties connected via 1,2,3-triazole bridges and evaluate their anticancer activities against three human tumor cell lines: epidermoid carcinoma (KB), hepatocellular carcinoma (HepG2), and human lung adenocarcinoma (A549). Among the synthesized compounds, six of them (8c-h) displayed good to excellent antiproliferative activity in the low micromolar range across all three human cancer cell lines. In general, the m-bromide (8c) and m-iodide (8d) compounds exhibited superior anticancer activities compared to their o- and p-analogs, as well as the m-chloride and m-fluoride compounds. The most promising m-Br compound (8c) displayed 50 % inhibition of KB, HepG2, and A549 cell growth at concentrations of 7.7, 42.5, and 15.5 µM, respectively. Notably, the m-Br compound (8c) exhibited approximately 32-, 6-, and 16-fold lower activity in normal cells (Hek293) compared to KB, HepG2, and A549 tumor cells, respectively, indicating a significant tumor-selectivity.

Etiologies of fever of unknown origin in HIV/AIDS patients, Hanoi, Vietnam.

BACKGROUND: Fever of unknown origin (FUO) is a challenge for clinicians treating patients with HIV/AIDS. CD4 counts can be helpful in the diagnosis and treatment. This study aimed to determine several common etiologies of FUO stratified by CD4 count levels in HIV/AIDS patients. METHODS: A cross-sectional retrospective and prospective study was conducted in 195 HIV/AIDS patients with FUO admitted to the National Hospital for Tropical Diseases from January 2016 to June 2019. Clinical parameters, immune status, and etiologies for each patient were recorded. Odds ratios were calculated to compare the distributions of common etiologies in groups with two different CD4 count levels: < 50 cells/mm3 and ≥ 50 cells/mm3. RESULTS: The proportions of opportunistic infections and noninfectious etiologies were 93.3% and 3.6%, respectively. Tuberculosis was the most common opportunistic infection (46.7%), followed by talaromycosis (29.2%) and Pneumocystis jiroveci (PCP) infection (20.5%). Tuberculosis was predominant in all CD4 level groups. Most patients with talaromycosis had CD4 counts below 50 cells/mm3. In total, 53.8% of the patients were infected by one pathogen. The risks of tuberculosis and talaromycosis in FUO-HIV patients were high when their CD4 counts were below 50 cells/mm3. CONCLUSIONS: Opportunistic infections, especially tuberculosis, are still the leading cause of FUO in HIV/AIDS patients. Tuberculosis and Talaromyces marneffei (TM) infection should be considered in patients with CD4 cell counts < 50 cells/mm3. This study implies that guidelines for appropriate testing to identify the etiology of FUO in HIV/AIDS patient based on the CD4 cell count should be developed, thereby reducing resource waste.

Helicobacter pylori infection and eradication outcomes among Vietnamese patients in the same households: Findings from a non-randomized study.

OBJECTIVE: Familial transmission can possibly influence the infection and treatment of Helicobacter pylori. This study aimed to describe the prevalence of H. pylori infection and outcomes of eradication treatment among Vietnamese patients who live in the same households. METHODS: We conducted a prospective cohort study of Vietnamese household members with upper gastrointestinal complaints. Participants received esophagogastroduodenoscopy and H. pylori testing. The H. pylori-positive patients were treated and asked to return for follow-up within 4 months. To explore factors associated with H. pylori infection at baseline, we performed multilevel logistic regression to account for the clustering effect of living in the same households. To explore factors associated with eradication failure, we used Poisson regression with robust variance estimation to estimate the risk ratio. RESULTS: The prevalence of H. pylori infection was 83.5% and highest among children <12 years old (92.2%) in 1,272 patients from 482 households. There were variations in H. pylori infection across households (intraclass correlation = 0.14, 95% confidence interval (CI) 0.05, 0.33). Children aged <12 years had higher odds of H. pylori infection (odds ratio = 3.41, 95%CI 2.11, 5.50). At follow-up, H. pylori was eradicated in 264 of 341 patients (77.4%). The risk of eradication failure was lower for the sequential regimen with tetracycline. CONCLUSION: H. pylori infection was common among people living in the same households. Eradication success for H. pylori was higher for the tetracycline sequential regimen. More research should be focused on how family factors influence H. pylori infection and on eradication treatment.