Artem Oganesyan

Purpose Around 40% of patients undergoing systemic chemotherapy develop oral mucositis (OM), a major cause of morbidity in cancer patients. There are only a few options for preventing and treating OM. This study examines the tolerability of a novel oral device (Bocaliner™), designed to enhance the effects of oral topical therapies, in patients with hematologic malignancies receiving chemotherapy. Methods Data from phase 1/phase 2 randomized controlled trial SPOM (Study for the Prevention of Oral Mucositis) was analyzed. Patients from the Yeolyan Hematology and Oncology Center (Yerevan, Armenia) were randomized into two groups: benzydamine or saline mouthwash. Half of the patients in each study group were randomly assigned to Bocaliner™. Tolerability and safety questionnaires on days 1 and 14 of chemotherapy were completed. Results Twenty-eight patients (mean age of 49 years; 50% female) received oral devices and completed the study. On the tryout of the device, 22 (78.6%) patients reported tolerating it well, and six (21.4%) reported some discomfort. After 14 days, 15 patients (35.7%) reported benefit from the use, with six (21.4%) of patients stating the device helped to reduce pain, four (14.3%) indicating that it helped them to eat, and five (17.8%) claiming both. Adverse events included discomfort (n = 2, 7.1%), pain around the cheekbone (n = 3, 10.7%), nausea (n = 2, 7.1%), and increased salivation (n = 1, 3.6%); none of these led to discontinuation of the use. Eighteen (64%) participants said they would use the device again. OM developed in five patients (17.8%). Conclusions The use of a new medical device designed to enhance oral topical medications in combination with oral topical therapy is well tolerated among patients with hematologic malignancies on chemotherapy. Trial registration. ClinicalTrials.gov registry ID: NCT05338398 (Date of registry: April 15, 2022).

Background: The association between clonal hematopoiesis (CH) and nonmyeloid subsequent malignant neoplasms (SMNs) after autologous hematopoietic cell transplantation (HCT) has not been explored. Methods: This was a retrospective cohort study of 1931 consecutive patients who underwent HCT between 2010 and 2016 at a single center. DNA from pre-HCT mobilized blood products was sequenced to identify CH variants (variant allele frequency [VAF] ≥2%). The primary outcome was 8-year(y) cumulative incidence of nonmyeloid SMNs. Multivariable regression analysis was used to evaluate the association between CH and nonmyeloid SMNs, as well as cause-specific mortality. Results: Median age at HCT was 58.8 y (range = 18.4-78.1 y); 389 patients (20.1% of the cohort) had at least 1 CH variant and 94 (4.9%) had ≥2 variants. The 8 y cumulative incidence of nonmyeloid SMNs was significantly higher in patients with CH compared with those without (15.1% vs 7.2%, P < .001), and increased by VAF: 7.2% (VAF <2%), 14.0% (VAF 2% to <10%), 19.4% (VAF ≥10%); P = .001. Patients with CH had a 2-fold increased risk of nonmyeloid SMNs (standardized incidence ratio = 1.9), compared with the general population. In multivariable analysis, CH was an independent and significant risk factor for nonmyeloid SMNs (hazard ratio [HR] = 1.72, 95% confidence interval [CI] = 1.15 to 2.59). Finally, patients with CH had significantly worse survival, primarily due to the higher risk of nonrelapse mortality (HR = 2.97, 95% CI = 1.90 to 4.64). Conclusions: CH was significantly associated with the risk of nonmyeloid SMNs after HCT, and the magnitude of association increased by VAF. Clonal hematopoiesis may serve as a biomarker for identifying HCT survivors at higher risk for developing nonmyeloid SMNs.

Monoclonal gammopathy of clinical significance (MGCS) represents a new clinical entity referring to a myriad of pathological conditions associated with the monoclonal gammopathy of undetermined significance (MGUS). The establishment of MGCS expands our current understanding of the pathophysiology of a range of diseases, in which the M protein is often found. Aside from the kidney, the three main organ systems most affected by monoclonal gammopathy include the peripheral nervous system, skin, and eye. The optimal management of these MGUS-related conditions is not known yet due to the paucity of clinical data, the rarity of some syndromes, and limited awareness among healthcare professionals. Currently, two main treatment approaches exist. The first one resembles the now-established therapeutic strategy for monoclonal gammopathy of renal significance (MGRS), in which chemotherapy with anti-myeloma agents is used to target clonal lesion that is thought to be the culprit of the complex clinical presentation. The second approach includes various systemic immunomodulatory or immunosuppressive options, including intravenous immunoglobulins, corticosteroids, or biological agents. Although some conditions of the MGCS spectrum can be effectively managed with therapies aiming at the etiology or pathogenesis of the disease, evidence regarding other pathologies is severely limited to individual patient data from case reports or series. Future research should pursue filling the gap in knowledge and finding the optimal treatment for this novel clinical category.

Background: Patients with solid cancers and hematopoietic malignancy can experience systemic symptoms compatible with adult-onset Still’s disease (AOSD). The newly described VEXAS, associated with somatic UBA1 mutations, exhibits an overlap of clinical and/or biological pictures with auto inflammatory signs and myelodysplastic syndrome (MDS). Objectives: To describe a cohort of patients with signs of undifferentiated systemic autoinflammatory disorder (USAID) concordant with AOSD and MDS/chronic myelomonocytic leukemia (CMML) and the prevalence of VEXAS proposed management and outcome. Methods: A French multicenter retrospective study from the MINHEMON study group also used for other published works with the support of multidisciplinary and complementary networks of physicians and a control group of 104 MDS/CMML. Results: Twenty-six patients were included with a median age at first signs of USAID of 70.5 years with male predominance (4:1). Five patients met the criteria for confirmed AOSD. The most frequent subtypes were MDS with a blast excess (31%) and MDS with multilineage dysplasia (18%). Seven patients presented with acute myeloid leukemia and twelve died during a median follow-up of 2.5 years. Six out of 18 tested patients displayed a somatic UBA1 mutation concordant with VEXAS, including one woman. High-dose corticosteroids led to a response in 13/16 cases and targeted biological therapy alone or in association in 10/12 patients (anakinra, tocilizumab, and infliximab). Azacytidine resulted in complete or partial response in systemic symptoms for 10/12 (83%) patients including 3 VEXAS. Conclusions: Systemic form of VEXAS syndrome can mimic AOSD. The suspicion of USAID or AOSD in older males with atypia should prompt an evaluation of underlying MDS and assessment of somatic UBA1 mutation.

There is an established association between air pollution and cardiovascular disease (CVD), which is likely to be mediated by systemic inflammation. The present study evaluated links between long-term exposure to ambient air pollution and high-sensitivity C reactive protein (hs-CRP) in an older Chinese adult cohort (n = 7915) enrolled in the World Health Organization (WHO) study on global aging and adult health (SAGE) China Wave 1 in 2008–2010. Multilevel linear and logistic regression models were used to assess the associations of particulate matter (PM) and nitrogen dioxide (NO₂) on log-transformed hs-CRP levels and odds ratios of CVD risk derived from CRP levels adjusted for confounders. A satellite-based spatial statistical model was applied to estimate the average community exposure to outdoor air pollutants (PM with an aerodynamic diameter of 10 μm or less (PM₁₀), 2.5 μm or less (PM_2.5), and 1 μm or less (PM₁) and NO₂) for each participant of the study. hs-CRP levels were drawn from dried blood spots of each participant. Each 10 μg/m³ increment in PM₁₀, PM_2.5, PM₁, and NO₂ was associated with 12.8% (95% confidence interval; (CI): 9.1, 16.6), 15.7% (95% CI: 10.9, 20.8), 10.2% (95% CI: 7.3, 13.2), and 11.8% (95% CI: 7.9, 15.8) higher serum levels of hs-CRP, respectively. Our findings suggest that air pollution may be an important factor in increasing systemic inflammation in older Chinese adults.

Background: Long-term exposure to ambient air pollution leads to respiratory morbidity and mortality; however, the evidence of the effect on lung function and chronic obstructive pulmonary disease (COPD) in older adult populations is inconsistent. Objective: To address this knowledge gap, we investigated the associations between particulate matter (PM), nitrogen dioxide (NO₂) exposure and lung function, as well as COPD prevalence, in older Chinese adults. Methods: We used data from the WHO Study on global AGEing and adult health (SAGE) China Wave 1, which includes 11, 693 participants from 64 townships in China. A cross-sectional analysis explored the association between satellite-based air pollution exposure estimates (PM with an aerodynamic diameter of ≤10 µm [PM₁₀], ≤2.5 µm [PM_2.5] and NO₂) and forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), the FEV₁/FVC ratio and COPD (defined as post-bronchodilator FEV₁/FVC 3) increase in PM_2.5 was associated with lower FEV₁ (−71.88 mL, 95% CI –92.13 to –51.64) and FEV₁/FVC (−2.81, 95% CI −3.37 to –2.25). For NO₂, an IQR increment of 26.8 µg/m³ was associated with decreases in FEV₁ (−60.12 mL, 95% CI –84.00 to –36.23) and FVC (−32.33 mL, 95% CI –56.35 to –8.32). A 31.2 µg/m³ IQR increase in PM₁₀ was linked to reduced FEV₁ (−8.86 mL, 95% CI −5.40 to 23.11) and FEV₁/FVC (−1.85, 95% CI −2.24 to –1.46). These associations were stronger for participants with COPD. Also, COPD prevalence was linked to higher levels of PM_2.5 (POR 1.35, 95% CI 1.26 to 1.43), PM₁₀ (POR 1.24, 95% CI 1.18 to 1.29) and NO₂ (POR 1.04, 95% CI 0.98 to 1.11). Conclusion: Ambient air pollution was associated with lower lung function, especially in individuals with COPD, and increased COPD prevalence in older Chinese adults.