Ambient carbon monoxide correlates with mortality risk of hemodialysis patients: comparing results of control selection in the case-crossover designs.

BACKGROUND: Growing evidence suggests that environmental air pollution adversely affects kidney health. To date, the association between carbon monoxide (CO) and mortality in patients with end-stage renal disease (ESRD) has not been examined. METHODS: Among 134,478 dialysis patients in the Korean ESRD cohort between 2001 and 2014, 8,130 deceased hemodialysis patients were enrolled, and data were analyzed using bidirectional, unidirectional, and time-stratified case-crossover design. We examined the association between short-term CO concentration and mortality in patients with ESRD. We used a two-pollutant model, adjusted for temperature as a climate factor and for nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter less than 10 µm in diameter as air pollution variables other than CO. RESULTS: Characteristics of the study population included age (66.2 ± 12.1 years), sex (male, 59.1%; female, 40.9%), and comorbidities (diabetes, 55.6%; hypertension, 14.4%). Concentration of CO was significantly associated with all-cause mortality in the three case-crossover designs using the two-pollutant model adjusted for SO2. Patients with diabetes or age older than 75 years had a higher risk of mortality than patients without diabetes or those younger than 75 years. CONCLUSION: Findings presented here suggest that higher CO concentration is correlated with increased all-cause mortality in hemodialysis patients, especially in older high-risk patients.

Inhaled Corticosteroids and COVID-19 Risk and Mortality: A Nationwide Cohort Study.

Inhaled corticosteroids (ICS) could increase both the risk of coronavirus disease 2019 (COVID-19) and experiencing poor outcomes. To compare the clinical outcomes between ICS users and nonusers, COVID-19-related claims in the Korean Health Insurance Review and Assessment database were evaluated. To evaluate susceptibility to COVID-19 among patients with COPD or asthma, a nested case-control study was performed using the same database. In total, 7341 patients were confirmed to have COVID-19, including 114 ICS users and 7227 nonusers. Among 5910 patients who were hospitalized, death was observed for 9% of ICS users and 4% of nonusers. However, this association was not significant when adjusted for age, sex, region, comorbidities, and hospital type (aOR, 0.94; 95% CI, 0.43-2.07). The case-control analysis of COPD compared 640 cases with COVID-19 to 2560 matched controls without COVID-19, and the analysis of asthma compared 90 cases with COVID-19 to 360 matched controls without COVID-19. Use of ICS was not significantly associated with COVID-19 among patients with COPD (aOR, 1.02; 95% CI, 0.46-2.25) or asthma (aOR, 0.38; 95% CI, 0.13-1.17). Prior ICS use was not significantly associated with COVID-19 in patients with COPD or asthma, nor with clinical outcomes among patients with COVID-19.

The impact of sunlight exposure on mortality of patients with end stage renal disease.

Recent data suggest that reduced sunlight exposure is associated with increased mortality in the general population. To date, the association between sunlight exposure and mortality in dialysis patients has not been examined. Among 134,478 dialysis patients in the Korean end-stage renal disease (ESRD) cohort from 2001 to 2014, 31,291 patients were enrolled from seven metropolitan cities, and data were analyzed using bi-directional case-crossover design. We examined the association between short-term sunlight exposure and mortality in ESRD patients. We adjusted for temperature, humidity, and daily concentrations of nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), carbon monoxide (CO), and particle matter (PM10) as confounders. The characteristics of the study population included age (65.6 ± 12.26 (mean ± standard deviation [SD]) years), sex (male, 59.96%; female, 41.04%), comorbidity (diabetes, 53.58%; hypertension, 40.5%), and kidney dialysis type (hemodialysis, 73.02%; peritoneal dialysis, 26.98%). The mean ± SD follow-up time was 4.68 ± 4.37 years. The daily sunlight exposure was significantly decreased in the case group compared with the control group (P = 0.004). Sunlight exposure was associated with all-cause death overall (ORs [95% CI]: 0.99 [0.98-0.99], P = 0.042) in a fully adjusted model. Patients with diabetes (ORs [95% CI]: 0.98 [0.97-0.99], P = 0.016) or aged higher than 75 years (ORs [95% CI]; 0.97 [0.96-0.99], P = 0.020) had higher risks of mortality than patients without diabetes or aged below 75 years, respectively. These findings suggest that sunlight exposure is inversely correlated with all-cause mortality in dialysis patients.

Constitutive activation of alternative nuclear factor kappa B pathway in canine diffuse large B-cell lymphoma contributes to tumor cell survival and is a target of new adjuvant therapies.

Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1). We further demonstrate that a small interfering RNA inhibits the activation of the NFκB pathway and induces apoptosis in canine DLBCL cells. In conclusion, the ANFκBP facilitates survival of canine DLBCL cells, and thus, dogs with spontaneous DLBCL can provide a useful large animal model to study therapies targeting the ANFκBP.

A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma.

We conducted a prospective phase I study to evaluate safety of an orally administered Salmonella encoding IL-2 (SalpIL2) in combination with amputation and adjuvant doxorubicin for canine appendicular osteosarcoma. Efficacy was assessed as a secondary measure. The first dose of SalpIL2 was administered to 19 dogs on Day 0; amputation was done after 10 days with chemotherapy following 2 weeks later. SalpIL2 was administered concurrent with chemotherapy, for a total of five doses of doxorubicin and six doses of SalpIL2. There were six reportable events prior to chemotherapy, but none appeared due to SalpIL2. Dogs receiving SalpIL2 had significantly longer disease-free interval (DFI) than a comparison group of dogs treated with doxorubicin alone. Dogs treated using lower doses of SalpIL2 also had longer DFI than dogs treated using the highest SalpIL2 dose. The data indicate that SalpIL2 is safe and well tolerated, which supports additional testing to establish the potential for SalpIL2 as a novel form of adjuvant therapy for dogs with osteosarcoma.