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Background: NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs). Methods: This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations. The cutoff value (10 units/mL) of NY-ESO-1 and XAGE1 Ab was determined based on Ab levels in non-malignant controls, and NY-ESO-1/XAGE1 Abs in NSCLC were measured before nivolumab. Differences in PFS and OS between the Ab-positive and Ab-negative groups were retrospectively analyzed using Cox regression analysis after applying inverse probability of treatment weighting (IPTW). Results: NY-ESO-1/XAGE1 Abs were positive in 28 NSCLC, who responded more highly to nivolumab than the Ab-negatives (response rate 50.0% vs. 15.5 %, p < 0.0007). The IPTW-adjusted positives and negatives for NY-ESO-1/XAGE1 Abs were 24.5 and 70.2, respectively. The Ab-positives showed longer IPTW-adjusted PFS (HR = 0.59, 95 % CI: 0.39–0.90, p = 0.014) and IPTW-adjusted OS (HR = 0.51, 95 % CI: 0.32–0.81, p = 0.004) than the Ab-negatives. Among NSCLC harboring driver genes, the Ab-positives (n = 10) showed longer PFS (HR = 0.34, 95 % CI: 0.13–0.89, p = 0.029) and OS (HR = 0.27, 95 % CI: 0.098–0.75, p = 0.012) than the Ab-negatives (n = 11). Conclusion: Our immunoassay of NY-ESO-1/XAGE1 Abs is probably useful for predicting the clinical benefit with nivolumab in NSCLC, including those harboring driver genes. These results suggest that our immunoassay may be useful in ICI monotherapy for NSCLC.

Objective: To examine the association between hyperkalemia and long-term cardiovascular and renal outcomes in patients with chronic kidney disease. Patients and Methods: An observational retrospective cohort study was performed using a Japanese hospital claims registry, Medical Data Vision (April 1, 2008, to September 30, 2018). Of 1,208,894 patients with at least 1 potassium measurement, 167,465 patients with chronic kidney disease were selected based on International Classification of Diseases, Tenth Revision codes or estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. Hyperkalemia was defined as at least 2 potassium measurements of 5.1 mmol/L or greater within 12 months. Normokalemic controls were patients without a record of potassium levels of 5.1 mmol/L or greater and 3.5 mmol/L or less. Changes in eGFRs and hazard ratios of death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction were assessed between propensity score–matched hyperkalemic patients and normokalemic controls. Results: Of 16,133 hyperkalemic patients and 11,898 normokalemic controls eligible for analyses, 5859 (36.3%) patients and 5859 (49.2%) controls were selected after propensity score matching. The mean follow-up period was 3.5 years. The 3-year eGFR change in patients and controls was −5.75 and −1.79 mL/min/1.73 m2, respectively. Overall, hyperkalemic patients had higher risks for death, hospitalization for cardiac events, heart failure, and renal replacement therapy introduction than controls, with hazard ratios of 4.40 (95% CI, 3.74 to 5.18), 1.95 (95% CI, 1.59 to 2.39), 5.09 (95% CI, 4.17 to 6.21), and 7.54 (95% CI, 5.73 to 9.91), respectively. Conclusion: Hyperkalemia was associated with significant risks for mortality and adverse clinical outcomes, with more rapid decline of renal function. These findings underscore the significance of hyperkalemia as a predisposition to future adverse events in patients with chronic kidney disease.

Background: Previous studies have shown that hyponatremia is associated with greater mortality in hemodialysis (HD) patients. However, there have been few reports regarding the importance of the change in serum sodium (SNa) concentration (ΔSNa) during dialysis sessions. To investigate the relationships of pre-dialysis hyponatremia and ΔSNa during a dialysis session with mortality, we analyzed data from a national registry of Japanese patients with end-stage kidney disease. Methods: We identified 178,114 patients in the database who were undergoing HD 3 times weekly. The study outcome was 2-year all-cause mortality, and the baseline SNa concentrations were categorized into quintiles. We evaluated the relationships of SNa concentration and ΔSNa with mortality using Cox proportional hazards models. Results: During a 2-year follow-up period, 25,928 patients died. Each 1-mEq/l reduction in pre-HD SNa concentration was associated with a cumulatively greater risk of all-cause mortality (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.05–1.06). In contrast, a larger ΔSNa was associated with higher all-cause mortality (HR for a 1-mEq/l increase in ΔSNa, 1.02; 95% CI 1.01–1.02). The combination of low pre-HD SNa concentration and large ΔSNa was also associated with higher mortality (HR 1.09; 95% CI 1.05–1.13). Participants with the lowest SNa concentration (≤136 mEq/L) and the highest ΔSNa (>4 mEq/L) showed higher mortality than those with an intermediate pre-HD SNa concentration (137–140 mEq/L) and the lowest ΔSNa (≤2 mEq/L). Conclusions: Lower pre-HD SNa concentration and higher ΔSNa are associated with a greater risk of mortality in patients undergoing HD.

Introduction: An abnormal serum potassium (S-K) level is an important electrolyte disturbance. However, its relation to clinical outcomes in real-world patients, particularly hyperkalemia burden, is not extensively studied. Methods: An observational retrospective cohort study using a Japanese hospital claims database was done (April 2008–September 2017; N = 1,022,087). Associations between index S-K level and 3-year survival were modeled using cubic spline regression. Cox regression model was applied to estimate the time to death according to different S-K levels. Prevalence, patient characteristics, treatment patterns, and management of patients with hyperkalemia from first episode were assessed. Results: Hyperkalemia prevalence was 67.9 (95% confidence interval [CI]: 67.1–68.8) per 1000 and increased in patients with chronic kidney disease (CKD) (227.9; 95% CI: 224.3–231.5), heart failure (134.0; 95% CI: 131.2–136.8), and renin-angiotensin-aldosterone system inhibitor (RAASi) use (142.2; 95% CI: 139.6–144.7). U-shaped associations between S-K level and 3-year survival were observed with nadir 4.0 mEq/l. The risk of death was increased at S-K 5.1–5.4 mEq with hazard ratio of 7.6 (95% CI: 7.2–8.0). The 3-year mortality rate in patients with CKD stages 3a, 3b, 4, and 5 with normokalemia were 1.51%, 3.93%, 10.86%, and 12.09%, whereas that in patients with CKD stage 3a at S-K 5.1–5.4, 5.5–5.9, and ≥6.0 mEq/l increased to 10.31%, 11.43%, and 22.64%, respectively. Despite treatment with loop diuretics (18.5%) and potassium binders (5.8%), >30% of patients had persistently high S-K (≥5.1 mEq/l). Conclusion: This study provides real-world insight on hyperkalemia based on a large number of patients with various medical backgrounds. Keywords: chronic kidney disease, congestive heart failure, hyperkalemia, renin-angiotensin-aldosterone inhibitor, renin angiotensin system

Rationale & Objective: Hyperkalemia is a common electrolyte abnormality of chronic kidney disease and heart failure associated with increased mortality and morbidity. We aimed to assess the long-term economic burden of hyperkalemia. Design: Observational cohort study using a Japanese nationwide hospital claims database (April 1, 2008, to September 30, 2018). Setting & Population: : Patients 18 years or older with at least 1 serum potassium value (N = 1,208,894). Exposures: Hyperkalemia defined with the presence of at least 2 serum potassium values ≥ 5.1 mmol/L. Outcome Measures: Direct health care costs and resource use in patients with hyperkalemia within and after 12 months from first hyperkalemia episodes. Analytical Approach: Health care costs and resource use were compared with propensity score–matched or nonmatched normokalemic controls. Multivariable regression analysis was performed to examine factors associated with health care costs. Results: 27,534 patients with hyperkalemia and 233,098 normokalemic controls were studied. Mean ± SD age was 73±13 years in patients with hyperkalemia; among them, 59% and 35% had chronic kidney disease and heart failure, respectively. In the propensity score–matched cohort (n = 5,859 in each group), average numbers of hospitalizations per patient per year in patients with hyperkalemia within and after 12 months were 1.2 and 1.6 times higher, respectively, compared with those in patients with normokalemia. The total cost per patient in patients with hyperkalemia was higher than for controls, with mean differences of $8,611 (95% CI, $8,046-$9,175) within 12 months and $5,150 (95% CI, $4,733-$5,566) after 12 months. The number of repeat hyperkalemic episodes was the factor with the strongest association with long-term health care costs, whereas severity of hyperkalemia was not associated. Limitations: This study used secondary data; therefore, residual confounders may not be fully excluded. Conclusions: Hyperkalemia was associated with significant long-term economic burden with frequent hospitalizations due to recurrent episodes, indicating the importance of hyperkalemia treatment for the sake of reducing health economic burdens and clinical complications.

Objective: To determine the phase that facilitates flap observation of the ascending aorta in Stanford type A acute aortic dissection with perfused false lumen. Methods: We reconstructed retrospective Electrocardiogram-gated Computed Tomography Angiography images of the ascending aorta of all 20 patients to 20 phases of curved-multiplanar reconstruction in 5% increment. One radiologist created and randomized 10 cross-sectional images of each phase for every patient and two radiologists scored these images on a 5-point scale depending on the degree of flap stoppage. We calculated the average score for each phase of each case and compared them among the three groups. Results: Image scores were significantly better in the 65 %–100 % R-R interval group than those in the 5%–30 % (p < 2e-16) and 35 %–60 % R-R interval groups(p = 7.2e-10). Similar scores were observed in the Heart Rate > 70 group (p = 0.00039, 2.2e-14). Moreover a similar tendency was observed in the arrhythmia group (p = 0.0035, 0.294). No difference was found in the degree of flap stoppage in the 65 %–100 % R-R interval group between the Heart Rate > 70 and Heart Rate ≤ 70 groups (p = 0.466) and between the arrhythmia and non-arrhythmia groups (p = 0.1240). Conclusion: In observing the ascending aorta, We obtained a good image at 65 %–100 % R-R interval and similar tendency was observed in the patients with arrhythmia.