Hemolysis Precedes Urine Color Change in Patients Undergoing Open-Heart Surgery on Cardiopulmonary Bypass.

PURPOSE: Red-colored urine often occurs in patients in the perioperative period who undergo cardiac surgery using cardiopulmonary bypass (CPB). This urine color change has been utilized for approximating hemolysis during CPB without a proven relationship for ongoing hemolysis. This case series study aimed to examine the relationship between plasma free hemoglobin (Hb) levels and quantified measures of urine color. METHODS: Ten patients were enrolled in this study. Blood and urine were collected for analyses for the following time points: before surgery, two hours after the initiation of CPB, every 30 min during CPB thereafter, and 0, 2, 4, 12, and 24 hours after the completion of CPB. We measured free Hb in plasma and urine using the azide-methemoglobin method. Photographs of urine were obtained, and the luminance of the three basic colors (red/green/blue) was analyzed by quantitative luminance contrast analysis to find a correlation for hemolysis. RESULTS: Median levels of plasma free Hb were 0.015 (0.010-0.080, n = 10) g/dL at baseline. During the CPB, increases in plasma free Hb levels were measured: median plasma free Hb levels were increased to 0.100 g/dL (0.020-0.240, p = 0.039, vs. baseline, n = 9) at two hours into CPB, median and range, respectively. In contrast, increases in urinary free Hb levels and/or urine color changes were measured only after cessation of CPB in nine patients. CONCLUSION: Urine color change or elevation of urinary free Hb levels followed the elevation of plasma free Hb levels with considerable delay.

Change in the efficacy of influenza vaccination after repeated inoculation under antigenic mismatch: A systematic review and meta-analysis.

OBJECTIVES: To examine the effects of repeated influenza vaccination on medically-attended influenza (MAI) and acute respiratory illness (ARI) risk according to the antigenic matching between vaccine and circulating virus strains. METHODS: We performed a systematic review and meta-analysis of randomized studies that compared the risk of MAI and ARI between subjects who had been vaccinated for two consecutive seasons (multiple vaccine group) and those who had been vaccinated in the current season and not in the previous season (single vaccine group). RESULTS: Of 1467 articles identified, eight studies covering ten seasons were included in meta-analyses. Six studies assessed efficacy against MAI in children, yielding the risk ratios (RR) of 2.04 (95% CI 1.29-3.22) when circulating strains mismatched vaccine strains, and 0.64 (0.33-1.22) when circulating strains matched vaccine strains. When stratified by vaccine types, the reduced efficacy was significant for live-attenuated influenza vaccine only. Three studies investigated efficacy against ARI in children, with the RR of 0.96 (0.81-1.15). The results on adults and the elderly were scarce. CONCLUSIONS: Influenza vaccine efficacy against mismatch strains was lower in repeatedly vaccinated children as compared with those vaccinated for the current season only. The scarcity of available studies may call for further randomized controlled trials on repeated influenza vaccination.

Impaired degradation of WNK1 and WNK4 kinases causes PHAII in mutant KLHL3 knock-in mice.

Pseudohypoaldosteronism type II (PHAII) is a hereditary disease characterized by salt-sensitive hypertension, hyperkalemia and metabolic acidosis, and genes encoding with-no-lysine kinase 1 (WNK1) and WNK4 kinases are known to be responsible. Recently, Kelch-like 3 (KLHL3) and Cullin3, components of KLHL3-Cullin3 E3 ligase, were newly identified as responsible for PHAII. We have reported that WNK4 is the substrate of KLHL3-Cullin3 E3 ligase-mediated ubiquitination. However, WNK1 and Na-Cl cotransporter (NCC) were also reported to be a substrate of KLHL3-Cullin3 E3 ligase by other groups. Therefore, it remains unclear which molecule is the target(s) of KLHL3. To investigate the pathogenesis of PHAII caused by KLHL3 mutation, we generated and analyzed KLHL3(R528H/+) knock-in mice. KLHL3(R528H/+) knock-in mice exhibited salt-sensitive hypertension, hyperkalemia and metabolic acidosis. Moreover, the phosphorylation of NCC was increased in the KLHL3(R528H/+) mouse kidney, indicating that the KLHL3(R528H/+) knock-in mouse is an ideal mouse model of PHAII. Interestingly, the protein expression of both WNK1 and WNK4 was significantly increased in the KLHL3(R528H/+) mouse kidney, confirming that increases in these WNK kinases activated the WNK-OSR1/SPAK-NCC phosphorylation cascade in KLHL3(R528H/+) knock-in mice. To examine whether mutant KLHL3 R528H can interact with WNK kinases, we measured the binding of TAMRA-labeled WNK1 and WNK4 peptides to full-length KLHL3 using fluorescence correlation spectroscopy, and found that neither WNK1 nor WNK4 bound to mutant KLHL3 R528H. Thus, we found that increased protein expression levels of WNK1 and WNK4 kinases cause PHAII by KLHL3 R528H mutation due to impaired KLHL3-Cullin3-mediated ubiquitination.