Long-Term Prognosis of Hyperferritinemia Induced by Intravenous Iron Therapy in Patients Undergoing Maintenance Hemodialysis: A 10-Year, Single-Center Study

Optimal ferritin level in hemodialysis patients between Japan and other countries is controversial. Long-term side effects of iron supplementation in these patients remain unclear. We aimed to elucidate whether past hyperferritinemia in hemodialysis patients was associated with high risk of death and cerebrovascular and cardiovascular diseases (CCVDs). This small retrospective cohort study included approximately 44 patients unintentionally supplemented with excessive intravenous iron. A significantly higher risk of CCVDs was observed in patients with initial serum ferritin levels ≥1000 ng/mL than in the remaining patients. High ferritin levels slowly decreased to <300 ng/mL in a median of 24.2 (10.5–46.5) months without treatment. However, compared with the remaining patients, only patients whose ferritin levels did not decrease to <300 ng/mL steadily had a significantly higher risk of all-cause death (hazard ratio, 9.6). Long-term hyperferritinemia due to intravenous iron therapy is a risk factor for death in maintenance hemodialysis patients. For a prolonged better prognosis, intravenous iron should be carefully administered so as to avoid hyperferritinemia in patients with hemodialysis

Potential Inaccuracies in Chloride Measurements in Patients with Severe Metabolic Acidosis

Background. To address the cause(s) of the significant differences in chloride (Cl-) concentrations between point-of-care blood gas analyzers and central laboratory analyzers. Methods. Cl- concentrations measured simultaneously by a blood gas analyzer (ABL800 FLEX) and a central laboratory analyzer (Hitachi7600) were collected in patients with severe acidemia (pH<7.20) (n=32) and were examined for correlations between differences in Cl- and factors associated with the acid-base status. Cl- concentrations were measured with both analyzers for samples with different concentrations of lactate, inorganic phosphate, or bicarbonate (HCO3   −). Results. The differences in Cl- concentrations were correlated with HCO3   − concentrations (r=0.72, P<0.0001) and anion gap (r=0.69, P<0.0001). Only the addition of HCO3   − proportionately increased Cl- levels measured by a Hitachi7600, but it did not affect those measured by an ABL800FLEX. Conclusion. Cl- measurements with some analyzers may be influenced by HCO3   − concentrations, which could result in the observed discrepancies

Availability of Home sleep apnea test equipment LS-140 on a comparison with Polysomnography

OBJECTIVE: The prevalence of obstructive sleep apnea (OSA) in Japan is 9% among males and 3% among females. Up to 2.5 million patients are estimated to suffer from the disease, but limited number of facilities are capable of carrying out polysomnography (PSG), leaving more than 80% of these individuals are undiagnosed. In recent years, the development of new portable sleep monitoring (PMs) devices has been remarkable. We evaluate the correlation between the results of the LS-140 PMs device (Fukuda Denshi Tech Co. Ltd.), released in 2017, and those of PSG. METHODS: We obtained contemporaneous data from the same patients by equipping 58 patients with PMs (LS-140) devices while they underwent PSG. Our primary outcome was Case 2 of the intraclass correlation coefficient (ICC), i.e., the ICC (2.1). And we used a Bland-Altman analysis to compare the apnea-hypopnea index (AHI) given by PSG and the respiratory event index (REI) given by LS-140 and examined the sensitivity and specificity of the REI relative to the AHI in the diagnosis of OSA. We also carried out the same comparison but in terms of the presence or absence of periodic limb movements (PLMs). RESULTS: The ICC (2.1) between The REI and the AHI was 0.944, a rather high value (p<0.0001). The mean difference between AHI and REI values was –3.6 (p<0.0001), indicating a negative fixed bias. Sensitivity may decrease in groups with PLMs. CONCLUSION: The REI and the AHI are highly correlated, giving LS-140 sufficient diagnostic sensitivity and specificity to screen for OSA

Atf1 Is a Target of the Mitogen-activated Protein Kinase Pmk1 and Regulates Cell Integrity in Fission Yeast

In fission yeast, knockout of the calcineurin gene resulted in hypersensitivity to Cl−, and the overexpression of pmp1+ encoding a dual-specificity phosphatase for Pmk1 mitogen-activated protein kinase (MAPK) or the knockout of the components of the Pmk1 pathway complemented the Cl− hypersensitivity of calcineurin deletion. Here, we showed that the overexpression of ptc1+ and ptc3+, both encoding type 2C protein phosphatase (PP2C), previously known to inactivate the Wis1–Spc1–Atf1 stress-activated MAPK signaling pathway, suppressed the Cl− hypersensitivity of calcineurin deletion. We also demonstrated that the mRNA levels of these two PP2Cs and pyp2+, another negative regulator of Spc1, are dependent on Pmk1. Notably, the deletion of Atf1, but not that of Spc1, displayed hypersensitivity to the cell wall-damaging agents and also suppressed the Cl− hypersensitivity of calcineurin deletion, both of which are characteristic phenotypes shared by the mutation of the components of the Pmk1 MAPK pathway. Moreover, micafungin treatment induced Pmk1 hyperactivation that resulted in Atf1 hyperphosphorylation. Together, our results suggest that PP2C is involved in a negative feedback loop of the Pmk1 signaling, and results also demonstrate that Atf1 is a key component of the cell integrity signaling downstream of Pmk1 MAPK