Association between Vitamin D and Heart Failure Mortality in 10,974 Hospitalized Individuals

A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 ± 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, p < 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both p < 0.001). In the sub-group analysis, mortalities in patients with age < 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and β-blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials.     

Pig kidney xenotransplantation: Progress toward clinical trials

Pig organ xenotransplantation offers a solution to the shortage of deceased human organs for transplantation. The pathobiological response to a pig xenograft is complex, involving antibody, complement, coagulation, inflammatory, and cellular responses. To overcome these barriers, genetic manipulation of the organ‐source pigs has largely been directed to two major aims—(a) deletion of expression of the known carbohydrate xenoantigens against which humans have natural (preformed) antibodies, and (b) transgenic expression of human protective proteins, for example, complement‐ and coagulation‐regulatory proteins. Conventional (FDA‐approved) immunosuppressive therapy is unsuccessful in preventing an adaptive immune response to pig cells, but blockade of the CD40:CD154 costimulation pathway is successful. Survival of genetically engineered pig kidneys in immunosuppressed nonhuman primates can now be measured in months. Non‐immunological aspects, for example, pig renal function, a hypovolemia syndrome, and rapid growth of the pig kidney after transplantation, are briefly discussed. We suggest that patients on the wait‐list for a deceased human kidney graft who are unlikely to receive one due to long waiting times are those for whom kidney xenotransplantation might first be considered. The potential risk of infection, public attitudes to xenotransplantation, and ethical, regulatory, and financial aspects are briefly addressed.     

Iron,coronary artery calcification,and mortality in patients undergoing hemodialysis

ObjectiveA high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients.MethodsWe studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston’s CACS were obtained at baseline for two groups of patients: those with CACS ≥400 (n = 109) and those with CACS <400 (n = 64). Logistic regression analyses for CACS ≥400 and Cox proportional hazard analyses for mortality were conducted.ResultsThe median (interquartile range) age and duration of dialysis of the participants were 67 (60–75) years and 73 (37–138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS ≥400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT ≥21% was significantly associated with CACS ≥400 (odds ratio 0.46, p<0.05). TSAT ≥17%, Fe ≥63 µg/dL, and ferritin ≥200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05).ConclusionWe have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS ≥400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.     

The anti-proliferative effect of proliferating cell nuclear antigen-specific antisense oligonucleotides on human gastric cancer cell lines

The proliferating cell nuclear antigen (PCNA) is a nuclear protein that leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high proliferative activity, PCNA is suspected of playing an important role in the proliferation and advancement of gastric cancer. Thus, the effects of antisense oligonucleotides specific for PCNA mRNA were examined in seven gastric cancer cell lines. It was found that treatment with antisense oligonucleotides at concentrations of 10–40 M dose-dependently inhibited the growth of all cell lines; however, random sequence oligonucleotides did not modify the proliferation of any type of cells. These results indicate that PCNA is essential for cell proliferation in gastric cancer cells, and that the growth inhibitory effect results from the inhibition of PCNA gene expression. Therefore, PCNA-specific antisense oligonucleotides may be effective in the treatment of gastric cancer.     

Development of a simple method for the washout correction of 123I-IMP SPECT and its application to a quantitative rCBF method

We have developed a simple method to correct the washout of tracer from the brain based on the two-compartment model in brain early SPECT using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). This correction was applied to a new quantitative method of regional cerebral blood flow (rCBF) in combination with the microsphere method by continuous arterial sampling previously reported. Data acquisition of 123I-IMP early SPECT was started from 35 min after 123I-IMP i.v. injection, and the time activity curve of whole brain on anterior head planar images was monitored immediately after 123I-IMP i.v. injection for the correction of washout of tracer from the brain. The usefulness of this method was evaluated in 12 patients with various brain diseases by comparison with the results obtained from the super-early SPECT at 7-10 min after 123I-IMP i.v. injection. The washout rates in cases of early SPECT corrected by this method ranged from 16.91% to 39.34% with a mean +/- SD of 27.72 +/- 5.44%. The contrast of hypo- to hyperperfusion regions on early SPECT was improved by the correction of the washout, and its intracerebral distribution was similar to the simultaneously obtained super-early SPECT images. These results indicated that the present correction method for the washout was useful for more correct quantification of rCBF.     

Endothelin antagonist treatment for successful liver transplantation from non-heart-beating donors

BACKGROUND: With the shortage of cadaveric donors, non-heart-beating donors (NHBDs) are a potential source of liver allografts. However, warm ischemic injury in NHBDs seriously affects the viability of graft liver. Endothelin (ET)-1 has been reported to be involved in the hepatic microcirculatory disturbances after ischemia-reperfusion. METHODS: In a porcine orthotopic liver transplantation model, changes in the serum and liver tissue ET-1 concentration were measured and the effects of an ET receptor antagonist, TAK-044, were evaluated. After cardiac arrest of the donors, liver allografts were subjected to 90 min of warm ischemia, flushed, and preserved for 4 hr at 4 degrees C. The pigs were divided into two groups: a control group (no drug treatment) and a drug-treated group, in which donors and recipients were treated with TAK-044 (10 mg/kg body, drip intravenous injection). Both groups had six donor/recipient pairs. RESULTS: -The ET-1 concentration in the hepatic venous blood increased after reperfusion of the graft in the control group recipients. ET-1 in the graft liver significantly increased during the cold preservation period. TAK-044 treatment significantly increased recipient 7-day survival rate. After reperfusion of the graft, the concentrations of serum liver enzymes and arterial lactate in the drug-treated group were significantly lower than in the control group. The postoperative increase in portal venous pressure was significantly reduced in the drug-treated group. Measurements of liver enzymes in the washed-out preservation fluid at the time of graft rinsing indicated that TAK-044 treatment of the donors significantly suppressed liver enzyme release during ischemia. CONCLUSIONS: These findings indicate TAK-044 treatment has protective effects on postoperative function of hepatic allografts procured from NHBDs.     

Metastable Equilibrium Solubility Behavior of Bone Mineral

Previous studies have shown that carbonated apatites with a range of carbonate contents and crystallinities exhibit the phenomenon of metastable equilibrium solubility (MES) distributions. The purpose of the present study was to investigate the solubility behavior of bone mineral using the concepts of MES and MES distributions and, together with crystallinity and chemical composition data, examine the similarity of bone mineral to carbonated apatite (CAP). Bone samples were harvested from 1-, 5-, and 8-month-old rats. The organic components of the bone samples were removed by hydrazine deproteination. Carbonated apatite was synthesized by the hydrolysis of dicalcium phosphate dihydrate (DCPD) in a NaHCO₃-containing media at 50°C. The MES distributions of bone mineral and CAP were determined by equilibrating predetermined amounts of CAP or bone mineral in a series of 0.1 M acetate buffers containing calculated levels of calcium and phosphate and maintained at essentially constant pHs of 5.0, 5.3, 5.7, and 6.5. From the compositions of the equilibrating buffer solutions, ion activity products based upon the stoichiometries of octacalcium phosphate, hydroxyapatite, and carbonated apatite were calculated in an attempt to determine the function governing the dissolution of CAP and bone mineral. The results of this study demonstrated that the MES distribution phenomenon appeared to hold for bone mineral and that the changes in crystallinity of bone mineral with age correlated well with changes in the MES values. A CAP sample was prepared that was found to be an excellent synthetic prototype closely mimicking the physicochemical behavior of bone mineral from an 8-month-old rat. Another finding of this study was that the ion activity product function based upon the hydroxyapatite stoichiometry well described the MES results obtained with both CAP and bone mineral. The interpretation that a surface complex with hydroxyapatite stoichiometry governs the solubility behavior of bone mineral is, therefore, consistent with the experimental data. Other calcium phosphate stoichiometries for the surface complex showed systematic variations in the MES profiles when the pH of the equilibrating solution was varied. Received: 30 October 1997 / Accepted: 1 October 1998