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.     

Validation and reliability of a Japanese version of the Shoulder Pain and Disability Index: A cross-sectional study

BackgroundThe Shoulder Pain and Disability Index (SPADI) is a simple disease specific questionnaire that is used to evaluate the impact of shoulder disorders. The purpose of this study was to translate the SPADI into Japanese (SPADI-Jp) and evaluate its reliability and validity in Japanese patients with shoulder disorders.MethodsCross-cultural adaptation of the SPADI was performed according to international guidelines. A total of 100 patients with shoulder disorders participated in this study. Each participant was asked to finish the SPADI-Jp, Disability of Arm, Shoulder and Hand (DASH), and the Short-Form 36 (SF-36) at the initial visit. Thirty-four patients repeated the SPADI-Jp to assess the test–retest reliability. The test–retest reliability was quantified using the interclass correlation coefficient (ICC), while Cronbach's alpha was calculated to assess the internal consistency. The construct validity was assessed using Spearman's rank correlation coefficients.ResultsInternal consistency in the SPADI-Jp was very high (0.969), as measured by the Cronbach's alpha. The ICC of the SPADI-Jp was 0.930. There was a strong, positive correlation between the DASH and the SPADI-Jp (r = 0.837, p < 0.001). The SPADI-Jp was significantly correlated with most of the SF-36 subscales. The correlations of the SPADI-Jp with physical subscales of the SF-36 were stronger than those with the other subscales.ConclusionsWe demonstrated that the SPADI-Jp is a reliable and valid self-assessment tool. Because cross-cultural adaptation, validation, and reliability of the disease-specific questionnaire for shoulder pain and disability have not been evaluated in Japan, the SPADI-Jp can be useful for evaluating such patients in the Japanese population.     

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.     

Effects of nicotine on cultured cells suggest that it can influence the formation and resorption of bone

The acute effects of nicotine [1-methyl-2-(3-pyridyl)pyrrolidine] on the formation and resorption of bone were examined in cultures of clonal rat calvarial osteogenic cells (ROB-C26) and clonal mouse calvarial preosteoblastic cells (MC3T3-E1), as well as in osteoclast-like cells formed during coculture of mouse bone marrow cells and clonal stromal cells from mouse bone marrow, ST2 cells, at concentrations that occur in the saliva of smokeless tobacco users. Nicotine stimulated the rate of deposition of Ca(2+) by ROB-C26 cells, as well as the alkaline phosphatase activity of these cells, in a dose-dependent manner. However, both activities decreased in MC3T3-E1 cells that had been exposed to nicotine. These results indicate that nicotine affected osteoblastic differentiation in osteoblast-like cells. By contrast, nicotine reduced, in a dose-dependent manner, the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) and the formation of pits on slices of dentine, both of which are typical characteristics of osteoclasts. Our results suggest that nicotine might have critical effects on bone metabolism.     

A case of ductal carcinoma in situ (DCIS; non-comedo type) detected by ultrasonography: Demonstration of occult multiple foci

We report a case of ductal carcinoma in situ (DCIS) of the breast detected by ultrasonographic mass screening in a 51-year-old woman. In a mass screening program for breast cancer, physical examination with inspection and palpation, and ultrasonography (US) were performed. A hypoechoic mass with a slightly irregular margin was detected by US in the lateral upper quadrant of the right breast, at a distance 2 cm from the edge of the nipple. The mass was not detected by physical examinations or by mammography (MMG). The mass, which measured 0.8 x 0.5 cm and was examined by fine needle aspiration biopsy (FNAB) under US guidance, was cytologically diagnosed as class X. Modified radical mastectomy (Auchincloss method) was performed with the patient's consent. Pathological examination of the resected specimen revealed DCIS (noncomedo type) and occult multiple foci of malignancy which was considered tracking centripetally underneath the nipple. This case suggests that US and FNAB performed under US guidance are useful in the detection and diagnosis, respectively, of a breast mass. We should take multifocality into consideration, particularly with tendency tracking to the nipple, in the treatment of small breast cancers such as DCIS.     

Fecal incontinence successfully managed by antegrade continence enema in children: A report of two cases

Two children with intractable fecal incontinence after correction of high anorectal malformations were successfully managed by the daily administration of a glycerin enema into the cecum via an appendicocecostomy or tubularized cecostomy, according to the method of Malone's antegrade continence enema (ACE). Fluoroscopic defecography performed during this procedure in each patient disclosed that the glycerin enema promptly evoked cecal peristalsis, which was transmitted to the distal colon and rectum, and squeezed out almost all the fecal matter, evacuating it from the anus. However, two enemas within a short interval were required to achieve a complete washout of feces. Although this report describes only two patients, our experience confirmed that the ACE was very effective and that adding the word continence to antegrade enema was justifiable. Moreover, fluoroscopic defecography was proven to play a significant role in determining the appropriate regimens of this technique to achieve complete washout of the feces.     

Intrathecal substance P depresses the tail-flick response — Antagonism by naloxone

Summary Substance P injected into the lumbar subarachnoid space of rats depressed the tail-flick response to radiant heat in a dose-dependent way. The effective doses ranged from 0.1 g to 100 g per rat (ED 50: 1.5 g/rat). The maximum of the effect was reached 20 min after intrathecal injection and the effect lasted for about 30 min. An antinociceptive effect was also observed after intrathecal injection of substance P 1 g to spinal rats. The depression of the tail-flick response produced by intrathecal administration of substance P was abolished by intrathecal (5 g/rat) or i.p. (0.5 mg/kg) injections of naloxone.Supported by the Sonderforschungsbereich 38 Membranforschung