The reno-protective effect of hydration with sodium bicarbonate plus N-acetylcysteine in patients undergoing emergency percutaneous coronary intervention: the RENO Study.

OBJECTIVES: This study was designed to determine the effectiveness of a protocol for rapid intravenous hydration to prevent contrast-induced nephropathy (CIN) in patients undergoing emergency percutaneous coronary intervention (PCI). BACKGROUND: Contrast-induced nephropathy frequently complicates PCI, resulting in prolonged hospitalization and increased in-hospital and long-term morbidity and mortality. Little is known regarding prevention of CIN in patients undergoing urgent PCI. METHODS: We conducted a prospective, controlled, randomized, single-center trial in 111 consecutive patients with acute coronary syndrome undergoing emergency PCI. As part of the hydration therapy, 56 patients (group A) received an infusion of sodium bicarbonate plus N-acetylcysteine (N-AC) started just before contrast injection and continued for 12 h after PCI. The remaining 55 patients (group B) received the standard hydration protocol consisting of intravenous isotonic saline for 12 h after PCI. In both groups, 2 doses of oral N-AC were administered the next day. RESULTS: The 2 groups were similar with respect to age, gender, diabetes mellitus, and baseline serum creatinine. A serum creatinine concentration >0.5 mg/dl from baseline after emergency PCI was observed in 1 patient in group A (1.8%) and in 12 patients in group B (21.8%; p < 0.001). Acute anuric renal failure was observed in 1 patient (1.8%) in group A and in 7 patients (12.7%) in group B (p = 0.032). CONCLUSIONS: Rapid intravenous hydration with sodium bicarbonate plus N-AC before contrast injection is effective and safe in the prevention of CIN in patients undergoing emergency PCI.     

Analysis of incidence and clinical outcomes in patients with thromboembolic events and invasive exocrine pancreatic cancer

BACKGROUND:

Pancreatic adenocarcinoma is among the most common malignancies associated with thromboembolic events (TEs); however, reported incidence figures vary significantly and contain small patient cohorts. Pancreatic cancer‐specific thrombosis studies examining the correlation between clinical variables, including thrombosis timing and the impact of thrombosis on survival, have not been reported.

METHODS:

Survival analyses were performed relating to the development and timing of a TE in 1915 patients administered chemotherapy at Memorial Sloan‐Kettering Cancer Center with invasive exocrine pancreatic cancer from January 1, 2000 to December 31, 2009. TE timing, relative to clinical parameters including laboratory data, erythropoietin‐stimulating agent use, and body mass index (BMI), were also analyzed.

RESULTS:

A thrombosis was identified in 690 (36%) patients. After adjusting for patients with pancreatic surgery and thrombosis (n = 127), developing a TE significantly increased the risk of death (hazard ratio [HR], 2.6; 95% confidence interval [CI], 2.3‐2.8; P < .01). Patients with an early TE (within 1.5 months from pancreatic cancer diagnosis) had a significantly higher risk of death (HR, 2.1; 95% CI, 1.7‐2.5; P < .01) compared with patients with late TE or no TE. Erythropoietin‐stimulating agent use and an elevated international normalized ratio were associated with significantly shorter time to thrombosis. Low BMI was associated with significantly longer time to thrombosis.

CONCLUSIONS:

TEs are common in exocrine pancreatic cancer, with coagulopathy, erythropoietin‐stimulating agent use, and underweight BMI influencing thrombosis timing. TEs, particularly early ones, confer a significantly worse prognosis, suggesting a biological significance, underscoring the relevance of ongoing prophylaxis trials, and raising the question of whether early TEs should be considered a stratification factor for clinical trials. Cancer 2012;118: 3053–61. © 2011 American Cancer Society.     

Interventions to Try to Prevent Preterm Birth in Women With a History of Conization: A Systematic Review and Meta-analyses

Objectives

The most effective preterm birth (PTB) intervention is unknown for women who are at risk of PTB due to a history of conization. The objective of this systematic review was to determine whether PTB interventions, progesterone, cerclage, and pessary decrease the risk of PTB compared to no treatment in singleton—and separately in twin—pregnancies of women with history of conization.

Ferromagnetism and Superconductivity in CaRuO3/YBa2Cu3O7-δ Heterostructures

The deposition of a ferromagnetic layer can affect the properties of high-temperature superconductors underneath. We investigated the influence of ferromagnetic CaRuO₃ on the properties of YBa₂Cu₃O_7-x (YBCO) superconducting thin films when the layers are either in direct contact or separated by a barrier layer of 5 nm SrTiO₃. Detailed measurements of the magnetic moment of the superconductor and ferromagnet as a function of temperature and magnetic field have been performed using SQUID magnetometry. Magnetometry and relaxation measurements show that the modification of the superconducting properties of YBCO strongly depends on the interaction with the ferromagnetic layer on top. The barrier layer has a significant impact on both the supercon-ducting properties of the YBCO film and the ferromagnetic ordering of CaRuO₃. The physical properties mentioned above were discussed in correlation with the materials’ structure determined by XRD analysis.     

Some anti-chronic inflammatory compounds are DNA polymerase lambda-specific inhibitors

We previously reported that a phenolic compound, petasiphenol, was a selective inhibitor of DNA polymerase lambda (pol lambda) in vitro. We found here that another phenolic compound, curcumin (diferuloylmethane), which is known as an anti-chronic inflammatory agent and is structurally quite similar to petasiphenol, was also a potent pol lambda inhibitor. The IC(50) values of petasiphenol and curcumin were 7.8 and 7.0 microM, respectively. Curcumin, as well as petasiphenol, did not influence the activities of replicative DNA polymerases, such as alpha, gamma, delta, and epsilon, but also showed no effect even on the pol beta activity belonging to the X family. Curcumin could prevent the growth of human NUGC-3 cancer cells with LD(50) values of 13 microM, and halted them at the G2/M phase in the cell cycle, whereas petasiphenol suppressed the cell growth at 66 microM and arrested the cells at the G1 phase. These data showed that curcumin and petasiphenol were slightly different functionally. We also previously reported that novel anti-inflammatory terpeno benzoic acids and triterpenoids were inhibitors of mammalian DNA polymerases. They could also efficiently inhibit the pol lambda activity, although they influenced the other polymerase species to the same extent, suggesting that there may be a physiological relationship between pol lambda inhibition and anti-12-O-tetradecanoylphorbol-13-acetate-induced inflammation. Expectedly, petasiphenol also showed an anti-12-O-tetradecanoylphorbol-13-acetate-induced inflammatory effect in mice. This finding may provide clues to investigating the molecular mechanism of inflammation.     

Variants in the ATM gene associated with a reduced risk of contralateral breast cancer

Between 5% and 10% of women who survive a first primary breast cancer will subsequently develop a second primary cancer in the contralateral breast. The Women's Environment, Cancer, and Radiation Epidemiology Study was designed to identify genetic and environmental determinants of contralateral breast cancer (CBC). In this study, 708 women with asynchronous CBC served as cases and 1,397 women with unilateral breast cancer served as controls. ATM, a serine-threonine kinase, controls the cellular response to DNA double-strand breaks, and has been implicated in breast cancer risk. Complete mutation screening of the ATM gene in all 2,105 study participants identified 240 distinct sequence variants; only 15 were observed in >1% of subjects. Among the rare variants, deleterious alleles resulting in loss of ATM function were associated with a nonsignificant increase in risk of CBC. In contrast, carriers of common variants had a statistically significant reduction in risk of CBC. Four of these 15 variants were individually associated with a significantly decreased risk of second primary breast cancer [c.1899-55T>G, rate ratio (RR), 0.5; 95% confidence interval (CI), 0.3-0.8; c.3161C>G, RR, 0.5; 95% CI, 0.3-0.9; c.5558A>T, RR, 0.2; 95% CI, 0.1-0.6; c.6348-54T>C RR, 0.2; 95% CI, 0.1-0.8]. These data suggest that some alleles of ATM may exert an antineoplastic effect, perhaps by altering the activity of ATM as an initiator of DNA damage responses or a regulator of p53.     

Insomnia severity in chronic kidney disease patients with various therapies

The prevalence of insomnia is greater in end-stage renal disease. The aim of our study was to determine the frequency of insomnia and subclinical insomnia in patients with various dialysis therapy and kidney transplant recipients, in order to assess the severity of insomnia and examine whether there is a difference in severity among groups. In cross-sectional study, we evaluated 120 patients with terminal renal failure. Based on therapy, patients were divided into four groups: hemodiafiltration, standard bicarbonate dialysis, peritoneal dialysis and kidney transplant recipients. The severity of insomnia was evaluated through the use of the Insomnia Severity Index (ISI). Most patients who reported any kind of insomnia problems with ISI were on conventional dialysis (80%), followed by hemodiafiltration (76.7%) and peritoneal dialysis (63.3%). Transplant recipients had least difficulties with insomnia (46.7%). Insomnia Severity Index showed that insomnia in end-stage renal patients is not very severe. Most of the patients had “no clinically significant insomnia”. Our findings indicate that patients on hemodiafiltration and transplant recipients have a significantly lower score on Insomnia Severity Index. Patients with end-stage renal disease have high frequency insomnia problems. However, our study shows that insomnia in these patients is not severe. Insomnia is the most frequent and severest in patients on standard bicarbonate dialysis.     

Usefulness of changes in left ventricular wall thickness to predict full or partial pressure reperfusion in ST-elevation acute myocardial infarction

Experimental studies have shown that if an acute transmural myocardial infarction is reperfused at full pressure there is an immediate and persisting increase in end-diastolic wall thickness (EDWT) due to massive intramural edema, with the amount of edema inversely related to the residual stenosis in the infarct-related artery. This study investigated if these findings are paralleled in the clinical setting and whether the resultant myocardial substrate differs after percutaneous coronary intervention (PCI) versus thrombolysis (the latter having a higher incidence of residual flow limiting stenosis in the culprit vessel). Eighty-eight consecutive patients with ST-elevation myocardial infarction were enrolled. Twenty-seven patients underwent primary PCI, 23 had rescue PCI, and 38 had thrombolysis. Standard M-mode and 2-dimensional echocardiographies were performed within 12 hours. Regional EDWT was measured in 904 infarct-related segments after the different reperfusion strategies and compared with 504 remote noninfarcted segments. EDWT of infarct-related segments after primary PCI was significantly increased compared with normal segments. At follow-up, after 6 months, EDWT of these segments was significantly decreased, indicating transmural infarction. EDWT of infarct-related segments after thrombolysis did not differ from that of normal segments. After rescue PCI, EDWT of infarct-related segments was significantly decreased compared with that of normal segments. In conclusion, full-pressure restoration of epicardial blood flow after transmural myocardial infarction causes an immediate increase in EDWT, easily detected by echocardiography. In contrast, pressure-limiting reperfusion (typical for thrombolysis) resultsin normal EDWT. This confirms experimental data that PCI and thrombolysis can differ in their resultant myocardial substrate.