Effect of proton pump inhibitors and other commonly prescribed drugs on rescanning of patients undergoing myocardial perfusion imaging: a case-control study.

OBJECTIVES: Proton pump inhibitor use is associated with increased gastric wall activity on myocardial perfusion imaging; however, the clinical impact is unknown. We sought to determine the association of the use of proton pump inhibitors and nine other commonly prescribed classes of medications on the risk of rescanning patients undergoing myocardial perfusion imaging. METHODS: A matched case-control study was performed including 337 rescanned cases and 337 same-day controls from a total of 5432 patients undergoing myocardial perfusion imaging (MPI) over a 4-year period. RESULTS: The odds of rescanning was higher in patients taking a proton pump inhibitor than those not [adjusted odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-2.2] and in those taking an angiotensin-converting enzyme inhibitor than those not (adjusted OR, 1.5; 95% CI, 1.0-2.2) adjusted for age, sex and BMI category. Eight other commonly prescribed medications showed no associations with rescanning. Among the cases of rescanning, the culprit organ site of extracardiac activity was the left lobe of the liver, 48%; gastric wall, 31%; gastric lumen, 12%; spleen, 7% and bowel <1%. Proton pump inhibitor use was strongly associated with rescanning due to gastric wall uptake (adjusted OR, 6.3; 95% CI, 2.8-14.1) but not the other causes of rescanning. CONCLUSIONS: Proton pump inhibitor use and angiotensin-converting enzyme inhibitor use are associated with an increased risk of rescanning of patients undergoing MPI. Gastric wall activity is likely to account for the excess cases of rescanning in those taking a proton pump inhibitor.

Complement Initiation Varies by Sex in Intestinal Ischemia Reperfusion Injury.

Intestinal ischemia reperfusion (IR)-induced tissue injury represents an acute inflammatory response with significant morbidity and mortality. The mechanism of IR-induced injury is not fully elucidated, but recent studies suggest a critical role for complement activation and for differences between sexes. To test the hypothesis that complement initiation differs by sex in intestinal IR, we performed intestinal IR on male and female WT C57B6L/, C1q-/-, MBL-/-, or properdin (P)-/- mice. Intestinal injury, C3b and C5a production and ex vivo secretions were analyzed. Initial studies demonstrated a difference in complement mRNA and protein in male and female WT mice. In response to IR, male C1q-, MBL- and P-deficient mice sustained less injury than male WT mice. In contrast, only female MBL-/- mice sustained significantly less injury than female wildtype mice. Importantly, wildtype, C1q-/- and P-/- female mice sustained significant less injury than the corresponding male mice. In addition, both C1q and MBL expression and deposition increased in WT male mice, while only elevated MBL expression and deposition occurred in WT female mice. These data suggested that males use both C1q and MBL pathways, while females tend to depend on lectin pathway during intestinal IR. Females produced significantly less serum C5a in MBL-/- and P-/- mice. Our findings suggested that complement activation plays a critical role in intestinal IR in a sex-dependent manner.

Prognostic importance of coincidental coronary artery calcification on FDG-PET/CT oncology studies.

Coronary artery calcification (CAC) on body CT imaging is considered a coincidental finding in cancer patients. In order to determine the significance of CAC in cancer patients we evaluated the prognostic utility of CAC detected on oncology FDG-PET/CT studies. A retrospective study was performed of consecutive FDG-PET/CT studies from January to March 2011. CAC was identified on the CT portion of FDG/PET-CT studies. Chart review documented statin use, the Framingham risk score (FRS) (includes age, diabetes, hypertension, dyslipidemia and smoking), the primary malignancy and metastases. The primary end point was a composite of death and cardiovascular (CV) events (non-fatal myocardial infarction (MI), PCI or coronary artery bypass surgery (CABG)). 266 patients had a median follow up of 41 months (95% CI 31-56 months). CAC was noted in 140 patients. Based on CAC, potentially 84 patients would have had a change in statin prescribing (p < 0.01). CAC was associated with the primary end point on univariable and multivariable analysis (OR 2.6 (95% CI 1.42-4.77) (p < 0.01). On univariable Kaplan-Meier survival analysis, CAC was associated with decreased survival only in the absence of metastases (p < 0.01). Cox proportional hazard modelling demonstrated CAC was associated with mortality and cardiac events in patients without metastases, whereas FRS was not (For CAC: HR 1.69 (95% CI 1.22-2.35), p = 0.002). CAC is commonly detected with oncology FDG-PET/CT. In cancer patients CAC was associated with an increased risk of clinical events. CAC reduced survival free time in patients without metastases. CAC might therefore be considered more than a coincidentaloma in patients without metastases.

Eicosanoid production varies by sex in mesenteric ischemia reperfusion injury.

Intestinal ischemia/reperfusion (I/R)-induced injury is an inflammatory response with significant morbidity and mortality. The early inflammatory response includes neutrophil infiltration. However, the majority of rodent studies utilize male mice despite a sexual dimorphism in intestinal I/R-related diseases. We hypothesized that sex may alter inflammation by changing neutrophil infiltration and eicosanoid production. To test this hypothesis, male and female C57Bl/6 mice were subjected to sham treatment or 30 min intestinal ischemia followed by a time course of reperfusion. We demonstrate that compared to male mice, females sustain significantly less intestinal I/R-induced tissue damage and produced significant LTB4 concentrations. Male mice release PGE2. Finally, treatment with a COX-2 specific inhibitor, NS-398, attenuated I/R-induced injury, total peroxidase level, and PGE2 production in males, but not in similarly treated female mice. Thus, I/R-induced eicosanoid production and neutrophil infiltration varies between sexes suggesting that distinct therapeutic intervention may be needed in clinical ischemic diseases.

Beta2 glycoprotein I-derived therapeutic peptides induce sFlt-1 secretion to reduce melanoma vascularity and growth.

Melanoma, a form of skin cancer, is one of the most common cancers in young men and women. Tumors require angiogenesis to provide oxygen and nutrients for growth. Pro-angiogenic molecules such as VEGF and anti-angiogenic molecules such as sFlt-1 control angiogenesis. In addition, the serum protein, Beta2 Glycoprotein I (ß2-GPI) induces or inhibits angiogenesis depending on conformation and concentration. ß2-GPI binds to proteins and negatively charged phospholipids on hypoxic endothelial cells present in the tumor microenvironment. We hypothesized that peptides derived from the binding domain of ß2-GPI would regulate angiogenesis and melanoma growth. In vitro analyses determined the peptides reduced endothelial cell migration and sFlt-1 secretion. In a syngeneic, immunocompetent mouse melanoma model, ß2-GPI-derived peptides also reduced melanoma growth in a dose-dependent response with increased sFlt-1 and attenuated vascular markers compared to negative controls. Importantly, administration of peptide with sFlt-1 antibody resulted in tumor growth. These data demonstrate the therapeutic potential of novel ß2-GPI-derived peptides to attenuate tumor growth and endothelial migration is sFlt-1 dependent.

Sensitized photon upconversion in anthracene-based zirconium metal-organic frameworks.

Sensitized upconversion is explored in three metal-organic frameworks (MOFs) constructed from the anthracene dicarboxylate (ADC) derivatives and zirconium nodes, 9,10-ADC (9,10-MOF), 2,6-ADC (2,6-MOF) and 1,4-ADC (1,4-MOF). Selective excitation of surface-bound Pd(ii) mesoporphyrin IX (PdMP) gives rise to delayed fluorescence (τ = 370 ± 30 ns) from anthracene in the 9,10-MOF. The overall upconversion efficiency of the Pd@9,10-MOF is 0.46 ± 0.05% with a threshold intensity of 104 ± 26 mW cm-2.