HR‐MAS MRS of the pancreas reveals reduced lipid and elevated lactate and taurine associated with early pancreatic cancer

The prognosis for patients with pancreatic cancer is extremely poor, as evidenced by the disease's five‐year survival rate of ~5%. New approaches are therefore urgently needed to improve detection, treatment, and monitoring of pancreatic cancer. MRS‐detectable metabolic changes provide useful biomarkers for tumor detection and response‐monitoring in other cancers. The goal of this study was to identify MRS‐detectable biomarkers of pancreatic cancer that could enhance currently available imaging approaches. We used ¹H high‐resolution magic angle spinning MRS to probe metabolite levels in pancreatic tissue samples from mouse models and patients. In mice, the levels of lipids dropped significantly in pancreata with lipopolysaccharide‐induced inflammation, in pancreata with pre‐cancerous metaplasia (4 week old p48‐Cre;LSL‐Kras^G12D mice), and in pancreata with pancreatic intraepithelial neoplasia, which precedes invasive pancreatic cancer (8 week old p48‐Cre LSL‐Kras^G12D mice), to 26 ± 19% (p = 0.03), 19 ± 16% (p = 0.04), and 26 ± 10% (p = 0.05) of controls, respectively. Lactate and taurine remained unchanged in inflammation and in pre‐cancerous metaplasia but increased significantly in pancreatic intraepithelial neoplasia to 266 ± 61% (p = 0.0001) and 999 ± 174% (p < 0.00001) of controls, respectively. Importantly, analysis of patient biopsies was consistent with the mouse findings. Lipids dropped in pancreatitis and in invasive cancer biopsies to 29 ± 15% (p = 0.01) and 26 ± 38% (p = 0.02) of normal tissue. In addition, lactate and taurine levels remained unchanged in inflammation but rose in tumor samples to 244 ± 155% (p = 0.02) and 188 ± 67% (p = 0.02), respectively, compared with normal tissue. Based on these findings, we propose that a drop in lipid levels could serve to inform on pancreatitis and cancer‐associated inflammation, whereas elevated lactate and taurine could serve to identify the presence of pancreatic intraepithelial neoplasia and invasive tumor. Our findings may help enhance current imaging methods to improve early pancreatic cancer detection and monitoring. Copyright © 2014 John Wiley & Sons, Ltd.     

Simultaneous Detection of Major Drug Resistance Mutations of HIV-1 Subtype B Viruses from Dried Blood Spot Specimens by Multiplex Allele-Specific Assay

A multiplex allele-specific (MAS) assay has been developed for the detection of HIV-1 subtype C drug resistance mutations (DRMs). We have optimized the MAS assay to determine subtype B DRMs in dried blood spots (DBS) collected from patients on antiretroviral therapy. The new assay accurately detected DRMs, including low-abundance mutations that were often missed by Sanger sequencing.     

Molecular remodeling in the failing human heart

Heart failure is a progressive and fatal disease process. Arrhythmias and progressive cardiac dysfunction account for most of the morbidity and mortality in patients with heart failure. In general, the physiologic mechanisms responsible for progressive myocyte dysfunction, remodeling, and arrhythmias involve signaling mechanisms that alter myocardial gene expression. These changes in gene expression are complex and involve contractile proteins, ion channels, Ca++ handling, apoptosis, cell metabolism, the extracellular matrix, signal transduction pathways, and growth factors.     

Tumor treating fields in combination with gemcitabine or gemcitabine plus nab-paclitaxel in pancreatic cancer: Results of the PANOVA phase 2 study

Background

Tumor Treating Fields (TTFields), low intensity alternating electric fields with antimitotic activity, have demonstrated survival benefit in patients with glioblastoma. This phase 2 PANOVA study was conducted to examine the combination of TTFields plus chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC).

The patterns of use and factors associated with the patient admission of hospital emergencies for asthma and chronic obstructive pulmonary disease

The aim of this study was to describe the epidemiological characteristics of emergencies caused by asthma and chronic obstructive pulmonary disease (COPD) at the Hospital Clínico Universitario of Valencia (Spain) and to analyze factors related to hospital admissions for the same causes. Emergency room medical records for 1993 to 1995 of patients older than 14 years of age were examined to identify those due to asthma or COPD, according to established protocol. Demographic variables were described, followed by Poisson regression analysis of time and seasonal factors affecting emergencies. Factors related to hospital admission were analyzed by logistic regression, taking into account age group, sex, place of residence, and the year, month, day and hour of emergency room arrival. Asthma patients amounted to 1% of emergencies, while COPD patients accounted for 2%. The admission rate for women with asthma was higher than for men (F/M ratio = 0.78), whereas the rate for men with COPD was higher than for women (F/M ratio = 3.14). The largest age groups with asthma emergencies included young people aged 15 to 24 years old and those over 60. Hospital admissions or transfers to other hospitals were ordered for 17.4% of asthma patients and 38.8% of COPD patients. Nearly a third of COPD patients and a fifth of asthma patients were readmitted within the ten days following the first emergency. Clear temporal patterns of COPD emergency were observed for month (most occurring in winter), day of the week (most on Monday) and hour of the day (most during daytime hours, with fewer at midday). The time patterns were less evident for asthma emergencies, although the likelihood of admission because of asthma varied by month and day of the week. Emergency room records may be useful for studying the patterns of respiratory disease presentation. Other possible uses are epidemiologic monitoring and evaluation of health care quality.     

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is an autonomic dominant disease characterized by hamartomatous polyps and mucocutaneous hyperpigmentation. We present 16 cases; females were more affected. The most common presenting complaints were of gastrointestinal tract. All polyps found were hamartomatous with general distribution through gastrointestinal tract. Endoscopic polypectomy should be carried out for treatment. Radiologic, endoscopic and histologic studies should be conducted for long-term follow-up, because of high risk of malignancy.     

Necrotizing granulomatous vasculitis in advanced HIV infection

We describe the first case of granulomatous necrotizing vasculitis not restricted to the central nervous system in an HIV-infected patient. No mycobacteria or drugs potentially associated with granuloma formation were involved in this patient, suggesting that the cause of this vasculitis was probably autoimmune. The development of granulomatous vascular inflammation in this patient with less than 200 CD4 cells/microl might have been due to immune overactivation. After starting potent antiretroviral therapy a profound immune deactivation was observed and the vasculitis did not relapse.