Atherosclerosis in women with endometriosis

OBJECTIVE: This study aims to determine whether women with endometriosis have greater subclinical atherosclerosis than the general population. STUDY DESIGN: This case-control study included 66 women with endometriosis and 66 controls matched for age and body mass index. All subjects were >or=35 years old. Exclusion criteria were obesity, diabetes, hypertension, hyperlipidemia, renal or metabolic diseases. Before laparoscopy, all patients underwent a measurement of intima-media thickness (IMT) and distensibility coefficient (DC) on the common carotid artery. In addition, blood samples were taken to determine the levels of lipids, fibrinogen, C-reactive protein, homocysteine, fasting glycemia, antithrombin III, plasminogen, protein C, protein S, and activated protein C resistance. RESULTS: All the biochemical parameters evaluated had similar levels in the two study groups. IMT was similar in women with endometriosis and in controls both on left (p=0.330) and right (p=0.648) carotid artery. Similarly, no significant difference was observed in the DC between women with endometriosis and controls both on left (p=0.539) and right (p=0.178) carotid artery. No significant difference was observed in IMT and DC between women with mild and severe endometriosis. CONCLUSION: Women with endometriosis do not have more subclinical atherosclerosis than the general population.     

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

Multimodal study of pelvic splenosis: a rare cause of abdominal pain

We present a rare case of pelvic splenosis, in a 46-year-old man, with a previous history of partial splenectomy, complaining of nonspecific pain in the lower abdominal quadrants. Splenosis is a benign acquired condition, defined as a heterotopic autotransplantation of splenic tissue in other compartments of the body, caused by rupture of the splenic capsule following trauma or splenectomy. Splenosis is often asymptomatic and incidentally found and does not require treatment. Surgery is indicated only in patients presenting with symptoms or complications. In our case, the multimodal imaging study (ultrasound, MRI, CT, and scintigraphy) allowed a correct differential diagnosis without resorting to invasive procedures, susceptible to complications     

Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET.

Patients with mild cognitive impairment (MCI) represent a risk population for progressing to dementia of the Alzheimer type (DAT). However, clinical criteria do not ensure reliable individual prognosis in these patients. The objective of this longitudinal, prospective study was to examine the value of (18)F-FDG PET of cerebral glucose metabolism and of genetic susceptibility, as defined by an APOEepsilon4-positive genotype, with regard to the early diagnosis of DAT in patients with MCI. METHODS: In 30 patients with the diagnosis of MCI (16 female, 14 male; age, 70 +/- 8 y), baseline and follow-up examinations (mean observation period, 16 mo) were performed. In all patients, the APOE genotype was assessed and cerebral glucose metabolism was evaluated at baseline using cranial (18)F-FDG PET. Individual PET data were screened for findings suggestive of Alzheimer's disease (AD), with the help of an automated computer program. After stereotactical normalization of the PET images, this program performs an observer-independent statistical comparison with an age-matched reference database (n = 22). RESULTS: In 43% of all MCI subjects, a PET scan suggestive of AD pathology according to our predefined criteria was observed at baseline (PET+); 57% of all MCI patients were carriers of the APOE epsilon4 allele (e4+). In 40% of all patients, progression of symptoms within the observation period justified the clinical diagnosis of probable DAT at the time of follow-up reevaluation. Statistical evaluation revealed the best results for PET with regard to early diagnosis of DAT in MCI patients (sensitivity, 92%; specificity, 89%). Classification according to the APOE genotype was significantly less successful (sensitivity, 75%; specificity, 56%). However, a combination of both diagnostic tests allowed early diagnosis with either very high specificity (PET+ AND e4+: sensitivity, 67%; specificity, 100%) or very high sensitivity (PET+ OR e4+: sensitivity, 100%; specificity, 44%). CONCLUSION: (18)F-FDG PET of cerebral glucose metabolism is a valuable diagnostic tool for the prediction of clinical outcome in individual MCI patients. Results are superior to the exclusive assessment of the APOE genotype. A combination of both functional imaging and genotyping may allow an early high-risk or low-risk stratification of patients with either very high sensitivity or very high specificity. This may be valuable, for example, for patient selection in scientific studies.     

Effects on Smokers of Exposure to Graphic Warning Images

Background and Objectives : Several countries have introduced graphic warning images aimed at discouraging smoking. The objective of this study was to evaluate the impact on smokers of graphic warnings showing cosmetically important harm caused by smoking. Methods : Fifty‐six adult smokers were randomly assigned to view either written smoking warnings or the same written warnings with related graphic images. The smokers viewed the warnings at a rate of one per week for 4 weeks. The smokers were assessed before and after the warnings with regard to stage of change toward smoking cessation and level of smoking. Results : The randomized control trial showed that the warnings with graphic images led to significantly more progress in stage of change toward smoking cessation than written warnings alone. However, the images did not lead to decreases in smoking rates. Conclusions and Scientific Significance : The results indicate that written smoking warnings accompanied by images of cosmetically important harm caused by smoking have more potential than warnings alone in prompting changes in the direction of quitting. (Am J Addict 2012;21:555–557)     

Hepatitis E Virus Genotype 4 Outbreak,Italy, 2011

During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries.