Interrelationship between noninvasive predictors of atherosclerosis: transthoracic coronary flow reserve, flow-mediated dilation, carotid intima-media thickness, aortic stiffness, aortic distensibility, elastic modulus, and brachial artery diameter

BACKGROUND: In this study, we searched for a correlation between transthoracic coronary flow reserve (CFR) and well-established surrogates of coronary atherosclerosis. METHODS: The study was conducted on 136 healthy subjects (mean age: 39.9 +/- 7.3 years) who were free of coronary risk factors. Transthoracic echocardiography was used to measure the aortic stiffness index (AoSI), aortic distensibility (AoD), and aortic elastic modulus (AoEM). High-resolution ultrasound was used to measure brachial artery endothelium-dependent and independent vasomotion and carotid intima-media thickness (IMT). In addition, transthoracic second harmonic Doppler echocardiography was used to measure CFR. RESULTS: All of the parameters significantly correlated with each other except brachial endothelium-independent dilation. CFR correlated significantly with brachial endothelium-dependent dilation (EDD) (r = 0.302, P < 0.01), carotid IMT (r =-0.388, P < 0.01), brachial artery diameter (r = 0.340, P < 0.01), AoD (r = 0.275, P < 0.01), AoS (r =-0.299, P < 0.01), and AoEM (r =-0.30,7 P < 0.01). Carotid IMT correlated significantly with brachial EDD and modestly with brachial artery diameter, AoD, AoS, and AoEM.In multivariate analysis, carotid IMT (beta=-0.323, P < 0.0001) and brachial artery diameter (beta = -0.259, P = 0.001) were significant independent predictors of CFR. The left ventricular mass index (beta= 0.371, P < 0.0001), brachial EDD (beta = -0.232, P = 0.002), and CFR (beta = -0.228, P = 0.003) were significant predictors for IMT. CONCLUSION: Transthoracic CFR correlated significantly with well-established noninvasive predictors of atherosclerosis, and we suggest that it can be used as a surrogate for coronary atherosclerosis.     

Resistance of primary murine CD4+ T cells to Helicobacter pylori vacuolating cytotoxin

Persistent colonization of the human stomach by Helicobacter pylori is a risk factor for the development of gastric cancer and peptic ulcer disease. H. pylori secretes a toxin, VacA, that targets human gastric epithelial cells and T lymphocytes and enhances the ability of H. pylori to colonize the stomach in a mouse model. To examine how VacA contributes to H. pylori colonization of the mouse stomach, we investigated whether murine T lymphocytes were susceptible to VacA activity. VacA inhibited interleukin-2 (IL-2) production by a murine T-cell line (LBRM-33), similar to its effects on a human T-cell line (Jurkat), but did not inhibit IL-2 production by primary murine splenocytes or CD4+ T cells. VacA inhibited activation-induced proliferation of primary human CD4+ T cells but did not inhibit the proliferation of primary murine CD4+ T cells. Flow cytometry studies indicated that the levels of VacA binding to primary murine CD4+ T cells were significantly lower than levels of VacA binding to human CD4+ T cells. This suggests that the resistance of primary murine CD4+ T cells to VacA is attributable, at least in part, to impaired VacA binding to these cells.     

International validation of the prognostic value of lymphovascular invasion in patients treated with radical cystectomy

Study Type – Prognosis (retrospective cohort)
Level of Evidence 2b

OBJECTIVE

To externally validate the prognostic value of lymphovascular invasion (LVI) in a large international cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).

PATIENTS AND METHODS

We collected data from 4257 patients treated with RC and pelvic lymphadenectomy for UCB, without neoadjuvant chemotherapy, at 12 centres. LVI was defined as presence of nests of tumour cells within an endothelium‐lined space.

RESULTS

LVI was detected in 1407 patients (33.1%); the proportion of LVI increased with advancing stage, higher grade, soft‐tissue surgical margin involvement, and lymph node metastasis (P < 0.001 for all). In standard multivariate models, LVI was associated with both disease recurrence (hazard ratio 1.43, P < 0.001) and cancer‐specific mortality (1.45, P < 0.001). In the entire cohort, adding LVI to a base model that included standard features improved only minimally its predictive accuracy for both recurrence and cancer‐specific mortality (by 1.1% and 1.2%, respectively). In 3122 patients with negative lymph nodes, LVI remained independently associated with and improved the predictive accuracy of the standard predictors for recurrence (hazard ratio 1.68, P < 0.001; +2.3%) and cancer‐specific mortality (1.70, P < 0.001; +2.4%). By contrast, in 1071 node‐positive patients, LVI only marginally improved the prediction of cancer‐specific recurrence (hazard ratio 1.20, P < 0.001; +0.2%) and survival (1.23, P < 0.001; +0.5%).

CONCLUSIONS

LVI is strongly associated with clinical outcome in node‐negative patients treated with RC. The assessment of LVI might help to identify patients who could benefit from adjuvant therapy after RC. After confirmation in different populations, LVI should be included in the staging of UCB.     

The Effects of Desflurane on Human Platelet Aggregation In Vitro

In view of the possible antiplatelet effects of general anesthetics, we investigated the in vitro effects of desflurane, a new inhalation agent, on platelet aggregation. For 15 patients who underwent elective operations, blood was sampled with desflurane induction before and after anesthesia but prior to surgery so that platelet aggregation in the drawn blood could be tested before desflurane anesthesia and again after exposure to the anesthetic. Platelet aggregation was measured with a whole-blood aggregometer. Adenosine diphosphate (ADP), collagen, and ristocetin were used as aggregating agents. Our results showed that aggregation in response to ADP, collagen, or ristocetin was not inhibited in patients who received desflurane anesthesia. This study with an in vitro model showed that desflurane had no influence on platelets in clinically relevant doses.     

Serum M65 as a Biomarker for Metastatic Renal Cell Carcinoma

Introduction/BackgroundEffective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently need in metastatic RCC. M30 and M65 are released during apoptotic cell death and precisely reflect epithelial tumor cell death. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates for patients with metastatic RCC.Patients and MethodsThirty-nine patients with metastatic RCC and 39 healthy control subjects were included in this study. Serum M30 and M65 levels were measured by ELISA.ResultsThe median ages of the patients and control subjects were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and control subjects (53.7 vs. 49.1 U/L; P = .31). The median serum M65 level was significantly higher in patients than in control subjects (334.0 vs. 179.1 U/L; P < .001). Receiver operating characteristic analysis revealed that the best cutoff value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/L. The median PFS of patients whose M65 levels were ≤ 313.6 U/L was better than that of patients whose M65 levels were > 313.6 U/L (P = .03).ConclusionTo the best of our knowledge, this is the first study to evaluate serum M30 and M65 levels in patients with RCC. Serum M65 levels were significantly elevated in patients with metastatic RCC compared with healthy individuals. In addition, the serum M65 level could be predictive of PFS in patients with RCC.     

Migraine as a risk factor for young patients with ischemic stroke: a case–control study

Neurological Sciences - Studies have suggested a possible association of migraine and increased risk of ischemic stroke in young adults, particularly in smokers and in women who use oral...