Significantly elevated Helicobacter pylori density and different genotype distribution in erosions as compared with normal gastric biopsy specimen detected by quantitative real-time PCR

BACKGROUND AND AIM: Determination of the local densities of Helicobacter pylori and its genotypic variations in gastric biopsy specimens by using novel real-time PCR-based methods could support the precise diagnosis and understanding of H. pylori infections. METHODS: Serial dilutions of H. pylori (0.016-16 microg/microl), control, bacterial, and human DNA samples were prepared. Fresh-frozen gastric biopsy specimens were taken from 103 patients, and the DNA was isolated. Quantitative determination of the ureaseA gene using hybridization probes with parallel evaluation of an internal human control gene (beta-globin) was performed by real-time PCR. CagA and VacA s1 genotypic characterizations were also performed. The data were compared with urea breath test (UBT), histology, and serological testing. RESULTS: The presence of H. pylori could be detected by ureaseA-fluorescence energy transfer (53%), UBT (51%), serological testing (48%), and histology (52%) when compared with the gold standard (54%). A significant correlation was found between the quantitative real-time ureaseA/beta-globin ratio-based H. pylori frequency and the UBT results (P<0.01). Significantly increased bacterial density was found in the erosions when compared with the healthy part of the antrum and corpus (P<0.01). Real-time PCR VacA s1 results were in significant correlation (P<0.01) with those of serological tests, but CagA results were not. The genomic profiles (VAC/GAC) were different in 13.7% of the cases, which involved three different locations in the stomach. CONCLUSION: Real-time PCR was the most reliable method for H. pylori diagnosis. Furthermore, quantification and genotyping could also be performed using this technique. The density of H. pylori was significantly increased in macroscopic erosions.     

Heart rate variability before the onset of ventricular tachycardia: differences between slow and fast arrhythmias

BACKGROUND: We tested whether or not heart rate variability (HRV) changes can serve as early signs of ventricular tachycardia (VT) and predict slow and fast VT in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: We studied the ICD stored 1000 beat-to-beat intervals before the onset of VT (131 episodes) and during a control time without VT (74 series) in 63 chronic heart failure ICD patients. Standard HRV parameters as well as two nonlinear parameters, namely 'Polvar10' from symbolic dynamics and the finite time growth rates 'Fitgra9' were calculated. Comparing the control and the VT series, no linear HRV parameter showed a significant difference. The nonlinear parameters detected a significant increase in short phases with low variability before the onset of VT (for time series with less than 10% ectopy, P<0.05). Subdividing VT into fast (cycle length 270 ms) events, we found that the onset of slow VT was characterized by a significant increase in heart rate, whereas fast VT was triggered during decreased heart rates, compared to the control series. CONCLUSIONS: Our data may permit the development of automatic ICD algorithms based on nonlinear dynamic HRV parameters to predict VT before it starts. Furthermore, they may facilitate improved prevention strategies.     

Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.     

Correlates of the shift in heart rate variability with an active postural change in a healthy population sample: The Atherosclerosis Risk In Communities study

Background The heart rate variability (HRV) response to postural change is a sensitive measure of the shift in autonomic balance from parasympathetic to sympathetic predominance that, when attenuated or absent, has been correlated with prevalent disease in patient populations. In a healthy population sample, we evaluated whether the shift in HRV with postural change differed by demographic characteristics as well as whether it differed between participants with established coronary heart disease (CHD) risk factors and their counterparts. Methods HRV was measured for 2 minutes in the supine and standing positions in a biracial sample of men and women (aged 45-64 years) without clinical CHD from the Atherosclerosis Risk In Communities Study (n = 7686). Mean differences among supine and standing mean R-R interval lengths, the SD of R-R intervals, and high-frequency power (HF) were compared by demographic characteristics (age, race, and sex) and CHD risk factors (smoking, obesity, physical activity, hypertension, and diabetes). Multivariable linear regression models were used to adjust for demographic characteristics. Results Smaller changes in R-R intervals and larger changes in SD of R-R intervals with standing were found among participants who were obese, less physically active than their counterparts, hypertensive, and diabetic. Smaller changes in HF were identified in male and white participants, but there were no differences in HF by CHD risk factors once models were adjusted for demographic characteristics. Conclusions These simple noninvasive measures can be used to detect differences in cardiac autonomic balance that may be markers for autonomic impairment in healthy adults. (Am Heart J 2002;143:808-13.)     

Prognostic value of aerobic capacity and exercise oxygen pulse in postaortic dissection patients

BackgroundAlthough recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient''s physical rehabilitation and assess their cardiovascular prognosis.DesignWe aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed‐up after acute aortic dissection.MethodsPatients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow‐up was done after CPET for new aortic event and major cardio‐vascular events (MCE) not directly related to the aorta.ResultsAmong the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22‐1.84) mlO2/beat, that is, 97 (83–113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow‐up of 39(20‐51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (<85% of predicted value) was independently predictive of aortic event recurrence, while low peak oxygen uptake (<70% of predicted value) was an independent predictor of MCE occurrence.ConclusionCPET is safe in postaortic dissection patients should be used to not only to personalize exercise rehabilitation, but also to identify those patients with the highest risk for new aortic events and MCE not directly related to aorta.     

Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data

Background: We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients.

Methods: We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model.

Results: A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% – 9.4) and 16.4% (95% CI 16.19% – 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 – 75), 71 (66 – 80+), 74.5 (65 – 89), 75 (66 – 81+) and 79.5 (60 – 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 – 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 – 1.87, p < 0.00001).

Conclusion: Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.     

Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation

We made the hypothesis that donor and recipient gene polymorphisms that drive the host response to microorganisms could be associated with infections after bone marrow transplantation (BMT). HLA-identical BMT was performed for patients with acute (n = 39) or chronic leukemia (n = 68). Genotyping was performed in 107 D/R DNA pairs for gene polymorphisms of cytokines (tumor necrosis factor-alpha [TNF-alpha] and TNF-beta, interleukin-1 receptor antagonist [IL-1Ra], IL-6, and IL-10), adhesion molecules (CD31 and CD54), Fcgammareceptors (FcgammaRIIa, IIIa, IIIb), mannose-binding lectin (MBL), and myeloperoxidase (MPO). First infection (overall) and first episodes of bacterial, viral, or invasive fungal infection were studied retrospectively for 180 days after BMT. Univariate and multivariate analyses, using death as a competing event, were performed to study risk factors. In multivariate analysis, first overall infections were increased in patients with the FcgammaRIIa R-131 genotype (hazard ratio [HR] = 1.92; P =.04), and severe bacterial infections were increased when the MPO donor genotype was AG or AA (HR = 2.16; P =.03). Viral and invasive fungal infections were not influenced by any genetic factor studied. Interestingly, we also found that (1) time to neutrophil recovery was shorter when donors were FcgammaRIIIb HNA-1a/HNA-1b (HR = 1.77; P =.002); (2) donor IL-1Ra (absence of IL-1RN*2) increased the risk for acute graft-versus-host disease (GVHD) (II-IV) (HR = 2.17; P =.017); and (3) recipient IL-10 (GG) and IL-1Ra genotypes increased the risk for chronic GVHD (P =.03 and P =.03, respectively). Finally, 180-day transplantation-related mortality rates were increased when donors were FcgammaRIIIb HNA-1a/HNA-1a or HNA-1b/HNA-1b (HR = 2.57; P =.05) and donor MPO genotype was AA (HR = 5.14; P =.004). In conclusion, donor and recipient gene polymorphisms are informative genetic risk factors for selecting donor/recipient pairs and could help in the understanding of mechanisms involved in host defenses of BM transplant recipients.