Usefulness of B-type natriuretic peptide levels to predict left ventricular filling pressures in patients with body mass index >35, 31 to 35, and < or =30 kg/m2

Noninvasive left ventricular (LV) pressure estimation in obese patients has not been well described. Simultaneous B-type natriuretic peptide (BNP) and echocardiographic Doppler examinations were performed in patients with dyspnea undergoing cardiac catheterization. Patients were divided into body mass index (BMI) >35 (markedly obese), 31 to 35 (obese), and < or =30 kg/m2 (nonobese). BNP levels and mitral early diastolic/tissue Doppler annular velocity (E/Ea) were compared with invasively measured LV end-diastolic and pre-atrial (pre-A) pressures. Seventy-two patients were studied. Except for BMI, LV mass index, and LV diastolic dimension, there were no significant differences in baseline, echocardiographic Doppler, or hemodynamic characteristics among the groups. However, BNP was significantly lower in markedly obese compared with obese and nonobese patients (116 +/- 187 vs 241 +/- 674 and 277 +/- 352 pg/ml, respectively; p = 0.03). BNP did not correlate with LV pre-A pressure in markedly obese patients (R = 0.13, p = 0.47), whereas BNP significantly correlated with this variable in the obese (R = 0.64) and nonobese (R = 0.58) groups. Mitral E/Ea significantly correlated with LV pre-A and LV end-diastolic pressures in all BMI groups. In markedly obese patients with dyspnea, BNP did not correlate with invasively measured LV filling pressure, whereas this correlated in obese and nonobese patients. However, mitral E/Ea significantly correlated with LV filling pressures in all BMI groups. In conclusion, BNP is not recommended for LV filling pressure estimation in ambulatory patients with dyspnea with BMI >35 kg/m2.     

A Systematic Review of Randomized Controlled Trials on the Effectiveness of Computer-Tailored Physical Activity and Dietary Behavior Promotion Programs: an Update

Background

A review update is necessary to document evidence regarding the effectiveness of computer-tailored physical activity and nutrition education.

Purpose

The purpose of this study was to summarize the latest evidence on the effectiveness of computer-tailored physical activity and nutrition education, and to compare the results to the 2006 review.

Methods

Databases were searched for randomized controlled trials evaluating computer-tailored physical activity and nutrition education aimed at primary prevention in adults, published from September 2004 through June 2011.

Results

Compared to the findings in 2006, a larger proportion of studies found positive effects for computer-tailored programs compared to generic or no information, including those for physical activity promotion. Effect sizes were small and generally at short- or medium-term follow-up.

Conclusions

The results of the 2006 review were confirmed and reinforced. Future interventions should focus on establishing larger effect sizes and sustained effects and include more generic health education control groups and objective measurements of dietary behavior.     

The innate immune system in transplantation

The vertebrate innate immune system consists of inflammatory cells and soluble mediators that comprise the first line of defense against microbial infection and, importantly, trigger antigen-specific T and B cell responses that lead to lasting immunity. The molecular mechanisms responsible for microbial non-self recognition by the innate immune system have been elucidated for a large number of pathogens. How the innate immune system recognizes non-microbial non-self, such as organ transplants, is less clear. In this review, we approach this question by describing the principal mechanisms of non-self, or ‘damaged’ self, recognition by the innate immune system (pattern recognition receptors, the missing self theory, and the danger hypothesis) and discussing whether and how these mechanisms apply to allograft rejection.     

Embryonic chimerism does not induce tolerance in an invertebrate model organism

In colonial marine invertebrates, allorecognition restricts somatic fusion and thus, chimerism, to histocompatible individuals. Little is understood, however, about how invertebrates respond to chimerism formed across histocompatibility barriers or whether embryonic exposure to histoincompatible cells induces allotolerance. We here evaded natural allorecognition barriers by generating well mixed embryonic chimeras of Hydractinia symbiolongicarpus (Cnidaria:Hydrozoa) and developed molecular markers to detect chimerism in both histocompatible and histoincompatible settings. Histocompatible chimeras exhibited markedly higher growth rates and survivorship than histoincompatible pairings. Histoincompatible chimeras were unstable, with chimerism being undetectable by 4 wk of age. In contrast, colonies generated from histocompatible pairings remained chimeric at markedly higher frequencies and longer durations. Histoincompatible chimeras that lost detectable chimerism retained the fusibility/rejection characteristics of the remaining component of the chimera but not that of the lost component. Chimerism across histocompatibility barriers in an invertebrate model organism was unstable and did not induce tolerance.     

Free fatty acids,glucose, and insulin in type 2 diabetes mellitus

Xu et al used the HOMA2 model to estimate the β-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels. This method is based on the assumption that the glucose-insulin axis is central for the metabolic activities, which led to type 2 diabetes. However, significant downregulation of both the NKX2-1 gene and the TPD52L3 gene force an increase in the release of free fatty acids (FFAs) into the blood circulation, which leads to a marked reduction in membrane flexibility. These data favor a FFA-glucose-insulin axis. The authors are invited to extend their study with the introduction of the saturation index (number of carbon-carbon double bonds per 100 fatty-acyl chains), as observed in erythrocytes.     

Precision estimates of relative and absolute cerebral blood flow in Alzheimer’s disease and cognitively normal individuals

Alzheimer’s disease is characterized by regional reductions in cerebral blood flow (CBF). Although the gold standard for measuring CBF is [¹⁵O]H₂O PET, proxies of relative CBF, derived from the early distribution phase of amyloid and tau tracers, have gained attention. The present study assessed precision of [¹⁵O]H₂O derived relative and absolute CBF, and compared precision of these measures with that of (relative) CBF proxies. Dynamic [¹⁵O]H₂O, [¹⁸F]florbetapir and [¹⁸F]flortaucipir PET test-retest (TrT) datasets with eleven, nine and fourteen subjects, respectively, were included. Analyses were performed using an arterial input model and/or a simplified reference tissue model, depending on the data available. Relative CBF values (i.e. K₁/K₁′ and/or R₁) were obtained using cerebellar cortex as reference tissue and TrT repeatability (i.e. precision) was calculated and compared between tracers, parameters and clinical groups. Relative CBF had significantly better TrT repeatability than absolute CBF derived from [¹⁵O]H₂O (r = −0.53), while best TrT repeatability was observed for [¹⁸F]florbetapir and [¹⁸F]flortaucipir R₁ (r = −0.23, r = −0.33). Furthermore, only R₁ showed, better TrT repeatability for cognitively normal individuals. High precision of CBF proxies could be due to a compensatory effect of the extraction fraction, although changes in extraction fraction could also bias these proxies, but not the gold standard.     

Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer

Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next-generation sequencing (NGS). Circulating cell-free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre-treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre-treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre-treatment ctDNA detection had a sensitivity of 47% (95% CI 24–71) (8/17), specificity of 85% (95% CI 42–99) (6/7), positive predictive value (PPV) of 89% (95% CI 51–99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17–67) (6/15) for detecting major residual disease (>10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post-nCRT ctDNA detection had a sensitivity of 21% (95% CI 6–51) (3/14), specificity of 100% (95% CI 56–100) (7/7), PPV of 100% (95% CI 31–100) (3/3), and NPV of 39% (95% CI 18–64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre-treatment and post-nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.