Correlation Between NT-proBNP Values and Changes in Functional Capacity in Patients with Chronic Heart Failure

OBJECTIVE: We set out to evaluate whether changes in N-terminal pro-brain natriuretic peptide (proBNP) can predict changes in functional capacity, as determined by cardiopulmonary exercise testing (CPET), in patients with chronic heart failure (CHF) due to dilated cardiomyopathy (DCM). METHODS: We studied 37 patients with CHF due to DCM, 81% non-ischemic, 28 male, who performed symptom-limited treadmill CPET, with the modified Bruce protocol, in two consecutive evaluations, with determination of proBNP after 10 minutes rest prior to CPET. The time between evaluations was 9.6+/-5.5 months, and age at first evaluation was 41.1+/-13.9 years (21 to 67). RESULTS IN THE FIRST AND SECOND EVALUATIONS RESPECTIVELY WERE: NYHA functional class >II 51% and 16% (p<0.001), sinus rhythm 89% and 86.5% (NS), left ventricular ejection fraction 24.9+/-8.9% and 26.6+/-8.6% (NS), creatinine 1.03+/-0.25 and 1.09+/-0.42 mg/dl (NS), taking ACE inhibitors or ARBs 94.5% and 100% (NS), beta-blockers 73% and 97.3% (p<0.001), and spironolactone 89% and 89% (NS). We analyzed the absolute and percentage variation (AV and PV) in peak oxygen uptake (pVO2--ml/kg/min) and proBNP (pg/ml) between the two evaluations. RESULTS: (1) pVO2 AV: -17.4 to 15.2 (1.9+/-5.7); pVO2 PV: -56.1 to 84% (11.0+/-25.2); proBNP AV: -12850 to 5983 (-778.4+/-3332.5); proBNP PV: -99.0 to 379.5% (-8.8+/-86.3); (2) The correlations obtained--r value and p value [r (p)]--are shown in the table below; (3) We considered that a coefficient of variation of pVO2 PV of >10% represented a significant change in functional capacity. On ROC curve analysis, a proBNP PV value of 28% showed 80% sensitivity and 79% specificity for pVO2 PV of >10% (AUC=0.876, p=0.01, 95% CI 0.75 to 0.99). CONCLUSIONS: In patients with CHF due to DCM, changes in proBNP values correlate with variations in pVO2, as assessed by CPET. However, our results suggest that only a proBNP PV of >28% predicts a significant change in functional capacity

Evidence-based practice educational intervention studies: A systematic review of what is taught and how it is measured

Abstract Background Despite the established interest in evidence-based practice (EBP) as a core competence for clinicians, evidence for how best to teach and evaluate EBP remains weak. We sought to systematically assess coverage of the five EBP steps, review the outcome domains measured, and assess the properties of the instruments used in studies evaluating EBP educational interventions. Methods We conducted a systematic review of controlled studies (i.e. studies with a separate control group) which had investigated the effect of EBP educational interventions. We used citation analysis technique and tracked the forward and backward citations of the index articles (i.e. the systematic reviews and primary studies included in an overview of the effect of EBP teaching) using Web of Science until May 2017. We extracted information on intervention content (grouped into the five EBP steps), and the outcome domains assessed. We also searched the literature for published reliability and validity data of the EBP instruments used. Results Of 1831 records identified, 302 full-text articles were screened, and 85 included. Of these, 46 (54%) studies were randomised trials, 51 (60%) included postgraduate level participants, and 63 (75%) taught medical professionals. EBP Step 3 (critical appraisal) was the most frequently taught step (63 studies; 74%). Only 10 (12%) of the studies taught content which addressed all five EBP steps. Of the 85 studies, 52 (61%) evaluated EBP skills, 39 (46%) knowledge, 35 (41%) attitudes, 19 (22%) behaviours, 15 (18%) self-efficacy, and 7 (8%) measured reactions to EBP teaching delivery. Of the 24 instruments used in the included studies, 6 were high-quality (achieved ≥3 types of established validity evidence) and these were used in 14 (29%) of the 52 studies that measured EBP skills; 14 (41%) of the 39 studies that measured EBP knowledge; and 8 (26%) of the 35 studies that measured EBP attitude. Conclusions Most EBP educational interventions which have been evaluated in controlled studies focus on teaching only some of the EBP steps (predominantly critically appraisal of evidence) and did not use high-quality instruments to measure outcomes. Educational packages and instruments which address all EBP steps are needed to improve EBP teaching

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Benefits of Cardiac Resynchronization Therapy in "Very Dilated Cardiomyopathy"

INTRODUCTION: Recent clinical trials have studied parameters that could predict response to cardiac resynchronization therapy (CRT) in patients with advanced heart failure. Left ventricular end-diastolic dimension (LVEDD) is regarded as a possible predictor of response to CRT. OBJECTIVE: To study the response to CRT in patients with very dilated cardiomyopathy, i.e. those at a more advanced stage of the pathology, analyzing both the responder rate and reverse remodeling in two groups of patients classified according to LVEDD. METHODS: We performed a retrospective analysis of 71 patients who underwent CRT (aged 62 +/- 11 years; 65% male; 93% in NYHA functional class > or = III; 31% with ischemic cardiomyopathy; left ventricular ejection fraction [LVEF] 25.6 +/- 6.8%; 32% in atrial fibrillation; QRS 176 +/- 31 ms). Twenty-two (31%) patients with LVEDD > or = 45 mm/m2 (49.2 +/- 3.5 mm/m2) were considered to have very dilated cardiomyopathy (Group A) and 49 patients had LVEDD > 37 mm/m2 and or = 1 NYHA class) and by echocardiography, with a minimum 15% increase over baseline LVEF combined with a reduction in LVEDD (reverse remodeling). RESULTS: There were no significant differences in baseline demographic characteristics between the two groups. At six-month followup, we observed an improvement in LVEF (delta 8.5 +/- 11.8%) and a reduction in LVEDD (delta 3.7 +/- 6.8 mm/m2), with fifty-seven (79%) patients being classified as clinical responders. The percentage of patients with reverse remodeling was similar in both groups (64% vs. 73%, p = NS), as were percentages of improved LVEF (delta 6.3 +/- 11% vs. delta 9.6 +/- 12%; p = NS) and decreased LVEDD (delta 3.7 +/- 5.5 mm/m2 vs. delta 3.7 +/- 7.4 mm/m2; p = NS). We found a higher percentage of clinical responders in patients with very dilated cardiomyopathy (96% vs. 72%, p < 0.05). CONCLUSION: In this study, a significant number of responders showed reverse remodeling after CRT. Although a higher percentage of patients with very dilated cardiomyopathy showed improvement in functional class, the extent of reverse remodeling was similar in both groups

Bilateral Spontaneous Chylothorax After Severe Vomiting In Children

Objective To report the case of a child with bilateral chylothorax due to infrequent etiology: thoracic duct injury after severe vomiting. Case description Girl, 7 years old, with chronic facial swelling started after hyperemesis. During examination, she also presented with bilateral pleural effusion, with chylous fluid obtained during thoracentesis. After extensive clinical, laboratory, and radiological investigation of the chylothorax etiology, it was found to be secondary to thoracic duct injury by the increased intrathoracic pressure caused by the initial manifestation of vomiting, supported by lymphoscintigraphy findings. Comments Except for the neonatal period, chylothorax is an infrequent finding of pleural effusion in children. There are various causes, including trauma, malignancy, infection, and inflammatory diseases; however, the etiology described in this study is poorly reported in the literature. © 201634451852

Identification of candidate pelagic marine protected areas through a seabird seasonal-, multispecific- and extinction risk-based approach

With increasing pressure on the oceans from environmental change, there has been a global call for improved protection of marine ecosystems through the implementation of marine protected areas (MPAs). Here, we used species distribution modelling (SDM) of tracking data from 14 seabird species to identify key marine areas in the southwest Atlantic Ocean, valuing areas based on seabird species occurrence, seasonality and extinction risk. We also compared overlaps between the outputs generated by the SDM and layers representing important human threats (fishing intensity, ship density, plastic and oil pollution, ocean acidification), and calculated loss in conservation value using fishing and ship density as cost layers. The key marine areas were located on the southern Patagonian Shelf, overlapping extensively with areas of high fishing activity, and did not change seasonally, while seasonal areas were located off south and southeast Brazil and overlapped with areas of high plastic pollution and ocean acidification. Non-seasonal key areas were located off northeast Brazil on an area of high biodiversity, and with relatively low human impacts. We found support for the use of seasonal areas depending on the seabird assemblage used, because there was a loss in conservation value for the seasonal compared to the non-seasonal approach when using ‘cost’ layers. Our approach, accounting for seasonal changes in seabird assemblages and their risk of extinction, identified additional candidate areas for incorporation in the network of pelagic MPAs

Non-specific binding of antibodies in immunohistochemistry: fallacies and facts

The current protocols for blocking background staining in immunohistochemistry are based on conflicting reports. Background staining is thought to occur as a result of either non-specific antibody (Ab) binding to endogenous Fc receptors (FcRs) or a combination of ionic and hydrophobic interactions. In this study, cell and tissue samples were processed according to routine protocols either with or without a blocking step (goat serum or BSA). Surprisingly, no Abs in samples processed without a blocking step showed any propensity for non-specific binding leading to background staining, implying that endogenous FcRs do not retain their ability to bind the Fc portion of Abs after standard fixation. Likewise, we did not find any non-specific Ab binding ascribable to either ionic or hydrophobic interactions. We determined that traditionally used protein blocking steps are unnecessary in the immunostaining of routinely fixed cell and tissue samples