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Although efficacy of ustekinumab (UST) has been demonstrated through randomized trials, data from real-life prospective cohorts are still limited. Our aim was to evaluate clinical efficacy, drug sustainability, dose intensification and results from therapeutic drug monitoring in UST treated patients with Crohn's disease (CD) using a prospective, nationwide, multicenter cohort. Patients from 10 Inflammatory Bowel Disease centers were enrolled between 2019 January and 2020 May. Patient demographics, disease phenotype, treatment history, clinical disease activity (Crohn's Disease Activity Index(CDAI), Harvey Bradshaw Index(HBI)), biomarkers, and serum drug levels were obtained. Evaluations were performed at week8 (post-induction), w16–20, w32–36, and w52–56 follow-up visits. A total of 142 patients were included [57.4% female; complex disease behavior (B2/B3):48%, previous anti-TNF exposition:97%]. Clinical response and remission rates after induction(w8) were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores. The one-year clinical remission rate was 58%/57.3%(CDAI/HBI). Composite clinical and biomarker remission (CDAI<150 and C-reactive protein<10 mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16–20/w32–36 and w52–56. Drug sustainability was 81.9%(standard deviation(SD): 3.4) at 1 year(1y). Probability of dose intensification was high and introduced early, 42.2%(SD:4.2) at ~w32 and 51.9%(SD:4.4%) at 1y. Ustekinumab showed favorable drug sustainability and clinical efficacy in a patient population with severe disease phenotype and previous anti-tumor necrosis factor (anti-TNF) failure, however frequent dose intensification was required. [ABSTRACT FROM AUTHOR]

Malawi has not yet transitioned from the use of wood to more sustainable and efficient means of energy production. This aggravates the already dire problem of deforestation and contributes to severe fuelwood scarcity. The rural sellers of fuelwood, whose livelihoods depend upon access to the commodity, are particularly incentivized to find means of stabilizing their supply. Although agroforestry fuelwood technology (AFT) options such as private and communal woodlots are available for increasing sustainable supplies, Malawians largely have not adopted them. This study investigates the use of agroforestry in general, and AFT in particular, by rural fuelwood sellers in Malawi through analysis of survey results gathered during a large-scale agroforestry extension effort. The findings indicate that fuelwood sellers are 125% and 43% more likely to use AFT than the general population in the North and South regions of the country, respectively. Moreover, binary regression showed that the use of AFT in particular was directly related to the ability to sell fuelwood in the South (i.e., increasing its likelihood by 4.5 times). Based on the findings, the authors propose that for Malawi and similarly situated countries, household composition should be considered in policy and extension recommendations. Communal woodlots may be promoted for the general population in patrilocal areas with high numbers of female-headed households or particularly weak tenure scenarios, while individual woodlots within broader agroforestry prescriptions may be preferred for male-headed households. For both situations, the role of agroforestry in improving environmental conditions and thereby increasing future output levels should be emphasized. • Fuelwood sellers are 125% & 43% more likely to use agroforestry than others in the North & South Malawi • Tenure scenarios, gender, and perceptions of agroforestry fuelwood technology's environmental benefits affect its adoption • Individual woodlots within broader agroforestry prescriptions may be preferred by male-headed households • It may be beneficial to promote communal woodlots to female headed households [ABSTRACT FROM AUTHOR]

Background--The predictive value of fractional flow reserve (FFR) measured immediately after percutaneous coronary intervention (PCI) with drug-eluting stent placement has not been prospectively investigated. We investigated the potential of post-PCI FFR measurements to predict clinical outcome in patients from FAME 1 and 2 trials (Fractional Flow Reserve or Angiography for Multivessel Evaluation). Methods and Results--All patients of FAME 1 and FAME 2 who had post-PCI FFR measurement were included. The primary outcome was vessel-oriented composite end point at 2 years, defined as vessel-related cardiovascular death, vessel-related spontaneous myocardial infarction, and ischemia-driven target vessel revascularization. Eight hundred thirty-eight vessels in 639 patients were analyzed. Baseline FFR values did not differ between vessels with versus without vessel-oriented composite end point (0.66±0.11 versus 0.63±0.14, respectively; P=0.207). Post-PCI FFR was significantly lower in vessels with vessel-oriented composite end point (0.88±0.06 versus 0.90±0.06, respectively; P=0.019). Comparing the 2-year outcome of lower and upper tertiles of post-PCI FFR significant difference was found favoring upper tertile in terms of overall vessel-oriented composite end point (9.2% versus 3.8%, respectively; hazard ratio, 1.46; 95% confidence interval, 1.02-2.08; P=0.037) and target vessel revascularization (7.0% versus 2.4%, respectively; hazard ratio, 1.59; 95% confidence interval, 1.03-2.46; P=0.037). When adjusted to sex, hypertension, diabetes mellitus, target vessel, serial stenosis, and baseline percentage diameter stenosis, a strong trend was preserved in terms of target vessel revascularization (harzard ratio, 1.55; 95% confidence interval, 0.97-2.46; P=0.066), favoring the upper tertile. Post-PCI FFR of 0.92 was found to have the highest diagnostic accuracy; however, the positive likelihood ratio remained low (<1.4). Conclusions--A higher post-PCI FFR value is associated with a better vessel-related outcome. However, its predictive value is too low to advocate its use as a surrogate clinical end point. [ABSTRACT FROM AUTHOR]

Cardiac imaging procedures are a cornerstone of the diagnosis and management of patients with cardiac disease. The optimal management of the patient with stable ischemic heart disease or ischemic heart failure often rests on the totality of symptom burden, patient risk, and disease severity, whether assessed anatomically or functionally. Recent trials have demonstrated the power of flow measurements to direct revascularization as well as the strengths and limitations of ischemia and viability/hibernation imaging as markers of risk to direct interventions. They have also highlighted the challenges in evaluating imaging or functional testing to direct therapies, because imaging does not directly affect outcome itself, rather it affects the management decisions that may result in a positive outcome. Ongoing studies with randomized designs, such as FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation), ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), and AIMI-HF (Alternative Imaging Modalities in Ischemic Heart Failure) (IMAGE-HF [Imaging Modalities to Assist with Guiding Therapy in The Evaluation of Patients with Heart Failure]), will provide the highest level of evidence to support practice changes that may further clarify the role of cardiac imaging in the evaluation of these patients and result in improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background There is no data on the impact of coronary computed tomography angiography (coronary CTA), as an addition to angiography, on the outcomes of percutaneous coronary interventions (PCI) in bifurcation lesions. Methods Patients with stable coronary artery disease scheduled for elective bifurcation PCI were randomized 1:1 to planning the procedure based on coronary CTA and angiography (CTA group) or angiography alone (CA group). The primary efficacy endpoint was the immediate angiographic result. Secondary efficacy endpoints were: a) procedural characteristics and b) postprocedural fractional flow reserve (FFR) in the side branch (SB) in a subgroup of patients. Safety outcomes were: a) periprocedural myocardial infarction, b) contrast use and c) radiation dose. Results PCI of 45 lesions in the CTA group and 47 lesions in the CA group was performed. Postprocedural lumen diameters in the main branch (MB) and SB, frequency of SB compromise or occlusion and mean SB FFR values were not different between study groups. Two or more stents were implanted less frequently in the CTA group than in the CA group (18% vs. 43%, p = 0.01). This difference was driven by less frequent MB 2-stent overlap in the CTA group (7 vs. 21%, p = 0.046) and numerically less SB stenting (11% vs. 21%, p = 0.07). Proximal optimization technique was used more frequently in the CTA group (44% vs. 21%, p = 0.018). Conclusions CTA-assisted bifurcation PCI leads to similar immediate results compared with angiography alone, however is associated with higher use of single-stent procedures with proximal optimization, less frequent 2-stent overlap and less SB stenting. [ABSTRACT FROM AUTHOR]

Objectives This study sought to assess the impact of a wide range of mean right atrial pressure (P ra ) on fractional flow reserve (FFR) measurements. Background FFR invasively assesses the ischemic potential of coronary stenoses. FFR is calculated as the ratio of mean distal coronary pressure (P d ) to mean aortic pressure (P a ) during maximal hyperemia. The P ra is considered to have little impact if it is within normal range, so it is neglected in the formula. Methods In 1,676 stenoses of 1,235 patients undergoing left-right heart catheterization for ischemic (642 [52%]) or valvular heart disease (593 [48%]), the authors compared the FFR values calculated without accounting for P ra (FFR= P d /P a ) to the corresponding myocardial fractional flow reserve (FFR myo ) values accounting for P ra (FFR myo = P d − P ra /P a − P ra ). Results The median P ra was 7 (interquartile range [IQR]: 5 to 10) mm Hg with a maximum of 27 mm Hg. The correlation and agreement between FFR and FFR myo was excellent (R 2 = 0.987; slope 1.096 ± 0.003). The median FFR (0.85; IQR: 0.78 to 0.91) was slightly but statistically significantly higher than the median FFR myo (0.83; IQR: 0.76 to 0.90; p < 0.001) with a median difference of 0.01 (IQR: 0.01 to 0.02). Values of FFR above the cutoff of 0.80 provided an FFR myo ≤0.80 in 110 (9%) stenoses. No FFR value above 0.80 provided an FFR myo ≤0.75. Conclusions The difference between FFR and FFR myo was minimal even in patients with markedly increased P ra . FFR values above the gray zone (i.e., >0.80) did not yield values below the gray zone (i.e., ≤0.75) in any case, which suggests that the impact of right atrial pressure on FFR measurement is indeed negligible. [ABSTRACT FROM AUTHOR]

Objectives The present study sought to establish the dosage of intracoronary (IC) adenosine associated with minimal side effects and above which no further increase in flow can be expected. Background Despite the widespread adoption of IC adenosine in clinical practice, no wide-ranging, dose-response study has been conducted. A recurring debate still exists regarding its optimal dose. Methods In 30 patients, Doppler-derived flow velocity measurements were obtained in 10 right coronary arteries (RCAs) and 20 left coronary arteries (LCAs) free of stenoses >20% in diameter. Flow velocity was measured at baseline and after 8 ml bolus administrations of arterial blood, saline, contrast medium, and 9 escalating doses of adenosine (4 to 500 μg). The hyperemic value was expressed in percent of the maximum flow velocity reached in a given artery (Q/Q max , %). Results Q/Q max did not increase significantly beyond dosages of 60 μg for the RCA and 160 μg for LCA. Heart rate did not change, whereas mean arterial blood pressure decreased by a maximum of 7% (p < 0.05) after bolus injections of IC adenosine. The incidence of transient A-V blocks was 40% after injection of 100 μg in the RCA and was 15% after injection of 200 μg in the LCA. The duration of the plateau reached 12 ± 13 s after injection of 100 μg in the RCA and 21 ± 6 s after the injection of 200 μg in the LCA. A progressive prolongation of the time needed to return to baseline was observed. Hyperemic response after injection of 8 ml of contrast medium reached 65 ± 36% of that achieved after injection of 200 μg of adenosine. Conclusions This wide-ranging, dose-response study indicates that an IC adenosine bolus injection of 100 μg in the RCA and 200 μg in the LCA induces maximum hyperemia while being associated with minimal side effects. [ABSTRACT FROM AUTHOR]

The giant magnetoresistance (GMR) and structure was investigated for electrodeposited Co/Cu multilayers prepared by a conventional galvanostatic/potentiostatic pulse combination from a pure sulfate electrolyte with various layer thicknesses, total multilayer thickness and Cu deposition potential. X-ray diffraction (XRD) measurements revealed superlattice satellite reflections for many of the multilayers having sufficiently large thickness (at least 2 nm) of both constituent layers. The bilayer repeats derived from the positions of the visible superlattice reflections were typically 10 - 20% higher than the nominal values. The observed GMR was found to be dominated by the multilayer-like ferromagnetic (FM) contribution even for multilayers without visible superlattice satellites. There was always also a modest superparamagnetic (SPM) contribution to the GMR and this term was the largest for multilayers with very thin (0.5 nm) magnetic layers containing apparently a small amount of magnetically decoupled SPM regions. No oscillatory GMR behavior with spacer thickness was observed at any magnetic layer thickness. The saturation of the coercivity as measured by the peak position of the MR(H) curves indicated a complete decoupling of magnetic layers for large spacer thicknesses. The GMR increased with total multilayer thickness which could be ascribed to an increasing SPM contribution to the GMR due to an increasing surface roughness, also indicated by the increasing coercivity. For multilayers with Cu layers deposited at more and more positive potentials, the GMRfm term increased and the GMRspm term decreased. At the same time, a corresponding reduction of surface roughness measured with atomic force microscopy indicated an improvement of the multilayer structural quality which was, however, not accompanied by an increase of the superlattice reflection intensities. The present results underline that whereas the structural quality as characterized by the surface roughness generally correlates fairly well with the magnitude of the GMR, the microstructural features determining the amplitude of superlattice reflections apparently do not have a direct influence on the GMR. [ABSTRACT FROM AUTHOR]

Until recently, our understanding of coronary artery disease (CAD) has been largely based on a purely anatomical approach as derived from the invasive angiogram. The confirmation of the diagnosis of “significant” CAD, the assessment of its extent, the risk stratification of patients, the therapeutic decisions, the definition of study end-points, and the validation of non-invasive testing, all mainly relied on “eyeballing” the angiogram, i.e. a subjective evaluation of the presence of at least 50% (or 70%) diameter stenosis.With the development of invasive, wire-based, means to quantify coronary pressure and flow with high spatial resolution, one realized that purely angiographic metrics correlated poorly with functional information. Currently, it is admitted that both anatomical and functional information are needed to define CAD and to optimize its management. In the present review, we summarize the main characteristics of invasive functional indices of ischemia and perfusion. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to develop a new model for assessment of stenosis severity in a bifurcation lesion including its core. The diagnostic performance of this model, powered by 3-dimensional quantitative coronary angiography to predict the functional significance of obstructive bifurcation stenoses, was evaluated using fractional flow reserve (FFR) as the reference standard. Background Development of advanced quantitative models might help to establish a relationship between bifurcation anatomy and FFR. Methods Patients who had undergone coronary angiography and interventions in 5 European cardiology centers were randomly selected and analyzed. Different bifurcation fractal laws, including Murray, Finet, and HK laws, were implemented in the bifurcation model, resulting in different degrees of stenosis severity. Results A total of 78 bifurcation lesions in 73 patients were analyzed. In 51 (65%) bifurcations, FFR was measured in the main vessel. A total of 34 (43.6%) interrogated vessels had an FFR ≤0.80. Correlation between FFR and diameter stenosis was poor by conventional straight analysis (ρ = −0.23, p < 0.001) but significantly improved by bifurcation analyses: the highest by the HK law (ρ = −0.50, p < 0.001), followed by the Finet law (ρ = −0.49, p < 0.001), and the Murray law (ρ = −0.41, p < 0.001). The area under the receiver-operating characteristics curve for predicting FFR ≤0.80 was significantly higher by bifurcation analysis compared with straight analysis: 0.72 (95% confidence interval: 0.61 to 0.82) versus 0.60 (95% confidence interval: 0.49 to 0.71; p = 0.001). Applying a threshold of ≥50% diameter stenosis, as assessed by the bifurcation model, to predict FFR ≤0.80 resulted in 23 true positives, 27 true negatives, 17 false positives, and 11 false negatives. Conclusions The new bifurcation model provides a comprehensive assessment of bifurcation anatomy. Compared with straight analysis, identification of lesions with preserved FFR values in obstructive bifurcation stenoses was improved. Nevertheless, accuracy was limited by using solely anatomical parameters. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The aim of this study was to determine the impact of downstream coronary stenosis in the left anterior descending coronary artery (LAD) or left circumflex coronary artery (LCx) on the assessment of fractional flow reserve (FFR) across an intermediate left main coronary artery (LMCA) stenosis in humans with the pressure wire positioned in the nondiseased downstream vessel. BACKGROUND: Accurate assessment of intermediate LMCA disease is critical for guiding decisions regarding revascularization. In theory, FFR across an intermediate LMCA stenosis will be affected by downstream disease, even if the pressure wire is positioned in the nondiseased downstream vessel. METHODS: After percutaneous coronary intervention of the LAD, LCx, or both, an intermediate LMCA stenosis was created with a deflated balloon catheter. FFR was measured in the LAD and LCx coronary arteries before and after creation of downstream stenosis by inflating an angioplasty balloon within the newly placed stent. The true FFR (FFRtrue) of the LMCA, measured in the nondiseased downstream vessel in the absence of stenosis in the other vessel, was compared with the apparent FFR (FFRapp) measured in the presence of stenosis. RESULTS: In 25 patients, 91 pairs of measurements were made, 71 with LAD stenosis and 20 with LCx stenosis. FFRtrue of the LMCA was significantly lower than FFRapp (0.81 ± 0.08 vs. 0.83 ± 0.08, p < 0.001), although the numerical difference was small. This difference correlated with the severity of the downstream disease (r 0.35, p < 0.001). In all cases in which FFRapp was >0.85, FFRtrue was >0.80. CONCLUSIONS: In most cases, downstream disease does not have a clinically significant impact on the assessment of FFR across an intermediate LMCA stenosis with the pressure wire positioned in the nondiseased vessel. [ABSTRACT FROM AUTHOR]

Fractional flow reserve (FFR) measurement of intermediate coronary stenoses is recommended by guidelines when demonstration of ischemia by noninvasive testing is unavailable. The study aims to evaluate the penetration of this recommendation into current thinking about revascularization strategies for stable coronary artery disease.International Survey on Interventional Strategy was conducted via a web-based platform. First, participants’ experiences in interventional cardiology were queried. Second, 5 complete angiograms were provided, presenting only focal intermediate stenoses. FFR and quantitative coronary angiography values were known; however, remained undisclosed. Determination of stenosis significance was asked for each lesion. In cases of uncertainty, the most appropriate adjunctive invasive diagnostic method among quantitative coronary angiography, intravascular ultrasound, optical coherence tomography, or FFR needed to be selected. International Survey on Interventional Strategy was taken by 495 participants who provided 4421 lesion evaluations. In 3158 (71%) decisions, participants relied solely on angiographic appearance that was discordant in 47% with the known FFR, using 0.80 as cutoff value. The use of FFR and imaging modalities was requested in 21% and 8%, respectively. Comparing 4 groups of participants according to the experience in FFR, angiogram-based decisions were less frequent with increasing experience (77% versus 72% versus 69% versus 67%, respectively; P<0.001). As a result, requests for FFR were more frequent (14% versus 19% versus 24% versus 28%, respectively; P<0.001) and rates of discordant decisions decreased (51% versus 49% versus 47% versus 43%, respectively; P<0.022).The findings confirm that, even when all potential external constraints are virtually eliminated, visual estimation continues to dominate the treatment decisions for intermediate stenoses, indicative of a worrisome disconnect between recommendations and current practice. [ABSTRACT FROM AUTHOR]

The article discusses the budgetary developments adjusted to election cycles between 1997 and 2006 and its role on the balanced progress of the economic growth in Hungary. It is stated that the pace of the economic growth is influenced by the increases in spending in relation to the individual election years with different size and structure. It notes that exports drag down the gross domestic product (GDP) growth in 1998 while being boosted by an increase in state-funded investment.

Supplemental Digital Content is available in the text. Background—: Fractional flow reserve (FFR)-guided coronary artery bypass graft (CABG) surgery has been associated with lower number of graft anastomoses, lower rate of on-pump surgery, and higher graft patency rate as compared with angiography-guided CABG surgery. However, no clinical benefit has been reported to date. Methods and Results—: Consecutive patients (n=627) treated by CABG between 2006 and 2010 were retrospectively included. In 198 patients, at least 1 stenosis was grafted according to FFR (FFR-guided group), whereas in 429 patients all stenoses were grafted based on angiography (angiography-guided group). The 2 coprimary end points were overall death or myocardial infarction and major adverse cardiovascular events (composite of overall death, myocardial infarction, and target vessel revascularization) up to 6-year follow-up. In the FFR-guided group, patients were significantly younger (66 [57–73] versus 70 [63–76]; P<0.001), more often male (82% versus 72%; P=0.008), and less often diabetic (21% versus 30%; P=0.023). Clinical follow-up (median, 85 [66–104] months) was analyzed in 396 patients after 1:1 propensity-score matching for these 3 variables. The rate of overall death or myocardial infarction was significantly lower in the FFR-guided (n=31 [16%] versus n=49 [25%]; hazard ratio, 0.59 [95% confidence interval, 0.38–0.93]; P=0.020) as compared with the angiography-guided group. Major adverse cardiovascular events rate was also numerically lower in the FFR-guided than in the angiography-guided group (n=42 [21%] versus n=52 [26%]; hazard ratio, 0.77 [95% confidence interval, 0.51–1.16]; P=0.21). Conclusions—: FFR-guided CABG is associated with a significant reduction in the rate of overall death or myocardial infarction at 6-year follow-up as compared with angiography-guided CABG. [ABSTRACT FROM AUTHOR]