Left bundle branch block causes relative but not absolute septal underperfusion during exercise

Aims Left bundle branch block (LBBB) often causes septal perfusion defects in radionuclide myocardial perfusion imaging using exercise (Ex) but rarely using vasodilator stress. We studied whether this is due to an underlying structural disease inherent to spontaneous LBBB or whether it is also found in temporary LBBB induced by right ventricular pacing (PM) indicating a functional rather than a structural alteration. Methods and results Regional myocardial blood flow (MBF) at rest and at Ex was measured with(15)O-H(2)O and PET in 10 age-matched healthy volunteers (controls), 10 LBBB patients and 10 PM patients with right ventricular pacing off and on (PM off and PM on). Although at Ex septal MBF tended to be higher in LBBB than in controls (3.04 +/- 1.18 vs. 2.27 +/- 0.72 mL/min/g; P= ns), the ratio septal/lateral MBF was 19% lower in LBBB than in controls (P < 0.05). Similarly, switching PM on at Ex decreased the ratio septal/lateral MBF by 17% (P < 0.005). Conclusion The apparent septal perfusion defect in LBBB is mainly due to a relative lateral hyperperfusion rather than to an absolute septal flow decrease. This pattern seems to be reversibly inducible by right ventricular pacing, suggesting a functional rather than a structural alteratio

Why do you drink caffeine? The development of the Motives for Caffeine Consumption Questionnaire (MCCQ) and its relationship with gender, age and the types of caffeinated beverages

Caffeine is the most popular psychoactive substance that is consumed worldwide. As motives influence behavior, investigation of the motivational background of caffeine consumption should help provide a better understanding of the popularity of caffeinated products. The present study aimed (i) to explore and operationalize the motives of caffeine consumption and (ii) to reveal possible differences in the motives regarding gender, age and the type of caffeinated products consumed. Motives for caffeine consumption were collected from regular caffeine consumers (N = 26) and were informed by a review of the relevant literature. Following this, a cross-sectional study was conducted on a convenience sample of Hungarian university students and working adults (N = 598). The participants completed the Motives for Caffeine Consumption Questionnaire and the Caffeine Consumption Questionnaire. Six motivational factors were identified: Alertness, Habit, Mood, Social, Taste and Symptom Management. Women had higher scores on Habit, Social, Taste and Symptom Management. Younger participants had higher scores on Alertness than the older group, and the older group had higher scores on Habit and Symptom Management. Five types of caffeine users were identified. Those who consumed (i) coffee, (ii) tea, (iii) energy drinks, (iv) coffee and tea and (v) mixed drinks. Several differences between the five groups were revealed across all motives except for Taste. The present study developed a robust psychometric instrument for assessing caffeine consumption motives. The factors varied in importance in relation to gender, age and caffeine consumption habits

Computed tomography segmental calcium score (SCS) to predict stenosis severity of calcified coronary lesions

To estimate the probability of ≥50 % coronary stenoses based on computed tomography (CT) segmental calcium score (SCS) and clinical factors. The Institutional Review Board approved the study. A training sample of 201 patients underwent CT calcium scoring and conventional coronary angiography (CCA). All patients consented to undergo CT before CCA after being informed of the additional radiation dose. SCS and calcification morphology were assessed in individual coronary segments. We explored the predictive value of patient’s symptoms, clinical history, SCS and calcification morphology. We developed a prediction model in the training sample based on these variables then tested it in an independent test sample. The odds ratio (OR) for ≥50 % coronary stenosis was 1.8-fold greater (p = 0.006) in patients with typical chest pain, twofold (p = 0.014) greater in patients with acute coronary syndromes, twofold greater (p < 0.001) in patients with prior myocardial infarction. Spotty calcifications had an OR for ≥50 % stenosis 2.3-fold (p < 0.001) greater than the absence of calcifications, wide calcifications 2.7-fold (p < 0.001) greater, diffuse calcifications 4.6-fold (p < 0.001) greater. In middle segments, each unit of SCS had an OR 1.2-fold (p < 0.001) greater than in distal segments; in proximal segments the OR was 1.1-fold greater (p = 0.021). The ROC curve area of the prediction model was 0.795 (0.95 confidence interval 0.602–0.843). Validation in a test sample of 201 independent patients showed consistent diagnostic performance. In conjunction with calcification morphology, anatomical location, patient’s symptoms and clinical history, SCS can be helpful to estimate the probability of ≥50 % coronary stenosis

OSIRIS-REx Contamination Control Strategy and Implementation

OSIRIS-REx will return pristine samples of carbonaceous asteroid Bennu. This manuscript describes how pristine was defined based on expectations of Bennu and on a realistic understanding of what is achievable with a constrained schedule and budget, and how that definition flowed to requirements and implementation. To return a pristine sample, the OSIRIS-REx spacecraft sampling hardware was maintained at Level 100 A/2 and less than 180 nanograms per square centimeter of amino acids and hydrazine on the sampler head through precision cleaning, control of materials, and vigilance. Contamination is further characterized via witness material exposed to the spacecraft assembly and testing environment as well as in space. This characterization provided knowledge of the expected background and will be used in conjunction with archived spacecraft components for comparison with the samples when they are delivered to Earth for analysis. Most of all, the cleanliness of the OSIRIS-REx spacecraft was achieved through communication between scientists, engineers, managers, and technicians

Transjugular Intrahepatic Portosystemic Shunt: Devices Evolution, Technical Tips and Future Perspectives

Portal hypertension (PH) constitutes a pivotal factor in the progression of cirrhosis, giving rise to severe complications and a diminished survival rate. The transjugular intrahepatic portosystemic shunt (TIPS) procedure has undergone significant evolution, with advancements in stent technology assuming a central role in managing PH-related complications. This review aims to outline the progression of TIPS and emphasizes the significant influence of stent advancement on its effectiveness. Initially, the use of bare metal stents (BMSs) was limited due to frequent dysfunction. However, the advent of expanding polytetrafluoroethylene-covered stent grafts (ePTFE-SGs) heralded a transformative era, greatly enhancing patency rates. Further innovation culminated in the creation of ePTFE-SGs with controlled expansion, enabling precise adjustment of TIPS diameters. Comparative analyses demonstrated the superiority of ePTFE-SGs over BMSs, resulting in improved patency, fewer complications, and higher survival rates. Additional technical findings highlight the importance of central stent placement and adequate stent length, as well as the use of smaller calibers to reduce the risk of shunt-related complications. However, improving TIPS through technical means alone is inadequate for optimizing patient outcomes. An extensive understanding of hemodynamic, cardiac, and systemic factors is required to predict outcomes and tailor a personalized approach. Looking forward, the ongoing progress in SG technology, paired with the control of clinical factors that can impact outcomes, holds the promise of reshaping the management of PH-related complications in cirrhosis

Caffeine Impairs Myocardial Blood Flow Response to Physical Exercise in Patients with Coronary Artery Disease as well as in Age-Matched Controls

BACKGROUND: Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD). METHODOLOGY/PRINCIPAL FINDINGS: MBF was measured with (15)O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58+/-13 years) and in CAD patients (n = 15, mean age 61+/-9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26+/-0.56 vs. 2.02+/-0.56, P<0.005), remote (2.40+/-0.70 vs. 1.78+/-0.46, P<0.001) and in stenotic segments (1.90+/-0.41 vs. 1.38+/-0.30, P<0.001). Caffeine decreased MPR significantly by 14% in controls (P<0.05 vs. baseline). In CAD patients MPR decreased by 18% (P<0.05 vs. baseline) in remote and by 25% in stenotic segments (P<0.01 vs. baseline). CONCLUSIONS: We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls

Humoral predictors of malignancy in IPMN: A review of the literature

Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule &gt;5 mm, main pancreatic duct diameter &gt;10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (&gt;37 U/mL), main pancreatic duct diameter 5–9.9 mm, cyst diameter &gt;40 mm, enhancing mural nodules &lt;5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate &gt;5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma

Assessment of myocardial perfusion by dynamic O-15-labeled water PET imaging: validation of a new fast factor analysis

BACKGROUND: Factor analysis (FA) is an established method for separating myocardium from blood pool by use of oxygen 15-labeled water and positron emission tomography for analyzing myocardial blood flow (MBF). Conventional FA methods generating images from sinograms (sinoFA) are time-consuming, whereas FA can be performed on the reconstructed images (reconFA) in a fraction of time. We validated the MBF values obtained by reconFA versus sinoFA. METHODS AND RESULTS: In 23 volunteers (mean age, 26.6 +/- 3.4 years) MBF was calculated from sinoFA and reconFA and blindly reanalyzed 1 month later by the same observer. Intraobserver agreement and reconFA-versus-sinoFA agreement were assessed according to Bland and Altman (BA). Reproducibility proved excellent for global sinoFA (r = 0.968; P < .001; BA limits, -0.617 to 0.676 mL x min(-1) x g(-1)) and slightly superior for reconFA (r = 0.979; P < .001; BA limits, -0.538 to 0.558 mL x min(-1) x g(-1)), with wider limits of agreement for segmental MBF from sinoFA (r = 0.777; P < .001; BA limits, -1.676 to 1.656 mL x min(-1) x g(-1)) and reconFA (r = 0.844; P < .001; BA limits, -1.999 to 1.992 mL x min(-1) x g(-1)). In addition, sinoFA and reconFA showed excellent correlation (r = 0.975, P < .001) and agreement (BA limits, -0.528 to 0.648 mL x min(-1) x g(-1)) for global and segmental values (r = 0.955; P < .001; BA limits, -1.371 to 1.491 mL x min(-1) x g(-1)). CONCLUSIONS: Use of reconFA allows rapid and reliable quantitative MBF assessment with O-15-labeled water

Episodic overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt does not increase mortality in patients with cirrhosis

Background &amp; Aims: Overt hepatic encephalopathy (OHE) is a major complication of transjugular intrahepatic portosystemic shunt (TIPS) placement, given its high incidence and possibility of refractoriness to medical treatment. Nevertheless, the impact of post-TIPS OHE on mortality has not been investigated in a large population. Methods: We designed a multicenter, non-inferiority, observational study to evaluate the mortality rate at 30 months in patients with and without OHE after TIPS. We analyzed a database of 614 patients who underwent TIPS in three Italian centers and estimated the cumulative incidence of OHE and mortality with competitive risk analyses, setting the non-inferiority limit at 0.12. Results: During a median follow-up of 30 months (IQR 12-30), 293 patients developed at least one episode of OHE. Twenty-seven (9.2%) of them experienced recurrent/persistent OHE. Patients with OHE were older (64 [57-71] vs. 59 [50-67] years, p &lt;0.001), had lower albumin (3.1 [2.8-3.5] vs. 3.25 [2.9-3.6] g/dl, p = 0.023), and had a higher prevalence of pre-TIPS OHE (15.4% vs. 9.0%, p = 0.023). Child-Pugh and MELD scores were similar. The 30-month difference in mortality between patients with and without post-TIPS OHE was 0.03 (95% CI -0.042 to 0.102). Multivariable analysis showed that age (subdistribution hazard ratio 1.04, 95% CI 1.02–1.05, p &lt;0.001) and MELD score (subdistribution hazard ratio 1.09, 95% CI 1.05–1.13, p &lt;0.001), but not post-TIPS OHE, were associated with a higher mortality rate. Similar results were obtained when patients undergoing TIPS for variceal re-bleeding prophylaxis (n = 356) or refractory ascites (n = 258) were analyzed separately. The proportion of patients with persistent OHE after TIPS was significantly higher in the group of patients who died. The robustness of these results was increased following propensity score matching. Conclusion: Episodic OHE after TIPS is not associated with mortality in patients undergoing TIPS, regardless of the indication. Impact and implications: Overt hepatic encephalopathy (OHE) is a common complication in patients with advanced liver disease and it is particularly frequent following transjugular intrahepatic portosystemic shunt (TIPS) placement. In patients with cirrhosis outside the setting of TIPS, the development of OHE negatively impacts survival, regardless of the severity of cirrhosis or the presence of acute-on-chronic liver failure. In this multicenter, non-inferiority, observational study we demonstrated that post-TIPS OHE does not increase the risk of mortality in patients undergoing TIPS, irrespective of the indication. This finding alleviates concerns regarding the weight of this complication after TIPS. Intensive research to improve patient selection and risk stratification remains crucial to enhance the quality of life of patients and caregivers and to avoid undermining the positive effects of TIPS on survival

Assessment of portal hypertension severity using machine learning models in patients with compensated cirrhosis

Background &amp; Aims: In individuals with compensated advanced chronic liver disease (cACLD), the severity of portal hypertension (PH) determines the risk of decompensation. Invasive measurement of the hepatic venous pressure gradient (HVPG) is the diagnostic gold standard for PH. We evaluated the utility of machine learning models (MLMs) based on standard laboratory parameters to predict the severity of PH in individuals with cACLD. Methods: A detailed laboratory workup of individuals with cACLD recruited from the Vienna cohort (NCT03267615) was utilised to predict clinically significant portal hypertension (CSPH, i.e., HVPG ≥10 mmHg) and severe PH (i.e., HVPG ≥16 mmHg). The MLMs were then evaluated in individual external datasets and optimised in the merged cohort. Results: Among 1,232 participants with cACLD, the prevalence of CSPH/severe PH was similar in the Vienna (n = 163, 67.4%/35.0%) and validation (n = 1,069, 70.3%/34.7%) cohorts. The MLMs were based on 3 (3P: platelet count, bilirubin, international normalised ratio) or 5 (5P: +cholinesterase, +gamma-glutamyl transferase, +activated partial thromboplastin time replacing international normalised ratio) laboratory parameters. The MLMs performed robustly in the Vienna cohort. 5P-MLM had the best AUCs for CSPH (0.813) and severe PH (0.887) and compared favourably to liver stiffness measurement (AUC: 0.808). Their performance in external validation datasets was heterogeneous (AUCs: 0.589-0.887). Training on the merged cohort optimised model performance for CSPH (AUCs for 3P and 5P: 0.775 and 0.789, respectively) and severe PH (0.737 and 0.828, respectively). Conclusions: Internally trained MLMs reliably predicted PH severity in the Vienna cACLD cohort but exhibited heterogeneous results on external validation. The proposed 3P/5P online tool can reliably identify individuals with CSPH or severe PH, who are thus at risk of hepatic decompensation. Impact and implications: We used machine learning models based on widely available laboratory parameters to develop a non-invasive model to predict the severity of portal hypertension in individuals with compensated cirrhosis, who currently require invasive measurement of hepatic venous pressure gradient. We validated our findings in a large multicentre cohort of individuals with advanced chronic liver disease (cACLD) of any cause. Finally, we provide a readily available online calculator, based on 3 (platelet count, bilirubin, international normalised ratio) or 5 (platelet count, bilirubin, activated partial thromboplastin time, gamma-glutamyltransferase, choline-esterase) widely available laboratory parameters, that clinicians can use to predict the likelihood of their patients with cACLD having clinically significant or severe portal hypertension