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

SARS-CoV2 RNA detection in a pancreatic pseudocyst sample

The involvement of gastrointestinal system in SARS-CoV2 related disease, COVID-19, is increasingly recognized. COVID-19 associated pancreatic injury has been suggested, but its correlation with pancreatic disease is still unclear. In this case report, we describe the detection of SARS-CoV2 RNA in a pancreatic pseudocyst fluid sample collected from a patient with SARS-CoV2 associated pneumonia and a pancreatic pseudocyst developed as a complication of an acute edematous pancreatitis. The detection of SARS-CoV2 within the pancreatic collection arise the question of whether this virus has a tropism for pancreatic tissue and whether it plays a role in pancreatic diseases occurrence

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

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

Impact of cardiac hybrid single-photon emission computed tomography/computed tomography imaging on choice of treatment strategy in coronary artery disease

Aims Cardiac hybrid imaging by fusing single-photon emission computed tomography (SPECT) myocardial perfusion imaging with coronary computed tomography angiography (CCTA) provides important complementary diagnostic information for coronary artery disease (CAD) assessment. We aimed at assessing the impact of cardiac hybrid imaging on the choice of treatment strategy selection for CAD. Methods and results Three hundred and eighteen consecutive patients underwent a 1 day stress/rest (99m)Tc-tetrofosmin SPECT and a CCTA on a separate scanner for evaluation of CAD. Patients were divided into one of the following three groups according to findings in the hybrid images obtained by fusing SPECT and CCTA: (i) matched finding of stenosis by CCTA and corresponding reversible SPECT defect; (ii) unmatched CCTA and SPECT finding; (iii) normal finding by both CCTA and SPECT. Follow-up was confined to the first 60 days after hybrid imaging as this allows best to assess treatment strategy decisions including the revascularization procedure triggered by its findings. Hybrid images revealed matched, unmatched, and normal findings in 51, 74, and 193 patients. The revascularization rate within 60 days was 41, 11, and 0% for matched, unmatched, and normal findings, respectively (P< 0.001 for all inter-group comparisons). Conclusion Cardiac hybrid imaging with SPECT and CCTA provides an added clinical value for decision making with regard to treatment strategy for CAD

Kaposi's Sarcoma-Associated Herpesvirus ORF45 Interacts with Kinesin-2 Transporting Viral Capsid-Tegument Complexes along Microtubules

Open reading frame (ORF) 45 of Kaposi's sarcoma-associated herpesvirus (KSHV) is a tegument protein. A genetic analysis with a null mutant suggested a possible role for this protein in the events leading to viral egress. In this study, ORF45 was found to interact with KIF3A, a kinesin-2 motor protein that transports cargoes along microtubules to cell periphery in a yeast two-hybrid screen. The association was confirmed by both co-immunoprecipitation and immunoflorescence approaches in primary effusion lymphoma cells following virus reactivation. ORF45 principally mediated the docking of entire viral capsid-tegument complexes onto the cargo-binding domain of KIF3A. Microtubules served as the major highways for transportation of these complexes as evidenced by drastically reduced viral titers upon treatment of cells with a microtubule depolymerizer, nocodazole. Confocal microscopic images further revealed close association of viral particles with microtubules. Inhibition of KIF3A–ORF45 interaction either by the use of a headless dominant negative (DN) mutant of KIF3A or through shRNA-mediated silencing of endogenous KIF3A expression noticeably decreased KSHV egress reflecting as appreciable reductions in the release of extracellular virions. Both these approaches, however, failed to impact HSV-1 egress, demonstrating the specificity of KIF3A in KSHV transportation. This study thus reports on transportation of KSHV viral complexes on microtubules by KIF3A, a kinesin motor thus far not implicated in virus transportation. All these findings shed light on the understudied but significant events in the KSHV life cycle, delineating a crucial role of a KSHV tegument protein in cellular transport of viral particles

Accuracy of dual-source CT coronary angiography: first experience in a high pre-test probability population without heart rate control

The aim of this study was to assess the diagnostic accuracy of dual-source computed tomography (DSCT) for evaluation of coronary artery disease (CAD) in a population with extensive coronary calcifications without heart rate control. Thirty patients (24 male, 6 female, mean age 63.1±11.3 years) with a high pre-test probability of CAD underwent DSCT coronary angiography and invasive coronary angiography (ICA) within 14±9 days. No beta-blockers were administered prior to the scan. Two readers independently assessed image quality of all coronary segments with a diameter ≥1.5 mm using a four-point score (1: excellent to 4: not assessable) and qualitatively assessed significant stenoses as narrowing of the luminal diameter >50%. Causes of false-positive (FP) and false-negative (FN) ratings were assigned to calcifications or motion artifacts. ICA was considered the standard of reference. Mean body mass index was 28.3±3.9 kg/m(2) (range 22.4–36.3 kg/m(2)), mean heart rate during CT was 70.3±14.2 bpm (range 47–102 bpm), and mean Agatston score was 821±904 (range 0–3,110). Image quality was diagnostic (scores 1–3) in 98.6% (414/420) of segments (mean image quality score 1.68±0.75); six segments in three patients were considered not assessable (1.4%). DSCT correctly identified 54 of 56 significant coronary stenoses. Severe calcifications accounted for false ratings in nine segments (eight FP/one FN) and motion artifacts in two segments (one FP/one FN). Overall sensitivity, specificity, positive and negative predictive value for evaluating CAD were 96.4, 97.5, 85.7, and 99.4%, respectively. First experience indicates that DSCT coronary angiography provides high diagnostic accuracy for assessment of CAD in a high pre-test probability population with extensive coronary calcifications and without heart rate control

Focus on the research utility of intravascular ultrasound - comparison with other invasive modalities

Intravascular ultrasound (IVUS) is an invasive modality which provides cross-sectional images of a coronary artery. In these images both the lumen and outer vessel wall can be identified and accurate estimations of their dimensions and of the plaque burden can be obtained. In addition, further processing of the IVUS backscatter signal helps in the characterization of the type of the plaque and thus it has been used to study the natural history of the atherosclerotic evolution. On the other hand its indigenous limitations do not allow IVUS to assess accurately stent struts coverage, existence of thrombus or exact site of plaque rupture and to identify some of the features associated with increased plaque vulnerability. In order this information to be obtained, other modalities such as optical coherence tomography, angioscopy, near infrared spectroscopy and intravascular magnetic resonance imaging have either been utilized or are under evaluation. The aim of this review article is to present the current utilities of IVUS in research and to discuss its advantages and disadvantages over the other imaging techniques