Monoclonal Autoantibody Against a Cryptic Epitope on Tissue-Adherent Low-Density Lipoprotein for Molecular Imaging in Atherosclerosis

BackgroundAntibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis.ObjectivesThe authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants.MethodsThe authors created hybridomas from an unimmunized low-density lipoprotein (LDL) receptor-deficient (Ldlr^?/?) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization.ResultsLO9 reacted well with native LDL bound to immobilized matrix components and less well to oxidized LDL. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. The authors localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. Furthermore, in vivo near-infrared fluorescence molecular tomographic imaging, and ex vivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr^?/? mice, in the vicinity of macrophages.ConclusionsThe authors believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.     

Barrett’s esophagus after sleeve gastrectomy: a systematic review and meta-analysis

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Development and Validation of a Score for Fibrotic Nonalcoholic Steatohepatitis

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Comprehensive Evaluation of Left Ventricle Dysfunction by a New Computed Tomography Scanner: The E-PLURIBUS Study

BackgroundAlthough cardiac magnetic resonance (CMR) is considered the gold standard for myocardial fibrosis detection, cardiac computed tomography (CCT) is emerging as a promising alternative.ObjectivesThe purpose of this study was to assess feasibility and diagnostic accuracy of a comprehensive functional and anatomical evaluation with CCT as compared with CMR in patients with newly diagnosed left ventricular dysfunction (LVD).MethodsA total of 128 consecutive patients with newly diagnosed LVD were screened. Based on the exclusion criteria, 28 cases were excluded. CCT was performed within 10 days from CMR. Biventricular volumes and ejection fraction, and presence and pattern of delayed enhancement (DE), were determined, along with evaluation of coronary arteries among patients undergoing invasive angiography in the 6 months after CCT.ResultsSix cases were excluded because of claustrophobia at CMR. Among the 94 patients who formed the study population, the concordance between CCT and CMR in suggesting the cause of the LVD was high (94.7%, 89/94 patients) in the overall population and was 100% for identifying ischemic cardiomyopathy. The CCT diagnostic rate for DE assessment was also high (96.7%, 1,544/1,598 territories) and similar to that of CMR (97.4%; P = 0.345, CCT vs CMR). Moreover, CCT showed high diagnostic accuracy in the detection of DE (94.8%, 95% CI: 93.6%-95.8%) in a territory-based analysis. Biventricular volumes and function parameters as measured by CCT and CMR were similar, without significant differences with the exception of a modest difference in RV volume. CCT was confirmed to be accurate for assessing arterial coronary circulation. The mean radiation exposure of the whole CCT was 7.78 ± 2.53 mSv (0.84 ± 0.24 mSv for DE).ConclusionsCCT performed with low-dose whole-heart coverage scanner and high-concentration contrast agent appears an effective noninvasive tool for a comprehensive assessment of patients with newly diagnosed LVD.     

Diagnostic yield and therapeutic impact of novel motorized spiral enteroscopy in small-bowel disorders: a single-center,real-world experience from a tertiary care hospital (with video)

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Dynamic Stress Computed Tomography Perfusion With a Whole-Heart Coverage Scanner in Addition to Coronary Computed Tomography Angiography and Fractional Flow Reserve Computed Tomography Derived

ObjectivesThe aims of the study were to test the diagnostic accuracy of integrated evaluation of dynamic myocardial computed tomography perfusion (CTP) on top of coronary computed tomography angiography (cCTA) plus fractional flow reserve computed tomography derived (FFR_CT) by using a whole-heart coverage computed tomography (CT) scanner as compared with clinically indicated invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR).BackgroundRecently, new techniques such as dynamic stress computed tomography perfusion (stress-CTP) emerged as potential strategies to combine anatomical and functional evaluation in a one-shot scan. However, previous experiences with this technique were associated with high radiation exposure.MethodsEighty-five consecutive symptomatic patients scheduled for ICA were prospectively enrolled. All patients underwent rest cCTA followed by stress dynamic CTP with a whole-heart coverage CT scanner (Revolution CT, GE Healthcare, Milwaukee, Wisconsin). FFR_CT was also measured by using the rest cCTA dataset. The diagnostic accuracy to detect functionally significant coronary artery disease (CAD) in a vessel-based model of cCTA alone, cCTA+FFR_CT, cCTA+CTP, or cCTA+FFR_CT+CTP were assessed and compared by using ICA and invasive FFR as reference. The overall effective dose of dynamic CTP was also measured.ResultsThe prevalence of obstructive CAD and functionally significant CAD was 77% and 57%, respectively. The sensitivity and specificity of cCTA alone, cCTA+FFR_CT, and cCTA+CTP were 83% and 66%, 86% and 75%, and 73% and 86%, respectively. Both the addition of FFR_CT and CTP improves the area under the curve (AUC: 0.876 and 0.878, respectively) as compared with cCTA alone (0.826; p < 0.05). The sequential strategy of cCTA+FFR_CT+CTP showed the highest AUC (0.919; p < 0.05) as compared with all other strategies. The mean effective radiation dose (ED) for cCTA and stress CTP was 2.8 ± 1.2 mSv and 5.3 ± 0.7 mSv, respectively.ConclusionsThe addition of dynamic stress CTP on top of cCTA and FFR_CT provides additional diagnostic accuracy with acceptable radiation exposure.     

Endoscopist biopsy rate as a quality indicator for outpatient gastroscopy: a multicenter cohort study with validation

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Diagnostic yield and technical performance of the novel motorized spiral enteroscopy compared with single-balloon enteroscopy in suspected Crohn's disease: a prospective study (with video)

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Serum HBcrAg and Hepatocellular Carcinoma in a Taiwanese Population Seronegative for HBsAg and Anti-HCV

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Biomechanical Stress Profiling of Coronary Atherosclerosis: Identifying a Multifactorial Metric to Evaluate Plaque Rupture Risk

ObjectivesThe purpose of this study was to derive a biomechanical stress metric that was based on the multifactorial assessment of coronary plaque morphology, likely related to the propensity of plaque rupture in patients.BackgroundPlaque rupture, the most frequent cause of coronary thrombosis, occurs at locations of elevated tensile stress in necrotic core fibroatheromas (NCFAs). Finite element modeling (FEM), typically used to calculate tensile stress, is computationally intensive and impractical as a clinical tool for locating rupture-prone plaques. This study derived a multifactorial stress equation (MSE) that accurately computes peak stress in NCFAs by combining the influence of several morphological parameters.MethodsIntravascular ultrasound and optical frequency domain imaging were conducted in 30 patients, and plaque morphological parameters were defined in 61 NCFAs. Multivariate regression analysis was applied to derive the MSE and compute a peak stress metric (PSM) that was based on the analysis of plaque morphological parameters. The accuracy of the MSE was determined by comparing PSM with FEM-derived peak stress values. The ability of the PSM in locating plaque rupture sites was tested in 3 additional patients.ResultsThe following parameters were found to be independently associated with peak stress: fibrous cap thickness (p < 0.0001), necrotic core angle (p = 0.024), necrotic core thickness (p < 0.0001), lumen area (p < 0.0001), necrotic core including calcium areas (p = 0.017), and plaque area (p = 0.003). The PSM showed excellent correlation (R = 0.85; p < 0.0001) with FEM-derived peak stress, thus confirming the accuracy of the MSE. In only 56% (n = 34) of plaques, the thinnest fibrous cap thickness was a determining parameter in identifying the cross section with highest PSM. In coronary segments with plaque ruptures, the MSE precisely located the rupture site.ConclusionsThe MSE shows potential to calculate the PSM in coronary lesions rapidly. However, further studies are warranted to investigate the use of biomechanical stress profiling for the prognostic evaluation of patients with atherosclerosis.     

Pancreatic resections in patients who refuse blood transfusions. The application of a perioperative protocol for a true bloodless surgery

BackgroundThe refusal of blood transfusions compels surgeons to face ethical and clinical issues. A single-institution experience with a dedicated perioperative blood management protocol was reviewed to assess feasibility and short-term outcomes of true bloodless pancreatic surgery.MethodsThe institutional database was reviewed to identify patients who refused transfusion and were scheduled for elective pancreatic surgery from 2010 through 2018. A protocol to optimize the hemoglobin values by administration of drugs stimulating erythropoiesis was systematically used.ResultsPerioperative outcomes of 32 Jehovah’s Witnesses patients were included. Median age was 67 years (range, 31–77). Nineteen (59.4%) patients were treated with preoperative erythropoietin. Twenty-four (75%) patients underwent pylorus-preserving pancreaticoduodenectomy, 4 (12.5%) distal pancreatectomy (DP) with splenectomy, 3 (9.4%) spleen-preserving DP, and 1 (3.1%) total pancreatectomy. Median estimated blood loss and surgical duration were 400 mL (range, 100–1000) and 470 min (range, 290–595), respectively. Median preoperative hemoglobin was 13.9 g/dL (range, 11.7–15.8) while median postoperative nadir hemoglobin was 10.5 g/dL (range, 7.1–14.1). The most common histological diagnosis (n = 15, 46.9%) was pancreatic ductal adenocarcinoma. Clavien-Dindo grade I-II complications occurred in fourteen (43.8%) patients while one (3.1%) patient had a Clavien-Dindo grade IIIa complication wich was an abdominal collection that required percutaneous drainage. Six (18.8%) patients presented biochemical leak or postoperative pancreatic fistula grade B. Median hospital stay was 16 days (range, 8–54) with no patient requiring transfusion or re-operation and no 90-day mortality.ConclusionsA multidisciplinary approach and specific perioperative management allowed performing pancreatic resections in patients who refused transfusion with good short-term outcomes.     

Identification of patients with malignant biliary strictures using a cholangioscopy-based deep learning artificial intelligence (with video)

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Pericoronary Adipose Tissue as a Marker of Cardiovascular Risk: JACC Review Topic of the Week

Vascular inflammation is a key driver in atherosclerotic progression and plaque rupture. Recent evidence has shown that coronary computed tomography provides a noninvasive method of quantifying coronary inflammation by mapping changes in pericoronary adipose tissue (PCAT) radiodensity, which are associated with cardiovascular diseases. However, there are significant knowledge gaps in the performance and measurement of PCAT that complicate its interpretation. In this review the authors aim to summarize the role of PCAT in cardiac imaging and explore the clinical implications and applicability as a novel biomarker of cardiovascular risk, as well as to discuss its limitations and potential pitfalls.     

Cost-Effectiveness of a Risk-Tailored Pancreatic Cancer Early Detection Strategy Among Patients With New-Onset Diabetes

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Campylobacter fetus bacteremia complicated by multiple splenic abscesses and multivisceral signs in a renal transplant recipient: a case report and review of the literature

We report a rare case of Campylobacter fetus bacteremia in a 50-year-old woman following kidney transplantation. Bacteremia was complicated by multivisceral signs such as multiple splenic abscesses, bacterial hepatitis, erythema nodosum and reactive arthritis. Despite a prolonged diagnostic delay, the diagnosis was made on blood culture identification and the global outcome was favorable with adequate antibiotherapy. Reports in the literature describe a high rate of mortality for Campylobacter spp. septicemia, with most patients being immunocompromised. However, Campylobacter spp. has been rarely described in renal transplant patients. Moreover, a splenic septic localization due to Campylobacter spp. has been reported only once to our knowledge. Clinicians should be aware of the diagnostic difficulties related to the frequent negativity of stool samples in C. fetus septicemia, in order to implement a tailored medical strategy. Some data suggest that rapid introduction of adapted antibiotic therapy is associated with a reduction in mortality.