Research Spotlight

Sundaram, V., P. Shah, N. Mahmud, C. C. Lindenmeyer, A. S. Klein, R. J. Wong, C. J. Karvellas, S. K. Asrani and R. Jalan (2020). “Patients with severe acute-on-chronic liver failure are disadvantaged by model for end-stage liver disease-based organ allocation policy.” Aliment Pharmacol Ther Jul 29. [Epub ahead of print.].

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BACKGROUND: Mortality for patients with acute-on-chronic liver failure (ACLF) may be underestimated by the model for end-stage liver disease-sodium (MELD-Na) score. AIM: To assess waitlist outcomes across varying grades of ACLF among a cohort of patients listed with a MELD-Na score ≥35, and therefore having similar priority for liver transplantation. METHODS: We analysed the United Network for Organ Sharing (UNOS) database, years 2010-2017. Waitlist outcomes were evaluated using Fine and Gray’s competing risks regression. RESULTS: We identified 6342 candidates at listing with a MELD-Na score ≥35, of whom 3122 had ACLF-3. Extra-hepatic organ failures were present primarily in patients with four to six organ failures. Competing risks regression revealed that candidates listed with ACLF-3 had a significantly higher risk for 90-day waitlist mortality (Sub-hazard ratio (SHR) = 1.41; 95% confidence interval [CI] 1.12-1.78) relative to patients with lower ACLF grades. Subgroup analysis of ACLF-3 revealed that both the presence of three organ failures (SHR = 1.40, 95% CI 1.20-1.63) or four to six organ failures at listing (SHR = 3.01; 95% CI 2.54-3.58) was associated with increased waitlist death. Candidates with four to six organ failures also had the lowest likelihood of receiving liver transplantation (SHR = 0.61, 95% CI 0.54-0.68). The Share 35 rule was associated with reduced 90-day waitlist mortality among the full cohort of patients listed with ACLF-3 and MELD-Na score ≥35 (SHR = 0.59; 95% CI 0.49-0.70). However, Share 35 rule implementation was not associated with reduced waitlist mortality among patients with four to six organ failures (SHR = 0.76; 95% CI 0.58-1.02). CONCLUSION: The MELD-Na score disadvantages patients with ACLF-3, both with and without extra-hepatic organ failures. Incorporation of organ failures into allocation policy warrants further exploration.

Struyvenberg, M. R., A. J. de Groof, R. Fonollà, F. van der Sommen, P. H. N. de With, E. J. Schoon, B. Weusten, C. L. Leggett, A. Kahn, A. J. Trindade, E. K. Ganguly, V. J. A. Konda, C. J. Lightdale, D. K. Pleskow, A. Sethi, M. S. Smith, M. B. Wallace, H. C. Wolfsen, G. J. Tearney, S. L. Meijer, M. Vieth, R. Pouw, W. L. Curvers and J. J. Bergman (2020). “Prospective development and validation of a volumetric laser endomicroscopy computer algorithm for detection of Barrett’s neoplasia.” Gastrointest Endosc Jul 28;S0016-5107(20)34647-2. [Epub ahead of print.].

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BACKGROUND AND AIMS: Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used to detect Barrett’s esophagus (BE) dysplasia. However, real-time interpretation of VLE scans is complex and time-consuming. Computer-aided detection (CAD) may aid in the process of VLE image interpretation. Our aim was to train and validate a CAD algorithm for VLE-based detection of BE neoplasia. METHODS: The multicenter, VLE PREDICT study, prospectively enrolled 47 BE patients. In total, 229 nondysplastic BE, and 89 neoplastic (HGD/EAC) targets were laser marked under VLE guidance and subsequently biopsied for histological diagnosis. Deep convolutional neural networks were used to construct a CAD algorithm for differentiation between nondysplastic and neoplastic BE tissue. The CAD algorithm was trained on a set consisting of the first 22 patients (134 NDBE and 38 neoplastic targets) and validated on a separate test set of patients 23 to 47 (95 NDBE and 51 neoplastic targets). Finally, algorithm performance was benchmarked against the performance of 10 VLE experts. RESULTS: Using the Training set to construct the algorithm resulted in an accuracy of 92%, sensitivity of 95% and specificity of 92%. When performance was assessed on the Test set, accuracy, sensitivity, and specificity were 85%, 91%, and 82%, respectively. The algorithm outperformed all 10 VLE experts, who demonstrated an overall accuracy of 77%, sensitivity of 70%, and specificity of 81%. CONCLUSIONS: We developed, validated, and benchmarked a VLE CAD algorithm for detection of BE neoplasia using prospectively collected and biopsy-correlated VLE targets. The algorithm detected neoplasia with high accuracy and outperformed 10 VLE experts.

Singhania, N., S. Bansal, D. P. Nimmatoori, A. A. Ejaz, P. A. McCullough and G. Singhania (2020). “Current Overview on Hypercoagulability in COVID-19.” Am J Cardiovasc Drugs Aug 4;1-11. [Epub ahead of print.]. 1-11.

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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought many unique pathologies, such as coagulopathy, prompting a desperate need for effective management. COVID-19-associated coagulopathy (CAC) can cause various thromboembolic complications, especially in critically ill patients. The pathogenesis is likely due to endothelial injury, immobilization, and an increase in circulating prothrombotic factors. Data on treatment are limited, although prophylactic anticoagulation is advised in all hospitalized patients. Herein, we have comprehensively reviewed the current literature available on CAC and highlight the pathogenesis, clinical features, and management of CAC.

Shi, C., X. Wang, L. Wang, Q. Meng, D. Guo, L. Chen, M. Dai, G. Wang, R. Cooney and J. Luo (2020). “A nanotrap improves survival in severe sepsis by attenuating hyperinflammation.” Nat Commun 11(1): 3384.

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Targeting single mediators has failed to reduce the mortality of sepsis. We developed a telodendrimer (TD) nanotrap (NT) to capture various biomolecules via multivalent, hybrid and synergistic interactions. Here, we report that the immobilization of TD-NTs in size-exclusive hydrogel resins simultaneously adsorbs septic molecules, e.g. lipopolysaccharides (LPS), cytokines and damage- or pathogen-associated molecular patterns (DAMPs/PAMPs) from blood with high efficiency (92-99%). Distinct surface charges displayed on the majority of pro-inflammatory cytokines (negative) and anti-inflammatory cytokines (positive) allow for the selective capture via TD NTs with different charge moieties. The efficacy of NT therapies in murine sepsis is both time-dependent and charge-dependent. The combination of the optimized NT therapy with a moderate antibiotic treatment results in a 100% survival in severe septic mice by controlling both infection and hyperinflammation, whereas survival are only 50-60% with the individual therapies. Cytokine analysis, inflammatory gene activation and tissue histopathology strongly support the survival benefits of treatments.

Roberts, W. C. (2020). “Importance of Acquiring Financial Security for Physicians.” Am J Med Jul 16;S0002-9343(20)30601-X. [Epub ahead of print.].

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This review tries to make the case that physicians should be adequately rewarded financially so that they can have a clear fiduciary responsibility to do only what is best for their patients without unseemly personal financial gain. To develop financial security physicians need to save a portion of their income regularly to invest. The stock market is the best place to increase one’s monetary worth over a long period.