Research Spotlight

Panchani, N., Schulz, P., Van Zyl, J., Felius, J., Baxter, R., Yoon, E.T., Baldawi, H., Bindra, A. and Asrani, S.K. (2021). “Liver stiffness and prediction of cardiac outcomes in patients with acute decompensated heart failure.” Clin Transplant Nov 24;e14545. [Epub ahead of print]. e14545.

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BACKGROUND: In acute decompensated heart failure (ADHF), noninvasive markers that predict morbidity and mortality are limited. Liver stiffness measurement (LSM) increases with hepatic fibrosis; however, it may be falsely elevated in patients with ADHF in the absence of liver disease. We investigated whether elevated LSM predicts cardiac outcomes in ADHF. METHODS: In a prospective study, we examined 52 ADHF patients without liver disease between 2016 and 2017. Patients underwent liver 2D shear wave elastography (SWE) and were followed for 12 months to assess the outcomes of left ventricular assist device (LVAD), heart transplant (HT) or death. RESULTS: The median LSM was elevated in patients who received an LVAD or HT within 30-days compared to those who did not (median [IQR]: 55.6 [22.5 – 63.4] vs 13.8 [9.5 – 40.3] kPa, p = .049). Moreover, the risk of composite outcome was highest in the 3rd tertile (> 39.8 kPa compared to 1(st) and 2(nd) combined, HR 2.83, 95% CI 1.20- 6.67, p = .02). Each 1-kPa increase in LSM was associated with a 1%-increase in the incidence rate of readmissions (IRR 1.01, 95% CI 1.00-1.02, p = .01). CONCLUSIONS: LSM may serve as a novel noninvasive tool to determine LVAD, HT, or death in patients with ADHF.

Asrani, S.K., Ghabril, M.S., Kuo, A., Merriman, R.B., Morgan, T., Parikh, N.D., Ovchinsky, N., Kanwal, F., Volk, M.L., Ho, C., Serper, M., Mehta, S., Agopian, V., Cabrera, R., Chernyak, V., El-Serag, H.B., Heimbach, J., Ioannou, G.N., Kaplan, D., Marrero, J., Mehta, N., Singal, A., Salem, R., Taddei, T., Walling, A. and Tapper, E.B. (2021). “Quality measures in HCC care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.” Hepatology Nov 15. [Epub ahead of print].

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BACKGROUND AND AIMS: The burden of hepatocellular carcinoma (HCC) is substantial. To address gaps in HCC care, the American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) aimed to develop a standard set of process-based measures and patient-reported outcomes along the HCC care continuum. APPROACH AND RESULTS: We identified candidate process and outcomes measures for HCC care based on structured literature review. A 13-member panel with content expertise across the HCC care continuum evaluated candidate measures on importance and performance gap using a modified Delphi approach (two rounds of rating) to define the final set of measures. Candidate patient-reported outcomes (PRO) based on a structured scoping review were ranked by 74 patients with HCC across 7 diverse institutions. Out of 135 measures, 29 measures made the final set. These covered surveillance (6 measures), diagnosis (6 measures), staging (2 measures), treatment (10 measures), and outcomes (5 measures). Examples included the use of ultrasound (± alpha-fetoprotein [AFP]) every 6 months, need for surveillance in high-risk populations, diagnostic testing for patients with a new AFP elevation, multidisciplinary liver tumor board (MLTB) review of Liver Imaging-Reporting and Data System 4 lesions, standard evaluation at diagnosis, treatment recommendations based on Barcelona Clinic Liver Cancer staging, MLTB discussion of treatment options, appropriate referral for evaluation of liver transplantation candidacy, and role of palliative therapy. PROs include those related to pain, anxiety, fear of treatment, and uncertainty about the best individual treatment and the future. CONCLUSIONS: The AASLD PMC has developed a set of explicit quality measures in HCC care to help bridge the gap between guideline recommendations and measurable processes and outcomes. Measurement and subsequent implementation of these metrics could be a central step in the improvement of patient care and outcomes in this high-risk population.

Kamoun, M., Askar, M., Kearns, J.D., Bui, T.M., Nguyen, M., Brown, N.K. and Duquesnoy, R.J. (2021). “Immunogenetics of heteroclitic recognition of HLA-DQB1 55R eplet specificity by human alloantibody.” Hum Immunol Nov 20;S0198-8859(21)00254-8. [ Epub ahead of print].

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Heteroclitic antibodies bind to a related antigen with higher affinity than to the immunizing antigen to which they were generated. This uncommon phenomenon is not well characterized for antibodies to HLA antigens. Here we analyzed allosera reactivity from two transplant recipients sensitized to mismatched donor alleles DQB1*06:01 and DQB1*06:02 respectively. Epitope analysis demonstrated the reactivity of both sera was restricted to DQB1*04, 05, and 06 alleles, with a specificity associated with the 55R eplet. Serum from one of these subjects (TE) was significantly more reactive with DQB1*04 alleles than the immunizing DQB1*06:01 or other alleles, a pattern not present in serum from the other patient. Antibody absorption/elution experiments using B cell lines expressing DQB1*06:01 or DQB1*04:02 alleles confirmed that the heteroclitic TE antibody eluted from cells carrying DQB1*06:01 was significantly more reactive with beads carrying the DQB1*04 alleles than with the DQB1*06 or other alleles. The significantly higher reactivity of the heteroclitic alloantibody with DQB1*04 specificity was explained structurally by variations of amino acid residues within 3.5 Å of 55R. These findings have important implications for the interpretation of DQ alloantibody cross-reactivity frequently observed in transplant recipients.

Thakkar, A., Agarwala, A. and Michos, E.D. (2021). “Secondary Prevention of Cardiovascular Disease in Women: Closing the Gap.” Eur Cardiol 16: e41.

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Cardiovascular disease (CVD) remains the leading cause of death in women globally. Younger women (<55 years of age) who experience MI are less likely to receive guideline-directed medical therapy (GDMT), have a greater likelihood of readmission and have higher rates of mortality than similarly aged men. Women have been under-represented in CVD clinical trials, which limits the generalisability of results into practice. Available evidence indicates that women derive a similar benefit as men from secondary prevention pharmacological therapies, such as statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, icosapent ethyl, antiplatelet therapy, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. Women are less likely to be enrolled in cardiac rehabilitation programs than men. Mitigating risk and improving outcomes is dependent on proper identification of CVD in women, using appropriate GDMT and continuing to promote lifestyle modifications. Future research directed at advancing our understanding of CVD in women will allow us to further develop and tailor CVD guidelines appropriate by sex and to close the gap between diagnoses, treatment and mortality.

Khanlar, L.N., Abdou, A., Takagaki, T., Mori, S., Ikeda, M., Nikaido, T., Zandinejad, A. and Tagami, J. (2021). “The effects of different silicatization and silanization protocols on the bond durability of resin cements to new high-translucent zirconia.” Clin Oral Investig Dec 3. [Epub ahead of print].

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OBJECTIVE: The aim of this study was to assess the influence of different silicatization protocols with various silane treatment methods on the bond performance to high-translucent zirconia. MATERIALS AND METHODS: High-translucent zirconia specimens were assigned to five groups according to mechanical surface pretreatment: as-sintered (Con), 0.2 MPa alumina sandblasting (AB2), tribochemical silica coating (TSC), 0.2 and 0.4 MPa glass bead air abrasion (GB2) and (GB4). Each group was subjected to 4 different cementation protocols: Panavia SA Universal (SAU), Panavia SA plus (SAP), silane + SAP (S-SAP), and Universal adhesive + SAP (U-SAP). Tensile bond strength (TBS) was measured after 24 h and 10,000 thermocycling (TC). Surface topography, surface energy, and elemental composition of the abraded zirconia surface analyses were completed. TBS data was analyzed using the Weibull analysis method. Surface roughness and surface energy were compared by one-way ANOVA analysis of variance (α = 0.05). RESULTS: After 24 h, higher TBS was achieved with all cementation protocols in AB2 and TSC, also, in GB2 with all protocols except U-SAP, and in GB4 with SAU and S-SAP. After aging, GB4/S-SAP, GB2/S-SAP, AB2/U-SAP, and TSC/S-SAP showed the highest bond strength. GB groups showed the lowest surface roughness and highest surface energy. CONCLUSION: Glass bead abrasion achieved the durable bond strength to high-translucent zirconia using a separate silane coupling agent while altered surface chemistry, surface energy, and roughness without effect on morphology. CLINICAL RELEVANCE: Glass bead air abrasion is an alternative to alumina sandblasting and tribochemical silica coating and improves bond strength to high translucent zirconia.