Research Spotlight

Burbick, H., G. N. Glickman and M. Umorin (2021). “The Evolving Landscape of the American Board of Endodontics Certification Process: What it Means for the Future of the Specialty.” J Endod 47(10): 1566-1574.

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INTRODUCTION: The American Board of Endodontics certification is an evolving process to ensure the continuing existence of the specialty of endodontics. Recent examination changes have resulted in greater numbers of Diplomates. To fully understand the implications of such changes and evaluate current Diplomates’ views of the examination process, a specific set of questions was developed focusing on beliefs and perceptions, age relationships, test components, and hypotheticals for potential changes. An analysis of the examination process has never been reported in the literature, and, as such, the survey was designed to provide the endodontic community with critical information on the past, current, and potentially future examination process. METHODS: A Web-based survey consisting of 25 questions was e-mailed to 1522 Diplomates. RESULTS: A total of 736 Diplomates responded to the survey for a response rate of 48.4%. Descriptive statistics and regression analysis (p < .05) were used to explore relationships in the data. CONCLUSIONS: A lack of perceived importance of being board certified was a major barrier. Respondents opposed de-emphasizing literature, offering the oral examination in a videoconferencing virtual format, eliminating mandatory recalls, and entirely removing 1 component of the examination to increase the numbers of Diplomates. Respondents supported reviewing the case history portfolio examination on a rolling basis. Respondents disagreed that molar cases alone demonstrated clinical competency. Older Diplomates felt the strongest that the meaning of being a Diplomate has been diluted by the changes in the certification process. The authors believe the American Association of Endodontists, program directors, and the College of Diplomates must continually emphasize the importance and value of board certification as the process continues to evolve.

Aminoshariae, A., A. Azarpazhooh, A. R. Diogenes, A. F. Fouad, G. N. Glickman, A. Kishen, A. M. Letra, L. Levin, R. S. Roda, F. C. Setzer, F. R. Tay and K. M. Hargreaves (2021). “Insights into the October 2021 Issue of the Journal of Endodontics.” J Endod 47(10): 1547-1549.

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Welcome to the October 2021 issue of the Journal of Endodontics (JOE). Here we share some of our favorite articles that are published in this issue of the journal. We hope you look forward to reading these and other articles in JOE.

Toda Nakamura, M., H. Zhang, D. Guo, H. Ueharu, H. Pan, G. Scott, M. Harris, M. Ray, J. Q. Feng, S. E. Harris, L. F. Bonewald and Y. Mishina (2021). “Podoplanin is dispensable for mineralized tissue formation and maintenance in the Swiss outbred mouse background.” Genesis: e23450.

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Podoplanin, PDPN, is a mucin-type transmembrane glycoprotein widely expressed in many tissues, including lung, kidney, lymph nodes, and mineralized tissues. Its function is critical for lymphatic formation, differentiation of type I alveolar epithelial lung cells, and for bone response to biomechanical loading. It has previously been shown that Pdpn null mice die at birth due to respiratory failure emphasizing the importance of Pdpn in alveolar lung development. During the course of generation of Pdpn mutant mice, we found that most Pdpn null mice in the 129S6 and C57BL6/J mixed genetic background die at the perinatal stage, similar to previously published studies with Pdpn null mice, while all Pdpn null mice bred with Swiss outbred mice survived. Surviving mutant mice in the 129S6 and C57BL6/J mixed genetic background showed alterations in the osteocyte lacunocanalicular network, especially reduced osteocyte canaliculi in the tibial cortex with increased tibial trabecular bone. However, adult Pdpn null mice in the Swiss outbred background showed no overt differences in their osteocyte lacunocnalicular network, bone density, and no overt differences when challenged with exercise. Together, these data suggest that genetic variations present in the Swiss outbred mice compensate for the loss of function of PDPN in lung, kidney, and bone.

Ceglia, V., S. Zurawski, M. Montes, A. Bouteau, Z. Wang, J. Ellis, B. Z. Igyártó, Y. Lévy and G. Zurawski (2021). “Anti-CD40 Antibodies Fused to CD40 Ligand Have Superagonist Properties.” J Immunol 207(8): 2060-2076.

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CD40 is a potent activating receptor within the TNFR family expressed on APCs of the immune system, and it regulates many aspects of B and T cell immunity via interaction with CD40 ligand (CD40L; CD154) expressed on the surface of activated T cells. Soluble CD40L and agonistic mAbs directed to CD40 are being explored as adjuvants in therapeutic or vaccination settings. Some anti-CD40 Abs can synergize with soluble monomeric CD40L. We show that direct fusion of CD40L to certain agonistic anti-CD40 Abs confers superagonist properties, reducing the dose required for efficacy, notably greatly increasing total cytokine secretion by human dendritic cells. The tetravalent configuration of anti-CD40-CD40L Abs promotes CD40 cell surface clustering and internalization and is the likely mechanism of increased receptor activation. CD40L fused to either the L or H chain C termini, with or without flexible linkers, were all superagonists with greater potency than CD40L trimer. The increased anti-CD40-CD40L Ab potency was independent of higher order aggregation. Moreover, the anti-CD40-CD40L Ab showed higher potency in vivo in human CD40 transgenic mice compared with the parental anti-CD40 Ab. To broaden the concept of fusing agonistic Ab to natural ligand, we fused OX40L to an agonistic OX40 Ab, and this resulted in dramatically increased efficacy for proliferation and cytokine production of activated human CD4(+) T cells as well as releasing the Ab from dependency on cross-linking. This work shows that directly fusing antireceptor Abs to ligand is a useful strategy to dramatically increase agonist potency.

Fan, J., K. Hammonds, B. Izekor, C. Jones, P. McGrade, J. B. Michel and R. J. Widmer (2021). “Association of Maximum Troponin Levels With Diagnosis of Acute Myocardial Infarction and Elevated Risk of Mortality.” Ochsner J 21(3): 261-266.

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Background: Cardiac troponins I and T are highly sensitive and specific markers for acute myocardial infarction (AMI). However, a wide range of non-AMI conditions can also cause significant elevations in cardiac troponins. Given the deleterious impact of misdiagnosis of AMI, the ability to risk-stratify patients who present with an elevated troponin is paramount. We hypothesized that the maximum troponin level would be more predictive of mortality and the diagnosis of AMI than the initial troponin level or change in troponin level. Methods: Patient records from a 9-hospital system (n=30,173) in Texas were reviewed during a 24-month period in 2016-2017. Data collected for patients aged ≥40 years included International Classification of Diseases, Tenth Revision diagnoses, troponin I, demographic data (age, sex, smoking history, and chronic medical conditions), and death during hospitalization. We used logistic regression with the Firth penalized likelihood approach to determine the predictive ability of initial, maximum, and change in troponin level for mortality and the diagnosis of AMI. Results: Demographic characteristics of our cohort included a median age of 70 years, with 48.05% male and 51.95% female. The most common preexisting risk factor was hypertension in 78.81% of the cohort. Notable findings from the logistic regression include the predictive ability of maximum troponin on the odds of death by 0.7% for each unit of increase in troponin value. Also, the odds of AMI increased by 3.1% for each unit of increase in the maximum troponin value. Conclusion: Regardless of the level, a detectable amount of troponin in the serum results in a significantly elevated risk of mortality. Many patients with elevated troponin levels leave the hospital without a specific diagnosis, which can lead to poor outcomes because a detectable troponin does not represent a no-risk population. Our study demonstrates that maximum troponin level is a more sensitive and specific predictor of mortality than initial or change in troponin. Similarly, maximum troponin is the most predictive of AMI vs other causes of troponin elevation, likely because of the correlation between rising troponin levels and cardiomyocyte damage. Further studies are needed to correlate maximum troponin levels and clinical manifestations, which may be helpful in redefining AMI so that AMI can be distinguished more easily from non-AMI diagnoses.