Research Spotlight

Alves do Monte, F., Sung Park, M., Gokani, V., Singhal, M., Ma, C., Aruwajoye, O. O., Niese, B., Liu, X. and Kim, H. K. W. (2020). “Development of a novel minimally invasive technique to washout necrotic bone marrow content from epiphyseal bone: A preliminary cadaveric bone study.” Orthop Traumatol Surg Res Mar 4. pii: S1877-0568(20)30052-9. [Epub ahead of print].

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INTRODUCTION: Legg-Calve-Perthes disease is a juvenile ischemic osteonecrosis which produces extensive necrotic cell debris and release of damage associated molecular patterns (DAMPs) in the femoral head. The necrotic bone environment induces a chronic inflammatory repair response with excessive bone resorption leading to deformity and early osteoarthritis. Currently there is no minimally invasive method to clear the necrotic materials from the bone to decrease the inflammatory burden of the necrotic environment and to improve the healing process. HYPOTHESIS: We hypothesized that a novel minimally invasive two-needle saline washing technique would be effective to remove cell debris, proteins, and fat from the marrow space of porcine cadaveric humeral heads (HHs). MATERIALS AND METHODS: Twenty-two HHs were subjected to three freeze-thaw cycles to simulate osteonecrosis prior to the wash procedure which consisted of placement of two 15-gauge intraosseous needles followed by incremental saline wash. After the washout procedure, the solutions were collected for measurements of turbidity, protein concentration, and cell count. The HHs were analyzed by optical scanning and histology. RESULTS: The solution collected after each wash showed a significant decrease in the turbidity, cell count, and protein concentration (p<0.05). Histologic assessment showed significantly decreased cell debris and adipocytes in the washed group compared to the unwashed group (p<0.001). DISCUSSION/CONCLUSION: The two-needle intraosseous wash technique effectively removed cell debris and proteins from the marrow space. The technique may be used to reduce the necrotic cell debris and DAMPs present in the necrotic bone. LEVEL OF EVIDENCE: III, in vitro comparative study.

Al Shaikhly, B., Harrel, S. K., Umorin, M., Augsburger, R. A. and Jalali, P. (2020). “Comparison of a Dental Operating Microscope and High-resolution Videoscope for Endodontic Procedures.” J Endod Mar 2. pii: S0099-2399(20)30039-X. [Epub ahead of print].

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INTRODUCTION: The purpose of this study was to compare a dental operating microscope (DOM) with a high-resolution videoscope (VS) in terms of depth of field (DOF), resolution, and effect on fine motor skills. METHODS: Two observers used test targets to measure the resolution and DOF of the DOM and the VS. In addition, 18 participants (12 dental students and 6 endodontic residents) performed an accuracy test on a manikin head using DOM, VS, or loupes. Each participant completed a posttest survey. RESULTS: The 3 magnifications of the DOM had higher resolutions and DOF (resolution: 32, 40.3, and 50.8 line pairs/mm; DOF: 15, 10, and 6 mm) than the VS (resolution: 20.1 line pairs/mm; DOF: 5 mm). Accuracy testing showed the DOM produced better results than the VS for both resident and student groups (P < .001); however, the VS was not significantly different than loupes. The residents performed better than the students using the DOM and the VS (P < .001). The students in general took 1.3 times longer than the residents to perform the accuracy test, irrespective of the magnification device used. The DOM and the VS required on average 1.9 and 2.8 times longer compared with loupes, respectively. Most participants reported a preference for the DOM with regard to visualization and ease of use. Comments also suggested that the VS has value in diagnosis and magnification in endodontics. CONCLUSIONS: Considering the findings from this study, the DOM stands out as the leading magnification tool in endodontics. However, the VS has potential in endodontic procedures and might be used as an adjunct to other visualization aids.

Dangas, G. D., J. G. P. Tijssen, J. Wohrle, L. Sondergaard, M. Gilard, H. Mollmann, R. R. Makkar, H. C. Herrmann, G. Giustino, S. Baldus, O. De Backer, A. H. C. Guimaraes, L. Gullestad, A. Kini, D. von Lewinski, M. Mack, R. Moreno, U. Schafer, J. Seeger, D. Tchetche, K. Thomitzek, M. Valgimigli, P. Vranckx, R. C. Welsh, P. Wildgoose, A. A. Volkl, A. Zazula, R. G. M. van Amsterdam, R. Mehran and S. Windecker (2020). “A Controlled Trial of Rivaroxaban after Transcatheter Aortic-Valve Replacement.” New England Journal of Medicine 382(2): 120-129.

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BACKGROUND: Whether the direct factor Xa inhibitor rivaroxaban can prevent thromboembolic events after transcatheter aortic-valve replacement (TAVR) is unclear. METHODS: We randomly assigned 1644 patients without an established indication for oral anticoagulation after successful TAVR to receive rivaroxaban at a dose of 10 mg daily (with aspirin at a dose of 75 to 100 mg daily for the first 3 months) (rivaroxaban group) or aspirin at a dose of 75 to 100 mg daily (with clopidogrel at a dose of 75 mg daily for the first 3 months) (antiplatelet group). The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated prematurely by the data and safety monitoring board because of safety concerns. RESULTS: After a median of 17 months, death or a first thromboembolic event (intention-to-treat analysis) had occurred in 105 patients in the rivaroxaban group and in 78 patients in the antiplatelet group (incidence rates, 9.8 and 7.2 per 100 person-years, respectively; hazard ratio with rivaroxaban, 1.35; 95% confidence interval [CI], 1.01 to 1.81; P = 0.04). Major, disabling, or life-threatening bleeding (intention-to-treat analysis) had occurred in 46 and 31 patients, respectively (4.3 and 2.8 per 100 person-years; hazard ratio, 1.50; 95% CI, 0.95 to 2.37; P = 0.08). A total of 64 deaths occurred in the rivaroxaban group and 38 in the antiplatelet group (5.8 and 3.4 per 100 person-years, respectively; hazard ratio, 1.69; 95% CI, 1.13 to 2.53). CONCLUSIONS: In patients without an established indication for oral anticoagulation after successful TAVR, a treatment strategy including rivaroxaban at a dose of 10 mg daily was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than an antiplatelet-based strategy. (Funded by Bayer and Janssen Pharmaceuticals; GALILEO ClinicalTrials.gov number, NCT02556203.).

Makkar, R. R., V. H. Thourani, M. J. Mack, S. K. Kodali, S. Kapadia, J. G. Webb, S. H. Yoon, A. Trento, L. G. Svensson, H. C. Herrmann, W. Y. Szeto, D. C. Miller, L. Satler, D. J. Cohen, T. M. Dewey, V. Babaliaros, M. R. Williams, D. J. Kereiakes, A. Zajarias, K. L. Greason, B. K. Whisenant, R. W. Hodson, D. L. Brown, W. F. Fearon, M. J. Russo, P. Pibarot, R. T. Hahn, W. A. Jaber, E. Rogers, K. Xu, J. Wheeler, M. C. Alu, C. R. Smith and M. B. Leon (2020). “Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.” New England Journal of Medicine 382(9): 1-11.

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BACKGROUND: There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve replacement in patients with severe aortic stenosis and intermediate surgical risk. METHODS: We enrolled 2032 intermediate-risk patients with severe, symptomatic aortic stenosis at 57 centers. Patients were stratified according to intended transfemoral or transthoracic access (76.3% and 23.7%, respectively) and were randomly assigned to undergo either TAVR or surgical replacement. Clinical, echocardiographic, and health-status outcomes were followed for 5 years. The primary end point was death from any cause or disabling stroke. RESULTS: At 5 years, there was no significant difference in the incidence of death from any cause or disabling stroke between the TAVR group and the surgery group (47.9% and 43.4%, respectively; hazard ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; P = 0.21). Results were similar for the transfemoral-access cohort (44.5% and 42.0%, respectively; hazard ratio, 1.02; 95% CI, 0.87 to 1.20), but the incidence of death or disabling stroke was higher after TAVR than after surgery in the transthoracic-access cohort (59.3% vs. 48.3%; hazard ratio, 1.32; 95% CI, 1.02 to 1.71). At 5 years, more patients in the TAVR group than in the surgery group had at least mild paravalvular aortic regurgitation (33.3% vs. 6.3%). Repeat hospitalizations were more frequent after TAVR than after surgery (33.3% vs. 25.2%), as were aortic-valve reinterventions (3.2% vs. 0.8%). Improvement in health status at 5 years was similar for TAVR and surgery. CONCLUSIONS: Among patients with aortic stenosis who were at intermediate surgical risk, there was no significant difference in the incidence of death or disabling stroke at 5 years after TAVR as compared with surgical aortic-valve replacement. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Spechler, S. J. (2020). “Medical versus Surgical Treatment for Refractory Heartburn. Reply.”
New England Journal of Medicine 382(3): 297-298.

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Our trial, sponsored by the Department of Veterans Affairs, spanned more than a decade from planning to publication and presented numerous challenges that threatened its successful completion. We agree with Yadlapati and Pandolfino that future RCTs that compare interventional therapies for patients with GERD will encounter similarly daunting obstacles. A rigid requirement for such difficult and expensive RCTs to validate new endosurgical techniques will delay their implementation and may well discourage investigators and their industry partners from developing new devices. On the other hand, there is considerable potential for harm in using invasive treatments whose efficacy is substantiated only by low-quality evidence. Pragmatic yet valid alternatives to RCTs are highly desirable and would facilitate the introduction of sorely needed new treatments for GERD. We also agree with Nicolaides et al. that ensuring patient compliance with PPI dosing is a simple clinical maneuver that works in a substantial minority of patients with PPI-refractory heartburn. Since PPIs bind only to gastric proton pumps that are actively secreting acid, patients should take PPIs 30 to 60 minutes before meals to ensure that the drugs are in the bloodstream when the greatest number of proton pumps are activated by food. Switching PPIs may also be effective, since PPI potencies vary widely, and individual patients can exhibit considerable variability in response to different PPIs. These simple maneuvers can spare many patients the expense, inconvenience, and risk of invasive tests and alternative treatments. Patients in our medical treatment groups were given instructions to avoid lying down for 3 hours after meals and to avoid bedtime snacks. We did not specifically mandate other lifestyle modifications intended to address reflux, such as weight loss, avoidance of foods that may induce heartburn, elevation of the head of the bed, and smoking cessation. The body-mass index (the weight in kilograms divided by the square of the height in meters) in 86% of our patients with reflux-related heartburn was greater than 25, and we agree with Gardner that there are high-quality data showing that weight loss can ameliorate GERD symptoms in obese persons. However, evidence supporting the efficacy of the other lifestyle modifications for patients with GERD is far less robust, and none (including weight loss) have been shown to be effective in patients with heartburn that is refractory to twice-daily PPI therapy, the subject of our trial. The health benefits of smoking cessation and weight loss for obese persons go far beyond any reduction in GERD symptoms, and we certainly support those recommendations. However, our trial was designed specifically to compare the effectiveness of antireflux surgery with that of medications for PPI-refractory heartburn. (Text of author’s reply to commentators on: Spechler SJ, Hunter JG, Jones KM, et al. Randomized trial of medical versus surgical treatment for refractory heartburn. N Engl J Med 2019;381:1513-1523.)