Research Spotlight

Tolia, V. N., T. M. Bahr, M. M. Bennett, G. Martin, R. G. Greenberg, M. M. Laughon and R. H. Clark (2019). “The Association of Hydrocortisone Dosage on Mortality in Infants Born Extremely Premature.” J Pediatr 207: 143-147.

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OBJECTIVE: To characterize common dosing strategies and to investigate the association between hydrocortisone dosage and in-hospital mortality in infants born extremely premature. STUDY DESIGN: We performed a retrospective review of a cohort of infants born less-than-or-equal-to 30 weeks’ gestational age from 2010 to 2016 from the Pediatrix Clinical Data Warehouse who received hydrocortisone in the first 14 postnatal days. Infants were divided by initial hydrocortisone dosage (high: >2 mg/kg/d vs low: less-than-or-equal-to 2 mg/kg/d). Baseline characteristics and medication coexposures were compared and mortality was evaluated in a multivariable analysis. RESULTS: A total of 1427 infants were included, 733 with high dosage (51%) and 694 with low dosage (49%). The groups were similar with regard to baseline characteristics. Infants in the high-dosage group had significantly more exposure to any vasopressors (89% vs 84%, P < .001) and greater mortality (50% vs 23%, P < .001) vs the low-dosage group. High dosage of hydrocortisone was associated independently with death (aOR 3.27, 95% CI 2.47-4.34, P < .001) in a multivariable regression analysis including propensity scoring for dosage and other covariates. When the cohort was split into quartiles by dosage, mortality was lower in the lower-dosage quartiles compared with the higher quartiles (mortality range 13%-50%). CONCLUSIONS: In this retrospective analysis of a large sample of infants born premature, increased initial hydrocortisone dosage was associated independently with increased mortality. Trials to assess the impact of hydrocortisone dosage in this population are needed.

Thourani, V. H., S. M. O’Brien, J. J. Kelly, D. J. Cohen, E. D. Peterson, M. J. Mack, D. M. Shahian, F. L. Grover, J. D. Carroll, J. M. Brennan, J. Forcillo, S. V. Arnold, S. Vemulapalli, S. Fitzgerald, D. R. Holmes, J. E. Bavaria and F. H. Edwards (2019). “Development and Application of a Risk Prediction Model for In-Hospital Stroke After Transcatheter Aortic Valve Replacement: A Report From The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.” Ann Thorac Surg 107(4): 1097-1103.

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BACKGROUND: Stroke is a serious complication after transcatheter aortic valve replacement (TAVR), yet predictive models are not available. A new risk model for in-hospital stroke after TAVR was developed and used to estimate site-specific performance. METHODS: We included 97,600 TAVR procedures from 521 sites in The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry from July 2014 to June 2017. Association between baseline covariates and in-hospital stroke was estimated by logistic regression. Discrimination was evaluated by C-statistic. Calibration was tested internally via cross-validation. Hierarchical modeling was used to estimate risk-adjusted site-specific performance. RESULTS: Median age was 82 years, 44,926 (46.0%) were women, and 1,839 (1.9%) had in-hospital stroke. Covariates associated with stroke (odds ratio) included transapical access (1.44), access excluding transapical and transfemoral (1.77), prior stroke (1.57), prior transient ischemic attack (1.50), preprocedural shock, inotropes or mechanical assist device (1.48), smoking (1.28), porcelain aorta (1.23), peripheral arterial disease (1.21), age per 5 years (1.11), glomerular filtration rate per 5 mL/min (0.97), body surface area per m(2) (0.55 male; 0.43 female), and prior aortic valve (0.78) and nonaortic valvular (0.42) procedures. The C-statistic was 0.622. Calibration curves demonstrated agreement between observed and expected stroke rates. Hierarchical modeling showed 10 (1.9%) centers with significantly higher odds ratios for in-hospital stroke than their peers. CONCLUSIONS: A risk model for in-hospital stroke after TAVR was developed from The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry and used to estimate site-specific stroke performance. This model can serve as a valuable resource for quality improvement, clinical decision making, and patient counseling.

Tappa, K., U. Jammalamadaka, J. A. Weisman, D. H. Ballard, D. D. Wolford, C. Pascual-Garrido, L. M. Wolford, P. K. Woodard and D. K. Mills (2019). “3D Printing Custom Bioactive and Absorbable Surgical Screws, Pins, and Bone Plates for Localized Drug Delivery.” J Funct Biomater 10(2): E17.

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Additive manufacturing has great potential for personalized medicine in osseous fixation surgery, including maxillofacial and orthopedic applications. The purpose of this study was to demonstrate 3D printing methods for the fabrication of patient-specific fixation implants that allow for localized drug delivery. 3D printing was used to fabricate gentamicin (GS) and methotrexate (MTX)-loaded fixation devices, including screws, pins, and bone plates. Scaffolds with different infill ratios of polylactic acid (PLA), both without drugs and impregnated with GS and MTX, were printed into cylindrical and rectangular-shaped constructs for compressive and flexural strength mechanical testing, respectively. Bland PLA constructs showed significantly higher flexural strength when printed in a Y axis at 100% infill compared to other axes and infill ratios; however, there was no significant difference in flexural strength between other axes and infill ratios. GS and MTX-impregnated constructs had significantly lower flexural and compressive strength as compared to the bland PLA constructs. GS-impregnated implants demonstrated bacterial inhibition in plate cultures. Similarly, MTX-impregnated implants demonstrated a cytotoxic effect in osteosarcoma assays. This proof of concept work shows the potential of developing 3D printed screws and plating materials with the requisite mechanical properties and orientations. Drug-impregnated implants were technically successful and had an anti-bacterial and chemotherapeutic effect, but drug addition significantly decreased the flexural and compressive strengths of the custom implants.

Swank, C., S. Sikka, S. Driver, M. Bennett and L. Callender (2019). “Feasibility of integrating robotic exoskeleton gait training in inpatient rehabilitation.” Disabil Rehabil Assist Technol Mar 19: 1-9. [Epub ahead of print].

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OBJECTIVE: Learning to walk is a major goal of inpatient rehabilitation and robotic exoskeletons may provide a new gait training approach. Our purpose was to determine the feasibility of integrating the Ekso Gait Training device into inpatient rehabilitation in a neurologic population. DESIGN: Longitudinal cohort design and convenience sample including physical therapists trained to use the Ekso Bionics Ekso GT robotic exoskeleton or inpatients with stroke or SCI. Therapists completed a focus group and survey at baseline and 6 months after initial Ekso training. Patients completed a survey indicating their satisfaction with using the Ekso. RESULTS: Twenty-five patients used the Ekso an average of 4.5 sessions during their 38.5-day rehabilitation stay. Survey and focus group feedback revealed that therapists encountered measurement difficulties with the Ekso and limited treatment time influencing effectiveness of usage. After 6 months, therapists reported an improvement in feasibility. Patients tolerated Ekso sessions well, without any complications or adverse incidents, and reported improved mobility post session. CONCLUSION: Integrating Ekso gait training into clinical practice was not seamless but appears feasible. Barriers were addressed within the rehabilitation team and received administrative support in a process lasting several months. Patients enjoyed walking in Ekso and felt secure within the device. Implications for rehabilitation Integrating Ekso gait training into clinical practice during inpatient rehabilitation is feasible. Overcoming barriers to implementation required administrative support and clinician persistence over several months. Patients tolerated Ekso sessions well, without any complications or adverse incidents.

Sundaram, V., R. Jalan, T. Wu, M. L. Volk, S. K. Asrani, A. S. Klein and R. J. Wong (2019). “Factors Associated with Survival of Patients With Severe Acute-On-Chronic Liver Failure Before and After Liver Transplantation.” Gastroenterology 156(5): 1381-1391.e1383.

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BACKGROUND & AIMS: Liver transplantation for patients with acute-on-chronic liver failure (ACLF) with 3 or more failing organs (ACLF-3) is controversial. We compared liver waitlist mortality or removal according to model for end-stage liver disease (MELD) score vs ACLF category. We also studied factors associated with reduced odds of survival for 1 year after liver transplantation in patients with ACLF-3. METHODS: We analyzed data from the United Network for Organ Sharing (UNOS) from 2005 through 2016. We identified patients who were on the waitlist (100,594) and those who received liver transplants (50,552). Patients with ACLF were identified based on the European Association for the Study of the Liver-chronic liver failure criteria. Outcomes were evaluated with competing risks regression, Kaplan-Meier analysis, and Cox proportional hazards regression. RESULTS: Patients with ACLF-3 were more likely to die or be removed from the waitlist, regardless of MELD-sodium (MELD-Na) score, compared with the other ACLF groups; the proportion was greatest for patients with an ACLF-3 score and MELD-Na score below 25 (43.8% at 28 days). Mechanical ventilation at liver transplantation (hazard ratio [HR] 1.49; 95% confidence interval [CI] 1.22-1.84), donor risk index above 1.7 (HR 1.22; 95% CI 1.09-1.35), and liver transplantation within 30 days of listing (HR 0.89; 95% CI 0.81-0.98) were independently associated with survival for 1 year after liver transplantation CONCLUSIONS: In an analysis of data from the UNOS registry, we found high mortality among patients with ACLF-3 on the liver transplant waitlist, even among those with lower MELD-Na scores. So, certain patients with ACLF-3 have poor outcomes regardless of MELD-Na score. Liver transplantation increases odds of survival for these patients, particularly if performed within 30 days of placement on the waitlist. Mechanical ventilation at liver transplantation and use of marginal organs were associated with increased risk of death.