Research Spotlight

Sankaranarayanan, G., L. Wooley, D. Hogg, D. Dorozhkin, J. Olasky, S. Chauhan, J. W. Fleshman, S. De, D. Scott and D. B. Jones (2018). “Immersive virtual reality-based training improves response in a simulated operating room fire scenario.” Surg Endosc. Jan 25. [Epub ahead of print].

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BACKGROUND: SAGES FUSE curriculum provides didactic knowledge on OR fire prevention. The objective of this study is to evaluate the impact of an immersive virtual reality (VR)-based OR fire training simulation system in combination with FUSE didactics. METHODS: The study compared a control with a simulation group. After a pre-test questionnaire that assessed the baseline knowledge, both groups were given didactic material that consists of a 10-min presentation and reading materials about precautions and stopping an OR fire from the FUSE manual. The simulation group practiced on the OR fire simulation for one session that consisted of five trials within a week from the pre-test. One week later, both groups were reassessed using a questionnaire. A week after the post-test both groups also participated in a simulated OR fire scenario while their performance was videotaped for assessment. RESULTS: A total of 20 subjects (ten per group) participated in this IRB approved study. Median test scores for the control group increased from 5.5 to 9.00 (p = 0.011) and for the simulation group it increased from 5.0 to 8.5 (p = 0.005). Both groups started at the same baseline (pre-test, p = 0.529) and reached similar level in cognitive knowledge (post-test, p = 0.853). However, when tested in the mock OR fire scenario, 70% of the simulation group subjects were able to perform the correct sequence of steps in extinguishing the simulated fire whereas only 20% subjects in the control group were able to do so (p = 0.003). The simulation group was better than control group in correctly identifying the oxidizer (p = 0.03) and ignition source (p = 0.014). CONCLUSIONS: Interactive VR-based hands-on training was found to be a relatively inexpensive and effective mode for teaching OR fire prevention and management scenarios.

Roffman, J. L., L. J. Petruzzi, A. S. Tanner, H. E. Brown, H. Eryilmaz, N. F. Ho, M. Giegold, N. J. Silverstein, T. Bottiglieri, D. S. Manoach, J. W. Smoller, D. C. Henderson and D. C. Goff (2018). “Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial.” Mol Psychiatry 23(2): 316-322.

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Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received l-methylfolate 15 mg or placebo for 12 weeks. Patients were maintained on stable doses of antipsychotic medications. The pre-defined primary outcome was change in plasma methylfolate at 12 weeks. Secondary outcomes included change in symptoms (Positive and Negative Syndrome Scale (PANSS), Scale for Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia), cognition (Measurement and Treatment Research to Improve Cognition in Schizophrenia composite) and three complementary magnetic resonance imaging measures (working memory-related activation, resting connectivity, cortical thickness). Primary, mixed model, intent-to-treat analyses covaried for six genetic variants in the folate pathway previously associated with symptom severity and/or response to folate supplementation. Analyses were repeated without covariates to evaluate dependence on genotype. Compared with placebo, l-methylfolate increased plasma methylfolate levels (d=1.00, P=0.0009) and improved PANSS Total (d=0.61, P=0.03) as well as PANSS Negative and General Psychopathology subscales. Although PANSS Total and General Psychopathology changes were influenced by genotype, significant PANSS Negative changes occurred regardless of genotype. No treatment differences were seen in other symptom rating scales or cognitive composite scores. Patients receiving l-methylfolate exhibited convergent changes in ventromedial prefrontal physiology, including increased task-induced deactivation, altered limbic connectivity and increased cortical thickness. In conclusion, l-methylfolate supplementation was associated with salutary physiological changes and selective symptomatic improvement in this study of schizophrenia patients, warranting larger clinical trials. ClinicalTrials.gov, NCT01091506.

Roden-Foreman, J. W., N. R. Rapier, L. Yelverton and M. L. Foreman (2018). “Avoiding Cribari gridlock: the Standardized Triage Assessment Tool improves the accuracy of the Cribari Matrix Method in identifying potential over- and undertriage.” J Trauma Acute Care Surg. Jan 24. [Epub ahead of print].

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BACKGROUND: The Cribari matrix method (CMM) is the standard to identify potential over- and undertriage but requires case reviews to correct for the fact that Injury Severity Score does not account for physiology or comorbidities, nor is it well correlated with resource consumption. Further, the secondary reviews introduce undesirable subjectivity. This study assessed if the Standardized Triage Assessment Tool (STAT)-a combination of the CMM and the Need For Trauma Intervention-could more accurately determine over- and undertriage than the CMM alone. METHODS: The registry of an ACS verified Level I adult trauma center in Texas was queried for all new ED traumas 2013-2016 (n = 11,110). Binary logistic regressions were used to test the associations between the triage determinations of each metric against indicators of injury severity (risk factors, complications, and mortality) and resource consumption (number of procedures in three days and total length of stay). RESULTS: Both metrics were associated with the indicators of injury severity and resource consumption in the expected directions, but STAT had stronger or equivalent associations with all variables tested. Using the CMM, there was 50.4% overtriage and 9.1% undertriage. Using STAT, overtriage was reduced to 30.8% (relative reduction = 38.9%) and undertriage was reduced to 3.3% (relative reduction = 63.7%). CONCLUSIONS: Using the CMM with secondary case reviews makes valid multi-institutional triage rate comparisons impossible because of the subjective and unstandardized nature of these reviews. STAT’s out-of-box triage determinations (i.e., without manual case review) outperformed CMM in almost every tested variable for both over- and undertriage. STAT, an automatic, standardized method offers significant improvements compared to the current subjective system. Further, by accounting for both anatomic injury severity and resource consumption, STAT may allow trauma centers to better allocate resources and predict patient needs with fewer cases requiring manual review. LEVEL OF EVIDENCE: diagnostic criteria, level II.

Roberts, W. C., N. Kondapalli and J. M. Guileyardo (2018). “Morphologic Findings in Donor (Transplanted) Hearts at Necropsy Early and Late After Orthotopic Heart Transplantation.” Am J Cardiol 121(2): 217-240.

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Little necropsy information is available on donor hearts in place in recipients for varying periods. Necropsy studies were performed in 79 patients who had survived from 1 day to 17 years after orthotopic heart transplantation (OHT). At OHT, the 79 patients ranged in age from 3 to 70 years (mean 51), and at death, from 20 to 76 years (mean 54). The native hearts tended to be larger than the donor hearts in the 22 patients surviving 60 days, suggesting that the donor hearts increased in weight with time. Cardiac adiposity increased with time. Grossly visible myocardial lesions were seen in 24 (30%) of the 79 cases: necrosis only in 20; fibrosis only in 2, and both in 2. One or more epicardial coronary arteries were narrowed >75% in cross-sectional area in 25 (32%), 1 of whom was in the group surviving 60 days. The lymphocytic infiltrates were largest in the subepicardial adipose tissue, next in myocardium, and least in endocardium. The quantity of the cellular infiltrates varied considerably among the patients. In conclusion, with time, the donor hearts tended to increase in weight, in the quantity of adipose tissue, in the amounts of coronary narrowing, in the frequency of ventricular cavity dilatation (particularly the right ventricle), and in the frequency of lymphocytic infiltrates (evidence of rejection).

Paulson, A. S., L. M. Hess, A. M. Liepa, Z. L. Cui, K. M. Aguilar, J. Clark and W. Schelman (2018). “Ramucirumab for the treatment of patients with gastric or gastroesophageal junction cancer in community oncology practices.” Gastric Cancer. Feb 3. [Epub ahead of print].

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BACKGROUND: Limited real-world research has investigated ramucirumab for the treatment of patients with gastric or gastroesophageal junction (GEJ) cancer. This study was designed to describe ramucirumab monotherapy or combination therapy use in a community oncology practice setting. METHODS: This was a retrospective observational cohort study to describe the treatment of adult patients with gastric or GEJ cancer who initiated ramucirumab treatment between 4/21/14 and 6/30/16 within the US Oncology Network. Kaplan-Meier method and Cox proportional hazards regression analyses were used to assess clinical outcomes. Multivariable logistic regression models were used to assess patient-level predictors of ramucirumab monotherapy or combination therapy. RESULTS: A total of 505 patients (mean age 64.4 years; 75.1% male) were included in the analysis; subgroups included: monotherapy (22.8%; n = 115), combination therapy (77.2%; n = 390). Monotherapy patients were significantly older (67.7 vs. 63.4 years; P = 0.0006), received ramucirumab approximately 3 months later after diagnosis (16.9 vs. 14.1 months; P = 0.0318) and more frequently initiated ramucirumab in the third or later lines of treatment (38.3 vs. 8.2%; P<0.0001) than patients receiving combination therapy. Median overall survival (OS) for monotherapy and combination therapy from the start of second-line therapy was 5.5 months (confidence interval [CI] 4.3, 7.8) and 7.4 months (CI 6.6, 8.8), respectively. CONCLUSIONS: The results showed that patients who received ramucirumab monotherapy started ramucirumab therapy later after diagnosis and were older than those who received ramucirumab in combination. Additionally, survival data suggest that outcomes observed in community oncology practices are similar to data from phase 3 clinical trials.