Research Spotlight

Hammond, F.M., Malec, J.F., Corrigan, J.D., Whiteneck, G.G., Hart, T., Dams-O’Connor, K., Novack, T.A., Bogner, J., Dahdah, M.N., Eagye, C.B., Sevigny, M. and Ketchum, J.M. (2021). “Patterns of Functional Change Five to Ten Years after Moderate-Severe Traumatic Brain Injury.” J Neurotrauma 38(11): 1526-1534.

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This study aims to characterize the patterns of functional change experienced between 5 and 10 years after moderate-severe traumatic brain injury (TBI). The study included TBI Model Systems national database participants (N = 372) at six sites who experienced TBI, received inpatient rehabilitation, and were followed at 5 and 10 years post-TBI. Outcome measures included self- or proxy-reported Functional Independence Measure (FIM(TM)) structured interview at 5 and 10 years post-TBI and domain change indices (DCIs) at 10 years to assess subjective change over the previous 5 years. When all seven FIM and subjective DCI subscales were considered together, 69% reported improvement in at least one subscale and 41% reported decline in at least one subscale; 51% reported more domains improved than declined, and 20% reported more domains declined than improved. Age at injury, post-traumatic amnesia duration, FIM, and depression and anxiety at year 5 were associated with FIM change and DCI measures. Although most persons with moderate-severe TBI do not experience widespread change from year 5 to 10 on individual FIM subscales or perceived domain-specific subscales, the vast majority do report change in one or more domains, with more improvement than decline and more change in subjective DCI than in FIM. Clinicians and researchers should be alert to the possibility of both positive and deleterious changes many years after TBI.

Pham, V., Nguyen, L., Hedin, R.J., Shaver, C., Hammonds, K.A.P. and Culp, W.C., Jr. (2021). “Coronavirus Disease 2019: Anesthesia Machine Circuit Pressure During Use as an Improvised Intensive Care Unit Ventilator.” Anesth Analg 132(5): 1191-1198.

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BACKGROUND: Use of anesthesia machines as improvised intensive care unit (ICU) ventilators may occur in locations where waste anesthesia gas suction (WAGS) is unavailable. Anecdotal reports suggest as much as 18 cm H2O positive end-expiratory pressure (PEEP) being inadvertently applied under these circumstances, accompanied by inaccurate pressure readings by the anesthesia machine. We hypothesized that resistance within closed anesthesia gas scavenging systems (AGSS) disconnected from WAGS may inadvertently increase circuit pressures. METHODS: An anesthesia machine was connected to an anesthesia breathing circuit, a reference manometer, and a standard bag reservoir to simulate a lung. Ventilation was initiated as follows: volume control, tidal volume (TV) 500 mL, respiratory rate 12, ratio of inspiration to expiration times (I:E) 1:1.9, fraction of inspired oxygen (Fio2) 1.0, fresh gas flow (FGF) rate 2.0 liters per minute (LPM), and PEEP 0 cm H2O. After engaging the ventilator, PEEP and peak inspiratory pressure (PIP) were measured by the reference manometer and the anesthesia machine display simultaneously. The process was repeated using prescribed PEEP levels of 5, 10, 15, and 20 cm H2O. Measurements were repeated with the WAGS disconnected and then were performed again at FGF of 4, 6, 8, 10, and 15 LPM. This process was completed on 3 anesthesia machines: Dräger Perseus A500, Dräger Apollo, and the GE Avance CS2. Simple linear regression was used to assess differences. RESULTS: Utilizing nonparametric Bland-Altman analysis, the reference and machine manometer measurements of PIP demonstrated median differences of -0.40 cm H2O (95% limits of agreement [LOA], -1.00 to 0.55) for the Dräger Apollo, -0.40 cm H2O (95% LOA, -1.10 to 0.41) for the Dräger Perseus, and 1.70 cm H2O (95% LOA, 0.80-3.00) for the GE Avance CS2. At FGF 2 LPM and PEEP 0 cm H2O with the WAGS disconnected, the Dräger Apollo had a difference in PEEP of 0.02 cm H2O (95% confidence interval [CI], -0.04 to 0.08; P = .53); the Dräger Perseus A500, <0.0001 cm H2O (95% CI, -0.11 to 0.11; P = 1.00); and the GE Avance CS2, 8.62 cm H2O (95% CI, 8.55-8.69; P < .0001). After removing the hose connected to the AGSS and the visual indicator bag on the GE Avance CS2, the PEEP difference was 0.12 cm H2O (95% CI, 0.059-0.181; P = .0002). CONCLUSIONS: Displayed airway pressure measurements are clinically accurate in the setting of disconnected WAGS. The Dräger Perseus A500 and Apollo with open scavenging systems do not deliver inadvertent continuous positive airway pressure (CPAP) with WAGS disconnected, but the GE Avance CS2 with a closed AGSS does. This increase in airway pressure can be mitigated by the manufacturer's recommended alterations. Anesthesiologists should be aware of the potential clinically important increases in pressure that may be inadvertently delivered on some anesthesia machines, should the WAGS not be properly connected.

LoRusso, P.M., Sekulic, A., Sosman, J.A., Liang, W.S., Carpten, J., Craig, D.W., Solit, D.B., Bryce, A.H., Kiefer, J.A., Aldrich, J., Nasser, S., Halperin, R., Byron, S.A., Pilat, M.J., Boerner, S.A., Durecki, D., Hendricks, W.P.D., Enriquez, D., Izatt, T., Keats, J., Legendre, C., Markovic, S.N., Weise, A., Naveed, F., Schmidt, J., Basu, G.D., Sekar, S., Adkins, J., Tassone, E., Sivaprakasam, K., Zismann, V., Calvert, V.S., Petricoin, E.F., Fecher, L.A., Lao, C., Eder, J.P., Vogelzang, N.J., Perlmutter, J., Gorman, M., Manica, B., Fox, L., Schork, N., Zelterman, D., DeVeaux, M., Joseph, R.W., Cowey, C.L. and Trent, J.M. (2021). “Identifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial.” PLoS One 16(4): e0248097.

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Although combination BRAF and MEK inhibitors are highly effective for the 40-50% of cutaneous metastatic melanomas harboring BRAFV600 mutations, targeted agents have been ineffective for BRAFV600wild-type (wt) metastatic melanomas. The SU2C Genomics-Enabled Medicine for Melanoma Trial utilized a Simon two-stage optimal design to assess whether comprehensive genomic profiling improves selection of molecular-based therapies for BRAFV600wt metastatic melanoma patients who had progressed on standard-of-care therapy, which may include immunotherapy. Of the response-evaluable patients, binimetinib was selected for 20 patients randomized to the genomics-enabled arm, and nine were treated on the alternate treatment arm. Response rates for 27 patients treated with targeted recommendations included one (4%) partial response, 18 (67%) with stable disease, and eight (30%) with progressive disease. Post-trial genomic and protein pathway activation mapping identified additional drug classes that may be considered for future studies. Our results highlight the complexity and heterogeneity of metastatic melanomas, as well as how the lack of response in this trial may be associated with limitations including monotherapy drug selection and the dearth of available single and combination molecularly-driven therapies to treat BRAFV600wt metastatic melanomas.

Taniguchi, A., Alejandro, S.F., Kane, J.M., Daoud, Y., Tanaka, Y., Ford, S.E. and Brodsky, J.W. (2021). “Association of Cavovarus Foot Alignment With Peroneal Tendon Tears.” Foot Ankle Int: 1071100721990348.

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BACKGROUND: Although it is a widely accepted clinical principle that cavovarus deformity predisposes to peroneal tendon problems, there are limited data to support that assumption. This study tested the hypothesis that cavovarus is associated with peroneal tendon tears and evaluated which radiographic measures correlated with that association. METHODS: A retrospective comparison of radiographic measures of cavovarus in 234 consecutive patients operatively treated for chronically symptomatic peroneal tendon tears was compared to a matched control group. Measures included calcaneal pitch, anteroposterior (AP) talometatarsal and talocalcaneal angles, and talonavicular coverage angle. A novel coordinate system analyzed midfoot and hindfoot components of cavovarus. Analysis of variance was used to compare cohorts, and a Tukey-Kramer test used to analyze 3 subgroups of brevis and longus tears, and concomitant tears. RESULTS: The distribution of tears was 73% peroneus brevis, 8% longus, and 19% both tendons. Compared with controls, the study group, and subgroups, had multiple measures of increased cavovarus, including greater calcaneal pitch (P = .0001), decreased AP talo-first metatarsal angle (P = .0001), and increased talonavicular coverage angle (P = .0001). Elevated medial longitudinal arch, and rotational changes in the radiographic profiles of the hindfoot were found with the coordinate system described by Yokokura. CONCLUSION: This study found a statistically significant association of increased cavovarus deformity with peroneal tendon tears, compared to controls. It documented the relative incidence of tears of peroneus brevis, peroneus longus, and concomitant tears in a large surgical series. It demonstrated which simple radiographic angles and complex coordinate measurements of cavovarus deformity were significantly associated with peroneal tendon tears. LEVEL OF EVIDENCE: Level III, retrospective comparative cohort study.

O’Toole, R.V., Joshi, M., Carlini, A.R., Murray, C.K., Allen, L.E., Huang, Y., Scharfstein, D.O., O’Hara, N.N., Gary, J.L., Bosse, M.J., Castillo, R.C., Bishop, J.A., Weaver, M.J., Firoozabadi, R., Hsu, J.R., Karunakar, M.A., Seymour, R.B., Sims, S.H., Churchill, C., Brennan, M.L., Gonzales, G., Reilly, R.M., Zura, R.D., Howes, C.R., Mir, H.R., Wagstrom, E.A., Westberg, J., Gaski, G.E., Kempton, L.B., Natoli, R.M., Sorkin, A.T., Virkus, W.W., Hill, L.C., Hymes, R.A., Holzman, M., Malekzadeh, A.S., Schulman, J.E., Ramsey, L., Cuff, J.A.N., Haaser, S., Osgood, G.M., Shafiq, B., Laljani, V., Lee, O.C., Krause, P.C., Rowe, C.J., Hilliard, C.L., Morandi, M.M., Mullins, A., Achor, T.S., Choo, A.M., Munz, J.W., Boutte, S.J., Vallier, H.A., Breslin, M.A., Frisch, H.M., Kaufman, A.M., Large, T.M., LeCroy, C.M., Riggsbee, C., Smith, C.S., Crickard, C.V., Phieffer, L.S., Sheridan, E., Jones, C.B., Sietsema, D.L., Reid, J.S., Ringenbach, K., Hayda, R., Evans, A.R., Crisco, M.J., Rivera, J.C., Osborn, P.M., Kimmel, J., Stawicki, S.P., Nwachuku, C.O., Wojda, T.R., Rehman, S., Donnelly, J.M., Caroom, C., Jenkins, M.D., Boulton, C.L., Costales, T.G., LeBrun, C.T., Manson, T.T., Mascarenhas, D.C., Nascone, J.W., Pollak, A.N., Sciadini, M.F., Slobogean, G.P., Berger, P.Z., Connelly, D.W., Degani, Y., Howe, A.L., Marinos, D.P., Montalvo, R.N., Reahl, G.B., Schoonover, C.D., Schroder, L.K., Vang, S., Bergin, P.F., Graves, M.L., Russell, G.V., Spitler, C.A., Hydrick, J.M., Teague, D., Ertl, W., Hickerson, L.E., Moloney, G.B., Weinlein, J.C., Zelle, B.A., Agarwal, A., Karia, R.A., Sathy, A.K., Au, B., Maroto, M., Sanders, D., Higgins, T.F., Haller, J.M., Rothberg, D.L., Weiss, D.B., Yarboro, S.R., McVey, E.D., Lester-Ballard, V., Goodspeed, D., Lang, G.J., Whiting, P.S., Siy, A.B., Obremskey, W.T., Jahangir, A.A., Attum, B., Burgos, E.J., Molina, C.S., Rodriguez-Buitrago, A., Gajari, V., Trochez, K.M., Halvorson, J.J., Miller, A.N., Goodman, J.B., Holden, M.B., McAndrew, C.M., Gardner, M.J., Ricci, W.M., Spraggs-Hughes, A., Collins, S.C., Taylor, T.J. and Zadnik, M. (2021). “Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial.” JAMA Surg 156(5): e207259.

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IMPORTANCE: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist. OBJECTIVE: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections. DESIGN, SETTING, AND PARTICIPANTS: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers. INTERVENTIONS: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder. MAIN OUTCOMES AND MEASURES: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence. RESULTS: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections. CONCLUSIONS AND RELEVANCE: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02227446.