Research Spotlight

Shutze, W., Gable, D., Ogola, G., Yasin, T., Madhukar, N., Kamma, B., Alniem, Y. and Eidt, J. (2021). “Sex, Age, and Other Barriers for Prosthetics Referral Following Amputation and the Impact on Survival.” J Vasc Surg May 31;S0741-5214(21)00839-9. [Epub ahead of print].

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BACKGROUND: Despite advances in peripheral vascular disease treatment, lower extremity amputation continues to be necessary in a significant number of patients. Up to 80% of amputees are not referred for prosthetic fitting. The factors contributing to referral decisions have not been adequately investigated, nor has the impact of prosthetic referral on survival. We characterized differences between patients who were successfully referred to our in-house prosthetists compared to those that were not, and identified factors associated with prosthetic referral and predictive of survival. METHODS: This was a retrospective analysis of all patients that underwent lower-extremity amputation by surgeons in our practice from January 1, 2010 to June 30, 2017. Age, sex, race, body mass index (BMI), diabetes, hypertension, hyperlipidemia, end stage renal disease, prior coronary artery bypass graft surgery, congestive heart failure, tobacco use, American Society of Anesthesiologists (ASA) score, previous arterial procedure, chronic obstructive pulmonary disease, statin use, postoperative ambulatory status, level of amputation, stump revision, and referral for prosthesis were collected. Survival was determined from a combination of sources, including the Social Security Death Master Index, multiple genealogic registries, and internet searches. Multivariable logistic regression was used to determine risk factors associated with prosthesis referral. Multivariable Cox proportional hazard regression with time dependent covariates was performed to assess risk factors associated with 5-year mortality. RESULTS: There were 293 patients included in this study. Mean age was 66 years and mean body mass index 27 kg/m(2). The majority of patients were male (69%), white (53%), with diabetes (65.4%) and hypertension (77.5%), and underwent below-the-knee amputation (BKA) (73%), . Prosthetic referral occurred in 123 (42.0%). Overall 5-year survival was 61.7% (95%CI, 55.9%-68.1%) (BKA 64.7% [95%CI, 57.9%-72.3%], above-the-knee amputation 53.8 % [95%CI, 43.4%-66.6%]). On multivariate analysis age >70 years, female sex, diabetes, ASA score 4 or 5, and current tobacco use were associated with no referral for prosthetic fitting. Patients with BMI 25-30, a previous arterial procedure, BKA, and history of stump revision were more likely to be referred. Factors associated with decreased survival were: increasing age, higher ASA class, Black race, and BMI; prosthetics referral was seen to be protective. CONCLUSION: We identified multiple patient factors associated with prosthetic referral, as well as several characteristics predictive of reduced survival after amputation. Being referred for prosthetic fitting was associated with improved survival not explained by patient characteristics and comorbidities. Further research is needed to determine whether the factors identified as associated with non-referral are markers for patient characteristics that make them clinically unsuitable for prosthetic fitting or if they are symptoms of unconscious bias or of patient’s access to care.

Baker, S.E., Escamilla, K., Jacobs, M., Sherhart, R., Trello-Rishel, K. and Fuehrlein, B. (2021). “Manikin-Based Simulation: an Update to the Clerkship Experience.” Acad Psychiatry May 18; 1-2. [Epub ahead of print]. 1-2.

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High-fidelity manikin-based simulation (MBS) was introduced into the psychiatry clerkship experience at Yale University several years ago [1]. Despite its growing popularity and use in other specialties, this technology is not widely incorporated into psychiatry education [2]. Our group wished to study student attitudes toward this technologically driven educational tool as part of a psychiatry clerkship experience to understand if it would be well received by students and could be utilized more widely.[No abstract; excerpt from article].

Zerem, A., Ben-Sira, L., Vigdorovich, N., Leibovitz, Z., Fisher, Y., Schiffmann, R., Grishchuk, Y., Misko, A.L., Orenstein, N., Lev, D., Lerman-Sagie, T. and Kidron, D. (2021). “White matter abnormalities and iron deposition in prenatal mucolipidosis IV- fetal imaging and pathology.” Metab Brain Dis May 8. [Epub ahead of print].

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Mucolipidosis type IV (MLIV; OMIM 252,650) is an autosomal recessive lysosomal disorder caused by mutations in MCOLN1. MLIV causes psychomotor impairment and progressive vision loss. The major hallmarks of postnatal brain MRI are hypomyelination and thin corpus callosum. Human brain pathology data is scarce and demonstrates storage of various inclusion bodies in all neuronal cell types. The current study describes novel fetal brain MRI and neuropathology findings in a fetus with MLIV. Fetal MRI was performed at 32 and 35 weeks of gestation due to an older sibling with spastic quadriparesis, visual impairment and hypomyelination. Following abnormal fetal MRI results, the parents requested termination of pregnancy according to Israeli regulations. Fetal autopsy was performed after approval of the high committee for pregnancy termination. A genetic diagnosis of MLIV was established in the fetus and sibling. Sequential fetal brain MRI showed progressive curvilinear hypointensities on T2-weighted images in the frontal deep white matter and a thin corpus callosum. Fetal brain pathology exhibited a thin corpus callosum and hypercellular white matter composed of reactive astrocytes and microglia, multifocal white matter abnormalities with mineralized deposits, and numerous aggregates of microglia with focal intracellular iron accumulation most prominent in the frontal lobes. This is the first description in the literature of brain MRI and neuropathology in a fetus with MLIV. The findings demonstrate prenatal white matter involvement with significant activation of microglia and astrocytes and impaired iron metabolism.

Leede, E., Kempema, J., Wilson, C., Rios Tovar, A.J., Cook, A., Fox, E., Regner, J., Richmond, R., Carrick, M. and Brown, C.V.R. (2021). “A multicenter investigation of the hemodynamic effects of induction agents for trauma rapid sequence intubation.” J Trauma Acute Care Surg 90(6): 1009-1013.

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BACKGROUND: Several options exist for induction agents during rapid sequence intubation (RSI) in trauma patients, including etomidate, ketamine, and propofol. These drugs have reported variable hemodynamic effects (hypotension with propofol and sympathomimetic effects with ketamine) that could affect trauma resuscitations. The purpose of this study was to compare the hemodynamic effects of these three induction agents during emergency department RSI in adult trauma. We hypothesized that these drugs would display a differing hemodynamic profile during RSI. METHODS: We performed a retrospective (2014-2019), multicenter trial of adult (≥18 years) trauma patients admitted to eight ACS-verified Level I trauma centers who underwent emergency department RSI. Variables collected included systolic blood pressure (SBP) and pulse before and after RSI. The primary outcomes were change in heart rate and SBP before and after RSI. RESULTS: There were 2,092 patients who met criteria, 85% received etomidate (E), 8% ketamine (K), and 7% propofol (P). Before RSI, the ketamine group had a lower SBP (E, 135 vs. K, 125 vs. P, 135 mm Hg, p = 0.04) but there was no difference in pulse (E, 104 vs. K, 107 vs. P, 105 bpm, p = 0.45). After RSI, there were no differences in SBP (E, 135 vs. K, 130 vs. P, 133 mm Hg, p = 0.34) or pulse (E, 106 vs. K, 110 vs. P, 104 bpm, p = 0.08). There was no difference in the average change of SBP (E, 0.2 vs. K, 5.2 vs. P, -1.8 mm Hg, p = 0.4) or pulse (E, 1.7 vs. K, 3.5 bpm vs. P, -0.96, p = 0.24) during RSI. CONCLUSION: Contrary to our hypothesis, there was no difference in the hemodynamic effect for etomidate versus ketamine versus propofol during RSI in trauma patients. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Prabhu, R.S., Dhakal, R., Vaslow, Z.K., Dan, T., Mishra, M.V., Murphy, E.S., Patel, T.R., Asher, A.L., Yang, K., Manning, M.A., Stern, J.D., Patel, A.R., Wardak, Z., Woodworth, G.F., Chao, S.T., Mohammadi, A. and Burri, S.H. (2021). “Preoperative radiosurgery for resected brain metastases: the PROPS-BM multicenter cohort study.” Int J Radiat Oncol Biol Phys May 28;S0360-3016(21)00666-0. [Epub ahead of print].

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PURPOSE: Preoperative radiosurgery (SRS) is a feasible alternative to postoperative SRS with potential benefits in adverse radiation effect (ARE) and leptomeningeal disease (LMD) relapse. However, previous studies are limited by small patient numbers and single institutional design. Our aim was to evaluate preoperative SRS outcomes and prognostic factors from a large multicenter cohort (Trial name BLINDED). METHODS AND MATERIALS: Patients with brain metastases (BM) from solid cancers, of which at least 1 lesion was treated with preoperative SRS and underwent planned resection were included from 5 institutions. SRS to synchronous intact BM was allowed. Radiographic meningeal disease was categorized as nodular (nMD) or classical “sugarcoating” (cLMD). RESULTS: The cohort included 242 patients with 253 index lesions. Most patients (62.4%) had a single BM, 93.7% underwent gross total resection (GTR), and 98.8% were treated with a single fraction to a median dose of 15 Gy to a median gross tumor volume of 9.9cc. Cavity local recurrence (LR) at 1 and 2-years was 15% and 17.9%, respectively. Subtotal resection (STR) was a strong independent predictor of LR (hazard ratio 9.1, p<0.001). MD and any grade ARE at 1 and 2-years was 6.1% and 7.6%, and 4.7% and 6.8%, respectively. Median and 2-year overall survival (OS) was 16.9 months and 38.4%, respectively. The majority of MD was cLMD type (13 of 19 pts with MD, 68.4%). Ten of 242 pts (4.1%) experienced grade ≥3 postoperative surgical complications. CONCLUSIONS: This multicenter study represents the largest cohort treated with preoperative SRS to our knowledge. The favorable outcomes previously demonstrated in single institution studies are confirmed in this expanded multicenter analysis without evidence of excessive postoperative surgical complication risk. STR, though infrequent, is associated with significantly worse cavity LR. A randomized trial between preoperative and postoperative SRS is warranted and currently being designed.