Baylor Research Institute

Malek, A.J., Robinson, B.D., Hitt, A.R., Shaver, C.N., Tharakan, B. and Isbell, C.L. (2020). “Doxycycline improves traumatic brain injury outcomes in a murine survival model.” J Trauma Acute Care Surg 89(3): 435-440.

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BACKGROUND: Traumatic brain injury (TBI) has significant morbidity and cost implications. Primary treatment modalities aim to decrease intracranial pressure; however, therapies targeting the underlying pathophysiology of a TBI are limited. The TBI-induced microvascular leak and secondary injury are largely due to proteolysis of the blood-brain barrier (BBB) by matrix metalloproteinase-9. We previously observed doxycycline’s inhibitory affinity on matrix metalloproteinase-9 resulting in preserved BBB integrity in nonsurvival murine studies. This study sought to determine the effect of doxycycline on functional motor and behavioral outcomes in the setting of a TBI murine survival model. METHODS: C57BL/6J mice were assigned to a sham, TBI, or TBI with doxycycline arm. A moderate TBI was induced utilizing a controlled cortical impactor. The TBI with doxycycline cohort received a dose of doxycycline (20 mg/kg) 2 hours after injury and every 12 hours until postoperative day (POD) 6. All mice underwent preoperative testing for weight, modified neurological severity score, wire grip, and ataxia analysis (DigiGait). Postoperative testing was performed on POD 1, POD 3, and POD 6 for the same measures. SAS 9.4 was used for comparative analysis. RESULTS: Fifteen sham mice, 15 TBI mice, and 10 TBI with doxycycline mice were studied. Mice treated with doxycycline had significantly improved modified neurological severity score and wire grip scores at POD 1 (all p < 0.05). Mice treated with doxycycline had significantly improved ataxia scores by POD 3 and POD 6 (all p < 0.05). There was no significant difference in rate of weight change between the three groups. CONCLUSION: Mice treated with doxycycline following TBI demonstrated improved behavioral and motor function suggesting doxycycline's role in preserving murine BBB integrity. Examining the role of doxycycline in human TBIs is warranted given the relative universal accessibility, affordability, and safety profile of doxycycline.

Thai, K.H., Smith, J.C., Stutz, J., Sung, J., Shaver, C. and El Tayeb, M. (2020). “Urethral complications while using 26-French versus 28-French resectoscope sheaths in Holmium Laser Enucleation of the Prostate: A Retrospective Observational Study.” J Endourol Sep 1. [Epub ahead of print.].

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OBJECTIVE: To determine the rate of the urethral stricture (US) and bladder neck contracture (BNC) between patients who undergo Holmium Laser Enucleation of Prostate (HoLEP) surgery with 26Fr vs. 28Fr resectoscope sheaths (RS). Studies report rates of 2.8-4.4% and 3.6-5.4% for US and BNC, respectively. To date, there are no studies that have shown the difference between resectoscope sheath size and urethral complications. METHODS: We retrospectively reviewed charts of patients who had HoLEP surgery between August 2015 to June 2018, by a single surgeon. Prior history of US or BNC were excluded. The operative set-up for a HoLEP includes Ho:YAG laser, urethral dilation, a 26Fr or 28Fr continuous flow RS, and a tissue morcellator. Primary endpoints include postoperative US or BNC. Secondary endpoints include postoperative catheterization time, success of voiding trial and urinary incontinence. Statistical analysis was performed using appropriate methods. RESULTS: Out of 502 HoLEP patients, 339 consecutive patients had surgery with 28Fr RS (Group A) and 163 consecutive patients had surgery with a 26Fr RS (Group B). Twelve patients (A) and three patients (B) had post-op US (p=0.41). Eight (A) and zero (B) patients had post-op BNC (p=0.0585). SUI at 6 weeks, 3-6 months, and 1 year, was present in 15.9% (both A & B), 6.5% (A) vs 6.1% (B) (p=0.88), and 3.2% (A) vs 1.8% (B) (p=0.564), respectively. Both blood loss and change in hemoglobin were higher in 28Fr group with no significant difference in rate of transfusion. Conclusions Resectoscope sheath size had no impact on the rate of US or BNC, however lower incidence in the 26Fr sheath cohort for both. 28Fr sheath had larger change in hemoglobin levels and estimated blood loss, but the higher rate of transfusion was not statistically significant. No difference in the stress incontinence rates, length of stay, and enucleation rates.

Edwards, A.S., Kaplan, B. and Jie, T. (2020). “A Primer on Machine Learning.” Transplantation Aug 18. [Epub ahead of print.].

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In transplant medicine, large collections of data from patients, and various procedures have been stored and organized in registries and databases. With the increase in data volume, there has been a demand for tools that can handle the challenges presented by so called “big data”. In recent years, mathematical and statistical tools such as machine learning are being utilized in an increasing number of analyses. In addition, machine learning has been utilized in various other domains where a large amount of complex data needs to be interrogated (eg, genomics). While the term ‘machine learning’ has become a term commonly mentioned, the techniques, strengths, and limitations are often not fully understood by readers of transplant literature. This commentary will cover some of the history and basic concepts of Machine learning. [No abstract; excerpt from article.].

Ochoa, C., J. Baron-Lee, C. Popescu and K. M. Busl (2020). “Electronic patient portal utilization by neurology patients and association with outcomes.” Health Informatics J Jul 17;1460458220938533. [Epub ahead of print.].

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Existing literature on electronic patient portals demonstrates mixed findings for portal user demographic patterns and relationships between portal usage and clinical outcomes. This study sought to determine characteristics of portal users specific to a neurology patient population and examine whether usage predicted decreased clinic visits and risk of hospitalization. A cross-sectional analysis on 13,483 patients seen at a tertiary neurology outpatient clinic over a 1-year period found significant associations between demographics, and interactions between age, sex, and race. Black and Hispanic patients were less likely to be portal users. While females had higher odds of portal usage overall, their probability decreased with increasing age. Portal users had higher rates of clinic utilization but no difference in hospitalization risk. These results highlight demographics that may need strategic targeting to increase portal uptake and the need for other interventions for populations more likely to experience health events resulting in hospitalization.

Matsuyama, T., R. Kandimalla, T. Ishikawa, N. Takahashi, Y. Yamada, M. Yasuno, Y. Kinugasa, T. F. Hansen, M. Fakih, H. Uetake, B. Győrffy and A. Goel (2020). “A novel mesenchymal-associated transcriptomic signature for risk-stratification and therapeutic response prediction in colorectal cancer.” Int J Cancer Jul 13. [Epub ahead of print.].

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Risk stratification in Stage II and III colorectal cancer (CRC) patients is critical, as it allows patient selection for adjuvant chemotherapy. In view of the inadequacy of current clinicopathological features for risk-stratification, we undertook a systematic and comprehensive biomarker discovery effort to develop a risk-assessment signature in CRC patients. The biomarker discovery phase examined 853 CRC patients, and identified a gene signature for predicting recurrence-free survival (RFS). This signature was validated in a meta-analysis of 1212 patients from nine independent datasets, and its performance was compared against established prognostic signatures and consensus molecular subtypes (CMS). In addition, a risk-prediction model was trained (n = 142), and subsequently validated in an independent clinical cohort (n = 286). As a result, this mesenchymal-associated transcriptomic signature (MATS) identified high-risk CRC patients with poor RFS in the discovery (hazard ratio [HR]: 1.79), and nine validation cohorts (HR: 1.86). In multivariate analysis, MATS was the most significant predictor of RFS compared to established prognostic signatures and CMS subtypes. Intriguingly, MATS robustly identified CMS4-subtype in multiple CRC cohorts (AUC = 0.92-0.99). In the two clinical cohorts, MATS stratified low and high-risk groups with a 5-year RFS in the training (HR: 4.11) and validation cohorts (HR: 2.55), as well as predicted response to adjuvant therapy in Stage II and III CRC patients. We report a novel prognostic and predictive biomarker signature in CRC, which is superior to currently used approaches and have the potential for clinical translation in near future.