Targeted metagenomic assessment reflects critical colonization in battlefield injuries.

IMPORTANCE: Microbial contamination in combat wounds can lead to opportunistic infections and adverse outcomes. However, current microbiological detection has a limited ability to capture microbial functional genes. This work describes the application of targeted metagenomic sequencing to profile wound bioburden and capture relevant wound-associated signatures for clinical utility. Ultimately, the ability to detect such signatures will help guide clinical decisions regarding wound care and management and aid in the prediction of wound outcomes.

A Novel Paradigm for Surgical Skills Training and Assessment of Competency.

Importance: Sustainment of comprehensive procedural skills in trauma surgery is a particular problem for surgeons in rural, global, and combat settings. Trauma care often requires open surgical procedures for low-frequency/high-risk injuries at a time when open surgical experience is declining in general and trauma surgery training. Objective: To determine whether general surgeons participating in a 2-day standardized trauma skills course demonstrate measurable improvement in accuracy and independent performance of specific trauma skills. Design, Setting, and Participants: General surgeons in active surgical practice were enrolled from a simulation center with anatomic laboratory from October 2019 to October 2020. Differences in pretraining/training and posttraining performance outcomes were examined using (1) pretraining/posttraining surveys, (2) pretraining/posttraining knowledge assessment, and (3) training/posttraining faculty assessment. Analysis took place in November 2020. Interventions: A 2-day standardized, immersive, cadaver-based skills course, developed with best practices in instructional design, that teaches and assesses 24 trauma surgical procedures was used. Main Outcomes and Measures: Trauma surgery capability, as measured by confidence, knowledge, abilities, and independent performance of specific trauma surgical procedures; 3-month posttraining skill transfer. Results: The study cohort included 65 active-duty general surgeons, of which 16 (25%) were women and 49 (75%) were men. The mean (SD) age was 38.5 (4.2) years. Before and during training, 1 of 65 participants (1%) were able to accurately perform all 24 procedures without guidance. After course training, 64 participants (99%) met the benchmark performance requirements for the 24 trauma procedures, and 51 (78%) were able to perform them without guidance. Procedural confidence and knowledge increased significantly from before to after the course. At 3 months after training, 37 participants (56%) reported skill transfer to trauma or other procedures. Conclusions and Relevance: In this study, direct measurement of procedural performance following standardized training demonstrated significant improvement in skill performance in a broad array of trauma procedures. This model may be useful for assessment of procedural competence in other specialties.

Scoping Evidence Review on Training and Skills Assessment for Open Emergency Surgery.

OBJECTIVE: Scope evidence on technical performance metrics for open emergency surgery. Identify surgical performance metrics and procedures used in trauma training courses. DESIGN: Structured literature searches of electronic databases were conducted from January 2010 to December 2019 to identify systematic reviews of tools to measure surgical skills employed in vascular or trauma surgery evaluation and training. SETTING AND PARTICIPANTS: Faculty of Shock Trauma Anesthesiology Research Center, University of Maryland School of Medicine, Uniformed Services University of Health Sciences, Bethesda, Maryland and Implementation Science, King's College, London. RESULTS: The evidence from 21 systematic reviews including over 54,000 subjects enrolled into over 840 eligible studies, identified that the Objective Structured Assessment of Technical Skill was used for elective surgery not for emergency trauma and vascular control surgery procedures. The Individual Procedure Score (IPS), used to evaluate emergency trauma procedures performed before and after training, distinguished performance of residents from experts and practicing surgeons. IPS predicted surgeons who make critical errors and need remediation interventions. No metrics showed Kirkpatrick's Level 4 evidence of technical skills training benefit to emergency surgery outcomes. CONCLUSIONS: Expert benchmarks, errors, complication rates, task completion time, task-specific checklists, global rating scales, Objective Structured Assessment of Technical Skills, and IPS were found to identify surgeons, at all levels of seniority, who are in need of remediation of technical skills for open surgical hemorrhage control. Large-scale, multicenter studies are needed to evaluate any benefit of trauma technical skills training on patient outcomes.

Lessons of War: Turning Data Into Decisions.

BACKGROUND: Recent conflicts in Afghanistan and Iraq produced a substantial number of critically wounded service-members. We collected biomarker and clinical information from 73 patients who sustained 116 life-threatening combat wounds, and sought to determine if the data could be used to predict the likelihood of wound failure. METHODS: From each patient, we collected clinical information, serum, wound effluent, and tissue prior to and at each surgical débridement. Inflammatory cytokines were quantified in both the serum and effluent, as were gene expression targets. The primary outcome was successful wound healing. Computer intensive methods were used to derive prognostic models that were internally validated using target shuffling and cross-validation methods. A second cohort of eighteen critically injured civilian patients was evaluated to determine if similar inflammatory responses were observed. FINDINGS: The best-performing models enhanced clinical observation with biomarker data from the serum and wound effluent, an indicator that systemic inflammatory conditions contribute to local wound failure. A Random Forest model containing ten variables demonstrated the highest accuracy (AUC 0.79). Decision Curve Analysis indicated that the use of this model would improve clinical outcomes and reduce unnecessary surgical procedures. Civilian trauma patients demonstrated similar inflammatory responses and an equivalent wound failure rate, indicating that the model may be generalizable to civilian settings. INTERPRETATION: Using advanced analytics, we successfully codified clinical and biomarker data from combat patients into a potentially generalizable decision support tool. Analysis of inflammatory data from critically ill patients with acute injury may inform decision-making to improve clinical outcomes and reduce healthcare costs. FUNDING: United States Department of Defense Health Programs.

Incidence, predictors, costs, and outcome of renal cell carcinoma after kidney transplantation: USRDS experience.

INTRODUCTION: We carried out an analysis of the United States Renal Data System to determine the incidence, risk factors, prognosis, and costs associated with the diagnosis of renal cell carcinoma (RCC) after kidney transplantation. METHODS: This is a retrospective cohort of 40,821 Medicare primary renal transplant recipients transplanted from January 1, 2000, to July 1, 2005, and followed up till December 31, 2005, excluding those with prior RCC or nephrectomy. Kaplan-Meier analysis was performed to determine the time of occurrence of RCC, and Cox regression was used to determine factors associated with RCC. RESULTS: Three hundred sixty-eight patients were diagnosed with RCC within 3 years after transplant (incidence of 3.16 per 1000 person years). The 3-year incidence of RCC posttransplant was 9.29 per 1000 person years (2.3%) for those with pretransplant cysts and 3.08 per 1000 person years (0.7%) without pretransplant cysts. RCC was diagnosed disproportionately early posttransplant in patients with cysts. Cysts were independently associated with increased risk of RCC, as was male gender, older recipient, donor age, African American recipient, increased time on dialysis and acute rejection within first year posttransplant. RCC was associated with increased risk of mortality with a higher risk with pretransplant cysts. Patients who developed RCC had higher cumulative median costs ($55,456 at 2 years) than those who did not develop RCC ($40,369). There was no "clustering" of RCC in individual states or centers more than would be expected by chance. CONCLUSION: RCC was diagnosed disproportionately early in patients with pretransplant renal cysts and was associated with a worse prognosis and increased costs.

Incidence, predictors and outcomes of transplant renal artery stenosis after kidney transplantation: analysis of USRDS.

OBJECTIVE: We analyzed the United States Renal Data System registry to study the risks, predictors, and outcomes of transplant renal artery stenosis (TRAS) in contemporary practice. METHODS: The study sampled comprised adults with Medicare primary insurance who received kidney transplants in 2000-2005. We examined associations of recipient, donor and transplant factors with time-to-TRAS by the Kaplan-Meier method and multivariate Cox regression. Survival analysis methods were employed to estimate graft survival after TRAS, and to model TRAS as a time-dependent outcome predictor. Kaplan-Meier analysis was used to estimate time to allograft loss in patients who did or did not have an angioplasty procedure for TRAS. RESULTS: There were 823 cases of TRAS among 41,867 transplant patients, with an incidence rate of 8.3 (95% CI 7.8-8.9) cases per 1,000 patient-years. Mean time to diagnosis of TRAS was 0.83 + or - 0.81 years after transplant. Factors associated with TRAS were older recipient and donor age, extended criteria donors, induction immunosuppression, delayed graft function, and ischemic heart disease. There was no association of TRAS with deceased donors, prolonged cold ischemia time, acute rejection or cytomegalovirus status. TRAS was associated with increased risk of graft loss (including death; adjusted hazard ratio 2.84, 95% CI 1.70-4.72). Among the 823 patients with TRAS, 145 (17.6%) underwent angioplasty. Graft survival after TRAS was not significantly different in patients treated with angioplasty compared to those without angioplasty. CONCLUSIONS: TRAS is an important complication that predicts adverse patient and graft outcomes. Treatment strategies for TRAS warrant prospective investigation in clinical trials.

Development of a clinical decision model for thyroid nodules.

BACKGROUND: Thyroid nodules represent a common problem brought to medical attention. Four to seven percent of the United States adult population (10-18 million people) has a palpable thyroid nodule, however the majority (>95%) of thyroid nodules are benign. While, fine needle aspiration remains the most cost effective and accurate diagnostic tool for thyroid nodules in current practice, over 20% of patients undergoing FNA of a thyroid nodule have indeterminate cytology (follicular neoplasm) with associated malignancy risk prevalence of 20-30%. These patients require thyroid lobectomy/isthmusectomy purely for the purpose of attaining a definitive diagnosis. Given that the majority (70-80%) of these patients have benign surgical pathology, thyroidectomy in these patients is conducted principally with diagnostic intent. Clinical models predictive of malignancy risk are needed to support treatment decisions in patients with thyroid nodules in order to reduce morbidity associated with unnecessary diagnostic surgery. METHODS: Data were analyzed from a completed prospective cohort trial conducted over a 4-year period involving 216 patients with thyroid nodules undergoing ultrasound (US), electrical impedance scanning (EIS) and fine needle aspiration cytology (FNA) prior to thyroidectomy. A Bayesian model was designed to predict malignancy in thyroid nodules based on multivariate dependence relationships between independent covariates. Ten-fold cross-validation was performed to estimate classifier error wherein the data set was randomized into ten separate and unique train and test sets consisting of a training set (90% of records) and a test set (10% of records). A receiver-operating-characteristics (ROC) curve of these predictions and area under the curve (AUC) were calculated to determine model robustness for predicting malignancy in thyroid nodules. RESULTS: Thyroid nodule size, FNA cytology, US and EIS characteristics were highly predictive of malignancy. Cross validation of the model created with Bayesian Network Analysis effectively predicted malignancy [AUC = 0.88 (95%CI: 0.82-0.94)] in thyroid nodules. The positive and negative predictive values of the model are 83% (95%CI: 76%-91%) and 79% (95%CI: 72%-86%), respectively. CONCLUSION: An integrated predictive decision model using Bayesian inference incorporating readily obtainable thyroid nodule measures is clinically relevant, as it effectively predicts malignancy in thyroid nodules. This model warrants further validation testing in prospective clinical trials.

Assessment of cadaveric organ viability during pulsatile perfusion using infrared imaging.

Assessment of pulsatile perfusion (PP) is limited to measurements of flow (V) and resistance (R). We investigated infrared (IR) imaging during PP as a means for precise organ assessment. IR was used to monitor 10 porcine kidneys during 18 hr of PP in an uncontrolled Donation after Cardiac Death model. An IR camera (Lockheed Martin) was focused on the anterior surfaces of the kidneys. The degree of temperature homogeneity was compared with standard measurements of V and R. IR thermal images correlated with V and R (R=0.92, P<0.001). IR detected an increase in homogeneity during PP by comparing standard deviation differences before and after PP (P=0.002), which was not evident by standard measurements of V and R. Finally, IR assessment allowed for measurement of dynamic changes in perfusion.

Enhanced surgical imaging: laparoscopic vessel identification and assessment of tissue oxygenation.

BACKGROUND: Inherent to minimally invasive procedures are loss of tactile feedback and loss of three-dimensional assessment. Tasks such as vessel identification and dissection are not trivial for the inexperienced laparoscopic surgeon. Advanced surgical imaging, such as 3-charge-coupled device (3-CCD) image enhancement, can be used to assist with these more challenging tasks and, in addition, offers a method to noninvasively monitor tissue oxygenation during operations. STUDY DESIGN: In this study, 3-CCD image enhancement is used for identification of vessels in 25 laparoscopic donor and partial nephrectomy patients. The algorithm is then applied to two laparoscopic nephrectomy patients involving multiple renal arteries. We also use the 3-CCD camera to qualitatively monitor renal parenchymal oxygenation during 10 laparoscopic donor nephrectomies (LDNs). RESULTS: The mean region of interest (ROI) intensity values obtained for the renal artery and vein (68.40 +/- 8.44 and 45.96 +/- 8.65, respectively) are used to calculate a threshold intensity value (59.00) that allows for objective vessel differentiation. In addition, we examined the renal parenchyma during LDNs. Mean ROI intensity values were calculated for the renal parenchyma at two distinct time points: before vessel stapling (nonischemic) and just before extraction from the abdomen (ischemic). The nonischemic mean ROI intensity values are statistically different from the ischemic mean ROI intensity values (p < 0.05), even with short ischemia times. CONCLUSIONS: We have developed a technique, 3-CCD image enhancement, for identification of vasculature and monitoring of parenchymal oxygenation. This technique requires no additional laparoscopic operating room equipment and has real-time video capability.

Assessment of critical renal ischemia with real-time infrared imaging.

BACKGROUND: Currently visual and tactile clues such as color, mottling, and tissue turgor are used in the operating room for subjective assessments of organ ischemia. Studies have demonstrated that infrared (IR) imaging is a reliable tool to identify perfusion of brain tumors and kidneys during human surgery. Intraoperative IR imaging has the potential for more objective real-time detection and quantitative assessment of organ viability including early ischemia. We hypothesize, by detecting variations of the IR signal, we can assess the degree to which renal surface temperature reflects underlying renal ischemia. To address this hypothesis, IR imaging-derived temperature fluctuations were evaluated during laparotomy in a porcine model (n = 15). These temperature profiles then underwent spectral (frequency) analysis to assess their relationship to well-described oscillations of the microcirculation. MATERIALS AND METHODS: An IR camera was positioned 30-60 cm above the exposed kidneys. Images (3-5 mum wavelength) were collected (1.0/s) at baseline, during warm renal ischemia, and during reperfusion. Dominant frequency (DF) of the tissue temperature fluctuations were determined by a Fourier transformation (spectral) analysis. RESULTS: IR images immediately showed which segments of the kidney were ischemic. DF at approximately 0.008 Hz that corresponds to blood flow oscillations was observed in thermal profiles. The oscillations were diminished or disappeared after 25 min of warm ischemia and were recovered with reperfusion in a time-dependent fashion. Oscillations were attenuated substantially in ischemic segments, but not in perfused segments of the kidney. CONCLUSIONS: The described oscillations can be measured noninvasively using IR imaging in the operating room, as represented by the DF, and may be an early marker of critical renal ischemia.

Solid organ transplantation at the National Institutes of Health: development of a research-based transplantation practice.

The National Institutes of Health has established a clinical transplant research program focusing on translational research in kidney transplantation. The program has been developed with a multidisciplinary approach under a common administrative structure that integrates transplant physicians and surgeons with clinical laboratory and data analysis support personnel. The program has achieved excellent clinical outcomes despite focusing exclusively on investigational methods and serving a diverse and medically complex patient population. Novel approaches toward consenting, computer integration, and tissue acquisition have been layered over interventional and observational studies to serve the scientific mission while delivering quality transplant care.