Deficient Generation of Spike-Specific Long-Lived Plasma Cells in the Bone Marrow After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Generation of a stable long-lived plasma cell (LLPC) population is the sine qua non of durable antibody responses after vaccination or infection. We studied 20 individuals with a prior coronavirus disease 2019 infection and characterized the antibody response using bone marrow aspiration and plasma samples. We noted deficient generation of spike-specific LLPCs in the bone marrow after severe acute respiratory syndrome coronavirus 2 infection. Furthermore, while the regression model explained 98% of the observed variance in anti-tetanus immunoglobulin G levels based on LLPC enzyme-linked immunospot assay, we were unable to fit the same model with anti-spike antibodies, again pointing to the lack of LLPC contribution to circulating anti-spike antibodies.

Comprehensive single-cell RNA-seq analysis using deep interpretable generative modeling guided by biological hierarchy knowledge.

Recent advances in microfluidics and sequencing technologies allow researchers to explore cellular heterogeneity at single-cell resolution. In recent years, deep learning frameworks, such as generative models, have brought great changes to the analysis of transcriptomic data. Nevertheless, relying on the potential space of these generative models alone is insufficient to generate biological explanations. In addition, most of the previous work based on generative models is limited to shallow neural networks with one to three layers of latent variables, which may limit the capabilities of the models. Here, we propose a deep interpretable generative model called d-scIGM for single-cell data analysis. d-scIGM combines sawtooth connectivity techniques and residual networks, thereby constructing a deep generative framework. In addition, d-scIGM incorporates hierarchical prior knowledge of biological domains to enhance the interpretability of the model. We show that d-scIGM achieves excellent performance in a variety of fundamental tasks, including clustering, visualization, and pseudo-temporal inference. Through topic pathway studies, we found that d-scIGM-learned topics are better enriched for biologically meaningful pathways compared to the baseline models. Furthermore, the analysis of drug response data shows that d-scIGM can capture drug response patterns in large-scale experiments, which provides a promising way to elucidate the underlying biological mechanisms. Lastly, in the melanoma dataset, d-scIGM accurately identified different cell types and revealed multiple melanin-related driver genes and key pathways, which are critical for understanding disease mechanisms and drug development.

Multiple sclerosis disease activity, a multi-biomarker score of disease activity and response to treatment in multiple sclerosis.

Regular assessment of disease activity in relapsing-remitting multiple sclerosis (RRMS) is required to optimize clinical outcomes. Biomarkers can be a valuable tool for measuring disease activity in multiple sclerosis (MS) if they reflect the pathological processes underlying MS pathogenicity. In this pilot study, we combined multiple biomarkers previously analyzed in RRMS patients into an MS disease activity (MSDA) score to evaluate their ability to predict relapses and treatment response to glatiramer acetate (GA). Response Gene to Complement 32 (RGC-32), FasL, IL-21, SIRT1, phosphorylated SIRT1 (p-SIRT1), and JNK1 p54 levels were used to generate cut-off values for each biomarker. Any value below the cutoff for RGC-32, FasL SIRT1, or p-SIRT1 or above the cutoff for IL-21 or JNK1 p54 was given a +1 value, indicating relapse or lack of response to GA. Any value above the cutoff value for RGC-32, FasL, SIRT1, p-SIRT1 or below that for IL-21 or JNK1 p54 was given a -1 value, indicating clinical stability or response to GA. An MSDA score above +1 indicated a relapse or lack of response to treatment. An MSDA score below -1 indicated clinical stability or response to treatment. Our results showed that the MSDA scores generated using either four or six biomarkers had a higher sensitivity and specificity and significantly correlated with the expanded disability status scale. Although these results suggest that the MSDA test can be useful for monitoring therapeutic response to biologic agents and assessing clinically challenging situations, the present findings need to be confirmed in larger studies.

USP11 promotes prostate cancer progression by up-regulating AR and c-Myc activity.

Androgen receptor (AR) is a main driver for castration-resistant prostate cancer (CRPC). c-Myc is an oncogene underlying prostate tumorigenesis. Here, we find that the deubiquitinase USP11 targets both AR and c-Myc in prostate cancer (PCa). USP11 expression was up-regulated in metastatic PCa and CRPC. USP11 knockdown (KD) significantly inhibited PCa cell growth. Our RNA-seq studies revealed AR and c-Myc as the top transcription factors altered after USP11 KD. ChIP-seq analysis showed that either USP11 KD or replacement of endogenous USP11 with a catalytic-inactive USP11 mutant significantly decreased chromatin binding by AR and c-Myc. We find that USP11 employs two mechanisms to up-regulate AR and c-Myc levels: namely, deubiquitination of AR and c-Myc proteins to increase their stability and deubiquitination of H2A-K119Ub, a repressive histone mark, on promoters of AR and c-Myc genes to increase their transcription. AR and c-Myc reexpression in USP11-KD PCa cells partly rescued cell growth defects. Thus, our studies reveal a tumor-promoting role for USP11 in aggressive PCa through upregulation of AR and c-Myc activities and support USP11 as a potential target against PCa.

Iodine-based dual-energy CT predicts early neurological decline from cerebral edema after large hemispheric infarction.

Background & Purpose: Ischemia affecting two thirds of the MCA territory predicts development of malignant cerebral edema. However, early infarcts are hard to diagnose on conventional head CT. We hypothesize that high-energy (190keV) virtual monochromatic images (VMI) from dual-energy CT (DECT) imaging enables earlier detection of secondary injury from malignant cerebral edema (MCE). Methods: Consecutive LHI patients with NIHSS ≥ 15 and DECT within 10 hours of reperfusion from May 2020 to March 2022 were included. We excluded patients with parenchymal hematoma-type 2 transformation. Retrospective analysis of clinical and novel variables included VMI Alberta Stroke Program Early CT Score (ASPECTS), total iodine content, and VMI infarct volume. Primary outcome was early neurological decline (END). Secondary outcomes included hemorrhagic transformation, decompressive craniectomy (DC), and medical treatment of MCE. Fisher's exact test and Wilcoxon test were used for univariate analysis. Logistic regression was used to develop prediction models for categorical outcomes. Results: Eighty-four LHI patients with a median age of 67.5 [IQR 57,78] years and NIHSS 22 [IQR 18,25] were included. Twenty-nine patients had END. VMI ASPECTS, total iodine content, and VMI infarct volume were associated with END. VMI ASPECTS, VMI infarct volume, and total iodine content were predictors of END after adjusting for age, sex, initial NIHSS, and tPA administration, with a AUROC of 0.691 [0.572,0.810], 0.877 [0.800, 0.954], and 0.845 [0.750, 0.940]. By including all three predictors, the model achieved AUROC of 0.903 [0.84,0.97] and was cross validated by leave one out method with AUROC of 0.827. Conclusion: DECT with high-energy VMI and iodine quantification is superior to conventional CT ASPECTS and is a novel predictor for early neurological decline due to malignant cerebral edema after large hemispheric infarction.

Replacement of Antiretroviral Therapy with HIV Broadly Neutralizing Antibodies to Maximize the Effectiveness of Chemotherapy in HIV Patients with Lung Cancer.

Non-small cell lung cancer (NSCLC) is the most fatal non-AIDS defining cancer in people living with HIV (PWH) on antiretroviral therapy (ART). Treatment of malignancies in PWH requires concomitant cancer therapy and ART, which can lead to potential drug-drug interactions (DDIs) and overlapping toxicities. In this study, we hypothesize that replacement of ART with HIV broadly neutralizing antibodies (bNAbs) during cancer chemotherapy (chemo) may maintain HIV suppression and tumor inhibition while minimizing DDIs and overlapping toxicities. We compared HIV suppression, tumor inhibition, and toxicity between conventional treatment (ART plus chemo) and a new modality (bNAbs plus chemo) in humanized mice. Humanized mice infected with HIVYU2 and xenografted with human NSCLC A549 cells were treated with NSCLC chemo (cisplatin and gemcitabine) and first-line ART (dolutegravir, tenofovir disoproxil difumarate, and emtricitabine) or bNAbs (N49P9.6-FR and PGT 121) at human equivalent drug doses. We monitored plasma HIV RNA, tumor volume, and toxicities over five cycles of chemo. We found that chemo plus ART or bNAbs were equally effective at maintaining suppression of HIV viremia and tumor growth. Comparative analysis showed that mice on ART and chemo had significant reductions in body weight and significant increases in plasma creatinine concentrations compared with mice on bNAbs and chemo, which suggests that a combination of bNAbs and chemo produces less renal toxicity than an ART and chemo combination. These data suggest that bNAb therapy during concomitant chemo may be an improved treatment option over ART for PWH and NSCLC, and possibly other cancers, because bNAbs maintain HIV suppression while minimizing DDIs and toxicities.

SMAD3 promotes expression and activity of the androgen receptor in prostate cancer.

Overexpression of androgen receptor (AR) is the primary cause of castration-resistant prostate cancer, although mechanisms upregulating AR transcription in this context are not well understood. Our RNA-seq studies revealed that SMAD3 knockdown decreased levels of AR and AR target genes, whereas SMAD4 or SMAD2 knockdown had little or no effect. ChIP-seq analysis showed that SMAD3 knockdown decreased global binding of AR to chromatin. Mechanistically, we show that SMAD3 binds to intron 3 of the AR gene to promote AR expression. Targeting these binding sites by CRISPRi reduced transcript levels of AR and AR targets. In addition, ∼50% of AR and SMAD3 ChIP-seq peaks overlapped, and SMAD3 may also cooperate with or co-activate AR for AR target expression. Functionally, AR re-expression in SMAD3-knockdown cells partially rescued AR target expression and cell growth defects. The SMAD3 peak in AR intron 3 overlapped with H3K27ac ChIP-seq and ATAC-seq peaks in datasets of prostate cancer. AR and SMAD3 mRNAs were upregulated in datasets of metastatic prostate cancer and CRPC compared with primary prostate cancer. A SMAD3 PROTAC inhibitor reduced levels of AR, AR-V7 and AR targets in prostate cancer cells. This study suggests that SMAD3 could be targeted to inhibit AR in prostate cancer.

Leveraging Continuous Vital Sign Measurements for Real-Time Assessment of Autonomic Nervous System Dysfunction After Brain Injury: A Narrative Review of Current and Future Applications.

Subtle and profound changes in autonomic nervous system (ANS) function affecting sympathetic and parasympathetic homeostasis occur as a result of critical illness. Changes in ANS function are particularly salient in neurocritical illness, when direct structural and functional perturbations to autonomic network pathways occur and may herald impending clinical deterioration or intervenable evolving mechanisms of secondary injury. Sympathetic and parasympathetic balance can be measured quantitatively at the bedside using multiple methods, most readily by extracting data from electrocardiographic or photoplethysmography waveforms. Work from our group and others has demonstrated that data-analytic techniques can identify quantitative physiologic changes that precede clinical detection of meaningful events, and therefore may provide an important window for time-sensitive therapies. Here, we review data-analytic approaches to measuring ANS dysfunction from routine bedside physiologic data streams and integrating this data into multimodal machine learning-based model development to better understand phenotypical expression of pathophysiologic mechanisms and perhaps even serve as early detection signals. Attention will be given to examples from our work in acute traumatic brain injury on detection and monitoring of paroxysmal sympathetic hyperactivity and prediction of neurologic deterioration, and in large hemispheric infarction on prediction of malignant cerebral edema. We also discuss future clinical applications and data-analytic challenges and future directions.

MNBDR: A Module Network Based Method for Drug Repositioning.

Drug repurposing/repositioning, which aims to find novel indications for existing drugs, contributes to reducing the time and cost for drug development. For the recent decade, gene expression profiles of drug stimulating samples have been successfully used in drug repurposing. However, most of the existing methods neglect the gene modules and the interactions among the modules, although the cross-talks among pathways are common in drug response. It is essential to develop a method that utilizes the cross-talks information to predict the reliable candidate associations. In this study, we developed MNBDR (Module Network Based Drug Repositioning), a novel method that based on module network to screen drugs. It integrated protein-protein interactions and gene expression profile of human, to predict drug candidates for diseases. Specifically, the MNBDR mined dense modules through protein-protein interaction (PPI) network and constructed a module network to reveal cross-talks among modules. Then, together with the module network, based on existing gene expression data set of drug stimulation samples and disease samples, we used random walk algorithms to capture essential modules in disease development and proposed a new indicator to screen potential drugs for a given disease. Results showed MNBDR could provide better performance than popular methods. Moreover, functional analysis of the essential modules in the network indicated our method could reveal biological mechanism in drug response.

Learning and memory retention deficits in prepubertal guinea pigs prenatally exposed to low levels of the organophosphorus insecticide malathion.

High doses of malathion, an organophosphorus (OP) insecticide ubiquitously used in agriculture, residential settings, and public health programs worldwide, induce a well-defined toxidrome that results from the inhibition of acetylcholinesterase (AChE). However, prenatal exposures to malathion levels that are below the threshold for AChE inhibition have been associated with increased risks of neurodevelopmental disorders, including autism spectrum disorder with intellectual disability comorbidity. The present study tested the hypothesis that prenatal exposures to a non-AChE-inhibiting dose of malathion are causally related to sex-biased cognitive deficits later in life in a precocial species. To this end, pregnant guinea pigs were injected subcutaneously with malathion (20 mg/kg) or vehicle (peanut oil, 0.5 ml/kg) once daily between approximate gestational days 53 and 63. This malathion dose regimen caused no significant AChE inhibition in the brain or blood of dams and offspring and had no significant effect on the postnatal growth of the offspring. Around postnatal day 30, locomotor activity and habituation, a form of non-associative learning, were comparable between malathion- and peanut oil-exposed offspring. However, in the Morris water maze, malathion-exposed offspring presented significant sex-dependent spatial learning deficits in addition to memory impairments. These results are far-reaching as they indicate that: (i) malathion is a developmental neurotoxicant and (ii) AChE inhibition is not an adequate biomarker to derive safety limits of malathion exposures during gestation. Continued studies are necessary to identify the time and dose dependence of the developmental neurotoxicity of malathion and the mechanisms underlying the detrimental effects of this insecticide in the developing brain.

The Role of Crosstalk between AR3 and E2F1 in Drug Resistance in Prostate Cancer Cells.

BACKGROUND: Drug resistance is one of the most prevalent causes of death in advanced prostate cancer patients. Combination therapies that target cancer cells via different mechanisms to overcome resistance have gained increased attention in recent years. However, the optimal drug combinations and the underlying mechanisms are yet to be fully explored. AIM AND METHODS: The aim of this study is to investigate drug combinations that inhibit the growth of drug-resistant cells and determine the underlying mechanisms of their actions. In addition, we also established cell lines that are resistant to combination treatments and tested new compounds to overcome the phenomenon of double drug-resistance. RESULTS: Our results show that the combination of enzalutamide (ENZ) and docetaxel (DTX) effectively inhibit the growth of prostate cancer cells that are resistant to either drug alone. The downregulation of transcription factor E2F1 plays a crucial role in cellular inhibition in response to the combined therapy. Notably, we found that the androgen receptor (AR) variant AR3 (a.k.a. AR-V7), but not AR full length (AR-FL), positively regulates E2F1 expression in these cells. E2F1 in turn regulates AR3 and forms a positive regulatory feedforward loop. We also established double drug-resistant cell lines that are resistant to ENZ+DTX combination therapy and found that the expression of both AR3 and E2F1 was restored in these cells. Furthermore, we identified that auranofin, an FDA-approved drug for the treatment of rheumatoid arthritis, overcame drug resistance and inhibited the growth of drug-resistant prostate cancer cells both in vitro and in vivo. CONCLUSION AND SIGNIFICANCE: This proof-of-principle study demonstrates that targeting the E2F1/AR3 feedforward loop via a combination therapy or a multi-targeting drug could circumvent castration resistance in prostate cancer.

Complications associated with the current sequential pharmacological management of early postnatal hypotension in extremely premature infants.

Early postnatal hypotension in premature infants is treated with escalating doses of vasopressor-inotropes (VI), followed by hydrocortisone if VI therapy fails. The adverse effects of this standard clinical practice have not been well reported. In a retrospective case-control study, we compared the complications associated with VI and hydrocortisone (HCVI) treatments in extremely low-birth-weight infants (≤1000 g) with contemporaneous normotensive medication-naïve controls via standard univariate and multivariate analyses. Birth weight, gestational age, and receipt of antenatal steroids did not differ between VI (n = 74) and control (n = 124) groups, while the occurrence of gestational diabetes mellitus and risks for patent ductus arteriosus, intraventricular-periventricular hemorrhage, spontaneous intestinal perforation, ventriculomegaly, and bronchopulmonary dsyplasia were higher in VI. Infants in the HCVI group (n = 69) had lower birth weight, gestational age, and receipt of antenatal steroids and higher risks for intraventricular-periventricular hemorrhage, bronchopulmonary dysplasia, air leaks, and patent ductus arteriosus than controls. Whereas the occurrences of spontaneous intestinal perforation, ventriculomegaly, and maternal diabetes mellitus did not differ, that of maternal hypertension trended to be lower in HCVI recipients (P = 0.06). In conclusion, hypotensive extremely low-birth-weight infants treated with VI or with HCVI are susceptible to intraventricular-periventricular hemorrhage, bronchopulmonary dysplasia, and patent ductus arteriosus. Furthermore, those who receive inotropes are at risk for spontaneous intestinal perforation and ventriculomegaly. Maternal diabetes mellitus increases the occurrence of hypotension, which responds to VI. Maternal hypertension does not contribute to VI responsive and tends to decrease the occurrence of VI-refractory hypotension.

Current policies and practicing surgeon perspectives on parental leave.

BACKGROUND: The aim of this study is to evaluate the components of current parental leave policies in surgical practice and evaluate surgeon perceptions of parental leave. METHODS: Practicing surgeons were recruited to complete a survey via social media outlets and e-mail. Participants were asked questions regarding existing policies and their perspectives towards parental leave. RESULTS: The survey was completed by 431 surgeons, of which 90% were female and 45% in academics. The majority (84%) of women took <12 weeks leave, and 24% were fully funded. All male respondents took <4 weeks, of which 55% was fully paid. Discrimination was experienced by 31%. The majority support paid parental leave (94%) without impact on time to promotion (87%) or partnership (85%). CONCLUSIONS: There is variance in current parental leave policies regarding length and compensation. Most respondents support paid parental leave and are in favor of policies that support new parents during and after pregnancy.

Percentage of Mortal Encounters Transferred in Emergency General Surgery.

BACKGROUND: Despite the frequent occurrence of interhospital transfers in emergency general surgery (EGS), rates of transfer of complications are undescribed. Improved understanding of hospital transfer patterns has a multitude of implications, including quality measurement. The objective of this study was to describe individual hospital transfer rates of mortal encounters. MATERIALS AND METHODS: A retrospective review was undertaken from 2013 to 2015 of the Maryland Health Services Cost Review Commission database. Two groups of EGS encounters were identified: encounters with death following transfer and encounters with death without transfer. The percentage of mortal encounters transferred was defined as the percentage of EGS hospital encounters with mortality initially presenting to a hospital transferred to another hospital before death at the receiving hospital. RESULTS: Overall, 370,242 total EGS encounters were included, with 17,003 (4.6%) of the total EGS encounters with mortality. Encounters with death without transfer encompassed 15,604 (91.8%) of mortal EGS encounters and encounters with death following transfer 1399 (8.2%). EGS disease categories of esophageal varices or perforation, necrotizing fasciitis, enterocutaneous fistula, and pancreatitis had over 10% of these total mortal encounters with death following transfer. For individual hospitals, percentage of mortal encounters transferred ranged from 0.8% to 35.2%. The percentage of mortal encounters transferred was inversely correlated with annual EGS hospital volume for all state hospitals (P < 0.001, r = -0.57). CONCLUSIONS: Broad variability in individual hospital practices exists for mortality transferred to other institutions. Application of this knowledge of percentage of mortal encounters transferred includes consideration in hospital quality metrics.

Interhospital Transfers with Wide Variability in Emergency General Surgery.

Interhospital transfer of emergency general surgery (EGS) patients is a common occurrence. Modern individual hospital practices for interhospital transfers have unknown variability. A retrospective review of the Maryland Health Services Cost Review Commission database was undertaken from 2013 to 2015. EGS encounters were divided into three groups: encounters not transferred, encounters transferred from a hospital, and encounters transferred to a hospital. In total, 380,405 EGS encounters were identified, including 12,153 (3.2%) encounters transferred to a hospital, 10,163 (2.7%) encounters transferred from a hospital, and 358,089 (94.1%) encounters not transferred. For individual hospitals, percentage of encounters transferred to a hospital ranged from 0 to 30.05 per cent, encounters transferred from a hospital from 0.02 to 14.62 per cent, and encounters not transferred from 69.25 to 99.95 per cent of total encounters at individual hospitals. Percentage of encounters transferred from individual hospitals was inversely correlated with annual EGS hospital volume (P < 0.001, r = -0.59), whereas percentage of encounters transferred to individual hospitals was directly correlated with annual EGS hospital volume (P < 0.001, r = 0.51). Individual hospital practices for interhospital transfer of EGS patients have substantial variability. This is the first study to describe individual hospital interhospital transfer practices for EGS.

Cadaver-Based Trauma Procedural Skills Training: Skills Retention 30 Months after Training among Practicing Surgeons in Comparison to Experts or More Recently Trained Residents.

BACKGROUND: Long-term retention of trauma procedural core-competency skills and need for re-training after a 1-day cadaver-based course remains unknown. We measured and compared technical skills for trauma core competencies at mean 14 months (38 residents), 30 months (35 practicing surgeons), and 46 months (10 experts) after training to determine if skill degradation occurs with time. Technical performance during extremity vascular exposures and lower-extremity fasciotomy in fresh cadavers measured by validated individual procedure score (IPS) was the primary outcome. STUDY DESIGN: We performed a prospective study between May 2013 and September 2016. RESULTS: Practicing surgeons had lower IPS and IPS component scores (p = 0.02 to 0.001) than residents (p < 0.05) and experts (p < 0.002) for vascular procedures. Frequencies of errors were no different among residents and experts. Practicing surgeons made more critical errors (p < 0.05) than experts or residents. Experts had shortest time to proximal vascular control. Fasciotomy procedural errors occurred in all participants. Cluster analysis of anatomy vs procedural steps identified tertiles of performance and wide variance (32.5% practicing surgeons, 26.5% residents vs 13% experts) for vascular procedures. Vascular control duration > 20 minutes (n = 21) and failure to decompress fasciotomy compartments were correlated with incorrect landmarks and skin incisions. Modeling found interval trauma skills experience, not time since training, was associated with lower IPS. CONCLUSIONS: Practicing surgeons with low trauma skills experience since training had lower IPS and component scores (p = 0.02 to 0.001) and more errors compared with experts and residents (p < 0.05). Surgeons, including experts with low interval experience performing trauma procedures, may benefit from refreshing of correct landmarks and skin incision placement identification.

Assessment of Anatomical Knowledge and Core Trauma Competency Vascular Skills.

Objectives: Surgical residents express confidence in performing specific vascular exposures before training, but such self-reported confidence did not correlate with co-located evaluator ratings. This study reports residents' self-confidence evaluated before and after Advanced Surgical Skills for Exposure in Trauma (ASSET) cadaver-based training, and 12-18 mo later. We hypothesize that residents will better judge their own skill after ASSET than before when compared with evaluator ratings. Methods: Forty PGY2-7 surgical residents performed four procedures: axillary artery (AA), brachial artery (BA), femoral artery exposure and control (FA), and lower extremity fasciotomy (FAS) at the three evaluations. Using 5-point Likert scales, surgeons self-assessed their confidence in anatomical understanding and procedure performance after each procedure and evaluators rated each surgeon accordingly. Results: For all the three evaluations, residents consistently rated their anatomical understanding (p < 0.04) and surgical performance (p < 0.03) higher than evaluators for both FA and FAS. Residents rated their anatomical understanding and surgical performance higher (p < 0.005) than evaluators for BA after training and up to 18 mo later. Only for third AA evaluation were there no rating differences. Conclusions: Residents overrate their anatomical understanding and performance abilities for BA, FA, and FAS even after performing the procedures and being debriefed three times in 18 mo.

Head-camera video recordings of trauma core competency procedures can evaluate surgical resident's technical performance as well as colocated evaluators.

BACKGROUND: Unbiased evaluation of trauma core competency procedures is necessary to determine if residency and predeployment training courses are useful. We tested whether a previously validated individual procedure score (IPS) for individual procedure vascular exposure and fasciotomy (FAS) performance skills could discriminate training status by comparing IPS of evaluators colocated with surgeons to blind video evaluations. METHODS: Performance of axillary artery (AA), brachial artery (BA), and femoral artery (FA) vascular exposures and lower extremity FAS on fresh cadavers by 40 PGY-2 to PGY-6 residents was video-recorded from head-mounted cameras. Two colocated trained evaluators assessed IPS before and after training. One surgeon in each pretraining tertile of IPS for each procedure was randomly identified for blind video review. The same 12 surgeons were video-recorded repeating the procedures less than 4 weeks after training. Five evaluators independently reviewed all 96 randomly arranged deidentified videos. Inter-rater reliability/consistency, intraclass correlation coefficients were compared by colocated versus video review of IPS, and errors. Study methodology and bias were judged by Medical Education Research Study Quality Instrument and the Quality Assessment of Diagnostic Accuracy Studies criteria. RESULTS: There were no differences (p ≥ 0.5) in IPS for AA, FA, FAS, whether evaluators were colocated or reviewed video recordings. Evaluator consistency was 0.29 (BA) - 0.77 (FA). Video and colocated evaluators were in total agreement (p = 1.0) for error recognition. Intraclass correlation coefficient was 0.73 to 0.92, dependent on procedure. Correlations video versus colocated evaluations were 0.5 to 0.9. Except for BA, blinded video evaluators discriminated (p < 0.002) whether procedures were performed before training versus after training. Study methodology by Medical Education Research Study Quality Instrument criteria scored 15.5/19, Quality Assessment of Diagnostic Accuracy Studies 2 showed low bias risk. CONCLUSION: Video evaluations of AA, FA, and FAS procedures with IPS are unbiased, valid, and have potential for formative assessments of competency. LEVEL OF EVIDENCE: Prognostic study, level II.

Performance of Vascular Exposure and Fasciotomy Among Surgical Residents Before and After Training Compared With Experts.

Importance: Surgical patient outcomes are related to surgeon skills. Objective: To measure resident surgeon technical and nontechnical skills for trauma core competencies before and after training and up to 18 months later and to compare resident performance with the performance of expert traumatologists. Design, Setting, and Participants: This longitudinal study performed from May 1, 2013, through February 29, 2016, at Maryland State Anatomy Board cadaver laboratories included 40 surgical residents and 10 expert traumatologists. Interventions: Performance was measured during extremity vascular exposures and lower extremity fasciotomy in fresh cadavers before and after taking the Advanced Surgical Skills for Exposure in Trauma (ASSET) course. Main Outcomes and Measures: The primary outcome variable was individual procedure score (IPS), with secondary outcomes of IPSs on 5 components of technical and nontechnical skills, Global Rating Scale scores, errors, and time to complete the procedure. Two trained evaluators located in the same laboratory evaluated performance with a standardized script and mobile touch-screen data collection. Results: Thirty-eight (95%) of 40 surgical residents (mean [SD] age, 31 [2.9] years) who were evaluated before and within 4 weeks of ASSET training completed follow-up evaluations 12 to 18 months later (mean [SD], 14 [2.7] months). The experts (mean [SD] age, 52 [10.0] years) were significantly older and had a longer (mean [SD], 46 [16.3] months) interval since taking the ASSET course (both P < .001). Overall resident cohort performance improved with increased anatomy knowledge, correct procedural steps, and decreased errors from 60% to 19% after the ASSET course regardless of clinical year of training (P < .001). For 21 of 40 residents (52%), correct vascular procedural steps plotted against anatomy knowledge (the 2 IPS components most improved with training) indicates the resident's performance was within 1 nearest-neighbor classifier of experts after ASSET training. Five residents had no improvement with training. The Trauma Readiness Index for experts (mean [SD], 74 [4]) was significantly different compared with the trained residents (mean [SD], 48 [7] before training vs 63 [7] after training [P = .004] and vs 64 [6] 14 months later [P = .002]). Critical errors that might lead to patient death were identified by pretraining IPS decile of less than 0.5. At follow-up, frequency of resident critical errors was no different from experts. The IPSs ranged from 31.6% to 76.9% among residents for core trauma competency procedures. Modeling revealed that interval experience, rather than time since training, affected skill retention up to 18 months later. Only 4 experts and 16 residents (40%) adequately decompressed and confirmed entry into all 4 lower extremity compartments. Conclusions and Relevance: This study found that ASSET training improved resident procedural skills for up to 18 months. Performance was highly variable. Interval experience after training affected performance. Pretraining skill identified competency of residents vs experts. Extremity vascular and fasciotomy performance evaluations suggest the need for specific anatomical training interventions in residents with IPS deciles less than 0.5.