bluuebunny/crossref_metadata_2025 huggingface dataset:
Tibial spine avulsion fractures: treatment update
Authors: Tuca Maria , Bernal Nazira , Luderowski Eva , Green Daniel W.
Published: December 2018

Purpose of review

The purpose of this review is to summarize and clarify the current framework for treating tibial spine avulsion fractures (TSAFs). We will discuss how these fractures are classified both on plain radiographs and MRI as well as report the incidence of concomitant soft tissue injury, an important consideration that guides treatment. We will also compare guidelines for nonsurgical versus surgical treatment and summarize frequently used surgical techniques. Finally, we will review outcomes following treatment, including common complications.

Recent findings

Although TSAFs only constitute 2–5% of all pediatric knee injuries, the incidence is increasing. A recently developed MRI-based system for evaluating TSAFs is another tool that aids in the treatment of these injuries.

TSAFs can be classified using plain radiographs as well as MRI. Type I fractures are usually treated with immobilization whereas type II fractures typically undergo an initial attempt at closed reduction followed by arthroscopic or open reduction and fixation if needed. Type III fractures are indicated directly for arthroscopic surgery and both suture and screw fixation produce good clinical outcomes. All-epiphyseal or transphyseal approaches can minimize the risk of physeal injury in skeletally immature patients. Common complications following TSAF injury and treatment are residual laxity, knee stiffness, and nonunion or malunion.
Preparing Chief Nurse Successors
Authors: Batcheller Joyce , Yoder Linda H. , Yoder-Wise Patricia S. , Williams Samantha
Published: December 2018

The traditional role of the chief nursing officer (CNO) is expanding to include new clinical areas and patient populations. Chief nursing officers find themselves challenged to balance both system and site priorities, compounded with the expectation to lead their organization during a merger, acquisition, or hospital closure and the changes in healthcare reimbursement. Chief nursing officers must anticipate emerging issues and be prepared to manage those issues. They are at high risk politically when a new chief executive officer is named and when hospitals are having financial concerns. How do we lead in times of turbulence? How can we ensure that high-potential candidates are prepared for the CNO role and what are the most critical competencies they will need? To address these concerns, we created a Chief Nursing Officer Academy (CNOA) that is designed for new and aspiring CNOs. This article provides an overview of the CNOA and a program evaluation of the outcomes for the participants.
Mortality Risk in Homebound Older Adults Predicted From Routinely Collected Nursing Data
Authors: Sullivan Suzanne S. , Hewner Sharon , Chandola Varun , Westra Bonnie L.
Published: December 2018

Background

Newer analytic approaches for developing predictive models provide a method of creating decision support to translate findings into practice.

Objectives

The aim of this study was to develop and validate a clinically interpretable predictive model for 12-month mortality risk among community-dwelling older adults. This is done by using routinely collected nursing assessment data to aide homecare nurses in identifying older adults who are at risk for decline, providing an opportunity to develop care plans that support patient and family goals for care.

Methods

A retrospective secondary analysis of Medicare and Medicaid data of 635,590 Outcome and Assessment Information Set (OASIS-C) start-of-care assessments from January 1, 2012, to December 31, 2012, was linked to the Master Beneficiary Summary File (2012–2013) for date of death. The decision tree was benchmarked against gold standards for predictive modeling, logistic regression, and artificial neural network (ANN). The models underwent k-fold cross-validation and were compared using area under the curve (AUC) and other data science metrics, including Matthews correlation coefficient (MCC).

Results

Decision tree variables associated with 12-month mortality risk included OASIS items: age, (M1034) overall status, (M1800–M1890) activities of daily living total score, cancer, frailty, (M1410) oxygen, and (M2020) oral medication management. The final models had good discrimination: decision tree, AUC = .71, 95% confidence interval (CI) [.705, .712], sensitivity = .73, specificity = .58, MCC = .31; ANN, AUC = .74, 95% CI [.74, .74], sensitivity = .68, specificity = .68, MCC = .35; and logistic regression, AUC = .74, 95% CI [.735, .742], sensitivity = .64, specificity = .70, MCC = .35.

Discussion

The AUC and 95% CI for the decision tree are slightly less accurate than logistic regression and ANN; however, the decision tree was more accurate in detecting mortality. The OASIS data set was useful to predict 12-month mortality risk. The decision tree is an interpretable predictive model developed from routinely collected nursing data that may be incorporated into a decision support tool to identify older adults at risk for death.
Determinants of Dual-Task Training Effect Size in Parkinson Disease: Who Will Benefit Most?
Authors: Strouwen Carolien , Molenaar Esther A. L. M. , Münks Liesbeth , Broeder Sanne , Ginis Pieter , Bloem Bastiaan R. , Nieuwboer Alice , Heremans Elke
Published: December 2018

Background and Purpose:

Dual-task interventions show positive effects in people with Parkinson disease (PD), but it remains unclear which factors determine the size of these benefits. As a secondary analysis of the DUALITY trial, the aim of this study was to assess the determinants of the effect size after 2 types of dual-task practice.

Methods:

We randomly allocated 121 participants with PD to receive either integrated or consecutive dual-task training. Dual-task walking performance was assessed during (i) a backward digit span task (digit), (ii) an auditory Stroop task (Stroop), and (iii) a functional mobile phone task. Baseline descriptive, motor, and cognitive variables were correlated with the change in dual-task gait velocity after the intervention. Factors correlated with the change in dual-task gait velocity postintervention (P < 0.20) were entered into a stepwise forward multiple linear regression model.

Results:

Lower dual-task gait velocity and higher cognitive capacity (Scales for Outcomes in Parkinson's Disease-Cognition [ScopaCog]) at baseline were related to larger improvements in dual-task gait velocity after both integrated and consecutive dual-task training for all 3 tasks (β[gait] = −0.45, β[ScopaCog] = 0.34, R
2 = 0.23, P < 0.001, for digit; β[gait] = −0.52, β[ScopaCog] = 0.29, R
2 = 0.26, P < 0.001, for Stroop; and β[gait] = −0.40, β[ScopaCog] = 0.30, R
2 = 0.18, P < 0.001, for mobile phone task).

Discussion and Conclusions:

Participants with PD who showed a slow dual-task gait velocity and good cognitive functioning at baseline benefited most from the dual-task training, irrespective of the type of training and type of dual-task outcome.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A242).
Auditory Cueing for Gait Impairment in Persons With Parkinson Disease: A Pilot Study of Changes in Response With Disease Progression
Authors: Lirani-Silva Ellen , Lord Sue , Moat Dionne , Rochester Lynn , Morris Rosie
Published: December 2018

Background and Purpose:

Gait impairments in persons with Parkinson disease (PD) are difficult to manage. Auditory cueing has been shown to be an effective therapy. However, the optimal time to introduce cues with respect to disease stage has not yet been established. This longitudinal study examines the effect of auditory cues on gait characteristics in people with early PD at 2 time points, 3 years apart.

Methods:

We assessed 25 people with PD from the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation-Parkinson's disease (ICICLE-PD) study. Participants walked with and without an auditory cue set at individual cadence. Characteristics of step velocity, step length, step time, step length variability, and step time variability were collected using an instrumented walkway. In a subset of 9 participants with PD, all assessments were repeated 3 years later. Twenty-nine healthy older adults were assessed at 1 time point to provide comparison data.

Results:

At baseline, independent of group, step velocity, step length, and step time improved with auditory cue; however, there was an increase in step time variability, indicating a worsening of gait with the cue. Three years later, in the smaller subset the response to cue was improved, demonstrated by increased step velocity and length but step time variability was no longer increased.

Discussion and Conclusions:

This pilot study indicates that people with early PD have small benefits from auditory cues and the benefit increases as disease progresses. Early in disease the benefit of cue may come at the cost of increased variability. Therefore, the time to introduce an auditory cue in PD rehabilitation may be important to optimize therapeutic effect.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A243).
Symmetrical Apophyses on the Posterior Margins of the Thyroid Cartilage
Authors: Porzionato Andrea , Macchi Veronica , Mazzarolo Cristina , Morra Aldo , Sanudo Jose , De Caro Raffaele
Published: December 2018

Differential diagnosis between normal/variant anatomy and pathological/traumatic findings represents one of the main matters of investigation of the so-called forensic clinical anatomy. In the literature, many anatomical variations of the laryngeal thyroid cartilage have been reported, with potential implications in forensic pathology. They include triticeal cartilages, foramen thyroideum, asymmetry, segmentation or agenesis of the superior thyroid horns, bone connections with the hyoid bone, absence of cricothyroid facets, hypertrophy of the inferior thyroid tubercle, and asymmetries in the thyroid notch, isthmus, or length of the inferior horn. In this report, we describe a laryngeal anatomical variation never described before, consisting of 2 apophyses symmetrically arising from the posterior margins of the thyroid laminae. Postmortem computed tomography performed on the laryngeal visceral block excluded previous traumatic injuries or natural pathologies of the laryngeal cartilages, confirming the congenital origin of the finding. An “omega epiglottis” and 3 laryngeal cysts in the piriform sinuses also coexisted, suggesting the possibility of underlying common developmental mechanisms.
Immunoreactivity for Sox10 in Basaloid Neoplasms of The Skin
Authors: Bush James W. , Gru Alejandro A. , Wick Mark R.
Published: December 2018

Basaloid tumors of the skin pose a diagnostic challenge to pathologists, because the differential diagnosis is broad, sometimes with subtle differentiating features. We evaluated SOX10 expression in 120 primary cutaneous tumors with epidermal, sweat glandular, neuroendocrine/neuroectodermal, follicular, and sebaceous lineages. Our findings were compared with those of previous studies that evaluated SOX10 in tumors of the skin. SOX10 staining was seen in the majority of sweat gland tumors with the exception of syringoma and microcystic adnexal carcinoma. There were no immunoreactive cases among epidermal, neuroendocrine/neuroectodermal, follicular, or sebaceous tumors. These findings are comparable to reported in previous studies, and show SOX10 can be a useful adjunct in the differential diagnosis of nodular basaloid skin tumors. That marker has less utility in the assessment of sclerosing basaloid cutaneous neoplasms, because such tumors are almost uniformly nonreactive for it.
Criteria for Clinically Relevant Bleeding in Critically Ill Children: An International Survey*
Authors: Karam Oliver , Nellis Marianne E. , Zantek Nicole D. , Lacroix Jacques , Faustino E. Vincent S.
Published: December 2018

Objectives:

Bleeding, a feared complication of critical illness, is frequent in critically ill children. However, the concept of clinically relevant bleeding is ill-defined in this population. There are many established diagnostic criteria for bleeding, but only one estimates bleeding in critically ill adults, and none exist for critically ill children. Our objective was to identify the factors that influence pediatric intensivists’ perception of clinically relevant bleeding.

Design:

Self-administered, web-based survey with 9-point Likert scales, to qualify the clinical significance of 103 bleeding characteristics in critically ill children.

Setting:

Online survey.

Subjects:

Pediatric critical care physicians and nurse practitioners.

Interventions:

None.

Measurements and Main Results:

The response rate was 40%, with 225 respondents from 16 countries. Characteristics most frequently identified as clinically relevant were bleeding in critical locations (e.g., pericardium, pleural space, CNS, and lungs); requiring interventions; leading to physiologic repercussions, including organ failure; and of prolonged duration. Quantifiable bleeding greater than 5 mL/kg/hr for more than 1 hour was frequently considered clinically relevant. Respondents identified the following characteristics as clinically irrelevant: dressings required to be changed no less frequently than every 6 hours, streaks of blood in gastric tubes, streaks of blood in endotracheal tubes or blood in endotracheal tubes only during suctioning, lightly blood-tinged urine, quantifiable bleeding less than 1 mL/kg/hr, and noncoalescing petechiae. Perception of the clinical relevance of bleeding was not associated with the respondent’s geographical location of clinical practice or years of experience.

Conclusions:

This international survey provides a better understanding of the factors that influence the pediatric intensivists’ assessment of the clinical relevance of bleeding in critically ill children. It provides the foundation for the development of a validated, diagnostic definition of clinically relevant bleeding in this population.
Matching into Integrated Plastic Surgery: The Value of Research Fellowships
Authors: Mehta Karan , Sinno Sammy , Thanik Vishal , Weichman Katie , Janis Jeffrey E. , Patel Ashit
Published: December 2018

Background:

Integrated plastic surgery residency applicants sometimes complete research fellowships before residency. The average productivity and the impact of these fellowships on subsequent application to residency are unknown. The purpose of this study was to provide objective data to better understand the utility and productivity of a research fellowship.

Methods:

A national survey was conducted in which integrated plastic surgery residency applicants from 2013 to 2016 were surveyed regarding their experiences with research fellowships. American Council of Academic Plastic Surgeons members were also surveyed to elicit their perspectives on the value of these fellowships.

Results:

Six hundred twenty-one integrated plastic surgery applicants from 2013 to 2016 were included in the study. Twenty-five percent of applicants participated in a research fellowship. Applicants who completed research fellowships were more likely to match into plastic surgery compared to those who did not (97 percent versus 81 percent, respectively; p < 0.05). Fellows were highly satisfied with their fellowship experience and produced an average of five publications and presentations per fellowship year. Sixty-three percent of research fellowships were performed to strengthen applications to categorical integrated plastic surgery residency. American Council of Academic Plastic Surgeons members considered three or four publications/presentations productive. Most do not recommend research fellowships to all medical students.

Conclusions:

Research fellowships can effectively prepare for categorical plastic surgery by improving publication and presentation experience. This is the first study to show that applicants who completed research fellowships were highly satisfied with their experience, accomplished higher than expected levels of productivity, and statistically significantly matched into an integrated plastic surgery residency more often than applicants without research fellowships.
Analysis of Keloid Response to 5-Fluorouracil Treatment and Long-Term Prevention of Keloid Recurrence
Authors: LaRanger Ryan , Karimpour-Fard Anis , Costa Christopher , Mathes David , Wright Woodring E. , Chong Tae
Published: December 2018

Keloids are benign fibroproliferative skin tumors that can cause disfigurement and disability. Although they frequently recur after excision or medical management and can affect 6 to 16 percent of African Americans, there is no gold standard therapy. Keloids are challenging to study because there are no animal or in vitro models of this disorder. This makes it very difficult to validate data from treated tissue samples or cells and develop targeted therapies for this disease. In this study, the authors demonstrate that intralesional 5-fluorouracil injection after keloid excision prevents recurrence for 2 years, with no reported adverse events. The authors analyze the expression of treated and untreated biopsy specimens of the same keloids in their native context to capture insights that may be missed by in vitro cell culture models and correct for intrakeloid variability. Random forest analysis of the microarray data dramatically increased the statistical power of the authors’ results, permitting hypothesis-free creation of a gene expression profile of 5-fluorouracil–treated keloids. Through this analysis, the authors found a set of genes, including YAP1 and CCL-2, whose expression changes predict 5-fluorouracil therapy status and include genes that have not previously been associated with keloid biology and are of unknown function. The authors further describe keloid heterogeneity for the first time using multidimensional analysis of their microarray results. The methods and tools the authors developed in this research may overcome some of the challenges in studying keloids and developing effective treatments for this disease.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Muscle-Derived Stem Cell–Enriched Scaffolds Are Capable of Enhanced Healing of a Murine Volumetric Muscle Loss Defect
Authors: Wang Howard D. , Lough Denver M. , Kurlander David E. , Lopez Joseph , Quan Amy , Kumar Anand R.
Published: December 2018

Background:

Volumetric muscle loss secondary to traumatic or surgical causes can lead to functional and aesthetic impairments. The authors hypothesize that an implantable muscle-derived stem cell–enriched collagen scaffold could significantly augment muscle regeneration in a murine model of volumetric muscle loss.

Methods:

Murine muscle-derived stem cells were isolated using a modified preplating technique and seeded onto type 1 collagen scaffolds to create the muscle-derived stem cell–enriched collagen scaffolds. Murine rectus femoris defects of 5 mm were created and randomized to one of three conditions (n = 6 per group): untreated controls, collagen scaffold only, and muscle-derived stem cell–enriched collagen scaffolds. In vivo muscle healing was quantified using micro–computed tomography. Muscle explants were analyzed using standard histology and whole-mount immunofluorescence at 8 weeks.

Results:

In vivo experiments demonstrated significantly greater quadriceps cross-sectional area in the muscle-derived stem cell–enriched collagen scaffold group compared with controls on micro–computed tomography (0.74 ± 0.21 versus 0.55 ± 0.06 versus 0.49 ± 0.04 ratio of experimental to naive quadriceps cross-sectional area; p < 0.05). Muscle explants of the muscle-derived stem cell–enriched collagen scaffold group demonstrated significantly higher cellular density compared with controls (1185 ± 360 versus 359 ± 62 versus 197 ± 68 nuclei/high-power field; p < 0.01). Immunofluorescence for laminin and myosin heavy chain confirmed formation of organized muscle fibers within the defect of the muscle-derived stem cell–enriched collagen scaffold group only. However, appreciable confocal colocalization of myosin heavy chain with green fluorescent protein expression was low.

Conclusions:

The results of this study indicate that muscle-derived stem cell–enriched scaffolds significantly improved skeletal muscle regeneration in a murine muscle defect model. Based on the low fluorescent colocalization, host progenitor cells appear to contribute significantly to intradefect myogenesis, suggesting that deployment of a viable muscle-derived stem cell–enriched scaffold stimulates a regenerative mitogen response in native tissues.
Superficial Circumflex Iliac Artery Perforator Flap: An Anatomical Study of the Correlation of the Superficial and the Deep Branches of the Artery and Evaluation of Perfusion from the Deep Branch to the Sartorius Muscle and the Iliac Bone
Authors: Yoshimatsu Hidehiko , Steinbacher Johannes , Meng Stefan , Hamscha Ulrike M. , Weninger Wolfgang J. , Tinhofer Ines E. , Harima Mitsunobu , Fuse Yuma , Yamamoto Takumi , Tzou Chieh Han John
Published: December 2018

Background:

Harvesting the sartorius muscle and the iliac bone with a superficial circumflex iliac artery (SCIA) perforator flap can be a challenging procedure. The aim of this study was to describe the anatomical topology of the deep branch of the SCIA in fresh cadavers, which has not been reported in detail.

Methods:

Twenty groin regions from 10 fresh cadavers were dissected. The characteristics and landmarks of the SCIA system, including branches to the sartorius muscle and the iliac bone, were examined. Perfusion of the sartorius muscle and the iliac bone by means of the deep branch of the SCIA was evaluated with indocyanine green angiography and computed tomographic angiography.

Results:

The superficial and the deep branches were identifiable in all specimens. In 85 percent of the specimens, the bifurcation point could be seen within 2 cm from a fixed site: 6 cm from the pubic tubercle to the anterior superior iliac spine, and 3 cm caudal from that point. The deep branch in each case gave off branches to the sartorius muscle and the iliac bone. The cephalad portion of the sartorius muscle (up to 8 cm from the anterior superior iliac spine) and the superficial portion of the iliac bone (up to 1.5 cm from the iliac crest) were perfused by the deep branch of the SCIA.

Conclusions:

In all specimens, both the superficial branch and the deep branch of the SCIA were found. The deep branch was found consistently to give off perfusing branches to the sartorius muscle and the iliac bone.
Ultralow Dose Dynamic Expiratory Computed Tomography for Evaluation of Tracheomalacia
Authors: Cohen Stuart L. , Ben-Levi Eran , Karp Jason B. , Lazzaro Richard S. , Shah Amar , Rahmani Navid , Shah Rakesh D.
Published: December 2018

Objective

The aim of this study was to determine the average effective radiation dose and feasibility of ultralow dose dynamic expiratory computed tomography (CT) for evaluation of tracheomalacia (ULD) and to evaluate factors that impact image quality.

Methods

This is a retrospective study of 64 consecutive patients from September to October 2016 for the evaluation of tracheomalacia. All studies were performed with routine inspiration chest CT followed by ULD z(kilovoltage peak (kVp) 80, 100, or 120 and fixed milliamperage 10) or typical dose CT (TD) (kVp 100 or 120 with automated milliamperage) dynamic expiration CT. Image quality was considered diagnostic if the trachea area could be accurately measured for tracheomalacia assessment, and diagnostic studies were graded fair, good, or excellent. Scan length, image quality, and effective radiation dose were compared for ULD versus TD and ULD at 100 kVp versus ULD at 80 kVp. For ULD studies, patient factors were compared across image quality.

Results

The ULD had a mean effective radiation dose of 0.08 mSv, with all studies of diagnostic image quality. The ULD showed 95% reduction in effective radiation dose (P < 0.001), 14% significant reduction in scan length (P = 0.029), and qualitatively decreased image quality compared w2 ith TD (P < 0.001). The ULD at 100 kVp had significantly better image quality compared with ULD at 80 kVp (P = 0.041) with higher effective radiation dose (0.09 vs 0.05 mSv) (P < 0.001). Body mass index significantly impacted image quality for all ULD studies but not for ULD at 80 or 100 kVp.

Conclusion

For evaluation of tracheomalacia, ULD showed low effective radiation dose less than 0.1 mSv and maintained diagnostic image quality.
Diagnostic Value of Contrast-Enhanced Spectral Mammography in Comparison to Magnetic Resonance Imaging in Breast Lesions
Authors: Xing Dong , Lv Yongbin , Sun Bolin , Xie Haizhu , Dong Jianjun , Hao Cuijuan , Chen Qianqian , Chi Xiaoxiao
Published: December 2018

Objective

The aim of this study was to evaluate the diagnostic value between contrast-enhanced spectral mammography (CESM) and breast magnetic resonance imaging (MRI) in breast disease.

Methods

Two hundred thirty-five patients who were suspected of having breast abnormalities by clinical examination or mammography underwent CESM and MRI examination. Using histopathologic results as the criterion standard, the diagnostic performance of CESM and MRI was investigated. The areas under receiver operating characteristic curves were applied to analyze diagnostic efficiency. The Pearson correlation coefficients between CESM versus pathology and MRI versus pathology were calculated.

Results

Two hundred sixty-three breast lesions were found in 235 patients, in which 177 were malignant and 86 were benign. By evaluating the diagnostic value, sensitivity, positive predictive value, negative predictive value, and false-negative rate from CESM examination were comparable to those from MRI (91.5%, 94.7%, 83.7%, and 8.5% vs 91.5%, 90.5%, 82.1%, and 8.5%). Importantly, the accuracy and the specificity were higher for CESM than those for MRI (81% and 89.5% vs 80.2% and 71.7%), whereas the false-positive rate was lower (10.5% vs 19.8%). The areas under receiver operating characteristic curves of CESM and MRI were 0.950 and 0.939, displaying the equivalent diagnostic efficiency (P = 0.48).

For the agreement between measurements, mean tumor sizes were 3.1 cm for CESM and 3.4 cm for MRI compared with 3.2 cm on histopathologic results. The Pearson correlation coefficient of CESM versus histopathology (r = 0.774, P = 0.000) was consistent with MRI versus histopathology (r = 0.771, P = 0.000).

Conclusions

Our results show better accuracy, specificity, and false-positive rate of CESM in breast cancer detection than MRI. Contrast-enhanced spectral mammography displayed a good correlation with histopathology in assessing the lesion size of breast cancer, which is consistent with MRI.
A model for spatiotemporal injury surveillance: implications for the evolution of a trauma system
Authors: Jansen Jan O. , Emerson Phil , Morrison Jonathan J. , Cornulier Thomas
Published: December 2018

BACKGROUND

Geographic variations in case volume have important implications for trauma system configuration and have been recognized for some time. However, temporal trends in these distributions have received relatively little attention. The aim of this study was to propose a model to facilitate the spatiotemporal surveillance of injuries, using Scotland as a case study.

METHODS

Retrospective analysis of 5 years (2009–2013) of trauma incident location data. We analyzed the study population as a whole, as well as predefined subgroups, such as those with abnormal physiologic signs. To leverage sufficient statistical power to detect temporal trends in rare events over short time periods and small spatial units, we used a geographically weighted regression model.

RESULTS

There were 509,725 incidents. There were increases in case volume in Glasgow, the central southern part of the country, the northern parts of the Highlands, the Northeast, and the Orkney and Shetland Islands. Statistically significant changes were mostly restricted to major cities. Decreases in the number of incidents were seen in the Hebrides, Western Scotland, Fife and Lothian, and the Borders. Statistically significant changes were seen mostly in Fife and Lothian, the West, some areas of the Borders, and in the Peterhead area. Subgroup analyses showed markedly different spatiotemporal patterns.

CONCLUSIONS

This project has demonstrated the feasibility of population-based spatiotemporal injury surveillance. Even over a relatively short period, the geographic distribution of where injuries occur may change, and different injuries present different spatiotemporal patterns. These findings have implications for health policy and service delivery.

LEVEL OF EVIDENCE

Epidemiologic study, level V.
Platelet dysfunction during trauma involves diverse signaling pathways and an inhibitory activity in patient-derived plasma
Authors: Verni Christopher C. , Davila Antonio , Balian Steve , Sims Carrie A. , Diamond Scott L.
Published: December 2018

BACKGROUND

Trauma-induced coagulopathy occurs in about 25% of injured patients and accounts for about 10% of deaths worldwide. Upon injury, hemostatic function may decline due to vascular dysfunction, clotting factor deficiencies, hyperfibrinolysis, and/or platelet dysfunction. We investigated agonist-induced calcium signaling in platelets obtained over time from trauma patients.

METHODS

Platelets from trauma patients and healthy donors were monitored via intracellular calcium mobilization and flow cytometry markers (α2bβ3 activation, P-selectin display, and phosphatidylserine exposure) following stimulation with a panel of agonists (adenosine 5′-diphosphate sodium salt, U46619, convulxin, PAR-1/4 activating peptides, iloprost) used in isolation or in pairwise tests. Furthermore, healthy donor platelets were tested in heterologous plasma isolated from healthy subjects and trauma patients.

RESULTS

When exposed to agonists over the first 24 hours postinjury, trauma patient platelets mobilized less calcium in comparison to healthy platelets. Partial recovery of platelet activity was observed in about a third of patients after 120 hours, although not fully obtaining healthy baseline function. Flow cytometry markers of trauma platelets were similar to healthy platelets prior to stimulation, but were depressed in trauma platelets stimulated with adenosine 5′-diphosphate sodium salt or convulxin. Also, washed healthy platelets showed a significant reduction in calcium mobilization when reconstituted in plasma from trauma patients, relative to healthy plasma, at all plasma doses tested.

CONCLUSION

Platelet dysfunction in trauma patients included poor response to multiple agonists relevant to hemostatic function. Furthermore, the inhibitor effect of patient plasma on healthy platelets suggests that soluble plasma species may downregulate endogenous or transfused platelets during trauma.
Accurate risk stratification for development of organ/space surgical site infections after emergent trauma laparotomy
Authors: Wei Shuyan , Green Charles , Kao Lillian S. , Padilla-Jones Brandy B. , Truong Van Thi Thanh , Wade Charles E. , Harvin John A.
Published: December 2018

BACKGROUND

Organ/space surgical site infection (OS-SSI) develops frequently after trauma laparotomies and is associated with significant morbidity. No valid model exists to accurately risk-stratify the probability of OS-SSI development after emergent laparotomy. Risk stratification for OS-SSI in these patients could guide promising, but unproven, interventions for OS-SSI prevention, such as more frequent dosing of intraoperative antibiotics or direct peritoneal resuscitation. We hypothesize that in trauma patients who undergo emergent laparotomy, probability of OS-SSI can be accurately estimated using patient data available during the index operation.

METHODS

Retrospective review was performed on a prospectively maintained database of emergent trauma laparotomies from 2011 to 2016. Patient demographics and risk factors for OS-SSI were collected. We performed Bayesian multilevel logistic regression to develop the model based on a 70% training sample. Evaluation of model fit using area under the curve was performed on a 30% test sample. The Bayesian approach allowed the model to address clustering of patients within physician while implementing regularization to improve predictive performance on test data.

RESULTS

One hundred seventy-two (15%) of 1,171 patients who underwent laparotomy developed OS-SSI. Variables thought to affect development of surgical site infections and were available to the surgeon near the conclusion of the trauma laparotomy were included in the model. Two variables that contributed most to OS-SSIs were damage-control laparotomy and colon resection. The area under the curve of the predictive model validated on the test sample was 0.78 (95% confidence interval, 0.71–0.85).

CONCLUSION

Using a combination of factors available to surgeons before the end of an emergent laparotomy, the probability of OS-SSI could be accurately estimated using this retrospective cohort. A Web-based calculator is under design to allow the real-time estimation of probability of OS-SSI intraoperatively. Prospective validation of its generalizability to other trauma cohorts and of its utility at the point of care is required.

LEVEL OF EVIDENCE

Prognostic study, level IV.
Management of duodenal trauma: A retrospective review from the Panamerican Trauma Society
Authors: Ferrada Paula , Wolfe Luke , Duchesne Juan , Fraga Gustavo P. , Benjamin Elizabeth , Alvarez Augustin , Campbell Andre , Wybourn Christopher , Garcia Alberto , Morales Carlos , Correa Julieta , Pereira Bruno M. , Ribeiro Marcelo , Quiodettis Martha , Peck Gregory , Salamea Juan C. , Kruger Victor F. , Ivatury Rao R. , Scalea Thomas
Published: December 2018

INTRODUCTION

The operative management of duodenal trauma remains controversial. Our hypothesis is that a simplified operative approach could lead to better outcomes.

METHODS

We conducted an international multicenter study, involving 13 centers. We performed a retrospective review from January 2007 to December of 2016. Data on demographics, mechanism of trauma, blood loss, operative time, and associated injured organs were collected. Outcomes included postoperative intra-abdominal sepsis, leak, need for unplanned surgery, length of stay, renal failure, and mortality. We used the Research Electronic Data Capture tool to store the data. Poisson regression using a backward selection method was used to identify independent predictors of mortality.

RESULTS

We collected data of 372 patients with duodenal injuries. Although the duodenal trauma was complex (median Injury Severity Score [ISS], 18 [interquartile range, 2–3]; Abbreviated Injury Scale, 3.5 [3–4]; American Association for the Surgery of Trauma grade, 3 [2–3]), primary repair alone was the most common type of operative management (80%, n = 299). Overall mortality was 24%. On univariate analysis, mortality was associated with male gender, lower admission systolic blood pressure, need for transfusion before operative repair, higher intraoperative blood loss, longer operative time, renal failure requiring renal replacement therapy, higher ISS, and associated pancreatic injury. Poisson regression showed higher ISS, associated pancreatic injury, postoperative renal failure requiring renal replacement therapy, the need for preoperative transfusion, and male gender remained significant predictors of mortality. Duodenal suture line leak was statistically significantly lower, and patients had primary repair over every American Association for the Surgery of Trauma grade of injury.

CONCLUSIONS

The need for transfusion prior to the operating room, associated pancreatic injuries, and postoperative renal failure are predictors of mortality for patients with duodenal injuries. Primary repair alone is a common and safe operative repair even for complex injuries when feasible.

LEVEL OF EVIDENCE

Therapeutic study, level IV.
Chemogenetic ligands for translational neurotheranostics
Authors: Bonaventura Jordi , Eldridge Mark A. , Hu Feng , Gomez Juan L. , Sanchez-Soto Marta , Abramyan Ara M. , Lam Sherry , Boehm Matthew , Ruiz Christina , Farrell Mitchell , Moreno Andrea , Faress Islam Mustafa Galal , Andersen Niels , Lin John Y. , Moaddel Ruin , Morris Patrick , Shi Lei , Sibley David R. , Mahler Stephen V. , Nabavi Sadegh , Pomper Martin G. , Bonci Antonello , Horti Andrew G. , Richmond Barry J. , Michaelides Michael
Published: December 2018

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for precision medicine-based clinical theranostics. DREADD ligands developed to date are not appropriate for such translational applications. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine. The second-generation DREADD agonist, Compound 21 (C21), was developed to overcome these limitations. We found that C21 has low brain penetrance, weak affinity, and low in vivo DREADD occupancy. To address these drawbacks, we developed two new DREADD agonists, JHU37152 and JHU37160, and the first dedicated positron emission tomography (PET) DREADD radiotracer, [18F]JHU37107. JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [18F]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons and at their long-range projections, enabling for the first time, noninvasive and longitudinal neuronal projection mapping and potential for neurotheranostic applications.
EpiSmokEr: A robust classifier to determine smoking status from DNA methylation data
Authors: Bollepalli Sailalitha , Korhonen Tellervo , Kaprio Jaakko , Ollikainen Miina , Anders Simon
Published: December 2018

Self-reported smoking status is prone to misclassification due to under-reporting, while biomarkers like cotinine can only measure recent exposure. Smoking strongly influences DNA methylation, with current, former and never smokers exhibiting different methylation profiles. Recently, two approaches were proposed to calculate scores based on smoking-responsive DNA methylation loci, to serve as reliable indicators of long-term exposure and potential biomarkers to estimate smoking behavior. However, these two methodologies need significant improvements to make them globally applicable to all populations and to achieve an optimal classification of individuals with unknown smoking habits. To advance the practical applicability of the smoking-associated methylation signals, we used machine learning methodology to train a classifier for smoking status prediction. We show the prediction performance of our classifier on three independent whole-blood test datasets demonstrating its robustness and global applicability. Furthermore, we show the cross-tissue functionality of our classifier in tissues other than blood. Additionally, we provide the community with an R package,EpiSmokEr, facilitating implementation of our classifier to predict smoking status in future studies.
Restoring ventilatory control using an adaptive bioelectronic system
Authors: Siu Ricardo , Abbas James J , Hillen Brian K , Gomes Jefferson , Coxe Stefany , Castelli Jonathan , Renaud Sylvie , Jung Ranu
Published: December 2018

Ventilatory pacing via electrical stimulation of the phrenic nerve or of the diaphragm has been shown to enhance quality of life compared to mechanical ventilation. However, commercially-available ventilatory pacing devices require initial manual specification of stimulation parameters and frequent adjustment to achieve and maintain suitable ventilation over long periods of time. Here, we have developed an adaptive, closed-loop, neuromorphic, pattern-shaping controller capable of automatically determining a suitable stimulation pattern and adapting it to maintain a desired breath volume profile on a breath-by-breath basis. In vivo studies in anesthetized intact and C2-hemisected male Sprague-Dawley rats indicated that the controller was capable of automatically adapting stimulation parameters to attain a desired volume profile. Despite diaphragm hemiparesis, the controller was able to achieve a desired volume in the injured animals that did not differ from the tidal volume observed prior to injury (p=0.39). The closed-loop controller was developed and parametrized in a computational testbed prior to in-vivo assessment. This bioelectronic technology could serve as an individualized and autonomous respiratory pacing approach for support or recovery from ventilatory deficiency.
Ancestral and offspring nutrition interact to affect life history traits inDrosophila melanogaster
Authors: Deas Joseph B. , Blondel Leo , Extavour Cassandra G.
Published: December 2018

Ancestral environmental conditions can impact descendant phenotypes through a variety of epigenetic mechanisms. Previous studies on transgenerational effects inDrosophila melanogastersuggest that parental nutrition may affect the body size, developmental duration, and egg size of the next generation. However, it is unknown whether these effects on phenotype remain stable across generations, or if specific generations have general responses to ancestral diet. In the current study, we examined the effect on multiple life history phenotypes of changing diet quality across three generations. Our analysis revealed unforeseen patterns in how phenotypes respond to dietary restriction. Our generalized linear model showed that when considering only two generations, offspring phenotypes were primarily affected by their own diet, and to a lesser extent by the diet of their parents or the interaction between the two generations. Surprisingly, however, when considering three generations, offspring phenotypes were primarily impacted by their grandparents’ diet and their own diet. Interactions amongst different generations’ diets affected development time, egg volume, and pupal mass more than ovariole number or wing length. Further, pairwise comparisons of diet groups from the same generation revealed commonalities in strong responses to rich vs. poor diet: ovariole number, pupal mass, and wing length responded more strongly to poor diet than to rich diet, while development time responded strongly to both rich and poor diets. To improve investigations into the mechanisms and consequences of transgenerational, epigenetic inheritance, future studies should closely examine how phenotypes change across a higher number of generations, and consider responses to broader variability in diet treatments.
Variations in visual sensitivity predict motion sickness in virtual reality
Authors: Fulvio Jacqueline M. , Ji Mohan , Rokers Bas
Published: December 2018

Severity of motion sickness varies across individuals. While some experience immediate symptoms, others seem relatively immune. We explored a potential explanation for such individual variability based on cue conflict theory. According to cue conflict theory, sensory signals that lead to mutually incompatible perceptual interpretations will produce physical discomfort. A direct consequence of such theory is that individuals with greater sensitivity to visual (or vestibular) sensory cues should show greater susceptibility, because they would be more likely to detect a conflict. Using virtual reality (VR), we first assessed individual sensitivity to a number of visual cues and subsequently induced moderate levels of motion sickness using stereoscopic movies presented in the VR headset. We found that an observer’s sensitivity to motion parallax cues predicted severity of motion sickness symptoms. We also evaluated evidence for another reported source of variability in motion sickness severity in VR, namely sex, but found little support. We speculate that previously-reported sex differences might have been due to poor personalization of VR displays, which default to male settings and introduce cue conflicts for the majority of females. Our results identify a sensory sensitivity-based predictor of motion sickness, which can be used to personalize VR experiences and mitigate discomfort.
Automated image processing to support the analysis of between-year transmission of Leptosphaeria maculans in field conditions
Authors: Bousset Lydia , Palerme Marcellino , Leclerc Melen , Parisey Nicolas
Published: December 2018

Understanding the transmission of inoculum between periods where the host plants are present is central for predicting the development of plant diseases and optimising mitigation strategies. However, the production at the end of the growing period, the survival during the intercrop period, and the emergence or emission of inoculum after sowing or planting can be highly variable, difficult to assess and generally inferred indirectly from symptoms data. As a result, there is a lack of large data sets which is a major brake for the study of these epidemiological processes. Here we focus on Leptosphaeria maculans that causes the black leg of oilseed rape. After having infected leaves, at early stages of the plant, and migrating into the stem, it causes a basal stem canker before harvest. It then survives on stubble left in the field from which ascospores are emitted at the beginning of the next growing period. In this study we first developed an image processing framework to estimate the density of fruiting bodies produced on stubble. Then, we used this framework to analyse automatically a large number of stems collected in oilseed rape fields among a cultivated area. Having performed a quality assessment of the processing chain we used the output data to investigate how the potential level of inoculum may change with the source field, the considered year and the stem canker severity at harvest. Besides the insights gain into the blackleg of oilseed rape, this work shows how image-based phenotyping may support epidemiological studies by increasing substantially the precision of high throughput disease data.
Identifying and Interpreting Subgroups in Health Care Utilization Data with Count Mixture Regression Models
Authors: Kurz Christoph , Hatfield Laura
Published: December 2018

Inpatient care is a large share of total health care spending, making analysis of inpatient utilization patterns an important part of understanding what drives health care spending growth. Common features of inpatient utilization measures such as length of stay and spending include zero inflation, over-dispersion, and skewness, all of which complicate statistical modeling. Moreover, latent subgroups of patients may have distinct patterns of utilization and relationships between that utilization and observed covariates. In this work, we apply and compare likelihood-based and parametric Bayesian mixtures of Negative Binomial and zero-inflated Negative Binomial regression models. In a simulation, we find that the Bayesian approach finds the true number of mixture components more accurately than using information criteria to select among likelihood-based finite mixture models. When we apply the models to data on hospital lengths of stay for patients with lung cancer, we find distinct subgroups of patients with different means and variances of hospital days, health and treatment covariates, and relationships between covariates and length of stay.