bluuebunny/crossref_metadata_2025 huggingface dataset:
“Paying it forward”: The link between providers’ civility climate, civility toward patients and patient experience outcomes
Authors: Oppel Eva-Maria , Mohr David C.
Published: July 2018

Background:

Interpersonal relationships are increasingly recognized as an important determinant for care performance and quality in the health care context. An unresolved issue in health care research is whether and to which extent providers’ perceptions of their work relationships are associated with their interactions with patients and, in turn, patient experience outcomes.

Purpose:

The aim of this study was to investigate the extent to which nurses’ experiences of their work relationship climate (i.e., civility climate) affect their interactions with patients (i.e., civility towards patients), which in turn contribute to patient experience outcomes (i.e., overall hospital rating, willingness to return, intent to recommend). Furthermore, we analyze the mediating role of civility toward patients in the relation between civility climate and patient experience outcomes.

Methodology:

The 2011 study sample comprised responses from 6,019 nurses and 38,619 patients at 123 Veterans Health Administration acute care inpatient hospitals located in the United States. We developed and empirically tested a theoretical model using multilevel regression modeling and assessing multilevel mediation.

Results:

The results indicate a positive association between civility climate and civility toward patients. With regard to patient experience outcomes, the analyses reveal a direct effect of civility climate on overall hospital rating, intent to recommend, and willingness to return and an indirect effect mediated by civility toward patients.

Conclusion and Practice Implications:

This is one of the first studies theorizing and testing the extent to which relationship climate among providers affect their interactions with patients. The findings provide support that providers who experience a positive civility climate are more likely to pay forward this relationship experience and engage in civility toward patients. The results point to the importance of a civility climate for ensuring and potentially improving patient experience of care.
High-Resolution Anterior Segment Optical Coherence Tomography in Intraepithelial Versus Invasive Ocular Surface Squamous Neoplasia
Authors: Singh Swati , Mittal Ruchi , Ghosh Arnav , Tripathy Devjyoti , Rath Suryasnata
Published: July 2018

Purpose:

To evaluate the imaging characteristics of intraepithelial and invasive ocular surface squamous neoplasia (OSSN) on high-resolution anterior segment optical coherence tomography (ASOCT).

Methods:

In this prospective cross-sectional study, 17 consecutive patients (10 intraepithelial and 7 invasive) with histopathologically proven OSSN were included. All patients underwent slit-lamp imaging and time-domain ASOCT at premarked sites. Management included standard complete surgical excision with margin clearance and cryotherapy for all cases. The correlation between imaging characteristics and histopathology sections at the premarked sites was analyzed to determine surrogate markers that may help differentiate intraepithelial from invasive OSSN. In addition, 3 patients with presumed OSSN underwent serial ASOCT for surveillance.

Results:

All tumors were staged as T3N0M0 except 2 that were staged as T1N0M0 by the eighth edition of the American Joint Committee on Cancer (AJCC). Mean age was comparable between the 2 groups (56 years vs. 54 years for intraepithelial and invasive groups, respectively, P = 0.79). ASOCT characteristics included all cases (100%) showing a hyperreflective thickened epithelium and abrupt transition between normal and abnormal epithelium. Nine of 10 (90%) intraepithelial OSSN showed a clear plane of separation. A hyperreflective basal membrane was seen in 60% of intraepithelial OSSN, and hyporeflective zones were seen in 57% of invasive OSSN. Mean thickness was 924 and 1662 µm in intraepithelial and invasive OSSN, respectively (P = 0.02, Mann–Whitney test).

Conclusions:

A visible clear plane of separation and increased thickness on ASOCT may serve as surrogate markers of intraepithelial OSSN and help differentiate it from invasive OSSN.
Survival Analysis of Corneal Densitometry After Collagen Cross-Linking for Progressive Keratoconus
Authors: Chan Tommy C. Y. , Chan Jason C. K. , Wang Yu Meng , Rapuano Christopher J.
Published: July 2018

Purpose:

To evaluate the history of densitometric data in patients with keratoconus undergoing corneal cross-linking.

Methods:

Twenty-two eyes of 22 patients with keratoconus were included. Corneal tomography and densitometry measurements were performed before and after accelerated corneal cross-linking. The duration of corneal haze was defined as the time between cross-linking and densitometry measurements returning to the preoperative value. Survival analysis of corneal haze after cross-linking was performed. Preoperative and postoperative corneal densitometry, maximum keratometry (Kmax), and central corneal thickness were compared.

Results:

The duration of corneal haze was 18.2 ± 3.8 months at the first zone of 0 to 2 mm and 10.9 ± 2.5 months at the second zone of 2 to 6 mm. There was no change in Kmax between the preoperative period and the time at which corneal haze resolved (P = 0.394 at the first zone; P = 0.658 at the second zone). Compared with the measurement taken at resolution of corneal haze, Kmax at 1 year after haze resolution was lower (62.0 ± 9.9 D to 61.2 ± 9.9 D, P = 0.008 at the first zone; 63.6 ± 10.9 D to 62.5 ± 10.1 D, P = 0.016 at the second zone). There was a decrease of central corneal thickness between the preoperative period and the time at which corneal haze resolved (470.8 ± 34.1 μm to 464.8 ± 34.5 μm, P = 0.047 at the first zone; 465.0 ± 35.3 μm to 454.7 ± 37.2 μm, P = 0.001 at the second zone), but it remained unchanged after haze resolution (P = 0.146 at the first zone; P = 0.067 at the second zone).

Conclusions:

Corneal cross-linking halted keratoconus progression when detectable haze was present. There was continuous corneal flattening measured at 1 year after haze resolution. Thinning of the cornea was seen only when haze was detectable after cross-linking.
Novel Sternal Reconstruction with Custom Three-Dimensional–Printed Titanium PoreStar Prosthesis
Authors: Tran Minh D. , Varzaly Jason A. , Chan Justin C.Y. , Caplash Yugesh , Worthington Michael G.
Published: July 2018

Resection of sternal tumors can leave large defects, which exposes major mediastinal structures, and can affect respiratory mechanics. If feasible, resection is potentially a complex reconstructive challenge to restore normal and functional anatomy using conventional techniques. We report the first Australian use of a three-dimensional–printed titanium and PoreStar prosthesis in a 39-year-old woman for reconstruction after major surgical resection of the sternum for metastatic breast cancer. The patient successfully underwent excision of the sternum and costal cartilages as well as implantation of the prosthesis. We conclude that three-dimensional–printed prostheses are technically feasible to deliver excellent cosmetic result.
Posttraumatic Growth of Stroke Survivors and Its Correlation With Rumination and Social Support
Authors: Peng Zhou-yuan , Wan Li-hong
Published: July 2018

Objective: This study focused on gaining insight into the positive changes of stroke survivors. This study aimed to describe the level of posttraumatic growth (PTG) and explore its correlation with rumination and social support in stroke survivors. The impacts of individual characteristics on PTG were also discussed. Methods: A descriptive correlation design was used in this study. Stroke survivors from a tertiary hospital in Guangzhou City were investigated. The Posttraumatic Growth Inventory, Chinese version of Event Related Rumination Inventory, and Perceived Social Support Scale were used to assess the level of PTG, rumination, and social support. Results: The mean (SD) score of the Posttraumatic Growth Inventory was 61.12 (25.41). There were moderate positive correlations between PTG with rumination and social support among stroke survivors (r
1 = 0.392, r
2 = 0.336, P < .01). The level of education, support from family, and deliberate rumination accounted for 34.6% of the total variance in PTG (F = 11.554, P < .001). Conclusions: The phenomenon of PTG of stroke patients in hospital existed, but it was at a low level. Stroke survivors with a higher level of rumination, social support, and a university level education had a higher level of PTG.
Secondary Brain Injury: A Concept Analysis
Authors: Ortega-Pérez Stefany , Amaya-Rey María Consuelo
Published: July 2018

Background: Traumatic brain injury and cerebrovascular disease may lead to motor, behavioral, and/or cognitive disabilities. The associated neurologic and vascular damage triggers a chain of events that lead to a secondary brain injury (SBI), a preventable cause of adverse neurological outcomes. Proper prevention of these factors may limit undesirable outcomes. This article presents a concept analysis that aims to form a single definition of the term secondary brain injury for nursing personnel. Methodology: Concept analysis was used to clarify the concept of SBI. An electronic search was performed on existing nursing literature dating from 1995 to 2016 on PubMed, MEDLINE, Ovid Journal, Wiley, and ProQuest. Results: A clear definition and description of the attributes, antecedents, and consequences of SBI increases the knowledge and level of recognition of the secondary injuries. This may lead to strategies that reduce the risk of long-term effects (disability) and poor clinical outcomes. Conclusions: This concept analysis contributes to the endeavor of identifying phenomena that are pertinent for nursing; it also provides a basis for future research that leads to improving nursing interventions and creating educational programs and healthcare policies that prevent or eliminate the consequences of SBI.
Effects of Different Head-of-Bed Elevations and Body Positions on Intracranial Pressure and Cerebral Perfusion Pressure in Neurosurgical Patients
Authors: Altun Uğraş Gülay , Yüksel Serpil , Temiz Zeynep , Eroğlu Selin , Şirin Keziban , Turan Yüksel
Published: July 2018

Purpose: The aim of this study was to evaluate the effects of different head of bed (HOB) elevations and body positions on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) and to identify safe positions for neurosurgical patients with different Glasgow Coma Scale (GCS) scores. Methods: This study with a quasi-experimental, prospective repeated measures is designed with control over the intervention consisted of 30 patients hospitalized in the neurocritical care units (NCU). Patients’ HOB was elevated (degree of 15,30,45) and the patients were at supine, left lateral and right lateral positions. ICP and CPP were recorded for each patient. Results: It was found that ICP increased and CPP decreased at supine, left and right lateral positions with different HOB elevations, which, however, did not reach statistical significance. When patients with a GCS score of 3–8 were at degree of 15 right and left lateral positions and 45 right lateral position; and when patients with a GCS score of 13–15 were positioned at degree of 15 left lateral, ICP and CPP changed significantly. Conclusion: The results of this study showed that different positions the patients’ HOB (degree of 15,30,45) led to slight insignificant changes in ICP and CPP; and these values were maintained within the ranges established by recent guidelines.
Effectiveness of a Tailored Lifestyle Management Program for Middle-Aged Women With Coronary Artery Disease: A Preliminary Study
Authors: TSAI Ching-Ching , LI Ai-Hsien , TU Chung-Ming , HWANG Kai-Lin , JENG Chii
Published: July 2018

Background:

Coronary artery disease (CAD) is a leading cause of death in women. Many of the risk factors for CAD relate to lifestyle and thus may be influenced by lifestyle modification. However, middle-aged women often find it difficult to adjust their lifestyle behaviors. Thus, providing individualized treatment is crucial to reducing the risk and incidence of CAD in this population.

Purpose:

The aim of this study was to explore the effectiveness of a tailored lifestyle management program (TLMP) for middle-aged women with CAD.

Methods:

An experimental design was employed. Thirty-five middle-aged women with CAD (with stenosis [> 50%] of at least one main artery as determined by cardiac catheterization examination results) were recruited. The 35 women were randomlyassigned to the experimental group (n = 17) or the control group (n = 18). Both groups received regular health education during their hospitalization. After discharge, the experimental group received the 12-week, home-based TLMP. A generalized estimating equation was used to examine the effects of the TLMP on metabolic and biomarker indicators for CAD.

Results:

The average age of participants was 56.1 ± 5.6 years. No significant demographic differences were identified between the two groups. Compared with the control group, the experimental group had a significantly higher high-density lipoprotein level (B = 7.83, p < .001), a lower level of total cholesterol (B = −49.21, p = .04), and a lower waist circumference (B = −6.42, p < .001).

Conclusions/Implications for Practice:

This study suggests that using tailored interventions is an effective approach to improving high-density lipoprotein, total cholesterol, and waist circumference in middle-aged women with CAD. This result is expected to have important implications for women’s healthcare, particularly in terms of preventing the incidence of CAD.
Scratching Below the Surface: Screening for Posttraumatic Stress Symptoms Following Hospitalization With the Pediatric Trauma Service
Authors: Cline Virginia Depp , Whitaker Brian , Duran Petra A. , Ratcliff Kelly , Rosenfeld Eric H. , Naik-Mathuria Bindi
Published: July 2018

Significant progress has occurred medically for children who have experienced traumatic injuries; however, attention to their psychological adjustment has only more recently been a focus in research and clinical practice. These needs do not cease at discharge but, instead, require monitoring to determine whether further assessment and/or intervention are required. Our team, inclusive of the Psychology Service and the Trauma Service, identified 2 established screening measures (based on age) that were completed by patients during their outpatient follow-up visits postdischarge. Should a patient screen positive, the Trauma Service referred them to the Psychology Service for further evaluation and possible treatment (i.e., trauma-focused cognitive-behavioral therapy). Of 881 trauma activations, 31 (4%) patients were screened at an outpatient follow-up appointment through pediatric surgery/trauma clinic. Of these completed screening tools, 29% screened positive and warranted a referral to Psychology. Intervention was recommended for the majority of the patients evaluated; however, half of these did not return for this intervention. A collaboration between the Psychology Service and the Trauma Service is a vital step toward providing stepped care for patients after unintentional injuries. This allows for evaluation of patient needs and then a referral source to meet these identified needs. Future directions include increasing the number of screened patients, perhaps with use of technological supports (i.e., REDCap) or expansion into other clinics and consideration of ways to increase family's use of psychological intervention.

Level of Evidence: Therapeutic/Care management Level IV
The FRAIL Questionnaire: A Useful Tool for Bedside Screening of Geriatric Trauma Patients
Authors: Maxwell Cathy A. , Dietrich Mary S. , Miller Richard S.
Published: July 2018

Frailty screening is a priority in acute care. Using secondary data from our prior study, we derived a 5-item FRAIL Questionnaire (instrument) score for 188 geriatric trauma patients and aimed to examine the influence of preinjury physical frailty (as measured by FRAIL) on 1-year outcomes. The study used a secondary data analysis design. Patients were 65 years and older admitted through the emergency department (ED) between October 2013 and March 2014. The 5 items of the FRAIL instrument were identified within data sources of our prior study, and a preinjury FRAIL score was created for each patient. For data analysis, frequencies, measures of central tendency, and linear and logistic regression models were used. Median age of the patients was 77 years (interquartile range [IQR] = 69–86), and median Injury Severity Score = 10 (IQR = 9–17). Upon admission to the ED, 63 patients (34%) were screened as frail (FRAIL score ≥3), 71 (38%) as prefrail (score = 1–2), and 54 (29%) as nonfrail (score = 0). Frequencies for components of the FRAIL score were as follows: fatigue (N = 123; 65%), resistance (N = 61; 32%), ambulation (N = 76; 40%), illnesses (N = 51; 27%), and loss of weight (N = 11; 6%). After controlling for age, comorbidities, injury severity, and cognitive status, preinjury FRAIL scores explained 13% of the variability in function as measured by the Barthel Index (N = 129, β = .36, p < .001). Forty-seven patients died (26%) within 1 year. Logistic regression analysis revealed that the higher the preinjury FRAIL score, the greater the likelihood of mortality within 1 year (OR = 1.74, p = .001; 95% CI [1.27, 2.39)]. The FRAIL Questionnaire predicts 1-year functional status and mortality and is a useful tool for bedside screening.
Resuscitative Strategies in the Trauma Patient: The Past, the Present, and the Future
Authors: Eick Brody G. , Denke Nancy J.
Published: July 2018

Over the last decade, trends in fluid resuscitation have changed dramatically as have our practices. Research is driving trauma centers across the globe to initiate modifications in fluid resuscitation of the hemorrhagic trauma patients both in the prehospital and intrahospital arena. This is being done by combining the theory of permissive hypotension and damage control surgery with hemostatic resuscitation as the preferred methods of resuscitation in patients with hemorrhagic shock. The literature illustrates that previous strategies we considered to be beneficial are actually detrimental to the outcomes of these severely injured patients. This complex and continuously changing adaptation in practice must be made without losing our strategic focus of improvement of outcomes and recognition of the morbidity associated with bleeding of the trauma patient. Designating limits on large-volume crystalloid resuscitation will prevent cellular injury. These wiser resuscitation strategies are key in the efforts to reduce mortality and to improve outcomes. This article is to serve as a review of each of the resuscitative fluid strategies as well as new methods of trauma resuscitation.
Facial profile and additional features in fetuses with trisomy 21
Authors: Radhakrishnan Periyasamy , Nayak Shalini S. , Shukla Anju , Girisha Katta M.
Published: July 2018

Aneuploidies occur in about 5% of clinically recognized pregnancies. Facial gestalt is a vital tool for the clinical diagnosis of trisomy 21. Facial anomalies are subtle in fetal life and challenging for a clinician not familiar with perinatal dysmorphology. Here, we present the facial profile and additional features in six fetuses with Down syndrome as a visual aid. We present the facial photographs of six fetuses with genetically confirmed trisomy 21. These photographs will serve as a diagnostic aid for trisomy 21 in perinatal dysmorphology. We noted punctate calcifications in two fetuses with trisomy 21.
Vonoprazan versus proton-pump inhibitors for gastric endoscopic submucosal dissection-induced ulcers: a systematic review and meta-analysis
Authors: Jaruvongvanich Veeravich , Poonsombudlert Kittika , Ungprasert Patompong
Published: July 2018

Acid secretion inhibitors are usually prescribed to promote the healing of artificial ulcers caused by endoscopic submucosal dissection (ESD) to reduce the risk of gastric perforation and delayed bleeding. Vonoprazan is a newer agent that has been shown to be more potent than a proton-pump inhibitor (PPI). However, it remains unclear whether vonoprazan is more effective than PPI in promoting healing of ulcers caused by ESD. Medline and Embase databases were searched through January 2018 for studies that compared the rate of complete healing of ulcers caused by ESD and post-ESD delayed bleeding in patients who received vonoprazan versus those who received PPI after ESD. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect model, generic inverse variance method. The between-study heterogeneity was quantified using the Q-statistic and I
2. A total of six studies consisting of 461 patients were identified. The likelihood that ulcers caused by ESD were completely healed at 4–8 weeks after the procedure was significantly higher among patients who received vonoprazan compared with those who received PPI, with a pooled OR of 2.27 (95% CI=1.38–3.73; I
2=0%). The risk of developing post-ESD delayed bleeding was also numerically lower among those who received vonoprazan, with a pooled OR of 0.79, although the result did not reach statistical significance (95% CI=0.18–3.49; I
2=29%). This study found that patients who received vonoprazan after ESD had a significantly higher rate of completely healed ulcers compared with those who received PPI.
Megakaryocyte modification of platelets in thrombocytopenia
Authors: Roweth Harvey G. , Parvin Somayje , Machlus Kellie R.
Published: July 2018

Purpose of review

Platelets are small, anucleate cells that circulate within the blood and play essential roles in preserving vascular integrity. However, abnormalities in either platelet production or destruction can result in thrombocytopenia, clinically defined by a platelet count lower than 150 000/μL of whole blood. Thrombocytopenia is frequently associated with impaired hemostatic responses to vascular injury and can be life-threatening because of bleeding complications. Megakaryocytes are the precursor cells responsible for platelet production, a process commonly referred to as thrombopoiesis. This review specifically discusses how perturbation of molecular mechanisms governing megakaryocyte differentiation and development manifest in various forms of thrombocytopenia.

Recent findings

This review highlights the identification of novel transcriptional regulators of megakaryocyte maturation and platelet production. We also provide an update into the essential role of cytoskeletal regulation in thrombopoiesis, and how both megakaryopoiesis and platelet production are altered by anticancer therapeutics. Lastly, we focus on recent investigative approaches to treat thrombocytopenia and discuss future prospects in the field of megakaryocyte research.

In patients where thrombocytopenia is not due to heightened platelet destruction or clearance, defects in megakaryocyte development should be considered.
Piecemeal Deglutition and the Implications for Pressure Impedance Dysphagia Assessment in Pediatrics
Authors: Ferris Lara , King Sebastian , McCall Lisa , Rommel Nathalie , Scholten Ingrid , Teague Warwick , Doeltgen Sebastian , Omari Taher
Published: July 2018

Objectives:

High‐resolution impedance manometry (HRIM) enables biomechanical swallow assessment. Piecemeal deglutition (PD) defines swallowing of a single bolus in 2 or more portions. We investigated PD sequences on HRIM recordings to ascertain appropriate swallow selection for analysis and to determine the impact of PD on swallow function measures.

Methods:

Pharyngo‐esophageal motility and bolus flow were assessed in 27 children (19 M, mean age 15 months) with repaired esophageal atresia and trachea‐esophageal fistula, but who were asymptomatic of oropharyngeal dysphagia. A consistent volume of between 2 and 5 mL saline boluses was given to each patient. Retrospectively, PD sequences were defined based on the number of swallows required to clear the bolus from the oral cavity: pattern A = 1–2 swallows; pattern B = 3 swallows; and pattern C = 4+ swallows. The largest bolus volume swallowed was noted as the dominant swallow in each pattern. Pressure Flow Analysis defined contractility, distension and flow timing metrics. Data were averaged for each PD pattern, and compared with dominant swallows from each pattern.

Results:

PD pattern B (43.7%) was the most prevalent across the cohort. PD patterns were similarly distributed across age groups (G1: <1 years, G2: 1–4 years). Differences in upper esophageal sphincter distension and pharyngeal flow timing measures were, however, seen in relation to both age and PD pattern, whereby a larger pharynx in older children elicited greater distension for a longer latency, and for larger volumes.

Conclusions:

PD reduces bolus volume, and biomechanical swallow measures are impacted. PD is a necessary consideration for accurate HRIM analysis of swallow function. Selection of dominant swallows from a PD sequence provides a swallow profile which best represents a child's swallow function, and should always be reported and interpreted in context of the PD sequence observed.
Erythromycin and Reflux Events in Premature Neonates
Authors: Ballengee Cortney R. , Davalian Faranek , Conaway Mark R. , Sauer Cary G. , Kaufman David A.
Published: July 2018

Objective:

Gastroesophageal reflux disease (GERD) in premature neonates may manifest as apnea, bradycardia, growth failure, aspiration, or feeding intolerance. Erythromycin ethylsuccinate (EES), is often used as a pro‐kinetic in the management of GERD, despite lack of evidence or safety from randomized controlled trials. We sought to study the efficacy of enteral EES at a dose of 50 mg · kg−1 · day−1 in decreasing the frequency of gastroesophageal reflux events as determined by pH‐multichannel intraluminal impedance (pH‐MII) monitoring.

Methods:

In a randomized, double‐blind, placebo‐controlled trial, eligible premature neonates with clinical signs of GERD underwent 24‐hour pH‐MII monitoring. If >5 reflux events were identified on pH‐MII, then subjects were randomized to receive either EES or placebo. Repeat 24‐hour pH‐MII was performed on day 7 of study treatment and compared to initial pH‐MII.

Results:

Forty‐three premature neonates were enrolled. Of those, 31 neonates were randomized, 15 to EES and 16 to placebo with a median (IQR) pretreatment total reflux events per 24 hours of 23 (16–40) and 29 (12–40), respectively. Day 7 total events per 24 hours decreased by 4 events in the EES group to 19 (15–33) and by 10 events in the placebo group to 19 (11–26) (P = 0.09). There were no differences in pretreatment and day 7 acidic and nonacidic reflux, proximal reflux, total or percent reflux time, median or longest bolus clearance time, or nurse‐reported apnea events between groups.

Conclusions:

Enteral EES did not decrease reflux events on 24‐hour pH‐MII at the dose studied. Therefore, it may be ineffective in the treatment of GERD in premature neonates.
An Academic-Practice Partnership
Authors: Roach Ashley , Hooke Sherrill
Published: July 2018

Background

Through the Veterans Affairs Nursing Academic Partnership (VANAP), baccalaureate nursing students and faculty participated in practice innovations in a Veterans Affairs Health Care System. Nationally, VANAP has attempted to bridge gaps between theory and practice and across care settings.

Approach

In a population health course, nursing students were placed in both inpatient and outpatient settings. Through activities such as postconferences and population-based projects, students joined forces with Veterans Affairs staff on issues that affected veterans' health care.

Outcomes

Two student groups worked on amputation prevention from opposite ends of the spectrum. Their projects, with the continuation of these by faculty and staff, resulted in 47% decrease in vascular-related hospital readmissions.

Conclusions

Student placements in settings across the care continuum improved communication between the settings. The enhanced partnership between the 2 organizations addressed a relevant, meaningful patient care issue.
Quetiapine protects the blood-brain barrier in traumatic brain injury
Authors: Robinson Bobby Darnell , Isbell Claire Larson , Anasooya Shaji Chinchusha , Kurek Stanley , Regner Justin L. , Tharakan Binu
Published: July 2018

BACKGROUND

The integrity of the blood-brain barrier (BBB) is paramount in limiting vasogenic edema following traumatic brain injury (TBI). The purpose of this study was to ascertain if quetiapine, an atypical antipsychotic commonly used in trauma/critical care for delirium, protects the BBB and attenuates hyperpermeability in TBI.

METHODS

The effect of quetiapine on hyperpermeability was examined through molecular modeling, cellular models in vitro and small animal models in vivo. Molecular docking was performed with AutoDock Vina to matrix metalloproteinase-9. Rat brain microvascular endothelial cells (BMECs) were pretreated with quetiapine (20 μM; 1 hour) followed by an inflammatory activator (20 μg/mL chitosan; 2 hours) and compared to controls. Immunofluorescence localization for tight junction proteins zonula occludens-1 and adherens junction protein β-catenin was performed. Human BMECs were grown as a monolayer and pretreated with quetiapine (20 μM; 1 hour) followed by chitosan (20 μg/mL; 2 hours), and transendothelial electrical resistance was measured. C57BL/6 mice (n = 5/group) underwent mild to moderate TBI (controlled cortical impactor) or sham craniotomy. The treatment group was given 10 mg/kg quetiapine intravenously 10 minutes after TBI. The difference in fluorescence intensity between intravascular and interstitium (ΔI) represented BBB hyperpermeability. A matrix metalloproteinase-9 activity assay was performed in brain tissue from animals in the experimental groups ex vivo.

RESULTS

In silico studies showed quetiapine thermodynamically favorable binding to MMP-9. Junctional localization of zonula occludens-1 and β-catenin showed retained integrity in quetiapine-treated cells as compared with the chitosan group in rat BMECs. Quetiapine attenuated monolayer permeability compared with chitosan group (p< 0.05) in human BMECs. In the animal studies, there was a significant decrease in BBB hyperpermeability and MMP-9 activity when compared between the TBI and TBI plus quetiapine groups (p< 0.05).

CONCLUSION

Quetiapine treatment may have novel anti-inflammatory properties to provide protection to the BBB by preserving tight junction integrity.

LEVEL OF EVIDENCE

level IV.
Hypobaria during long-range flight resulted in significantly increased histopathological evidence of lung and brain damage in a swine model
Authors: Scultetus Anke H. , Jefferson Michelle A. , Haque Ashraful , Ho Lam Thuy Vi Tran , Hazzard Brittany , Saha Biswajit K. , Chun Steve J. , Auker Charles R. , Moon-Massat Paula F. , McCarron Richard M. , Malone Debra L.
Published: July 2018

BACKGROUND

Aeromedical evacuation to definitive care is standard in current military conflicts. However, there is minimal knowledge on the effects of hypobaria (HYPO) on either the flight crew or patients. The effects of HYPO were investigated using healthy swine.

METHODS

Anesthetized Yorkshire swine underwent a simulated 4 h “transport” to an altitude of 2,441 m (8,000 feet.; HYPO, N = 6) or at normobaric conditions (NORMO, N = 6). Physiologic and biochemical data were collected. Organ damage was assessed for hemorrhage, inflammation, edema, necrosis, and for lungs only, microatelectasis.

RESULTS

All parameters were similar prior to and after “transport” with no significant effects of HYPO on hemodynamic, neurologic, or oxygen transport parameters, nor on blood gas, chemistry, or complete blood count data. However, the overall Lung Injury Score was significantly worse in the HYPO than the NORMO group (10.78 ± 1.22 vs. 2.31 ± 0.71, respectively) with more edema/fibrin/hemorrhage in the subpleural, interlobular and alveolar space, more congestion in alveolar septa, and evidence of microatelectasis (vs. no microatelectasis in the NORMO group). There was also increased severity of pulmonary neutrophilic (1.69 ± 0.20 vs. 0.19 ± 0.13) and histiocytic inflammation (1.83 ± 0.23 vs. 0.47 ± 0.17) for HYPO versus NORMO, respectively. On the other hand, there was increased renal inflammation in NORMO compared with HYPO (1.00 ± 0.13 vs. 0.33 ± 0.17, respectively). There were no histopathological differences in brain (whole or individual regions), liver, pancreas, or adrenals.

CONCLUSION

Hypobaria, itself, may have an adverse effect on the respiratory system, even in healthy individuals, and this may be superimposed on combat casualties where there may be preexisting lung injury. The additional effects of anesthesia and controlled ventilation on these results are unknown, and further studies are indicated using awake models to better characterize the mechanisms for this pathology and the factors that influence its severity.
Use of diaphragm pacing in the management of acute cervical spinal cord injury
Authors: Kerwin Andrew J. , Yorkgitis Brian K. , Ebler David J. , Madbak Firas G. , Hsu Albert T. , Crandall Marie L.
Published: July 2018

BACKGROUND

Cervical spinal cord injury (CSCI) is devastating. Respiratory failure, ventilator-associated pneumonia (VAP), sepsis, and death frequently occur. Case reports of diaphragm pacing system (DPS) have suggested earlier liberation from mechanical ventilation in acute CSCI patients. We hypothesized DPS implantation would decrease VAP and facilitate liberation from ventilation.

METHODS

We performed a retrospective review of patients with acute CSCI managed at a single Level 1 trauma center between January 2005 and May 2017. Routine demographics were collected. Patients underwent propensity matching based on age, injury severity score, ventilator days, hospital length of stay, and need for tracheostomy. Outcome measures included hospital length of stay, intensive care unit length of stay, ventilator days (vent days), incidence of VAP, and mortality. Bivariate and multivariate logistic and linear regression statistics were performed using STATA Version 10.

RESULTS

Between July 2011 and May 2017, all patients with acute CSCI were evaluated for DPS implantation. Forty patients who had laparoscopic DPS implantation (DPS) were matched to 61 who did not (NO DPS). Median time to liberation after DPS implantation was 7 days. Hospital length of stay and mortality were significantly lower on bivariate analysis in DPS patients. Diaphragm pacing system placement was not found to be associated with statistically significant differences in these outcomes on risk-adjusted multivariate models that included admission year.

CONCLUSIONS

Diaphragm pacing system implantation in patients with acute CSCI can be one part of a comprehensive critical care program to improve outcomes. However, the association of DPS with the marked improved mortality seen on bivariate analysis may be due solely to improvements in critical care throughout the study period. Further studies to define the benefits of DPS implantation are needed.

LEVEL OF EVIDENCE

Therapeutic, level IV.
Inability to predict subprophylactic anti–factor Xa levels in trauma patients receiving early low-molecular-weight heparin
Authors: Imran Jonathan B. , Madni Tarik D. , Clark Audra T. , Rizk Paul , Huang Emily , Minshall Christian T. , Taveras Luis R. , Cunningham Holly B. , Eastman Alexander L. , Koshy Jojo P. , Kacir Cory D. , Cripps Michael W.
Published: July 2018

BACKGROUND

Standard low-molecular-weight heparin dosing may be suboptimal for venous thromboembolism prophylaxis. We aimed to identify independent predictors of subprophylactic Xa (subXa) levels in trauma patients treated under a novel early chemoprophylaxis algorithm.

METHODS

A retrospective analysis of trauma patients from July 2016 to June 2017 who received enoxaparin 40 mg twice daily and had peak Xa levels drawn was performed. Patients were divided into cohorts based on having a subXa (<0.2 IU/mL) or prophylactic (≥0.2 IU/mL) Xa level.

RESULTS

In all, 124 patients were included, of which 38 (31%) had subXa levels, and 17 (14%) had Xa levels greater than 0.4 IU/mL. Of the subXa cohort, 35 (92%) had their dosage increased, and the repeat Xa testing that was done in 32 revealed that only 75% reached prophylactic levels. The median time to the initiation of chemoprophylaxis was 21.9 hours (interquartile range [IQR], 11.45–35.07 hours). Patients who were defined as having lower risk of having a complication as a result of bleeding had a shorter time to starting prophylaxis than those at higher risk (18.39 hours [IQR 5.76–26.51 hours] vs. 29.5 hours [IQR 16.23–63.07 hours], p < 0.01).

There was no difference in demographics, weight, body mass index, creatinine, creatinine clearance, injury severity score, type of injury, weight-based dose, time to chemoprophylaxis, or bleeding complications between the cohorts. No independent predictors of subXa level were identified on multivariable logistic regression.

CONCLUSIONS

A significant number of trauma patients fail to achieve prophylactic Xa levels. Intrinsic factors may prevent adequate prophylaxis even with earlier administration and higher dosing of low-molecular-weight heparin.

LEVEL OF EVIDENCE

Therapeutic, level IV
Perhaps it's not the platelet: Ristocetin uncovers the potential role of von Willebrand factor in impaired platelet aggregation following traumatic brain injury
Authors: Kornblith Lucy Z. , Robles Anamaria J. , Conroy Amanda S. , Hendrickson Carolyn M. , Calfee Carolyn S. , Fields Alexander T. , Callcut Rachael A. , Cohen Mitchell J.
Published: July 2018

BACKGROUND

Injury to the blood-brain barrier exposes endothelium rich in von Willebrand factor (vWF), which may play a role in altered platelet aggregation following traumatic brain injury (TBI). Ristocetin is an antimicrobial substance that induces vWF-mediated aggregation of platelets. We examined these mechanisms in injured patients by measuring the aggregation response of platelets to stimulating agonists (including ristocetin) via whole-blood multiple-electrode platelet aggregometry. We hypothesized that patients with TBI have an altered platelet aggregation response to ristocetin stimulation compared with patients without TBI.

METHODS

Blood was collected from 233 trauma patients without thrombocytopenia. Platelet aggregation was assessed using multiple-electrode platelet aggregometry (Multiplate). Platelet aggregation response to stimulating agonists collagen, thrombin receptor-activating peptide 6, adenosine diphosphate, arachidonic acid, and ristocetin was measured. Factor activity was measured.

RESULTS

Of the 233 patients, 23% had TBI. There were no differences in platelet aggregation responses to any agonists between TBI and non-TBI patients except ristocetin. Platelet aggregation response to ristocetin stimulation was significantly lower in TBI patients (p = 0.03). Patients with TBI also had higher factor VIII activity (215% vs. 156%, p = 0.01). In multivariate analysis, there was a significant independent association of impaired platelet aggregation response to ristocetin stimulation with TBI (odds ratio, 3.05; p = 0.04).

CONCLUSIONS

Given the importance of platelets in hemostasis, understanding the mechanisms of impaired platelet aggregation following injury is critical. The impaired platelet aggregation response to ristocetin stimulation and corresponding increase in factor VIII activity in TBI patients may be secondary to a TBI-induced effect on vWF quantity (due to injury-driven consumption of vWF) or vWF function with resultant increase in circulating factor VIII activity (due to impaired carrying capacity of vWF). Given there are multiple known therapies for vWF deficits including desmopressin, purified and recombinant vWF, and estrogens, these lines of investigation are particularly compelling in patients with TBI and hemorrhage.

LEVEL OF EVIDENCE

Prognostic study, level II.
Metabolic Concepts in Idiopathic Intracranial Hypertension and Their Potential for Therapeutic Intervention
Authors: Hornby Catherine , Mollan Susan P. , Botfield Hannah , O'Reilly Michael W. , Sinclair Alexandra J.
Published: July 2018

Background:

Traditional risk factors associated with idiopathic intracranial hypertension (IIH) include obesity, weight gain, and female sex. The incidence of IIH is increasing and yet the underlying trigger and the fueling pathological mechanisms are still poorly understood.

Evidence Acquisition:

Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, and neurosurgery literature was made.

Results:

The facts that implicate sex and obesity in IIH and headache are examined. The role of fat distribution in IIH is questioned, and the concept of adipose tissue functioning as an endocrine organ driving IIH is discussed. The impact of androgen metabolism in IIH is reviewed as is the emerging role of glucagon-like-peptide-1 analogues in modulating intracranial pressure. This introduces the concept of developing targeted disease-modifying therapeutic strategies for IIH.

Conclusions:

This review will discuss the possible role of the adipose/gut/brain metabolism axis in IIH and speculate how this may impact the pathogenesis of IIH and therapeutic opportunities.
Application of a novel molecular method to age free‐living wild Bechstein's bats
Authors: Wright Patrick G. R. , Mathews Fiona , Schofield Henry , Morris Colin , Burrage Joe , Smith Adam , Dempster Emma L. , Hamilton Patrick B.
Published: July 2018

The age profile of populations fundamentally affects their conservation status. Yet, age is frequently difficult to assess in wild animals. Here, we assessed the use of DNA methylation of homologous genes to establish the age structure of a rare and elusive wild mammal: the Bechstein's bat (Myotis bechsteinii). We collected 62 wing punches from individuals whose ages were known as a result of a long‐term banding study. DNA methylation was measured at seven CpG sites from three genes, which have previously shown age‐associated changes in humans and laboratory mice. All CpG sites from the tested genes showed a significant relationship between DNA methylation and age, both individually and in combination (multiple linear regression R2 = 0.58, p < 0.001). Despite slight approximation around estimates, the approach is sufficiently precise to place animals into practically useful age cohorts. This method is of considerable practical benefit as it can reliably age individual bats. It is also much faster than traditional capture–mark–recapture techniques, with the potential to collect information on the age structure of an entire colony from a single sampling session to better inform conservation actions for Bechstein's bats. By identifying three genes where DNA methylation correlates with age across distantly related species, this study also suggests that the technique can potentially be applied across a wide range of mammals.
Quantifying vegetation and canopy structural complexity from terrestrial LiDARdata using theforestr rpackage
Authors: Atkins Jeff W. , Bohrer Gil , Fahey Robert T. , Hardiman Brady S. , Morin Timothy H. , Stovall Atticus E. L. , Zimmerman Naupaka , Gough Christopher M.
Published: July 2018

Terrestrial LiDAR(light detection and ranging) technologies have created new means of quantifying forest canopy structure, allowing not only the estimation of biomass, but also descriptions of the position and variability in canopy elements in space. Such measures provide novel structural information broadly useful to ecologists.

There is a growing need for both a detailed taxonomy of forest canopy structural complexity (CSC) and open, transparent, and flexible tools to quantify complexity in ways that will advance foundational ecological knowledge of structure‐function relationships.

TheCSCtaxonomy we present groups structural descriptors into five categories: leaf area and density, canopy height, canopy arrangement, canopy openness, and canopy variability. This paper also introduces therpackageforestr, the first open‐sourcerpackage for the calculation ofCSCmetrics from terrestrial LiDARdata.

Therpackageforestris an analysis toolbox that works with portable canopy LiDAR(PCL) data and other pixelated/voxelized point clouds derived from terrestrial LiDARscanning (TLS) data to calculateCSCmetrics of interest to ecologists, modellers, forest managers, and remote sensing scientists.
Quantification of the Leydig cell compartment in testicular biopsies and association with biochemical Leydig cell dysfunction in testicular cancer survivors
Authors: Tarsitano M. G. , Bandak M. , Jørgensen N. , Skakkebæk N. E. , Juul A. , Lenzi A. , Daugaard G. , Rajpert‐De Meyts E.
Published: July 2018

A simple histological method to evaluate the Leydig cell compartment is lacking. We aimed to establish such a method and to investigate if Leydig cell hyperplasia of the biopsy contralateral to the tumour‐bearing testicle in patients with testicular germ cell cancer is associated with biochemical signs of Leydig cell dysfunction after long‐term follow‐up. A case group of 50 long‐term testicular germ cell cancer survivors without human chorionic gonadotropin elevation, 10 testicular germ cell cancer patients with elevated human chorionic gonadotropin and 10 controls without testicular malignancy were included. For each subject, 2–4 representative sections from their testicular biopsies were selected for analysis. Using the image processing program ImageJ (V.1.48, NIH), an area with a minimum of 50 tubules was selected and delineated (total selected area) and the total Leydig cell area was calculated by adding up every delineated Leydig cell group within the total selected area. Four different methods were tested for the ability to quantify the Leydig cell compartment. In the 50 testicular germ cell cancer survivors, associations between the area of the Leydig cell compartment and serum levels of testosterone and luteinising hormone were investigated using linear regression analysis. The Leydig cell compartment was best quantified by the total Leydig cell area/total selected area index, which was significantly larger in the human chorionic gonadotropin‐positive patients than in controls (P = 0.00001). In the 50 human chorionic gonadotropin‐negative testicular germ cell cancer survivors, increasing total Leydig cell area/total selected area was significantly associated with decreased levels of total testosterone and decreased total testosterone/luteinising hormone ratio after a median of 9‐year follow‐up. In conclusion, a new simple method, total Leydig cell area/total selected area, was established to estimate the Leydig cell compartment in testicular biopsies. The index identified Leydig cell hyperplasia in the contralateral biopsy in patients with testicular germ cell cancer, and it was associated with long‐term biochemical Leydig cell dysfunction. Although in testicular germ cell cancer survivors, the clinical value is limited because the contralateral biopsies are not commonly available, we propose a closer andrological follow‐up in any patient with an increased total Leydig cell area/total selected area index.