No Link Between Inadvertent Surgical Glove Contamination and Surgical Site Infection in Patients Undergoing Elective Neurosurgical Operations.

INTRODUCTION: Controllable factors associated with surgical site infections (SSIs) have focused on reducing contamination of the surgical field with potential pathogens. The aim of this prospective study is to determine the incidence of glove contamination in a series of elective neurosurgical operations and determine the relationship of such glove contamination to subsequent SSI. We hypothesize that contamination of surgical gloves is associated with subsequent SSI. METHODS: In this prospective quality improvement study, gloves of the surgical team were swabbed for standard culture just prior to wound closure of elective neurosurgical operations. Patient characteristics, surgical details, and occurrence of subsequent SSIs were collected retrospectively from the electronic medical records. Data were analyzed with χ2 with Fisher's exact test and Student's t test. RESULTS: Surgical glove contamination occurred in 10 of 96 elective neurosurgical cases (10.4%). SSIs occurred in 6 cases (6.2%), but no SSI occurred in a case in which surgical glove contamination occurred (P = 1). SSI was associated with younger patient age (P = 0.0448), and surgical glove contamination was associated with less resident experience (P = 0.0354). CONCLUSIONS: Surgical glove contamination identified at the time of wound closure does not correlate with the development of subsequent SSI in elective neurosurgical operations.

Multi-Center Validation of the McGovern Pediatric Blunt Cerebrovascular Injury Screening Score.

Blunt cerebrovascular injury (BCVI) is defined as blunt trauma to the head and neck leading to damage to the vertebral and/or carotid arteries; debate exists regarding which children are considered at high risk for BCVI and in need of angiographic/vessel imaging. We previously proposed a screening tool, the McGovern score, to identify pediatric trauma patients at high risk for BCVI, and we aim to validate the McGovern score by pooling data from multiple pediatric trauma centers. This is a multi-center, hospital-based, cohort study from all prospectively registered pediatric (<16 years of age) trauma patients who presented to the emergency department (ED) between 2003 and 2017 at six Level 1 pediatric trauma centers. The registry was retrospectively queried for patients who received a computed tomography angiogram (CTA) as a screening method for BCVI. Age, length of follow-up, mechanism of injury (MOI), arrival Glasgow Coma Scale (GCS) score, and focal neurological deficit were recorded. Radiological variables queried were the presence of a carotid canal fracture, petrous temporal bone fracture, and CT presence of infarction. Patients with BCVI were queried for mode of treatment, type of intracranial injury, artery damaged, and BCVI injury grade. The McGovern score was calculated for all patients who underwent CTA across all data groups. A total of 1012 patients underwent CTA; 72 of these patients were found to have BCVI, 51 of which were in the validation cohort. Across all data groups, the McGovern score has a >80% sensitivity (SN) and >98% negative predictive value (NPV). The McGovern score for pediatric BCVI is an effective, generalizable screening tool.

Peripheral Arterial Disease Prevalence in a Population-Based Sample of People with Diabetes on the Caribbean Island of Barbados.

Background: Peripheral arterial disease (PAD) is a risk factor for amputation and systemic atherosclerotic disease. Barbados has a high diabetes prevalence, and 89% of diabetes-related hospital admissions are for foot problems. Foot examination is infrequent in Barbados primary care. The prevalence and potential risk factors for PAD in people with diabetes in Barbados were studied. Methods: Multistage probability sampling was used to select a representative population sample of people ≥25 years of age with known diabetes or fasting blood glucose ≥7 mmol/L or HbA1c ≥6.5%. We administered the Edinburgh claudication questionnaire and assessed the ankle brachial pressure index (ABI) and Doppler waveform in both dorsalis pedis and posterior tibial arteries. Participants were classified into categories based on ABI as follows: PAD ≤0.90 in any leg; borderline 0.91 to 0.99 in one leg and the other not ≤0.90 or >0.4; normal 1.00 to 1.40 in both legs; and non-compressible >1.40 in one leg and the other not ≤0.9. Waveforms crossing the zero-flow baseline were categorised as normal. Multivariable logistic regression assessed the associations of potential risk factors with PAD. Results: Of 236 participants (74% response rate, 33% male, median age 58.6 years), 51% had previously diagnosed diabetes. Of nine people with symptoms of definite or atypical claudication, four had PAD and one had non-compressible arteries. ABI prevalence (95% CI) was PAD 18.6% (13.8, 24.6), borderline 21.9% (16.6, 28.4), normal 55.5% (49.4, 61.5) and non-compressible 3.9% (1.6, 9.3). Increasing age and female gender were independently associated with PAD. Over 80% of normal legs (ABI 1.00 to 1.40) had normal posterior tibial and dorsalis pedis waveforms, while only 23% legs with PAD (ABI ≤0.90) had normal waveforms in both arteries (Kappa = 0.43). Conclusion: Asymptomatic PAD is common in people with diabetes and requires ABI screening to detect it. Female gender is associated with PAD.

Linac-based hypofractionated stereotactic radiotherapy for metastases involving the brainstem.

The long-term efficacy and complications of hypofractionated stereotactic radiotherapy (hSRT) to metastases involving the brainstem are not well reported. Our objective is to review the results of metastases intrinsic to or abutting the brainstem treatedwith hSRT.Patients treated with hSRT in 5 fractions at our institution from 2016 to 2020 were retrospectively reviewed. Varian Eclipse v13.7 TPS was used for treatment planning. MRI images were fused with CT images acquired at the time of simulation, and contoured structures include the brainstem, the GTV, and a 2 mm margin was used to generate the PTV. MR imaging was performed at 3-month intervals. Survival was assessed at the last available follow-up; tumor control was assessed at 6 and 12 months and toxicity was assessed based on the Radiation Therapy Oncology Group grading system at regular follow-up. Twenty patients were treated with 5 fraction treatment dose plans ranging from 20 Gy - 31.25 Gy. GTV mean volume was 3.5 cc ±â€¯4.3 cc (range 0.1 cc - 18.9 cc). The median overall survival was 6.5 months (range: 1 to 29 months). The twelve-month tumor control rate was 80%. Toxicity was generally mild, with only one patient demonstrating Grade 3 toxicity. Two patients had radiographic progression, but neither required surgical intervention. In our series, hSRT resulted in similar rates of survival, tumor control, and toxicity as compared with published single fraction series. Dose escalation of lesions adjacent to the brainstem can be considered and maybe more feasible with a hypofractionated regimen of 5 fractions.

Diabetes prevention in the Caribbean using Lifestyle Intervention and Metformin Escalation (LIME): Protocol for a hybrid Type-1 effectiveness-implementation trial using a quasi-experimental study design.

BACKGROUND: Globally, several diabetes prevention interventions have been shown to be cost-effective, yet they have had limited adaptation, implementation, and evaluation in the Caribbean and among Caribbean-descent individuals, where the burden of type 2 diabetes is high. We report on the protocol for the Lifestyle Intervention with Metformin Escalation (LIME) study - an evidence-based diabetes prevention intervention to reduce the incidence of diabetes among Caribbean-descent individuals with prediabetes. METHODS: LIME is a hybrid type-I effectiveness-implementation quasi-experimental study taking place in 4 clinical sites in Barbados, Trinidad, the U.S. Virgin Islands, and Puerto Rico. LIME targets individuals who self-identify as Caribbean or Caribbean-descent and have high-risk prediabetes with a hemoglobin A1c (HbA1c) between 6 and 6.4%. Eligible participants in the intervention arm are enrolled in a six-week lifestyle modification workshop. Six months later, individuals who have not lost at least 5% of their bodyweight or continue to have an HbA1c of 6% or higher are prescribed metformin medication. In total, participants are followed for one year. The primary effectiveness outcome is proportion of individuals who lower their HbA1c below 6%. DISCUSSION: LIME is a unique diabetes prevention intervention for Caribbean and Caribbean-descent individuals. LIME utilizes a tailored lifestyle change curriculum, incorporates appropriate metformin prescribing when lifestyle change alone is insufficient, targets the highest-risk individuals with prediabetes, and is based in a clinical setting to ensure sustainability.

2020 family medicine postgraduate examinations at The University of the West Indies: successes and challenges in the time of COVID-19 pandemic.

Little has been published regarding postgraduate assessments during the COVID-19 pandemic. There is an urgent need to graduate well-trained specialists including family physicians who play a key role in patient care. The successes and challenges encountered in mounting qualifying 2020 Family Medicine examinations during the COVID-19 pandemic at the University of the West Indies are described in this paper. Human resource, planning, use of technology and virtual environments are discussed, which enabled successful examinations at this multicampus regional site.

Reliability of an Automated Computerized Hematoma Volumetric Analysis Protocol in Patients with Chronic Subdural Hemorrhage.

BACKGROUND: Hematoma volume in chronic subdural hematoma (CSDH) may predict neurologic deterioration and need for surgical evacuation. Several computer software-assisted methods exist for accurate volume measurements of intracerebral hemorrhage, but no reliable method has been identified for measurement of CSDH volume. METHODS: A total of 30 consecutive patients with CSDH from 2018-2019 admitted to our institution were selected. The noncontrast computed tomography head studies were reviewed by 2 residents. The region of interest method on a Horos Open Source Medical Image Viewer (version 3.3.6) was utilized for volume measurement by each resident (resident-1 and resident-2) independently. Resident-1 repeated the protocol on the same studies 1 month later. We calculated the intra- and interobserver reliability of hematoma volume measurements using the Bland-Altman method. RESULTS: Mean age of the patients was 79 years (range, 50-92 years). For interobserver analysis, resident-1 mean hematoma volume was 85.46 cm3 (range, 6.40-178.63 cm3) and was 87.15 cm3 (range, 8.79-165.97 cm3) for resident-2. The Bland-Altman coefficient of variation was 13.15% (range, 0.07%-46.29%, 97% within the limits of acceptance). For intraobserver analysis, the initial average volume measured by resident-1 was 85.46 cm3 (range, 6.40-178.63 cm3) and subsequent was 95.26 cm3 (range, 10.48-182.99 cm3). The Bland-Altman coefficient of variation was 13.76% (range, 0.81%-48.34%, 97% within the limits of acceptance). CONCLUSIONS: We are reporting inter- and intraobserver reliability for a novel volumetric analysis of CSDH volume using Horos Medical Image Viewer region of interest generated volume calculation. This method is accurate and efficient and could have important clinical and research implications for risk stratification.

Red blood cell phenotype fidelity following glycerol cryopreservation optimized for research purposes.

Intact red blood cells (RBCs) are required for phenotypic analyses. In order to allow separation (time and location) between subject encounter and sample analysis, we developed a research-specific RBC cryopreservation protocol and assessed its impact on data fidelity for key biochemical and physiological assays. RBCs drawn from healthy volunteers were aliquotted for immediate analysis or following glycerol-based cryopreservation, thawing, and deglycerolization. RBC phenotype was assessed by (1) scanning electron microscopy (SEM) imaging and standard morphometric RBC indices, (2) osmotic fragility, (3) deformability, (4) endothelial adhesion, (5) oxygen (O2) affinity, (6) ability to regulate hypoxic vasodilation, (7) nitric oxide (NO) content, (8) metabolomic phenotyping (at steady state, tracing with [1,2,3-13C3]glucose ± oxidative challenge with superoxide thermal source; SOTS-1), as well as in vivo quantification (following human to mouse RBC xenotransfusion) of (9) blood oxygenation content mapping and flow dynamics (velocity and adhesion). Our revised glycerolization protocol (40% v/v final) resulted in >98.5% RBC recovery following freezing (-80°C) and thawing (37°C), with no difference compared to the standard reported method (40% w/v final). Full deglycerolization (>99.9% glycerol removal) of 40% v/v final samples resulted in total cumulative lysis of ~8%, compared to ~12-15% with the standard method. The post cryopreservation/deglycerolization RBC phenotype was indistinguishable from that for fresh RBCs with regard to physical RBC parameters (morphology, volume, and density), osmotic fragility, deformability, endothelial adhesivity, O2 affinity, vasoregulation, metabolomics, and flow dynamics. These results indicate that RBC cryopreservation/deglycerolization in 40% v/v glycerol final does not significantly impact RBC phenotype (compared to fresh cells).

Effects of platelet dysfunction and platelet transfusion on outcomes in traumatic brain injury patients.

OBJECTIVE: Platelet inhibition in traumatic brain injury (TBI) may be due to injury or antiplatelet medication use pre-injury. This study aims to identify factors associated with increased platelet arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition and determine if platelet transfusion reduces platelet dysfunction and affects outcome. METHODS: Prospective thromboelastography (TEG) assays were collected on adult patients with TBI with intracranial injuries detected by computed tomography (CT). Outcomes included in-hospital mortality, and CT lesion expansion. RESULTS: Of 153 patients, ADP inhibition was increased in moderate and severe TBI compared to mild TBI (p = 0.0011). P2Y12 inhibiting medications had increased ADP inhibition (p = 0.0077). Admission ADP inhibition was not associated with in-hospital mortality (p = 0.24) or CT lesion expansion (p = 0.94). Mean reduction of ADP inhibition from platelet transfusion (-15.1%) relative to no transfusion (+ 11.7%) was not statistically different (p = 0.0472). CONCLUSIONS: Mild TBI results in less ADP inhibition compared to moderate and severe TBI, suggesting a dose response relationship between TBI severity and degree of platelet dysfunction. Further, study is warranted to determine efficacy and parameters for platelet transfusion in patients with TBI.

Assessing effects of pressure on tumor and normal tissue physiology using an automated self-calibrated, pressure-sensing probe for diffuse reflectance spectroscopy.

Diffuse reflectance spectroscopy (DRS) represents a quantitative, noninvasive, nondestructive means of assessing vascular oxygenation, vascularity, and structural properties. However, it is known that such measurements can be influenced by the effects of pressure, which is a major concern for reproducible and operator-independent assessment of tissues. Second, regular calibration is a necessary component of quantitative DRS to account for factors such as lamp decay and fiber bending. Without a means of reliably controlling for these factors, the accuracy of any such assessments will be reduced, and potentially biased. To address these issues, a self-calibrating, pressure-controlled DRS system is described and applied to both a patient-derived xenograft glioma model, as well as a set of healthy volunteers for assessments of oral mucosal tissues. It was shown that pressure had a significant effect on the derived optical parameters, and that the effects on the optical parameters were magnified with increasing time and pressure levels. These findings indicate that not only is it critical to integrate a pressure sensor into a DRS device, but that it is also important to do so in an automated way to trigger a measurement as soon as possible after probe contact is made to minimize the perturbation to the tissue site.

Pediatric blunt cerebrovascular injury: the McGovern screening score.

OBJECTIVE The objective of this study was to assess the incidence, diagnosis, and treatment of pediatric blunt cerebrovascular injury (BCVI) at a busy Level 1 trauma center and to develop a tool for accurately predicting pediatric BCVI and the need for diagnostic testing. METHODS This is a retrospective cohort study of a prospectively collected database of pediatric patients who had sustained blunt trauma (patient age range 0-15 years) and were treated at a Level 1 trauma center between 2005 and 2015. Digital subtraction angiography, MR angiography, or CT angiography was used to confirm BCVI. Recently, the Utah score has emerged as a screening tool specifically targeted toward evaluating BCVI risk in the pediatric population. Using logistical regression and adding mechanism of injury as a logit, the McGovern score was able to use the Utah score as a starting point to create a more sensitive screening tool to identify which pediatric trauma patients should receive angiographic imaging due to a high risk for BCVI. RESULTS A total of 12,614 patients (mean age 6.6 years) were admitted with blunt trauma and prospectively registered in the trauma database. Of these, 460 (3.6%) patients underwent angiography after blunt trauma: 295 (64.1%), 107 (23.3%), 6 (1.3%), and 52 (11.3%) patients underwent CT angiography, MR angiography, digital subtraction angiography, and a combination of imaging modalities, respectively. The BCVI incidence (n = 21; 0.17%) was lower than that in a comparable adult group (p < 0.05). The mean patient was age 10.4 years with a mean follow-up of 7.5 months. Eleven patients (52.4%) were involved in a motor vehicle collision, with a mean Glasgow Coma Scale score of 8.6. There were 8 patients (38.1%) with carotid canal fracture, 6 patients (28.6%) with petrous bone fracture, and 2 patients (9.5%) with infarction on initial presentation. Eight patients (38.1%) were managed with observation alone. The Denver, modified Memphis, Eastern Association for the Surgery of Trauma (EAST), and Utah scores, which are the currently used screening tools for BCVI, misclassified 6 (28.6%), 6 (28.6%), 7 (33.3%), and 10 (47.6%) patients with BCVI, respectively, as "low risk" and not in need of subsequent angiographic imaging. By incorporating the mechanism of injury into the score, the McGovern score only misclassified 4 (19.0%) children, all of whom were managed conservatively with no treatment or aspirin. CONCLUSIONS With a low incidence of pediatric BCVI and a nonsurgical treatment paradigm, a more conservative approach than the Biffl scale should be adopted. The Denver, modified Memphis, EAST, and Utah scores did not accurately predict BCVI in our equally large cohort. The McGovern score is the first BCVI screening tool to incorporate the mechanism of injury into its screening criteria, thereby potentially allowing physicians to minimize unnecessary radiation and determine which high-risk patients are truly in need of angiographic imaging.

Coagulopathy in the Setting of Mild Traumatic Brain Injury: Truths and Consequences.

Mild traumatic brain injury (mTBI) is a common, although poorly-defined clinical entity. Despite its initially mild presentation, patients with mTBI can rapidly deteriorate, often due to significant expansion of intracranial hemorrhage. TBI-associated coagulopathy is the topic of significant clinical and basic science research. Unlike trauma-induced coagulopathy (TIC), TBI-associated coagulopathy does not generally follow widespread injury or global hypoperfusion, suggesting a distinct pathogenesis. Although the fundamental mechanisms of TBI-associated coagulopathy are far from clearly elucidated, several candidate molecules (tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), tissue factor (TF), and brain-derived microparticles (BDMP)) have been proposed which might explain how even minor brain injury can induce local and systemic coagulopathy. Here, we review the incidence, proposed mechanisms, and common clinical tests relevant to mTBI-associated coagulopathy and briefly summarize our own institutional experience in addition to identifying areas for further research.

Proton MR spectroscopy of lesion evolution in multiple sclerosis: Steady-state metabolism and its relationship to conventional imaging.

Although MRI assessment of white matter lesions is essential for the clinical management of multiple sclerosis, the processes leading to the formation of lesions and underlying their subsequent MRI appearance are incompletely understood. We used proton MR spectroscopy to study the evolution of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI) in pre-lesional tissue, persistent and transient new lesions, as well as in chronic lesions, and related the results to quantitative MRI measures of T1-hypointensity and T2-volume. Within 10 patients with relapsing-remitting course, there were 180 regions-of-interest consisting of up to seven semi-annual follow-ups of normal-appearing white matter (NAWM, n = 10), pre-lesional tissue giving rise to acute lesions which resolved (n = 3) or persisted (n = 3), and of moderately (n = 9) and severely hypointense (n = 6) chronic lesions. Compared with NAWM, pre-lesional tissue had higher Cr and Cho, while compared with lesions, pre-lesional tissue had higher NAA. Resolving acute lesions showed similar NAA levels pre- and post-formation, suggesting no long-term axonal damage. In chronic lesions, there was an increase in mI, suggesting accumulating astrogliosis. Lesion volume was a better predictor of axonal health than T1-hypointensity, with lesions larger than 1.5 cm3 uniformly exhibiting very low (<4.5 millimolar) NAA concentrations. A positive correlation between longitudinal changes in Cho and in lesion volume in moderately hypointense lesions implied that lesion size is mediated by chronic inflammation. These and other results are integrated in a discussion on the steady-state metabolism of lesion evolution in multiple sclerosis, viewed in the context of conventional MRI measures. Hum Brain Mapp 38:4047-4063, 2017. © 2017 Wiley Periodicals, Inc.

Barriers experienced by patients with multiple sclerosis in seeking care for lower urinary tract symptoms.

AIM: The Actionable Bladder Symptom and Screening Tool (ABSST) is used to identify multiple sclerosis (MS) patients in possible need of evaluation for urinary symptoms. The primary objective of this study was to identify barriers experienced by MS patients in seeking evaluation for urinary symptoms. We also assessed the utility of ABSST tool in identifying patients that will follow up with urologic evaluation. METHODS: This was a prospective observational study where 100 patients with MS were enrolled from an MS center. Patients completed demographic information, questions to assess barriers to care, a short form of the ABSST, and incontinence questionnaires. An ABSST score >3 met criteria for referral and evaluation. One year after enrollment, follow up calls assessed whether patients had seen a urinary specialist. RESULTS: The most common barriers to seeking care included "Doctor never referred" (16%) and "Doctor never asked" (13%). Thirty-eight percent (n = 8/21) of men stated "Doctor never referred" compared to 10% (n = 8/79) of women (P = 0.002). Twenty-seven patients had an ABSST Score ≥3 and were more interested in seeing a specialist compared to those scoring <3 (88.9%, n = 24/27 vs. 26%, n = 19/73; P = <0.001). After 1 year, 70 patients were reached for follow up. A total of 57.9% (n = 11/19) patients who followed up for evaluation screened positive on the ABSST. CONCLUSIONS: The ABSST is a valuable tool to identify MS patients with urinary symptoms who will likely follow up for genitourinary evaluation. However, other barriers beyond awareness exist and prevent patients from being evaluated.

The relationship of cortical folding and brain arteriovenous malformations.

BACKGROUND: The pathogenesis of human intracranial arteriovenous malformations (AVMs) is not well understood; this study aims to quantitatively assess cortical folding in patients with these lesions. METHODS: Seven adult participants, 4 male and 3 female, with unruptured, surgically unresectable intracranial AVMs were prospectively enrolled in the study, with a mean age of 42.1 years and Spetzler-Martin grade range of II-IV. High-resolution brain MRI T1 and T2 sequences were obtained. After standard preprocessing, segmentation and registration techniques, three measures of cortical folding, the depth difference index (DDI), coordinate distance index (CDI) and gyrification index (GI)), were calculated for the affected and unaffected hemispheres of each subject as well as a healthy control subject set. RESULTS: Of the three metrics, CDI, DDI and GI, used for cortical folding assessment, none demonstrated significant differences between the participants and previously studied healthy adults. There was a significant negative correlation between the DDI ratio between affected and unaffected hemispheres and AVM volume (correlation coefficient r = -0.74, p = 0.04). CONCLUSION: This study is the first to quantitatively assess human brain cortical folding in the presence of intracranial AVMs and no significant differences between AVM-affected versus unaffected hemispheres were found in a small dataset. We suggest longitudinal, larger human MRI-based cortical folding studies to assess whether AVMs are congenital lesions of vascular development or de novo, dynamic lesions.

Factors associated with benign multiple sclerosis in the New York State MS Consortium (NYSMSC).

BACKGROUND: This retrospective analysis explored prognostic factors associated with a benign multiple sclerosis (BMS) disease course at baseline and over the 4-year follow-up. METHODS: Patients from the centralized New York State Multiple Sclerosis Consortium registry were classified as having BMS according to 3 different criteria centered on disease duration and disability. Additional analyses explored prognostic factors associated with BMS using the most conservative disability criteria (Expanded Disability Status Scale ≤2 and disease duration ≥10 years). RESULTS: Among 6258 patients who fulfilled eligibility criteria, 19.8 % to 33.3 % were characterized as having BMS, at baseline depending on classification criteria used. Positive prognostic factors for BMS at baseline included female sex (p < 0.0001) and younger age at onset (p < 0.0001); negative prognostic factors included progressive-onset type of MS and African-American race. Of the 1237 BMS patients (per most conservative criteria), 742 were followed for a median of 4 years to explore effect of disease-modifying treatment (DMT) on benign status. DMT (p = 0.009) and longer disease duration (p = 0.007) were the only significant positive predictors of maintaining BMS at follow-up. The protective effect was stronger for patients taking DMT at both enrollment and follow-up (OR = 0.71; p = 0.006). CONCLUSIONS: There is a need for development of more reliable prognostic indicators of BMS. Use of DMT was significantly associated with maintaining a benign disease state.

Conservative fluid management prevents age-associated ventilator induced mortality.

BACKGROUND: Approximately 800 thousand patients require mechanical ventilation in the United States annually with an in-hospital mortality rate of over 30%. The majority of patients requiring mechanical ventilation are over the age of 65 and advanced age is known to increase the severity of ventilator-induced lung injury (VILI) and in-hospital mortality rates. However, the mechanisms which predispose aging ventilator patients to increased mortality rates are not fully understood. Ventilation with conservative fluid management decreases mortality rates in acute respiratory distress patients, but to date there has been no investigation of the effect of conservative fluid management on VILI and ventilator associated mortality rates. We hypothesized that age-associated increases in susceptibility and incidence of pulmonary edema strongly promote age-related increases in ventilator associated mortality. METHODS: 2month old and 20month old male C57BL6 mice were mechanically ventilated with either high tidal volume (HVT) or low tidal volume (LVT) for up to 4h with either liberal or conservative fluid support. During ventilation, lung compliance, total lung capacity, and hysteresis curves were quantified. Following ventilation, bronchoalveolar lavage fluid was analyzed for total protein content and inflammatory cell infiltration. Wet to dry ratios were used to directly measure edema in excised lungs. Lung histology was performed to quantify alveolar barrier damage/destruction. Age matched non-ventilated mice were used as controls. RESULTS: At 4h, both advanced age and HVT ventilation significantly increased markers of inflammation and injury, degraded pulmonary mechanics, and decreased survival rates. Conservative fluid support significantly diminished pulmonary edema and improved pulmonary mechanics by 1h in advanced age HVT subjects. In 4h ventilations, conservative fluid support significantly diminished pulmonary edema, improved lung mechanics, and resulted in significantly lower mortality rates in older subjects. CONCLUSION: Our study demonstrates that conservative fluid alone can attenuate the age associated increase in ventilator associated mortality.

Quantification of normal-appearing white matter tract integrity in multiple sclerosis: a diffusion kurtosis imaging study.

Our aim was to characterize the nature and extent of pathological changes in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS) using novel diffusion kurtosis imaging-derived white matter tract integrity (WMTI) metrics and to investigate the association between these WMTI metrics and clinical parameters. Thirty-two patients with relapsing-remitting MS and 19 age- and gender-matched healthy controls underwent MRI and neurological examination. Maps of mean diffusivity, fractional anisotropy and WMTI metrics (intra-axonal diffusivity, axonal water fraction, tortuosity and axial and radial extra-axonal diffusivity) were created. Tract-based spatial statistics analysis was performed to assess for differences in the NAWM between patients and controls. A region of interest analysis of the corpus callosum was also performed to assess for group differences and to evaluate correlations between WMTI metrics and measures of disease severity. Mean diffusivity and radial extra-axonal diffusivity were significantly increased while fractional anisotropy, axonal water fraction, intra-axonal diffusivity and tortuosity were decreased in MS patients compared with controls (p values ranging from <0.001 to <0.05). Axonal water fraction in the corpus callosum was significantly associated with the expanded disability status scale score (ρ = -0.39, p = 0.035). With the exception of the axial extra-axonal diffusivity, all metrics were correlated with the symbol digits modality test score (p values ranging from 0.001 to <0.05). WMTI metrics are thus sensitive to changes in the NAWM of MS patients and might provide a more pathologically specific, clinically meaningful and practical complement to standard diffusion tensor imaging-derived metrics.

Development and characterization of a naturally derived lung extracellular matrix hydrogel.

The complexity and rapid clearance mechanisms of lung tissue make it difficult to develop effective treatments for many chronic pathologies. We are investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system. The main objectives of this study include effective decellularization of porcine lung tissue, development of a hydrogel from the porcine ECM, and characterization of the material's composition, mechanical properties, and ability to support cellular growth. Our evaluation of the decellularized tissue indicated successful removal of cellular material and immunogenic remnants in the ECM. The self-assembly of the lung ECM hydrogel was rapid, reaching maximum modulus values within 3 min at 37°C. Rheological characterization showed the lung ECM hydrogel to have a concentration dependent storage modulus between 15 and 60 Pa. The purpose of this study was to evaluate our novel ECM derived hydrogel and measure its ability to support 3D culture of MSCs in vitro and in vivo delivery of MSCs. Our in vitro experiments using human mesenchymal stem cells demonstrated our novel ECM hydrogel's ability to enhance cellular attachment and viability. Our in vivo experiments demonstrated that rat MSC delivery in pre-gel solution significantly increased cell retention in the lung over 24 h in an emphysema rat model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1922-1935, 2016.