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A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis

Wed, 02/24/2016 - 4:13pm

T cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-lived after Mtb challenge. To compare memory and naïve CD8+ T cell function during their response to Mtb, we track their expansions using TB10.4-specific retrogenic CD8+ T cells. We find that the primary (naïve) response outnumbers the secondary (memory) response during Mtb challenge, an effect moderated by increased TCR affinity. To determine whether the expansion of polyclonal memory T cells is restrained following Mtb challenge, we used TCRβ deep sequencing to track TB10.4-specific CD8+ T cells after vaccination and subsequent challenge in intact mice. Successful memory T cells, defined by their clonal expansion after Mtb challenge, express similar CDR3β sequences suggesting TCR selection by antigen. Thus, both TCR-dependent and -independent factors affect the fitness of memory CD8+ responses. The impaired expansion of the majority of memory T cell clonotypes may explain why some TB vaccines have not provided better protection.

Skeletal Characterization of Smurf2-Deficient Mice and In Vitro Analysis of Smurf2-Deficient Chondrocytes

Wed, 02/24/2016 - 2:49pm

Overexpression of Smad ubiquitin regulatory factor 2 (Smurf2) in chondrocytes was reported to cause spontaneous osteoarthritis (OA) in mice. However, it is unclear whether Smurf2 is involved in bone and cartilage homeostasis and if it is required for OA pathogenesis. Here we characterized age-related changes in the bone and articular cartilage of Smurf2-deficient (MT) mice by microCT and histology, and examined whether reduced Smurf2 expression affected the severity of OA upon surgical destabilization of the medial meniscus (DMM). Using immature articular chondrocytes (iMAC) from MT and wild-type (WT) mice, we also examined how Smurf2 deficiency affects chondrogenic and catabolic gene expressions and Smurf2 and Smurf1 proteins upon TGF-β3 or IL-1β treatment in culture. We found no differences in cortical, subchondral and trabecular bone between WT and MT in young (4 months) and old mice (16-24 months). The articular cartilage and age-related alterations between WT and MT were also similar. However, 2 months following DMM, young MT showed milder OA compared to WT (~70% vs ~30% normal or exhibiting only mild OA cartilage phenotype). The majority of the older WT and MT mice developed moderate/severe OA 2 months after DMM, but a higher subset of aged MT cartilage (27% vs. 9% WT) remained largely normal. Chondrogenic gene expression (Sox9, Col2, Acan) trended higher in MT iMACs than WT with/without TGF-β3 treatment. IL-1β treatment suppressed chondrgenic gene expression, but Sox9 expression in MT remained significantly higher than WT. Smurf2 protein in WT iMACs increased upon TGF-β3 treatment and decreased upon IL-1β treatment in a dose-dependent manner. Smurf1 protein elevated more in MT than WT upon TGF-β3 treatment, suggesting a potential, but very mild compensatory effect. Overall, our data support a role of Smurf2 in regulating OA development but suggest that inhibiting Smurf2 alone may not be sufficient to prevent or consistently mitigate post-traumatic OA across a broad age range.

Elimination of waste: creation of a successful Lean colonoscopy program at an academic medical center

Mon, 02/22/2016 - 4:47pm

OBJECTIVE: Lean processes involve streamlining methods and maximizing efficiency. Well established in the manufacturing industry, they are increasingly being applied to health care. The objective of this study was to determine feasibility and effectiveness of applying Lean principles to an academic medical center colonoscopy unit.

METHODS: Lean process improvement involved training endoscopy personnel, observing patients, mapping the value stream, analyzing patient flow, designing and implementing new processes, and finally re-observing the process. Our primary endpoint was total colonoscopy time (minutes from check-in to discharge) with secondary endpoints of individual segment times and unit colonoscopy capacity.

RESULTS: A total of 217 patients were included (November 2013-May 2014), with 107 pre-Lean and 110 post-Lean intervention. Pre-Lean total colonoscopy time was 134 min. After implementation of the Lean process, mean colonoscopy time decreased by 10 % to 121 min (p = 0.01). The three steps of the process affected by the Lean intervention (time to achieve adequate sedation, time to recovery, and time to discharge) decreased from 3.7 to 2.4 min (p < 0.01), 4.0 to 3.4 min (p = 0.09), and 41.2 to 35.4 min (p = 0.05), respectively. Overall, unit capacity of colonoscopies increased from 39.6 per day to 43.6. Post-Lean patient satisfaction surveys demonstrated an average score of 4.5/5.0 (n = 73) regarding waiting time, 4.9/5.0 (n = 60) regarding how favorably this experienced compared to prior colonoscopy experiences, and 4.9/5.0 (n = 74) regarding professionalism of staff. One hundred percentage of respondents (n = 69) stated they would recommend our institution to a friend for colonoscopy.

DISCUSSION: With no additional utilization of resources, a single Lean process improvement cycle increased productivity and capacity of our colonoscopy unit. We expect this to result in increased patient access and revenue while maintaining patient satisfaction. We believe these results are widely generalizable to other colonoscopy units as well as other process-based interventions in health care.

Mount Auburn Cemetery and its importance to the history of anesthesia

Mon, 02/22/2016 - 4:40pm

Boston, Massachusetts, is home to many sites related to the first public demonstration of ether, including the Ether Dome, the Ether Monument, and several homes in which William T. G. Morton lived. Notably, many of the participants in Morton’s successful demonstration of ether are buried in nearby Mount Auburn Cemetery in Cambridge, Massachusetts. Here we explore how changing burial customs in early 19th-century America brought so many of these individuals to rest in one location. We explain how Mount Auburn Cemetery was established, the difficulties it faced, how it evolved, and the role it plays today. Moreover, we describe some of its remarkable features and explore some unusual structures located within this institution so very closely associated with the history of anesthesia.

Effects of an in-house coordinator and practitioner referral rather than proxy referral on tissue donation rates

Mon, 02/22/2016 - 4:40pm

INTRODUCTION: Timely referral of patients following asystolic death to an organ procurement organization (OPO) may increase tissue donation rates. Lack of education of health care providers and nonphysicians (admitting department) about timely referral to the OPO following asystolic death may adversely affect tissue donation rates. We hypothesized that using an in-house donation coordinator for provider education and changing the responsibility for calling the OPO from the admitting department to the licensed independent practitioner (LIP) declaring death would increase timely referral and tissue donation rates.

METHODS: An education program was developed in 2005 by a newly hired in-house coordinator to highlight the importance of tissue donation. In addition, to improve timely referrals to the OPO after death, the instructions accompanying the working copy of the death certificate were altered to require the patient's LIP to call the OPO within 1 hour of death (early 2007). Rates for both timely referrals and tissue donors were modeled by a Poisson regression model with a log link function.

RESULTS: Timely referral rates rose from 48% before the interventions to 72% after the intervention (P < .0001). The number of tissue donors per number of referrals also increased significantly (P = .025) over that period.

CONCLUSIONS: An in-house donation coordinator initiated education program and LIP referral rather than referral by other parties following asystolic death results in higher tissue donation rates.

Critical care in patients undergoing lumbar spine fusion: a population-based study

Mon, 02/22/2016 - 4:40pm

BACKGROUND: Data on the utilization of critical care services (CCSs) among patients who underwent spine fusion are rare. Given the increasing popularity of this procedure, information regarding demographics and risk factors for the use of these advanced services is needed in order to appropriately allocate resources, educate clinical staff, and identify targets for future research.

METHODS: We analyzed hospital discharge data of patients who underwent lumbar spine fusion in approximately 400 US hospitals between 2006 and 2010. Patient, procedure, and health care system-related demographics for those requiring CCS were compared to those who did not. Outcomes such as mortality, complications, disposition status, and hospital charges were compared among groups and risk factors for the utilization of CCS identified.

RESULTS: A total of 95 434 entries of patients who underwent posterior lumbar spine fusion surgery between 2006 and 2010 were identified. Approximately 10% of the patients required CCS. On average, patients requiring CCS were older and had a higher comorbidity burden, developed more complications, had longer hospital stays and higher costs, and were less likely to be discharged home compared to non-CCS patients. Risk factors with increased odds for requiring CCS included advanced age, increasing comorbidity burden, increasing surgical invasiveness, and presence of postoperative complications, especially pulmonary.

CONCLUSIONS: Approximately, 10% of the patients undergoing lumbar spine surgery require CCS. Utilizing the present data, critical care physicians and administrators can identify patients at risk, educate clinical staff, identify targets for intervention, and allocate resources to meet the needs of this particular patient population.

T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial

Mon, 02/22/2016 - 4:39pm

BACKGROUND: Microbiologic cultures, the current gold standard diagnostic method for invasive Candida infections, have low specificity and take up to 2-5 days to grow. We present the results of the first extensive multicenter clinical trial of a new nanodiagnostic approach, T2 magnetic resonance (T2MR), for diagnosis of candidemia.

METHODS: Blood specimens were collected from 1801 hospitalized patients who had a blood culture ordered for routine standard of care; 250 of them were manually supplemented with concentrations from < 1 to 100 colony-forming units (CFUs)/mL for 5 different Candida species.

RESULTS: T2MR demonstrated an overall specificity per assay of 99.4% (95% confidence interval [CI], 99.1%-99.6%) with a mean time to negative result of 4.2 +/- 0.9 hours. Subanalysis yielded a specificity of 98.9% (95% CI, 98.3%-99.4%) for Candida albicans/Candida tropicalis, 99.3% (95% CI, 98.7%-99.6%) for Candida parapsilosis, and 99.9% (95% CI, 99.7%-100.0%) for Candida krusei/Candida glabrata. The overall sensitivity was found to be 91.1% (95% CI, 86.9%-94.2%) with a mean time of 4.4 +/- 1.0 hours for detection and species identification. The subgroup analysis showed a sensitivity of 92.3% (95% CI, 85.4%-96.6%) for C. albicans/C. tropicalis, 94.2% (95% CI, 84.1%-98.8%) for C. parapsilosis, and 88.1% (95% CI, 80.2%-93.7%) for C. krusei/C. glabrata. The limit of detection was 1 CFU/mL for C. tropicalis and C. krusei, 2 CFU/mL for C. albicans and C. glabrata, and 3 CFU/mL for C. parapsilosis. The negative predictive value was estimated to range from 99.5% to 99.0% in a study population with 5% and 10% prevalence of candidemia, respectively.

CONCLUSIONS: T2MR is the first fully automated technology that directly analyzes whole blood specimens to identify species without the need for prior isolation of Candida species, and represents a breakthrough shift into a new era of molecular diagnostics.

CLINICAL TRIALS REGISTRATION: NCT01752166.

The epidemiology of Staphylococcus aureus transmission in the anesthesia work area

Mon, 02/22/2016 - 4:39pm

BACKGROUND: Little is known regarding the epidemiology of intraoperative Staphylococcus aureus transmission. The primary aim of this study was to examine the mode of transmission, reservoir of origin, transmission locations, and antibiotic susceptibility for frequently encountered S aureus strains (phenotypes) in the anesthesia work area. Our secondary aims were to examine phenotypic associations with 30-day postoperative patient cultures, phenotypic growth rates, and risk factors for phenotypic isolation.

METHODS: S aureus isolates previously identified as possible intraoperative bacterial transmission events by class of pathogen, temporal association, and analytical profile indexing were subjected to antibiotic disk diffusion sensitivity. The combination of these techniques was then used to confirm S aureus transmission events and to classify them as occurring within or between operative cases (mode). The origin of S aureus transmission events was determined via use of a previously validated experimental model and links to 30-day postoperative patient cultures confirmed via pulsed-field gel electrophoresis. Growth rates were assessed via time-to-positivity analysis, and risk factors for isolation were characterized via logistic regression.

RESULTS: One hundred seventy S aureus isolates previously implicated as possible intraoperative transmission events were further subdivided by analytical profile indexing phenotype. Two phenotypes, phenotype P (patients) and phenotype H (hands), accounted for 65% of isolates. Phenotype P and phenotype H contributed to at least 1 confirmed transmission event in 39% and 28% of cases, respectively. Patient skin surfaces (odds ratio [OR], 8.40; 95% confidence interval [CI], 2.30-30.73) and environmental (OR, 10.89; 95% CI, 1.29-92.13) samples were more likely than provider hands (referent) to have phenotype P positivity. Phenotype P was more likely than phenotype H to be resistant to methicillin (OR, 4.38; 95% CI, 1.59-12.06; P = 0.004) and to be linked to 30-day postoperative patient cultures (risk ratio, 36.63 [risk difference, 0.174; 95% CI, 0.019-0.328]; P < 0.001). Phenotype P exhibited a faster growth rate for methicillin resistant and for methicillin susceptible than phenotype H (phenotype P: median, 10.32H; interquartile range, 10.08-10.56; phenotype H: median, 10.56H; interquartile range, 10.32-10.8; P = 0.012). Risk factors for isolation of phenotype P included age (OR, 14.11; 95% CI, 3.12-63.5; P = 0.001) and patient exposure to the hospital ward (OR, 41.11; 95% CI, 5.30-318.78; P < 0.001).

CONCLUSIONS: Two S aureus phenotypes are frequently transmitted in the anesthesia work area. A patient and environmentally derived phenotype is associated with increased risk of antibiotic resistance and links to 30-day postoperative patient cultures as compared with a provider hand-derived phenotype. Future work should be directed toward improved screening and decolonization of patients entering the perioperative arena and improved intraoperative environmental cleaning to attenuate postoperative health care-associated infections.

The dynamics of Enterococcus transmission from bacterial reservoirs commonly encountered by anesthesia providers

Mon, 02/22/2016 - 4:38pm

BACKGROUND: Enterococci, the second leading cause of health care-associated infections, have evolved from commensal and harmless organisms to multidrug-resistant bacteria associated with a significant increase in patient morbidity and mortality. Prevention of ongoing spread of this organism within and between hospitals is important. In this study, we characterized Enterococcus transmission dynamics for bacterial reservoirs commonly encountered by anesthesia providers during the routine administration of general anesthesia.

METHODS: Enterococcus isolates previously obtained from bacterial reservoirs frequently encountered by anesthesiologists (patient nasopharynx and axilla, anesthesia provider hands, and the adjustable pressure-limiting valve and agent dial of the anesthesia machine) at 3 major academic medical centers were identified as possible intraoperative bacterial transmission events by class of pathogen, temporal association, and phenotypic analysis (analytical profile indexing). They were then subjected to antibiotic disk diffusion sensitivity for transmission event confirmation. Isolates involved in confirmed transmission events were further analyzed to characterize the frequency, mode, origin, location of transmission events, and antibiotic susceptibility of transmitted pathogens.

RESULTS: Three hundred eighty-nine anesthesia reservoir isolates were previously identified by gross morphology and simple rapid tests as Enterococcus. The combination of further analytical profile indexing analysis and temporal association implicated 43% (166/389) of those isolates in possible intraoperative bacterial transmission events. Approximately, 30% (49/166) of possible transmission events were confirmed by additional antibiotic disk diffusion analysis. Two phenotypes, E5 and E7, explained 80% (39/49) of confirmed transmission events. For both phenotypes, provider hands were a common reservoir of origin proximal to the transmission event (96% [72/75] hand origin for E7 and 89% [50/56] hand origin for E5) and site of transmission (94% [16/17] hand transmission location for E7 and 86% [19/22] hand transmission location for E5).

CONCLUSIONS: Anesthesia provider hand contamination is a common proximal source and transmission location for Enterococcus transmission events in the anesthesia work area. Future work should evaluate the impact of intraoperative hand hygiene improvement strategies on the dynamics of intraoperative Enterococcus transmission.

Hand hygiene knowledge and perceptions among anesthesia providers

Mon, 02/22/2016 - 4:38pm

BACKGROUND: Health care worker compliance with hand hygiene guidelines is an important measure for health care-associated infection prevention, yet overall compliance across all health care arenas remains low. A correct answer to 4 of 4 structured questions pertaining to indications for hand decontamination (according to types of contact) has been associated with improved health care provider hand hygiene compliance when compared to those health care providers answering incorrectly for 1 or more questions. A better understanding of knowledge deficits among anesthesia providers may lead to hand hygiene improvement strategies. In this study, our primary aims were to characterize and identify predictors for hand hygiene knowledge deficits among anesthesia providers.

METHODS: We modified this previously tested survey instrument to measure anesthesia provider hand hygiene knowledge regarding the 5 moments of hand hygiene across national and multicenter groups. Complete knowledge was defined by correct answers to 5 questions addressing the 5 moments for hand hygiene and received a score of 1. Incomplete knowledge was defined by an incorrect answer to 1 or more of the 5 questions and received a score of 0. We used a multilevel random-effects XTMELOGIT logistic model clustering at the respondent and geographic location for insufficient knowledge and forward/backward stepwise logistic regression analysis to identify predictors for incomplete knowledge.

RESULTS: The survey response rates were 55.8% and 18.2% for the multicenter and national survey study groups, respectively. One or more knowledge deficits occurred with 81.6% of survey respondents, with the mean number of correct answers 2.89 (95% confidence interval, 2.78- 2.99). Failure of providers to recognize prior contact with the environment and prior contact with the patient as hand hygiene opportunities contributed to the low mean. Several cognitive factors were associated with a reduced risk of incomplete knowledge including providers responding positively to washing their hands after contact with the environment (odds ratio [OR] 0.23, 0.14-0.37, P < 0.001), disinfecting their environment during patient care (OR 0.54, 0.35-0.82, P = 0.004), believing that they can influence their colleagues (OR 0.43, 0.27-0.68, P < 0.001), and intending to adhere to guidelines (OR 0.56, 0.36-0.86, P = 0.008). These covariates were associated with an area under receiver operator characteristics curve of 0.79 (95% confidence interval, 0.74-0.83).

CONCLUSIONS: Anesthesia provider knowledge deficits around to hand hygiene guidelines occur frequently and are often due to failure to recognize opportunities for hand hygiene after prior contact with contaminated patient and environmental reservoirs. Intraoperative hand hygiene improvement programs should address these knowledge deficits. Predictors for incomplete knowledge as identified in this study should be validated in future studies.

Transmission dynamics of gram-negative bacterial pathogens in the anesthesia work area

Mon, 02/22/2016 - 4:38pm

BACKGROUND: Gram-negative organisms are a major health care concern with increasing prevalence of infection and community spread. Our primary aim was to characterize the transmission dynamics of frequently encountered gram-negative bacteria in the anesthesia work area environment (AWE). Our secondary aim was to examine links between these transmission events and 30-day postoperative health care-associated infections (HCAIs).

METHODS: Gram-negative isolates obtained from the AWE (patient nasopharynx and axilla, anesthesia provider hands, and the adjustable pressure-limiting valve and agent dial of the anesthesia machine) at 3 major academic medical centers were identified as possible intraoperative bacterial transmission events by class of pathogen, temporal association, and phenotypic analysis (analytical profile indexing). The top 5 frequently encountered genera were subjected to antibiotic disk diffusion sensitivity to identify epidemiologically related transmission events. Complete multivariable logistic regression analysis and binomial tests of proportion were then used to examine the relative contributions of reservoirs of origin and within- and between-case modes of transmission, respectively, to epidemiologically related transmission events. Analyses were conducted with and without the inclusion of duplicate transmission events of the same genera occurring in a given study unit (first and second case of the day in each operating room observed) to examine the potential effect of statistical dependency. Transmitted isolates were compared by pulsed-field gel electrophoresis to disease-causing bacteria for 30-day postoperative HCAIs.

RESULTS: The top 5 frequently encountered gram-negative genera included Acinetobacter, Pseudomonas, Brevundimonas, Enterobacter, and Moraxella that together accounted for 81% (767/945) of possible transmission events. For all isolates, 22% (167/767) of possible transmission events were identified by antibiotic susceptibility patterns as epidemiologically related and underwent further study of transmission dynamics. There were 20 duplicates involving within- and between-case transmission events. Thus, approximately 19% (147/767) of isolates excluding duplicates were considered epidemiologically related. Contaminated provider hand reservoirs were less likely (all isolates, odds ratio 0.12, 95% confidence interval 0.03-0.50, P = 0.004; without duplicate events, odds ratio 0.05, 95% confidence interval 0.01-0.49, P = 0.010) than contaminated patient or environmental sites to serve as the reservoir of origin for epidemiologically related transmission events. Within- and between-case modes of gram-negative bacilli transmission occurred at similar rates (all isolates, 7% between-case, 5.2% within-case, binomial P value 0.176; without duplicates, 6.3% between-case, 3.7% within-case, binomial P value 0.036). Overall, 4.0% (23/548) of patients suffered from HCAIs and had an intraoperative exposure to gram-negative isolates. In 8.0% (2/23) of those patients, gram-negative bacteria were linked by pulsed-field gel electrophoresis to the causative organism of infection. Patient and provider hands were identified as the reservoirs of origin and the environment confirmed as a vehicle for between-case transmission events linked to HCAIs.

CONCLUSIONS: Between- and within-case AWE gram-negative bacterial transmission occurs frequently and is linked by pulsed-field gel electrophoresis to 30-day postoperative infections. Provider hands are less likely than contaminated environmental or patient skin surfaces to serve as the reservoir of origin for transmission events.

Blood Transfusions May Have Limited Effect on Muscle Oxygenation After Total Knee Arthroplasty

Mon, 02/22/2016 - 4:37pm

BACKGROUND: Traditionally, blood transfusions in the perioperative setting are used to maintain adequate delivery of nutrients and oxygen to organs. However, the effect of blood administration on tissue oxygenation in the perioperative setting remains poorly understood.

QUESTIONS/PURPOSES: The aim of this study was to determine changes in muscle tissue oxygenation saturation (SmO2) in response to perioperative blood transfusions.

PATIENTS AND METHODS: Patients undergoing total knee arthroplasty were enrolled. SmO2, continuous hemoglobin (SpHb), stroke volume (SV), cardiac index, and standard hemodynamic parameters including heart rate (HR), mean arterial blood pressure (MAP), and arterial oxygen saturation (SO2) were recorded. To assess fluid responsiveness, a passive leg raise (PLR) test was performed before the transfusions were started.

RESULTS: Twenty-eight patients were included in the analysis. Mean (+/-SD) SmO2 before transfusion was 63.18 +/- 10.04%, SpHb was 9.27 +/- 1.16 g/dl, and cardiac index was 2.62 +/- 0.75 L/min/m(2). A significant increase during the course of blood transfusion was found for SmO2 (+3.44 +/- 5.81% [95% confidence interval (CI) 1.04 to 5.84], p = 0.007), SpHb (0.74 +/- 0.92 g/dl [95% CI 0.35 to 1.12], p < 0.001), and cardiac index (0.38 +/- 0.51 L/min/m2 [95% CI 0.15 to 0.60], p = 0.002), respectively. However, the correlation between SmO2 and SpHb over the course of the transfusion was negligible (rho = 0.25 [95% CI -0.03 to 0.48]). A similar lack of correlation was found when analyzing data of those patients who showed a positive leg raise test before the start of the transfusion (rho = 0.37 [95% CI -0.11 to 0.84]).

CONCLUSION: We detected a statistically significant increase in SmO2 during the course of a single unit blood transfusion compared to baseline. However, there was no evidence of a correlation between longitudinal SmO2 and SpHb measurements.

Safety and efficacy of commonly used antiemetics

Mon, 02/22/2016 - 4:37pm

INTRODUCTION: Clinicians use antiemetic drugs in a multitude of scenarios. Despite the differences in subspecialty and etiology of the nausea, practitioners of all subspecialties use the same drugs in similar ways to provide relief for their patients.

AREAS COVERED: Multiple classes of antiemetics are used frequently but no single treatment course works for all types of patients. The complex etiology of nausea often requires a multimodal approach that targets the same symptom through different sites of action. Antiemetics have unique side effects and safety profiles which are covered in this review. Antihistamines, phenothiazines, corticosteroids, benzamindes, anticholinergic, neurokinin-1 antagonists, 5-HT3 receptor antagonist and cannabinoids are discussed. These drugs were evaluated based on an in-depth literature review including a review of the original research that led to many of the drugs initial FDA approval, via internet and PubMed searches.

EXPERT OPINION: The key to providing relief for patients suffering from nausea and vomiting is to consider multiple drugs to approach the nausea in a systematic way. Anesthesiologists identify patients who are at high risk of nausea and vomiting based on physical characteristics and surgical procedures. Oncologists treat nausea based on the prescribed chemotherapeutics regimen and known risk of emesis while palliative care physicians and others balance the etiology of the nausea while optimizing patients other co morbid conditions.

The Modified Apnea Test During Brain Death Determination: An Alternative in Patients With Hypoxia

Mon, 02/22/2016 - 4:37pm

INTRODUCTION: Conventional apnea testing in patients with severe hypoxemia or hemodynamic instability with removal from the ventilator support is unsafe. We describe an alternative approach to apnea testing, which may be used in patients with hypoxia unable to undergo conventional apnea testing.

METHODS: Case Report. A 42-year-old man had a severe traumatic brain injury resulting in diffuse cerebral edema and subarachnoid hemorrhage with herniation. His presentation was complicated by hypoxic respiratory failure from pulmonary contusions and hemorrhagic shock. On hospital day 2, the patient lost brain stem reflexes. Brain death testing with conventional apnea testing was attempted but aborted due to hypoxia.

RESULTS: A modified apnea test was applied, which had been approved by appropriate hospital committees including critical care operations, ethics, and the brain death protocol council. Minute ventilation was gradually decreased by > /=50% to attain a PaCo2 level > /=20 mm Hg above baseline. The ventilation mode was then switched from volume control to continuous positive airway pressure while observing the patient for signs of respiration for a duration of 60 seconds.

CONCLUSION: The modified apnea test does not require circuit disconnection and can be successfully applied to determine brain death without compromising safety in high-risk patients having severe hypoxia.

Life after acute fibrinous and organizing pneumonia: a case report of a patient 30 months after diagnosis and review of the literature

Mon, 02/22/2016 - 4:37pm

Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern recently described in the literature with fewer than 120 cases published. AFOP is often difficult to diagnose and may be mistaken for other pulmonary disorders such as interstitial pneumonias or pneumonitides. Patients often present with vague symptoms of cough, dyspnea, hemoptysis, fatigue, and occasionally respiratory failure. Radiological findings show diffuse patchy opacities and ground glass appearance of the lungs. On histologic examination, intra-alveolar fibrin balls are observed. We discuss a case of a man who presented with hemoptysis and dyspnea and whose open lung biopsy revealed AFOP. We will describe the presentation, diagnosis, and post-discharge course, and review the current literature. There are only 4 cases which have reported the patients' course of disease after 1 year, the longest being 2 years. To our knowledge, this is the only case of AFOP in the literature that describes the course of a patient more than 2 years after the diagnosis of AFOP, and is the most comprehensive review of the current literature.

Feasibility of Small Animal Anatomical and Functional Imaging with Neutrons: A Monte Carlo Simulation Study

Thu, 02/18/2016 - 12:09pm

A novel technique is presented for obtaining a single in-vivo image containing both functional and anatomical information in a small animal model such as a mouse. This technique, which incorporates appropriate image neutron-scatter rejection and uses a neutron opaque contrast agent, is based on neutron radiographic technology and was demonstrated through a series of Monte Carlo simulations. With respect to functional imaging, this technique can be useful in biomedical and biological research because it could achieve a spatial resolution orders of magnitude better than what presently can be achieved with current functional imaging technologies such as nuclear medicine (PET, SPECT) and fMRI. For these studies, Monte Carlo simulations were performed with thermal (0.025 eV) neutrons in a 3 cm thick phantom using the MCNP5 simulations software. The goals of these studies were to determine: 1) the extent that scattered neutrons degrade image contrast; 2) the contrasts of various normal and diseased tissues under conditions of complete scatter rejection; 3) the concentrations of Boron-10 and Gadolinium-157 required for contrast differentiation in functional imaging; and 4) the efficacy of collimation for neutron scatter image rejection. Results demonstrate that with proper neutron-scatter rejection, a neutron fluence of 2 ×107 n/cm2 will provide a signal to noise ratio of at least one ( S/N ≥ 1) when attempting to image various 300 μm thick tissues placed in a 3 cm thick phantom. Similarly, a neutron fluence of only 1 ×107 n/cm2 is required to differentiate a 300 μm thick diseased tissue relative to its normal tissue counterpart. The utility of a B-10 contrast agent was demonstrated at a concentration of 50 μg/g to achieve S/N ≥ 1 in 0.3 mm thick tissues while Gd-157 requires only slightly more than 10 μg/g to achieve the same level of differentiation. Lastly, neutr- n collimator with an L/D ratio from 50 to 200 were calculated to provide appropriate scatter rejection for thick tissue biological imaging with neutrons.

Aneurysm permeability following coil embolization: packing density and coil distribution

Thu, 02/18/2016 - 12:09pm

BACKGROUND: Rates of durable aneurysm occlusion following coil embolization vary widely, and a better understanding of coil mass mechanics is desired. The goal of this study is to evaluate the impact of packing density and coil uniformity on aneurysm permeability.

METHODS: Aneurysm models were coiled using either Guglielmi detachable coils or Target coils. The permeability was assessed by taking the ratio of microspheres passing through the coil mass to those in the working fluid. Aneurysms containing coil masses were sectioned for image analysis to determine surface area fraction and coil uniformity.

RESULTS: All aneurysms were coiled to a packing density of at least 27%. Packing density, surface area fraction of the dome and neck, and uniformity of the dome were significantly correlated (p < 0.05). Hence, multivariate principal components-based partial least squares regression models were used to predict permeability. Similar loading vectors were obtained for packing and uniformity measures. Coil mass permeability was modeled better with the inclusion of packing and uniformity measures of the dome (r(2)=0.73) than with packing density alone (r(2)=0.45). The analysis indicates the importance of including a uniformity measure for coil distribution in the dome along with packing measures.

CONCLUSIONS: A densely packed aneurysm with a high degree of coil mass uniformity will reduce permeability.

Treatment failure of fetal posterior communicating artery aneurysms with the pipeline embolization device

Thu, 02/18/2016 - 12:09pm

Aneurysms that involve the internal carotid artery and posterior communicating artery junction and incorporate a fetal posterior cerebral artery are known as fetal posterior communicating artery aneurysms. We report the outcomes of four patients with fetal posterior communicating artery aneurysms who underwent treatment with the pipeline embolization device with or without adjunctive coil embolization. In our study, all four patients failed to achieve aneurysm occlusion at the last follow-up evaluation. Based on our results, we currently do not recommend the use of the flow diverter for the treatment of fetal posterior communicating artery aneurysms.

Phenoxide-Bridged Zinc(II)-Bis(dipicolylamine) Probes for Molecular Imaging of Cell Death

Thu, 02/18/2016 - 12:09pm

Cell death is involved in many pathological conditions, and there is a need for clinical and preclinical imaging agents that can target and report cell death. One of the best known biomarkers of cell death is exposure of the anionic phospholipid phosphatidylserine (PS) on the surface of dead and dying cells. Synthetic zinc(II)-bis(dipicolylamine) (Zn2BDPA) coordination complexes are known to selectively recognize PS-rich membranes and act as cell death molecular imaging agents. However, there is a need to improve in vivo imaging performance by selectively increasing target affinity and decreasing off-target accumulation. This present study compared the cell death targeting ability of two new deep-red fluorescent probes containing phenoxide-bridged Zn2BDPA complexes. One probe was a bivalent version of the other and associated more strongly with PS-rich liposome membranes. However, the bivalent probe exhibited self-quenching on the membrane surface, so the monovalent version produced brighter micrographs of dead and dying cells in cell culture and also better fluorescence imaging contrast in two living animal models of cell death (rat implanted tumor with necrotic core and mouse thymus atrophy). An 111In-labeled radiotracer version of the monovalent probe also exhibited selective cell death targeting ability in the mouse thymus atrophy model, with relatively high amounts detected in dead and dying tissue and low off-target accumulation in nonclearance organs. The in vivo biodistribution profile is the most favorable yet reported for a Zn2BDPA complex; thus, the monovalent phenoxide-bridged Zn2BDPA scaffold is a promising candidate for further development as a cell death imaging agent in living subjects.

Imaging Inflammation in Cerebrovascular Disease

Thu, 02/18/2016 - 12:09pm

Imaging inflammation in large intracranial artery pathology may play an important role in the diagnosis of and risk stratification for a variety of cerebrovascular diseases. Looking beyond the lumen has already generated widespread excitement in the stroke community, and the potential to unveil molecular processes in the vessel wall is a natural evolution to develop a more comprehensive understanding of the pathogenesis of diseases, such as ICAD and brain aneurysms.