Associations of cardiometabolic polygenic risk scores with cardiovascular disease in African Americans.

Background: Cardiovascular disease (CVD) is a complex disease, and genetic factors contribute individually or cumulatively to CVD risk. While African American women and men are disproportionately affected by CVD, their lack of representation in genomic investigations may widen disparities in health. We investigated the associations of cardiometabolic polygenic risk scores (PRSs) with CVD risk in African Americans. Methods: We used the Jackson Heart Study, a prospective cohort study of CVD in African American adults and the predicted atherosclerotic cardiovascular disease (ASCVD) 10-year risk. We included 40-79 years old adults without a history of coronary heart disease (CHD) or stroke at baseline. We derived genome-wide PRSs for systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, LDL cholesterol, hemoglobin A1c (HbA1c), triglycerides, and C-reactive protein (CRP) separately for each of the participants, using African-origin UK Biobank participants' genome-wide association summary statistics. We estimated the associations between PRSs and 10-year predicted ASCVD risk adjusting for age, sex, study visit date, and genetic ancestry using linear and logistic regression models. Results: Participants (n=2,077) were 63% female and 66% never-smokers. They had mean (SD) 56 (10) years of age, 127.8 (16.3) mmHg SBP, 76.3 (8.7) mmHg DBP, 200.4 (40.2) mg/dL total cholesterol, 51.7 (14.7) mg/dL HDL cholesterol, 127.2 (36.7) mg/dL LDL cholesterol, 6.0 (1.3) mmol/mol HbA1c, 108.9 (81.7) mg/dL triglycerides and 0.53 (1.1) CRP. Their median (interquartile range) predicted 10-year predicted ASCVD risk was 8.0 (4.0-15.0). Participants in the >75th percentile for HbA1c PRS had 1.42 percentage-point greater predicted 10-year ASCVD risk (1.42 [95% CI: 0.58-2.26]) and higher odds of ≥10% predicted 10-year ASCVD risk (OR: 1.46 [95% CI: 1.03-2.07]) compared with those in the <25th percentile for HbA1c PRS. Participants in the >75th percentile for SBP PRS had higher odds of ≥10% predicted 10-year ASCVD risk (OR: 1.52 [95% CI: 1.07-2.15]) compared with those in the <25th percentile for SBP PRS. Conclusion: Among 40-79 years old African Americans without CHD and stroke, higher PRSs for HbA1c and SBP were associated with CVD risk. PRSs may help stratify individuals based on their clinical risk factors for CVD early prevention and clinical management.

Influences of sociodemographic characteristics and parental HPV vaccination hesitancy on HPV vaccination coverage in five US states.

BACKGROUND: In the United States (US), half of new human papillomavirus (HPV) infections occur among young people aged 15-24 years. Despite the effectiveness of HPV vaccination in protecting against HPV-associated cancers, its coverage among adolescents remains suboptimal. This study examined the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage in five US states with disproportionately low adolescent coverage rates compared to the national average. METHODS: Responses to an online Qualtrics survey from 926 parents of children aged 9-17 years in Arkansas, Mississippi, Missouri, Tennessee, and Southern Illinois in July 2021 were analyzed using multivariate logistic regression to estimate the association of sociodemographic characteristics and HPV vaccination hesitancy with HPV vaccination coverage. RESULTS: Of the parents, 78 % were female, 76 % were non-Hispanic White, 61.9 % lived in rural areas, 22 % were classified as HPV vaccine hesitant, and 42 % had vaccinated their oldest child between the ages of 9-17 years against HPV. Children of vaccine hesitant parents were less likely to have received any doses of the HPV vaccine than children of non-vaccine hesitant parents (AOR: 0.17, 95 % CI:0.11-0.27). Male children were less likely to have initiated the HPV vaccine series than female children (AOR: 0.70, 95 % CI:0.50-0.97). Older children (13-17 vs 9-12 years), receiving the meningococcal conjugate or most recent seasonal influenza vaccine were all associated with higher likelihoods of receiving any doses of the HPV vaccine (AOR: 6.01, 95 % CI:3.98-9.08; AOR: 2.24, 95 % CI:1.27-3.95; AOR: 2.41, 95 % CI:1.73-3.36, respectively). CONCLUSIONS: Adolescent HPV vaccination coverage remains low in our targeted states. Children's age, sex, and parental vaccine hesitancy were significantly associated with likelihood of HPV vaccination. These findings offer the opportunity for targeted interventions among parents in regions with low vaccine uptake and underscore the importance of developing and implementing strategies to address parental HPV vaccination hesitancy to improve uptake in the US.

Descriptive Analysis of Combat-Associated Aspiration Pneumonia.

BACKGROUND: Airway obstruction is the second leading cause of potentially preventable death on the battlefield. The treatment for airway obstruction is intubation or advanced airway adjunct, which has a known risk of aspiration. We sought to describe the variables associated with aspiration pneumonia after prehospital airway intervention. METHODS: This is a sub-analysis of previously described data from the Department of Defense Trauma Registry (DoDTR) from 2007 to 2020. We included casualties that had at least one prehospital airway intervention with documentation of subsequent aspiration pneumonia or pneumonia within three days of the intervention. We used a generalized linear model with Firth bias estimates to test for associations. RESULTS: There were 1,509 casualties that underwent prehospital airway device placement. Of these, 41 (2.7%) met inclusion criteria into the aspiration pneumonia cohort. The demographics had no statistical difference between the groups. The non-aspiration cohort had fewer median ventilator days (2 versus 6, p < 0.001), intensive care unit days (2 versus 7, p < 0.001, and hospital days [3 versus 8, p < 0.001]). Survival was lower in the non-aspiration cohort (74.2% versus 90.2%, p = 0.017). The administration of succinylcholine was higher in the non-aspiration cohort (28.0% versus 12.2%, p = 0.031). In our multivariable model, only the administration of succinylcholine was significant and was associated with lower probability of aspiration pneumonia (odds ratio 0.56). CONCLUSION: Overall, the incidence of aspiration pneumonia was low in our cohort. The administration of succinylcholine was associated with a lower odds of developing aspiration pneumonia.

More sophisticated than a drink cooler or an old sphygmomanometer but still not adequate for prehospital blood: A market review of commercially available equipment for prehospital blood transport and administration.

BACKGROUND: Hemorrhage is the leading cause of death in trauma patients with most fatalities occurring before reaching a higher level of care-this applies to both the civilian setting and the military combat setting. Hemostatic resuscitation with increased emphasis on blood transfusion while limiting use of crystalloids has become routine in trauma care. However, the prehospital setting-especially in combat-presents unique challenges with regard to storage, transport, and administration. We sought to evaluate available technology on the market for storage and administration technology that is relevant to the prehospital setting. STUDY DESIGN AND METHODS: We conducted a market review of available technology through subject-matter expert inquiry, reviews of published literature, reviews of Federal Drug Administration databases, internal military publications, and searches of Google. RESULTS: We reviewed and described a total of 103 blood transporters, 22 infusers, and 6 warmers. CONCLUSIONS: The risk of on-scene fatality in trauma patients and recent developments in trauma care demonstrate the need for prehospital transfusion. These transfusions have been logistically prohibited in many operations. We have reviewed the current commercially available equipment and recommended pursuit of equipment that improves accessibility to field transfusion. Current technology has limited applicability for the prehospital setting and is further limited for the military setting.

Interaction of Np(v) with borate in alkaline, dilute-to-concentrated, NaCl and MgCl2 solutions.

The interaction of Np(v) with borate was investigated in 0.1-5.0 M NaCl and 0.25-4.5 M MgCl2 solutions with 7.2 ≤ pHm ≤ 10.0 (pHm = -log[H+]) and 0.004 M ≤ [B]tot ≤ 0.16 M. Experiments were performed under an Ar-atmosphere at T = (22 ± 2) °C using a combination of under- and oversaturation solubility experiments, NIR spectroscopy, and extensive solid phase characterization. A bathochromic shift (≈5 nm) in the Np(v) band at λ = 980 nm indicates the formation of weak Np(v)-borate complexes under mildly alkaline pHm-conditions. The identification of an isosbestic point supports the formation of a single Np(v)-borate species in dilute MgCl2 systems, whereas a more complex aqueous speciation (eventually involving the formation of several Np(v)-borate species) is observed in concentrated MgCl2 solutions. The solubility of freshly prepared NpO2OH(am) remained largely unaltered in NaCl and MgCl2 solutions with [B]tot = 0.04 M within the timeframe of this study (t ≤ 300 days). At [B]tot = 0.16 M, a kinetically hindered but very significant drop in the solubility of Np(v) (3-4 log10-units, compared to borate-free systems) was observed in NaCl and dilute MgCl2 solutions with pHm ≤ 9. The drop in the solubility was accompanied by a clear change in the colour of the solid phase (from green to white-greyish). XRD and TEM analyses showed that the amorphous NpO2OH(am) "starting material" transformed into crystalline solid phases with similar XRD patterns in NaCl and MgCl2 systems. XPS, SEM-EDS and EXAFS further indicated that borate and Na/Mg participate stoichiometrically in the formation of such solid phases. Additional undersaturation solubility experiments using the newly formed Na-Np(v)-borate(cr) and Mg-Np(v)-borate(cr) compounds further confirmed the low solubility ([Np(v)]aq ≈ 10-6-10-7 M) of such solid phases in mildly alkaline pHm-conditions. The formation of these solid phases represents a previously unreported retention mechanism for the highly mobile Np(v) under boundary conditions (pHm, [B]tot, ionic strength) of relevance to certain repository concepts for nuclear waste disposal.

Epigenetic regulation of POMC; implications for nutritional programming, obesity and metabolic disease.

Proopiomelanocortin (POMC) is a key mediator of satiety. Epigenetic marks such as DNA methylation may modulate POMC expression and provide a biological link between early life exposures and later phenotype. Animal studies suggest epigenetic marks at POMC are influenced by maternal energy excess and restriction, prenatal stress and Triclosan exposure. Postnatal factors including energy excess, folate, vitamin A, conjugated linoleic acid and leptin may also affect POMC methylation. Recent human studies suggest POMC DNA methylation is influenced by maternal nutrition in early pregnancy and associated with childhood and adult obesity. Studies in children propose a link between POMC DNA methylation and elevated lipids and insulin, independent of body habitus. This review brings together evidence from animal and human studies and suggests that POMC is sensitive to nutritional programming and is associated with a wide range of weight-related and metabolic outcomes.

Factors influencing fall prevention for patients with spinal cord injury from the perspectives of administrators in Canadian rehabilitation hospitals.

BACKGROUND: Fall prevention is a priority in Canadian tertiary rehabilitation hospitals. We aimed to understand the perspectives of hospital administrators on the challenges experienced when implementing fall prevention policies/procedures for patients with spinal cord injury (SCI) in tertiary rehabilitation hospitals. METHODS: Semi-structured interviews were conducted with 10 administrators employed in six Canadian tertiary rehabilitation hospitals. Guided by an interpretive description framework, interviews were analyzed using a constant comparison approach. RESULTS: Challenges with fall prevention experienced by administrators fell into the three categories: 1) fall prevention policy and procedural challenges (e.g. fall prevention policy not SCI-specific, expectation of zero falls, determining contributing factors, learning from falls, and overall effectiveness of the fall prevention policy), 2) clinician-related challenges (e.g. variable staff adherence with the organizations' fall prevention procedures, inconsistent delivery of fall prevention education, and integrating individualized fall risks to guide clinical practice), and 3) patient-related challenges (e.g. balancing risk vs independence and rehabilitation progress, responsibility for fall prevention, and non-preventable falls). CONCLUSIONS: Fall prevention policies/procedures required by the hospitals were insufficient for clinical practice in SCI rehabilitation.

The addition of metronomic chemotherapy does not improve outcome for canine splenic haemangiosarcoma.

OBJECTIVES: To determine whether the addition of metronomic chemotherapy improved outcome for dogs with splenic haemangiosarcoma treated with splenectomy and adjuvant maximum tolerated dose chemotherapy. MATERIALS AND METHODS: Medical records were examined retrospectively for dogs with splenic haemangiosarcoma that had undergone splenectomy followed by anthracycline-based chemotherapy. Thirty-nine dogs underwent splenectomy followed by maximum tolerated dose chemotherapy with an anthracycline, cyclophosphamide, or both (Group 1). Twenty-two dogs underwent splenectomy followed by adjuvant maximum tolerated dose chemotherapy with an anthracycline, cyclophosphamide, or both, plus metronomic chemotherapy (Group 2). Dogs in both groups were further separated into those treated with either maximum tolerated dose anthracycline or maximum tolerated dose anthracycline and cyclophosphamide. RESULTS: Median progression-free survival was 165 days and median overall survival time was 180 days in Group 1. Median progression-free survival was 185 days and median overall survival time was 212 days in Group 2. In both groups, the overall survival was shorter in dogs that had received maximum tolerated dose cyclophosphamide. CLINICAL SIGNIFICANCE: The addition of metronomic to maximum tolerated dose chemotherapy protocols does not appear to improve outcome in dogs with splenic haemangiosarcoma treated with splenectomy and maximum tolerated dose chemotherapy.

Parkinsonian GM2 synthase knockout mice lacking mature gangliosides develop urinary dysfunction and neurogenic bladder.

Parkinson's disease is a neurodegenerative disorder that reduces a patients' quality of life by the relentless progression of motor and non-motor symptoms. Among the non-motor symptoms is a condition called neurogenic bladder that is associated with detrusor muscle underactivity or overactivity occurring from neurologic damage. In Parkinson's disease, Lewy-body-like protein aggregation inside neurons typically contributes to pathology. This is associated with dopaminergic neuron loss in substantia nigra pars compacta (SNc) and in ventral tegmental area (VTA), both of which play a role in micturition. GM1 gangliosides are mature glycosphingolipids that enhance normal myelination and are reduced in Parkinson's brain. To explore the role of mature gangliosides in vivo, we obtained GM2 Synthase knockout (KO) mice, which develop parkinsonian pathology including a loss of SNc dopaminergic neurons, which we reconfirmed. However, bladder function and innervation have never been assessed in this model. We compared GM2 Synthase KO and wild type (WT) littermates' urination patterns from 9 to 19 months of age by counting small and large void spots produced during 1 h tests. Because male and female mice had different patterns, we evaluated data by sex and genotype. Small void spots were significantly increased in 12-16 month GM2 Synthase KO females, consistent with overactive bladder. Similarly, at 9-12 month GM2 KO males tended to have more small void spots than WT males. As GM2 Synthase KO mice aged, both females and males had fewer small and large void spots, consistent with detrusor muscle underactivity. Ultrasounds confirmed bladder enlargement in GM2 Synthase KO mice compared to WT mice. Tyrosine hydroxylase (TH) immunohistochemistry revealed significant dopaminergic loss in GM2 Synthase KO VTA and SNc, and a trend toward TH loss in the GM2 KO periaqueductal gray (PAG) micturition centers. Levels of the nerve growth factor precursor, proNGF, were significantly increased in GM2 Synthase KO bladders and transmission electron micrographs showed atypical myelination of pelvic ganglion innervation in GM2 Synthase KO bladders. Cumulatively, our findings provide the first evidence that mature ganglioside loss affects micturition center TH neurons as well as proNGF dysregulation and abnormal innervation of the bladder. Thus, identifying therapies that will counteract these effects should be beneficial for those suffering from Parkinson's disease and related disorders.

Geographical differences in survival of dogs with non-Hodgkin lymphoma treated with a CHOP based chemotherapy protocol.

BACKGROUND: In humans geographical differences in the incidence and presentation of various cancers have been reported. However, much of this information has not been collected in veterinary oncology. AIM: The purpose of this study was to determine if a geographic difference in progression free survival exists for dogs with lymphoma treated within the US. MATERIALS AND METHODS: Medical records of 775 cases of canine lymphoma from 3 US regions (west, south and north), treated with CHOP chemotherapy, were retrospectively evaluated. Cases were collected from referral institutions and were required to have received at least one doxorubicin treatment and have follow up information regarding time to progression. RESULTS: Significant differences in sex (p = 0.05), weight (p = 0.049), stage (p < 0.001), immunophenotype (p = <0.001), and number of doxorubicin doses (p = 0.001) were seen between regions. Upon univariate analysis, progression free survival (PFS) differed by region (p = 0.006), stage (p = 0.009), sub-stage (p = 0.0005), and immunophenotype (p = 0.001). A multivariable Cox regression model showed that dogs in the western region had a significantly shorter PFS when compared to the south and east. CONCLUSION: PFS was significantly affected by stage, sub-stage and phenotype.

Vitamin D binding protein genotype is associated with plasma 25OHD concentration in West African children.

Vitamin D is well known for its role in promoting skeletal health. Vitamin D status is determined conventionally by circulating 25-dihydroxyvitamin D (25OHD) concentration. There is evidence indicating that circulating 25OHD concentration is affected by variation in Gc, the gene encoding the vitamin D binding protein (DBP). The composite genotype of two single nucleotide polymorphisms (rs7041 and rs4588) results in different DBP isotypes (Gc1f, Gc1s and Gc2). The protein configurational differences among DBP isotypes affect DBP substrate binding affinity. The aims of this study were to determine 1) Gc variant frequencies in a population from an isolated rural region of The Gambia, West Africa (n=3129) with year-round opportunity for cutaneous vitamin D synthesis and 2) the effects of Gc variants on 25OHD concentration (n=237) in a genetically representative sub-group of children (mean (SD) age: 11.9 (4.8) years). The distribution of Gc variants was Gc1f: 0.86, Gc1s: 0.11 and Gc2: 0.03. The mean (SD) concentration of 25OHD was 59.6 (12.9) nmol/L and was significantly higher in those homozygous for Gc1f compared to other Gc variants (60.7 (13.1) vs. 56.6 (12.1) nmol/L, P=0.03). Plasma 25OHD and 1,25(OH)2D concentration was significantly associated with parathyroid hormone in Gc1f-1f but not in the other Gc variants combined. This study demonstrates that different Gc variants are associated with different 25OHD concentrations in a rural Gambian population. Gc1f-1f, thought to have the highest affinity for 25OHD, had the highest 25OHD concentration compared with lower affinity Gc variants. The considerable difference in Gc1f frequency observed in Gambians compared with other non-West African populations and associated differences in plasma 25OHD concentration, may have implications for the way in which vitamin D status should be interpreted across different ancestral groups.

Region-of-interest cone beam computed tomography (ROI CBCT) with a high resolution CMOS detector.

Cone beam computed tomography (CBCT) systems with rotational gantries that have standard flat panel detectors (FPD) are widely used for the 3D rendering of vascular structures using Feldkamp cone beam reconstruction algorithms. One of the inherent limitations of these systems is limited resolution (<3 lp/mm). There are systems available with higher resolution but their small FOV limits them to small animal imaging only. In this work, we report on region-of-interest (ROI) CBCT with a high resolution CMOS detector (75 µm pixels, 600 µm HR-CsI) mounted with motorized detector changer on a commercial FPD-based C-arm angiography gantry (194 µm pixels, 600 µm HL-CsI). A cylindrical CT phantom and neuro stents were imaged with both detectors. For each detector a total of 209 images were acquired in a rotational protocol. The technique parameters chosen for the FPD by the imaging system were used for the CMOS detector. The anti-scatter grid was removed and the incident scatter was kept the same for both detectors with identical collimator settings. The FPD images were reconstructed for the 10 cm x10 cm FOV and the CMOS images were reconstructed for a 3.84 cm × 3.84 cm FOV. Although the reconstructed images from the CMOS detector demonstrated comparable contrast to the FPD images, the reconstructed 3D images of the neuro stent clearly showed that the CMOS detector improved delineation of smaller objects such as the stent struts (~70 µm) compared to the FPD. Further development and the potential for substantial clinical impact are suggested.

State funding for health information technology and selected ambulatory healthcare quality measures.

BACKGROUND: Previous studies on the effects of health information technology (health IT) on ambulatory quality have had mixed results. New York State has invested heavily in health IT throughout the State, creating a unique opportunity to assess effects on health care quality across multiple communities. OBJECTIVE: To determine any association between primary care providers' receipt of funding from New York State's Healthcare Efficiency and Affordability Law for New Yorkers Program (HEAL NY) and ambulatory quality of care. METHODS: A statewide, longitudinal cohort study of primary care physicians in New York State was conducted. Data regarding which primary care physicians received funding through the HEAL NY program (Phase 5 or Phase 10) in 2008 or 2009 were obtained from the New York State Department of Health. Health care quality in 2010 was measured using claims data that had been aggregated across 7 commercial health plans across the state. Physicians were divided into 2 groups, based on receipt of HEAL funding (yes/no). Any association was measured between study group and each of 7 quality measures, all of which appear in the Stage 1 federal Meaningful Use program. Negative binomial regression was used, adjusting for provider gender and specialty. RESULTS: The study included 3,988 primary care providers, of whom 863 (22%) had received HEAL NY funding. The HEAL-funded physicians provided higher quality of care on 5 of the 7 measures: breast cancer screening, eye exams in patients with diabetes, nephropathy screening in patients with diabetes, influenza vaccination and pneumococcal vaccination (p<0.0001 for all adjusted comparisons). The HEAL-funded group provided higher quality of care by an absolute 2 to 6 percentage points per measure for those 5 measures. CONCLUSION: Primary care physicians who received state funding for health IT provided higher quality of care than those who did not receive such funding.

Association between use of a health information exchange system and hospital admissions.

OBJECTIVE: Relevant patient information is frequently difficult to obtain in emergency department (ED) visits. Improved provider access to previously inaccessible patient information may improve the quality of care and reduce hospital admissions. Health information exchange (HIE) systems enable access to longitudinal, community-wide patient information at the point of care. However, the ability of HIE to avert admissions is not well demonstrated. We sought to determine if HIE system usage is correlated with a reduction in admissions via the ED. METHODS: We identified 15,645 adults from New York State with an ED visit during a 6-month period, all of whom consented to have their information accessible in the HIE system, and were continuously enrolled in two area health plans. Using claims we determined if the ED encounter resulted in an admission. We used the HIE's system log files to determine usage during the encounter. We determined the association between HIE system use and the likelihood of admission to the hospital from the ED and potential cost savings. RESULTS: The HIE system was accessed during 2.4% of encounters. The odds of an admission were 30% lower when the system was accessed after controlling for confounding (odds ratio = 0.70; 95%C I= 0.52, 0.95). The annual savings in the sample was $357,000. CONCLUSION: These findings suggest that the use of an HIE system may reduce hospitalizations from the ED with resultant cost savings. This is an important outcome given the substantial financial investment in interventions designed to improve provider access to patient information in the US.

Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury.

The Hedgehog (Hh) pathway is a crucial regulator of muscle development during embryogenesis. We have previously demonstrated that Sonic hedgehog (Shh) regulates postnatal myogenesis in the adult skeletal muscle both directly, by acting on muscle satellite cells, and indirectly, by promoting the production of growth factors from interstitial fibroblasts. Here, we show that in mdx mice, the murine equivalent of Duchenne muscular dystrophy in humans, progression of the dystrophic pathology corresponds to progressive inhibition of the Hh signaling pathway in the skeletal muscle. We also show that the upregulation of the Hh pathway in response to injury and during regeneration is significantly impaired in mdx muscle. Shh treatment increases the proliferative potential of satellite cells isolated from the muscles of mdx mice. This treatment also increases the production of proregenerative factors, such as insulin-like growth factor-1 and vascular endothelial growth factor, from fibroblasts isolated from the muscle of mdx mice. In vivo, overexpression of the Hh pathway using a plasmid encoding the human Shh gene promotes successful regeneration after injury in terms of increased number of proliferating myogenic cells and newly formed myofibers, as well as enhanced vascularization and decreased fibrosis.

Evaluation of the oral antimitotic agent (ABT-751) in dogs with lymphoma.

BACKGROUND: ABT-751 is a novel orally available antimitotic agent that targets microtubule polymerization. This mechanism may suggest potential activity in canine lymphoma. OBJECTIVE: Determine a maximum tolerated dose for ABT-751, and assess long-term tolerability and activity in canine lymphoma. ANIMALS: Thirty dogs with newly diagnosed (n = 19) or relapsed (n = 11) non-Hodgkin's lymphoma. METHODS: Dogs (n = 11) were enrolled in a rapid dose escalation study to define the maximum tolerated dose. Upon definition of a maximally tolerated dose, a cohort expansion of 19 dogs allowed verification of long-term tolerability and assessment of activity. Study endpoints in the cohort expansion included chronic tolerability, response rate, response duration, and time to progression. Additional endpoints included serum pharmacokinetics, lymph node drug concentrations, and changes in circulating endothelial cells. RESULTS: The maximum tolerated dose of ABT-751 was 350 mg/m(2) PO q24h. Dose-limiting toxicities included vomiting and diarrhea, which resolved with a schedule adjustment to 350 mg/m(2) PO q48h. ABT-751 was consistently detected in lymphoma tissue samples from dogs treated at or above the maximum tolerated dose. In the cohort expansion, objective responses were seen in 3/15 (20%) dogs with a response duration ranging from 21 to 111 days. Decreases in circulating endothelial cells were seen in 10 dogs at day 7 (2 responding dogs and 8 nonresponding dogs). CONCLUSION: ABT-751 was well tolerated at 350 mg/m(2) PO q24h for 7 days and then q48h thereafter. Activity of ABT-751 suggested a rationale for additional studies of ABT-751 as part of a combination chemotherapy protocol for lymphoma or other canine cancers.

WE-G-217BCD-06: Fully Incorporated Scanning Geometry for Improved Accuracy in C-Arm CBCT Image Reconstruction.

PURPOSE: The adoption of C-arm cone-beam CT (CBCT) can minimize interruption to the interventional workflow. However, C-arm gantry rotation can be susceptible to gravity and mechanical instability, therefore resulting images with contamination of tilting and wobbling motion. The purpose of this work is to investigate and demonstrate potential improvement of C-arm CBCT images by tailoring and applying an innovative iterative algorithm that can fully incorporate accurate scanning geometry. METHODS: A clinical C-arm CBCT system (Toshiba Infinix-i, Japan) was used for collecting projection data of a patient's brain with aneurysm. A mask scan was performed before contrast was injected, and a contrast scan was performed during continuous contrast feeding. During each scan, 108 projections were acquired over a range of approximately 200 degrees within about 4.6 seconds. Logarithm subtraction was then carried out view by view to obtain 108 projections of virtually only the vasculature. An iterative algorithm, referred to as the ASD-POCS algorithm, was modified to fully incorporate calibration data characterizing the actual scan geometry that deviates from a circular trajectory due to gantry tilting and wobbling. We then applied both FDK and ASD-POCS algorithms to reconstructing image from the acquired patient data. RESULTS: In FDK reconstructions without considering C-arm tilting and wobbling motion, artifacts can be observed, which break vessel continuity and compromise image's clinical utility. We then performed FDK reconstructions by incorporating the system geometry in the back-projection step and obtained improved vessel continuity. Finally we applied the ASD- POCS algorithm by incorporating calibration data in the forward- and back- projector, and obtained reconstructions with further improvement on the recovery of small, secondary vascular branches. CONCLUSIONS: Appropriately developed iterative algorithms can improve C-arm CBCT image quality by fully incorporating scanning geometry, and can potentially enable spatial-resolution demanding applications which can be challenging to achieve with the FDK algorithm.

Extended Outcomes of Complex Coronary Disease in the Drug Eluting Stent Era.

BACKGROUND: Several randomized trials comparing bare-metal stents to Drug-Eluting Stents (DES) have demonstrated a significant reduction in Target Vessel Revascularization (TVR) and Target Lesion Revascularization (TLR) exists with the use of drug-eluting stents, without compromising survival. These conclusions are based on restricted inclusion criteria for patients and lesion. It is unknown if these results can be generalized to an unselected patient population and more complex disease. The objective of this study was to determine to what extent the availability of DES has impacted survival, TVR, and TLR in a large regional experience without the restriction of on-label indications. METHODS: Patients registered with the Northern New England Cardiovascular Disease Study Group's PCI registry with single vessel coronary disease undergoing a first PCI were sorted according to the Bare-Metal stent (BMS) era (2001 - 2002) or the Drug-Eluting stent (DES) era (2004 - 2005) based on the time period their first PCI took place. Totally, 6,093 BMS and 5,651 DES patients were identified. Outcomes of survival, TLR and TVR were measured after one year. RESULTS: After 1 year, survival was comparable, TLR was reduced by 4.9% (absolute) and TVR was reduced by 5.4% (absolute) in the DES era compared to the BMS era. The TLR/TVR differences remained significant after propensity matching in the DES era vs BMS era (Mortality: HR 1.00, 95% CI: 0.83 - 1.28; TLR: HR 0.40, 95% CI 0.32 - 0.46; TVR: HR 0.44, 95% CI 0.38 - 0.51). CONCLUSIONS: In large regional experience with a consecutive series of patients representing the contemporary practice of PCI, including both on and off label use, the frequent use of DES reduces the risk of TVR and TLR without compromising survival.

Ertapenem-resistant Enterobacteriaceae: risk factors for acquisition and outcomes.

BACKGROUND AND OBJECTIVE: Carbapenem resistance among Enterobacteriaceae is of concern because of increasing prevalence and limited therapeutic options. Limited research has been focused on understanding ertapenem resistance as a more sensitive marker for resistance to other carbapenems. We sought to determine risk factors for acquisition of ertapenem-resistant, meropenem-susceptible, or intermediate Enterobacteriaceae and to assess associated patient outcomes. DESIGN: Retrospective case-control study among adult hospitalized inpatients. SETTING: A 902-bed quaternary care urban hospital. RESULTS: Sixty-two cases of ertapenem-resistant Enterobacteriaceae were identified from March 14, 2006, through October 31, 2007, and 62 unmatched control patients were randomly selected from other inpatients with cultures positive for ertapenem-susceptible Enterobacteriaceae. Thirty-seven (60%) of case patient isolates were Enterobacter cloacae, 20 (32%) were Klebsiella pneumoniae, and 5 (8%) were other species of Enterobacteriaceae. Risk factors for ertapenem-resistant Enterobacteriaceae infection included intensive care unit stay (odds ratio [OR], 4.6 [95% confidence interval {CI}, 2.0-10.3]), vancomycin-resistant Enterococcus colonization (OR, 7.1 [95% CI, 2.4-21.4]), prior central venous catheter use (OR, 10.0 [95% CI, 3.0-33.1]), prior receipt of mechanical ventilation (OR, 5.8 [95% CI, 2.1-16.2]), exposure to any antibiotic during the 30 days prior to a positive culture result (OR, 18.5 [95% CI, 4.9-69.9]), use of a ß-lactam during the 30 days prior to a positive culture result (OR, 6.9 [95% CI, 3.0-16.0], and use of a carbapenem during the 30 days prior to a positive culture result (OR, 18.2 [95% CI, 2.6-130.0]). For the 62 case patients, 30-day outcomes from the time of positive culture result were 24 discharges (39%), 10 deaths (16%), and 28 continued hospitalizations (44%). The final end point of the hospitalization was discharge for 44 patients (71%) and death for 18 patients (29%). CONCLUSIONS: Ertapenem-resistant Enterobacteriaceae are important nosocomial pathogens. Multiple mechanisms of resistance may be in operation. Additional study of ertapenem resistance is needed.

Characterization of photoreceptor cell types in the little brown bat Myotis lucifugus (Vespertilionidae).

We report the expression of three visual opsins in the retina of the little brown bat (Myotis lucifugus, Vespertilionidae). Gene sequences for a rod-specific opsin and two cone-specific opsins were cloned from cDNA derived from bat eyes. Comparative sequence analyses indicate that the two cone opsins correspond to an ultraviolet short-wavelength opsin (SWS1) and a long-wavelength opsin (LWS). Immunocytochemistry using antisera to visual opsins revealed that the little brown bat retina contains two types of cone photoreceptors within a rod-dominated background. However, unlike other mammalian photoreceptors, M. lucifugus cones and rods are morphologically indistinguishable by light microscopy. Both photoreceptor types have a thin, elongated outer segment. Using microspectrophotometry we classified the absorption spectrum for the ubiquitous rods. Similar to other mammals, bat rhodopsin has an absorption peak near 500 nm. Although we were unable to confirm a spectral range, cellular and molecular analyses indicate that M. lucifugus expresses two types of cone visual pigments located within the photoreceptor layer. This study provides important insights into the visual capacity of a nocturnal microchiropteran species.