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Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study

Tue, 10/11/2016 - 4:44pm

The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged >/=45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF.

Trajectories of Risk Factors and Risk of New-Onset Atrial Fibrillation in the Framingham Heart Study

Tue, 10/11/2016 - 4:44pm

The associations of long-term patterns of risk factors and the risk of incident atrial fibrillation (AF) are incompletely characterized. Among 4351 Framingham Study participants (mean age 50+/-11 years at baseline examination, 57% women) from the original and offspring cohorts, we defined longitudinal patterns, referred to as trajectories, of AF risk factors and a composite AF risk score using approximately 16 years of data. We used Cox proportional hazards models to examine the association of trajectories to 15-year risk of AF. During follow-up, 719 participants developed AF. Five distinct trajectory groups were identified for systolic blood pressure (BP): groups 1 and 2 (normotensive throughout), group 3 (prehypertensive), group 4 (hypertensive initially with decreasing BP), and group 5 (hypertensive and increasing BP). In multivariable-adjusted analyses, compared with group 1, groups 4 (hazard ratio 2.05; 95% confidence interval 1.24-3.37) and 5 (hazard ratio 1.95; 95% confidence interval 1.08-3.49) were associated with incident AF. Three trajectory groups were identified for antihypertensive treatment. Compared with the group with no treatment throughout, the other 2 groups were associated with increased risk of incident AF. Distinct trajectories for diastolic BP, smoking, diabetes mellitus, and the composite risk score were not associated with increased 15-year risk of AF. Longitudinal trajectories may distinguish how exposures related to AF contribute toward prospective AF risk. Distinct trajectory groups with persistently elevated systolic BP and longer antihypertensive treatment are associated with increased risk of incident AF.

The associations of leptin, adiponectin and resistin with incident atrial fibrillation in women

Tue, 10/11/2016 - 4:44pm

OBJECTIVES: Higher body mass index (BMI) is an important risk factor for atrial fibrillation (AF). The adipokines leptin, adiponectin and resistin are correlates of BMI, but their association with incident AF is not well known. We explored this relationship in a large cohort of postmenopausal women.

METHODS: We studied an ethnically diverse cohort of community-dwelling postmenopausal women aged 50-79 who were nationally recruited at 40 clinical centres as part of the Women's Health Initiative investigation. Participants underwent measurements of baseline serum leptin, adiponectin and resistin levels and were followed for incident AF. Adipokine levels were log transformed and normalised using inverse probability weighting. Cox proportional hazard regression models were used to estimate associations with adjustment for known AF risk factors.

RESULTS: Of the 4937 participants included, 892 developed AF over a follow-up of 11.1 years. Those with AF had higher mean leptin (14.9 pg/mL vs 13.9 pg/mL), adiponectin (26.3 ug/mL vs 24.5 ug/mL) and resistin (12.9 ng/mL vs 12.1 ng/mL) levels. After multivariable adjustment, neither log leptin nor log adiponectin levels were significantly associated with incident AF. However, log resistin levels remained significantly associated with incident AF (HR=1.57 per 1 log (ng/mL) increase, p=0.006). Additional adjustment for inflammatory cytokines only partially attenuated the association between resistin and incident AF (HR=1.43, p=0.06 adjusting for C-reactive protein (CRP); HR=1.39, p=0.08 adjusting for IL-6). Adjusting for resistin partially attenuated the association between BMI and incident AF (HR=1.14 per 5 kg/m(2), p=0.006 without resistin; HR=1.12, p=0.02 with resistin).

CONCLUSIONS: In women, elevated levels of serum resistin are significantly associated with higher rates of incident AF and partially mediate the association between BMI and AF. In the same population, leptin and adiponectin levels are not significantly associated with AF.

Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphoma between 2003 and 2011: A historical cohort study

Tue, 10/11/2016 - 4:44pm

Discovering how to improve survival and establishing clinical reference points for children diagnosed with endemic Burkitt lymphoma (eBL) in resource-constrained settings has recaptured international attention. Using multivariate analyses, we evaluated 428 children with eBL in Kenya for age, gender, tumor stage, nutritional status, hemoglobin, lactate dehydrogenase (LDH), Epstein-Barr virus (EBV) and Plasmodium falciparum prior to induction of chemotherapy (cyclophosphamide, vincristine, methotrexate and doxorubicin) to identify predictive and prognostic biomarkers of survival. During this 10 year prospective study period, 22% died in-hospital and 78% completed six-courses of chemotherapy. Of those, 16% relapsed or died later; 31% achieved event-free-survival; and 31% were lost to follow-up; the overall one-year survival was 45%. After adjusting for covariates, low hemoglobin ( < 8 g/dL) and high LDH ( > 400 mU/ml) were associated with increased risk of death (adjusted Hazard Ratio (aHR) = 1.57 [0.97-2.41]) and aHR = 1.84, [0.91-3.69], respectively). Anemic children with malaria were 3.55 times more likely to die [1.10-11.44] compared to patients without anemia or malarial infection. EBV load did not differ by tumor stage nor was it associated with survival. System-level factors can also contribute to poor outcomes. Children were more likely to die when inadvertently overdosed by more than 115% of the correct dose of cyclophosphamide (a HR = 1.43 [0.84-2.43]) or doxorubicin (a HR = 1.25, [0.66-2.35]), compared with those receiving accurate doses of the respective agent in this setting. This study codifies risk factors associated with poor outcomes for eBL patients in Africa and provides a benchmark by which to assess improvements in survival for new chemotherapeutic approaches.

Inflammation Mediated by JNK in Myeloid Cells Promotes the Development of Hepatitis and Hepatocellular Carcinoma

Tue, 10/11/2016 - 10:56am

The cJun NH2-terminal kinase (JNK) signaling pathway is required for the development of hepatitis and hepatocellular carcinoma. A role for JNK in liver parenchymal cells has been proposed, but more recent studies have implicated non-parenchymal liver cells as the relevant site of JNK signaling. Here, we tested the hypothesis that myeloid cells mediate this function of JNK. We show that mice with myeloid cell-specific JNK deficiency exhibit reduced hepatic inflammation and suppression of both hepatitis and hepatocellular carcinoma. These data identify myeloid cells as a site of pro-inflammatory signaling by JNK that can promote liver pathology. Targeting myeloid cells with a drug that inhibits JNK may therefore provide therapeutic benefit for the treatment of inflammation-related liver disease.

Suppression of ischemia in arterial occlusive disease by JNK-promoted native collateral artery development

Tue, 10/11/2016 - 10:56am

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive sprouting angiogenesis, and defects in developmental vascular morphogenesis. Our analysis demonstrates that the MLK-JNK signaling pathway is a key regulatory mechanism that protects against ischemia in arterial occlusive disease.

alphavbeta6 Integrin Promotes Castrate-Resistant Prostate Cancer through JNK1-Mediated Activation of Androgen Receptor

Tue, 10/11/2016 - 10:56am

Androgen receptor signaling fuels prostate cancer and is a major therapeutic target. However, mechanisms of resistance to therapeutic androgen ablation are not well understood. Here, using a prostate cancer mouse model, Pten(pc-/-), carrying a prostate epithelial-specific Pten deletion, we show that the alphavbeta6 integrin is required for tumor growth in vivo of castrated as well as of noncastrated mice. We describe a novel signaling pathway that couples the alphavbeta6 integrin cell surface receptor to androgen receptor via activation of JNK1 and causes increased nuclear localization and activity of androgen receptor. This downstream kinase activation by alphavbeta6 is specific for JNK1, with no involvement of p38 or ERK kinase. In addition, differential phosphorylation of Akt is not observed under these conditions, nor is cell morphology affected by alphavbeta6 expression. This pathway, which is specific for alphavbeta6, because it is not regulated by a different alphav-containing integrin, alphavbeta3, promotes upregulation of survivin, which in turn supports anchorage-independent growth of alphavbeta6-expressing cells. Consistently, both alphavbeta6 and survivin are significantly increased in prostatic adenocarcinoma, but are not detected in normal prostatic epithelium. Neither XIAP nor Bcl-2 is affected by alphavbeta6 expression. In conclusion, we show that alphavbeta6 expression is required for prostate cancer progression, including castrate-resistant prostate cancer; mechanistically, by promoting activation of JNK1, the alphavbeta6 integrin causes androgen receptor-increased activity in the absence of androgen and consequent upregulation of survivin. These preclinical results pave the way for further clinical development of alphavbeta6 antagonists for prostate cancer therapy.

Expectations of gender in medical education

Fri, 10/07/2016 - 9:55am

This article is a discussion and comment on: Isaac C, Chertoff J, Lee B, Carne M. Do students’ and authors’ genders affect evaluations? A linguistic analysis of medical student performance evaluations. Acad Med. 2011;86(1):59-66.

Herb use, vitamin use, and diet in low-income, postpartum women

Fri, 10/07/2016 - 9:55am

INTRODUCTION: Little is known about herb use among underserved postpartum women and their patterns of communication about herb use with prenatal providers.

METHODS: We interviewed women from the postpartum unit at an urban hospital about herb use during pregnancy, socioeconomic factors, prenatal vitamin use, and diet. We asked women if they discussed use of herbs and vitamins with their prenatal care providers and asked about their satisfaction with these discussions. We reviewed inpatient chart medication lists for herb use.

RESULTS: Of 160 women surveyed, 39% reported using herbs during pregnancy. Sixty-five percent of participants took a prenatal vitamin. Fifty-seven percent of herb users (n = 40) reported taking prenatal vitamins. Herb users were significantly more likely to report making any dietary change during their pregnancies than non-herb users (P = .03). Only 38% of herb users discussed it with their prenatal providers, and 82% were satisfied with the conversation. Of all 160 participants, 125 had prenatal vitamin use documented, and no women had herbal medicine use documented in the medical record during their birth hospitalization.

DISCUSSION: We report a higher frequency of herb use during pregnancy than other studies. The fact that women of all backgrounds and economic statuses report using herbs during pregnancy makes it even more important for all women to be asked about their use of herbs.

Curricular factors associated with medical students' practice of the skin cancer examination: an educational enhancement initiative by the integrated skin exam consortium

Fri, 10/07/2016 - 9:55am

IMPORTANCE: As medical school curricula become progressively integrated, a need exists to optimize education related to the skin cancer examination (SCE) for melanoma, a relevant competency gap that influences secondary prevention efforts.

OBJECTIVES: To identify curricular factors associated with medical students' confidence, intent, and performance regarding the SCE.

DESIGN, SETTING, AND PARTICIPANTS: Survey-based cross-sectional study from the Integrated Skin Exam Consortium at accredited US medical schools among a volunteer sample of second-year students representing 8 geographically varied public and private institutions. Students were administered a questionnaire to assess characteristics, curricular exposures, and educational and practical experiences related to skin cancer, as well as knowledge of melanoma risk and a detection method.

MAIN OUTCOMES AND MEASURES: Primary outcomes were confidence in performing the SCE, intent to perform an integrated skin examination, and actual performance of the SCE.

RESULTS: Physical diagnosis session and clinical encounter were most predictive of confidence in performance of the SCE (odds ratios [ORs], 15.35 and 11.48, respectively). Other curricular factors associated with confidence included instruction time of at least 60 minutes on skin cancer (OR, 6.35), lecture on the SCE (OR, 7.54), knowledge of melanoma risk (OR, 3.71), and at least 1 opportunity to observe the SCE (OR, 2.70). Physical diagnosis session and at least 4 opportunities to observe the SCE were most predictive of intent to perform an integrated skin examination (ORs, 4.84 and 4.72, respectively). Other curricular factors associated with intent included knowledge of melanoma risk (OR, 1.83), clinical encounter (OR, 2.39), and at least 1 opportunity to observe the SCE (OR, 1.95). Clinical encounter, physical diagnosis session, and at least 1 opportunity to observe the SCE were most predictive of performance of the SCE (ORs, 21.67, 15.48, and 9.92, respectively). Other curricular factors associated with performance included instruction time of at least 60 minutes on skin cancer (OR, 2.42) and lecture on the SCE (OR, 5.04).

CONCLUSIONS AND RELEVANCE: To augment the practice of the SCE among medical students, course directors may design an integrated curriculum that includes at least 60 minutes of instruction related to melanoma and the SCE, a description of the integrated skin examination as part of the physical diagnosis course, and education on high-risk demographic groups and anatomic sites specific to men and women and on the ABCDEs of melanoma, and at least 1 opportunity to observe the SCE.

PedsQL correlates to PODCI in pediatric orthopaedic outpatient clinic

Fri, 10/07/2016 - 9:55am

PURPOSE: Quality-of-life (QOL) measures can be a valuable tool to assess the general welfare across a spectrum of patients in a pediatric orthopaedic outpatient clinic and can be a simple way to assess patient-based outcomes particularly for quality initiatives. The Pediatric Outcomes Data Collection Instrument (PODCI) is validated for many orthopaedic conditions but typically takes around 20 minutes to complete (86 questions). The Pediatric Quality of Life Inventory (PedsQL) takes < 4 minutes to complete (23 questions) but has not been assessed in an orthopaedic setting. We initiated this study to find the best method for assessing QOL in our outpatient clinic. A short pediatric QOL measure that is correlated to an established orthopaedic-specific QOL measure is needed; therefore, we compared the PedsQL to the PODCI in the outpatient orthopaedic clinic.

METHODS: This was a quality initiative project and as such did not require a priori IRB approval. Families of patients 2 to 18 years old who presented for follow-up after upper or lower extremity fractures or brachial plexus injuries in the orthopaedic clinic from October 2010 through August 2011 were asked to fill out both the PODCI and the PedsQL. Patients aged 5 years and older filled out a patient-report PedsQL; patients aged 11 years and older filled out the patient-report PODCI. Parents/guardians completed questionnaires for children of all ages. Most fracture patients (and/or their parent/guardian) repeated the questionnaires after 6 to 12 weeks. Data were then assessed for correlation between the PODCI and PedsQL.

RESULTS: A total of 428 parent/guardian reports for 283 patients and 172 self-reports for 104 patients were included. The correlation between the PODCI Global score and the PedsQL Total score for the parent/guardian-reported questionnaires for all injuries was 0.77 (95% confidence interval, 0.72-0.82). When categorized within domains and injuries, parent/guardian-reported correlations ranged from 0.23 to 0.79. In patients aged 11 years and older, the correlation between the PODCI and PedsQL for the patient-reported questionnaire for all injuries was 0.85 (95% confidence interval, 0.80-0.89). When categorized within domains and injuries, patient-reported correlations ranged from 0.30 to 0.99.

CONCLUSIONS: Utilizing the substantially shorter PedsQL in a high volume orthopaedic clinic as a substitute for the PODCI for quality improvement measures seems reasonable. Correlation between the PedsQL Global score and the PODCI Total score for orthopaedic patients is strong. Utilizing the patient-reported questionnaires when age appropriate is best. In this era of increased outcome reporting, PedsQL may be a valuable tool.

Early hospital readmission of nursing home residents and community-dwelling elderly adults discharged from the geriatrics service of an urban teaching hospital: patterns and risk factors

Fri, 10/07/2016 - 9:55am

OBJECTIVES: To compare rates and risk factors for early hospital readmission for nursing home residents and community-dwelling older adults.

DESIGN: Retrospective cohort study.

SETTING: Geriatric inpatient service at a large urban hospital.

PARTICIPANTS: Nursing home residents (n=625) and community-dwelling individuals (n=413) aged 65 and older admitted over a 1-year period.

MEASUREMENTS: Thirty-day readmissions.

RESULTS: There were 1,706 hospital admissions within the 1-year study period involving 1,038 individuals. The 30-day readmission rate was higher for subjects discharged to a nursing home than those discharged to the community (34.4% vs 22.6%, P < .001). Chronic kidney disease and pressure ulcers were associated with greater risk of readmission in both groups. Chronic obstructive pulmonary disease was a risk factor for readmission only in community-dwelling individuals. Congestive heart failure and dementia were associated with greater risk of readmission only in nursing home residents. Readmission rates varied between individual nursing homes by more than a factor of 2. Risk of readmission was 30% lower in nursing home residents cared for by hospitalist than nonhospitalist geriatricians.

CONCLUSION: Higher rates of hospital readmission for individuals discharged to nursing homes than to the community and differing patterns of risk factors for readmission indicate the importance of customized interventions to reduce readmission rates for two distinct elderly populations.

Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression

Thu, 10/06/2016 - 12:57pm

A premature termination codon (PTC) in the ORF of an mRNA generally leads to production of a truncated polypeptide, accelerated degradation of the mRNA, and depression of overall mRNA expression. Accordingly, nonsense mutations cause some of the most severe forms of inherited disorders. The small-molecule drug ataluren promotes therapeutic nonsense suppression and has been thought to mediate the insertion of near-cognate tRNAs at PTCs. However, direct evidence for this activity has been lacking. Here, we expressed multiple nonsense mutation reporters in human cells and yeast and identified the amino acids inserted when a PTC occupies the ribosomal A site in control, ataluren-treated, and aminoglycoside-treated cells. We find that ataluren's likely target is the ribosome and that it produces full-length protein by promoting insertion of near-cognate tRNAs at the site of the nonsense codon without apparent effects on transcription, mRNA processing, mRNA stability, or protein stability. The resulting readthrough proteins retain function and contain amino acid replacements similar to those derived from endogenous readthrough, namely Gln, Lys, or Tyr at UAA or UAG PTCs and Trp, Arg, or Cys at UGA PTCs. These insertion biases arise primarily from mRNA:tRNA mispairing at codon positions 1 and 3 and reflect, in part, the preferred use of certain nonstandard base pairs, e.g., U-G. Ataluren's retention of similar specificity of near-cognate tRNA insertion as occurs endogenously has important implications for its general use in therapeutic nonsense suppression.

Preclinical acute ischemic stroke modeling

Wed, 10/05/2016 - 4:20pm

Preclinical ischemic stroke is at the crossroads in search of reliable and robust simulation models as past experiences with their translation from the laboratory to the standard of clinical care have often been disappointing. The efficacy of neuroprotective agents is still elusive, and the use of thrombolytics alone is limited to the narrow time window of presentation from the onset of the deficit. Hence, the focus has shifted to interventional revascularization to salvage the parenchyma at the risk of infarction. As the burden of disease morbidity and mortality is so enormous, neurointerventionalists have adopted a more aggressive approach to mechanical revascularization with the limited approved tools available-the Penumbra and the MERCI retrieval system, and the recently incorporated stent retrievers. In fact, the interventional space is among the fastest growing fields in stroke research today. Assessing treatment efficacy in these scenarios is infinitely complex as the heterogeneity of the cerebrovasculature, physical and mechanical nature of the occlusive embolus and the time of presentation are all confounders in assessing treatment outcomes. As no single thromboembolic model is apt to address all of these questions, an integrated methodology with a combination of both in vitro and in vivo assessment needs to be adopted. This involves clinically relevant thromboembolic analogs in device evaluation in vascular replicas, thromboembolic stroke induction in large animal gyrencephalic ischemic stroke models for thrombolytic, imaging and neuroprotection research and a native cerebrovascular target for evaluation of the safety and efficacy of mechanical thrombectomy devices.

Cholecystostomy Treatment in an ICU Population: Complications and Risks

Wed, 10/05/2016 - 11:32am

BACKGROUND: Percutaneous cholecystostomy tube placement has widely been used as an alternative treatment to cholecystectomy, especially in advanced disease or critically ill patients. Reported postprocedural complication rates have varied significantly over the last decade. The goal of this study is to evaluate the safety of percutaneous cholecystostomy tube treatment in critically ill patients.

STUDY DESIGN: We performed a retrospective chart analysis of 96 critically ill patients who underwent cholecystostomy tube placement during an intensive care unit (ICU) stay between 2005 and 2010 in a tertiary care center in central Massachusetts. Complications within 72 hours of cholecystostomy tube placement and any morbidity or mortality relating to presence of cholecystostomy tube were considered.

RESULTS: A total of 65 male and 31 female patients with a mean age of 67.4 years underwent percutaneous cholecystostomy tube placement during an ICU stay. Sixty-six patients experienced a total of 121 complications, resulting in an overall complication rate of 69%. Fifty-four of these complications resulted from the actual procedure or the presence of the cholecystostomy tube; the other 67 complications occurred within 72 hours of the cholecystostomy procedure. Ten patients died. Tube dislodgment was the most common complication with a total of 34 episodes.

CONCLUSIONS: Cholecystostomy tube placement is associated with frequent complications, the most common of which is tube dislodgment. Severe complications may contribute to serious morbidity and death in an ICU population. Complication rates may be underreported in the medical literature. The potential impact of cholecystostomy tube placement in critically ill patients should not be underestimated.

Trigeminocardiac reflex caused by selective angiography of the middle meningeal artery

Wed, 10/05/2016 - 11:18am

We describe an interesting case of trigeminocardiac reflex (TCR) caused by selective angiography of the middle meningeal artery (MMA). A 28-year-old woman presented with a symptomatic meningioma. Preoperative tumour embolisation was performed. In the procedure, when selective MMA angiography was done with Omnipaque 300 mg I/mL for 3 mL by manual injection, the patient complained of flashing lights in her eye followed by vomiting and bradycardia down to 40 bpm without increased intracranial pressure signs. On selective MMA angiography, the choroidal crescent and arteries of the periorbital region were opacified by anastomosis from the MMA via the meningo-ophthalmic artery. We diagnosed that her symptoms were caused by selective MMA angiography leading to high pressure stimulation towards the ophthalmic nerve innervation around the orbit as a TCR. We suggest that the operator should be prepared to manage TCR during treatment with expected selective MMA angiography, and gentle low pressure contrast injection should be attempted.

Trigeminocardiac reflex caused by selective angiography of the middle meningeal artery

Wed, 10/05/2016 - 11:18am

We describe an interesting case of trigeminocardiac reflex (TCR) caused by selective angiography of the middle meningeal artery (MMA). A 28-year-old woman presented with a symptomatic meningioma. Preoperative tumour embolisation was performed. In the procedure, when selective MMA angiography was done with Omnipaque 300 mg I/mL for 3 mL by manual injection, the patient complained of flashing lights in her eye followed by vomiting and bradycardia down to 40 bpm without increased intracranial pressure signs. On selective MMA angiography, the choroidal crescent and arteries of the periorbital region were opacified by anastomosis from the MMA via the meningo-ophthalmic artery. We diagnosed that her symptoms were caused by selective MMA angiography leading to high pressure stimulation towards the ophthalmic nerve innervation around the orbit as a TCR. We suggest that the operator should be prepared to manage TCR during treatment with expected selective MMA angiography, and gentle low pressure contrast injection should be attempted.

How to Effectively Implement a Peer Review Process for Interventional Radiology Procedures

Wed, 10/05/2016 - 11:18am

The purpose of this communication is to share our experience in creating an interventional radiology (IR)-specific peer review process, provide our initial results, and discuss future modifications and refinements to the system so that our institution— and others—can improve on the process of implementing peer review moving forward

Hydrophobic-core PEGylated graft copolymer-stabilized nanoparticles composed of insoluble non-nucleoside reverse transcriptase inhibitors exhibit strong anti-HIV activity

Wed, 10/05/2016 - 11:18am

Benzophenone-uracil (BPU) scaffold-derived candidate compounds are efficient non-nucleoside reverse transcriptase inhibitors (NNRTI) with extremely low solubility in water. We proposed to use hydrophobic core (methoxypolyethylene glycol-polylysine) graft copolymer (HC-PGC) technology for stabilizing nanoparticle-based formulations of BPU NNRTI in water. Co-lyophilization of NNRTI/HC-PGC mixtures resulted in dry powders that could be easily reconstituted with the formation of 150-250 nm stable nanoparticles (NP). The NP and HC-PGC were non-toxic in experiments with TZM-bl reporter cells. Nanoparticles containing selected efficient candidate Z107 NNRTI preserved the ability to inhibit HIV-1 reverse transcriptase polymerase activities with no appreciable change of EC50. The formulation with HC-PGC bearing residues of oleic acid resulted in nanoparticles that were nearly identical in anti-HIV-1 potency when compared to Z107 solutions in DMSO (EC50=7.5+/-3.8 vs. 8.2+/-5.1 nM). Therefore, hydrophobic core macromolecular stabilizers form nanoparticles with insoluble NNRTI while preserving the antiviral activity of the drug cargo.

Library based x-ray scatter correction for dedicated cone beam breast CT

Wed, 10/05/2016 - 11:17am

PURPOSE: The image quality of dedicated cone beam breast CT (CBBCT) is limited by substantial scatter contamination, resulting in cupping artifacts and contrast-loss in reconstructed images. Such effects obscure the visibility of soft-tissue lesions and calcifications, which hinders breast cancer detection and diagnosis. In this work, we propose a library-based software approach to suppress scatter on CBBCT images with high efficiency, accuracy, and reliability.

METHODS: The authors precompute a scatter library on simplified breast models with different sizes using the geant4-based Monte Carlo (MC) toolkit. The breast is approximated as a semiellipsoid with homogeneous glandular/adipose tissue mixture. For scatter correction on real clinical data, the authors estimate the breast size from a first-pass breast CT reconstruction and then select the corresponding scatter distribution from the library. The selected scatter distribution from simplified breast models is spatially translated to match the projection data from the clinical scan and is subtracted from the measured projection for effective scatter correction. The method performance was evaluated using 15 sets of patient data, with a wide range of breast sizes representing about 95% of general population. Spatial nonuniformity (SNU) and contrast to signal deviation ratio (CDR) were used as metrics for evaluation.

RESULTS: Since the time-consuming MC simulation for library generation is precomputed, the authors' method efficiently corrects for scatter with minimal processing time. Furthermore, the authors find that a scatter library on a simple breast model with only one input parameter, i.e., the breast diameter, sufficiently guarantees improvements in SNU and CDR. For the 15 clinical datasets, the authors' method reduces the average SNU from 7.14% to 2.47% in coronal views and from 10.14% to 3.02% in sagittal views. On average, the CDR is improved by a factor of 1.49 in coronal views and 2.12 in sagittal views.

CONCLUSIONS: The library-based scatter correction does not require increase in radiation dose or hardware modifications, and it improves over the existing methods on implementation simplicity and computational efficiency. As demonstrated through patient studies, the authors' approach is effective and stable, and is therefore clinically attractive for CBBCT imaging.