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1.  Aortico-Left Atrial Fistula: A Rare Complication of Bioprosthetic Aortic Valve Endocarditis Secondary to Enterococcus faecalis 
Case Reports in Cardiology  2015;2015:473246.
Paravalvular aortic root abscess with intracardiac fistula formation is an exceedingly rare complication of infective endocarditis. This condition is even more rarely encountered in patients with bioprosthetic valve endocarditis. We report an unusual case of a 68-year-old Bosnian female with a bioprosthetic aortic valve, who developed an extensive aortic root abscess, complicated by an aortico-left atrial intracardiac fistula. This case illustrates that a high index of suspicion, prompt diagnosis by echocardiography, proper antibiotic therapy, and early surgical intervention are crucial to improving treatment outcomes for this rare condition.
PMCID: PMC4499373  PMID: 26246917
2.  The “Dual-Pathway” Strategy after Acute Coronary Syndrome: Rivaroxaban and Antiplatelet Agents in the ATLAS ACS 2-TIMI 51 Trial 
Cardiovascular Therapeutics  2014;32(5):224-232.
Acute coronary syndrome (ACS) is a medical emergency often associated with an occlusive coronary event with consequent myocardial underperfusion. Patients require immediate antiplatelet therapy and long-term antithrombotic prophylaxis to reduce the risk of recurrence. Acetylsalicylic acid (ASA) alone or in combination with a platelet P2Y12 inhibitor (dual antiplatelet therapy [DAPT]) has become the clinically accepted antithrombotic prophylaxis for patients post-ACS. Historically, studies assessing the utility of adding oral anticoagulants (OACs) have not demonstrated a clinical benefit with regard to acceptable bleeding risk. Studies with vitamin K antagonists (VKAs) such as warfarin demonstrated a potential to reduce the risk of subsequent death by reinfarction but this benefit was offset by increases in bleeding. Results from studies of two targeted non-VKA OACs also proved disappointing, with little or no apparent reduction in the rate of ischemic events seen. However, the recent ATLAS studies assessing rivaroxaban (an oral factor Xa inhibitor) in patients with ACS demonstrated a reduction in the composite endpoint of deaths from cardiovascular causes, myocardial infarction (MI), or stroke, and a reduction in the rate of stent thrombosis. This review provides an overview of the pivotal studies in which the addition of OACs to antiplatelet therapy (the so-called “dual-pathway” approach) has been investigated for the management of patients post-ACS and considers the results of the ATLAS studies and their potential impact on the management of patients after an acute event.
PMCID: PMC4285947  PMID: 24894120
Acute coronary syndrome; Anticoagulant; Antiplatelet; Bleeding; Ischemia
3.  Utility of carotid duplex ultrasonography in a general inner-city hospital 
Carotid Duplex Ultrasonography (CDUS) is one of the non-invasive imaging modalities used to evaluate for carotid artery stenosis. However, it is often used in patients with coronary artery disease (CAD), peripheral artery disease (PAD), before heart surgery, syncope and non-specific neurological symptoms although its value is unclear. Our study aimed to further investigate the yield of CDUS in these conditions.
A retrospective analysis was conducted on 827 consecutive carotid ultrasounds ordered between March 2013 and August 2013 at Newark Beth Israel Medical Center. Clinical characteristics such as age, sex, smoking status, systemic hypertension, diabetes mellitus, CAD, PAD, carotid bruit and indications for carotid ultrasound were included. Significant cerebrovascular disease (sCBVD) was defined as greater than or equal to 50% diameter reduction in internal carotid arteries (ICA) or any degree of occlusion in vertebrobasilar system.
Only 88 out of 827 (10.6%) patients had sCBVD. Using logistic regression analysis we identified age greater than 65 years (OR 2.1, 95% CI 1.2 to 3.7; P = 0.006), carotid bruit (OR 7.8, 95% CI 3.6 to 16.6; P <0.001) and history of prior carotid endarterectomy or carotid artery stenting (OR 5.8, 95% CI 2.3 to 14.8; P <0.001) as significant predictors of sCBVD.
Significant carotid artery stenosis is more likely in patients 65 years and older, presence of carotid bruit and prior CEA. On the other hand, it has low diagnostic yield in less than 65-year-old individuals, syncope and non-focal neurological symptoms. This highlights the need for better risk prediction models in order to promote optimal utilization.
PMCID: PMC4259086  PMID: 25422167
Carotid ultrasound; Cerebrovascular disease; Utilization
4.  An explorative study of metabolic responses to mental stress and yoga practices in yoga practitioners, non-yoga practitioners and individuals with metabolic syndrome 
Stress places a metabolic burden on homeostasis and is linked to heightened sympathetic activity, increased energy expenditure and pathology. The yogic state is a hypometabolic state that corresponds with mind-body coherence and reduced stress. This study aimed to investigate metabolic responses to stress and different yoga practices in regular yoga practitioners (YP), non-yoga practitioners (NY) and metabolic syndrome patients (MS).
YP (n = 16), NY (n = 15) and MS (n = 15) subjects underwent an experimental protocol that comprised of different 5-minute interventions including mental arithmetic stress test (MAST), alternate nostril breathing (ANB), Kapabhati breathing (KB) and meditation (Med) interspersed with 5 minutes of quiet resting (neutral condition (NC)). During the intervention periods continuous body weight adjusted oxygen consumption (VO2ml/min/kg) was measured using open circuit indirect calorimetry with a canopy hood.
This is the first study to report oxygen consumption (OC) in yoga practitioners during and after MAST and the first to report both within and between different populations. The results were analysed with SPSS 16 using 3X9 mixed factorial ANOVAs. The single between-subject factor was group (YP, NY and MS), the single within-subject factor was made up of the nine intervention phases (NC1, MAST, NC2, ANB, NC3, KB, NC4, Med, NC5). The results demonstrated that the regular YP group had significantly less OC and greater variability in their OC across all phases compared to the MS group (p = .003) and NY group (p = .01). All groups significantly raised their OC during the mental arithmetic stress, however the MS group had a significantly blunted post-stress recovery whereas the YP group rapidly recovered back to baseline levels with post stress recovery being greater than either the NY group or MS group.
Yoga practitioners have greater metabolic variability compared to non-yoga practitioners and metabolic syndrome patients with reduced oxygen requirements during resting conditions and more rapid post-stress recovery. OC in metabolic syndrome patients displays significantly blunted post-stress recovery demonstrating reduced metabolic resilience. Our results support the findings of previous randomised trials that suggest regular yoga practice may mitigate against the effects of metabolic syndrome.
Clinical trial number
ACTRN12614001075673; Date of Registration: 07/10/2014.
PMCID: PMC4247158  PMID: 25398263
Yoga; Meditation; Breathing; Metabolic syndrome; Oxygen consumption; Energy Expenditure; Metabolic rate; Stress reactivity; Stress recovery
5.  The importance of the one carbon cycle nutritional support in human male fertility: a preliminary clinical report 
Sperm chromatin structure is often impaired; mainly due to oxidative damage. Antioxidant treatments do not consistently produce fertility improvements and, when given at high doses, they might block essential oxidative processes such as chromatin compaction. This study was intended to assess the effect on male sub-fertility of a pure one carbon cycle nutritional support without strong antioxidants.
Male partners of couples resistant to at least 2 assisted reproductive technology (ART) attempts, with no evidence of organic causes of infertility and with either DNA fragmentation index (DFI) measured by Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) or nuclear decondensation index (SDI) measured by aniline blue staining exceeding 20%, were invited to take part in a trial of a nutritional support in preparation for a further ART attempt. The treatment consisted of a combination of B vitamins, zinc, a proprietary opuntia fig extract and small amounts of N-acetyl-cysteine and Vitamin E (Condensyl™), all effectors of the one carbon cycle.
84 patients were enrolled, they took 1 or 2 Condensyl™ tablets per day for 2 to 12 months. Positive response rates were 64.3% for SDI, 71.4% for DFI and 47.6% for both SDI and DFI. Eighteen couples (21%) experienced a spontaneous pregnancy before the planned ART cycle, all ended with a live birth. The remaining 66 couples underwent a new ART attempt (4 IUI; 18 IVF; 44 ICSI) resulting in 22 further clinical pregnancies and 15 live births. The clinical pregnancy rate (CPR) and the live birth rate (LBR) were 47.6% and 39.3% respectively. The full responders, i.e. the 40 patients achieving an improvement of both SDI and DFI, reported a CPR of 70% and a LBR of 57.5% (p < 0.001).
Nutritional support of the one carbon cycle without strong antioxidants improves both the SDI and the DFI in ART resistant male partners and results in high pregnancy rates suggesting a positive effect on their fertility potential.
PMCID: PMC4119238  PMID: 25073983
One carbon cycle; Methylation; Homocysteine; Sperm fertilizing ability; Oxidative damage
6.  A Methodological Review of Meditation Research 
Despite over 50 years of research into the states of consciousness induced by various meditation practices, no clear neurophysiological signatures of these states have been found. Much of this failure can be attributed to the narrow range of variables examined in most meditation studies, with the focus being restricted to a search for correlations between neurophysiological measures and particular practices, without documenting the content and context of these practices. We contend that more meaningful results can be obtained by expanding the methodological paradigm to include multiple domains including: the cultural setting (“the place”), the life situation of the meditator (“the person”), details of the particular meditation practice (‘the practice’), and the state of consciousness of the meditator (“the phenomenology”). Inclusion of variables from all these domains will improve the ability to predict the psychophysiological variables (“the psychophysiology”) associated with specific meditation states and thus explore the mysteries of human consciousness.
PMCID: PMC4076570  PMID: 25071607
meditation; consciousness; meditation states; methodology; subjective measures
7.  A Postmarket Surveillance Study on Electro-Neuro-Adaptive-Regulator Therapy 
The Electro-Neuro-Adaptive-Regulator (ENAR) device is a hand-held electrotherapy which is applied using energetic medicine principles and aspects of acupuncture theory. The aim of this paper is to report the findings of a postmarket survey of persons who have used the ENAR device. The conditions for which the therapy was used and its perceived effectiveness are discussed. A web-based survey of Australian recipients of ENAR therapy was completed by 481 respondents. Most (76%) used ENAR exclusively for pain relief for musculoskeletal disorders, especially back, shoulder, and neck pain; 8% used ENAR exclusively for nonmusculoskeletal disorders; while 16% used ENAR for both. Respondents reported a mean reduction in pain of 70% (t(423) = 38.73, P < .001) and functional improvement of 62% (t(423) = 10.45, P < .001) using 11-point numerical rating scales. Following ENAR treatment, medication reduction was reported by 91% of respondents. Most respondents reported high satisfaction following ENAR therapy, with between 15 and 20% achieving complete pain relief. The self-delivery of ENAR may, in part, account for the high level of satisfaction.
PMCID: PMC4068052  PMID: 24999365
10.  Low and then high frequency oscillations of distinct right cortical networks are progressively enhanced by medium and long term Satyananda Yoga meditation practice 
Meditation proficiency is related to trait-like (learned) effects on brain function, developed over time. Previous studies show increases in EEG power in lower frequency bands (theta, alpha) in experienced meditators in both meditation states and baseline conditions. Higher gamma band power has been found in advanced Buddhist meditators, yet it is not known if this occurs in Yoga meditation practices. This study used eLORETA to compare differences in cortical source activity underlying scalp EEG from intermediate (mean experience 4 years) and advanced (mean experience 30 years) Australian meditators from the Satyananda Yoga tradition during a body-steadiness meditation, mantra meditation, and non-meditation mental calculation condition. Intermediate Yoga meditators showed greater source activity in low frequencies (particularly theta and alpha1) during mental calculation, body-steadiness and mantra meditation. A similar spatial pattern of significant differences was found in all conditions but the number of significant voxels was double during body-steadiness and mantra meditation than in the non-meditation (calculation) condition. These differences were greatest in right (R) superior frontal and R precentral gyri and extended back to include the R parietal and occipital lobes. Advanced Yoga meditators showed greater activity in high frequencies (beta and especially gamma) in all conditions but greatly expanded during meditation practice. Across all conditions (meditation and non-meditation) differences were greatest in the same regions: R insula, R inferior frontal gyrus and R anterior temporal lobe. Distinct R core networks were identified in alpha1 (8–10 Hz) and gamma (25–42 Hz) bands, respectively. The voxels recruited to these networks greatly expanded during meditation practice to include homologous regions of the left hemisphere. Functional interpretation parallels traditionally described stages of development in Yoga proficiency.
PMCID: PMC4051196  PMID: 24959124
meditation; Yoga; EEG; eLORETA; neural networks; default mode network
12.  Appropriate Anti-Thrombotic/Anti-Thrombin Therapy for Thrombotic Lesions 
Current Cardiology Reviews  2012;8(3):181-191.
Managing coronary thrombus is a challenging task and requires adequate knowledge of the various antithrombotic agents available. In this article, we will briefly analyze the risk-benefit profile of antithrombotic agents, with critical analysis of the scientific evidence available to support their use. Since thrombus consists of platelets and coagulation cofactors, an effective antithrombotic strategy involves using one anticoagulant with two or more antiplatelet agents. Unfractionated heparin traditionally has been the most commonly used anticoagulant but is fast being replaced by relatively newer agents like LMWH, direct thrombin inhibitors, and Factor Xa inhibitors.
In recent years, the antiplatelet landscape has changed significantly with the availability of more potent and rapidly acting agents, like prasugrel and ticagrelor. These agents have demonstrated a sizeable reduction in ischemic outcomes in patients with ACS, who are treated invasively or otherwise, with some concern for an increased bleeding risk. Glycoprotein IIb/IIIa inhibitors have an established role in high risk NSTE ACS patients pretreated with dual antiplatelets, but its role in STEMI patients, treated with invasive approach and dual antiplatelets, has not been supported consistently across the studies. Additionally, in recent years, its place as a directly injected therapy into coronaries has been looked into with mixed results. In conclusion, a well-tailored antithrombotic strategy requires taking into account each patient’s individual risk factors and clinical presentation, with an effort to strike balance between not only preventing ischemic outcomes but also reducing bleeding complications.
PMCID: PMC3465822  PMID: 22920489
Antithrombotic therapy; Coronary thrombus; Acute coronary syndrome.
15.  Yoga in Australia: Results of a national survey 
International Journal of Yoga  2012;5(2):92-101.
The therapeutic benefits of yoga and meditation are well documented, yet little is known about the practice of yoga in Australia or elsewhere, whether as a physical activity, a form of therapy, a spiritual path or a lifestyle.
Materials and Methods:
To investigate the practice of yoga in Australia, a national survey of yoga practitioners was conducted utilizing a comprehensive web-based questionnaire. Respondents were self-selecting to participate. A total of 3,892 respondents completed the survey. Sixty overseas respondents and 1265 yoga teachers (to be reported separately) were excluded, leaving 2,567 yoga practitioner respondents.
The typical yoga survey respondent was a 41-year-old, tertiary educated, employed, health-conscious female (85% women). Asana (postures) and vinyasa (sequences of postures) represented 61% of the time spent practicing, with the other 39% devoted to the gentler practices of relaxation, pranayama (breathing techniques), meditation and instruction. Respondents commonly started practicing yoga for health and fitness but often continued practicing for stress management. One in five respondents practiced yoga for a specific health or medical reason which was seen to be improved by yoga practice. Of these, more people used yoga for stress management and anxiety than back, neck or shoulder problems, suggesting that mental health may be the primary health-related motivation for practicing yoga. Healthy lifestyle choices were seen to be more prevalent in respondents with more years of practice. Yoga-related injuries occurring under supervision in the previous 12 months were low at 2.4% of respondents.
Yoga practice was seen to assist in the management of specific health issues and medical conditions. Regular yoga practice may also exert a healthy lifestyle effect including vegetarianism, non-smoking, reduced alcohol consumption, increased exercise and reduced stress with resulting cost benefits to the community.
PMCID: PMC3410203  PMID: 22869991
Australia; cardiovascular; exercise; health; injuries; injury; medical; meditation; mental health; musculoskeletal; quality of life; survey; therapy; women's health; yoga
16.  Health and economic outcomes for exenatide once weekly, insulin, and pioglitazone therapies in the treatment of type 2 diabetes: a simulation analysis 
Patients with type 2 diabetes (T2DM) are at risk of long-term vascular complications. In trials, exenatide once weekly (ExQW), a GLP-1R agonist, improved glycemia, weight, blood pressure (BP), and lipids in patients with T2DM. We simulated potential effects of ExQW on vascular complications, survival, and medical costs over 20 years versus standard therapies.
Patients and methods
The Archimedes model was used to assess outcomes for ~25,000 virtual patients with T2DM (NHANES 1999–2006 [metformin ± sulfonylureas, age 57 years, body mass index 33 kg/m2, weight 94 kg, duration T2DM 9 years, hemoglobin A1c [A1C] 8.1%]). The effects of three treatment strategies were modeled and compared to moderate-adherence insulin therapy: advancement to high-adherence insulin at A1C ≥ 8% (treat to target A1C < 7%) and addition of pioglitazone (PIO) or ExQW from simulation start. ExQW effects on A1C, weight, BP, and lipids were modeled from clinical trial data. Costs, inflated to represent 2010 $US, were derived from Medicare data,, and publications. As ExQW was investigational, we omitted ExQW, PIO, and insulin pharmacy costs.
By year 1, ExQW treatment decreased A1C (~1.5%), weight (~2 kg), and systolic BP (~5 mmHg). PIO and high-adherence insulin decreased A1C by ~1%, increased weight, and did not affect systolic BP. After 20 years, A1C was ~7% with all strategies. ExQW decreased rates of cardiovascular and microvascular complications more than PIO or high-adherence insulin versus moderate-adherence insulin. Over 20 years, ExQW treatment resulted in increased quality-adjusted life-years (QALYs) of ~0.3 years/person and cost savings of $469/life-year versus moderate adherence insulin. For PIO or high-adherence insulin, QALYs were virtually unchanged, and costs/life-year versus moderate-adherence insulin increased by $69 and $87, respectively.
This long-term simulation demonstrated that ExQW treatment may decrease rates of cardiovascular and some microvascular complications of T2DM. Increased QALYs, and decreased costs were also projected.
PMCID: PMC3346268  PMID: 22566747
diabetes; modeling; exenatide; pioglitazone; insulin; cardiovascular risk
17.  Efficacy and Safety of a Chinese Herbal Medicine Formula (RCM-104) in the Management of Simple Obesity: A Randomized, Placebo-Controlled Clinical Trial 
Objective. This study was to evaluate the efficacy and safety of a Chinese herbal medicine formula (RCM-104) for the management of simple obesity. Method. Obese subjects aged between 18 and 60 years were selected for 12-week, double-blind, randomized, placebo-controlled trial. Subjects were randomly assigned to take 4 capsules of either the RCM-104 formula (n = 59) or placebo (n = 58), 3 times daily for 12 weeks. Measures of BW, BMI and WC, HC, WHR and BF composition were assessed at baseline and once every four weeks during the 12 week treatment period. Results. Of the 117 subjects randomised, 92 were included in the ITT analysis. The weight, BMI and BF in RCM-104 group were reduced by 1.5 kg, 0.6 kg/m2 and 0.9% and those in the placebo group were increased by 0.5 kg, 0.2 kg/m2 and 0.1% respectively. There were significant differences in BW and BMI (P < 0.05) between the two groups. Eleven items of the WLQOQ were significantly improved in the RCM-104 group while only 2 items were significantly improved in the placebo group. Adverse events were minor in both groups. Conclusion. RCM-104 treatment appears to be well tolerated and beneficial in reducing BW and BMI in obese subjects.
PMCID: PMC3328918  PMID: 22550541
18.  Acupuncture as analgesia for low back pain, ankle sprain and migraine in emergency departments: Study protocol for a randomized controlled trial 
Trials  2011;12:241.
Pain is the most common reason that patients present to an emergency department (ED) and is often inadequately managed. Evidence suggests that acupuncture is effective for pain relief, yet it is rarely practiced in the ED. The current study aims to assess the efficacy of acupuncture for providing effective analgesia to patients presenting with acute low back pain, migraine and ankle sprain at the EDs of four hospitals in Melbourne, Australia.
The study is a multi-site, randomized, assessor-blinded, controlled trial of acupuncture analgesia in patients who present to an ED with low back pain, migraine or ankle sprain. Patients will be block randomized to receive either acupuncture alone, acupuncture as an adjunct to pharmacotherapy or pharmacotherapy alone. Acupuncture will be applied according to Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Pain after one hour, measured using a visual analogue scale (VAS), is the primary outcome. Secondary outcomes measures include the following instruments; the Oswestry low back pain disability questionnaire, 24-hour Migraine Quality of Life questionnaire and Patient's Global Assessment of Ankle Injury Scale. These measures will be recorded at baseline, 1 hour after intervention, each hour until discharge and 48 ± 12 hours of ED discharge. Data will also be collected on the safety and acceptability of acupuncture and health resource utilization.
The results of this study will determine if acupuncture, alone or as an adjunct to pharmacotherapy provides effective, safe and acceptable pain relief for patients presenting to EDs with acute back pain, migraine or ankle sprain. The results will also identify the impact that acupuncture treatment may have upon health resource utilisation in the ED setting.
Trial registration
Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000989246
PMCID: PMC3339354  PMID: 22085683
Acupuncture; pain; ankle sprain; migraine; low back pain; emergency; acute
19.  The 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for Rheumatoid Arthritis 
Arthritis and rheumatism  2010;62(9):2582-2591.
The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set.
Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of “developing RA,” complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis.
The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach.
The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set.
PMCID: PMC3077961  PMID: 20872596
20.  Assessing Diet as a Modifiable Risk Factor for Pesticide Exposure 
The effects of pesticides on the general population, largely as a result of dietary exposure, are unclear. Adopting an organic diet appears to be an obvious solution for reducing dietary pesticide exposure and this is supported by biomonitoring studies in children. However, results of research into the effects of organic diets on pesticide exposure are difficult to interpret in light of the many complexities. Therefore future studies must be carefully designed. While biomonitoring can account for differences in overall exposure it cannot necessarily attribute the source. Due diligence must be given to appropriate selection of participants, target pesticides and analytical methods to ensure that the data generated will be both scientifically rigorous and clinically useful, while minimising the costs and difficulties associated with biomonitoring studies. Study design must also consider confounders such as the unpredictable nature of chemicals and inter- and intra-individual differences in exposure and other factors that might influence susceptibility to disease. Currently the most useful measures are non-specific urinary metabolites that measure a range of organophosphate and synthetic pyrethroid insecticides. These pesticides are in common use, frequently detected in population studies and may provide a broader overview of the impact of an organic diet on pesticide exposure than pesticide-specific metabolites. More population based studies are needed for comparative purposes and improvements in analytical methods are required before many other compounds can be considered for assessment.
PMCID: PMC3137997  PMID: 21776202
pesticides; exposure assessment; agricultural exposures; organic diets; biomonitoring
21.  Surgical treatment of a clival-C2 atypical teratoid/rhabdoid tumor 
The authors present the case of en bloc resection of a clival-C2 atypical teratoid/rhabdoid tumor. These aggressive lesions of early childhood generally occur in the cerebellum or cerebral hemispheres. This 7-year-old boy presented with pain on turning his head and was found to have a clival-C2 mass. A metastatic workup was negative for disseminated disease. A transoral biopsy procedure revealed an atypical teratoid/rhabdoid tumor on histological examination. The tumor was resected via a transoral approach, and the patient’s spine was stabilized with posterior instrumented fusion from the occiput to C-5. Postoperatively, the patient underwent 16 months of chemotherapy along with 6 weeks of overlapping radiation therapy. Twenty-seven months after the initial surgery he presented with leg pain and was found to have a solitary metastatic lesion at the conus medullaris. There was no local recurrence at the clivus. The conus tumor was resected and found to be consistent with the primary tumor. Several months later the patient presented with disseminated intrathecal disease and ultimately died 42 months after the initial resection.
PMCID: PMC2840717  PMID: 20043739
medulloblastoma; transoral approach; clivus; atypical teratoid/rhabdoid tumor
22.  Oral Antiplatelet Therapy for Acute and Chronic Management of NSTE ACS: Residual Ischemic Risk and Opportunities for Improvement 
Cardiovascular Drugs and Therapy  2009;23(6):489-499.
Non-ST-segment elevation acute coronary syndromes (NSTE ACS) are highly prevalent in the United States and globally, and are associated with significant morbidity and mortality.
The key role of platelet-mediated thrombosis in the pathogenesis of NSTE ACS is confirmed by the proven clinical benefits of antiplatelet agents (aspirin and a P2Y12 adenosine diphosphate [ADP] receptor antagonist) in this setting. Despite the documented advantages and broad use of antiplatelet therapy, the long-term morbidity and mortality rates remain significant, and the bleeding risk remains substantial. Residual risk can be attributed, at least in part, to the fact that thrombosis continues in the presence of current treatments because aspirin and P2Y12 ADP receptor antagonists each block only one of multiple platelet activation pathways, and thus do not impact other platelet activation pathways, such as the one triggered by interaction of thrombin with protease-activated receptor (PAR)-1, thereby exposing patients to continued accumulation of thrombotic events.
These considerations suggest that novel therapies with a different mechanism of action, when used in combination with current antiplatelet agents, may provide more comprehensive inhibition of platelet activation and additional reductions in morbidity and mortality, potentially without incremental bleeding risk.
PMCID: PMC2797418  PMID: 19890703
Non-ST-segment elevation acute coronary syndromes; Antiplatelet therapy; PAR-1; Percutaneous coronary intervention; Bleeding
23.  Schwannoma of the tongue: two case reports and review of the literature 
The aim of this study was to describe clinicopathologic and radiographic features of two cases of schwannoma involving the oral tongue and to review the literature of this unusual clinical entity. Case reports with review of the pathologic, radiologic and clinical data for two patients with schwannoma of the tongue are reported. Review of the literature of case reports of schwannomas (neurilemmomas) of the tongue from 1955 to 2006 with analysis of the patient’s age, gender, presenting symptom(s), tumor size, and surgical approach was undertaken. The two patients in our series presented with painless swelling of the tongue. Transoral excision was performed and pathologic examination confirmed the diagnosis of schwannoma in both the cases. A total of 126 cases of schwannoma of the tongue have been reported in the English literature over the past 51 years. Schwannomas of the tongue typically present in the third decade of life (33%), display no gender predilection (52.8% female; 47.2% male) and often present as a painless mass (69.6%). Schwannomas are likely to elicit distressing symptoms when they occur in the posterior one-third of the tongue (63.2 vs. 13.5%) or approach 3 cm in greatest dimension (33.0 vs. 18.2 mm). The vast majority of cases have been treated with transoral excision (94.8%). Recurrence after surgical excision has not been reported. Schwannoma of the tongue is a relatively rare tumor of the head and neck. Transoral resection allows for removal of this tumor in a manner that precludes recurrence, avoids causing morbidity of tongue function, and remains the standard approach for the treatment of the vast majority of these tumors.
PMCID: PMC2758150  PMID: 19130068
Schwannoma; Neurilemmoma; Lingual; Tongue
24.  Expanding the Recognition and Assessment of Bleeding Events Associated With Antiplatelet Therapy in Primary Care 
Mayo Clinic Proceedings  2009;84(2):149-160.
Antiplatelet therapy is an evidence-based, guideline-recommended, worldwide standard of care for treatment of patients with atherothrombosis. However, clinical implementation of the guidelines is suboptimal, in part because of physician and patient nonadherence. The increased risk of bleeding associated with antiplatelet therapy is often the reason for nonadherence, and several programs have been created to increase adherence to guideline treatment recommendations. Despite the relative success of such initiatives, including Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines, Guidelines Applied in Practice, and the American Heart Association's Get With the Guidelines and a Science Advisory, a current estimate is that less than 50% of atherothrombotic patients are taking antiplatelet therapies as recommended by national guidelines. A PubMed and MEDLINE search of the literature (January 1, 1983-May 15, 2008) was performed to examine the bleeding risks associated with various antiplatelet therapies. Relevant clinical trials, observational registry data, and other studies relevant to treatment and guideline recommendations were selected from articles generated through specific search terms. This comprehensive review contributes to the understanding of the benefit-to-risk ratio of antiplatelet therapy for patients with atherothrombosis.
PMCID: PMC2664586  PMID: 19181649
25.  Prediction of One-Year Survival in High-Risk Patients with Acute Coronary Syndromes: Results from the SYNERGY Trial 
Despite advances in pharmacologic therapy and invasive management strategies for patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), these patients still suffer substantial morbidity and mortality.
The objective of this study was to analyze independent predictors of 1-year mortality in patients with high-risk NSTE ACS.
A total of 9,978 patients were assigned to receive enoxaparin or unfractionated heparin (UFH) in this prospective, randomized, open-label, international trial.
Vital status at 1 year was collected. Univariable and multivariable predictors of 1-year mortality were identified. Three different multivariable regression models were constructed to identify: (1) predictors of 30-day mortality; (2) predictors of 1-year mortality; (3) predictors of 1-year mortality in 30-day survivors. The last model is the focus of this paper.
Overall, 9,922 (99.4%) of patients had 1-year follow-up. Of the 56 patients (37 UFH-assigned and 19 enoxaparin-assigned) without 1-year data, 11 patients were excluded because of withdrawal of consent, and 45 could not be located. One-year mortality was 7.5% (7.7% enoxaparin-assigned patients; 7.3% UFH-assigned patients; P = 0.4). In patients surviving 30 days after enrollment, independent predictors of 1-year mortality included factors known at baseline such as increased age, male sex, decreased weight, having ever smoked, decreased creatinine clearance, ST-segment depression, history of diabetes, history of angina, congestive heart failure, coronary artery bypass grafting, increased heart rate, rales, increased hematocrit, lowered hemoglobin, and higher platelet count. Factors predictive of mortality during the hospitalization and 30-day follow-up period were decreased weight at 30 days from baseline, atrial fibrillation, decreased nadir platelet, no use of beta-blockers and statins up to 30 days, and not receiving an intervention (c-index = 0.82).
Easily determined baseline clinical characteristics can be used to predict 1-year mortality with reasonable discriminative power. These models corroborate prior work in a contemporary aggressively managed population. A model to predict 1-year mortality in patients surviving at least 30 days may be quite helpful to healthcare providers in setting expectations and goals with patients after ACS.
PMCID: PMC2359476  PMID: 18196350
non-ST-segment elevation acute coronary syndrome; predictors; mortality; outcomes; low-molecular-weight heparin; unfractionated heparin

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