Continuing Medical Education Activity in Echocardiography

Article Title: Transesophageal Echocardiographic Assessment of Pulmonary Veins and Left Atrium in Patients Undergoing Atrial Fibrillation Ablation (Echocardiography 2011;28:774)     

Adjuvant radiotherapy for atypical and malignant meningiomas: a systematic review

Atypical meningiomas (AMs) and malignant meningiomas (MMs) are tumors with a lower incidence and poorer prognosis than benign meningiomas. The role of radiotherapy as an adjuvant to surgical resection, especially for AMs, is incompletely defined. In this study, the English-language literature was systematically reviewed for studies that reported tumor characteristics, treatment parameters, and clinical outcomes after adjuvant radiotherapy for AM and MM, including overall survival, progression-free survival, and/or time to recurrence or mortality. Clinical outcomes were further assessed in the context of resection status, timing of administration, and radiation dose. Outcomes after stereotactic radiosurgery were also examined. Treatment toxicity and other potential prognostic or confounding factors were appraised. Ten and 11 studies for AM and MM, respectively, met the inclusion criteria. The median 5-year progression-free survival and overall survival after adjuvant radiotherapy were 54.2% and 67.5%, respectively, for AM and 48% and 55.6% for MM. The complication rates were 11.1% for AM and 5.1% for MM. Incomplete resection and radiation dose <50 Gy conferred significantly poorer 5-year progression-free survival. Most studies were unable to demonstrate a statistically significant prognostic benefit for adjuvant radiotherapy in AM. In conclusion, adjuvant radiotherapy significantly improved local control of AMs and MMs, especially after subtotal resection. Study limitations, including inadequate statistical power, may underlie the studies'' inability to demonstrate a statistically significant benefit for adjuvant radiotherapy in AM. Because these tumors preferentially recur within 5 years of surgical resection, future studies should define whether early adjuvant therapy should become part of the standard treatment paradigm for completely excised tumors.     

Hepatitis E Virus: Current Concepts and Future Perspectives

For many years, hepatitis E was considered a disease found only in certain developing countries. In these geographical settings, hepatitis E virus (HEV) causes a self-limiting hepatitis in young adults, except in pregnant females, in whom the mortality is 25 %. Our understanding of HEV has changed radically in the past decade. It is now evident that HEV is a threat to global health. This review article considers the current concepts and future perspectives of HEV and its effects on human health, with particular reference to developed countries.     

Retrograde leptomeningeal venous approach for dural arteriovenous fistulas at foramen magnum

A 72-year-old man presented with sudden right homonymous hemianopsia. Work-up imaging revealed a left occipital haematoma and an arteriovenous fistula supplied by the meningeal branches to the clivus from the left vertebral artery (VA) with a rostral venous reflux into cortical veins. A microcatheter was advanced through brainstem veins into the venous collector. A compliant balloon was placed in the left VA facing the origin of feeders. The balloon was inflated to protect the vertebrobasilar circulation from embolic migration. Onyx was injected by the transvenous catheter. Control angiogram revealed exclusion of the lesion.Informed consent was obtained from the patient.     

The Impact of Pharmacy Students’ Remediation Status on NAPLEX First-Time Pass Rates

Objective. To determine whether there is a difference in pass rates on the North American Pharmacist Licensure Examination (NAPLEX) between students who did and did not require remediation for deficient course grades.Methods. Student-specific data were collected regarding course grade deficiencies and completion of a comprehensive examination or course for remediation. Student-specific first-time NAPLEX performance data for the graduating classes of 2008, 2009, and 2011were provided by the National Association of Boards of Pharmacy (NABP).Results. A significant difference was found in first-time NAPLEX mean pass rates between students who did not need to undergo remediation versus those who did ( 97% vs 70%).Conclusion. Students requiring remediation for deficient course grades had a lower pass rate on the NAPLEX compared with those who did not require remediation. The difference can be attributed to several factors and therefore further study is needed.     

Metabolism of [U‐13C]glucose in human brain tumors in vivo

Glioblastomas and brain metastases demonstrate avid uptake of 2‐[¹⁸F]fluoro‐2‐deoxyglucose by positron emission tomography and display perturbations of intracellular metabolite pools by ¹H MRS. These observations suggest that metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg effect, excess metabolism of glucose to lactate in the presence of oxygen, is a hallmark of cancer cells in culture. 2‐[¹⁸F]Fluoro‐2‐deoxyglucose‐positive tumors are assumed to metabolize glucose in a similar manner, with high rates of lactate formation relative to mitochondrial glucose oxidation, but few studies have specifically examined the metabolic fates of glucose in vivo. In particular, the capacity of human brain cancers to oxidize glucose in the tricarboxylic acid cycle is unknown. Here, we studied the metabolism of human brain tumors in situ. [U‐¹³ C]Glucose (uniformly labeled glucose, i.e. d ‐glucose labeled with ¹³ C in all six carbons) was infused during surgical resection, and tumor samples were subsequently subjected to ¹³C NMR spectroscopy. The analysis of tumor metabolites revealed lactate production, as expected. We also determined that pyruvate dehydrogenase, turnover of the tricarboxylic acid cycle, anaplerosis and de novo glutamine and glycine synthesis contributed significantly to the ultimate disposition of glucose carbon. Surprisingly, less than 50% of the acetyl‐coenzyme A pool was derived from blood‐borne glucose, suggesting that additional substrates contribute to tumor bioenergetics. This study illustrates a convenient approach that capitalizes on the high information content of ¹³C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse cancers growing in their native microenvironment. Copyright © 2012 John Wiley & Sons, Ltd.     

A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency

Isolated mitochondrial complex IV (cytochrome c oxidase) deficiency is an important cause of mitochondrial disease in children and adults. It is genetically heterogeneous, given that both mtDNA-encoded and nuclear-encoded gene products contribute to structural components and assembly factors. Pathogenic variants within these proteins are associated with clinical variability ranging from isolated organ involvement to multisystem disease presentations. Defects in more than 10 complex IV assembly factors have been described including a recent Lebanese founder mutation in PET100 in patients presenting with Leigh syndrome. We report the clinical and molecular investigation of a patient with a fatal, neonatal-onset isolated complex IV deficiency associated with multiorgan involvement born to consanguineous, first-cousin British Asian parents. Exome sequencing revealed a homozygous truncating variant (c.142C>T, p.(Gln48*)) in the PET100 gene that results in a complete loss of enzyme activity and assembly of the holocomplex. Our report confirms PET100 mutation as an important cause of isolated complex IV deficiency outside of the Lebanese population, extending the phenotypic spectrum associated with abnormalities within this gene.