A Model for Standardized and Proactive Advance Care Planning.

As the importance of Advance Care Planning (ACP) has become well-known and accepted, health systems have begun placing more emphasis on ACP. However, many health systems still have not standardized this process, and most health systems still approach ACP in a reactive-rather than proactive-manner. This paper discusses one system's innovative approach to ACP that standardizes ACP in the inpatient and outpatient settings, while focusing on a proactive rather than reactive orientation to ACP.

Moyamoya Disease in an 18-Month-Old Female Caucasian Complicated by Cerebral Hyperperfusion Syndrome Following Indirect Revascularization.

BACKGROUND Cerebral hyperperfusion syndrome is a rare complication of indirect revascularization due to moyamoya disease, but has not been reported previously in the pediatric population. We present a case of an 18-month-old girl with moyamoya disease that was treated with bilateral pial synangiosis and had complications consistent with cerebral hyperperfusion syndrome. This case report discusses the pathophysiological mechanisms involved in cerebral hyperperfusion in moyamoya syndrome. CASE REPORT An 18-month-old female Caucasian presented with seizures and weakness of the left side. Angiography confirmed bilateral cerebral moyamoya disease that was worse on the right side. Indirect revascularization with pial synangiosis was first performed on the right side to allow for healing. Five months later, pial synangiosis was then performed on the left side. Postoperatively, the patient experienced increased intracranial pressure (ICP), suggesting cerebral hyperperfusion syndrome. She was treated with a repeat lumbar puncture, a lumbar drain, and a lumbar shunt. CONCLUSIONS This report demonstrates a case of cerebral hyperperfusion syndrome as a complication of moyamoya disease in a pediatric patient. Although the patient progressed well after placement of a lumbar shunt, this case demonstrates the occurrence of cerebral hyperperfusion syndrome as a complication of revascularization in pediatric patients and highlights the need for further research in this area.

A Case of Non-Islet Cell Tumor Hypoglycemia (NICTH) Associated with Gastrointestinal Stromal Tumor (GIST).

BACKGROUND Non-islet cell tumor hypoglycemia (NICTH) is a newly recognized, but uncommon, paraneoplastic syndrome that is associated with tumors of mesenchymal origin. We report a case of NICTH associated with a gastrointestinal stromal tumor (GIST). CASE REPORT A 60-year-old man presented to the emergency department of our hospital after being found unconscious in his home. His serum blood glucose on hospital admission was 40 mg/dL. He reported a three-month history of diffuse abdominal pain, fatigue, and blurred vision. Laboratory medicine investigations showed reduced levels of insulin, C-peptide, insulin-like growth factor binding protein (IGFBP)-3, and insulin-like growth factor (IGF)-1, but his IGFBP-2 was increased. Computed tomography (CT) scan of the chest and abdomen showed an abdominal mass that involved the small bowel, mesentery, and omentum, with lesions in the right lung and the left rib. Histopathology of a CT-guided biopsy of the abdominal mass showed a low-grade sarcomatous spindle cell neoplasm that was positive for CD117 using immunohistochemistry and with an exon 11 c-KIT mutation. These findings were consistent with a diagnosis of GIST and treatment with imatinib commenced. CONCLUSIONS This case report has shown that hypoglycemia in the setting of low levels of insulin, C-peptide, IGF-1, and IGFBP-3 is suggestive of a diagnosis of NICTH, which should be investigated for an underlying source, which in this case, was confirmed to be a malignant GIST.

SIRT3 attenuates MPTP-induced nigrostriatal degeneration via enhancing mitochondrial antioxidant capacity.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, which is characterized by progressive degeneration of nigrostriatal dopaminergic neurons. There is a growing consensus that mitochondrial dysfunction and oxidative stress play a crucial role in PD pathogenesis. Sirtuin3 (SIRT3) is the major mitochondria NAD(+)-dependent deacetylase that acts as a regulator of mitochondrial protein function; it is essential for maintaining mitochondrial integrity. Although SIRT3 was reported to have anti-oxidative stress activity in an in vitro study, there is no explicit in vivo evidence for the involvement of SIRT3 in the etiology of PD. The present study shows that SIRT3 null mice do not exhibit motor and non-motor deficits compared with wild-type controls. However, SIRT3 deficiency dramatically exacerbated the degeneration of nigrostriatal dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. SIRT3 null mice exposed to MPTP also exhibited decreased superoxide dismutase 2, a specific mitochondrial antioxidant enzyme, and reduced glutathione peroxidase expression compared with wild-type controls. Taken together, these findings strongly support that SIRT3 has a possible role in MPTP-induced neurodegeneration via preserving free radical scavenging capacity in mitochondria.

Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson's disease.

Parkinson's disease (PD) is characterized by progressive loss of nigrostriatal dopaminergic neurons that results in motor deficits including resting tremor, rigidity, bradykinesia, and postural instability. Despite decades of intensive study, the underlying molecular mechanisms are not fully understood. Multiple lines of evidence indicate that mitochondrial dysfunction and oxidative stress contribute to neuronal death, which is the key feature of neurodegeneration. Mitochondria are pivotal organelles that host essential functions in neuronal viability including energy production, oxidative phosphorylation, calcium buffering, redox homeostasis and apoptosis. SIRT5, which localizes in the mitochondrial matrix, is nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylase. The physiological and pathophysiological functions of SIRT5 in vivo remain elusive although it is known to be an important energy sensor. Here, we investigated the role of SIRT5 in the pathogenesis of PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We present evidence that SIRT5 deficiency, by itself, does not affect motor and non-motor functions; however, lack of SIRT5 exacerbates MPTP-induced motor deficits. Consistently, MPTP-exposed SIRT5 knockout mice exhibited more severe nigrostriatal dopaminergic degeneration than that observed in wild-type controls. Furthermore, deletion of SIRT5 leads to a larger decrease, relative to control, in the expression level of manganese superoxide dismutase (SOD2), a mitochondria-specific antioxidant enzyme, after MPTP induction. These findings indicate that SIRT5 ameliorates MPTP-induced nigrostriatal dopaminergic degeneration via preserving mitochondrial antioxidant capacity.

Creation of a National, At-home Model for Ashkenazi Jewish Carrier Screening.

Ethnicity-based carrier screening for the Ashkenazi Jewish population has been available and encouraged by advocacy and community groups since the early 1970's. Both the American College of Medical Genetics and the American Congress of Obstetricians and Gynecologists recommend carrier screening for this population (Obstetrics and Gynecology, 114(4), 950-953, 2009; Genetics in Medicine, 10(1), 55-56, 2008). While many physicians inquire about ethnic background and offer appropriate carrier screening, studies show that a gap remains in implementing recommendations (Genetic testing and molecular biomarkers, 2011). In addition, education and outreach efforts targeting Jewish communities have had limited success in reaching this at-risk population. Despite efforts by the medical and Jewish communities, many Jews of reproductive age are not aware of screening, and remain at risk for having children with preventable diseases. Reaching this population, preferably pre-conception, and facilitating access to screening is critically important. To address this need, genetic counselors at Emory University developed JScreen, a national Jewish genetic disease screening program. The program includes a national marketing and PR campaign, online education, at-home saliva-based screening, post-test genetic counseling via telephone or secure video conferencing, and referrals for face-to-face genetic counseling as needed. Our goals are to create a successful education and screening program for this population and to develop a model that could potentially be used for other at-risk populations.