The mitochondrial citrate transporter,CIC, is essential for mitochondrial homeostasis

Dysregulation of the pathways that preserve mitochondrial integrity hallmarks many human diseases including diabetes, neurodegeration, aging and cancer. The mitochondrial citrate transporter gene, SLC25A1 or CIC, maps on chromosome 22q11.21, a region amplified in some tumors and deleted in developmental disorders known as velo-cardio-facial- and DiGeorge syndromes. We report here that in tumor cells CIC maintains mitochondrial integrity and bioenergetics, protects from mitochondrial damage and circumvents mitochondrial depletion via autophagy, hence promoting proliferation. CIC levels are increased in human cancers and its inhibition has anti-tumor activity, albeit with no toxicity on adult normal tissues. The knock-down of the CIC gene in zebrafish leads to mitochondria depletion and to proliferation defects that recapitulate features of human velo-cardio-facial syndrome, a phenotype rescued by blocking autophagy. Our findings reveal that CIC maintains mitochondrial homeostasis in metabolically active, high proliferating tissues and imply that this protein is a therapeutic target in cancer and likely, in other human diseases.     

Multimodality Imaging Approach towards Primary Aortic Sarcomas Arising after Endovascular Abdominal Aortic Aneurysm Repair: Case Series Report

Primary aortic neoplasms are rare. Aortic sarcoma arising after endovascular aneurysm repair (EVAR) is a scarce subset of primary aortic malignancies, reports of which are infrequent in the published literature. The diagnosis of aortic sarcoma is challenging due to its non-specific clinical presentation, and the prognosis is poor due to delayed diagnosis, rapid proliferation, and propensity for metastasis. Post-EVAR, aortic sarcomas may mimic other more common aortic processes on surveillance imaging. Radiologists are rarely knowledgeable about this rare entity for which multimodality imaging and awareness are invaluable in early diagnosis. A series of three pathologically confirmed cases are presented to display the multimodality imaging features and clinical presentations of aortic sarcoma arising after EVAR.     

MR susceptibility artefact associated with the use of Barricade coils for treatment of intracranial aneurysms

Magnetic resonance angiography (MRA) is commonly used to follow up patients after endovascular treatment for intracranial aneurysms. Magnetic resonance artefacts from coil constructs may impair image quality and jeopardise the evaluation of the effectiveness of treatment and review of adjacent vasculature. We present here a technical note on the usage of Barricade coils recently introduced at our institution. The MRA artefacts associated with these coils may make it impossible to ascertain aneurysm closure and anatomy. Hence these patients would need to be recalled for digital subtraction angiograms for a complete neuroradiological follow-up.     

Computed tomographic virtual colonoscopy computer-aided polyp detection in a screening population

BACKGROUND & AIMS: The sensitivity of computed tomographic (CT) virtual colonoscopy (CT colonography) for detecting polyps varies widely in recently reported large clinical trials. Our objective was to determine whether a computer program is as sensitive as optical colonoscopy for the detection of adenomatous colonic polyps on CT virtual colonoscopy. METHODS: The data set was a cohort of 1186 screening patients at 3 medical centers. All patients underwent same-day virtual and optical colonoscopy. Our enhanced gold standard combined segmental unblinded optical colonoscopy and retrospective identification of precise polyp locations. The data were randomized into separate training (n = 394) and test (n = 792) sets for analysis by a computer-aided polyp detection (CAD) program. RESULTS: For the test set, per-polyp and per-patient sensitivities for CAD were both 89.3% (25/28; 95% confidence interval, 71.8%-97.7%) for detecting retrospectively identifiable adenomatous polyps at least 1 cm in size. The false-positive rate was 2.1 (95% confidence interval, 2.0-2.2) false polyps per patient. Both carcinomas were detected by CAD at a false-positive rate of 0.7 per patient; only 1 of 2 was detected by optical colonoscopy before segmental unblinding. At both 8-mm and 10-mm adenoma size thresholds, the per-patient sensitivities of CAD were not significantly different from those of optical colonoscopy before segmental unblinding. CONCLUSIONS: The per-patient sensitivity of CT virtual colonoscopy CAD in an asymptomatic screening population is comparable to that of optical colonoscopy for adenomas > or = 8 mm and is generalizable to new CT virtual colonoscopy data.     

Association of glycated hemoglobin with carotid intimal medial thickness in Asian Indians with normal glucose tolerance

AimTo assess the association of glycated hemoglobin (HbA1c) levels with carotid intimal medial thickness (CIMT) in Asian Indians with normal glucose tolerance (NGT).MethodsSubjects with NGT were recruited from the Chennai Urban Rural Epidemiology Study carried out on a representative population of Chennai, South India. All subjects had fasting plasma glucose < 100 mg/dl (5.6 mmol/l) and 2-h post load plasma glucose < 140 mg/dl (7.8 mmol/l). HbA1c was measured using the Biorad Variant machine. CIMT was measured on the right common carotid artery using high-resolution B-mode ultrasonography.ResultsThe study group included 1383 NGT subjects, of whom 760 (54.9%) were women. The mean CIMT value in the 1st quartile of HbA1c (< 5.2%) was 0.65 and it increased significantly to 0.73 in the last quartile of HbA1c (> 5.8) (p < 0.001). Regression analysis showed that HbA1c had a strong association with CIMT after adjusting for age, gender, waist circumference, systolic and diastolic blood pressure, LDL cholesterol, serum triglycerides, HOMA-IR and smoking (ß - 0.046, p = 0.047).ConclusionEven among subjects with NGT, there is a significant increase in CIMT with increasing levels of HbA1c, showing the value of using HbA1c for diagnosis of glucose intolerance.     

Dual flow diversion stents for aneurysm treatment in a partial unfused basilar artery

Unfused basilar arteries, frequently but erroneously referred to as ‘fenestrations’, are not uncommonly associated with aneurysms. The difficulty in treating these aneurysms lie in the fact that they are often wide necked and frequently incorporate both channels of the unfused segment, with varying calibres of the channels, necessitating technically challenging treatment strategies. It is important to preserve both channels because of the potential presence of perforating arteries originating from these segments. There are numerous case reports of such aneurysms being treated by coils alone, coiling with balloon assistance and stent-assisted coiling in configurations such as ‘X’, ‘double barrel’ or waffle cone. We present an exemplary case, in which an aneurysm on a partial unfused basilar segment was treated with parallel flow diverters with an excellent result on follow-up imaging.     

Optimizing management of acute leukemia in community centers and when to refer

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High sodium causes hypertension: evidence from clinical trials and animal experiments

Hypertension is a cardiovascular disease affecting approximately one out of every seven people worldwide. High-sodium consumption has been generally accepted as a risk factor for developing hypertension. Today, global sodium consumption greatly exceeds guidelines recommended by all medical institutions. This review synthesizes the data of landmark mammalian and human studies which investigated the role of sodium in the pathogenesis of hypertension, along with modern studies questioning this relationship. Recent studies concerning the potential pathways by which high-sodium concentration induces hypertension were reviewed. Human trials and population studies revealed a strong correlation between high blood pressure and average dietary sodium; and animal studies found a dramatic reduction in vascular function in a variety of mammals treated with high-sodium diets. In spite of a few contrarian studies, we found overwhelming evidence that elevated sodium consumption could cause hypertension.