Discordant intracellular and plasma D-2-hydroxyglutarate levels in a patient with IDH2 mutated angioimmunoblastic T-cell lymphoma

Objectives: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma with mutations in genes encoding isocitrate dehydrogenase1 and 2 (IDH1 and IDH2). Mutant IDH generates the oncometabolite D-2-hydroxyglutarate (D-2HG). We report the first case of discordant intracellular and plasma D-2HG levels in a patient with IDH2 R172S mutated AITL. Methods: An 87-year-old woman was diagnosed with AITL in the groin lymph node by morphologic and immunophenotypic analyses, and molecular studies by DNA sequencing. D-2HG was measured in both tumoral tissue and in pre-treatment plasma by liquid chromatography-tandem mass spectrometry. Results: While D-2HG was markedly elevated in the tissue sample, its level in plasma was normal. We discuss this discordant D-2HG result within the context of previously reported discordant 2HG results in other IDH mutated tumors, and its implication for using circulating D-2HG as a biomarker of IDH mutation. In addition, this case also harbored mutations in RHOA, TET2, and TP53. The molecular pathogenesis is briefly discussed. Conclusion: While our case suggests that circulating D-2HG is not a reliable marker of IDH mutation in AITL, more cases need to be studied to arrive at a definite conclusion.     

State of the Art in Carotid Artery Stenting: Trial Data,Technical Aspects,and Limitations

The volume of carotid artery stenting (CAS) safety and efficacy data has grown exponentially over the last decade. Recent comparative data with carotid endarterectomy, the utility of embolic protection devices, peri-procedural medications, basic technical aspects of CAS, developments in carotid stent design, potential complications of CAS, and complication risk factors are discussed in this review.     

Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn’s Disease: A Randomized Controlled Trial

Background  

Increased intestinal permeability (IP) has been implicated in the etiopathogenesis, disease activity and relapse of Crohn’s disease (CD). Glutamine, the major fuel for the enterocytes, may improve IP.     

Total Economic Cost and Burden of Dengue in Nicaragua: 1996–2010

The burden of dengue in Nicaragua has been steadily rising during the last three decades; however, there have been few efforts to quantify the burden (measured in disability-adjusted life years [DALYs]) and cost to society. Using primary data from the Nicaraguan Ministry of Health (MINSA), the total cost and burden of dengue were calculated from 1996 to 2010. Total costs included both direct costs from medical expenditures and prevention activities and indirect costs from lost productivity. The annual disease burden ranged from 99 to 805 DALYs per million, with a majority associated with classic dengue fever. The total cost was estimated to be US$13.5 million/year (range: US$5.1–27.6 million). This analysis can help improve allocation of dengue control resources in Nicaragua and the region. As one of the most comprehensive analyses of its type to date in Nicaragua and Latin America, this study can serve as a model to determine the burden and cost of dengue.     

Sildenafil citrate rescues fetal growth in the catechol-O-methyl transferase knockout mouse model

Preeclampsia and fetal growth restriction are responsible for the majority of maternal and perinatal morbidity and mortality associated with complicated pregnancies. Although their etiologies are complex and multifactorial, both are associated with increased uterine artery resistance. Sildenafil citrate is able to rescue the dysfunction observed ex vivo in uterine arteries of women with preeclampsia. The ability of sildenafil citrate to increase uterine artery vasodilation, thereby decreasing uterine artery resistance and, hence, ameliorated preeclampsia and fetal growth restriction, was tested in a mouse model of preeclampsia, the catechol-O-methyl transferase knockout mouse (COMT(-/-)). COMT(-/-) and C57BL/6J mice were treated (0.2 mg/mL in drinking water, n=6-12) from gestational day 12.5 to 18.5. Measures of pup growth, including body weight, crown/rump length, and abdominal circumference, were reduced in COMT(-/-) mice; this was normalized after treatment with Sildenafil. COMT(-/-) mice also demonstrated abnormal umbilical Doppler waveforms, including reverse arterial blood flow velocity. This was normalized after treatment with Sildenafil. Abnormal uterine artery Doppler waveforms were not demonstrated in COMT(-/-) mice, although ex vivo responses of uterine arteries to phenylephrine were increased; moreover, treatment with Sildenafil did improve ex vivo sensitivity to an endothelium-dependent vasodilator. The data presented here demonstrate that Sildenafil can rescue pup growth and improve abnormal umbilical Doppler waveforms, providing support for a potential new therapeutic strategy targeting fetal growth restriction.     

Ten-year trends in the incidence,clinical profile and outcomes of acute-onset endophthalmitis following combined pars plana vitrectomy and sutureless,glueless and flapless scleral fixation of intraocular lenses

International Ophthalmology - To evaluate the frequency and outcomes of acute-onset endophthalmitis following combined pars plana vitrectomy and scleral fixation of intraocular lens. We evaluated...     

Intracorneal scleral patch supported cyanoacrylate application for corneal perforations secondary to rheumatoid arthritis

Purpose:To describe a new technique of intracorneal scleral patch (ICSP) supported cyanoacrylate tissue adhesive (CTA) application in corneal perforations, greater than 3.0 mm secondary to rheumatoid arthritis (RA).Methods:This Prospective, non-randomized, non-comparative, interventional series included 14 eyes (14 patients). All patients had corneal perforations sized 3.5 to 4.5 mm due to RA, which were treated with ICSP supported CTA application. A partial thickness scleral patch 1.0 mm larger than diameter of corneal perforation was prepared. A lamellar corneal pocket 0.5 mm all around the corneal perforation was created. The partial thickness scleral patch was placed in the corneal perforation site and the edge was fitted into the lamellar intracorneal pocket. A minimum quantity of CTA was applied on the scleral patch to seal the perforation.Results:The corneal perforations healed in 14 eyes (100%) in a mean 7.71 ± 1.14 (range, 6–9) weeks. One eye (7.14%) had inadvertent extrusion of ICSP due to premature removal of CTA but, Seidel''s test was negative, and the corneal epithelial defect healed with BCL alone. One eye each (7.14%) developed steroid induced cataract and glaucoma. None of eyes developed infective keratitis, re-opening of corneal perforation (necessitating repeat procedure) or enlargement of corneal perforation requiring penetrating keratoplasty (PKP).Conclusion:ICSP supported CTA application is a successful alternative option to emergency PKP in treating corneal perforations sized 3.5 to 4.5 mm with associated RA.     

Isolated vertebral artery injury secondary to suicidal neck stab

Traumatic vertebral artery injuries may be due to blunt or penetrating forces, the presentation of which can vary from being asymptomatic to a life threatening torrential bleed. The following case report describes an isolated vertebral artery injury with a rare mode of injury and presentation along with its management.