Graftmaster savior: Injury to a patent LIMA during pericardiectomy, when a covered stent came to the rescue.

A 71-year-old male with multivessel coronary artery disease who underwent bypass with saphenous vein grafts to a Marginal branch and distal RCA and LIMA to LAD in 1988, DM II, atrial fibrillation on Coumadin, TIA, obstructive sleep apnea and pulmonary hypertension was referred to our institution after extensive dyspnea evaluation with a diagnosis of constrictive pericarditis for pericardiectomy. He had normal left ventricular function, moderate mitral and tricuspid regurgitation. Coronary angiography revealed ostial LAD CTO, patent LIMA to mid LAD, second Marginal branch CTO with left-to-left collaterals and mid RCA CTO with left-to-right collaterals. Vein grafts to the Marginal branch and distal RCA were occluded. The pericardium was heavily calcified on CT of the chest. The LIMA was inadvertently injured leading to acute STEMI and ventricular fibrillation arrest treated with defibrillation once. Surgical repair was unsuccessful. A Graftmaster covered stent was successful deployed with restoration of TIMI III flow to the LAD territory. Pericardiectomy was completed via both the median resternotomy and left thoracotomy. Triple therapy with Aspirin, Clopidogrel, and Coumadin was initiated and maintained for 3 months without hemorrhagic or thrombotic complications. He has continued to do well in follow-up on Clopidogrel and Coumadin.

Trauma centers with higher rates of angiography have a lesser incidence of splenectomy in the management of blunt splenic injury.

BACKGROUND: Nonoperative management (NOM) for blunt splenic injury (BSI) is well-established. Angiography (ANGIO) has been shown to improve success rates with NOM. Protocols for NOM are not standardized and vary widely between centers. We hypothesized that trauma centers that performed ANGIO at a greater rate would demonstrate decreased rates of splenectomy compared with trauma centers that used ANGIO less frequently. METHODS: A large, multicenter, statewide database (Pennsylvania Trauma Systems Foundation) from 2007 to 2011 was used to generate the study cohort of patients with BSI (age ≥ 13). The cohort was divided into 2 populations based on admission to centers with high (≥13%) or low (<13%) rates of ANGIO. Patient demographics, grade of BSI, Injury Severity Score, level of trauma center designation, and patient volume were analyzed. Splenectomy rates were then compared between the 2 groups, and multivariable logistic regression for predictors of splenectomy (failed NOM) were also performed. RESULTS: The overall rate of splenectomy in the entire cohort was 21.0% (1,120 of 5,333 BSI patients). The high ANGIO group had a lesser rate of splenectoy compared with the low ANGIO group (19% vs 24%; P < .001). Treatment at high ANGIO centers was negatively associated with splenectomy compared with low ANGIO centers (odds ratio, 0.68; 95% CI 0.58-0.80; P < .001); this association was independent of the number of BSI admissions or level of trauma center designation. CONCLUSION: Treatment of BSI at trauma centers that performed ANGIO more frequently resulted in lesser splenectomy rates compared with centers with lesser rate of ANGIO. Inclusion of angiographic protocols for NOM of BSI should be considered strongly.

Disruption of planar cell polarity activity leads to developmental biliary defects.

Planar cell polarity (PCP) establishes polarity within an epithelial sheet. Defects in PCP are associated with developmental defects involving directional cell growth, including defects in kidney tubule elongation that lead to formation of kidney cysts. Given the strong association between kidney cyst formation and developmental biliary defects in patients and in animal models, we investigated the importance of PCP in biliary development. Here we report that in zebrafish, morpholino antisense oligonucleotide-mediated knockdown of PCP genes including prickle-1a (pk1a) led to developmental biliary abnormalities, as well as localization defects of the liver and other digestive organs. The defects in biliary development appear to be mediated via downstream PCP targets such as Rho kinase, Jun kinase (JNK), and both actin and microtubule components of the cytoskeleton. Knockdown of pk1a led to decreased expression of vhnf1, a homeodomain gene previously shown to be involved in biliary development and in kidney cyst formation; forced expression of vhnf1 mRNA led to rescue of the pk1a morphant phenotype. Our results demonstrate that PCP plays an important role in vertebrate biliary development, interacting with other factors known to be involved in biliary morphogenesis.

Regulation of homocysteine metabolism and methylation in human and mouse tissues.

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine (Hcy) metabolism involves multiple enzymes; however, tissue Hcy metabolism and its relevance to methylation remain unknown. Here, we established gene expression profiles of 8 Hcy metabolic and 12 methylation enzymes in 20 human and 19 mouse tissues through bioinformatic analysis using expression sequence tag clone counts in tissue cDNA libraries. We analyzed correlations between gene expression, Hcy, S-adenosylhomocysteine (SAH), and S-adenosylmethionine (SAM) levels, and SAM/SAH ratios in mouse tissues. Hcy metabolic and methylation enzymes were classified into two types. The expression of Type 1 enzymes positively correlated with tissue Hcy and SAH levels. These include cystathionine beta-synthase, cystathionine-gamma-lyase, paraxonase 1, 5,10-methylenetetrahydrofolate reductase, betaine:homocysteine methyltransferase, methionine adenosyltransferase, phosphatidylethanolamine N-methyltransferases and glycine N-methyltransferase. Type 2 enzyme expressions correlate with neither tissue Hcy nor SAH levels. These include SAH hydrolase, methionyl-tRNA synthase, 5-methyltetrahydrofolate:Hcy methyltransferase, S-adenosylmethionine decarboxylase, DNA methyltransferase 1/3a, isoprenylcysteine carboxyl methyltransferases, and histone-lysine N-methyltransferase. SAH is the only Hcy metabolite significantly correlated with Hcy levels and methylation enzyme expression. We established equations expressing combined effects of methylation enzymes on tissue SAH, SAM, and SAM/SAH ratios. Our study is the first to provide panoramic tissue gene expression profiles and mathematical models of tissue methylation regulation.