Administrative hospitalization database validation of cardiac procedure codes.

BACKGROUND: Although cardiac procedures are commonly used to treat cardiovascular disease, they are costly. Administrative data sources could be used to track cardiac procedures, but sources of such data have not been validated against clinical registries. OBJECTIVES: To examine accuracy of cardiac procedure coding in administrative databases versus a prospective clinical registry. SAMPLE: We examined a total of 182,018 common cardiac procedures including percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) surgery, valve surgery, and cardiac catheterization procedures during fiscal years 2005 and 2006 across 18 cardiac centers in Ontario, Canada. RESEARCH DESIGN: Accuracy of codes in the Canadian Institute for Health Information (CIHI) administrative databases were compared with the clinical registry of the Cardiac Care Network. RESULTS: Comparing 17,511 CIHI and 17,404 registry procedures for CABG surgery, the positive predictive value (PPV) of CIHI-coded CABG surgery was 97%. In 6229 CIHI-coded and 5885 registry-coded valve surgery procedures, the PPV of the administrative data source was 96%. Comparing 38,527 PCI procedures in CIHI to 38,601 in the registry, the PPV of CIHI was 94%. Among 119,751 CIHI-coded and 111,725 registry-coded cardiac catheterization procedures, the PPV of administrative data was 94%. When the procedure date window was expanded from the same day to ±1 days, the PPV was 96% (PCI) and exceeded 98% (CABG surgery), 97% (valve surgery), and 95% (cardiac catheterization). CONCLUSIONS: Using a clinical registry as the gold standard, the coding accuracy of common cardiac procedures in the CIHI administrative database was high.

Mammalian target of rapamycin (mTOR) induces proliferation and de-differentiation responses to three coordinate pathophysiologic stimuli (mechanical strain, hypoxia, and extracellular matrix remodeling) in rat bladder smooth muscle.

Maladaptive bladder muscle overgrowth and de-differentiation in human bladder obstructive conditions is instigated by coordinate responses to three stimuli: mechanical strain, tissue hypoxia, and extracellular matrix remodeling.( 1,2) Pathway analysis of genes induced by obstructive models of injury in bladder smooth muscle cells (BSMCs) identified a mammalian target of rapamycin (mTOR)-specific inhibitor as a potential pharmacological inhibitor. Strain-induced mTOR-specific S6K activation segregated differently from ERK1/2 activation in intact bladder ex vivo. Though rapamycin's antiproliferative effects in vascular smooth muscle cells are well known, its effects on BSMCs were previously unknown. Rapamycin significantly inhibited proliferation of BSMCs in response to mechanical strain, hypoxia, and denatured collagen. Rapamycin inhibited S6K at mTOR-sensitive phosphorylation sites in response to strain and hypoxia. Rapamycin also supported smooth muscle actin expression in response to strain or hypoxia-induced de-differentiation. Importantly, strain plus hypoxia synergistically augmented mTOR-dependent S6K activation, Mmp7 expression and proliferation. Forced expression of wild-type and constitutively active S6K resulted in loss of smooth muscle actin expression. Decreased smooth muscle actin, increased Mmp7 levels and mTOR pathway activation during in vivo partial bladder obstruction paralleled our in vitro studies. These results point to a coordinate role for mTOR in BSMCs responses to the three stimuli and a potential new therapeutic target for myopathic bladder disease.

Temporal factors in peripheral nerve reconstruction with suture scaffolds: an experimental study in rodents.

PURPOSE: This study investigated nerve regeneration following nerve repair with longitudinally oriented sutures, with emphasis on timing. Prior work in rodents has shown that suture scaffolds are comparable to nerve grafting when assessments are made at late time points. However, rodents have exceptional regenerative capacity, making it difficult to detect key differences at late time points. This study therefore investigated regeneration across suture scaffolds both at early (4 week) and late (12 week) endpoints. METHODS: Rodents were randomized to nerve gap, transection and repair, nerve grafting, and suture scaffold groups. Nerve regeneration was evaluated at 4 and 12 weeks. Histomorphometry parameters were evaluated using binary image analysis of toluidine blue-stained nerve cross sections. RESULTS: Compared to nerve grafts, suture scaffolds were associated with significantly decreased neural density (4208 +/- 3546 vs. 193 +/- 416, fibers/mm;2, p<0.05) and fiber width (1.92 +/- 1.21 vs. 0.75+/- 1.16, microm, p<0.05). At 12 weeks, differences between groups were no longer detectable. CONCLUSION: When evaluated at optimal time points for rodents, suture scaffolds fail to support regeneration comparable to the existing gold standard of nerve grafting. This finding raises significant concerns regarding the clinical application of suture scaffolds.

Pathologic bladder microenvironment attenuates smooth muscle differentiation of skin derived precursor cells: implications for tissue regeneration.

Smooth muscle cell containing organs (bladder, heart, blood vessels) are damaged by a variety of pathological conditions necessitating surgery or organ replacement. Currently, regeneration of contractile tissues is hampered by lack of functional smooth muscle cells. Multipotent skin derived progenitor cells (SKPs) can easily be isolated from adult skin and can be differentiated in vitro into contractile smooth muscle cells by exposure to FBS. Here we demonstrate an inhibitory effect of a pathologic contractile organ microenvironment on smooth muscle cell differentiation of SKPs. In vivo, urinary bladder strain induces microenvironmental changes leading to de-differentiation of fully differentiated bladder smooth muscle cells. Co-culture of SKPs with organoids isolated from ex vivo stretched bladders or exposure of SKPs to diffusible factors released by stretched bladders (e.g. bFGF) suppresses expression of smooth muscle markers (alpha SMactin, calponin, myocardin, myosin heavy chain) as demonstrated by qPCR and immunofluorescent staining. Rapamycin, an inhibitor of mTOR signalling, previously observed to prevent bladder strain induced de-differentiation of fully differentiated smooth muscle cells in vitro, inhibits FBS-induced smooth muscle cell differentiation of undifferentiated SKPs. These results suggest that intended precursor cell differentiation may be paradoxically suppressed by the disease context for which regeneration may be required. Organ-specific microenvironment contexts, particularly prevailing disease, may play a significant role in modulating or attenuating an intended stem cell phenotypic fate, possibly explaining the variable and inefficient differentiation of stem cell constructs in in vivo settings. These observations must be considered in drafting any regeneration strategies.