Healthcare utilization following spinal cord injury: Objective findings from a regional hospital registry

Objective: The purpose was to describe the prevalence and characteristics of healthcare utilization among individuals with spinal cord injury (SCI) from a Level I trauma center.

Design: Retrospective data analysis utilizing a local acute trauma registry for initial hospitalization and merged with the Dallas-Fort Worth Hospital Council registry to obtain subsequent health care utilization in the first post-injury year.

Setting: Dallas, TX, USA.

Participants: Six hundred and sixty four patients were admitted with an acute traumatic SCI from January 2003 through June 2014 to a Level I trauma center. Fifty five patients that expired during initial hospitalization and 18 patients with unspecified SCI (defined by ICD-9 with no etiology or level of injury specified) were not included in the analysis, leaving a final sample of 591.

Outcome Measures: Data included demographic and clinical characteristics, charges, and healthcare utilization.

Results: Mean age was 46.1?years (±18.9?years), the majority of patients were male (74%), and Caucasian (58%). Of the 591 patients, 345 (58%) had additional inpatient or emergency healthcare utilization accounting for 769 additional visits (median of 3 visits per person). Of the 769 encounters, 534 (69%) were inpatient and 235 (31%) were emergency visits not resulting in an admission. The most prevalent ICD-9 codes listed were pressure ulcer, neurogenic bowel, neurogenic bladder, urinary tract infection, fluid electrolyte imbalance, hypertension, and tobacco use.

Conclusion: Individuals with SCI experience high levels of healthcare utilization which are costly and may be preventable. Increasing our understanding of the prevalence and causes for healthcare utilization after acute SCI is important to target preventive strategies.     

Elucidation of the mechanism of mitochondrial iron loading in Friedreich's ataxia by analysis of a mouse mutant

We used the muscle creatine kinase (MCK) conditional frataxin knockout mouse to elucidate how frataxin deficiency alters iron metabolism. This is of significance because frataxin deficiency leads to Friedreich''s ataxia, a disease marked by neurologic and cardiologic degeneration. Using cardiac tissues, we demonstrate that frataxin deficiency leads to down-regulation of key molecules involved in 3 mitochondrial utilization pathways: iron-sulfur cluster (ISC) synthesis (iron-sulfur cluster scaffold protein1/2 and the cysteine desulferase Nfs1), mitochondrial iron storage (mitochondrial ferritin), and heme synthesis (5-aminolevulinate dehydratase, coproporphyrinogen oxidase, hydroxymethylbilane synthase, uroporphyrinogen III synthase, and ferrochelatase). This marked decrease in mitochondrial iron utilization and resultant reduced release of heme and ISC from the mitochondrion could contribute to the excessive mitochondrial iron observed. This effect is compounded by increased iron availability for mitochondrial uptake through (i) transferrin receptor1 up-regulation, increasing iron uptake from transferrin; (ii) decreased ferroportin1 expression, limiting iron export; (iii) increased expression of the heme catabolism enzyme heme oxygenase1 and down-regulation of ferritin-H and -L, both likely leading to increased “free iron” for mitochondrial uptake; and (iv) increased expression of the mammalian exocyst protein Sec15l1 and the mitochondrial iron importer mitoferrin-2 (Mfrn2), which facilitate cellular iron uptake and mitochondrial iron influx, respectively. Our results enable the construction of a model explaining the cytosolic iron deficiency and mitochondrial iron loading in the absence of frataxin, which is important for understanding the pathogenesis of Friedreich''s ataxia.     

Irs2 Inactivation Suppresses Tumor Progression in Pten+/− Mice

Mutations in the phosphatase and tensin homologue (PTEN)/phosphatidylinositol-3 kinase-α (PI3K) signaling pathway are frequently found in human cancer. In addition, Pten^+/− mice develop tumors in multiple organs because of the activation of the PI3K signaling cascade. Because activation of PI3K signaling leads to feedback inhibition of insulin receptor substrate-2 (IRS2) expression, an upstream activator of PI3K, we therefore anticipated that IRS2 expression would be low in tumors that lack PTEN. Surprisingly, however, an elevation of IRS2 was often detected in tumor samples in which PTEN levels were compromised. To determine the potential contribution of Irs2 to tumor progression, Pten^+/− mice were crossed with Irs2^+/− mice. Deletion of Irs2 did not affect the initiation of neoplasia found in Pten^+/− mice but suppressed cancer cell growth, proliferation, and invasion through the basement membrane. Deletion of Irs2 also attenuated the expression of Myc in prostatic intraepithelial neoplasia in Pten^+/− mice. In addition, the expression levels of IRS2 and MYC were highly correlated in human prostate cancer, and IRS2 could stimulate MYC expression in cultured cells. Our findings provide evidence that the PI3K-activating adaptor Irs2 contributes to tumor progression in Pten^+/− mice by stimulating both Myc and DNA synthesis.