Current State of Private Practice and Academic Interventional Radiology: Differences in Practice Structure, Case Mix, and Productivity.

PURPOSE: To investigate whether private practice interventional radiology (IR) groups self-report higher overall productivity given differing case mix and more diagnostic radiology interpretation. MATERIALS AND METHODS: A 60-question survey was distributed to 3,159 self-identified US IR physicians via the Society of Interventional Radiologists member search engine, with 357 responses (11.3% response rate). Of these responses, there were 258 unique practices from 34 US states. RESULTS: Out of 84 IR group responses, private practice IR (PPIR) physicians reported a minimal trend for higher annual work relative value units (wRVUs) per clinical full-time equivalent compared with academic IR physicians (8,000 versus 7,140, P = .202), but this did not reach statistical significance. PPIR groups reported fewer median weekly hours (50 versus 52), more frequent call (every 6 versus every 5 days), and significantly higher median tenured compensation ($573,000 versus $451,000, P = .000). Out of 179 responses, academic practices reported significantly higher case percentages of interventional oncology and complex hepatobiliary intervention (P <.001), and private practices reported significantly higher percentages of musculoskeletal intervention (P < .001) with a nonsignificant trend for stroke or neurologic intervention (P = .010). Private practices reported more wRVUs from the interpretation of diagnostic imaging, at 26% of total wRVU production compared with 7% of total wRVU production for academic practices (P < .001; n = 131). CONCLUSIONS: Self-reported data from private and academic IR groups suggest minimally higher wRVUs per clinical full-time equivalent among PPIRs with lower weekly work hours, more frequent call, differing case mix, and significantly higher tenured compensation among PPIR groups.

Relationship between different surgical methods, hemorrhage position, hemorrhage volume, surgical timing, and treatment outcome of hypertensive intracerebral hemorrhage.

BACKGROUND: The present study aimed to explore the relationship between surgical methods, hemorrhage position, hemorrhage volume, surgical timing and treatment outcome of hypertensive intracerebral hemorrhage (HICH). METHODS: A total of 1 310 patients, who had been admitted to six hospitals from January 2004 to January 2008, were divided into six groups according to different surgical methods: craniotomy through bone flap (group A), craniotomy through a small bone window (group B), stereotactic drilling drainage (group C1 and group C2), neuron-endoscopy operation (group D) and external ventricular drainage (group E) in consideration of hemorrhage position, hemorrhage volume and clinical practice. A retrospective analysis was made of surgical timing and curative effect of the surgical methods. RESULTS: The effectiveness rate of the methods was 74.12% for 1 310 patients after one-month follow-up. In this series, the disability rate was 44.82% 3-6 months after the operation. Among the 1 310 patients, 241 (18.40%) patients died after the operation. If hematoma volume was >80 mL and the operation was performed within 3 hours, the mortality rate of group A was significantly lower than that of groups B, C, D, and E (P<0.05). If hematoma volume was 50-80 mL and the operation was performed within 6-12 hours, the mortality rate of groups B and D was lower than that of groups A, C and E (P<0.05). If hematoma volume was 20-50 mL and the operation was performed within 6-24 hours, the mortality rate of group C was lower than that of groups A, B and D (P<0.05). CONCLUSIONS: Craniotomy through a bone flap is suitable for patients with a large hematoma and hernia of the brain. Stereotactic drilling drainage is suggested for patients with hematoma volume less than 80 mL. The curative effect of HICH individualized treatment would be improved via the suitable selection of operation time and surgical method according to the position and volume of hemorrhage.

Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat.

BACKGROUND/AIMS: In this study, we investigated the effect of dalteparin sodium, a low molecular weight (LMW)-heparin, on hepatic fibrogenesis caused by chronic carbon tetrachloride (CCl4) administration in the rat. METHODS: Female Wistar rats were given a single, or repeated intraperitoneal injections of CCl4 (1ml/kg, twice per week) and dalteparin (50IU/kg, daily) for 7 weeks. RESULTS: Dalteparin did not prevent acute CCl4-induced hepatic necrosis and elevation in serum aminotransferases levels; however, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were dramatically increased 24h after simultaneous administration of CCl4 and dalteparin. Interestingly, serum hepatocyte growth factor (HGF) levels 12h after injection of CCl4 were almost doubled when dalteparin was given simultaneously. Hepatic fibrosis following 7-week CCl4 treatment was markedly ameliorated by daily co-administration of dalteparin. Indeed, dalteparin largely inhibited CCl4-induction of smooth muscle alpha-actin expression, alpha1(I)procollagen and transforming growth factor (TGF)-beta1 mRNA levels in the liver. Further, dalteparin blunted platelet-derived growth factor (PDGF)-induced increases in 5-bromo-2'deoxyuridine (BrdU) uptake in 3-day cultured hepatic stellate cells (HSCs) in a dose-dependent manner. CONCLUSIONS: Dalteparin enhances hepatic regeneration and minimizes hepatic fibrogenesis caused by chronic CCl4 treatment. The mechanism underlying these effects most likely involves both up-regulation of HGF and inhibition of HSC proliferation.

The role of leptin in progression of non-alcoholic fatty liver disease.

Since non-alchoholic steatohepatitis (NASH) is often accompanied with metabolic syndrome comprising obesity, type-2 diabetes and hypertension, it is hypothesized that adipocytokines, insulin resistance and autonomic nervous system play crucial roles in disease progression of NASH. On the other hand, hepatic stellate cells (HSCs) have been shown to produce leptin when they get activated during hepatic fibrogenesis. Therefore, we investigated the role of leptin in fibrogenesis in the liver. Xenobiotics-induced liver fibrosis was extremely diminished in ob/ob mice and Zucker (fa/fa) rats, an inborn leptin- and leptin receptor (Ob-R)-deficient animal, respectively. Further, leptin increased transforming growth factor (TGF)-beta mRNA in isolated sinusoidal endothelial cells and Kupffer cells, suggesting that leptin promotes hepatic fibrogenesis through up-regulation of TGF-beta in the liver. Moreover, leptin augmented PDGF-dependent proliferation of HSCs by enhancing downstream intracellular signaling pathways via mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/Akt. Taken together, it is postulated that leptin acts as a profibrogenic cytokine in sinusoidal microenvironment. These findings indicate that leptin is one of the key regulators for inflammation and progression of fibrosis in various chronic liver diseases including NASH.

Leptin facilitates proliferation of hepatic stellate cells through up-regulation of platelet-derived growth factor receptor.

In the present study, we investigated the effect of leptin on proliferation of hepatic stellate cells (HSCs) in vitro. Proliferation of 3-day cultured rat HSCs was assessed by incorporation of 5-bromo-2'-deoxyuridine (BrdU) into the nuclei. The percentages of BrdU-positive cells were increased in the presence of PDGF-BB (5 ng/ml) for 8h as expected. Co-incubation with leptin (10-100 nM) potentiates this PDGF-dependent increase in BrdU positive cells in a dose-dependent manner. Messenger RNA for PDGF receptor alpha and beta subunits was increased almost 2- to 3-fold by incubation with leptin for 6h. Further, pre-incubation with leptin for 6h enhanced PDGF-induced increases in phospho-p44/42 MAP kinase and phospho-Akt levels in a dose-dependent manner. In the same condition, however, leptin per se did not increase phospho-STAT 3 and phospho-p44/42 MAP kinase levels. Instead, leptin increased phospho-Akt levels in HSCs within 30 min, suggesting that the phosphatidylinositol 3 kinase (PI3K)/Akt pathway is involved in the mechanism by which leptin accelerates the proliferation of HSCs. In conclusion, the present study clearly indicated that leptin potentiates PDGF-dependent proliferative responses of HSCs in vitro.

Expression of leptin receptors in hepatic sinusoidal cells.

Emerging evidence has suggested a critical role of leptin in hepatic inflammation and fibrogenesis, however, the precise mechanisms underlying the profibrogenic action of leptin in the liver has not been well elucidated. Therefore, the present study was designed to investigate the expression and functions of leptin receptors (Ob-R) in hepatic sinusoidal cells. Hepatic stellate cells (HSCs), Kupffer cells and sinusoidal endothelial cells (SECs) were isolated from rat livers by in situ collagenase perfusion followed by differential centrifugation technique, and expression of Ob-Ra and Ob-Rb, short and long Ob-R isoforms, respectively, were analyzed by RT-PCR. Ob-Ra mRNA was detected ubiquitously in HSCs and SECs. In contrast, Ob-Rb was detected clearly only in SECs and Kupffer cells, but not in 7-day cultured HSCs. Indeed, tyrosine-phosphorylation of STAT-3, a downstream event of Ob-Rb signaling, was observed in SECs, but not in HSCs, 1 hr after incubation with leptin. Further, leptin increased AP-1 DNA binding activity and TGF-beta 1 mRNA levels in Kupffer cells and SECs, whereas leptin failed to increase TGF-beta 1 mRNA in HSCs. These findings indicated that SECs and Kupffer cells, but not HSCs, express functional leptin receptors, through which leptin elicits production of TGF-beta 1. It is hypothesized therefore that leptin, produced systemically from adipocytes and locally from HSCs, up-regulates TGF-beta 1 thereby facilitate tissue repairing and fibrogenesis in the sinusoidal microenvironment.

Leptin is required for fibrogenic responses induced by thioacetamide in the murine liver.

In this study, we investigated hepatic fibrogenesis caused by long-term thioacetamide (TAA) administration in ob/ob mice, a naturally occurring leptin deficient animal. In the lean littermates, prominent hepatic fibrosis, as well as positive staining for alpha smooth muscle actin (alpha-SMA), was induced by treatment with TAA (200 microg/g, IP, 3 times per week) for 4 to 8 weeks as expected. In sharp contrast, almost no hepatic fibrosis developed in ob/ob mice given the equivalent doses of TAA, where specific staining for alpha-SMA barely was detected. Induction of alpha1(I) procollagen mRNA caused by TAA also was prevented in ob/ob mice almost completely. Further, transforming growth factor beta (TGF-beta) mRNA was increased in the liver after TAA treatment for 4 weeks in lean littermates, which also was prevented in ob/ob mice. Interestingly, fibrotic septa in the hepatic lobules, as well as increases in alpha1(I) procollagen mRNA, was observed in ob/ob mice, when they were injected with recombinant murine leptin (1 microg/g daily) in combination with TAA treatment. Leptin per se did not cause any fibrotic changes in the liver in ob/ob mice. These findings clearly indicated that leptin deficiency is responsible for the resistance to TAA-induced profibrogenic responses in ob/ob mice. In conclusion, leptin appears to promote profibrogenic responses in the liver, in part, by up-regulation of TGF-beta.

Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat.

BACKGROUND & AIMS: In this study, we investigated the role of leptin and its receptors (Ob-R) in profibrogenic responses in the liver using Zucker (fa/fa) rats, a natural occurring Ob-R-deficient animal. METHODS: Male Zucker (fa/fa) rats and their lean (+/?) littermates were given intraperitoneal injections of thioacetamide (TAA) (200 mg/kg body wt, 3 times/wk) for 4-8 weeks, and progression of hepatic fibrosis was evaluated. In vitro transactivation of hepatic stellate cells (HSCs) isolated from Zucker rats was evaluated by Western blotting and immunocytochemistry for alpha-smooth muscle actin and type I collagen. Further, a long-form Ob-R (Ob-Rb) in sinusoidal endothelial cells (SECs) and Kupffer cells was identified by reverse-transcription polymerase chain reaction. Moreover, transforming growth factor (TGF)-beta1 messenger RNA in LSE cells, a human SEC-derived cell line, was measured by Northern blotting. RESULTS: Although the normal liver does not produce leptin, activated HSCs produced leptin in vivo during fibrogenesis caused by TAA. In Zucker rats, TAA-induced hepatic fibrosis was prevented almost completely, whereas induction of TGF-beta1 and activation of HSCs were abolished. It is less likely, however, that leptin plays an essential role in the activation of HSCs as a strong autocrine regulator, because HSCs isolated from Zucker rats undergo normal transactivation process in vitro. In contrast, SECs and Kupffer cells contain Ob-Rb, through which leptin up-regulates the expression of matrix remodeling genes including TGF-beta1. CONCLUSIONS: Collectively, these findings indicated that leptin and its functional receptors (Ob-Rb) play a pivotal role in profibrogenic responses in the liver.