Inducible cAMP Early Repressor Regulates Corticosterone Suppression after Tricyclic Antidepressant Treatment

The cAMP-response element binding protein (CREB) is involved in antidepressant action, but the role of related CRE-binding transcription factors in the behavioral and endocrine responses to antidepressants is unclear. Alternative transcription of the cAMP response element-modulator (CREM) gene yields activator and repressor isoforms, including the strong repressor induciblecAMPearly repressor (ICER). ICER is highly expressed in hypothalamic tissues and upregulated after electroconvulsive seizure. Thus, ICER may be a novel mediator of antidepressant action at endocrine and/or behavioral levels. Here we establish that both subchronic and chronic desipramine (DMI) treatments upregulate hypothalamic ICER expression in wild-type mice. Behavioral responses to DMI in the forced swim and tail suspension tests are unchanged in mice lacking ICER. However, the ability of DMI to suppress an acute corticosterone response after swim stress is compromised in ICER-deficient mice, suggesting that increased hypothalamic ICER mRNA after DMI treatment may be required for suppression of corticosterone release. To investigate the mechanism underlying this response, we measured corticotropin releasing factor (CRF), an upstream modulator of corticosterone release. Using real-time quantitative PCR, we establish that hypothalamic CRF expression is significantly reduced after swim exposure in DMI-treated wild-type mice, however DMI is unable to blunt hypothalamic CRF expression in ICER-deficient mice. Furthermore, we demonstrate that ICER is enriched in CRF-expressing neurons in the paraventricular nucleus of the hypothalamus. These data indicate that ICER is required for DMI to reduce stress-induced corticosterone release through regulation of hypothalamic CRF expression, revealing a novel role for ICER in antidepressant regulation of the hypothalamic–pituitary adrenal axis

Efficacy of TACE in TIPS patients: comparison of treatment response to chemoembolization for hepatocellular carcinoma in patients with and without a transjugular intrahepatic portosystemic shunt.

PURPOSE: To compare treatment response after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients with and without a transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: A retrospective review of patients who underwent conventional TACE for HCC between January 2005 and December 2009 identified 10 patients with patent TIPS. From the same time period, 23 patients without TIPS were selected to control for comparable Model for End-Stage Liver Disease and Child-Pugh-Turcotte scores. The two groups showed similar distribution of Barcelona Clinic Liver Cancer and United Network of Organ Sharing stages. Target HCC lesions were evaluated according to the modified response evaluation criteria in solid tumors (mRECIST) guidelines. Transplantation rate, time to tumor progression, and overall survival (OS) were documented. RESULTS: After TACE, the rate of complete response was significantly greater in non-TIPS patients compared with TIPS patients (74 vs. 30 %, p = 0.03). Objective response rate (complete and partial response) trended greater in the non-TIPS group (83 vs. 50 %, p = 0.09). The liver transplantation rate was 80 and 74 % in the TIPS and non-TIPS groups, respectively (p = 1.0). Time to tumor progression was similar (p = 0.47) between the two groups. OS favored the non-TIPS group (p = 0.01) when censored for liver transplantation. CONCLUSION: TACE is less effective in achieving complete or partial response using mRECIST criteria in TIPS patients compared with those without a TIPS. Nevertheless, similar clinical outcomes may be achieved, particularly in TIPS patients who are liver-transplantation candidates

Efficacy of TACE in TIPS patients: comparison of treatment response to chemoembolization for hepatocellular carcinoma in patients with and without a transjugular intrahepatic portosystemic shunt.

PurposeTo compare treatment response after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) in patients with and without a transjugular intrahepatic portosystemic shunt (TIPS).Materials and methodsA retrospective review of patients who underwent conventional TACE for HCC between January 2005 and December 2009 identified 10 patients with patent TIPS. From the same time period, 23 patients without TIPS were selected to control for comparable Model for End-Stage Liver Disease and Child-Pugh-Turcotte scores. The two groups showed similar distribution of Barcelona Clinic Liver Cancer and United Network of Organ Sharing stages. Target HCC lesions were evaluated according to the modified response evaluation criteria in solid tumors (mRECIST) guidelines. Transplantation rate, time to tumor progression, and overall survival (OS) were documented.ResultsAfter TACE, the rate of complete response was significantly greater in non-TIPS patients compared with TIPS patients (74 vs. 30 %, p = 0.03). Objective response rate (complete and partial response) trended greater in the non-TIPS group (83 vs. 50 %, p = 0.09). The liver transplantation rate was 80 and 74 % in the TIPS and non-TIPS groups, respectively (p = 1.0). Time to tumor progression was similar (p = 0.47) between the two groups. OS favored the non-TIPS group (p = 0.01) when censored for liver transplantation.ConclusionTACE is less effective in achieving complete or partial response using mRECIST criteria in TIPS patients compared with those without a TIPS. Nevertheless, similar clinical outcomes may be achieved, particularly in TIPS patients who are liver-transplantation candidates

Clinical outcomes of percutaneous drainage of breast fluid collections after mastectomy with expander-based breast reconstruction.

PurposeTo determine clinical outcomes of patients who underwent imaging-guided percutaneous drainage of breast fluid collections after mastectomy and breast reconstruction.Materials and methodsA retrospective review was performed including all consecutive patients who underwent percutaneous drainage of fluid collections after mastectomy with tissue expander-based reconstruction between January 2007 and September 2012. During this period, 879 mastectomies (563 patients) with expander-based breast reconstruction were performed. Fluid collections developed in 28 patients (5%), which led to 30 imaging-guided percutaneous drainage procedures. The median follow-up time was 533 days. Patient characteristics, surgical technique, microbiology analysis, and clinical outcomes were reviewed.ResultsThe mean age of patients was 51.5 years (range, 30.9-69.4 y), and the median time between breast reconstruction and drainage was 35 days (range, 4-235 d). Erythema and swelling were the most common presenting symptoms. The median volume of fluid evacuated at the time of drain placement was 70 mL. Drains were left in place for a median 14 days (range, 6-34 d). Microorganisms were detected in the fluid in 12 of 30 drainage procedures, with Staphylococcus aureus being the most common microorganism. No further intervention was needed in 21 of 30 drainage procedures (70%). However, surgical intervention (removal of expanders) was needed after 6 (20%) drainage procedures, and additional percutaneous drainage procedures were performed after 3 (10%) drainage procedures.ConclusionsPercutaneous drainage is an effective means of treating postoperative fluid collections after expander-based breast reconstruction and can obviate the need for repeat surgery in most cases