Imaging assessment of a portable hemodialysis device: detection of possible failure modes and monitoring of functional performance.

BACKGROUND: The purpose of this study was to investigate the utility and limitations of various imaging modalities in the noninvasive assessment of a novel compact hemodialyzer under development for renal replacement therapy, with specific aim towards monitoring its functional performance. METHODS: The prototype is a 4×3×6 cm aluminum cartridge housing "blood" and "dialysate" flow paths arranged in parallel. A sheet of semipermeable silicon nanopore membranes forms the blood-dialysate interface, allowing passage of small molecules. Blood flow was simulated using a peristaltic pump to instill iodinated contrast through the blood compartment, while de-ionized water was instilled through the dialysate compartment at a matched rate in the countercurrent direction. Images were acquired under these flow conditions using multi-detector computed tomography (MDCT), fluoroscopy, high-resolution quantitative computed tomography (HR-QCT), and magnetic resonance imaging (MRI). MDCT was used to monitor contrast diffusion efficiency by plotting contrast density as a function of position along the path of flow through the cartridge during steady state infusion at 1 and 20 mL/min. Both linear and exponential regressions were used to model contrast decay along the flow path. RESULTS: Both linear and exponential models of contrast decay appeared to be reasonable approximations, yielding similar results for contrast diffusion during a single pass through the cartridge. There was no measurable difference in contrast diffusion when comparing 1 mL/min and 20 mL/min flow rates. Fluoroscopy allowed a gross qualitative assessment of flow within the device, and revealed flow inhomogeneity within the corner of the cartridge opposite the blood inlet port. MRI and HR-QCT were both severely limited due to the paramagnetic properties and high atomic number of the target material, respectively. During testing, we encountered several causes of device malfunction, including leak formation, trapped gas, and contrast-mediated nanopore clogging. We illustrate the imaging manifestations of each. CONCLUSIONS: Despite the inherent challenges in imaging a predominantly metallic device, some modalities show potential in the non-invasive assessment of a novel compact hemodialyzer. The approaches described here could potentially be translated to device evaluation in the implanted setting.

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.

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

PURPOSE: To determine clinical outcomes of patients who underwent imaging-guided percutaneous drainage of breast fluid collections after mastectomy and breast reconstruction. MATERIALS AND METHODS: A 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. RESULTS: The 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. CONCLUSIONS: Percutaneous 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.

Drainage of collections associated with hernia mesh: is it worthwhile?

PURPOSE: Synthetic mesh has revolutionized abdominal wall hernia repair. However, mesh infections present a clinical problem because the standard practice of surgical excision is fraught with increased morbidity. Here, single-institutional outcomes in managing mesh-related collections via percutaneous drainage are retrospectively reviewed to assess its effectiveness. MATERIALS AND METHODS: A total of 21 patients underwent drainage of perimesh collections. Three types of mesh were employed: polytetrafluoroethylene (PTFE; n = 5), polypropylene (n = 14), and porcine dermal collagen (n = 3). One patient received both polypropylene and PTFE. Drainage was performed with ultrasound guidance (n = 19) or surgical drain exchange (n = 2). Mesh type, culture results, fluid collection size, and location were analyzed with respect to need for mesh excision. RESULTS: Sixteen of 21 patients (76%) were successfully treated with drainage. One required additional surgical capsulectomy; the mesh was salvaged. Four required mesh excision because of recurrent infection (n = 2) or lack of improvement of clinical course (n = 2). Recurrent infection occurred in six patients, with mesh salvage via conservative management or new drainage in four. Fluid cultures were positive in 68% of patients (n = 13), with Staphylococcus aureus the most common organism. Cultures did not predict mesh excision (P = .26). The PTFE excision rate trended higher compared with polypropylene (40% vs 14%; P = .27). No porcine dermal collagen mesh was excised. Neither fluid collection size nor location predicted mesh excision. Mean follow-up was 319 days (range, 6-1,406 d). CONCLUSIONS: Percutaneous drainage of suspected mesh-related abscess is effective. The use of PTFE mesh trended toward a higher excision rate.

Erosion of anterior cervical plate into pharynx with pharyngotracheal fistula.

We report a 58-year-old woman who presented with dysphagia and recurrent episodes of coughing and choking during swallowing 10 years after anterior cervical discectomy and fusion with implantation of an anterior cervical plate. Barium esophagography revealed erosion of the cervical plate through the posterior wall of the pharyngoesophageal junction with an extraluminal collection that extended inferiorly as a track through the posterior wall of the trachea, producing a pharyngotracheal fistula. The pharyngeal perforation was repaired and the cervical hardware removed at surgery. This rare complication of anterior cervical discectomy and fusion should be recognized as a potentially serious but treatable long-term sequela of an anterior cervical plate.

Large or small bore, push or pull: a comparison of three classes of percutaneous fluoroscopic gastrostomy catheters.

PURPOSE: To compare the tube performance and complication rates of small-bore, large-bore push-type, and large-bore pull-type gastrostomy catheters. MATERIALS AND METHODS: A total of 160 patients (74 men, 86 women; mean age, 66.9 years, range, 22-95 y) underwent percutaneous fluoroscopic gastrostomy placement between January 2004 and March 2006. Choice of catheter was based on the preference of the attending radiologist. Data were collected retrospectively with institutional review board approval. Radiology reports provided information on the catheter, indication for gastrostomy, technical success, and immediate outcome. Chart review provided data on medical history, postprocedural complications, progress to feeding goal, and clinical outcomes. Statistical analysis was performed to compare the three classes of gastrostomy catheters. RESULTS: All 160 catheters were placed successfully. Patients who received small-bore catheters (14 F; n = 88) had significantly more tube complications (17% vs 5.6%) and were less likely to meet their feeding goal (P = .035) compared with patients with large-bore catheters (20 F; n = 72). No difference was observed in terms of major or minor complications. Large-bore push-type (n = 14) and pull-type catheters (n = 58) were similar in terms of complication rates. Patients who received large-bore push-type catheters achieved their feeding goals in significantly less time than those with large-bore pull-type catheters (average, 3.8 days vs 6.0 days; P = .04). CONCLUSIONS: Patients who received small-bore gastrostomy catheters are significantly more prone to tube dysfunction. Large-bore catheters should be preferentially used, with push-type catheters performing better with regard to the time to achieve feeding goal.

Mu-opioid receptor and CREB activation are required for nicotine reward.

Environmental cues associated with nicotine delivery are an important part of the stimulus that sustains smoking behavior and is often coupled with craving and relapse; however, the neuronal circuitry and molecular substrates underlying this process are still poorly understood. Exposure to an environment previously associated with rewarding properties of nicotine results in an increase of CREB phosphorylation similar to that seen following nicotine administration, and this response is absent in MOR(-/-) mice. Moreover, a single administration of an opioid receptor antagonist, naloxone, blocks both the conditioned molecular response (CREB phosphorylation) and the conditioned behavioral response (nicotine reward) in a place preference paradigm. Lastly, repeated nicotine administration results in increased expression of MORs. However, this effect, along with rewarding properties of nicotine, is blocked in mice with a targeted disruption in the CREB gene. Together, pharmacologic and genetic manipulations indicate that phosphorylation of CREB and upregulation of functional MORs are required for nicotine-conditioned reward.

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 inducible cAMP early 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.

Differential distribution of CREB in the mesolimbic dopamine reward pathway.

The transcription factor cAMP response element binding protein (CREB) has been implicated in the long-term neuronal plasticity associated with addiction. While CREB is expressed in many cells throughout the brain, very little is known about the relative concentrations of CREB protein in various brain regions. Studies in which CREB levels have been altered, either constitutively throughout the brain via gene targeting or transiently in specific brain regions, demonstrate variable roles for this protein in mediating reinforcing properties of drugs of abuse. To investigate the complex nature of CREB function in addiction, we examined the distribution of CREB protein in the nucleus accumbens (NAc) and ventral tegmental area (VTA), two brain regions that are part of the well-defined mesolimbic dopamine pathway involved in reward processing. Our data demonstrate significantly more CRE binding activity and CREB protein in the NAc compared to levels present in the VTA of wild-type mice. Phospho-CREB levels are increased in the NAc of both wild-type and CREBalphaDelta mutant animals after cocaine. However, morphine-induced increases of phospho-CREB levels are seen in the VTA of wild-type mice but not CREBalphaDelta mutant mice. Consequently, the 90% reduction of CREB in CREBalphaDelta mutant mice differentially affects CREB phosphorylation and induction of downstream targets of CREB in the NAc and VTA.