Effect of Impeller Design and Spacing on Gas Exchange in a Percutaneous Respiratory Assist Catheter

Providing partial respiratory assistance by removing carbon dioxide (CO₂) can improve clinical outcomes in patients suffering from acute exacerbations of chronic obstructive pulmonary disease and acute respiratory distress syndrome. An intravenous respiratory assist device with a small (25 Fr) insertion diameter eliminates the complexity and potential complications associated with external blood circuitry and can be inserted by nonspecialized surgeons. The impeller percutaneous respiratory assist catheter (IPRAC) is a highly efficient CO₂ removal device for percutaneous insertion to the vena cava via the right jugular or right femoral vein that utilizes an array of impellers rotating within a hollow‐fiber membrane bundle to enhance gas exchange. The objective of this study was to evaluate the effects of new impeller designs and impeller spacing on gas exchange in the IPRAC using computational fluid dynamics (CFD) and in vitro deionized water gas exchange testing. A CFD gas exchange and flow model was developed to guide a progressive impeller design process. Six impeller blade geometries were designed and tested in vitro in an IPRAC device with 2‐ or 10‐mm axial spacing and varying numbers of blades (2–5). The maximum CO₂ removal efficiency (exchange per unit surface area) achieved was 573 ± 8 mL/min/m² (40.1 mL/min absolute). The gas exchange rate was found to be largely independent of blade design and number of blades for the impellers tested but increased significantly (5–10%) with reduced axial spacing allowing for additional shaft impellers (23 vs. 14). CFD gas exchange predictions were within 2–13% of experimental values and accurately predicted the relative improvement with impellers at 2‐ versus 10‐mm axial spacing. The ability of CFD simulation to accurately forecast the effects of influential design parameters suggests it can be used to identify impeller traits that profoundly affect facilitated gas exchange.     

Open reconstruction of recurrent vesicourethral anastomotic stricture after radical prostatectomy

Objectives

To determine the outcomes of open vesicourethral anastomotic reconstruction (VUAR) for outlet stenosis following radical prostatectomy (RP).

Methods

Review of all cases of VUAR within an IRB-approved database was performed. Preoperative factors assessed included cancer treatment modality, duration of symptoms, prior treatments, and length of defect. Outcomes reviewed included length-of-stay (LOS), complications, maintenance of patency, continence, and need for additional procedures.

Results

Twelve cases of VUAR performed by a single surgeon (BJF) from 2004 to 2012 were identified. Surgical approaches were either abdominal (7), perineal (3), or abdominoperineal (2). All patients underwent prior RP, with 25 % having subsequent radiotherapy. Among patients with stenosis, 43 % were completely obliterated. Two cases had prior anastomotic disruption in the early postoperative period after RP. The median length of stenosis was 2.5 cm (range 1–5 cm) and median LOS was 3.0 days (range 1–7 days). At a median follow-up of 75.5 months (range 14–120 months), 92 % of men retained patency; only 25 % were continent.

Conclusion

In experienced hands, VUAR can restore durable patency for men afflicted with outlet stenosis after RP. Despite anatomic restoration, incontinence is likely.     

Urine kidney injury molecule-1: a potential non-invasive biomarker for patients with renal cell carcinoma

Background

KIM-1 staining is upregulated in proximal tubule-derived renal cell carcinoma (RCC) including clear renal cell carcinoma and papillary renal cell carcinoma, but not in chromophobe RCC (distal tubular tumor). This study was designed to prospectively examine urine KIM-1 level before and 1 month after removal of renal tumors.

Patients and design

A total of 19 patients were eventually enrolled in the study based on pre-operative imaging studies. Pre-operative and follow-up (1 month) urine KIM-1 levels were measured. The urine KIM-1 levels (uKIM-1) were then normalized to urine creatinine levels (uCr). Renal tumors were also stained for KIM-1 using immunohistochemical techniques.

Results

The KIM-1-negative staining group included 7 cases, and the KIM-1-positive group consisted of 12 cases. The percentage of KIM-1-positive staining RCC cells ranged from 10 to 100 %, and the staining intensity ranged from 1+ to 3+. In both groups, serum creatinine levels were both significantly elevated after nephrectomy. In the KIM-1-negative group, uKIM-1/uCr remained at a similar level before (0.37 ± 0.1 ng/mg Cr) and after nephrectomy (0.32 ± 0.01 ng/mg Cr). However, in the KIM-1-positive group, elevated uKIM-1/uCr at 1.20 ± 0.31 ng/mg Cr was significantly reduced to 0.36 ± 0.1 ng/mg Cr, which was similar to the pre-operative uKIM-1/uCr (0.37 ± 0.1 ng/mg Cr) in the KIM-1-negative group.

Conclusion

Our small but prospective study showed significant reduction in uKIM-1/uCr after nephrectomy in the KIM-1 positive group, suggesting that urine KIM-1 may serve as a surrogate biomarker for kidney cancer and a non-invasive pre-operative measure to evaluate the malignant potential of renal masses.     

Incentives and Disincentives for the Treatment of Depression and Anxiety: A Scoping Review

Objective:

There is widespread support for primary care to help address growing mental health care demands. Incentives and disincentives are widely used in the design of health care systems to help steer toward desired goals. The absence of a conceptual model to help understand the range of factors that influence the provision of primary mental health care inspired a scoping review of the literature. Understanding the incentives that promote and the disincentives that deter treatment for depression and anxiety in the primary care context will help to achieve goals of greater access to mental health care.

Method:

A review of the literature was conducted to answer the question, how are incentives and disincentives conceptualized in studies investigating the treatment of common mental disorders in primary care? A comprehensive search of MEDLINE, PsycINFO, CINAHL, and Google Scholar was undertaken using Arksey and O’Malley’s 5-stage methodological framework for scoping reviews.

Results:

We identified 27 studies. A range of incentives and disincentives influence the success of primary mental health care initiatives to treat depression and anxiety. Six types of incentives and disincentives can encourage or discourage treatment of depression and anxiety in primary care: attitudes and beliefs, training and core competencies, leadership, organizational, financial, and systemic.

Conclusions:

Understanding that there are 6 different types of incentives that influence treatment for anxiety and depression in primary care may help service planners who are trying to promote improved mental health care.     

Characterization of Renal Toxicity in Mice Administered the Marine Biotoxin Domoic Acid

Domoic acid (DA), an excitatory amino acid produced by diatoms belonging to the genus Pseudo-nitzschia, is a glutamate analog responsible for the neurologic condition referred to as amnesic shellfish poisoning. To date, the renal effects of DA have been underappreciated, although renal filtration is the primary route of systemic elimination and the kidney expresses ionotropic glutamate receptors. To characterize the renal effects of DA, we administered either a neurotoxic dose of DA or doses below the recognized limit of toxicity to adult Sv128/Black Swiss mice. DA preferentially accumulated in the kidney and elicited marked renal vascular and tubular damage consistent with acute tubular necrosis, apoptosis, and renal tubular cell desquamation, with toxic vacuolization and mitochondrial swelling as hallmarks of the cellular damage. Doses≥0.1 mg/kg DA elevated the renal injury biomarkers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, and doses≥0.005 mg/kg induced the early response genes c-fos and junb. Coadministration of DA with the broad spectrum excitatory amino acid antagonist kynurenic acid inhibited induction of c-fos, junb, and neutrophil gelatinase-associated lipocalin. These findings suggest that the kidney may be susceptible to excitotoxic agonists, and renal effects should be considered when examining glutamate receptor activation. Additionally, these results indicate that DA is a potent nephrotoxicant, and potential renal toxicity may require consideration when determining safe levels for human exposure.Domoic acid (DA), a water-soluble, heat-stable tricarboxylic acid produced by diatoms belonging to the genus Pseudo-nitzschia, is responsible for a condition known as amnesic shellfish poisoning in humans.^1–4 Shellfish, such as clams and mussels, and fish that accumulate DA serve as vectors of exposure to various species of birds and aquatic mammals in addition to humans.^5,6 Initially recognized as a human toxicant when more than 100 people became ill after eating contaminated mussels in eastern Canada in 1987, DA poisoning was defined by the occurrence of gastrointestinal or neurologic symptoms ranging from abdominal cramps and headache to more severe cases of memory loss, seizures, coma, and even death.^2,4 Increased awareness and governmental regulation, which set a limit of 20 μg DA/g in shellfish tissue, has reduced the incidence of DA toxicity in humans since the 1987 outbreak. However, there is concern that exposure will increase because of the growing presence of toxic diatom-producing algal blooms, which are often attributed to human factors, such as pollution, shipping, and global warming, leading to greater nutrient availability, greater distribution of algal species, and longer growth periods.^7–14 Although the overt gastrointestinal and neurologic manifestations have defined the disease, emerging evidence from animal and human studies support previously unrecognized threats and novel toxicologic syndromes caused by subclinical toxicity from acute and chronic DA exposures, which may ultimately challenge the adequacy of the current acceptable limit.^15–18DA is a potent activator of kainate receptors (KRs) as well as a subpopulation of α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptors (AMPARs).¹⁹ The toxic response produced by DA is a coordinated effort, which involves initial activation of KR and AMPAR by DA and secondary activation of N-methyl-D-aspartate receptors (NMDARs) by glutamate, and it is associated with an influx of Ca²⁺ across the plasma membrane, inflammation, neuronal cell injury and death, and neurobehavioral alterations.^19–22 Although they are extensively characterized in the central nervous system, glutamate receptors are also expressed at peripheral sites and have been shown to exhibit toxicity in multiple tissues, including the kidney, where NMDARs contribute to organ damage in models of ischemia-reperfusion injury and gentamicin nephrotoxicity.^23–26 There is limited information about the effects of DA on the kidney; however, oral dosing in coho salmon has shown that the kidney is a primary site of DA accumulation in this species, and studies in rodents have shown that renal excretion is the exclusive route of systemic DA elimination.^27,28 Examination of sea lions after DA poisoning has also revealed some evidence of interstitial nephritis, renal edema, and elevated BUN, although the exact cause of these findings cannot be definitively attributed to DA toxicity.^29,30 Furthermore, sea lions with acute DA toxicosis seem to have an elevated hematocrit,³¹ suggesting that water reabsorption or red blood cell production could be affected, both of which are functions of the kidney. Despite this circumstantial evidence, a detailed examination of the renal response to DA administration has not been fully explored. The purpose of the current study was to characterize the acute renal effects of DA at doses that produce neurotoxicity and neurobehavioral changes (1.0–2.5 mg/kg) as well as several lower doses (0.0005–0.5 mg/kg), which are considered below the limit of toxicity.