Emerging applications for ferumoxytol as a contrast agent in MRI

Ferumoxytol is an ultrasmall superparamagnetic iron oxide (USPIO) agent initially approved by the Food and Drug Administration (FDA) as an iron replacement therapy for patients with anemia due to chronic renal failure. Recently, ferumoxytol has been investigated extensively as an intravenous contrast agent in magnetic resonance imaging (MRI). Since it causes regional T₁ and T₂* shortening in vivo, conventional pulse sequences can be used following ferumoxytol administration to demonstrate signal enhancement or loss. Ferumoxytol can be administered as a rapid bolus and has a long intravascular half‐life on the order of 14–15 hours, making it a potentially useful agent for vascular and perfusion‐weighted MRI. In comparison to other USPIOs, ferumoxytol is less limited by allergic and idiosyncratic reactions. Furthermore, since ferumoxytol is an iron‐based agent with no potential for causing nephrogenic systemic fibrosis, it may be useful as an alternative to gadolinium‐based contrast agents in patients with compromised renal function. Ferumoxytol is ultimately taken up by macrophages/the reticuloendothelial system in the liver, spleen, and lymph nodes, and this uptake mechanism is being explored as a novel imaging technique for vascular lesions, tumors, and lymph nodes. This article reviews the properties of ferumoxytol relevant to MRI as well as many of the uses for the agent currently under investigation. J. Magn. Reson. Imaging 2015;41:884–898 . © 2014 Wiley Periodicals, Inc .     

Isolation and Antibiogram of Clostridium tetani from Clinically Diagnosed Tetanus Patients

Clostridium tetani, the etiologic agent of tetanus, produces a toxin that causes spastic paralysis in humans and other vertebrates. This study was aimed for isolation, identification, and determination of antimicrobial susceptibility of C. tetani from clinically diagnosed tetanus patients. Isolation was done from deep-punctured tissues of the foot and arm injuries of 80 clinically diagnosed tetanus patients from the Pakistan Institute of Medical Sciences hospital. We successfully screened out five C. tetani isolates out of 80 samples based on the strain-specific characteristics confirmed through biochemical testing and toxin production. A disc diffusion method was used for antimicrobial susceptibilities and C. tetani isolates showed susceptibility to cefoperazone, chloramphenicol, metronidazole, penicillin G, and tetracycline, but were found to be resistant to erythromycin and ofloxacin. During animal testing, all the infected mice developed symptoms of tetanus. The results showed that identification of C. tetani is possible using biochemical and molecular tools and that the strains of C. tetani isolated had not developed resistance against the antibiotics most often used for the treatment of tetanus.     

Laparoendoscopic single‐site (LESS) vs laparoscopic living‐donor nephrectomy: a systematic review and meta‐analysis

The aim of this study was to provide a systematic review and meta‐analysis of reports comparing laparoendoscopic single‐site (LESS) living‐donor nephrectomy (LDN) vs standard laparoscopic LDN (LLDN). A systematic review of the literature was performed in September 2013 using PubMed, Scopus, Ovid and The Cochrane library databases. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta‐analyses criteria. Weighted mean differences (WMDs) were used to measure continuous variables and odds ratios (ORs) to measure categorical ones. Nine publications meeting eligibility criteria were identified, including 461 LESS LDN and 1006 LLDN cases. There were more left‐side cases in the LESS LDN group (96.5% vs 88.6%, P < 0.001). Meta‐analysis of extractable data showed that LLDN had a shorter operative time (WMD 15.06 min, 95% confidence interval [CI] 4.9–25.1; P = 0.003), without a significant difference in warm ischaemia time (WMD 0.41 min, 95% CI –0.02 to 0.84; P = 0.06). Estimated blood loss was lower for LESS LDN (WMD ?22.09 mL, 95% CI –29.5 to –14.6; P < 0.001); however, this difference was not clinically significant. There was a greater likelihood of conversion for LESS LDN (OR 13.21, 95% CI 4.65–37.53; P < 0.001). Hospital stay was similar (WMD –0.11 days, 95% CI –0.33 to 0.12; P = 0.35), as well as the visual analogue pain score at discharge (WMD –0.31, 95% CI –0.96 to 0.35; P = 0.36), but the analgesic requirement was lower for LESS LDN (WMD –2.58 mg, 95% CI –5.01 to –0.15; P = 0.04). Moreover, there was no difference in the postoperative complication rate (OR 1.00, 95% CI 0.65–1.54; P = 0.99). Renal function of the recipient, as based on creatinine levels at 1 month, showed similar outcomes between groups (WMD 0.10 mg/dL, –0.09 to 0.29; P = 0.29). In conclusion, LESS LDN represents an emerging option for living kidney donation. This procedure offers comparable surgical and early functional outcomes to the conventional LLDN, with a lower analgesic requirement. However, it is more technically challenging than LLDN, as shown by a greater likelihood of conversion. The role of LESS LDN remains to be defined.     

Renal fractional flow reserve: a hemodynamic evaluation of moderate renal artery stenoses.

The objective of this study was to perform a hemodynamic evaluation of moderate (50-90%) renal artery stenosis (RAS) under conditions of rest and maximum hyperemia. Identifying patients with RAS who have hemodynamically significant stenoses and are most likely to benefit from revascularization is clinically important. Current methods used to evaluate RAS, including angiography, have limitations. Physiologic evaluation of RAS may have a role in identifying patients with hemodynamically significant stenosis. Patients with suspected renovascular hypertension due to aorto-ostial RAS were included in the study. Hyperemia was induced by administration of intrarenal papavarine. Translesional pressure gradients were measured and renal fractional flow reserve (FFR) was calculated using a 0.014' pressure guidewire. Thirteen patients and 14 arteries with moderately severe (50-90%) RAS were studied. The mean translesional pressure gradient rose from a baseline of 6.3 +/- 3.9 to 17.5 +/- 10.8 mm Hg with maximal hyperemia. The renal FFR ranged from 0.58 to 0.95. There was a poor correlation between angiographic stenosis measurement and the renal FFR (r = -0.18; P = 0.54) and the hyperemic translesional mean pressure gradient (r = 0.22; P = 0.44). There was an excellent correlation between renal FFR and the resting mean translesional pressure gradient (r = -0.76; P = 0.0016) and the hyperemic mean translesional pressure gradient (r = -0.94; P < 0.0001). Selective renal arterial papavarine administration induces maximum hyperemia, permitting the calculation of renal FFR in renal arteries with aorto-ostial stenoses. The renal FFR correlates well with other hemodynamic parameters of lesion severity, but poorly with angiographic measures of lesion severity.     

Numerical Modeling and Analysis of Ti6Al4V Alloy Chip for Biomedical Applications

The influence of cutting forces during the machining of titanium alloys has attained prime attention in selecting the optimal cutting conditions to improve the surface integrity of medical implants and biomedical devices. So far, it has not been easy to explain the chip morphology of Ti6Al4V and the thermo-mechanical interactions involved during the cutting process. This paper investigates the chip configuration of the Ti6Al4V alloy under dry milling conditions at a macro and micro scale by employing the Johnson-Cook material damage model. 2D modeling, numerical milling simulations, and post-processing were conducted using the Abaqus/Explicit commercial software. The uncut chip geometry was modeled with variable thicknesses to accomplish the macro to micro-scale cutting by adapting a trochoidal path. Numerical results, predicted for the cutting reaction forces and shearing zone temperatures, were found in close approximation to experimental ones with minor deviations. Further analyses evaluated the influence of cutting speeds and contact friction coefficients over the chip flow stress, equivalent plastic strain, and chip morphology. The methodology developed can be implemented in resolving the industrial problems in the biomedical sector for predicting the chip morphology of the Ti6Al4V alloy, fracture mechanisms of hard-to-cut materials, and the effects of different cutting parameters on workpiece integrity.     

Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study

Aims/hypothesis

The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes.

Methods

We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR >?3.4 mg/mmol) or an estimated (eGFR) <?60 ml min^?1 1.73 m^?2. CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability.

Results

Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (?9.0?±?17.8% vs ?3.3?±?10.3%, p?=?0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (β?=??3.5, p?=?0.03). Spectral analysis variables were also independent predictors of eGFR decline.

Conclusions/interpretation

CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.