Patient Blood Management in Neonates.

Patient blood management (PBM) is an evidence-based care package to improve patient outcomes by optimizing a patient's blood, minimizing blood loss, and the effective management and, when appropriate, the tolerance of anemia. It is relatively well-developed in adult medicine and remains in its infancy in neonatology. This review explores why evidence-based guidelines are insufficient, discusses the variations in neonatal transfusion practice and why this matters, and provides the key updates in neonatal transfusion practice. The authors give examples of a successful neonatal PBM program and single-center projects.

Comparison of Morphological and Histological Characteristics of Human and Sheep: Sheep as a Potential Model for Testing Midurethral Slings in vivo.

INTRODUCTION: The sheep was evaluated as a potential model for preclinical evaluation of urethral slings in vivo based on: (1) anatomical measurements of the sheep vagina and (2) histological tissue integration and host response to polypropylene (PP) slings. METHODS: Eight female, multiparous sheep were utilized. Three of 8 animals underwent surgery mimicking human tension-free vaginal tape protocols for midurethral slings and were euthanized at 6 months. The following measurements were obtained: vaginal length, maximum vaginal width with retraction, symphysis pubis length, and distance from the pubic bone to incision. Explanted sling samples from sheep and human were stained with hematoxylin and eosin for host reaction assessment. RESULTS: Geometric measurements were similar between humans and sheep. Sheep vaginal anatomy allowed sling placement similar to procedures in human surgeries, and all sheep recovered without problems. Comparative histology between the sheep and human indicated similar host reaction and collagen deposition around implants, confirming suitability of the sheep model for biomaterial response assessment. CONCLUSION: Sheep vaginal length is comparable to humans. Tissue integration and host response to PP slings showed chronic inflammation with rich collagen deposition around the material in both sheep and human specimens, highlighting the sheep as a potential animal model for preclinical testing of midurethral slings.

Topical lambda-cyhalothrin in reducing eye oscillations in a canine model of infantile nystagmus syndrome.

PURPOSE: To determine the ocular and systemic safety of using topical Lambda-Cyhalothrin (LCL) in a canine model of infantile nystagmus syndrome (INS). The rationale for this proposal is based on a case study of a patient whose INS improved after inadvertent ocular exposure to a pyrethroid pesticide containing LCL. METHODS: After in-vitro safety testing and IUCAC approval, we studied increasing concentrations of topical LCL drops (0.002% to 0.07%) in canines with a purposely bred defect in the RPE65 gene resulting in both retinal degeneration and INS. We collected data on ocular and systemic effects and performed eye-movement recordings (EMR). RESULTS: At the 0.07% concentration dose of LCL, there was minimal, reversible, conjunctival hyperemia. There was no other ocular or systemic toxicity. At the 0.06% dose, there was a visible decrease in the INS and EMR showed a 153%-240% increase in the nystagmus acuity function and a 30%-70% decrease in amplitude across gaze. There was also a 40%-60% decrease in intraocular pressure while on the drop in both eyes. CONCLUSION: This animal study suggests this new pharmacological agent has potential for topical treatment of both INS and diseases with raised intraocular pressure. Further, this new treatment approach confirms the importance of extraocular muscle proprioception in ocular motor diseases and their treatment.

Deletion of Gαq in the telencephalon alters specific neurobehavioral outcomes.

G(αq) -coupled receptors are ubiquitously expressed throughout the brain and body, and it has been shown that these receptors and associated signaling cascades are involved in a number of functional outputs, including motor function and learning and memory. Genetic alterations to G(αq) have been implicated in neurodevelopmental disorders such as Sturge-Weber syndrome. Some of these associated disease outcomes have been modeled in laboratory animals, but as G(αq) is expressed in all cell types, it is difficult to differentiate the underlying circuitry or causative neuronal population. To begin to address neuronal cell type diversity in G(αq) function, we utilized a conditional knockout mouse whereby G(αq) was eliminated from telencephalic glutamatergic neurons. Unlike the global G(αq) knockout mouse, we found that these conditional knockout mice were not physically different from control mice, nor did they exhibit any gross motor abnormalities. However, similarly to the constitutive knockout animal, G(αq) conditional knockout mice demonstrated apparent deficits in spatial working memory. Loss of G(αq) from glutamatergic neurons also produced enhanced sensitivity to cocaine-induced locomotion, suggesting that cortical G(αq) signaling may limit behavioral responses to psychostimulants. Screening for a variety of markers of forebrain neuronal architecture revealed no obvious differences in the conditional knockouts, suggesting that the loss of G(αq) in telencephalic excitatory neurons does not result in major alterations in brain structure or neuronal differentiation. Taken together, our results define specific modulation of spatial working memory and psychostimulant responses through disruptions in G(αq) signaling within cerebral cortical glutamatergic neurons.

The relationship between confidence and competence in the development of surgical skills.

BACKGROUND: Confidence is a crucial trait of any physician, but its development and relationship to proficiency are still unknown. This study aimed to evaluate the relationship between confidence and competency of medical students undergoing basic surgical skills training. METHODS: Medical students completed confidence surveys before and after participating in an introductory workshop across 2 samples. Performance was assessed via video recordings and compared with pretraining and posttraining confidence levels. RESULTS: Overall, 150 students completed the workshop over 2 years and were evaluated for competency. Most students (88%) reported improved confidence after training. Younger medical students exhibited lower pretraining confidence scores but were just as likely to achieve competence after training. There was no association between pretraining confidence and competence, but confidence was associated with demonstrated competence after training (p < 0.001). CONCLUSIONS: Most students reported improved confidence after a surgical skills workshop. Confidence was associated with competency only after training. Future training should investigate this relationship on nonnovice samples and identify training methods that can capitalize on these findings.

In vitro evaluation of antioxidant and anti-inflammatory properties of genistein-modified hemodialysis membranes.

Genistein-modified poly(amide):poly(vinyl pyrrolidone) (PA:PVP/G) hemodialysis membranes have been fabricated by coagulation via solvent (dimethyl sulfoxide, DMSO)/nonsolvent (water) exchange. The antioxidant and anti-inflammatory properties of the unmodified PA:PVP membranes were evaluated in vitro using human blood. It was found that these unmodified PA:PVP membranes were noncytotoxic to peripheral blood mononuclear cells (PBMC) but raised intracellular reactive oxygen species (ROS) levels. Pure genistein (in DMSO solution) was not only nontoxic to PBMC, but also suppressed the ROS levels in a manner dependent on genistein dosage. A similar dose-dependent suppression of ROS was found in genistein-modified PA (i.e., PA/G) membranes. However, the PVP addition had little or no effect in the suppression of ROS levels for the ternary PA:PVP/G system; the membrane ROS suppression was largely controlled by the genistein dosage. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin (IL-6) in whole blood were measured by ex vivo stimulation with lipopolysaccharide (LPS). The unmodified PA:PVP membranes drastically increased the level of TNF-α; however, the concentration of IL-1ß and IL-6 remained almost the same. The PA/G membranes reduced the concentration of IL-1ß and TNF-α even at very low genistein loadings, but it required a higher genistein loading to realize a similar effect in the case of IL-6. Of particular importance is that the genistein-modified blend membranes (PA:PVP/G) showed greater suppression of the concentrations of all three cytokines (TNF-α, IL-1ß, and IL-6) in comparison with those of the PA/G membranes, signifying the role of PVP in the enhanced anti-inflammatory properties of these genistein-modified membranes. Ultraviolet-visible (UV-vis) spectroscopy was employed to quantify any genistein leaching during the in vitro testing.

Does solitary incubation enhance egg water uptake and offspring quality in a lizard that produces single-egg clutches?

Many organisms invariably produce one offspring per reproductive bout, but experimental tests of adaptive explanations for this reproductive pattern are rare. To address this issue, we studied a lizard (Anolis sagrei) that produces one egg at a time to test the hypothesis that solitary incubation (due to single-egg clutches) eliminates competition with adjacent eggs for moisture and thus enhances offspring quality via increased egg water uptake during development. Our findings suggest that solitary incubation does not affect rates of moisture uptake by eggs or offspring size. However, egg moisture uptake and offspring size were negatively affected when eggs were adjacent to an egg that died during development. Depending on rates of infertile eggs or embryo mortality in the field, single-egg clutches may improve developmental environments and enhance offspring fitness. These results highlight the importance of considering the role of plastic embryonic responses during development in explaining reproductive patterns.

A nanostructured carbon-reinforced polyisobutylene-based thermoplastic elastomer.

This paper presents the synthesis and characterization of a polyisobutylene (PIB)-based nanostructured carbon-reinforced thermoplastic elastomer. This thermoplastic elastomer is based on a self-assembling block copolymer having a branched PIB core carrying -OH functional groups at each branch point, flanked by blocks of poly(isobutylene-co-para-methylstyrene). The block copolymer has thermolabile physical crosslinks and can be processed as a plastic, yet retains its rubbery properties at room temperature. The carbon-reinforced thermoplastic elastomer had more than twice the tensile strength of the neat polymer, exceeding the strength of medical grade silicone rubber, while remaining significantly softer. The carbon-reinforced thermoplastic elastomer displayed a high T(g) of 126 degrees C, rendering the material steam-sterilizable. The carbon also acted as a free radical trap, increasing the onset temperature of thermal decomposition in the neat polymer from 256.6 degrees C to 327.7 degrees C. The carbon-reinforced thermoplastic elastomer had the lowest water contact angle at 82 degrees and surface nano-topography. After 180 days of implantation into rabbit soft tissues, the carbon-reinforced thermoplastic elastomer had the thinnest tissue capsule around the microdumbbell specimens, with no eosinophiles present. The material also showed excellent integration into bones.

A method for the consistent creation and quantitative testing of postoperative pelvic adhesions in a porcine model.

INTRODUCTION: The assessment of methods for the prevention of postoperative pelvic adhesions is hampered by the lack of a quantifiable adhesion measurement technique. Currently available methods for adhesion model assessment rely on qualitative grading scales; a quantitative method would have many attendant benefits, including standardized reporting. METHODS: A technique was developed to generate consistent and significant adhesions in a swine model that are suitable for quantitative assessment using a Material Testing System (MTS) machine platform. In this method, the uterine horns are cannulated and then attached to the pelvic sidewall using loose silk sutures. The underlying sidewall and adjacent uterine serosa are injured with electrocautery. Following a two-week survival the entire complex of uterine horn and sidewall are excised en bloc and prepared for MTS testing. RESULTS: Extrication of the adhesion, as measured by the MTS platform, generates a quantitative assessment of adhesion strength that can be scaled and analyzed to produce several continuous variable descriptions. DISCUSSION: This technique represents a novel quantitative method for adhesion assessment in an animal model. This quantitative technique may then be applied to accurately assess a range of adhesion prevention techniques, producing results which can be standardized for comparison.

Drug-eluting stent coatings.

This paper reviews the development of coronary stents from a polymer scientist's view point, and presents the first results of an interdisciplinary team assembled for the development of new stent systems. Poly(styrene-b-isobutylene-b-styrene) block copolymer (SIBS), a nanostructured thermoplastic elastomer, is used in clinical practice as the drug-eluting polymeric coating on the Taxus coronary stent (trademark of Boston Scientific Co.). Our group has been developing new architectures comprising of arborescent (dendritic) polyisobutylene cores (D_SIBS), which were shown to be as biocompatible as SIBS. ElectroNanospray (Nanocopoeia Inc.) was used to coat test coupons and coronary stents with selected D(S)IBS polymers loaded with dexamethasone, a model drug. The surface topology varied from smooth to nanosized particulate coating. This paper will demonstrate how drug release profiles were influenced by both the molecular weight of the polyisobutylene core and spraying conditions of the polymer-drug mixture.

Novel method used to test pullout parameters of different nephrostomy catheters.

PURPOSE: To present a novel in-vitro pig model for testing the design and function of different internal catheter constructs, along with the resulting exit wound resulting from removal. MATERIALS AND METHODS: We compared the pullout parameters of two nephrostomy catheters that differ only in their internal loop design. RESULTS: Greater force, work, and displacement are necessary to extricate catheters with a double loop without increasing exit-wound size. CONCLUSION: Although the differences were not statistically significant, results from this model have potential clinical implications that may prompt further design modifications and prototype development to improve the retention of catheters in the kidney, thus reducing patient discomfort and costs associated with repeated catheter placement.

A simple cost-effective design for construction of a laparoscopic trainer.

BACKGROUND AND PURPOSE: Laparoscopic trainers have been shown to be effective tools for transitioning residents in surgical fields into live laparoscopic techniques. There have been few reports of homemade trainers, but each of these reports provides only scant detail about their construction, making production a novel task to those interested in employing this equipment. Virtual-reality trainers are gaining popularity and are exceptional modalities in the re-creation of laparoscopic surgery. In their present state, however, such trainers are very costly, making them unattainable by most urology residency programs. Numerous commercial non-virtual trainers are also available; however, these trainers are often cost-prohibitive or overly simplistic. METHODS AND RESULTS: We describe a detailed design template for creation of a laparoscopic trainer based on modifications of previous designs. This trainer can be made easily at a cost of approximately US$275.00 and may be used in conjunction with existing laparoscopic equipment. The methods described herein can be followed by any local machinist to create this trainer. CONCLUSION: The relatively low total cost, ready material availability, and ease of construction make this trainer an appropriate option for the training of residents in laparoscopic procedures.

Changes in quality of life during hemodialysis and peritoneal dialysis treatment: generic and disease specific measures.

Despite more than 20 yr of use, relative differences in health-related quality of life (HRQOL) between hemodialysis (HD) and peritoneal dialysis (PD) are not clearly known. The objective of this study was to compare self-reported HRQOL and overall health status for HD and PD patients at the initiation of dialysis therapy and 1 yr later. A prospective cohort of incident ESRD patients was enrolled between October 1995 and June 1998 at 81 outpatient dialysis units in 19 states and included 698 HD and 230 PD patients who completed a baseline CHOICE Health Experience Questionnaire. The main outcome measured was change in qualify-of-life scores from start of dialysis to 1 yr on dialysis and overall health status. Of 928 patients who completed the baseline questionnaire, 585 also completed the 12-mo questionnaire; 101 had died, 55 had received a kidney transplant, and 88 had moved to a new dialysis clinic. PD patients were slightly younger, were more likely to be white, were well-educated, were employed, were married, had less comorbidity, and had higher hematocrit. Unadjusted baseline scores showed better HRQOL for PD patients in both generic and ESRD domains (bodily pain, travel, diet restrictions, and dialysis access [P < 0.05]). At 1 yr, SF-36 scores improved, whereas some ESRD domains improved and others deteriorated. HD patients had greater improvements in two SF-36 domains (physical functioning and general health perception) than PD patients, but results were mixed for ESRD domains (PD is better for finances, HD is better for sleep and overall quality of life). HD and PD patients did not differ in change in overall health status. HD and PD are associated with similar HRQOL outcomes at 1 yr. Generic HRQOL in two domains improved more for HD patients. However, for ESRD-specific HRQOL, results were not consistent; some domains were better for PD patients whereas others were better for HD patients. In advising patients about modality choices, trade-offs should be discussed and individual preferences for specific aspects of HRQOL should be elicited.

Feasibility of a novel veno-veno circuit as a central rewarming method in a severely hypothermic canine model.

PURPOSE: Many victims of accidental hypothermia are successfully resuscitated, but questions remain regarding the optimum rewarming techniques. Most of the invasive warming techniques such as closed thoracic lavage, hemodialysis, peritoneal dialysis, and cardiopulmonary bypass require specialized personnel, equipment, and procedures that are not readily available in all facilities. The objective of this study was to investigate the technical feasibility of utilizing a novel veno-veno rewarming circuit to resuscitate severely hypothermic subjects. If this alternative invasive warming technique is successful, it could be available to treat hypothermic patients in virtually any emergency department setting. METHODS: The rewarming system consisted of a Baxter ThermaCyl warmer (Baxter Co., McGaw Park, IL), a roller pump, hemodialysis tubing, connectors, and 2 venous catheters. Blood was pumped from the body via the femoral vein, through the roller pump, into the warmer, and then returned to the body via the right jugular vein. Seven adult mongrel hounds of similar weights (20 to 25 kg) were anesthetized and instrumented for data collection. Temperature probes were placed in the rectum, the peritoneal cavity, and the esophagus to record core temperatures. Each animal was cooled by ice packing to a central core temperature of 29 degrees C and then rewarmed using the described veno-veno circuit. Vital signs, pulse oximetry, cardiac rhythm, and laboratory values were obtained prior to cooling the animals, and were repeated for every degree Celsius change once warming began. Christopher Haughn, MD, was the second place winner in the Basic Sciences Resident Competition at the Ohio American College of Surgeons meeting. RESULTS: Because of technical difficulties, data from 1 dog were not included in the results. Of the remaining 6 dogs, all were rewarmed from 29 degrees C to 37 degrees C. Adverse side effects included gross hematuria, acidemia (median pH decrease was 0.088), and decreases in haptoglobin (median decrease 13.5 g/dl), hemoglobin (median decrease 1.35 g/dl), and arterial pO(2) level (median decrease 167 mm Hg). Decreases in blood pressure and heart rate were also noted during the cooling process, but reversed upon rewarming. CONCLUSIONS: From this pilot study, we conclude that our novel veno-veno circuit rewarming is a feasible method of rewarming hypothermic subjects and warrants further investigation and comparison with other active warming methods.