Diagnosis and management of facial nerve palsy secondary to granulomatosis with polyangiitis - A systematic review.

OBJECTIVE: Granulomatosis with polyangiitis is associated with otolaryngologic complaints in 70-95 % of cases, with the most common being serous otitis media. In rare cases, patients may experience facial nerve palsy in conjunction with otologic or nasal symptoms; and, often, initially present to an otolaryngologist. It is important for healthcare professionals to be able to recognize the nuisances of facial nerve palsy as a potential presentation of granulomatosis with polyangiitis. STUDY DESIGN: Systematic review. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocol, PubMed and MED-LINE Databases were queried for articles published from January 2007 to December 2022 describing facial nerve palsy in the context of Granulomatosis with polyangiitis, formerly known as Wegener's Granulomatosis. The keywords included "facial nerve palsy", "facial palsy", "granulomatosis with polyangiitis", "Wegener's granulomatosis", "ANCA positive" in the title/abstract. All full-text articles available in English were screened, including single case presentations. Abstracts, commentaries, and publications deemed outside the scope of our study aims were excluded from review. After removal of duplicate articles, a total of 85 articles were screened. After applying inclusion and exclusion criteria, 14 articles were included in the review. RESULTS: There were a total of 28 reports of facial nerve palsy in the literature in patients who were eventually diagnosed with granulomatosis with polyangiitis. The patients' ages ranged from 14 to 68 years old. None of the patients had been previously diagnosed with GPA, and a majority of them presented initially with other otologic symptoms. Hearing loss was reported in 24 patients (86 %), otalgia was present in 11 patients (39 %), and otorrhea was present in 6 patients (21 %). Bilateral facial paralysis was reported in 10 patients in the literature (36 %). In total, 16 patients underwent surgery for facial paralysis: 6 tympanomastoidectomies, 4 mastoidectomies, 2 explorative tympanotomies. Surgery was generally considered ineffective in resolving facial weakness. All patients ended up receiving some combination of steroids and immunosuppressant, most commonly prednisolone and cyclophosphamide or rituximab, which was eventually transitioned to azathioprine for maintenance. Unlike auditory thresholds, which remained decreased in two patients, all patients recovered facial function following appropriate medical treatment of their vasculitis. CONCLUSIONS: Facial nerve paralysis in patients with granulomatosis with polyangiitis is a rare but treatable phenomenon. In patients with intractable otitis media, unresolving facial palsy, or a combination of otologic issues, it is important to consider GPA as a possible source. The prognosis for facial function appears to be excellent in patients who undergo appropriate treatment for vasculitis, but further studies are needed for confirmation.

Inguinal Bladder Hernia Indirectly Treated With Prostate Artery Embolization.

An inguinal bladder hernia (IBH) is an abnormal protrusion of the bladder into the inguinal canal accompanied by a peritoneum sheath that creates the hernia sac. Clinical presentations vary greatly from lower urinary tract symptoms (LUTS) and reduction in scrotal size after voiding to being entirely asymptomatic. Since inguinal bladder hernias are uncommon and often accompanied by varied and nonspecific symptoms, it is challenging to diagnose and rarely included in differentials. Currently, computerized tomography (CT) imaging with contrast or voiding cystourethrography is recommended for diagnosis. There is no consensus on the best treatment for inguinal bladder hernias, with options ranging from laparoscopic repair to catheterization. In this study, we report the case of inguinal bladder hernia in an 86-year-old male presenting with symptoms of recurrent hematuria and two failed voiding trials after a Foley catheter placement from prostatomegaly resulting in bladder diverticula, and IBH. He was treated with prostate artery embolization (PAE) to address LUTS related to benign prostatic hyperplasia (BPH). The resultant decreased prostatic volume resolved his symptoms of IBH, hematuria, and urinary retention.

Hematoma Disguised as Cancer.

Hematomas are often associated with benign processes such as sport-related injuries, postsurgical complications, and medications such as blood thinners. Rarely, hematomas can occur spontaneously without any identifiable cause or recollection of an inciting event. Such events can lead to inaccurately diagnosing a patient, which could delay or alter treatment and worsen the patient's prognosis. This patient reported sudden-onset abdominal pain with radiation to her back and denied any recent medication use or trauma while at home. The case highlights the key radiographic findings of magnetic resonance imaging (MRI) and contrast-enhanced ultrasound to eventually confirm an obscure case of hepatocellular carcinoma and help guide management.

Imaging of Hepatobiliary Cancer.

The liver and biliary tree are common sites of primary and secondary malignancies. MRI followed by CT is the mainstay for the imaging characterization of these malignancies with the dynamically acquired contrast enhanced phases being the most important for diagnosis. The liver imaging reporting and data system classification provides a useful framework for reporting lesions in patents with underlying cirrhosis or who are at high risk for developing hepatocellular carcinoma. Detection of metastases is improved with the use of liver specific MRI contrast agents and diffusion weighted sequences. Aside from hepatocellular carcinoma, which is often diagnosed noninvasively, other primary hepatobiliary tumors may require biopsy for definite diagnosis, especially when presenting with nonclassic imaging findings. In this review, we examine the imaging findings of common and less common hepatobiliary tumors.

Are There Ultrasound Features to Distinguish Small (<3 cm) Peripheral Renal Angiomyolipomas From Renal Cell Carcinomas?

BACKGROUND: Small echogenic renal masses are usually angiomyolipomas (AMLs), but some renal cell carcinomas (RCCs) can be echogenic and confused with an AML. OBJECTIVES: This is a study to evaluate any distinguishing demographic and sonographic features of small (<3 cm) peripheral AMLs versus peripheral RCCs. METHODS: This is a HIPAA-compliant retrospective review of the demographics and ultrasound features of peripheral renal AMLs compared with a group of peripheral RCCs. All AMLs had confirmation of macroscopic fat as noted on thin-cut CT or fat-saturation MRI sequence images. All RCCs were pathologically proven. Statistical analysis was used to compare findings in the two groups. RESULTS: There were a total of 52 patients with 56 AMLs, compared with 42 patients with 42 RCCs. There were 42 females in the AML group versus 10 females in the RCC group (P < .0001). The AML diameters (15.7 mm × 12.0 mm) were statistically significantly smaller (Plargest = .0085, Psmallest < .001) than the diameters of the RCCs (19.9 mm × 18.5 mm). Ultrasound features found to be statistically different between the two groups were the ratio of the largest dimension to the smallest dimension (P < .001), a lobulated versus smooth margin of the AML (26 vs 30) compared with the RCC group (3 vs 39) (P = .0012), and an "unusual" versus a round shape (P < .001) of the AML group (45 vs 11) compared with the RCC group (9 vs 33). In the multivariable model, the patient sex, margin, and mass shape were predictive of AML, with an area under the receiver operating characteristic curve of 0.92. CONCLUSION: For a small (<3 cm) peripheral echogenic mass in a female patient, a lobulated lesion with an unusual shape is highly predictive of being an AML.

Cerebrospinal fluid flushing as a means of neuroprotection.

Central nervous system (CNS) injury or disease states are often difficult to treat due to the closed system of the dura mater/blood-brain barrier and the bony skull and vertebrae. The closed system results in at least partial containment of any pro-inflammatory molecules, pathogens, or toxic byproducts in the case of brain or spinal cord lesions, which can result in a destructive feedback loop. Cervical-approach access techniques (lateral C1-C2, suboccipital and lateral atlanto-occipital space punctures) are less-common methods of cerebrospinal fluid (CSF) sampling due to the relative ease and safety of lumbar spinal taps. However, with improved image-guidance, these cervical-level CSF access points are still useful when there are certain contraindications and difficulties when attempting to sample the CSF via the typical lumbar spinal approach. With the advent of microcatheters and minimally invasive techniques, combined with body fluid filtration technology, the question arises: could dual microcatheters be introduced for inflow and outflow of purified or artificial CSF to break the destructive feedback loop and thus diminish CNS damage?. We hypothesize that intrathecal spinal catheters could be placed in 2 positions (e.g., via a cervical route and the typical lumbar spinal route) to allow for both an input and output to more effectively filter or "flush" the CSF. This could have broad implications in the treatment of strokes, traumatic brain or spinal cord injury, infections, autoimmune diseases, and even malignancies within the CNS-in short, any disease with abnormalities detectable in the CSF.

The effects of daily step goals of 10,000, 12,500, and 15,000 steps per day on neural activity to food cues: A 24-week dose-response randomized trial.

INTRODUCTION: The purpose of this study was to examine the effect of different levels of sustained physical activity on neural reflections of attention allocated toward food cues in first year college women. METHODS: Seventy-nine first-year college women (18.6 ± 0.5 years) were recruited to participate in the study. Women were randomly assigned to a daily step goal of 10,000, 12,500, or 15,000 for 24 weeks. Once during weeks 16-24, participants were shown pictures of plated meals or flowers with the neural response measured using the P300 and late positive potential (LPP) components of the scalp-recorded event-related potential. Diet was assessed using the automated 24-h recall. RESULTS: Both the P300 and LPP amplitudes were significantly more positive to food versus flower pictures (ps < .001). There was no interaction between step group and picture condition for the P300 and LPP. However, the 12,500-step group showed a significantly elevated LPP amplitude in comparison to the other groups for both food and flowers (F(2,74) = 8.84; p < .001). The effect size for the combined results (food and flowers) was 0.56 between 10,000 and 12,500-step groups, and 0.75 between the 12,500- and 15,000-step groups. In addition, the 12,500 group reduced caloric consumption over the course of the intervention (t(1,74) = 3.35, p = .001, dz  = 0.59). CONCLUSION: Habitual physical activity of 10,000, 12,500, or 15,000 steps per day does not preferentially alter neural reflections toward food cues compared to flowers. There may be a nonlinear response to pleasant visual cues, with 12,500 steps per day eliciting higher LPPs than either 10,000 or 15,000.

Using FDA-approved drugs as off-label fluorescent dyes for optical biopsies: from in silico design toex vivoproof-of-concept.

Optical biopsies bring the microscope to the patient rather than the tissue to the microscope, and may complement or replace the tissue-harvesting component of the traditional biopsy process with its associated risks. In general, optical biopsies are limited by the lack of endogenous tissue contrast and the small number of clinically approvedin vivodyes. This study tests multiple FDA-approved drugs that have structural similarity to research dyes as off-labelin situfluorescent alternatives to standardex vivohematoxylin & eosin tissue stain. Numerous drug-dye combinations shown here may facilitate relatively safe and fastin situor possiblyin vivostaining of tissue, enabling real-time optical biopsies and other advanced microscopy technologies, which have implications for the speed and performance of tissue- and cellular-level diagnostics.

In-vivo Performance of Seven Commercially Available Demineralized Bone Matrix Fiber and Putty Products in a Rat Posterolateral Fusion Model.

Introduction: Demineralized bone matrix (DBM) is a widely used bone graft in spinal fusion. Most commercial DBMs are composed of demineralized bone particles (~125-800 microns) suspended in a carrier that provides improved handling but dilutes the osteoinductive component. DBM fibers (DBF) provide improved osteoconductivity and do not require a carrier. It has been suggested that 100% DBF may offer improved performance over particulate-based DBMs with carrier. Study Design: Seven commercially available DBM products were tested in an athymic rat posterolateral fusion model. There were four 100% DBFs, two DBFs containing a carrier, and one particulate-based DBM containing carrier. Objective: The study objectives were to evaluate the in vivo performance: (1) compare fusion rate and fusion maturity of six commercially available DBFs and one particulate-based DBM, and (2) assess the effect of carrier on fusion outcomes for DBFs in a posterolateral fusion model. Methods: The DBF/DBM products evaluated were: StrandTM Family, Propel® DBM Fibers, Vesuvius® Demineralized Fibers, Optium® DBM Putty, Grafton® DBF, Grafton Flex, and DBX® Putty. Single-level posterolateral fusion was performed in 69 athymic rats. Fusion was assessed bilaterally after 4 weeks by manual palpation, radiograph and CT for bridging bone. Fusion mass maturity was assessed with a CT maturity grading scale and by histology. Statistical analysis was performed using Fishers Exact Test for categorical data and Kruskal-Wallis Test for non-parametric data. Results: Strand Family achieved 100% fusion (18/18) by manual palpation, radiographic and CT evaluation, significantly higher than Propel Fibers, Vesuvius Fibers, Optium Putty, and DBX Putty, and not statistically higher than Grafton DBF and Grafton Flex. Strand Family provided the highest fusion maturity, with CT maturity grade of 2.3/3.0 and 89% mature fusion rate. Fusion results suggest a detrimental effect of carrier on fusion performance. Conclusions: There were large variations in fusion performance for seven commercially available DBM products in an established preclinical fusion model. There were even significant differences between different 100% DBF products, suggesting that composition alone does not guarantee in vivo performance. In the absence of definitive clinical evidence, surgeons should carefully consider available data in valid animal models when selecting demineralized allograft options.

Bowel Penetration by Inferior Vena Cava Filters: Feasibility and Safety of Percutaneous Retrieval.

OBJECTIVE. The purpose of this study was to evaluate the safety and technical feasibility of inferior vena cava filter (IVCF) removal when filter elements penetrate adjacent bowel. MATERIALS AND METHODS. A multicenter retrospective review of IVCF retrievals between 2008 and 2018 was performed. Adult patients with either CT or endoscopic evidence of filter elements penetrating bowel before retrieval were included. Technical success of IVCF retrieval was recorded. Patient records were assessed for immediate, 30-day, and 90-day complications after retrieval. RESULTS. Thirty-nine consecutive adult patients (11 men and 28 women; mean age, 51.2 years; age range, 18-81 years) qualified for inclusion. Filter dwell time was a median of 148 days (range, 32-5395 days). No IVCFs were known to have migrated or caused iliocaval thrombosis. Five IVCFs (12.8%) had more than 15° tilt relative to the inferior vena cava (IVC) before retrieval. Three IVCFs (7.7%) had fractured elements identified at the time of retrieval. Mean international normalized ratio (INR) was 1.24 ± 0.53 (SD), and mean platelet count was 262 ± 139 × 103/µL. Ten patients (25.6%) were on antibiotics at the time of retrieval. All 39 IVCFs were successfully retrieved (technical success = 100%). Two patients experienced minor complications in the immediate postprocedural period, which resulted in a minor complication rate of 5.1%. There were no complications (major or minor) identified in any patient at 30 or 90 days after retrieval. The overall major complication rate was 0%. CONCLUSION. Endovascular retrieval of IVCFs with CT evidence of filter elements that have penetrated adjacent bowel is both safe and technically feasible.

Quantifying the presence of evidential value and selective reporting in food-related inhibitory control training: a p-curve analysis.

Meta-analyses suggest inhibitory control training (ICT) may be effective for reducing food intake. However, psychological research has come under scrutiny for lack of reliability. Selective reporting (only reporting significant results) is one factor contributing to the lack of reliability in published research. Therefore, estimates of food-related ICT effects may be inaccurate. We conducted p-curve analyses to assess the presence of selective reporting, evidential value, average effect size, and power in the food-related ICT literature. Extracted p-values were selected from articles included in food-related ICT meta-analyses and an updated literature search. Four p-curve analyses resulted in 'U'-shaped distributions, suggesting evidence for both a true underlying effect and selective reporting in the food-related ICT literature. Robust analyses suggested the evidence for an underlying effect was primarily driven by the smallest p-value. The average effect size from included studies was small (d = 0.04 to 0.25). Average power to detect this effect was also small (7% to 18%). Results suggest no clear support for or against a true effect for food-related ICT. Low average effect size and power across studies suggests estimated effects are likely inflated in published literature. Higher-powered, pre-registered, longitudinal food-related ICT studies are needed to test for the presence and magnitude of ICT effects.

The selective cathepsin K inhibitor MIV-711 attenuates joint pathology in experimental animal models of osteoarthritis.

BACKGROUND: MIV-711 is a highly potent and selective cathepsin K inhibitor. The current article summarizes the therapeutic effects of MIV-711 on joint pathology in rabbits subjected to anterior cruciate ligament transection (ACLT), and the prophylactic effects on joint pathology in dogs subjected to partial medial meniscectomy, two surgical models of osteoarthritis (OA). METHODS: Starting 1 week after surgery, rabbits were dosed daily via oral gavage with either MIV-711 or vehicle (n = 7/group) for 7 weeks. The four treatment groups were: (1) sham + vehicle; (2) ACLT + vehicle; (3) ACLT + MIV-711, 30 µmol/kg and (4) ACLT + MIV-711, 100 µmol/kg. Subchondral bone and articular cartilage structures were assessed by µCT, histomorphometry, and scoring. Dogs subjected to partial medial meniscectomy received either MIV-711 (30 µmol/kg) or vehicle (n = 15/group) via oral gavage once daily, starting 1 day before meniscectomy, for 28 days. Cartilage degradation was assessed at the macroscopic and microscopic levels. The exposures of MIV-711 were assessed in both studies and biomarkers reflecting bone resorption (HP-1 in rabbits, CTX-I in dogs) and cartilage degradation (CTX-II) were measured. RESULTS: In ACLT rabbits, MIV-711 decreased HP-1 levels by up to 72% (p < 0.001) and CTX-II levels by up to 74% (p < 0.001) compared to ACLT vehicle controls. ACLT surgery significantly reduced the total thickness of the subchondral bone plate and reduced trabecular bone volume in the femur and tibia. These effects were reversed by MIV-711. ACLT resulted in cartilage thickening, which was attenuated by MIV-711. MIV-711 did not affect osteophyte formation or Mankin scores. In dogs, MIV-711 reduced CTX-I and CTX-II levels by 86% (p < 0.001) and 80% (p < 0.001), respectively. Synovial CTX-II levels were reduced by 55-57% (p < 0.001) compared to baseline. MIV-711-treated animals had 25-37% lower macroscopic scores in the femur condyles and 13-33% lower macroscopic scores in the tibial plateaus. CONCLUSIONS: MIV-711 prevents subchondral bone loss and partially attenuates cartilage pathology in two animal models of OA. These beneficial effects of MIV-711 on joint pathology are observed in conjunction with decreases in bone and cartilage biomarkers that have been shown to be clinically attainable in human. The data support the further development of MIV-711 for the treatment of OA.

Recommendations for Low-Grade Carotid Stenosis Follow-up Based on a Single-Institution Database.

OBJECTIVES: The purpose of this study was to determine the incidences and rates of progression of varying degrees of carotid stenosis that do not require intervention according to the Asymptomatic Carotid Atherosclerosis Study, the European Carotid Surgery Trial, and the North American Symptomatic Carotid Endarterectomy Trial, and from this information, to provide evidence-based recommendations for follow-up imaging. METHODS: A retrospective review was performed of all carotid ultrasound examinations performed at a single institution from January 1995 through April 2015. Examinations following endarterectomy or stenting were excluded. Stenoses were classified by a modification of the criteria of Bluth et al (Radiographics 1988; 8:487-506). A Kaplan-Meier survival analysis was performed for stenosis progression and to provide information for follow-up recommendations. RESULTS: Most of the carotid arteries (91.6%) reviewed for this study showed 1% to 39% stenosis. However, only 6.8% of carotid arteries with 1% to 39% stenosis progressed compared to 38.9% of carotid arteries with 40% to 59% stenosis. A table of evidence-based follow-up recommendations is provided for patients with varying levels of stenosis. CONCLUSIONS: We provide evidence-based follow-up recommendations for patients who have low degrees of carotid stenosis. Different degrees of carotid stenosis progress at different rates and therefore should be followed at different intervals. Additionally, the most patients in our database showed 1% to 39% stenosis and did not have any follow-up imaging, suggesting that carotid ultrasound may not be overused for low degrees of stenosis.

Effect of 3 Commercially Available Botulinum Toxin Neuromodulators on Facial Synkinesis: A Randomized Clinical Trial.

IMPORTANCE: Botulinum toxin neuromodulators are an important treatment for facial synkinesis. Whether a difference in efficacy exists among the 3 different botulinum neuromodulators used in treating this condition remains unknown. OBJECTIVE: To evaluate the effectiveness of 3 commercially available botulinum toxin neuromodulators in the treatment of facial synkinesis. DESIGN, SETTING, AND PARTICIPANTS: In this single-blind, 3-arm comparison randomized clinical trial, 28 patients at the Facial Nerve Center, University of Utah, Salt Lake City, were randomized to onabotulinumtoxinA, abobotulinumtoxinA, or incobotulinumtoxinA treatment. Each patient was given the Synkinesis Assessment Questionnaire (SAQ) to assess severity of synkinesis before treatment and 1, 2, and 4 weeks after treatment, and improvements were compared among the groups. Data were collected from July 3, 2012, to March 31, 2015. INTERVENTIONS: Botulinum toxin type A neuromodulator (onabotulinumtoxinA, abobotulinumtoxinA, or incobotulinumtoxinA) injected into synkinetic areas of the face. MAIN OUTCOMES AND MEASURES: Synkinesis assessed using the SAQ (score range, 20-100; lower scores indicate less severe synkinesis) before treatment and 1, 2, and 4 weeks after treatment. RESULTS: A total of 28 patients (mean [SD] age, 49.1 [18.5] years; 8 [28.6%] male and 20 [71.4%] female), with 6 patients enrolled multiple times, received 38 treatments (15 onabotulinumtoxinA, 13 abobotulinumtoxinA, and 10 incobotulinumtoxinA). No significant difference existed in baseline pretreatment SAQ scores among the 3 groups. Mean (SD) SAQ score improvement at 4 weeks was 41% (31%) for the onabotulinumtoxinA, 42% (20%) for the abobotulinumtoxinA, and 17% (18%) for the incobotulinumtoxinA groups. No significant differences were noted in SAQ score improvements among the 3 groups at weeks 1 and 2 after treatment (week 1 mean improvements of 42% in the onabotulinumtoxinA, 45% in the abobotulinumtoxinA, and 26% in the incobotulinumtoxinA groups; P = .19; week 2 mean improvements of 43% in the onabotulinumtoxinA, 46% in the abobotulinumtoxinA, and 28% in the incobotulinumtoxinA groups; P = .20). The difference in mean SAQ score improvement for abobotulinumtoxinA vs incobotulinumtoxinA from pretreatment to 4 weeks after treatment was not significant (30 vs 12 points; P = .11) despite a significant difference in mean total SAQ score for abobotulinumtoxinA vs incobotulinumtoxinA (40.34 vs 58.00; P = .02). CONCLUSIONS AND RELEVANCE: AbobotulinumtoxinA had similar efficacy to onabotulinumtoxinA and incobotulinumtoxinA for the management of facial synkinesis up to 4 weeks after treatment. IncobotulinumtoxinA had significantly less effect on SAQ score improvement than onabotulinumtoxinA at 4 weeks, perhaps because of the shorter duration of action. Shorter intervals between treatments or larger doses may be required when using incobotulinumtoxinA treatment for facial synkinesis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03048383. LEVEL OF EVIDENCE: 1.

Volumetric analysis of day of injury computed tomography is associated with rehabilitation outcomes after traumatic brain injury.

BACKGROUND: Day-of-injury (DOI) brain lesion volumes in traumatic brain injury (TBI) patients are rarely used to predict long-term outcomes in the acute setting. The purpose of this study was to investigate the relationship between acute brain injury lesion volume and rehabilitation outcomes in patients with TBI at a level one trauma center. METHODS: Patients with TBI who were admitted to our rehabilitation unit after the acute care trauma service from February 2009-July 2011 were eligible for the study. Demographic data and outcome variables including cognitive and motor Functional Independence Measure (FIM) scores, length of stay (LOS) in the rehabilitation unit, and ability to return to home were obtained. The DOI quantitative injury lesion volumes and degree of midline shift were obtained from DOI brain computed tomography scans. A multiple stepwise regression model including 13 independent variables was created. This model was used to predict postrehabilitation outcomes, including FIM scores and ability to return to home. A p value less than 0.05 was considered significant. RESULTS: Ninety-six patients were enrolled in the study. Mean age was 43 ± 21 years, admission Glasgow Coma Score was 8.4 ± 4.8, Injury Severity Score was 24.7 ± 9.9, and head Abbreviated Injury Scale score was 3.73 ± 0.97. Acute hospital LOS was 12.3 ± 8.9 days, and rehabilitation LOS was 15.9 ± 9.3 days. Day-of-injury TBI lesion volumes were inversely associated with cognitive FIM scores at rehabilitation admission (p = 0.004) and discharge (p = 0.004) and inversely associated with ability to be discharged to home after rehabilitation (p = 0.006). CONCLUSION: In a cohort of patients with moderate to severe TBI requiring a rehabilitation unit stay after the acute care hospital stay, DOI brain injury lesion volumes are associated with worse cognitive FIM scores at the time of rehabilitation admission and discharge. Smaller-injury volumes were associated with eventual discharge to home. Volumetric neuroimaging in the acute injury phase may improve surgeons' ultimate outcome predictions in TBI patients. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level V.

Toxicity of Hexamoll(®) DINCH(®) following intravenous administration.

Alternative plasticizers to di(2-ethylhexyl) phthalate (DEHP) for blood bags have been sought for many years. Cyclohexane-1,2-dicarboxylic acid, diisononylester (Hexamoll(®) DINCH(®)) is an alternative that has been evaluated in preliminary studies for compatibility and efficacy to preserve whole blood. While Hexamoll(®) DINCH(®) has an extensive database for mammalian toxicity via oral administration, data were needed to evaluate toxicity from intravenous (IV) administration to support the use of the plasticizer Hexamoll(®) DINCH(®) in blood bags. A series of studies was performed by slow IV injection or IV infusion of Hexamoll(®) DINCH(®), a highly viscous, hydrophobic substance, suspended in Intralipid(®) 20% (20% intravenous fat emulsion). Rats were injected once, followed by 14 days of recovery; injected daily for 5 days followed by 5 days of recovery, or infused for 29 days (4h/day) followed by 14 days of recovery. Dose levels were 0, 62, 125, and 250-300mg/kg body weight/day. These dose levels represent the limits of suspension and far exceed any anticipated exposures from migration out of plasticized blood bags. Animals were observed for signs of toxicity; body weight and feed consumption were measured; blood collected for clinical chemistry and hematology; and tissues collected and processed for histopathology. Special emphasis was placed on evaluating endpoints and tissues that are commonly associated with plasticizer exposure in rodents. Urine was collected during the 4-week study to quantify urinary metabolites of Hexamoll(®) DINCH(®). The results of the studies indicate that no substance-related toxicity occurred: no effects on behavior, no effects on organ weight, no effect on serum chemistry including thyroid hormones; and no effect on major organs, especially no testicular toxicity and no indication for peroxisome proliferation in the liver. The only effects seen were petechia and granulomas related to dissipation of suspended Hexamoll(®) DINCH(®) in the aqueous environment of the blood. However, the results of metabolite analyses demonstrate that Hexamoll(®) DINCH(®) was bioavailable. Therefore, based on the lack of Hexamoll(®) DINCH(®)-related systemic toxicity with the exception of the physical limitations, the no-observed-adverse-effect level for parenterally administered Hexamoll(®) DINCH(®) is considered to be 300mg/kg bw/day.

Circulating membrane-derived microvesicles in redox biology.

Microparticles or microvesicles (MVs) are subcellular membrane blebs shed from all cells in response to various stimuli. MVs carry a battery of signaling molecules, many of them related to redox-regulated processes. The role of MVs, either as a cause or as a result of cellular redox signaling, has been increasingly recognized over the past decade. This is in part due to advances in flow cytometry and its detection of MVs. Notably, recent studies have shown that circulating MVs from platelets and endothelial cells drive reactive species-dependent angiogenesis; circulating MVs in cancer alter the microenvironment and enhance invasion through horizontal transfer of mutated proteins and nucleic acids and harbor redox-regulated matrix metalloproteinases and procoagulative surface molecules; and circulating MVs from red blood cells and other cells modulate cell-cell interactions through scavenging or production of nitric oxide and other free radicals. Although our recognition of MVs in redox-related processes is growing, especially in the vascular biology field, much remains unknown regarding the various biologic and pathologic functions of MVs. Like reactive oxygen and nitrogen species, MVs were originally believed to have a solely pathological role in biology. And like our understanding of reactive species, it is now clear that MVs also play an important role in normal growth, development, and homeostasis. We are just beginning to understand how MVs are involved in various biological processes-developmental, homeostatic, and pathological-and the role of MVs in redox signaling is a rich and exciting area of investigation.

Phosphatidylethanolamine is externalized at the surface of microparticles.

Microparticles (MPs) are membrane-bound vesicles shed normally or as a result of various (pathological) stimuli. MPs contain a wealth of bio-active macromolecules. Aminophospholipid phosphatidylserine (PS) is present on the surface of many MPs. As PS and phosphatidylethanolamine (PE) are related, yet distinct aminophospholipids, the purpose of this study was to systematically and directly assess PE exposure on MPs. We examined MPs from various human cellular sources (human breast cancer, endothelial, red and white blood cells) by flow cytometry using a PE-specific probe, duramycin, and two PS-specific probes, annexin V and lactadherin. PS and PE exposure percentage was comparable on vascular and blood cell-derived MPs (80-90% of MP-gated events). However, the percentage of malignant breast cancer MPs exposing PE (~90%) was significantly higher than PS (~50%). Thus, while PS and PE exposure can result from a general loss of membrane asymmetry, there may also be distinct mechanisms of PE and PS exposure on MPs that vary by cellular source.

Pulpal effects of enamel ablation with a microsecond pulsed lambda = 9.3-microm CO2 laser.

BACKGROUND AND OBJECTIVES: In vitro studies have shown that CO2 lasers operating at the highly absorbed 9.3 and 9.6-microm wavelengths with a pulse duration in the range of 10-20-microsecond are well suited for the efficient ablation of enamel and dentin with minimal peripheral thermal damage. Even though these CO2 lasers are highly promising, they have yet to receive FDA approval. Clinical studies are necessary to determine if excessive heat deposition in the tooth may have any detrimental pulpal effects, particularly at higher ablative fluencies. The purpose of this study was to evaluate the pulpal safety of laser irradiation of tooth occlusal surfaces under the conditions required for small conservative preparations confined to enamel. STUDY DESIGN/MATERIALS AND METHODS: Test subjects requiring removal of third molar teeth were recruited and teeth scheduled for extraction were irradiated using a pulsed CO2 laser at a wavelength of 9.3 microm operating at 25 or 50 Hz using a incident fluence of 20 J/cm(2) for a total of 3,000 laser pulses (36 J) for both rates with water cooling. Two control groups were used, one with no treatment and one with a small cut made with a conventional high-speed hand-piece. No anesthetic was used for any of the procedures and tooth vitality was evaluated prior to treatment by heat, cold and electrical testing. Short term effects were observed on teeth extracted within 72 hours after treatment and long term effects were observed on teeth extracted 90 days after treatment. The pulps of the teeth were fixed with formalin immediately after extraction and subjected to histological examination. Additionally, micro-thermocouple measurements were used to estimate the potential temperature rise in the pulp chamber of extracted teeth employing the same irradiation conditions used in vivo. RESULTS: Pulpal thermocouple measurements showed the internal temperature rise in the tooth was within safe limits, 3.3+/-1.4 degrees C without water cooling versus 1.7+/-1.6 degrees C with water-cooling, n = 25, P<0.05. None of the control or treatment groups showed any deleterious effects on pulpal tissues and none of the 29 test-subjects felt pain or discomfort after the procedure. Only two test-subjects felt discomfort from "cold sensitivity" during the procedure caused by the water-spray. CONCLUSION: It appears that this CO2 laser can ablate enamel safely without harming the pulp under the rate of energy deposition employed in this study.

Embolization of nonliver visceral tumors.

Catheter-directed embolization of visceral tumors, with the exception of the liver, has received limited attention in the literature. The visceral arterial anatomy can be complex and its understanding is critical for procedure planning and limiting complications. Embolization of splenic neoplasms is exceedingly rare. Preoperative embolization for adrenal, renal, and gut tumors plays an important role in select patients. Embolization has been used successfully in the treatment of pancreatic insulinomas and in limited cases of unresectable pancreatic adenocarcinomas. Embolization of bleeding visceral tumors can be accomplished with a high likelihood of success.