Outcomes of Soft Versus Bony Canal Wall Reconstruction with Mastoid Obliteration.

OBJECTIVE: To compare recidivism rates, audiometric outcomes, and postoperative complication rates between soft-wall canal wall reconstruction (S-CWR) versus bony-wall CWR (B-CWR) with mastoid obliteration (MO) in patients with cholesteatoma. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary neurotologic referral center. PATIENTS: Ninety patients aged ≥18 years old who underwent CWR with MO, either S-CWR or B-CWR, for cholesteatoma with one surgeon from January 2011 to January 2022. Patients were followed postoperatively for at least 12 months with or without second-look ossiculoplasty. INTERVENTIONS: Tympanomastoidectomy with CWR (soft vs. bony material) and mastoid obliteration. MAIN OUTCOME MEASURES: Recidivism rates; conversion rate to CWD; pre- versus postoperative pure tone averages, speech reception thresholds, word recognition scores, and air-bone gaps; postoperative complication rates. RESULTS: Middle ear and mastoid cholesteatoma recidivism rates were not significantly different between B-CWR (17.3%) and S-CWR (18.4%, p = 0.71). There was no significant difference in pre- versus postoperative change in ABG (B-CWR, -2.1 dB; S-CWR, +1.6 dB; p = 0.91) nor in the proportion of postoperative ABGs <20 dB (B-CWR, 41.3%; S-CWR, 30.7%; p = 0.42) between B-CWR and S-CWR. Further, there were no significant differences in complication rates between B-CWR and S-CWR other than increased minor TM perforations/retractions in B-CWR (63% vs. 40%, p = 0.03). CONCLUSIONS: Analysis of recidivism rates, audiometric outcomes and postoperative complications between B-CWR with MO versus S-CWR with MO revealed no significant difference. Both approaches are as effective in eradicating cholesteatoma while preserving relatively normal EAC anatomy and hearing. Surgeon preference and technical skill level may guide the surgeon's choice in approach.

Venous Outflow and Otosclerosis: An Unusual Case of Pulsatile Tinnitus.

We report resolution of right-sided pulsatile tinnitus in a 44-year-old male who underwent stapedectomy for fenestral otosclerosis. Initial workup revealed a mixed hearing loss and absent stapedial reflexes consistent with ossicular fixation. CT angiography demonstrated near complete stenosis of the left-sided transverse and sigmoid sinuses and dominant contralateral venous outflow. We hypothesized that the dominant right cerebral venous outflow tract created turbulent flow that was conducted to cochlea. Successful stapedectomy was performed, and the pulsatile tinnitus resolved. This case report demonstrates evidence that the sound of turbulent blood flow can be conducted through bone and an instance where the perception of vascular tinnitus was eliminated with stapedectomy.

Transcanal Transpromontorial Approaches to the Internal Auditory Canal: A Systematic Review.

OBJECTIVE: Exclusive endoscopic (EETTA) and expanded (ExpTTA) transcanal transpromontorial approaches have shown promising results for treating internal auditory canal (IAC) lesions. We reviewed the literature to answer the question: "Do EETTA and ExpTTA achieve high rates of complete resection and low rates of complications in treating patients with IAC pathologies?" DATA SOURCES: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched. REVIEW METHODS: Studies reporting EETTA/ExpTTA for IAC pathologies were included. Indications and techniques were discussed and meta-analyzed rates of outcomes and complications were obtained with random-effect model meta-analyses. RESULTS: We included 16 studies comprising 173 patients, all with non-serviceable hearing. Baseline FN function was mostly House-Brackmann-I (96.5%; 95% CI: 94.9-98.1%). Most lesions were vestibular/cochlear schwannomas (98.3%; 95% CI: 96.7-99.8%) of Koos-I (45.9%; 95% CI: 41.3-50.3%) or II (47.1%; 95% CI: 43-51.1%). EETTA was performed in 101 patients (58.4%; 95% CI: 52.4-64.3%) and ExpTTA in 72 (41.6%; 95% CI: 35.6-47.6%), achieving gross-total resection in all cases. Transient complications occurred in 30 patients (17.3%; 95% CI: 13.9-20.5%), with meta-analyzed rates of 9% (95% CI: 4-15%), comprising FN palsy with spontaneous resolution (10.4%; 95% CI: 7.7-13.1%). Persistent complications occurred in 34 patients (19.6%; 95% CI: 17.1-22.2%), with meta-analyzed rates of 12% (95% CI: 7-19%), comprising persistent FN palsy in 22 patients (12.7%; 95% CI: 10.2-15.2%). Mean follow-up was 16 months (range, 1-69; 95% CI: 14.7-17.4). Post-surgery FN function was stable in 131 patients (75.8%; 95% CI: 72.1-79.5%), worsened in 38 (21.9%; 95% CI: 18.8-25%), and improved in 4 (2.3%; 95% CI: 0.7-3.9%), with meta-analyzed rates of improved/stable response of 84% (95% CI: 76-90%). CONCLUSION: Transpromontorial approaches offer newer routes for IAC surgery, but their restricted indications and unfavorable FN outcomes currently limit their use. Laryngoscope, 133:2856-2867, 2023.

A proposed classification system for presigmoid approaches: a scoping review.

OBJECTIVE: The "presigmoid corridor" covers a spectrum of approaches using the petrous temporal bone either as a target in treating intracanalicular lesions or as a route to access the internal auditory canal (IAC), jugular foramen, or brainstem. Complex presigmoid approaches have been continuously developed and refined over the years, leading to great heterogeneity in their definitions and descriptions. Owing to the common use of the presigmoid corridor in lateral skull base surgery, a simple anatomy-based and self-explanatory classification is needed to delineate the operative perspective of the different variants of the presigmoid route. Herein, the authors conducted a scoping review of the literature with the aim of proposing a classification system for presigmoid approaches. METHODS: The PubMed, EMBASE, Scopus, and Web of Science databases were searched from inception to December 9, 2022, following the PRISMA Extension for Scoping Reviews guidelines to include clinical studies reporting the use of "stand-alone" presigmoid approaches. Findings were summarized based on the anatomical corridor, trajectory, and target lesions to classify the different variants of the presigmoid approach. RESULTS: Ninety-nine clinical studies were included for analysis, and the most common target lesions were vestibular schwannomas (60/99, 60.6%) and petroclival meningiomas (12/99, 12.1%). All approaches had a common entry pathway (i.e., mastoidectomy) but were differentiated into two main categories based on their relationship to the labyrinth: translabyrinthine or anterior corridor (80/99, 80.8%) and retrolabyrinthine or posterior corridor (20/99, 20.2%). The anterior corridor comprised 5 variations based on the extent of bone resection: 1) partial translabyrinthine (5/99, 5.1%), 2) transcrusal (2/99, 2.0%), 3) translabyrinthine proper (61/99, 61.6%), 4) transotic (5/99, 5.1%), and 5) transcochlear (17/99, 17.2%). The posterior corridor consisted of 4 variations based on the target area and trajectory in relation to the IAC: 6) retrolabyrinthine inframeatal (6/99, 6.1%), 7) retrolabyrinthine transmeatal (19/99, 19.2%), 8) retrolabyrinthine suprameatal (1/99, 1.0%), and 9) retrolabyrinthine trans-Trautman's triangle (2/99, 2.0%). CONCLUSIONS: Presigmoid approaches are becoming increasingly complex with the expansion of minimally invasive techniques. Descriptions of these approaches using the existing nomenclature can be imprecise or confusing. Therefore, the authors propose a comprehensive classification based on the operative anatomy that unequivocally describes presigmoid approaches simply, precisely, and efficiently.

Surgical Closure of the Eustachian Tube Through Middle Fossa and Transmastoid Approaches: A Pilot Cadaveric Anatomy Study.

BACKGROUND: Cerebrospinal fluid rhinorrhea after temporal bone surgery involves drainage from the Eustachian tube (ET) into the nasopharynx, causing significant patient morbidity. Variable anatomy of the ET accounts for failures of currently used ET obliteration techniques. OBJECTIVE: To describe the surgical anatomy of the ET and examine possible techniques for ET closure through middle fossa (MF) and transmastoid approaches. METHODS: We described the surgical anatomy of the ET from the MF and transmastoid approaches in 5 adult cadaveric heads, measuring morphometric and surgical anatomy parameters and establishing targets for definite ET obliteration. RESULTS: The osseous ET measured an average of 19.53 mm (±1.56 mm), with a mean diameter of 2.24 mm (±0.29 mm). The shortest distance between the greater superficial petrosal nerve and the ET junction was 6.61 mm (±0.61 mm). Shortest distances between the ET junction and the foramen spinosum and posterior border of the foramen ovale were 1.09 mm (±0.24 mm) and 2.03 mm (±0.30 mm), respectively. Closure of the cartilaginous ET may be performed by folding it in on itself, securing it by packing, suturing, or surgical clip ligation. CONCLUSION: Definite obliteration of the cartilaginous ET appears feasible and the most definite approach to eliminate egress of cerebrospinal fluid to the nasopharynx using the MF approach. This technique may be used as an adjunct to skull base procedures where ET closure is planned.

Petrous Carotid Artery Thrombosis in an Immunocompromised Patient Presenting With Mastoiditis, A Case Report.

OBJECTIVES: The neurotologic literature commonly describes venous sinus thrombosis as a complication of mastoiditis. However, thrombosis of the internal carotid artery in the setting of mastoiditis is rarely described. We aim to document a case of carotid artery thrombosis in a patient presenting with mastoiditis. METHODS: We describe this case and review relevant literature. RESULTS: A renal transplant patient was transferred to our hospital with a left middle cerebral artery (MCA) infarct due to acute mastoiditis. Examination demonstrated middle ear effusion and radiologic workup confirmed mastoid infection adjacent to the site of arterial thrombosis. During cortical mastoidectomy and facial recess approach to the middle ear, the petrous carotid bone was found to be dehiscent with pneumatization of the petrous apex. Thrombosis was found to resolve following surgery, IV antibiotics and anticoagulation. Clinically, his focal neurological deficits improved. Proximity of the infectious process to an exposed petrous carotid artery supports the hypothesis that this patient's thrombus was a product of infectious spread and extra-luminal compression. CONCLUSION: To our knowledge, this is the first report of MCA infarction due to petrous ICA arterial thrombus in the setting of mastoid infection. The patient's immunocompromised state may have predisposed and contributed to the adverse outcome. We advocate for aggressive management of acute mastoiditis in the immunocompromised to prevent or manage complications (such as venous thrombophlebitis as well as ICA thrombus) as these patients don't show typical signs of infection and inflammation.

Cochlear implantation: an effective modality for hearing restoration following vestibular schwannoma resection.

PURPOSE OF REVIEW: Preservation of hearing is one of the tenets of vestibular schwannoma management. In recent years, cochlear implants have been employed with increasing use in patients who have suffered profound sensorineural hearing loss due to the natural history of vestibular schwannoma or due to injury to neurovascular anatomy at time of surgical resection. RECENT FINDINGS: Cochlear implantation has been found to be an effective modality for hearing restoration following vestibular schwannoma. Simultaneous cochlear implantation has been employed by an increased number of centers around the world and has been shown to provide restoration of open set speech perception and return of binaural hearing. Ongoing use of electrically evoked auditory brainstem response (ABR) has improved our detection of viable cochlear nerves and provided insight into those who would benefit from this procedure. Finally, minimally invasive approaches to the internal auditory canal and intralabyrinthine tumors have been described. These methods frequently employ simultaneous cochlear implantation and have emphasized that hearing preservation remains possible with surgical excision despite the location of the tumor. SUMMARY: Cochlear implantation is an effective modality for hearing restoration following vestibular schwannoma excision.

Measuring image distortions arising from age-related macular degeneration: An Iterative Amsler Grid (IAG).

Metamorphopsia, perceived as distortion of a shape, is experienced in age-related macular degeneration (AMD): straight lines appear to be curved and wavy to AMD patients and some other retinal pathologies. Conventional clinical assessment largely relies on asking patients to identify irregularities in Amsler Grids - a standardized set of equally spaced vertical and horizontal lines. Perceived distortions or gaps in the grid are a sign of macular pathology. Here, we developed an iterative Amsler Grid (IAG) procedure to obtain a quantifiable map of visual deformations. Horizontal and vertical line segments representing metamorphopsia are displayed on a computer screen. Line segments appearing distorted are adjusted by participants using the computer mouse to change their orientation in several iteratively such that they appear straight. Control participants are able to reliably correct deformations that simulate metamorphopsia while maintaining fixation in the center. In a pilot experiment, we attempted to obtain deformation maps from a small number of AMD patients. Whereas some patients with extensive scotomas found this procedure challenging, others were comfortable using the IAG and generating deformation maps corresponding to their subjective reports. This procedure may potentially be used to quantify local distortions and map them reliably in patients with early AMD.

RNA-seq analysis of gene expression profiles in isolated stria vascularis from wild-type and Alport mice reveals key pathways underling Alport strial pathogenesis.

Previous work demonstrates that the hearing loss in Alport mice is caused by defects in the stria vascularis. As the animals age, progressive thickening of strial capillary basement membranes (SCBMs) occurs associated with elevated levels of extracellular matrix expression and hypoxia-related gene and protein expression. These conditions render the animals susceptible to noise-induced hearing loss. In an effort to develop a more comprehensive understanding of how the underlying mutation in the COL4A3 gene influences homeostasis in the stria vascularis, we performed vascular permeability studies combined with RNA-seq analysis using isolated stria vascularis from 7-week old wild-type and Alport mice on the 129 Sv background. Alport SCBMs were found to be less permeable than wild-type littermates. RNA-seq and bioinformatics analysis revealed 68 genes were induced and 61 genes suppressed in the stria from Alport mice relative to wild-type using a cut-off of 2-fold. These included pathways involving transcription factors associated with the regulation of pro-inflammatory responses as well as cytokines, chemokines, and chemokine receptors that are up- or down-regulated. Canonical pathways included modulation of genes associated with glucose and glucose-1-PO4 degradation, NAD biosynthesis, histidine degradation, calcium signaling, and glutamate receptor signaling (among others). In all, the data point to the Alport stria being in an inflammatory state with disruption in numerous metabolic pathways indicative of metabolic stress, a likely cause for the susceptibility of Alport mice to noise-induced hearing loss under conditions that do not cause permanent hearing loss in age/strain-matched wild-type mice. The work lays the foundation for studies aimed at understanding the nature of strial pathology in Alport mice. The modulation of these genes under conditions of therapeutic intervention may provide important pre-clinical data to justify trials in humans afflicted with the disease.

OCULAR TOXICITY AFTER INADVERTENT INTRACAMERAL INJECTION OF HIGH DOSE OF CEFUROXIME DURING CATARACT SURGERY: A CASE SERIES.

PURPOSE: To report ocular side effects after inadvertent intracameral injection of a high dose of cefuroxime. METHODS: Nineteen eyes of 19 patients were seen in our eye department 1 week after the referring surgeon had injected an erroneous dose of intracameral cefuroxime (12.5 mg/0.1 mL in 14 patients, Group A, and 10 mg/0.1 mL in 5 patients, Group B) at the end of a cataract surgery. A complete ophthalmic examination was performed postoperatively. RESULTS: Eight patients (42.10%) exhibited ocular side effects. One patient (Group A) developed a noninfectious panuveitis. One case (Group B) had a serous macular detachment. Five patients (4 from Group A and 1 from Group B) showed a disruption of the ellipsoid layer with temporary/permanent drop in visual acuity. One patient presented with color alteration (Group A), but electrodiagnostic studies did not reveal any significant alterations. CONCLUSION: Anterior and posterior inflammation has been described after intracameral injection of high dose of cefuroxime. In this study, 10 mg to 12.5 mg of intracameral cefuroxime is shown to be, principally, toxic to the retina with transient or permanent retinal changes on optical coherence tomography which correlate with visual outcomes postoperatively. Protocols to avoid dilution errors should be available in theaters during cataract surgery where such commercial preparations are not available.

Metabolism of deltamethrin and cis- and trans-permethrin by rat and human liver microsomes, liver cytosol and plasma preparations.

The metabolism of deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in liver microsomes, liver cytosol and plasma from male Sprague-Dawley rats aged 15, 21 and 90 days and from adult humans. DLM and CPM were metabolised by rat hepatic microsomal cytochrome P450 (CYP) enzymes and to a lesser extent by microsomal and cytosolic carboxylesterase (CES) enzymes, whereas TPM was metabolised to a greater extent by CES enzymes. In human liver, DLM and TPM were mainly metabolised by CES enzymes, whereas CPM was metabolised by CYP and CES enzymes. The metabolism of pyrethroids by cytosolic CES enzymes contributes to the overall hepatic clearance of these compounds. DLM, CPM and TPM were metabolised by rat, but not human, plasma CES enzymes. This study demonstrates that the ability of male rats to metabolise DLM, CPM and TPM by hepatic CYP and CES enzymes and plasma CES enzymes increases with age. In all instances, apparent intrinsic clearance values were lower in 15 than in 90 day old rats. As pyrethroid-induced neurotoxicity is due to the parent compound, these results suggest that DLM, CPM and TPM may be more neurotoxic to juvenile than to adult rats.

Metabolism of deltamethrin and cis- and trans-permethrin by human expressed cytochrome P450 and carboxylesterase enzymes.

The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes. DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CLint) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11. DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes. Apparent CLint values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CLint values for total metabolism (CYP and CES enzymes) per gram of adult human liver. Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.

Impact of Sensory and Motor Defects on Oral Function in an Animal Model.

OBJECTIVE: To evaluate the combined functional impact on swallowing of tongue sensory and motor loss using a rat model. STUDY DESIGN: Rats underwent selective neurectomies with transection of the motor (hypoglossal) nerve or motor and sensory (lingual) nerves. Postoperative functional parameters were followed for 2 weeks. SETTING: Translational research. SUBJECTS AND METHODS: Thirty-six adolescent male Wistar rats were divided into 4 groups: anesthetic (n = 6), sham surgery (n = 8), hypoglossal transection (n = 10), and hypoglossal and lingual transection (n = 12). Each morning on postoperative days 1 to 14, the water and food intake were quantified and the animal weighed. Two-way analyses of variance (SigmaPlot; SYSTAT, San Jose, California) were performed with factors of "group" and "postoperative day" (POD) to analyze whether a significant difference existed between water intake, pellet consumption, and weight change. RESULTS: The hypoglossal and lingual group consumed significantly less water during PODs 1 to 2 and significantly less food during PODs 1 to 3 than any other group. This established a significant difference in body weight between the hypoglossal and lingual group and all other groups for the duration of the study. Measured parameters in the hypoglossal group better approximated those of the control anesthetic and sham groups. CONCLUSIONS: The addition of a sensory loss to a motor deficit involving the oral tongue results in a measurably significant difference in weight gain, a marker of function, compared with rats with only a motor deficit. Additional studies are needed to determine if there would be similar findings in a model of sensate vs asensate oral tongue reconstruction.

Minimally Invasive Approach to the Lingual and Hypoglossal Nerves in the Adult Rat.

Surgical manipulation of the sensory and motor nerves of the rat tongue is often employed in studies evaluating the oral cavity functions of mastication and deglutition. A noninvasive, atraumatic approach that will then facilitate sufficient manipulation of these structures is required. In this study, we detail an approach that consistently allows identification of the hypoglossal (motor) and lingual (sensory) nerves of the rat. Six Wistar rats (250-500 g) were anesthetized and dissected either as fresh tissue (N = 3) or following transcardial perfusion with 4% paraformaldehyde (N = 3). Both fixed and non-fixed specimens of the rat head and neck were incised in the right submandibular region. The first animal in each group was used to gain a basic understanding of the regional muscular anatomy with reference to the hypoglossal and lingual nerves. Subsequent animals were used for the development of an efficient and minimally invasive approach to these nerves. The resultant approach begins as an incision through skin and platysma, followed by medial reflection of the digastric muscle. This allows visualization of the hypoglossal nerve in the region of the bifurcation of the common trunk into medial and lateral subdivisions. Next, the lingual nerve dissection is approached by reflection rostrally of the transversus mandibularis muscle and a caudal reflection of the mylohyoid muscle. This dissection reveals the geniohyoid muscle which when separated bluntly using forceps, exposes the lingual nerve. The anatomical approach described and illustrated herein will aid investigators in consistent identification of these two nerves as fundamental methods of their projects.

Association between kidney function, rehabilitation outcome, and survival in older patients discharged from inpatient rehabilitation.

BACKGROUND: Chronic kidney disease (CKD) is common in older people, but it is unclear if it affects survival and rehabilitation outcomes independent of comorbid conditions and physical function in this population. STUDY DESIGN: Cohort analysis of prospective, routinely collected, linked clinical data sets. SETTING & PARTICIPANTS: Patients discharged from a single inpatient geriatric rehabilitation center over a 12-year period. PREDICTORS: Admission estimated glomerular filtration rate (eGFR) category as a predictor of improvement in the 20-point Barthel score (activities of daily living measure) during rehabilitation; discharge eGFR category and Barthel score as predictors of survival postdischarge. OUTCOMES: Survival postdischarge was modeled using Cox regression analyses, unadjusted and adjusted for age, sex, morbidities (ischemic heart disease, chronic obstructive pulmonary disease, stroke, diabetes, and heart failure), Barthel score and eGFR category on discharge, and serum calcium, hemoglobin, and albumin levels. The effect of admission eGFR category on change in Barthel score during admission was modeled using analysis of covariance, adjusted for admission, Barthel score, and comorbid conditions. RESULTS: 3,012 patients were included; mean age, 84 years. 2,394 patients died during a mean follow-up of 8.3 years. Compared with patients with eGFR of 60 to 89mL/min/1.73m(2), adjusted HRs for death were 1.26 (95% CI, 1.13-1.40), 1.45 (95% CI, 1.29-1.63), and 1.68 (95% CI, 1.42-1.99) for eGFR categories of 45 to 59, 30 to 44, and <30mL/min/1.73m(2), respectively. The relationship between discharge Barthel score and survival was similar within each discharge eGFR category (HRs of 0.95, 0.93, 0.92, 0.95, and 0.90 per Barthel score point within eGFR categories of ≥90, 60-89, 45-59, 30-44, and <30mL/min/1.73m(2); P for interaction = 0.2). Similar improvements in Barthel score between admission and discharge were seen for each admission eGFR category. LIMITATIONS: Single-center study using routinely collected clinical data. CONCLUSIONS: eGFR category and Barthel score are independent risk markers for survival in older rehabilitation patients, but advanced CKD does not preclude successful rehabilitation.

Rapid vascular responses to anthrax lethal toxin in mice containing a segment of chromosome 11 from the CAST/Ei strain on a C57BL/6 genetic background.

Host allelic variation controls the response to B. anthracis and the disease course of anthrax. Mouse strains with macrophages that are responsive to anthrax lethal toxin (LT) show resistance to infection while mouse strains with LT non-responsive macrophages succumb more readily. B6.CAST.11M mice have a region of chromosome 11 from the CAST/Ei strain (a LT responsive strain) introgressed onto a LT non-responsive C57BL/6J genetic background. Previously, B6.CAST.11M mice were found to exhibit a rapid inflammatory reaction to LT termed the early response phenotype (ERP), and displayed greater resistance to B. anthracis infection compared to C57BL/6J mice. Several ERP features (e.g., bloat, hypothermia, labored breathing, dilated pinnae vessels) suggested vascular involvement. To test this, Evan's blue was used to assess vessel leakage and intravital microscopy was used to monitor microvascular blood flow. Increased vascular leakage was observed in lungs of B6.CAST.11M mice compared to C57BL/6J mice 1 hour after systemic administration of LT. Capillary blood flow was reduced in the small intestine mesentery without concomitant leukocyte emigration following systemic or topical application of LT, the latter suggesting a localized tissue mechanism in this response. Since LT activates the Nlrp1b inflammasome in B6.CAST.11M mice, the roles of inflammasome products, IL-1ß and IL-18, were examined. Topical application to the mesentery of IL-1ß but not IL-18 revealed pronounced slowing of blood flow in B6.CAST.11M mice that was not present in C57BL/6J mice. A neutralizing anti-IL-1ß antibody suppressed the slowing of blood flow induced by LT, indicating a role for IL-1ß in the response. Besides allelic differences controlling Nlrp1b inflammasome activation by LT observed previously, evidence presented here suggests that an additional genetic determinant(s) could regulate the vascular response to IL-1ß. These results demonstrate that vessel leakage and alterations to blood flow are part of the rapid response in mice resistant to B. anthracis infection.

Evaluation of the effectiveness and efficacy of Iyengar yoga therapy on chronic low back pain.

STUDY DESIGN: The effectiveness and efficacy of Iyengar yoga for chronic low back pain (CLBP) were assessed with intention-to-treat and per-protocol analysis. Ninety subjects were randomized to a yoga (n = 43) or control group (n = 47) receiving standard medical care. Participants were followed 6 months after completion of the intervention. OBJECTIVE: This study aimed to evaluate Iyengar yoga therapy on chronic low back pain. Yoga subjects were hypothesized to report greater reductions in functional disability, pain intensity, depression, and pain medication usage than controls. SUMMARY OF BACKGROUND DATA: CLBP is a musculoskeletal disorder with public health and economic impact. Pilot studies of yoga and back pain have reported significant changes in clinically important outcomes. METHODS: Subjects were recruited through self-referral and health professional referrals according to explicit inclusion/exclusion criteria. Yoga subjects participated in 24 weeks of biweekly yoga classes designed for CLBP. Outcomes were assessed at 12 (midway), 24 (immediately after), and 48 weeks (6-month follow-up) after the start of the intervention using the Oswestry Disability Questionnaire, a Visual Analog Scale, the Beck Depression Inventory, and a pain medication-usage questionnaire. RESULTS: Using intention-to-treat analysis with repeated measures ANOVA (group x time), significantly greater reductions in functional disability and pain intensity were observed in the yoga group when compared to the control group at 24 weeks. A significantly greater proportion of yoga subjects also reported clinical improvements at both 12 and 24 weeks. In addition, depression was significantly lower in yoga subjects. Furthermore, while a reduction in pain medication occurred, this was comparable in both groups. When results were analyzed using per-protocol analysis, improvements were observed for all outcomes in the yoga group, including agreater trend for reduced pain medication usage. Although slightly less than at 24 weeks, the yoga group had statistically significant reductions in functional disability, pain intensity, and depression compared to standard medical care 6-months postintervention. CONCLUSION: Yoga improves functional disability, pain intensity, and depression in adults with CLBP. There was also a clinically important trend for the yoga group to reduce their pain medication usage compared to the control group.