Long-term reversal of chronic pain behavior in rodents through elevation of spinal agmatine.

Chronic pain remains a significant burden worldwide, and treatments are often limited by safety or efficacy. The decarboxylated form of L-arginine, agmatine, antagonizes N-methyl-d-aspartate receptors, inhibits nitric oxide synthase, and reverses behavioral neuroplasticity. We hypothesized that expressing the proposed synthetic enzyme for agmatine in the sensory pathway could reduce chronic pain without motor deficits. Intrathecal delivery of an adeno-associated viral (AAV) vector carrying the gene for arginine decarboxylase (ADC) prevented the development of chronic neuropathic pain as induced by spared nerve injury in mice and rats and persistently reversed established hypersensitivity 266 days post-injury. Spinal long-term potentiation was inhibited by both exogenous agmatine and AAV-human ADC (hADC) vector pre-treatment but was enhanced in rats treated with anti-agmatine immunoneutralizing antibodies. These data suggest that endogenous agmatine modulates the neuroplasticity associated with chronic pain. Development of approaches to access this inhibitory control of neuroplasticity associated with chronic pain may yield important non-opioid pain-relieving options.

Prospective Trial to Compare Direct and Indirect Laryngoscopy Using C-MAC PM® with Macintosh Blade and D-Blade® in a Simulated Difficult Airway.

Objective. Evaluation of C-MAC PM® in combination with a standard Macintosh blade size 3 in direct and indirect laryngoscopy and D-Blade® in indirect laryngoscopy in a simulated difficult airway. Primary outcome was defined as the best view of the glottic structures. Secondary endpoints were subjective evaluation and assessment of the intubation process. Methods. Prospective monocentric, observational study on 48 adult patients without predictors for difficult laryngoscopy/tracheal intubation undergoing orthopedic surgery. Every participant preoperatively received a cervical collar to simulate a difficult airway. Direct and indirect laryngoscopy w/o the BURP maneuver with a standard Macintosh blade and indirect laryngoscopy w/o the BURP maneuver using D-Blade® were performed to evaluate if blade geometry and the BURP maneuver improve the glottic view as measured by the Cormack-Lehane score. Results. Using a C-MAC PM® laryngoscope, D-Blade® yielded improved glottic views compared with the Macintosh blade used with either the direct or indirect technique. Changing from direct laryngoscopy using a Macintosh blade to indirect videolaryngoscopy using C-MAC PM® with D-Blade® improved the Cormack-Lehane score from IIb, III, or IV to I or II in 31 cases. Conclusion. The combination of C-MAC PM® and D-Blade® significantly enhances the view of the glottis compared to direct laryngoscopy with a Macintosh blade in patients with a simulated difficult airway. Trial Registration Number. This trial is registered under number NCT03403946.

Distinguishing Bronchoscopic Changes of Mitral Stenosis From Carcinoma In Situ With Narrow Band Imaging.

A 75-year-old woman presented with minor hemoptysis. Past history included atrial fibrillation and rheumatic mitral stenosis. Bronchoscopy revealed a striking abnormality of widespread dilated mucosal and submucosal vessels. Initially the concern was whether there was widespread endobronchial malignancy; however, narrow band imaging (NBI) demonstrated the symmetrical uniform nature of the vessels. In addition, there was a focal area of in situ carcinoma with classic NBI features of malignancy. Following external-beam radiation therapy, NBI features had dramatically changed in the treated area which was now biopsy negative. The case highlights the utility of NBI in identifying endobronchial microvessel appearance even where there are widespread nonmalignant vessel changes in the bronchial mucosa.

Impact of Interhospital Transfer on Outcomes in Non-emergency Colorectal Surgery.

BACKGROUND: A paucity of data exists on the impact of transfer status on outcomes for patients undergoing non-emergency (urgent) colorectal surgery. This study characterized transferred patients undergoing urgent colorectal surgery and determined which patient comorbidities significantly contributed to poor outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2013 was used. Urgent direct admissions undergoing colon, rectum, or small bowel operations were compared to urgent transfers using bivariate and multivariable analysis models. Primary outcomes were overall complications, hospital length of stay, and mortality. RESULTS: A total of 82,151 admissions were analyzed. After multivariable analysis, direct admission patients had nearly similar risk of complications (RR = 0.95; 95% CI 0.91-0.99) and length of hospital stay (7% shorter; 95% CI 4-9%), as well as no difference in mortality (RR = 0.94; 95% CI 0.80-1.11). CONCLUSIONS: Transfer status alone confers minimal risk toward higher complication rates and longer hospital length of stay in patients undergoing urgent colorectal surgery, and the poor outcomes observed in this cohort are largely due to patient comorbidities and disease severity. Our results suggest that outcomes in transferred colorectal surgery patients undergoing urgent operations depend mainly on operative acuity and clinical factors, and to a lesser degree transfer status.

Force Perception Thresholds in Cochlear Implantation Surgery.

Tissue trauma is a frequent complication of cochlear implantation (CI) surgery, but the relationship between intracochlear trauma, electrode insertion forces, and surgeons' ability to perceive these forces is poorly understood. In this study, we simulated CI surgery using a benchtop apparatus to repeatedly apply small forces to the subjects' hands while reducing the variability in their hand movements. We used a psychophysical testing procedure to estimate the force perception thresholds of 10 otologic surgeons and found a median threshold of 20.4 mN. The results suggest that surgeons have the capability to sense at least some insertion forces and are likely to perceive severe trauma such as occurs when the electrode crosses from one scala to the other.

Initial radiographic tumor control is similar following single or multi-fractionated stereotactic radiosurgery for jugular paragangliomas.

OBJECTIVE: To evaluate radiographic tumor control and treatment-related toxicity in glomus jugulare tumors treated with stereotactic radiosurgery (SRS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic referral center. PATIENTS: Glomus jugulare tumors treated with SRS between 1998 and 2014 were identified. The data analysis only included patients with at least 18months of post-treatment follow up (FU). INTERVENTION: Patients were treated with either single fraction or fractionated SRS. MAIN OUTCOME MEASURE: Patient demographics and tumor characteristics were assessed. Radiographic control was determined by comparing pre and post treatment MRI, and was categorized as no change, regression, or progression. RESULTS: Eighteen patients were treated with SRS, and 14 met inclusion criteria. Median age at treatment was 55years (range 35-79), and 71.4% of patients were female. 5 patients (35.7%) received single fraction SRS (dose range 15-18Gy), and 9 (64.3%) fractionated therapy (dose 3-7Gy×3-15 fractions). Median tumor volume was 3.78cm(3) (range 1.15-30.6). Median FU was 28.8months (range 18.6-56.1), with a mean of 31.7months. At their last recorded MRI, 7 patients (50%) had tumor stability, 6 (42.9%) had improvement, and 1 (7.1%) had progression. Disease improvement and progression rates in the single fraction group were 40% and 0%, and in the multiple-fraction group, 44.4% and 11.1%, respectively. There was no statistically significant difference in disease improvement (p=0.88) or progression (p=0.48) rates between groups (unpaired t-test). CONCLUSIONS: At a median follow up of 28months, both single fraction and fractionated SRS appear to have comparable radiographic tumor control outcomes and toxicity profiles.

[Not Available]. / Atemwegsmanagement - Tracheotomie Revisited.

Since 5000 years tracheotomy is a common way for airway management. Generally, Tracheotomy will be divided in a surgical tracheotomy the percutaneous Tracheotomy. The surgical Tracheotomy takes place in the operation theater. The percutaneous Tracheotomy is one of the standard procedures in the Intensive care unit. There are many methods to perform the percutaneous Tracheotomy. The gist of every method is the seldinger procedure. Bronchoscopic supervision during the whole procedure is one of the most important things to prevent complications. However percutaneous and surgical tracheotomy are safe and have a low rate of complications.

Impact of 4D-(18)FDG-PET/CT imaging on target volume delineation in SBRT patients with central versus peripheral lung tumors. Multi-reader comparative study.

PURPOSE: Evaluation of the effect of co-registered 4D-(18)FDG-PET/CT for SBRT target delineation in patients with central versus peripheral lung tumors. METHODS: Analysis of internal target volume (ITV) delineation of central and peripheral lung lesions in 21 SBRT-patients. Manual delineation was performed by 4 observers in 2 contouring phases: on respiratory gated 4DCT with diagnostic 3DPET available aside (CT-ITV) and on co-registered 4DPET/CT (PET/CT-ITV). Comparative analysis of volumes and inter-reader agreement. RESULTS: 11 cases of peripheral and 10 central lesions were evaluated. In peripheral lesions, average CT-ITV was 6.2 cm(3) and PET/CT-ITV 8.6 cm(3), resembling a mean change in hypothetical radius of 2 mm. For both CT-ITVs and PET/CT-ITVs inter reader agreement was good and unchanged (0.733 and 0.716; p=0.58). All PET/CT-ITVs stayed within the PTVs derived from CT-ITVs. In central lesions, average CT-ITVs were 42.1 cm(3), PET/CT-ITVs 44.2 cm(3), without significant overall volume changes. Inter-reader agreement improved significantly (0.665 and 0.750; p<0.05). 2/10 PET/CT-ITVs exceeded the PTVs derived from CT-ITVs by >1 ml in average for all observers. CONCLUSION: The addition of co-registered 4DPET data to 4DCT based target volume delineation for SBRT of centrally located lung tumors increases the inter-observer agreement and may help to avoid geographic misses.

A case of sensorineural hearing loss involving a fibroepithelial polyp of the middle ear.

Primary middle ear neoplasms are rare, and commonly cause conductive hearing loss. When aural masses result in sensorineural hearing loss, malignant etiologies are often suspected. Fibroepithelial polyps are benign lesions commonly found in the skin and genitourinary tract and are not commonly identified as primary lesions of the middle ear. Here, we present a case of a benign fibroepithelial polyp of the middle ear causing sensorineural hearing loss and describe its surgical management. Imaging and histologic characteristics are reviewed.

Characterization of intracochlear rupture forces in fresh human cadaveric cochleae.

HYPOTHESIS: To develop a method to measure the forces required for a probe to translocate from the scala tympani (ST) to the scala vestibuli (SV) in fresh human cochleae. BACKGROUND: Translocation of cochlear implant electrodes from the ST to the SV may lead to suboptimal audiologic outcomes. Prior work investigating the rupture forces of human intracochlear membranes comes from a single study conducted on isolated ex vivo cadaveric specimens. METHODS: Fresh (postmortem <120 h), nonfixed, never-frozen human temporal bones underwent preparation consisting of surgical isolation of the cochleae and exposure of the osseous spiral lamina, basilar membrane, and Reissner's membrane complex by removing bone covering the ST and the SV. Each isolated cochlea was mounted to a force sensor using an adjustable mounting platform. A 300-µm-diameter ball-tipped probe was attached to a piezoelectric linear motor and advanced at 1 mm/s from the ST to the SV while recording force from the load cell concurrent with video. RESULTS: Ten specimens were successfully exposed and analyzed. The range of rupture forces was 42 to 122 mN, with a mean of 88 mN. Nine of the 10 specimens failed via simple puncture, whereas one failed by being avulsed from its medial attachment. CONCLUSION: Using a novel technique, we report the forces required to translocate a model of an electrode from the ST to the SV. Correlation to human perceptual ability is necessary to determine if a surgeon can detect such translocation during cochlear implant surgery.

Transnasal endoscopic resection of a calcifying cystic odontogenic tumor.

Calcifying cystic odontogenic tumor (CCOT) is a rare histologic subtype of odontogenic tumor. Treatment requires complete enucleation. We report what we believe is the first case of CCOT to be removed via a transnasal endoscopic approach. A 16-year-old boy was referred to our department by his dentist for evaluation of an expansile mass of the left maxillary sinus. The dentist had noted an area of hyperlucency of the left palate during a routine examination. Computed tomography confirmed the presence of a large tumor. Complete resection of the tumor was achieved via a transnasal endoscopic surgical approach. Resection of odontogenic tumors is necessary because of their tendency to expand and produce a mass effect on surrounding structures. We believe resection via an entirely transnasal endoscopic approach is a valuable and important technique in the treatment of odontogenic tumors that leaves the patient with a more cosmetically acceptable postoperative appearance.

Supraspinal gene transfer by intrathecal adeno-associated virus serotype 5.

We report the pattern of transgene expression across brain regions after intrathecal delivery of adeno-associated virus serotype 5 (AAV5). Labeling in hindbrain appeared to be primarily neuronal, and was detected in sensory nuclei of medulla, pontine nuclei, and all layers of cerebellar cortex. Expression in midbrain was minimal, and generally limited to isolated neurons and astrocytes in the cerebral peduncles. GFP immunoreactivity (-ir) in thalamus was most prominent in medial geniculate nucleus, and otherwise limited to posterior nuclei of the dorsal and lateral margins. Labeling was also observed in neurons and astrocytes of the hippocampal formation and amygdaloid complex. In the hippocampal formation, GFP-ir was found in neuronal cell bodies of the rostral ventral portion, but was largely restricted to fiber-like staining in the molecular layer of dentate gyrus and stratum lacunosum-moleculare of the rostral dorsal region. GFP-ir was seen in neurons and astroglia throughout caudal cortex, whereas in rostral regions of neocortex it was limited to isolated neurons and non-neuronal cells. Labeling was also present in olfactory bulb. These results demonstrate that intrathecal delivery of AAV5 vector leads to transgene expression in discrete CNS regions throughout the rostro-caudal extent of the neuraxis. A caudal-to-rostral gradient of decreasing GFP-ir was present in choroid plexus and Purkinje cells, suggesting that spread of virus through cerebrospinal fluid plays a role in the resulting transduction pattern. Other factors contributing to the observed expression pattern likely include variations in cell-surface receptors and inter-parenchymal space.

Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse.

Adeno-associated virus serotype 9 (AAV9)-mediated gene transfer has been reported in central nervous system (CNS) and peripheral tissues. The current study compared the pattern of expression of Green Fluorescent Protein (GFP) across the mouse CNS and selected peripheral tissues after intrathecal (i.t.) or intravenous (i.v.) delivery of equivalent doses of single-stranded AAV9 vector. After i.t. delivery, GFP immunoreactivity (-ir) was observed in spinal neurons, primary afferent fibers and corresponding primary sensory neurons at all spinal levels. Robust transduction was seen in small and large dorsal root ganglion (DRG) neurons as well as trigeminal and vagal primary afferent neurons. Transduction efficiency in sensory ganglia was substantially lower in i.v. treated mice. In brain, i.v. delivery yielded GFP-immunoreactivity (-ir) primarily in spinal trigeminal tract, pituitary, and scattered isolated neurons and astrocytes. In contrast, after i.t. delivery, GFP-ir was widespread throughout CNS, with greater intensity and more abundant neuropil-like staining at 6 weeks compared to 3 weeks. Brain regions with prominent GFP-ir included cranial nerve nuclei, ventral pons, cerebellar cortex, hippocampus, pituitary, choroid plexus, and selected nuclei of midbrain, thalamus and hypothalamus. In cortex, GFP-ir was associated with blood vessels, and was seen in both neurons and astrocytes. In the periphery, GFP-ir in colon and ileum was present in the enteric nervous system in both i.v. and i.t. treated mice. Liver and adrenal cortex, but not adrenal medulla, also showed abundant GFP-ir after both routes of delivery. In summary, i.t. delivery yielded higher transduction efficiency in sensory neurons and the CNS. The observation of comparable gene transfer to peripheral tissues using the two routes indicates that a component of i.t. delivered vector is redistributed from the subarachnoid space to the systemic circulation.