Differential spatial regulation of BMP molecules is associated with single-suture craniosynostosis.

Differential spatial regulation of BMP molecules is associated with single-suture craniosynostosis.

J Neurosurg Pediatr. 2016 Apr 1;:1-9

Authors: Whitton A, Hyzy SL, Britt C, Williams JK, Boyan BD, Olivares-Navarrete R

Abstract
OBJECTIVE The aim of this study was to examine messenger RNA (mRNA) levels of bone morphogenetic protein (BMP) ligands, receptors, and soluble inhibitors in cells isolated from single-suture synostoses from fused coronal, metopic, sagittal, and lambdoid sutures. METHODS Cells were isolated from bone collected from patients undergoing craniotomies at Children's Healthcare of Atlanta. Real-time polymerase chain reaction was used to examine mRNA levels in cells isolated from fused sutures or patent sutures in comparison with levels in normal bone from the same patient. RESULTS Cells isolated from fused sutures in cases of sagittal and coronal synostosis highly expressed BMP2, while cells isolated from fused metopic or lambdoid synostosis expressed high BMP4. Noggin, a BMP inhibitor, was lower in fused sutures and had high expression in patent sutures. CONCLUSIONS These results suggest that BMPs and inhibitors play a significant role in the regulation of suture fusion as well in the maintenance of patency in the normal suture.

PMID: 27035551 [PubMed - as supplied by publisher]

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Age-related carbon dioxide reactivity in children after moderate and severe traumatic brain injury.

Age-related carbon dioxide reactivity in children after moderate and severe traumatic brain injury.

J Neurosurg Pediatr. 2016 Apr 1;:1-6

Authors: Maa T, Yeates KO, Moore-Clingenpeel M, O'Brien NF

Abstract
OBJECTIVE The objective of this study is to assess carbon dioxide reactivity (CO2R) in children following traumatic brain injury (TBI). METHODS This prospective observational study enrolled children younger than 18 years old following moderate and severe TBI. Thirty-eight mechanically ventilated children had daily CO2R testing performed by measuring changes in their bilateral middle cerebral artery flow velocities using transcranial Doppler ultrasonography (TCD) after a transient increase in minute ventilation. The cohort was divided into 3 age groups: younger than 2 years (n = 12); 2 to 5 years old (n = 9); and older than 5 years (n = 17). RESULTS Children younger than 2 years old had a lower mean CO2R over time. The 2-5-year-old age group had higher mean CO2R than younger patients (p = 0.01), and the highest CO2R values compared with either of the other age groups (vs > 5 years old, p = 0.046; vs < 2 years old, p = 0.002). Having a lower minimum CO2R had a statistically significant negative effect on outcome at discharge (p = 0.0413). Impaired CO2R beyond Postinjury Day 4 trended toward having an effect on outcome at discharge (p = 0.0855). CONCLUSIONS Abnormal CO2R is prevalent in children following TBI, and the degree of impairment varies by age. No clinical or laboratory parameters were identified as risk factors for impaired CO2R. Lower minimum CO2R values are associated with worse outcome at discharge.

PMID: 27035550 [PubMed - as supplied by publisher]

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Is jugular bulb stenosis in vein of Galen aneurysmal malformation associated with bony remodeling of the jugular foramina?

Is jugular bulb stenosis in vein of Galen aneurysmal malformation associated with bony remodeling of the jugular foramina?

J Neurosurg Pediatr. 2016 Apr 1;:1-5

Authors: Saliou G, Dirks P, Slater LA, Krings T

Abstract
OBJECTIVE The etiology of jugular bulb stenosis (JBS) or occlusion in the context of vein of Galen aneurysmal malformations (VGAMs) is unknown. It can lead to decompensation of a lesion that was previously clinically stable. The aim of this study was to describe the natural history of JBS or occlusion in VGAM and to determine whether there is an association with bony remodeling of the jugular foramina. METHODS The authors identified all cases of JBS greater than 70% bilaterally involving patients seen at The Hospital for Sick Children between January 2007 and June 2014. The foramen diameters were measured on sagittal CT imaging, on a slice passing at the level of the jugular vein. The jugular foramen diameters were also compared to measurements obtained in a matched population of the same age group who had no VGAM and had undergone cerebral CT for a reason other than vascular disease. RESULTS Eight patients (6 male and 2 female) with bilateral JBS were included in this series. The median duration of clinical follow-up was 2.5 years (IQR 1.7-4.2 years). JBS was associated with bony narrowing the jugular foramina in 7 of the 8 patients over time. Between 1 and 2 years of age, patients with a VGAM demonstrated jugular foramen narrowing in comparison with a matched population (p = 0.015). CONCLUSIONS Jugular bulb stenosis or occlusion in VGAM may be associated with narrowing of the jugular foramina. These conditions seem to have a male predominance. If treatment is required, bony narrowing of the jugular foramina should be taken into account when deciding whether angioplasty and stent placement or surgical bypass might be appropriate therapeutic options.

PMID: 27035549 [PubMed - as supplied by publisher]

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Toward a better understanding of the cellular basis for cerebrospinal fluid shunt obstruction: report on the construction of a bank of explanted hydrocephalus devices.

Toward a better understanding of the cellular basis for cerebrospinal fluid shunt obstruction: report on the construction of a bank of explanted hydrocephalus devices.

J Neurosurg Pediatr. 2016 Apr 1;:1-11

Authors: Hanak BW, Ross EF, Harris CA, Browd SR, Shain W

Abstract
OBJECTIVE Shunt obstruction by cells and/or tissue is the most common cause of shunt failure. Ventricular catheter obstruction alone accounts for more than 50% of shunt failures in pediatric patients. The authors sought to systematically collect explanted ventricular catheters from the Seattle Children's Hospital with a focus on elucidating the cellular mechanisms underlying obstruction. METHODS In the operating room, explanted hardware was placed in 4% paraformaldehyde. Weekly, samples were transferred to buffer solution and stored at 4°C. After consent was obtained for their use, catheters were labeled using cell-specific markers for astrocytes (glial fibrillary acidic protein), microglia (ionized calcium-binding adapter molecule 1), and choroid plexus (transthyretin) in conjunction with a nuclear stain (Hoechst). Catheters were mounted in custom polycarbonate imaging chambers. Three-dimensional, multispectral, spinning-disk confocal microscopy was used to image catheter cerebrospinal fluid-intake holes (10× objective, 499.2-μm-thick z-stack, 2.4-μm step size, Olympus IX81 inverted microscope with motorized stage and charge-coupled device camera). Values are reported as the mean ± standard error of the mean and were compared using a 2-tailed Mann-Whitney U-test. Significance was defined at p < 0.05. RESULTS Thirty-six ventricular catheters have been imaged to date, resulting in the following observations: 1) Astrocytes and microglia are the dominant cell types bound directly to catheter surfaces; 2) cellular binding to catheters is ubiquitous even if no grossly visible tissue is apparent; and 3) immunohistochemical techniques are of limited utility when a catheter has been exposed to Bugbee wire electrocautery. Statistical analysis of 24 catheters was performed, after excluding 7 catheters exposed to Bugbee wire cautery, 3 that were poorly fixed, and 2 that demonstrated pronounced autofluorescence. This analysis revealed that catheters with a microglia-dominant cellular response tended to be implanted for shorter durations (24.7 ± 6.7 days) than those with an astrocyte-dominant response (1183 ± 642 days; p = 0.027). CONCLUSIONS Ventricular catheter occlusion remains a significant source of shunt morbidity in the pediatric population, and given their ability to intimately associate with catheter surfaces, astrocytes and microglia appear to be critical to this pathophysiology. Microglia tend to be the dominant cell type on catheters implanted for less than 2 months, while astrocytes tend to be the most prevalent cell type on catheters implanted for longer time courses and are noted to serve as an interface for the secondary attachment of ependymal cells and choroid plexus.

PMID: 27035548 [PubMed - as supplied by publisher]

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Severe holocord syrinx in a child with megalencephaly-capillary malformation syndrome.

Severe holocord syrinx in a child with megalencephaly-capillary malformation syndrome.

J Neurosurg Pediatr. 2016 Apr 1;:1-4

Authors: Segal D, Heary RF, Sabharwal S, Barry MT, Ming X

Abstract
The authors present the case of a child with megalencephaly-capillary malformation syndrome who developed a rapidly progressive holocord syringomyelia that was treated surgically. A 3-year-old boy with megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome presented with several months of right leg weakness, worsening scoliosis, and increased seizures. An MRI study of the brain demonstrated a Chiari I malformation and massively dilated syringomyelia extending from C-2 to the conus medullaris. The patient underwent an urgent suboccipital craniectomy with C1-3 laminectomies to relieve the CSF outflow obstruction with significant clinical improvement. Surgery was complicated by bleeding from intracranial vascular malformations. This report describes a very rapidly developing, massive holocord syringomyelia related to CSF obstruction due to an unusual congenital brain malformation and associated vascular overgrowth at the site. Serial, premorbid MRI studies demonstrated the very rapid progression from no Chiari malformation, to progressively greater cerebellar tonsillar herniation, to holocord syrinx. This complication has never been reported in MCAP syndrome and should be considered in any affected MCAP patient with a progressive neurological decline, even if previous spine imaging findings were normal. Surgical complications due to hemorrhage also need to be considered in this vascular brain malformation.

PMID: 27035547 [PubMed - as supplied by publisher]

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Letter to the Editor: Endoscope-assisted hemispherotomy and corpus callostomy.

Letter to the Editor: Endoscope-assisted hemispherotomy and corpus callostomy.

J Neurosurg Pediatr. 2016 Apr 1;:1-2

Authors: Chandra PS, Tripathi M

PMID: 27035546 [PubMed - as supplied by publisher]

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Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02).

Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02).

Brain Stimul. 2016 Jan 20;

Authors: Bauer S, Baier H, Baumgartner C, Bohlmann K, Fauser S, Graf W, Hillenbrand B, Hirsch M, Last C, Lerche H, Mayer T, Schulze-Bonhage A, Steinhoff BJ, Weber Y, Hartlep A, Rosenow F, Hamer HM

Abstract
BACKGROUND: Various brain stimulation techniques are in use to treat epilepsy. These methods usually require surgical implantation procedures. Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive technique to stimulate the left auricular branch of the vagus nerve at the ear conch.
OBJECTIVE: We performed a randomized, double-blind controlled trial (cMPsE02) to assess efficacy and safety of tVNS vs. control stimulation in patients with drug-resistant epilepsy.
METHODS: Primary objective was to demonstrate superiority of add-on therapy with tVNS (stimulation frequency 25 Hz, n = 39) versus active control (1 Hz, n = 37) in reducing seizure frequency over 20 weeks. Secondary objectives comprised reduction in seizure frequency from baseline to end of treatment, subgroup analyses and safety evaluation.
RESULTS: Treatment adherence was 84% in the 1 Hz group and 88% in the 25 Hz group, respectively. Stimulation intensity significantly differed between the 1 Hz group (1.02 ± 0.83 mA) and the 25 Hz group (0.50 ± 0.47 mA; p = 0.006). Mean seizure reduction per 28 days at end of treatment was -2.9% in the 1 Hz group and 23.4% in the 25 Hz group (p = 0.146). In contrast to controls, we found a significant reduction in seizure frequency in patients of the 25 Hz group who completed the full treatment period (20 weeks; n = 26, 34.2%, p = 0.034). Responder rates (25%, 50%) were similar in both groups. Subgroup analyses for seizure type and baseline seizure frequency revealed no significant differences. Adverse events were usually mild or moderate and comprised headache, ear pain, application site erythema, vertigo, fatigue, and nausea. Four serious adverse events were reported including one sudden unexplained death in epilepsy patients (SUDEP) in the 1 Hz group which was assessed as not treatment-related.
CONCLUSIONS: tVNS had a high treatment adherence and was well tolerated. Superiority of 25 Hz tVNS over 1 Hz tVNS could not be proven in this relatively small study, which might be attributed to the higher stimulation intensity in the control group. Efficacy data revealed results that justify further trials with larger patient numbers and longer observation periods.

PMID: 27033012 [PubMed - as supplied by publisher]

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Vertigo in childhood: a retrospective series of 100 children.

Related Articles

Vertigo in childhood: a retrospective series of 100 children.

Eur J Paediatr Neurol. 2015 Mar;19(2):226-32

Authors: Batu ED, Anlar B, Topçu M, Turanlı G, Aysun S

Abstract
OBJECTIVE: Evaluation and management of vertigo in children vary between institutions and medical specialties. The aim of this study is to describe the characteristics of vertigo in children presenting to a pediatric neurology referral center and to investigate the relationship between vertigo and migraine.
STUDY DESIGN: Patients <18 years old presenting with vertigo to Hacettepe University Ihsan Dogramaci Children's Hospital Neurology Unit between January 1996-January 2012 were included (n = 100). Data were obtained from patient files and phone interviews.
RESULTS: Mean age was 7.5 years. The most common etiological groups were benign paroxysmal vertigo of childhood (BPVC) (39%), psychogenic vertigo (21%), epileptic vertigo (15%), and migraine-associated vertigo (MAV) (11%). BPVC was the most common diagnosis in children ≤5 years of age while psychogenic vertigo prevailed in children >5 years. Staring episodes characterized epileptic vertigo patients (p = 0.021) while headache was more often described by MAV patients (p < 0.001). Vertigo attacks >5 min were uncommon in BPVC patients compared to others (p = 0.013). Twenty percent of BPVC patients contacted through phone interviews were experiencing migraine type headaches that started at a median age of 7.5 years. An algorithm for evaluation of children with vertigo was formed based on data obtained from this study and the literature. When this algorithm was applied to 100 cases of this series, 88 (88%) were correctly diagnosed.
CONCLUSION: While most vertigo cases in children can be diagnosed accurately by a detailed medical history, physical and neurological examination, a standard algorithm can help with the correct classification.

PMID: 25548116 [PubMed - indexed for MEDLINE]

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Subliminal galvanic-vestibular stimulation influences ego- and object-centred components of visual neglect.

Related Articles

Subliminal galvanic-vestibular stimulation influences ego- and object-centred components of visual neglect.

Neuropsychologia. 2015 Jul;74:170-7

Authors: Oppenländer K, Keller I, Karbach J, Schindler I, Kerkhoff G, Reinhart S

Abstract
Neglect patients show contralesional deficits in egocentric and object-centred visuospatial tasks. The extent to which these different phenomena are modulated by sensory stimulation remains to be clarified. Subliminal galvanic vestibular stimulation (GVS) induces imperceptible, polarity-specific changes in the cortical vestibular systems without the unpleasant side effects (nystagmus, vertigo) induced by caloric vestibular stimulation. While previous studies showed vestibular stimulation effects on egocentric spatial neglect phenomena, such effects were rarely demonstrated in object-centred neglect. Here, we applied bipolar subsensory GVS over the mastoids (mean intensity: 0.7mA) to investigate its influence on egocentric (digit cancellation, text copying), object-centred (copy of symmetrical figures), or both (line bisection) components of visual neglect in 24 patients with unilateral right hemisphere stroke. Patients were assigned to two patient groups (impaired vs. normal in the respective task) on the basis of cut-off scores derived from the literature or from normal controls. Both groups performed all tasks under three experimental conditions carried out on three separate days: (a) sham/baseline GVS where no electric current was applied, (b) left cathodal/right anodal (CL/AR) GVS and (c) left anodal/right cathodal (AL/CR) GVS, for a period of 20min per session. CL/AR GVS significantly improved line bisection and text copying whereas AL/CR GVS significantly ameliorated figure copying and digit cancellation. These GVS effects were selectively observed in the impaired- but not in the unimpaired patient group. In conclusion, subliminal GVS modulates ego- and object-centred components of visual neglect rapidly. Implications for neurorehabilitation are discussed.

PMID: 25445776 [PubMed - indexed for MEDLINE]

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Spontaneous Rupture of a Mycotic Superficial Femoral Artery

Publication date: Available online 1 April 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): H.Y. Zhang, F. Zhang




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Low-Grade Myofibroblastic Sarcoma of the Larynx.

Low-Grade Myofibroblastic Sarcoma of the Larynx.

J Craniofac Surg. 2016 Mar 30;

Authors: Vlad D, Albu S

Abstract
Low-grade myofibroblastic sarcoma is a malignant tumor of myofibroblasts, which has only recently become more clearly defined. It represents a rare entity that progresses in a slow-growing infiltrative pattern inside deep soft tissues. Due to its rarity and the plasticity of the myofibroblast, it can cause significant diagnostic difficulties. Differencing this neoplasm from other spindle cell tumors requires the use of ancillary techniques such as immunohistochemistry and/or electron microscopy. The authors report an unusual case of low-grade myofibroblastic sarcoma of the larynx in a 24-year-old woman, with atypical clinicopathologic presentation. The patient underwent direct laryngoscopy with excision of the malignant mass followed by adjuvant radiation therapy. The authors emphasize the uncommon location of this tumor type and discuss management options.

PMID: 27035601 [PubMed - as supplied by publisher]

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Airway Management with Cervical Spine Immobilisation: A Comparison between the Macintosh Laryngoscope, Truview Evo2, and Totaltrack VLM Used by Novices-A Manikin Study.

Airway Management with Cervical Spine Immobilisation: A Comparison between the Macintosh Laryngoscope, Truview Evo2, and Totaltrack VLM Used by Novices-A Manikin Study.

Biomed Res Int. 2016;2016:1297527

Authors: Aleksandrowicz D, Gaszyński T

Abstract
Airway management in patients with suspected cervical spine injury plays an important role in the pathway of care of trauma patients. The aim of this study was to evaluate three different airway devices during intubation of a patient with reduced cervical spine mobility. Forty students of the third year of emergency medicine studies participated in the study (F = 26, M = 14). The time required to obtain a view of the entry to the larynx and successful ventilation time were recorded. Cormack-Lehane laryngoscopic view and damage to the incisors were also assessed. All three airway devices were used by each student (a novice) and they were randomly chosen. The mean time required to obtain the entry-to-the-larynx view was the shortest for the Macintosh laryngoscope 13.4 s (±2.14). Truview Evo2 had the shortest successful ventilation time 35.7 s (±9.27). The best view of the entry to the larynx was obtained by the Totaltrack VLM device. The Truview Evo2 and Totaltrack VLM may be an alternative to the classic Macintosh laryngoscope for intubation of trauma patients with suspected injury to the cervical spine. The use of new devices enables achieving better laryngoscopic view as well as minimising incisor damage during intubation.

PMID: 27034926 [PubMed - as supplied by publisher]

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Functional results after total cricoidectomy with medial femoral condyle free flap reconstruction.

Functional results after total cricoidectomy with medial femoral condyle free flap reconstruction.

Eur Arch Otorhinolaryngol. 2016 Mar 31;

Authors: Banaszewski J, Gaggl A, Buerger H, Wierzbicka M, Pabiszczak M, Pastusiak T, Szyfter W

Abstract
Our goal was to describe a laryngeal-preserving single-stage procedure for the treatment of low-grade chondrosarcomas of the larynx: a total cricoidectomy with medial femoral condyle flap reconstruction. The study was designed as a case series of three consecutive patients with low-grade chondrosarcomas of the cricoid cartilage lamina, diameter 4.4, 5.2, 3.8 cm, respectively, who underwent total cricoidectomy in 2012. Single-staged reconstruction of the defect with medial femoral condyle flap including the periosteum and thin underlying cortical layer of the bone was conducted. Oncologic and functional results were observed during 3 years of follow-up. No evidence of tumor recurrence was detected during follow-up. One month after surgery, all patients were able to tolerate a soft diet and to speak satisfactorily. None of the patients reported aspiration after surgery nor experienced aspiration-related problems, which was confirmed by means of the Leipzig-Pearson scale. The speech ability was good, maximum phonation time was 14, 18, 21 s, respectively, and the voice handicap index scores ranged from 24 to 36 and had improved noticeably at 1, 3 and 6 months follow-up. Two patients were ultimately decannulated, and one female still has a tracheostomy; however, she is able to keep the tracheostoma closed for most of the time, maintaining good phonatory and swallowing functions. Total cricoidectomy with reconstruction by means of medial femoral condyle flap may replace the total laryngectomy in large low-grade chondrosarcomas of the cricoid cartilage.

PMID: 27034280 [PubMed - as supplied by publisher]

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Results and Survival of Locally Advanced AJCC 7th Edition T4a Laryngeal Squamous Cell Carcinoma Treated with Primary Total Laryngectomy and Postoperative Radiotherapy.

Results and Survival of Locally Advanced AJCC 7th Edition T4a Laryngeal Squamous Cell Carcinoma Treated with Primary Total Laryngectomy and Postoperative Radiotherapy.

Ann Surg Oncol. 2016 Mar 31;

Authors: Gorphe P, Matias M, Moya-Plana A, Tabarino F, Blanchard P, Tao Y, Janot F, Temam S

Abstract
PURPOSE: The objective of this study was to analyze the results and survival of patients with T4a laryngeal squamous cell carcinoma (SCC) treated, according to clinical practice guidelines, with total laryngectomy and postoperative radiotherapy (TL-PORT) in a large and homogeneous series.
METHODS: Initial staging assessment, treatment details, pathologic features, follow-up, and patterns of recurrence were retrospectively reviewed in a large series of 100 patients treated in our center between 2001 and 2013 for T4a laryngeal SCC with TL-PORT.
RESULTS: Two-, 5-, and 10-year overall survival rates were 65, 52.4, and 33.3 %, respectively, while 2-, 5-, and 10-year disease-free survival rates were 55, 42.6, and 31.8 %, respectively. In addition, 2-, 5-, and 10-year locoregional control rates were 77, 74, and 65.9 %, respectively. Central lymph node involvement was associated with pathologic subglottic extension (p = 0.01), lysis of the cricoid cartilage (p = 0.03), and tracheal extension (p = 0.02). Extracapsular spread of central lymph node metastases, the main prognostic factor identified by multivariate analysis, was associated with decreased locoregional control and survival rates.
CONCLUSION: In this homogenously treated cohort, with consistent guideline application, surgery for T4a larynx cancer remains a standard of care, with current results used as a benchmark.

PMID: 27034080 [PubMed - as supplied by publisher]

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Voxel-based morphometry in opera singers: increased gray-matter volume in right somatosensory and auditory cortices.

Voxel-based morphometry in opera singers: increased gray-matter volume in right somatosensory and auditory cortices.

Neuroimage. 2016 Mar 28;

Authors: Kleber B, Veit R, Moll CV, Gaser C, Birbaumer N, Lotze M

Abstract
In contrast to instrumental musicians, professional singers do not train on a specific instrument but perfectionate a motor system that has already been extensively trained during speech motor development. Previous functional imaging studies suggest that experience with singing is associated with enhanced somatosensory-based vocal motor control. However, experience-dependent structural plasticity in vocal musicians has rarely been studied. We investigated voxel-based morphometry (VBM) in 27 professional classical singers and compared gray matter volume in regions of the "singing-network" to an age-matched group of 28 healthy volunteers with no special singing experience. We found right hemispheric volume increases in professional singers in ventral primary somatosensory cortex (larynx S1) and adjacent rostral supramarginal gyrus (BA40), as well as in secondary somatosensory (S2) and primary auditory cortices (A1). Moreover, we found that earlier commencement with vocal training correlated with increased gray-matter volume in S1. However, in contrast to studies with instrumental musicians, this correlation only emerged in singers who began their formal training after the age of 14 years, when speech motor development has reached its first plateau. Structural data thus confirm and extend previous functional reports suggesting a pivotal role of somatosensation in vocal motor control with increased experience in singing. Results furthermore indicate a sensitive period for developing additional vocal skills after speech motor coordination has matured.

PMID: 27034024 [PubMed - as supplied by publisher]

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Subfascial drainage for management of cerebrospinal fluid leakage after posterior spine surgeryd---A prospective study based on Poiseuille's law.

Subfascial drainage for management of cerebrospinal fluid leakage after posterior spine surgeryd---A prospective study based on Poiseuille's law.

Chin J Traumatol. 2016 Feb 1;19(1):35-8

Authors: Fang Z, Jia YT, Tian R, Liu Y

Abstract
PURPOSE: Up to date, some approaches retarding the flow of cerebrospinal fluid (CSF) could be regarded as direct applications of the fluid mechanics (Poiseuille's law). However, there is a lack of the research on the efficacy of subfascial drainage for management of CSF leak after spine surgery based on the law. This is a prospective and comparative study on subfascial drainage for CSF.
METHODS: Every four months in the three years from January 2010 to December 2012, the patients were enrolled respectively in Group A, Group B and Group C, in which, the drainage tube was discontinued within postoperative 3-4 days, 5-6 days, 7-10 days. Results and complications of postoperative CSF leak were investigated, and mean wound healing time (MWHT) of the three groups was compared.
RESULTS: A total of 108 cases (Group A/B/C:35/32/41) of CSF leak following posterior spine surgery were admitted to Tianjin Union Medicine Center, and 92 cases have been followed up for more than 1 year (follow-up rate of 85.2%). Preoperative demographics were similar among the 3 groups. In Group A, 7 patients developed CSF leak through the wound (CSFLW), of which 5 cases had to undergo reoperation. One case in Group A was confirmed to have pseudomeningocele at the 1st month after surgery. The MWHT was (16.6±3.6) days. In Group B, 3 patients developed CSFLWand cured by reoperation, in which 1 case of superficial infection recovered well after reoperation. MWHT was (11.4±2.2) days. In Group C, CSFLWwas not found and MWHT was (10.1±2.9) days. The differences of MWHT among Groups A, B and C were statistically significant.
CONCLUSION: Postoperative subfascial drainage, which is used to decrease the subfascial space pressure (P₂), would help wound healing. When it is placed for more than 7 days, the wound resistance (Rw) would be strong enough to withstand the subarachnoid pressure (P₁). Meanwhile, the power trans- duction in a sequence of Rw > P₂ > P₁ will indirectly retard CSF leak at the durotomy site and accordingly facilitate the healing of damaged spinal dura mater.

PMID: 27033271 [PubMed - in process]

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Nestin+cells forming spheroids aggregates resembling tumorspheres in experimental ENU-induced gliomas.

Nestin+cells forming spheroids aggregates resembling tumorspheres in experimental ENU-induced gliomas.

Histol Histopathol. 2016 Apr 1;:11763

Authors: García-Blanco A, Bulnes S, Pomposo I, Carrasco A, Lafuente JV

Abstract
Nestin+cells from spheroid aggregates display typical histopathological features compatible with cell stemness. Nestin and CD133+cells found in glioblastomas, distributed frequently around aberrant vessels, are considered as potential cancer stem cells. They are possible targets for antitumoral therapy because they lead the tumorigenesis, invasiveness and angiogenesis. However, little is known about their role and presence in low-grade gliomas. The aim of this work is to localize and characterize the distribution of these cells inside tumors during the development of experimental endogenous glioma. For this study, a single dose of Ethyl-nitrosourea was injected into pregnant rats. Double immunofluorescences were performed in order to identify stem-like and differentiated cells. Low-grade gliomas display Nestin+cells distributed throughout the tumor. More malignant gliomas show, in addition to that, a perivascular location with some Nestin+cells co-expressing CD133 or VEGF, and the intratumoral spheroid aggregates of Nestin/CD133+cells. These structures are encapsulated by well-differentiated VEGF/GFAP+cells. Spheroid aggregates increase in size in the most malignant stages. Spheroid aggregates have morphological and phenotypic similarities to in vitro neurospheres and could be an in vivo analogue of them. These arrangements could be a reservoir of undifferentiated cells formed to escape adverse microenvironments.

PMID: 27033357 [PubMed - as supplied by publisher]

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Determination of boron concentration in oilfield water with a microfluidic ion exchange resin instrument

Publication date: 1 July 2016
Source:Talanta, Volume 154
Author(s): Cedric F.A. Floquet, Vincent J. Sieben, Bruce A. MacKay, Farshid Mostowfi
We developed and validated a microfluidic instrument for interference-free determination of boron in produced water. The instrument uses a boron-specific chelating resin to separate the analyte from its complex matrix. Ten produced water samples were analyzed with the instrument and the results were successfully validated against ICP-MS measurements. Removing interference effects enables precise boron measurement for wastewater even with high total dissolved solid (TDS) levels. 1,4-Piperazinediethanesulfonic acid conditions the resin and maintains the optimum pH for boron adsorption from the sample. Boron is then eluted from the resin using a 10% sulfuric acid solution and its concentration measured with the colorimetric carminic acid assay in 95% sulfuric acid. The use of a microfluidic mixer greatly enhances the sensitivity and kinetics of the carminic acid assay, by factors of 2 and 7.5, respectively, when compared against the same assay performed manually. A maximum sensitivity of 2.5mg⁻¹L, a precision of 4.2% over the 0–40.0mgL⁻¹ measuring range, a 0.3mgL⁻¹ limit of detection, and a sampling rate of up to four samples per hour were achieved. Automation and microfluidics reduce the operator workload and fluid manipulation errors, translating into safer and higher-quality measurements in the field.

Graphical abstract

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Validation of a sensitive LC/MSMS method for chloronucleoside analysis in biological matrixes and its applications

Publication date: 1 July 2016
Source:Talanta, Volume 154
Author(s): Caroline Noyon, Cédric Delporte, Damien Dufour, Melissa Cortese, Alexandre Rousseau, Philippe Poelvoorde, Jean Nève, Luc Vanhamme, Karim Zouaoui Boudjeltia, Thierry Roumeguère, Pierre Van Antwerpen
Myeloperoxidase promotes several kinds of damage and is involved in the development of various diseases (as atherosclerosis and cancers). An example of these damage is the chlorination of nucleic acids, which is considered as a specific marker of the MPO activity on those acids. This study aimed to develop and validate a method to analyze oxidized and MPO-specific chlorinated nucleosides in biological matrixes (cells, tissues and plasma). Although a lot of methods to quantify oxidized or chlorinated nucleosides have already been established, none of them took into account all these derivatives together.The new method used a Triple Quadrupole mass spectrometer fitted with a Jet Stream electrospray ionization source. This approach has two advantages compared with existing LC/MSMS analyses: it includes MPO-induced modifications in a unique analysis and obtains a better sensitivity. Our optimized method reached LOQs of 1.50pg and 1.42pg respectively for oxoG and oxo(d)G, being 4 times more sensitive than previous methods, and LOQs of 1.39pg, 1.30pg and 63.4 fg respectively for 5-chlorocytidine, 5-chloro-2′-deoxycytidine and 8-chloroguanosine. Developed method is also 25 times more sensitive for chloroguanosine than the best existing method. Nevertheless, this method is not specific enough for 8-chloro-(2′-deoxy)adenosine analysis.Examples of applications demonstrate the interest of this validated method. Indeed analysis of plasma from healthy donors highlighted exclusively the presence of 5-chlorocytidine (1.0±0.2nM) whereas analysis of treated endothelial cells by HOCl showed chlorination of guanosine and cytidine in cytoplasmic pools and chlorination of (deoxy)cytidine in DNA and RNA.In conclusion, this study shows that 5-chloro-2′-deoxycytidine, 5-chlorocytidine and 8-chloroguanosine are good markers allowing us to detect the MPO activity in biological fluids. The robust, specific and sensitive developed method enables future studies on MPO implications in human diseases.

Graphical abstract

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Application of a cholesterol stationary phase in the analysis of phosphorothioate oligonucleotides by means of ion pair chromatography coupled with tandem mass spectrometry

Publication date: 1 July 2016
Source:Talanta, Volume 154
Author(s): Sylwia Studzińska, Katarzyna Krzemińska, Michał Szumski, Bogusław Buszewski
The main aim of this study was the investigation of the influence of several ion pair reagents towards both the retention and the mass spectrometry sensitivity of phosphorothioate oligonucleotides. A cholesterol stationary phase was applied for the first time in the analysis of this group of compounds. The mobile phase composition was modified by changing the concentration and the type of amines and acetates or 1,1,1,3,3,3-hexafluoroisopropanol. It has been shown that the increase of amines concentration results in the retention factor increase for each oligonucleotide, on each adsorbent. The only exception was the mobile phase composed of triethylamine and 1,1,1,3,3,3-hexafluoroisopropanol. This is a consequence of interactions taking place between a cholesterol molecule and an alcohol. This effect was convenient when the mass spectrometry detection was applied, since it allowed an increase in the sensitivity. Moreover, optimization of the mobile phase composition and its impact on the efficiency of ionization process and on the sensitivity in mass spectrometry were also presented. The optimization of this new method, based on cholesterol stationary phase coupled with mass spectrometry detection, was finally applied for the determination of phosphorothioate oligonucleotides impurity in a real sample.

Graphical abstract

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In situ redox speciation analysis of chromium in water by diffusive gradients in thin films using a DE81 anion exchange membrane

Publication date: 1 July 2016
Source:Talanta, Volume 154
Author(s): Carlos A. Suárez, Thays V. de Simone, Amauri A. Menegário, Ana M.C.M. Rolisola, Karen S. Luko, Didier Gastmans, Fabiano T. da Conceição, Chang H. Kiang
A method for the in situ redox speciation analysis of chromium in water by the diffusive gradients in thin films (DGT) technique using a DE81 anion exchange membrane was successfully developed. For the selective uptake of Cr(VI), a DGT device containing an anion exchange membrane DE81 (cellulose acetate chromatographic paper) was used (DE81-DGT), while selective uptake of Cr(III) was carried out using DGT devices containing the Chelex-100 resin (Chelex-100-DGT). A correlation coefficient of 0.993 was obtained for the linearity of the immersion curves (mass versus time) using DE81-DGT. The diffusion coefficient values for Cr(VI) through the agarose diffusive layer were equal to 4.89±0.5×10⁻⁶cm²s⁻¹ and 3.95±0.02×10⁻⁶cm²s⁻¹ (T=23±1°C, I=0.03molL⁻¹ NaNO3) were obtained by using diffusion cell and immersion curves, respectively. The retention of Cr(VI) by the DE81 membrane in a synthetic sample and river water was not affected by the pH over a wide range 4–9). Recoveries of Cr(VI) between 90% and 120% from solutions of ionic strength ranging from 0.01 to 0. 5molL⁻¹ NaNO3 were achieved. Finally, the redox speciation analysis of Cr(III) and Cr(VI) in spiked river water and synthetic samples was performed with recoveries greater than 80% and 87% by using Chelex-100-DGT and DE81-DGT devices, respectively. Those results were in excellent agreement with the diphenylcarbazide spectrophotometric method.

Graphical abstract

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Electrochemical DNA biosensor based on poly(2,6-pyridinedicarboxylic acid) modified glassy carbon electrode for the determination of anticancer drug gemcitabine

Publication date: 1 July 2016
Source:Talanta, Volume 154
Author(s): Gözde Aydoğdu Tığ, Bülent Zeybek, Şule Pekyardımcı
In this study, a simple methodology was used to develop a new electrochemical DNA biosensor based on poly(2,6-pyridinedicarboxylic acid) (P(PDCA)) modified glassy carbon electrode (GCE). This modified electrode was used to monitor for the electrochemical interaction between the dsDNA and gemcitabine (GEM) for the first time. A decrease in oxidation signals of guanine after the interaction of the dsDNA with the GEM was used as an indicator for the selective determination of the GEM via differential pulse voltammetry (DPV). The guanine oxidation peak currents were linearly proportional to the concentrations of the GEM in the range of 1–30mgL^‒1. Limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.276mgL^‒1 and 0.922mgL^‒1, respectively. The reproducibility, repeatability, and applicability of the analysis to pharmaceutical dosage forms and human serum samples were also examined. In addition to DPV method, UV–vis and viscosity measurements were utilized to propose the interaction mechanism between the GEM and the dsDNA. The novel DNA biosensor could serve for sensitive, accurate and rapid determination of the GEM.

Graphical abstract

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Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma.

Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma.

Oncotarget. 2016 Mar 28;

Authors: Kakuki T, Kurose M, Takano KI, Kondoh A, Obata K, Nomura K, Miyata R, Kaneko Y, Konno T, Takahashi S, Hatakeyama T, Kohno T, Himi T, Kojima T

Abstract
Junctional adhesion molecule-A (JAM-A), which belongs to the IgG superfamily, is a tight junction molecule associated with epithelial and endothelial barrier function. Overexpression of JAM-A is also closely associated with invasion and metastasis of cancers such as breast cancer, lung cancer and pancreatic cancer. However, little is known about the mechanism in overexpression of JAM-A in head and neck squamous cell carcinoma (HNSCC). In the present study, we found high expression of JAM-A at the protein and mRNA levels in HNSCC tissues, including those of the oropahrynx, larynx, and hypopharynx, together with high protein expression of β-catenin, p63, ΔNp63 and GATA-3. Furthermore, in ELISA, a significant increase of soluble JAM-A in the sera of HNSCC patients was observed compared to healthy subjects. Knockdown of JAM-A by siRNA inhibited cell proliferation, invasion and migration in the HNSCC cell line Detroit562 in vitro. JAM-A expression in Detroit562 was increased via a distinct signal transduction pathway including NF-κB. Expression of JAM-A, β-catenin, p63 and ΔNp63 in Detroit562 was decreased under hypoxia. Knockdown of p63, ΔNp63 or GATA-3 by siRNAs reduced JAM-A expression in Detroit562. In primary cultured HNSCC cells in which CK7, p63, ΔNp63 and GATA-3 were detected, JAM-A expression was decreased by knockdown of p63 or ΔNp63. These results indicate that JAM-A is a biomarker of malignancy in HNSCC and that plasma soluble JAM-A may contribute to serum-based diagnosis of HNSCC. The mechanism of dysregulation of JAM-A via p63/GATA-3 is important in possible molecular targeted therapy for HNSCC.

PMID: 27036044 [PubMed - as supplied by publisher]

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Comparison of the RECIST and PERCIST criteria in solid tumors: a pooled analysis and review.

Comparison of the RECIST and PERCIST criteria in solid tumors: a pooled analysis and review.

Oncotarget. 2016 Mar 28;

Authors: Min SJ, Jang HJ, Kim JH

Abstract
The PET Response Criteria in Solid Tumors (PERCIST) is a new method for the quantitative assessment of metabolic changes in solid tumors. The assessments of tumor response between the RECIST and PERCIST have shown considerable difference in several studies. This pooled study was conducted to compare tumor response according to the two criteria in patients with solid tumors. We surveyed MEDLINE, EMBASE and PUBMED for articles with terms of the RECIST or PERCIST from 2009 and January 2016. There were six articles comparing the RECIST and PERCIST. A total of 268 patients were recruited; 81 with colorectal cancer, 60 with lung cancer, 48 with esophageal cancer, 28 with breast cancer, 14 with basal cell carcinoma, 12 with stomach cancer, 10 with head and neck cancer, and 16 with other rare cancers. The agreement of tumor response between the RECIST and PERCIST was moderate (k = 0.590). Of 268 patients, 101 (37.7%) showed discordance in the tumor responses between two criteria. When adopting the PERCIST, tumor response was upgraded in 85 patients and downgraded in 16. The estimated overall response rates were significantly different between two criteria (35.1% by RECIST vs. 54.1% by PERCIST, P < 0.0001). In conclusion, this pooled analysis demonstrates that the concordance of tumor responses between the RECIST and PERCIST criteria is not excellent. The PERCIST might be more suitable for assessing tumor response than the RECIST criteria.

PMID: 27036043 [PubMed - as supplied by publisher]

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MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib.

MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib.

Oncotarget. 2016 Mar 29;

Authors: Lassalle S, Zangari J, Popa A, Ilie M, Hofman V, Long E, Patey M, Tissier F, Belléannée G, Trouette H, Catargi B, Peyrottes I, Sadoul JL, Bordone O, Bonnetaud C, Butori C, Bozec A, Guevara N, Santini J, Hénaoui IS, Lemaire G, Blank O, Vielh P, Barbry P, Mari B, Brest P, Hofman P

Abstract
In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation and synergistically increased sensitivity to vandetanib, the clinically relevant treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and decreased AKT phosphorylation, affecting both cell proliferation and viability. We confirmed these results through SEC23A direct silencing in combination with vandetanib, highlighting the importance of SEC23A in the miR-375-associated increased sensitivity to vandetanib.Since the combination of increased expression of miR-375 and decreased expression of SEC23A point to sensitivity to vandetanib, we question if the expression levels of miR-375 and SEC23A should be evaluated as an indicator of eligibility for treatment of MTC patients with vandetanib.

PMID: 27036030 [PubMed - as supplied by publisher]

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Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma.

Genetic landscape of metastatic and recurrent head and neck squamous cell carcinoma.

J Clin Invest. 2016 Apr 1;126(4):1606

Authors: Hedberg ML, Goh G, Chiosea SI, Bauman JE, Freilino ML, Zeng Y, Wang L, Diergaarde BB, Gooding WE, Lui VW, Herbst RS, Lifton RP, Grandis JR

PMID: 27035818 [PubMed - as supplied by publisher]

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NOB1 silencing inhibits the growth and metastasis of laryngeal cancer cells through the regulation of JNK signaling pathway.

NOB1 silencing inhibits the growth and metastasis of laryngeal cancer cells through the regulation of JNK signaling pathway.

Oncol Rep. 2016 Mar 24;

Authors: Gao X, Wang J, Bai W, Ji W, Wang L

Abstract
Nin one binding protein (NOB1) plays important roles in the synthesis and degradation of proteins, thus having effects on the cellular process. In the present study, the expression level of NOB1 in laryngeal cancer patients was detected by quantitative PCR and western blotting, and the effect of NOB1 on growth and metastasis of laryngeal cancer cells was explored. Silence of NOB1 was found to inhibit the proliferation of laryngeal cancer cells, arrest cell cycle and induce cell apoptosis. NOB1 silence was also found to inhibit the migration and invasion of laryngeal cancer cells and to downregulate the protein levels of matrix metalloproteinases (MMPs)-2 and MMP-9. Further mechanism study revealed that the JNK signaling pathway was involved in the function of NOB1. Our present results suggest that NOB1 plays an oncogenic role in laryngeal cancer cells through the regulation of JNK signaling pathway, and lays a theoretical foundation for further exploration of NOB1.

PMID: 27035645 [PubMed - as supplied by publisher]

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Histologic Typing in Oropharyngeal Squamous Cell Carcinoma: A 4-Year Prospective Practice Study With p16 and High-Risk HPV mRNA Testing Correlation.

Histologic Typing in Oropharyngeal Squamous Cell Carcinoma: A 4-Year Prospective Practice Study With p16 and High-Risk HPV mRNA Testing Correlation.

Am J Surg Pathol. 2016 Mar 31;

Authors: Gondim DD, Haynes W, Wang X, Chernock RD, El-Mofty SK, Lewis JS

Abstract
Oropharyngeal squamous cell carcinomas (OPSCCs) associated with human papillomavirus (HPV) represent a distinct clinical and pathologic entity. The majority of HPV-related OPSCCs have a characteristic nonkeratinizing morphology. This study sought to determine the strength of the association between nonkeratinizing histology and HPV status compared with other squamous cell carcinoma variants in 4 years of routine clinical practice on a high-volume head and neck service. Primary and/or nodal metastatic tumors in all cases of OPSCC from 2010 to 2013 were typed by 1 of 3 head and neck pathologists as keratinizing, nonkeratinizing, nonkeratinizing with maturation, or another defined variant. All were assessed for p16 by immunohistochemistry with a 70% nuclear and cytoplasmic positivity cutoff as part of routine clinical practice. In addition, 70 consecutive cases from 1 year were "audited" for high-risk HPV mRNA by reverse transcription polymerase chain reaction and in situ hybridization. Of the 435 cases, the majority (90%) consisted of 1 of the 3 main types described and the rest (10%) of uncommon variants. Nonkeratinizing morphology had 99.1% and 100.0% positive predictive value for p16 and high-risk HPV mRNA positivity, respectively. Nonkeratinizing with maturation, keratinizing, and other specific squamous cell carcinoma variants were p16 positive in 91.8%, 22.8%, and 79.5%, respectively. All 47 nonkeratinizing OPSCCs tested for HPV mRNA were positive. In summary, strictly defined nonkeratinizing OPSCC (which constitutes ∼55% of all tumors) essentially implies positivity for both p16 and transcriptionally active high-risk HPV.

PMID: 27035614 [PubMed - as supplied by publisher]

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In Response to: Platelet-Rich Fibrin Plays a Role in Healing Acute-Traumatic Ear Drum Perforations.

In Response to: Platelet-Rich Fibrin Plays a Role in Healing Acute-Traumatic Ear Drum Perforations.

J Craniofac Surg. 2016 Mar 30;

Authors: Chen HY, Lou ZC

PMID: 27035603 [PubMed - as supplied by publisher]

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A Review of Tissue Expansion-Assisted Techniques of Cleft Palate Repair.

A Review of Tissue Expansion-Assisted Techniques of Cleft Palate Repair.

J Craniofac Surg. 2016 Mar 30;

Authors: Shash H, Al-Halabi B, Jozaghi Y, Aldekhayel S, Gilardino MS

Abstract
BACKGROUND: The purpose of this report was to examine current knowledge of use of tissue expansion techniques to assist cleft palate repair and to review and contrast various techniques reported.
METHODS: Two separate literature searches were conducted in the Cochrane Library, CINAHL, Medline and Embase databases, from database inception until December 2014 for use of mucoperiosteal expansion (MPE) and distraction osteogenesis (DO) in cleft palate repair.
RESULTS: Six articles, reporting a total of 51 patients of palatal MPE, were identified for discussion and analysis. Three different MPE techniques in primary cleft palate repair were described: intraoperative rapid expansion, tumescent injections, and a 2-stage repair with an osmotic expander. Average fistula rate was 26.19%. The search for use of DO on palatal clefts revealed 6 animal models, a finite element analysis study, and 1 case report. Moreover, 2 patients were reported of the use of DO to assist in secondary palatal fistula closure. No fistula rate could be calculated due to the heterogeneity of the data.
CONCLUSIONS: The experience with MPE in assisting cleft palate repair remains limited. Among expansion techniques, the use of osmotic expanders was associated with the highest rates of postoperative fistulae. The literature provides little evidence supporting the efficacy of MPE expansion in cleft palate repair. The majority of studies utilizing DO to assist primary cleft palate repair are in animal models with the exception of isolated case reports in human subjects. Although limited, the results demonstrate promise and the need for further research in this domain.

PMID: 27035596 [PubMed - as supplied by publisher]

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Identification of prognostic microRNA candidates for head and neck squamous cell carcinoma.

Identification of prognostic microRNA candidates for head and neck squamous cell carcinoma.

Oncol Rep. 2016 Mar 23;

Authors: Hui L, Wu H, Yang N, Guo X, Jang X

Abstract
The aim of the present study was to uncover potential prognostic microRNA (miRNA) markers in head and neck squamous cell carcinoma (HNSCC). miRNA expression profile and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Survival analysis was conducted by Kaplan-Meier method. Then, candidate prognostic miRNAs were screened via Cox proportional hazards regression analysis. Furthermore, target genes of miRNAs were predicted, and their interactions and functions were then analyzed. A total of 15 miRNAs were discovered to be significantly related to overall survival. Among them, miR-1251, miR-618 and miR-328 with p<0.05 were potentially significant prognostic factors of HNSCC. In the protein-protein interaction (PPI) network, the target gene of miR-328, MAX, interacted with multiple genes. The target gene of miR-618, E2F1, interacted with genes such as MAX, SMAD3 and IGF1. Furthermore, the target genes of miR-618 (e.g. E2F1 and SMAD3), and the target genes of miR-328 (e.g. MAX) were significantly enriched in the functions of transcriptional regulation. The target gene of miR-1251, IGF1, was associated with functions such as signal transduction. The above miRNAs (miR-1251, miR-618 and miR-328) may be potential prognostic markers in HNSCC.

PMID: 27035560 [PubMed - as supplied by publisher]

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Co‑inhibition of miRNA‑21 and miRNA‑221 induces apoptosis by enhancing the p53‑mediated expression of pro‑apoptotic miRNAs in laryngeal squamous cell carcinoma.

Co‑inhibition of miRNA‑21 and miRNA‑221 induces apoptosis by enhancing the p53‑mediated expression of pro‑apoptotic miRNAs in laryngeal squamous cell carcinoma.

Mol Med Rep. 2016 Mar 28;

Authors: Kan X, Sun Y, Lu J, Li M, Wang Y, Li Q, Liu Y, Liu M, Tian L

Abstract
Dysregulation of a numerous microRNAs (miRNAs) has been implicated in laryngeal squamous cell carcinoma (LSCC). Among those miRNAs, miR‑21 and miR‑221 are co‑overexpressed and commonly target the phosphatase and tensin homolog protein (PTEN) that is located in the PTEN‑Akt signaling pathway. The present study investigated whether co‑inhibition of miR‑21 and miR‑221 induced synergistic apoptosis of human LSCC cells. Methyl thiazolyl tetrazolium (MTT) and terminal deoxynucleotidyl‑transferase‑mediated deoxynucleotide triphosphate nick end labeling (TUNEL) assays were used to observe the potential effect of miR‑21 and miR‑221 on cell viability and apoptosis in cells co‑transfected with anti‑miRNA oligonucleotide (AMO)‑21 and AMO‑221. The protein expression levels of PTEN, Akt and p53 were determined by western blotting. The cellular abundance of 6 pro‑apoptotic miRNAs transcribed by p53 mediation, consisting of miR‑15a, miR‑16‑1, miR‑26a, miR‑34a, miR‑143 and miR‑203, was measured with using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). MTT results indicate that in vitro co‑transfection of AMO‑21 and AMO‑221 leads to a decline in cell viability, compared with the transfection of AMO alone. This result was verified by the detection of apoptosis using TUNEL assays. Co‑transfection of AMO‑21 and AMO‑221 resulted in a marked reduction in Akt phosphorylation and enhanced expression of PTEN and p53 were observed; consequently, leading to an amplification of the transcription of 6 pro‑apoptotic miRNAs. The present findings confirmed that co‑inhibition of miR‑21 and miR‑221 synergistically triggers cell apoptosis in vitro. The altered PTEN‑Akt signaling and p53‑mediated amplification of the transcription of pro‑apoptotic miRNAs may be involved in the observed synergistic effect. The present study provides novel insights into the mechanism underlying apoptosis‑associated miRNA‑miRNA mutual regulation in LSCC.

PMID: 27035337 [PubMed - as supplied by publisher]

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Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell Carcinoma Occurrence and Development.

Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell Carcinoma Occurrence and Development.

Sci Rep. 2016;6:24014

Authors: Liu YF, Chiang SL, Lin CY, Chang JG, Chung CM, Ko AM, Lin YZ, Lee CH, Lee KW, Chen MK, Hua CH, Tsai MH, Chen YC, Ko YC

Abstract
A number of genetic variants have been associated with cancer occurrence, however it may be the acquired somatic mutations (SMs) that drive cancer development. This study investigates the potential SMs and related genetic variants associated with the occurrence and development of head and neck squamous cell carcinoma (HNSCC). We identified several SMs in NOTCH1 from whole-exome sequencing and validated them in a 13-year cohort of 128 HNSCC patients using a high-resolution melting analysis and resequencing. Patients who have NOTCH1 SMs show higher 5-year relapse-free recurrence (P = 0.0013) and lower survival proportion (P = 0.0447) when the risk-associated SMs were analysed by Cox proportional hazard models. Interestingly, the NOTCH1 gene rs139994842 that shares linkage with SMs is associated with HNSCC risk (OR = 3.46), increasing when SMs in NOTCH1 are involved (OR = 7.74), and furthermore when there are SMs in conjunction to betel quid chewing (OR = 32.11), which is a related independent environmental risk factor after adjusting for substances use (alcohol, betel quid, cigarettes) and age. The findings indicate that betel quid chewing is highly associated with NOTCH1 SMs (especially with changes in EGF-like domains), and that rs139994842 may potentially serve as an early predictive and prognostic biomarker for the occurrence and development of HNSCC.

PMID: 27035284 [PubMed - as supplied by publisher]

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Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway.

Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway.

Int J Oncol. 2016 Mar 24;

Authors: Koguchi T, Tanikawa C, Mori J, Kojima Y, Matsuda K

Abstract
In response to various cellular stresses, p53 exerts its tumor suppressive effects such as apoptosis, cell cycle arrest, and senescence through the induction of its target genes. Recently, p53 was shown to control cellular homeostasis by regulating energy metabolism, glycolysis, antioxidant effect, and autophagy. However, its function in inositol synthesis was not reported. Through a microarray screening, we found that five genes related with myo-inositol metabolism were induced by p53. DNA damage enhanced intracellular myo-inositol content in HCT116 p53+/+ cells, but not in HCT116 p53-/- cells. We also indicated that inositol 3-phosphate synthase (ISYNA1) which encodes an enzyme essential for myo-inositol biosynthesis as a direct target of p53. Activated p53 regulated ISYNA1 expression through p53 response element in the seventh exon. Ectopic ISYNA1 expression increased myo-inositol levels in the cells and suppressed tumor cell growth. Knockdown of ISYNA1 caused resistance to adriamycin treatment, demonstrating the role of ISYNA1 in p53-mediated growth suppression. Furthermore, ISYNA1 expression was significantly associated with p53 mutation in bladder, breast cancer, head and neck squamous cell carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma. Our findings revealed a novel role of p53 in myo-inositol biosynthesis which could be a potential therapeutic target.

PMID: 27035231 [PubMed - as supplied by publisher]

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CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation.

CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation.

Mol Med Rep. 2016 Mar 21;

Authors: He H, Chai J, Zhang S, Ding L, Yan P, Du W, Yang Z

Abstract
Calcitonin-gene-related peptide (CGRP) is a neuropeptide, which is widely distributed throughout the central and peripheral nervous systems. Numerous mechanisms underlying the action of CGRP in osteoblast-associated cells have been suggested for bone growth and metabolism. The present study was designed to closely investigate the osteoblast‑ and osteoclast-associated mechanisms of the effect of CGRP administration on bone metabolism in primary osteoblasts. Primary osteoblasts were obtained from newborn rabbit calvaria and incubated with different concentrations of human CGRP (hCGRP), hCGRP and hCGRP (8‑37), or without treatment as a control. Intracellular calcium (Ca2+) and cyclic adenosine monophosphate (cAMP) were detected following treatment, as well as the expression levels of osteoblast differentiation markers, including activating transcription factor‑4 (ATF4) and osteocalcin (OC), and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG). The isolated primary osteoblasts were found to stain positively for ALP. hCGRP treatment had no significant effect on transient intracellular Ca2+ in the osteoblasts. Treatment of the osteoblasts with hCGRP led to elevations in the expression levels of cAMP, ATF4 and OPG, and downregulation in the expression of RANKL, in a dose‑dependent manner. These effects were markedly reversed by the addition of hCGRP (8‑37). The results of the present study demonstrated that CGRP administration not only stimulated osteoblast differentiation, as demonstrated by upregulated expression levels of ATF4 and OC in the hCGRP‑treated osteoblasts, but also inhibited OPG/RANKL‑regulated osteoclastogenesis. CGRP may act as a modulator of bone metabolism through osteoblast and osteoclast-associated mechanisms, which result in osteoblast formation with subsequent activation of bone formation.

PMID: 27035229 [PubMed - as supplied by publisher]

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Achalasia After Bariatric Surgery.

Achalasia After Bariatric Surgery.

J Laparoendosc Adv Surg Tech A. 2016 Apr 1;

Authors: Boules M, Corcelles R, Zelisko A, Batayyah E, Froylich D, Rodriguez J, Brethauer S, El-Hayek K, Kroh M

Abstract
BACKGROUND: Obesity is an epidemic on the rise. Increasing body mass index (BMI) has been associated with a number of comorbid diseases, including rarely reported motility disorders such as achalasia. Motility disorders are prevalent in obese patients, possibly more prevalent when compared to the nonobese population. Identification of motility disorders is important before bariatric surgery and may alter the planned type of procedure performed. Limited data exist regarding the development or existence of esophageal motility disorders after bariatric surgery. This study aims to characterize patients who have undergone bariatric surgery and subsequently developed or were diagnosed with achalasia.
METHODS: Patients with a diagnosis of achalasia who previously underwent bariatric surgery were identified. Data collected included baseline demographics, perioperative parameters, and postoperative outcomes. Descriptive statistics were computed for all variables.
RESULTS: Ten patients met the inclusion criteria. All patients had endoscopy and manometry confirming diagnosis of achalasia after previous bariatric surgery. Eight patients had undergone Roux-en-Y gastric bypass (RYGB), and two patients had vertical banded gastroplasty (VBG). Median length of time from bariatric surgery to diagnosis was 6 years. Two patients had undergone Botox(®) treatment, and five had gone through the scope esophageal dilations. All patients had a surgical intervention for achalasia, specifically Heller myotomy (HM) (n = 4 open, n = 4 laparoscopic) was performed in the eight RYGB patients, whereas near total gastrectomy and esophagectomy (n = 1), and transhiatal esophagectomy with a partial gastrectomy (n = 1), were performed in each of the patients who previously underwent VBG. These patients were considered to have end-stage achalasia. All patients showed significant decrease in BMI after bariatric surgery (11.1 ± 1.5 kg/m(2)). Six of the eight patients who underwent HM achieved resolution of achalasia symptoms at a mean time of 1.6 months and remained asymptomatic for the total follow-up of 36 months. One patient developed recurrent achalasia 2 years after HM and subsequently underwent a peroral endoscopic myotomy. One HM patient was lost to follow-up. The two patients who underwent esophagectomies were symptom free at 36 months.
CONCLUSION: Although the incidence of achalasia in the bariatric population is unknown, it does coexist and should be treated when identified. Dysmotility is not uncommon and rarely is the workup completed to identify achalasia before bariatric surgery. Increasing our attention to identify motility diseases preoperatively and specifically raising awareness that achalasia can occur after bariatric surgery will result in better care for patients. Our results suggest achalasia can be effectively treated with surgical therapy after previous bariatric surgery.

PMID: 27035633 [PubMed - as supplied by publisher]

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The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters.

The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters.

Cancer Lett. 2016 Mar 23;

Authors: Rigalli JP, Tocchetti GN, Arana MR, Villanueva SS, Catania VA, Theile D, Ruiz ML, Weiss J

Abstract
Breast cancer is the most frequent malignancy in women. Multidrug resistance due to overexpression of ABC drug transporters is a common cause of chemotherapy failure and disease recurrence. Genistein (GNT) is a phytoestrogen present in soybeans and hormone supplements. We investigated the effect of GNT on the expression and function of ABC transporters in MCF-7 and MDA-MB-231 breast cancer cell lines. Results demonstrated an induction at the protein level of ABCC1 and ABCG2 and of ABCC1 in MCF-7 and MDA-MB-231, respectively. MCF-7 cells showed a concomitant increase in doxorubicin and mitoxantrone efflux and resistance, dependent on ABCG2 activity. ABCC1 induction by GNT in MDA-MB-231 cells modified neither drug efflux nor chemoresistance due to simultaneous acute inhibition of the transporter activity by GNT. All inductions took place at the translational level, as no increment in mRNA was observed and protein increase was prevented by cycloheximide. miR-181a, already demonstrated to inhibit ABCG2 translation, was down-regulated by GNT, explaining translational induction. Effects were independent of classical estrogen receptors. Results suggest potential nutrient-drug interactions that could threaten chemotherapy efficacy, especially in ABCG2-expressing tumors treated with substrates of this transporter.

PMID: 27033456 [PubMed - as supplied by publisher]

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[Treatment of bone disease caused by gastrectomy].

Related Articles

[Treatment of bone disease caused by gastrectomy].

Clin Calcium. 2015 Nov;25(11):1681-8

Authors: Iwamoto J

Abstract
Gastrectomy is undergone mainly in patients with gastric cancer. Bone diseases(osteoporosis and osteomalacia)caused by gastractomy are associated with weight loss, calcium and vitamin D inadequancy, and malnutrition. Most patients after gastrectomy have multile risk factors of bone diseases and subsequently are at a higher risk for fractures. In particular, sex hormone deficiency and aging enhance the risk for fractures. The management of bone diseases caused by gastraectomy include adequet intake of calcium, vitamin D and protein, sunlight exposure, and regular weight-bearing exercise, as well as non-smoking and avoiding excess alcohol drinking. The patients at a high risk for fractures shoud be treated with bisphosphonates.

PMID: 26503874 [PubMed - indexed for MEDLINE]

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A randomized controlled trial of vitamin E and selenium on rate of decline in lung function.

Related Articles

A randomized controlled trial of vitamin E and selenium on rate of decline in lung function.

Respir Res. 2015;16:35

Authors: Cassano PA, Guertin KA, Kristal AR, Ritchie KE, Bertoia ML, Arnold KB, Crowley JJ, Hartline J, Goodman PJ, Tangen CM, Minasian LM, Lippman SM, Klein E

Abstract
BACKGROUND: The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers.
METHODS: The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 μg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function.
RESULTS: Compared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV1) or forced expiratory flow (FEF25-75). There was no evidence for a smoking by treatment interaction for FEV1, but selenium attenuated rate of decline in FEF25-75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF25-75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E.
CONCLUSIONS: Among all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF25-75, a marker of airflow.
TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00241865 .

PMID: 25889509 [PubMed - indexed for MEDLINE]

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Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers, in vitro dissolution, antioxidant potential and in vivo anti-platelet effect.

Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers, in vitro dissolution, antioxidant potential and in vivo anti-platelet effect.

Drug Dev Ind Pharm. 2016 Mar 31;:1-50

Authors: Nadal JM, Gomes ML, Borsato DM, Almeida MA, Barboza FM, Zawadzki SF, Farago PV, Zanin SM

Abstract
This paper aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray-dried SDs containing FA were successfully obtained. Relative solubility of FA was improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations showed suitable drug content values close to 100% whereas PLX-188 presented mean values between 70 and 90%. Agglomerates were observed depending on the carrier used. XRPD patterns and thermograms indicated that spray-drying led to drug amorphization and provided appropriate thermal stability, respectively. FTIR spectra demonstrated no remarkable interaction between carrier and drug for PEG 6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra which denoted intermolecular O-H•••O = C bonds. Spray-dried SDs played an important role in enhancing dissolution rate of FA when compared to pure drug. The free radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10% SDs was kept. This formulation also provided a statistically increased in vivo anti-platelet effect compared to pure drug. In summary, these formulations enhanced relative solubility and dissolution rate of FA and chosen formulation demonstrated suitable in vitro antioxidant activity and improved in vivo anti-platelet effect.

PMID: 27032626 [PubMed - as supplied by publisher]

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Novel gold nanoparticles coated with somatostatin as a potential delivery system for targeting somatostatin receptors.

Novel gold nanoparticles coated with somatostatin as a potential delivery system for targeting somatostatin receptors.

Drug Dev Ind Pharm. 2016 Mar 31;:1-37

Authors: Abdellatif AA, Zayed G, El-Bakry A, Zaky A, Saleem IY, Tawfeek HM

Abstract
Targeting of G-protein coupled receptors (GPCRs) like somatostatin-14 (SST-14) could have a potential interest in delivery of anti-cancer agents to tumor cells. Attachment of SST to different nano-carriers e.g., polymeric nanoparticles is limited due to the difficulty of interaction between SST itself and those nano-carriers. Furthermore, the instability problems associated with the final formulation. Attaching of SST to gold nanoparticles (AuNPs) using the positive and negative charge of SST and citrate-AuNPs could be considered a new technique to get stable non-aggregated AuNPs coated with SST. Different analyses techniques have been performed to proof the principle of coating between AuNPs and SST. Furthermore, cellular uptake study on HCC-1809 cell lines has been investigated to show the ability of AuNPs coated SST to enter the cells via SST receptors. Dynamic light scattering (DLS) indicated a successful coating of SST on the MUA-AuNPs surface. Furthermore, all the performed analysis including DLS, SDS-PAGE and UV-VIS absorption spectra indicated a successful coating of AuNPs with SST. Cellular uptake study on HCC-1806 cell lines showed that the number of AuNPs-SST per cell is significantly higher compared to citrate-AuNPs when quantified using inductively coupled plasma spectroscopy. Moreover, the binding of AuNPs-SST to cells can be suppressed by addition of antagonist, indicating that the binding of AuNPs-SST to cells is due to receptor-specific binding. In conclusion, AuNPs could be attached to SST via adsorption to get stable AuNPs coated SST. This new formulation has a potential to target SST receptors localized in many normal and tumor cells.

PMID: 27032509 [PubMed - as supplied by publisher]

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Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide based microspheres for nasal drug delivery.

Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide based microspheres for nasal drug delivery.

Drug Dev Ind Pharm. 2016 Mar 31;:1-33

Authors: Sharma N, Tyagi S, Gupta SK, Kulkarni GT, Bhatnagar A, Kumar N

Abstract
OBJECTIVE: Present work describes the application of natural plant polysaccharide as pharmaceutical mucoadhesive excipients in delivery systems to reduce the clearance rate through nasal cavity.
METHODS: Novel natural polysaccharide (Hibiscus rosasinensis) based mucoadhesive microspheres were prepared by using emulsion crosslinking method for the delivery of rizatriptan benzoate through nasal route. Mucoadhesive microspheres were characterized for different parameters and nasal clearance of (99m)Tc radiolabeled microspheres was determined by using gamma-scintigraphy.
RESULTS: Their FT-IR and XRD studies showed that the drug was stable during preparation of microspheres. Aerodynamic diameter of microspheres was in range 13.23±1.83 to 33.57±3.69 µm. Change in drug and polysaccharide ratio influenced the mucoadhesion, encapsulation efficiency and in-vitro release property. Scintigraphs taken at regular interval indicates that control solution was cleared rapidly from nasal cavity, whereas microspheres showed slower clearance (p < 0.005) with half-life of 160 min.
CONCLUSION: Natural polysaccharide based microspheres achieved extended residence by minimizing effect of mucociliary clearance with opportunity of sustained delivery for longer duration.

PMID: 27032438 [PubMed - as supplied by publisher]

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Hyperoside nanocrystals for HBV treatment: process optimization, in vitro and in vivo evaluation.

Hyperoside nanocrystals for HBV treatment: process optimization, in vitro and in vivo evaluation.

Drug Dev Ind Pharm. 2016 Mar 31;:1-32

Authors: Shen B, Wu N, Shen C, Zhang F, Wu Y, Xu P, Zhang L, Wu W, Lu Y, Han J, Wang Y, Yuan H

Abstract
The aim of this study was to develop hyperoside (Hyp) nanocrystals to enhance its dissolution rate, oral bioavailability and anti-HBV activity. Hyp nanocrystals were prepared using high pressure homogenization technique followed by lyophilization. A Box-Behnken design approach was employed for process optimization. The physicochemical properties, pharmacokinetics and anti-HBV activity in vivo of Hyp nanocrystal prepared with the optimized formulation were systematically investigated. Hyp nanocrystals prepared with the optimized formulation was found to be rod shaped with particle size of 384 ± 21 nm and PDI of 0.172 ± 0.027. XRPD studies suggested slight crystalline change in drug. Dissolution rate obtained from Hyp nanocrystals were markedly higher than pure Hyp. The nanocrystals exhibited enhanced Cmax (7.42 ± 0.73 vs. 3.80 ± 0.66 mg/L) and AUC0-t (193.61 ± 16.30 vs. 91.92 ±17.95 mg·h/L) with a 210.63% increase in relative bioavailability. Hyp nanocrystals exhibited significantly greater anti-HBV activity than Hyp. These results suggested that the developed nanocrystals formulation had a great potential as a viable approach to enhance the bioavailability of Hyp.

PMID: 27032257 [PubMed - as supplied by publisher]

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Is the 5-ports approach necessary in laparoscopic gastrectomy? Feasibility of reduced-port totally laparoscopic gastrectomy for the treatment of gastric cancer.

Is the 5-ports approach necessary in laparoscopic gastrectomy? Feasibility of reduced-port totally laparoscopic gastrectomy for the treatment of gastric cancer.

Int J Surg. 2016 Mar 28;

Authors: Seo HS, Lee HH

Abstract
BACKGROUND/AIM: Interest of gastric cancer patients in the quality of life postoperatively with respect to reduced scarring is increasing. This study aimed to evaluate the feasibility of reduced-port totally laparoscopic gastrectomy (RepTLG) for the treatment of gastric cancer.
METHODS: In total, 170 patients who underwent RepTLG (n=97) or conventional totally laparoscopic gastrectomy (cTLG) (n=73) were enrolled. Clinicopathological features, operative details, and short-term postoperative outcomes were analyzed retrospectively and compared between groups.
RESULTS: There were no significant differences for preoperative comorbidity between the RepTLG and c TLG groups, although patients in the RepTLG group were older than those in the cTLG group (63.5±11.1 vs. 59.3±10.6; p=0.014). Operating time was shorter in the RepTLG group compared to the cTLG group (187.5±67.7 min vs. 219.6±43.3 min; p<0.001) and duration of flatus of the RepTLG group was shorter than that of the cTLG group (2.7±0.6 days vs. 2.9±0.8 days; p=0.016).
CONCLUSION: RepTLG is a reliable scar reducing method with good operative and short-term outcomes for the treatment of gastric cancer compared with cTLG.

PMID: 27034118 [PubMed - as supplied by publisher]

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Evaluation of a New Needle Guidance System for Ultrasound: Results of a Prospective, Randomized, Blinded Study.

Background and Objectives: Accurate needle control during ultrasound (US)-guided nerve blocks may be an elusive goal for the anesthesiologist. Despite modifications to increase echogenicity, needle visibility still requires precise alignment within the transducer beam. In this study, we evaluated a magnetically guided ultrasound (MGU) system that produces a real-time, graphic display of the needle position and trajectory that is independent of the US beam. Methods: The MGU system was compared with echogenic needles and conventional ultrasound (CU) by anesthesiologists with and without prior experience performing US-guided nerve blocks. Participants were asked to perform tasks to quantify accuracy with respect to needle direction (directional accuracy) and needle tip position (positional accuracy). These evaluations were performed in a porcine tissue model. Results: Regarding directional accuracy, inexperienced subjects were able to contact a target capsule with a single needle pass during both in-plane (IP) and out-of-plane (OOP) approaches using the magnetic guidance system. By contrast, using CU, subjects required redirection 3.8 +/- 2.4 (P = 0.02), and 4.5 +/- 3.9 (P =0.04) times, respectively, for IP and OOP approaches. Experienced subjects contacted the target capsule with a single pass for both IP and OOP approaches when using the magnetic guidance system. With CU, experienced subjects were able to contact the target with a single pass using an IP approach but required redirection 3.4 +/- 2.8 (P = 0.046) times during OOP approaches. Positional accuracy was also superior for both inexperienced (P = 0.04) and experienced (P = 0.02) users during an OOP approach. Conclusions: In a tissue model, the MGU system improved control of needle trajectory and needle tip position for both inexperienced and experienced subjects. Copyright (C) 2016 by American Society of Regional Anesthesia and Pain Medicine.

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Anatomic Basis for Brachial Plexus Block at the Costoclavicular Space: A Cadaver Anatomic Study.

Background and Objectives: The costoclavicular space (CCS), which is located deep and posterior to the midpoint of the clavicle, may be a better site for infraclavicular brachial plexus block than the traditional lateral paracoracoid site. However, currently, there is paucity of data on the anatomy of the brachial plexus at the CCS. We undertook this cadaver anatomic study to define the anatomy of the cords of the brachial plexus at the CCS and thereby establish the anatomic basis for ultrasound-guided infraclavicular brachial plexus block at this proximal site. Methods: The anatomy and topography of the cords of the brachial plexus at the CCS was evaluated in 8 unembalmed (cryopreserved), thawed, fresh adult human cadavers using anatomic dissection, and transverse anatomic and histological sections, of the CCS. Results: The cords of the brachial plexus were located lateral and parallel to the axillary artery at the CCS. The topography of the cords, relative to the axillary artery and to one another, in the transverse (axial) plane was also consistent at the CCS. The lateral cord was the most superficial of the 3 cords and it was always anterior to both the medial and posterior cords. The medial cord was directly posterior to the lateral cord but medial to the posterior cord. The posterior cord was the lateral most of the 3 cords at the CCS and it was immediately lateral to the medial cord but posterolateral to the lateral cord. Conclusions: The cords of the brachial plexus are clustered together lateral to the axillary artery, and share a consistent relation relative to one another and to the axillary artery, at the CCS. Copyright (C) 2016 by American Society of Regional Anesthesia and Pain Medicine.

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Primary Failure of Thoracic Epidural Analgesia in Training Centers: The Invisible Elephant?.

In teaching centers, primary failure of thoracic epidural analgesia can be due to multiple etiologies. In addition to the difficult anatomy of the thoracic spine, the conventional end point-loss-of-resistance-lacks specificity. Furthermore, insufficient training compounds the problem: learning curves are nonexistent, pedagogical requirements are often inadequate, supervisors may be inexperienced, and exposure during residency is decreasing. Any viable solution needs to be multifaceted. Learning curves should be explored to determine the minimal number of blocks required for proficiency. The problem of decreasing caseload can be tackled with epidural simulators to supplement in vivo learning. From a technical standpoint, fluoroscopy and ultrasonography could be used to navigate the complex anatomy of the thoracic spine. Finally, correct identification of the thoracic epidural space should be confirmed with objective, real-time modalities such as neurostimulation and waveform analysis. Copyright (C) 2016 by American Society of Regional Anesthesia and Pain Medicine.

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Acute Epidural Hematoma Formation in Cervical Spine After Interlaminar Epidural Steroid Injection Despite Discontinuation of Clopidogrel.

Background: Perioperative management of patients on anticoagulant therapy prior to interventional pain procedures creates a challenge when balancing the risk of bleeding against thromboembolic events. Case Report: We report a case of epidural hematoma formation in the cervical spine following interlaminar epidural steroid injection in an elderly woman with chronic neck and arm pain, who was on clopidogrel therapy. Conclusions: This is the first reported case of hematoma formation immediately following an epidural steroid injection possibly associated with clopidogrel, even though established guidelines on the timing of the discontinuation of clopidogrel prior to the procedure were exceeded. Severe pain appears to be the first symptom of hematoma formation, and therefore immediate diagnostic workup and evacuation of hematoma are essential in preventing neurological damage. It may be advisable to carry out a test specific for clopidogrel such as the P2Y12 to ensure that there is no residual action on platelet aggregation function, particularly in patients who may be slow metabolizers of clopidogrel. Caution is advised prior to administering analgesics with antiplatelet effects such as ketorolac. Copyright (C) 2016 by American Society of Regional Anesthesia and Pain Medicine.

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Adductor Canal Block Versus Femoral Canal Block for Total Knee Arthroplasty: A Meta-Analysis: What Does the Evidence Suggest?.

No abstract available

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