Balancing the playing field: collaborative gaming for physical training

Multiplayer video games promoting exercise-based rehabilitation may facilitate motor learning, by increasing motivation through social interaction. However, a major design challenge is to enable meaningful int...

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6 Hz corneal kindling in mice triggers neurobehavioral comorbidities accompanied by relevant changes in c-Fos immunoreactivity throughout the brain

Summary

Objective

Besides seizures, patients with epilepsy are affected by a variety of cognitive and psychiatric comorbidities that further impair their quality of life. The present study provides an in-depth characterization of the behavioral alterations induced by 6 Hz corneal kindling. Furthermore, we correlate these behavioral changes to alterations in c-Fos protein expression throughout the brain following kindling.

Methods

Adolescent male Naval Medical Research Institute (NMRI) mice were kindled via repetitive subconvulsive 6 Hz corneal stimulations until they reached the fully kindled state (defined as 10 consecutive generalized seizures). Afterwards we performed an elaborate battery of behavioral tests and we evaluated c-Fos expression throughout the brain using immunohistochemistry.

Results

Fully kindled mice display an abnormal behavioral phenotype, characterized by basal and amphetamine-induced hyperlocomotion, anhedonia, social withdrawal, and deficits in short- and long-term memory. Moreover, 6 Hz corneal kindling enhances c-Fos immunoreactivity in the visual, parahippocampal, and motor cortices and the limbic system, whereas c-Fos⁺ cells are decreased in the orbital cortex of fully kindled mice.

Significance

The behavioral outcomes of 6 Hz corneal kindling cluster into 3 main categories: positive symptoms, negative symptoms, and cognitive impairment. These symptoms are accompanied by c-Fos activation in relevant brain regions once the fully kindled state is established. Based on the face validity of this model, we speculate that 6 Hz corneal kindling can be used to model not only pharmacoresistant limbic seizures, but also several neurobehavioral comorbidities that affect patients with epilepsy.

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Access to diagnostic and therapeutic facilities for psychogenic nonepileptic seizures: An international survey by the ILAE PNES Task Force—2nd Revision

Summary

Objective

Studies from a small number of countries suggest that patients with psychogenic nonepileptic seizures (PNES) have limited access to diagnostic and treatment services. The PNES Task Force of the International League Against Epilepsy (ILAE) carried out 2 surveys to explore the diagnosis and treatment of PNES around the world.

Methods

A short survey (8 questions) was sent to all 114 chapters of the ILAE. A longer survey (36 questions) was completed by healthcare professionals who see patients with seizures. Questions were separated into 5 sections: professional role, diagnostic methods, management, etiology, and access to health care.

Results

Responses were received from 63 different countries. The short survey was completed by 48 ILAE chapters, and the long survey by 1098 health professionals from 28 countries. PNES were recognized as a diagnostic and therapeutic problem in all countries. Trauma and mental health issues were most commonly recognized as etiologic factors. There was a clear relationship between income and access to diagnostic tests and expertise. Psychological therapy was most commonly considered the treatment of choice. Although financial difficulties were the most commonly reported problem with service access in low-income countries, in all countries stigma, lack of popular awareness, and lack of information posed challenges.

Significance

This global provider survey demonstrates that PNES are a health problem around the world. Health care for PNES could be improved with better education of healthcare professionals, the development of reliable and simple diagnostic procedures that do not rely on costly tests, and the provision of accessible information.

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Annals of Neurology: Volume 82, Number 5, November 2017

ON THE COVER: A 3-dimensional z-stack of images taken with a confocal microscope of synapses (stained green for synaptophysin) being phagocytosed by microglia (stained red for CD68), in the spinal cord of a mouse with knockout of the Abcd1 gene. Mutations in this gene in humans cause adrenoleukodystrophy, one component of which is adrenomyeloneuropathy, in which there is loss of spinal cord synapses.

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Issue Information - Masthead

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Issue Information - TOC

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Issue Information - Copyright

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Nasoseptal flap closure of the eustachian tube for recalcitrant cerebrospinal fluid rhinorrhea

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Easy insertion into the duct: The use of an angiocatheter as a sialendoscopy applicator

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First bite syndrome following transcervical arterial ligation after transoral robotic surgery

Objective

To assess the incidence of first bite syndrome (FBS) in transoral robotic surgical (TORS) patients undergoing transcervical arterial ligation.

Methods

Retrospective case series of all patients diagnosed with FBS following prophylactic transcervical arterial ligation of branches of the external carotid system between March 2010 and December 2016 at a single academic center.

Results

Six patients with FBS after TORS with transcervical arterial ligation were evaluated, representing 7% of all patients who underwent neck dissection with concomitant transcervical arterial ligation (6 of 83). Median presentation of FBS was 63 days, with an average duration of 66 days. Treatment ranged from observation to botulinum toxin injection.

Conclusion

Patients who undergo transcervical arterial ligation to minimize bleeding complications following TORS are at risk of developing first bite syndrome.

Level of Evidence

4. Laryngoscope, 2017

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The hospital otolaryngologist: The louisiana state university experience

Objectives/Hypothesis

To describe the implementation and impact of a hospital otolaryngologist in an academic medical center setting. Our hypothesis was that the hospital otolaryngologist would increase productivity of the Louisiana State University (LSU) faculty otolaryngologists and provide more timely access to inpatient otolaryngology services.

Study Design

Retrospective clinical and administrative database review.

Methods

A comparative database review was performed with data from the year predating the initiation of the hospitalist program (2013) to the first full year after initiation of the program (2014). A clinical database review including diagnoses and procedures was also performed.

Results

Overall outpatient clinic relative value units for the aggregated LSU faculty increased 16% (despite the fact that the direct outpatient contribution of the hospital otolaryngologist was negligible). Overall capture of inpatient consult codes increased 128%. The hospital otolaryngologist was responsible for 84.5% of inpatient consult codes. There was a 100% increase in outpatient consult codes for the LSU faculty, of which <1% was attributed to the otolaryngology hospitalist. No significant impact was seen on length of stay over the study interval. Clinical database review of the first 2 years of the program showed 3,707 total encounters with postoperative encounters the most common. Four hundred fifty-four inpatient procedures were logged. The most common surgical procedure was tracheostomy.

Conclusions

The otolaryngology hospitalist program is a viable clinical and economic model.

Level of Evidence

NA Laryngoscope, 2017

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Hirano's cover–body model and its unique laryngeal postures revisited

Objectives/Hypothesis

In 1974, Minoru Hirano proposed his theory of voice production that is now known as the cover–body theory. He described the thyroarytenoid (TA) and cricothyroid (CT) muscles as the major determinants of vocal fold shape and stiffness, and theorized four typical laryngeal configurations resulting from unique TA/CT activations, with implications for the resulting voice quality. In this study, we directly observed the vocal fold medial surface shape under Hirano's unique TA/CT activation conditions to obtain a three-dimensional (3D) understanding of these laryngeal configurations during muscle activation.

Study Design

In vivo canine hemilarynx model.

Methods

Flesh points were marked along the medial surface of the vocal fold. Selective TA and CT activation were performed via respective laryngeal nerves. 3D reconstructions of the vocal fold medial surface were derived using digital image correlation.

Results

Low level TA and CT activation yielded anteroposterior lengthening and vertical thinning of the vocal fold. When TA activation is far greater than CT, the vocal fold shortens and thickens. With slightly greater TA than CT, activation the vocal length is maintained on average, whereas its vertical thickness decreases. With CT far greater than TA activation, the vocal fold lengthens and thins. In all conditions, glottal contour changes remained minimal.

Conclusions

Analysis of the 3D geometry of the vocal fold medial surface under Hirano's four typical laryngeal configurations revealed that the key geometric changes during TA/CT interactions lie within the anteroposterior length and the vertical thickness of the vocal fold.

Level of Evidence

NA Laryngoscope, 2017

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The national landscape of unplanned 30-day readmissions after total laryngectomy

Objectives/Hypothesis

Examine rates of readmission after total laryngectomy and determine primary etiologies, timing, and risk factors for unplanned readmission.

Study Design

Retrospective cohort study.

Methods

The Nationwide Readmissions Database was queried for patients who underwent total laryngectomy between January 2013 and November 2013. Patient-, procedure-, admission-, and institution-level characteristics were compared for patients with and without unplanned 30-day readmission. Outcomes of interest included rates, etiology, and timing of readmission. Multivariate logistic regression was used to identify predictors of 30-day readmission.

Results

There were 2,931 total laryngectomies performed in 2013 with an unplanned readmission rate of 17.5%. Postoperative fistula accounted for 13.7% of readmissions. The odds of readmission were elevated for patients undergoing concurrent procedures, including primary tracheoesophageal fistulization (adjusted odds ratio [aOR]: 2.44, 95% confidence interval [CI]: 1.15-5.18, P = .02) and/or pedicle graft or flap procedures (aOR: 1.73, 95% CI: 1.13-2.66, P = .01). Additionally, patients with comorbid coagulopathy (aOR: 3.04, 95% CI: 1.13-8.22, P = .03), liver disease (aOR: 2.48, 95% CI: 1.08-5.71, P = .03), and valvular heart disease (aOR: 3.18, 95% CI: 1.20-8.41, P = .02) had increased risk for unplanned 30-day readmission. Private insurance and longer lengths of stay were associated with decreased odds of readmission.

Conclusions

Nearly one-fifth of total laryngectomy patients are readmitted to the hospital within 30 days of discharge. Risk factors identified in this nationally representative cohort should be carefully considered during the postoperative period to reduce preventable readmissions after total laryngectomy.

Level of Evidence

2c Laryngoscope, 2017

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Effect of topical nasal anesthetic on swallowing in healthy adults: A double-blind, high-resolution manometry study

Objective

Topical nasal anesthetic (TNA) is used when evaluating pharyngeal swallowing with high-resolution manometry (HRM). It is unclear if desensitizing the nasal mucosa improves procedure tolerability or affects pharyngeal pressure. This study evaluated the effects of TNA on comfort and pharyngeal pressure using HRM.

Methods

A double-blinded study was conducted with 20 healthy participants ( = 27 years). Participants performed five saliva and five 10-mL swallows during two exams with ManoScan HRM ESO catheter (Medtronic, Minneapolis, MN) randomized under placebo (nonanesthetic lubricant) and anesthetized (0.4 mL of 2% viscous lidocaine hydrochloride) conditions. Comfort was rated using a 100-mm visual analog scale (VAS). Pharyngeal HRM amplitude and timing were analyzed.

Results

VAS ratings were similar under placebo (mean = 38.4, standard deviation [SD] = 19.92) and TNA conditions (mean = 33.78, SD = 18.9), with no significant differences between placebo and anesthetized conditions (t[19] = 1.23, P = 0.23) or tolerability at first and second procedure (t[19] = 1.38, P = 0.18). Lower maximum and mean pharyngeal pressure were found for the TNA condition when compared to placebo (dry: maximum [−15.45 mmHg, standard error (SE) = 5.06 mmHg, P = 0.021]; mean [−5.22 mmHg, SE = 1.58 mmHg, P = 0.005]), and (liquid: maximum [−14.79 mmHg, SE = 5.01 mmHg, P = 0.010]; mean [−2.79 mmHg, SE = 1.99 mmHg, P = 0.008]).

Conclusion

This double-blind, randomized study is the first to investigate effects of TNA on tolerability and pharyngeal pressure using HRM. Results indicate TNA offered no significant difference in procedure comfort while affecting the magnitude of pharyngeal swallowing.

Level of Evidence

4. Laryngoscope, 2017

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When should you perform injection medialization for pediatric unilateral vocal fold immobility?

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Healthcare disparities in pediatric otolaryngology: A systematic review

Objectives

Multiple studies have reported healthcare disparities in particular settings and conditions within pediatric otolaryngology, but a systematic examination of the breadth of the problem within the field is lacking. This study's objectives are to synthesize the available evidence regarding healthcare disparities in pediatric otolaryngology, highlight recurrent themes with respect to etiologies and manifestations, and demonstrate potential impacts from patient and provider standpoints.

Methods

A qualitative systematic review of the PubMed, Ovid, and Cochrane databases for articles focusing on racial, ethnic, or socioeconomic disparities related to pediatric otolaryngology conditions or settings was conducted. United States-based studies of any design or publication date with analysis of children 0 to 18 years old were included.

Results

Of 711 abstracts identified, 39 met inclusion criteria. Manual review of references from these articles yielded 22 additional studies, for a total of 61. Disparities were identified in nearly every subspecialty within pediatric otolaryngology, with otologic conditions the most frequently studied (33 of 61). The most commonly cited disparities involved low socioeconomic status (25 of 61), inadequate insurance (23 of 61), nonwhite race (21 of 61), and barriers to accessing care (21 of 61). Only six articles found no disparities regarding the condition examined in their study.

Conclusion

Through a variety of study topics, designs, and settings, a growing body of literature documents disparities across the spectrum of pediatric otolaryngology care. The etiologies and manifestations of such disparities are myriad. This evidence suggests the need for interventions to address these disparities at various professional and institutional levels, ideally with methodological rigor to assess the effectiveness of such interventions. Laryngoscope, 2017

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Comparison of pediatric adenoidectomy techniques

Objectives

Evaluate the effects of electrocautery, microdebrider, and coblation techniques on outpatient pediatric adenoidectomy costs and complications.

Study Design

Observational retrospective cohort study.

Methods

An observational cohort study was performed in a multihospital network using a standardized accounting system. Children < 18 years of age who underwent outpatient adenoidectomy were included from January 2008 to September 2015. Cases with additional procedures were excluded. The cohorts were divided into children who underwent electrocautery, microdebrider, or coblator adenoidectomy. Data regarding costs, postoperative complications, and revision surgeries were analyzed.

Results

A total of 1,065 cases of adenoidectomy were performed with electrocautery (34.9%), microdebrider (26.1%), and coblation (39.0%). There was an increased after direct cost associated with the microdebrider, $833 (standard deviation [SD] $363) and the coblator, $797 (SD $262) compared to the electrocautery, $597 (SD $361) (P < 0.0001). There was a greater overall operating room (OR) time associated with use of the microdebrider (mean 28.7, SD 11.0 minutes) compared with both the electrocautery (mean 24.7, SD 8.1 minutes) and coblator (mean 26.2, SD 9.8 minutes) (P < 0.0001). No significant difference was found with regard to complication rates. The incidence of repeat adenoidectomies was significantly greater for microdebrider (9.7%) compared to electrocautery (2.7%; P = 0.0002) and coblator (5.3%; P = 0.0336) techniques.

Conclusion

These results suggest that adenoidectomy with electrocautery is significantly less expensive than microdebrider and coblator, with no differences in complication rates or surgical times among the techniques. Microdebrider adenoidectomy was associated with a longer overall OR time and a higher rate of adenoid regrowth, requiring revision surgery.

Level of Evidence

4. Laryngoscope, 2017

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Impact of an oral appliance on obstructive sleep apnea severity, quality of life, and biomarkers

Objective/Hypothesis

To investigate outcomes including efficacy, quality of life, and levels of inflammatory markers of a mandibular advancement device (MAD) for moderate-to-severe obstructive sleep apnea (OSA).

Study Design

Case-control study.

Methods

Patients with apnea-hypopnea index (AHI) ≥ 15/hr who only accepted MAD therapy (study group) or who refused any treatment (control group) were recruited. At baseline and at 6 months, polysomnography, Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), C-reactive protein (CRP), interleukin 1β, interleukin 6, and tumor necrosis factor α (TNF-α) were assessed in both groups.

Results

At baseline, the study group (n = 30) showed a higher percentage of rapid eye movement sleep and higher CRP levels (P < .05) than the control group (n = 10). At 6 months, the MAD significantly improved AHI and lowest oxygen saturation (P < .01), non–rapid eye movement (N)1 and N3 sleep stages (P < .05), ESS score (P < .05), FOSQ total score (P < .01), interleukin 1β (P < .05), and TNF-α (P < .01) compared with the untreated group. In the overall, moderate, and severe OSA groups, 63.3%, 75%, and 50%, respectively, achieved at least good response.

Conclusions

Use of a MAD significantly improved polysomnographic parameters, quality of life, and some inflammatory markers (CRP, IL-β, and TNF-α) in a significant proportion of patients with moderate OSA and in some patients with severe OSA. Hence, a MAD may be a viable alternative therapy in patients with moderate-to-severe OSA who refuse continuous positive airway pressure.

Level of Evidence

3b Laryngoscope, 2017

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Referral patterns from emergency department to otolaryngology clinic

Objectives/Hypothesis

Patients who present to the emergency department (ED) with various otolaryngologic disorders are frequently referred to an otolaryngologist for follow-up care. Our aim was to further characterize this group as it has not been well described in the literature.

Study Design

Cross-sectional retrospective study.

Methods

We reviewed the charts of patients seen during an 18-month period in an urban public hospital trauma center adult ED and referred to an otolaryngology clinic for follow-up care.

Results

Seven hundred thirty-eight patients were seen and referred; the most common diagnoses made by ED providers were peripheral vertigo (12%), otitis externa (8%), and nasal fractures (8%). Nine percent of patients were evaluated during their ED visit by an otolaryngology provider. Three hundred seventy-two (50%) patients returned for their otolaryngology clinic visit; facial trauma patients were least likely to return. The most common diagnoses made by otolaryngology providers were otitis externa (12%), peripheral vertigo (12%), and nasal fractures (7%). There was 50% concordance between patients' diagnoses made by ED and otolaryngology providers. The most common differences were otitis media versus otitis externa (10%) and acute pharyngitis versus laryngopharyngeal reflux (8%). During 37% of follow-up visits, an in-office procedure was performed, most commonly flexible fiberoptic laryngoscopy, cerumen removal, and nasal endoscopy.

Conclusions

Our analysis reports comprehensive characteristics of this referral group, identifying potential areas for improvement in patient management, resident education and efficiency. Otolaryngologists covering EDs should be familiar with this population in terms of types of cases that may affect their practices.

Level of Evidence

4. Laryngoscope, 2017

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Reviewers List

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Announcement

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Issue Information

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Course and predictors of post-traumatic stress disorder in a cohort of psychologically distressed patients with cancer: A 4-year follow-up study

BACKGROUND

Scant evidence exists on the long-term course of cancer-related post-traumatic stress disorder (PTSD). This is among the few studies worldwide, and the first in the South-East Asian region, to prospectively evaluate PTSD in patients with cancer using gold-standard clinical interviews. The objective of the study was to assess the course and predictors of PTSD in adult patients with cancer in a South-East Asian population.

METHODS

A prospective, longitudinal study was conducted in a cohort of 469 consecutively recruited patients (aged ≥18 years) with various cancer types within 1 month of diagnosis at a single oncology referral center. Only patients who had significant psychological distress (Hospital Anxiety and Depression Scale total cutoff score ≥16) underwent the PTSD module of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (SCID) at at 6-months follow-up. All patients completed the SCID at the 4-year follow-up assessment regardless of their initial Hospital Anxiety and Depression Scale score.

RESULTS

In an analysis combining patients who had both full and subsyndromal PTSD, there was a 21.7% incidence of PTSD at the 6-month follow-up assessment (n = 44 of 203 SCID-interviewed patients), with rates dropping to 6.1% at the 4-year follow-up assessment (n = 15 of 245 SCID-interviewed patients). Patients with breast cancer (compared with those who had other types of cancer) were 3.68 times less likely to develop PTSD at 6-months, but not at 4-years follow-up.

CONCLUSIONS

The overall rates of PTSD decreased with time, but one-third of patients (34.1%) who were initially diagnosed had persistent or worsening PTSD 4 years later. There is a need for early identification of this subset of patients who have cancer with PTSD to design risk-targeted interventions. Cancer 2017. © 2017 American Cancer Society.

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When the body becomes no more than the sum of its parts: the neural correlates of scrambled versus intact sexualized bodies

Recent research found that configural information is less important for the processing of sexualized bodies than for the processing of nonsexualized bodies. The present investigation aims to expand these findings by directly manipulating configural versus analytic processing of sexualized and nonsexualized bodies. We posited that disrupting first-order relational information through scrambling should be associated with larger N170 amplitudes (scrambling effect) for nonsexualized bodies, whereas the scrambling manipulation should not modulate N170 amplitudes associated with sexualized bodies and objects. We presented images of scrambled versus intact sexualized bodies, nonsexualized bodies, and objects while the N170 was recorded. Consistent with our hypothesis, we found that the scrambling manipulation was associated with larger N170 amplitudes for nonsexualized bodies (i.e. scrambling effect), whereas no scrambling effect emerged for sexualized bodies and objects. This research is the first to show that sexualized bodies are processed analytically at a neural level. Implications for the literature in body perception and objectification will be discussed. Correspondence to Philippe Bernard, PhD, Center for Social and Cultural Psychology, Université Libre de Bruxelles, CP 122, Avenue F. Roosevelt, 50, 1050 Brussels, Belgium e-mail: pbernard@ulb.ac.be Received September 27, 2017 Accepted October 7, 2017 © 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Mitochondrial fusion and fission proteins and the recognition memory of imprinting in domestic chicks

Visual imprinting is a learning process through which young, visually naive animals come to recognize a visual stimulus by being exposed to it (training) and subsequently approach the stimulus in preference to others. A large body of evidence indicates that a restricted part of the forebrain, the intermediate medial mesopallium (IMM), is a memory region for visual imprinting in the domestic chick. Previous studies have shown learning-related up-regulation of several mitochondrial proteins in the IMM 24 h after training. Learning-related increases in transcription factors involved in mitochondrial biogenesis were found without significant change in mitochondrial DNA copy number, but the issue of whether mitochondrial fusion or fission processes change with learning was unresolved. The present study enquired whether proteins involved in mitochondrial fusion and fission contribute to memory following imprinting. Tissue was sampled from the left and right IMM, and the left and right posterior pole of the nidopallium (a control brain region not involved in imprinting). The amounts of the following proteins were measured by Western immunoblotting 24 h after training: mitochondrial mitofusin-1 (MTF-1, as indicator of mitochondrial fusion), membrane dynamin-related protein-1 (DRP-1, as indicator of mitochondrial fission) and cytoplasmic DRP-1. Learning-related increases in MTF-1 and DRP-1 were observed bilaterally in the IMM, but not in either side of the posterior pole of the nidopallium. Cytoplasmic DRP-1 was not changed significantly in any region studied. The results implicate increased, balanced levels of mitochondrial fusion and fission in memory formation up to 24 h after training. Supplementary Video Abstract (Supplemental digital content 1, http://ift.tt/2AfqqIE). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://ift.tt/1iwynXF Correspondence to Brian J. McCabe, PhD, Sub-department of Animal Behaviour, Madingley, Cambridge CB23 8AA, UK Tel: +44 122 374 7300; fax: +44 122 374 1802; e-mail: bjm1@cam.ac.uk Received July 29, 2017 Accepted August 21, 2017 © 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Alpha band frequency differences between low-trait and high-trait anxious individuals

Trait anxiety has been shown to cause significant impairments on attentional tasks. Current research has identified alpha band frequency differences between low-trait and high-trait anxious individuals. Here, we further investigated the underlying alpha band frequency differences between low-trait and high-trait anxious individuals during their resting state and the completion of an inhibition executive functioning task. Using human participants and quantitative electroencephalographic recordings, we measured alpha band frequency in individuals both high and low in trait anxiety during their resting state, and while they completed an Eriksen Flanker Task. Results indicated that high-trait anxious individuals exhibit a desynchronization in alpha band frequency from a resting state to when they complete the Eriksen Flanker Task. This suggests that high-trait anxious individuals maintain fewer attentional resources at rest and must martial resources for task performance as compared with low-trait anxious individuals, who appear to maintain stable cognitive resources between rest and task performance. These findings add to the cognitive neuroscience literature surrounding the role of alpha band frequency in low-trait and high-trait anxious individuals. Correspondence to Richard T. Ward, MA, Department of Psychological Science, Ball State University, Muncie, IN 47306, USA Tel: +1 859 536 0507; e-mail: rtward@bsu.edu Received August 1, 2017 Accepted September 5, 2017 © 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

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Standardised noxious stimulation-guided individual adjustment of remifentanil target-controlled infusion to prevent haemodynamic responses to laryngoscopy and surgical incision: A randomised controlled trial

BACKGROUND The surgical plethysmographic index (SPI) is one of the available indexes of the nociception–antinociception (NAN) balance. Individually adjusting the NAN balance to prevent somatic responses to noxious stimulation remains a challenge. OBJECTIVES To assess whether guiding remifentanil administration according to the SPI response to a calibrated noxious stimulus (NANCAL) can blunt the haemodynamic response to tracheal intubation and surgical incision. DESIGN Prospective randomised multicentre controlled study. SETTING Two Belgian university hospitals from January 2014 to April 2015. PATIENTS After ethic review board approval and informed consent, 48 American Society of Anesthesiologists I or II adult patients scheduled for surgery under general anaesthesia were enrolled. INTERVENTIONS Patients were randomly assigned to a SPI group, where remifentanil effect-site concentration was adjusted according to NANCAL, or a control group, where it was fixed at 4 ng ml−1. Propofol concentration was always adjusted to maintain the bispectral index close to 40. NANCAL consisted of a 100 Hz, 60 mA electrical tetanic stimulation during 30 s at the wrist before tracheal intubation and before surgical incision. MAIN OUTCOME MEASURES The primary endpoint was the efficacy of the NANCAL-guided remifentanil administration to prevent the haemodynamic response to tracheal intubation and surgical incision. The secondary aim was to compare the ability of SPI, analgesia nociception index, pupil diameter and mean arterial pressure response to NANCAL to predict the haemodynamic response to tracheal intubation and surgical incision. RESULTS Our SPI response to NANCAL-based correcting scheme for remifentanil administration was not superior to a fixed remifentanil concentration at blunting the haemodynamic response to tracheal intubation or surgical incision. Among all tested NAN balance indices, only mean arterial pressure had significant predictive ability with regard to the haemodynamic response to surgical incision. CONCLUSION Further research is needed to define the best NANCAL stimulus and the best remifentanil correcting scheme to help individualised tailoring of antinociception for each specific subpopulation of surgical patients. TRIAL REGISTRATION Clinicaltrials.gov NCT: 02884310; http://ift.tt/2B2PCiQ. Correspondence to Aline Defresne, MD, Department of Anaesthesia and Intensive Care Medicine, CHR Citadelle, Bd du 12eme de Ligne, 1, 4000 Liege, Belgium E-mail: adefresne@chu.ulg.ac.be © 2017 European Society of Anaesthesiology

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End-of-treatment positron emission tomography after uniform first-line therapy of B cell posttransplant lymphoproliferative disorder identifies patients at low risk of relapse in the prospective German PTLD registry

Background Fluorine-18 fluorodeoxyglucose (18F-FDG) - positron-emission tomography (PET) is a recommended standard in the staging and response assessment of 18F-FDG-avid lymphoma. Posttransplant lymphoproliferative disorder (PTLD) can be detected by 18F-FDG-PET at diagnosis with high sensitivity and specificity. However, the role of response assessment by end of treatment (EOT)-PET has only been addressed in small case series. Methods We performed a retrospective, multi-center study of 37 patients with CD20-positive posttransplant lymphoproliferative disorder (PTLD) after solid organ transplantation (SOT) treated with uniform, up-to-date first-line protocols in the prospective German PTLD registry who had received EOT-18F-FDG-PET between 2006 and 2014. Median follow-up was 5.0 years. Any nonphysiological 18F-FDG uptake (Deauville score greater 2) was interpreted as PET-positive. Results By computed tomography (CT) final staging, 18 out of 37 patients had a complete response (CR), 18 had a partial response and 1 patient had stable disease. EOT PET was negative in 24/37 patients and positive in 13/37. The positive predictive value of EOT PET for PTLD relapse was 38% and the negative predictive value 92%. Time to progression (TTP) and progression-free-survival (PFS) were significantly longer in the PET negative group (p=0.019 and p=0.013). In the 18 patients in a partial response by CT staging, we noted highly significant differences in overall survival (p=0.001), TTP (p=0.007), and PFS (p

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Lung transplantation as a therapeutic option in acute respiratory distress syndrome

Background Lung transplantation (LTPL) is considered as a salvage therapeutic option in patients with end-stage lung disease. However, there is a lack of sufficient data on the use of LTPL in patients with acute respiratory distress syndrome (ARDS). While there are few case reports on lung transplant for ARDS, no case series exist up to date. The aim of this study was to evaluate the clinical outcomes of patients with ARDS in accordance with the LTPL status. Methods Patients who had severe ARDS (PaO2/FiO2 ratio ≤ 100 mmHg with positive end expiratory pressure ≥ 5 cmH2O) and were listed for LTPL with no underlying end-stage lung disease were included in this single-center retrospective study. Demographic and clinical data of the patients were collected and analyzed. Results Fourteen patients were listed for LTPL due to severe ARDS. All patients received mechanical ventilation, and 12 (86%) patients underwent extracorporeal membrane oxygenation. Of the nine patients who underwent LTPL, eight (89%) survived, whereas only one patient (20%) out of those who did not receive LTPL survived. The median survival time of the patients who underwent LTPL was 1996 days (interquartile range (IQR), 872–2239), compared with 49 days (IQR, 872–2239) in patients who did not undergo LTPL. The median survival time after LTPL was 64 months (IQR, 28–72). The three-year survival rate of the recipients was 78%. Conclusions LTPL may be considered as a therapeutic option in a select group of patients with severe ARDS. However, the irreversibility of the patient's lung status should be considered. Correspondence to: Seung-Il Park, M.D.: Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea, E-mail: sipark@amc.seoul.kr, Sang-Bum Hong, M.D.: Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea, E-mail:sbhong@amc.seoul.kr Seung-Il Park, M.D. and Sang-Bum Hong, M.D. equally contributed to this study. Contributions: Conception and design: SH, SP, TS; Acquisition, analysis and interpretation: YC, SL, SC, HK, YK, DK, KD, IC; Drafting the manuscript for important intellectual content: YC, SH, SP, TS. Conflicts of interest: The authors declare no conflicts of interest. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Incidence and Risk Factors of Intracranial Hemorrhage in Liver Transplant Recipients

Background Intracranial hemorrhage after liver transplantation is an infrequently reported complication but one which can have devastating consequences. Methods We performed a retrospective cross-sectional analysis of all liver transplants performed between January 2010 and June 2015 at a single high-volume institution using a prospectively maintained electronic database and query of the electronic medical record. Cases of intracranial hemorrhage were adjudicated as either spontaneous intraparenchymal (IPH) or extra-axial (EAH) hemorrhages. Patients with confirmed intracranial hemorrhage were compared with all other liver transplant recipients. Risk factors were identified by univariate analysis and logistic regression models for IPH and EAH. Results Thirty-one (5.2%) of 595 liver transplant recipients developed an intracranial hemorrhage within 12 months of transplantation, 15 IPH and 16 EAH. The majority of intracranial hemorrhages were diagnosed within 1 month of transplantation. Eight (26%) intracranial hemorrhage patients died during hospitalization. Fourteen (45%) intracranial hemorrhage patients died within 1 year of transplantation and 1-year mortality was greater than in patients without intracranial hemorrhage (11.2%, p

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Lung Isolation in the Patient With a Difficult Airway

One-lung ventilation is routinely used to facilitate exposure for thoracic surgical procedures and can be achieved via several lung isolation techniques. The optimal method for lung isolation depends on a number of factors that include (1) the indication for lung isolation, (2) anatomic features of the upper and lower airway, (3) availability of equipment and devices, and (4) the anesthesiologist's proficiency and preferences. Though double-lumen endobronchial tubes (DLTs) are most commonly utilized to achieve lung isolation, the use of endobronchial blockers offer advantages in patients with challenging airway anatomy. Anesthesiologists should be familiar with existing alternatives to the DLT for lung isolation and alternative techniques for DLT placement in the patient with a difficult airway. Newer technologies such as videolaryngoscopy with or without adjunctive fiberoptic bronchoscopy may facilitate intubation and lung isolation in difficult airway management. Accepted for publication October 3, 2017. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Randal S. Blank, MD, PhD, Department of Anesthesiology, Thoracic Anesthesia, University of Virginia Health System, PO Box 800710-0710, Charlottesville, VA 22908. Address e-mail to rsb8p@virginia.edu. © 2017 International Anesthesia Research Society

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Ultrasound-Assisted Versus Fluoroscopic-Guided Lumbar Sympathetic Ganglion Block: A Prospective and Randomized Study

BACKGROUND: Fluoroscopy (FL)-guided lumbar sympathetic ganglion block (LSGB) is widely performed to diagnose and manage various diseases associated with sympathetically maintained pain. Recently, numerous ultrasound (US)-assisted procedures in pain medicine have been attempted, showing an advantage of low radiation exposure. This randomized, prospective trial compared the procedural outcomes and complications between FL-guided and US-assisted LSGBs. METHODS: Fifty LSGBs were randomly divided into 2 groups: FL-guided (FL group) or US-assisted (US group) LSGB group. Both groups received FL-guided or US-assisted LSGB with 10 mL of 0.25% levobupivacaine. The primary end point was the total procedure time. Secondary outcomes were success rate, imaging time, onset time (based on temperature rise), dosage of radiation exposure, other procedure-related outcomes, and complications. RESULTS: Total procedure time and success rate were not statistically different between the 2 groups, whereas imaging time of the US group was longer than that of the FL group (P = .012). The onset time was faster in the US group (P = .019), and bone touching during the procedure was less frequent in the US group (P = .001). Moreover, radiation exposure was significantly lower in the US group than in the FL group (P

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Perioperative Noninvasive Blood Pressure Monitoring

The most commonly monitored variable for perioperative hemodynamic management is blood pressure. Several indirect noninvasive blood pressure monitoring techniques have been developed over the last century, including intermittent techniques such as auscultation (Riva-Rocci and Korotkoff) and oscillometry (Marey) and continuous techniques. With the introduction of automated noninvasive blood pressure devices in the 1970s, the oscillometric technique quickly became and remains the standard for automated, intermittent blood pressure measurement. It tends to estimate more extreme high and low blood pressures closer to normal than what invasive measurements indicate. The accuracy of the oscillometric maximum amplitude algorithm for estimating mean arterial pressure is affected by multiple factors, including the cuff size and shape, the shape of the arterial compliance curve and arterial pressure pulse, and pulse pressure itself. Additionally, the technique typically assumes a consistent arterial compliance and arterial pressure pulse, thus changes in arterial compliance and arrhythmias that lead to variation in the pressure pulse can affect accuracy. Volume clamping, based on the Penaz principle, and arterial tonometry provide continuous tracking of the arterial pressure pulse. The ubiquitous use of blood pressure monitoring is in contrast with the lack of evidence for optimal perioperative blood pressure targets. Accepted for publication September 27, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Kai Kuck, PhD, Department of Anesthesiology, University of Utah Medical School, 30 N 1900 E Room 3c444, Salt Lake City, UT 84132. Address e-mail to kai.kuck@hsc.utah.edu. © 2017 International Anesthesia Research Society

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How to Survive in Anaesthesia, 5th ed

No abstract available

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Two-Year Follow-Up Survey: Views of US Anesthesiologists About Health Care Costs and Future Practice Roles

Anesthesiologists' perspectives on US health care finance reform are increasingly germane to recent policy reforms. The aim of this follow-up survey was to examine how anesthesiologists' views of health care costs and future practice roles have changed since 2014. Six thousand randomly chosen active members of the American Society of Anesthesiologists were again surveyed and were also asked several new questions regarding specialties and perioperative management. Results showed an increase in self-reported understanding of the perioperative surgical home. Government, insurance companies, and pharmaceutical companies saw an increase in perceived "major responsibility" for cost reduction. Respondents vastly preferred that patient care under the perioperative surgical home be multidisciplinary. Accepted for publication September 1, 2017. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Joseph B. Rinehart, MD, Department of Anesthesiology & Perioperative Care, University of California, Irvine, 101 The City Dr S, Orange, CA 92868. Address e-mail to jrinehar@uci.edu. © 2017 International Anesthesia Research Society

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Reducing Maternal Mortality in Papua New Guinea: Contextualizing Access to Safe Surgery and Anesthesia

Papua New Guinea has one of the world's highest maternal mortality rates with approximately 215 women dying per 100,000 live births. The sustainable development goals outline key priority areas for achieving a reduction in maternal mortality including a focus on universal health coverage with safe surgery and anesthesia for all pregnant women. This narrative review addresses the issue of reducing maternal mortality in Papua New Guinea by contextualizing the need for safe obstetric surgery and anesthesia within a structure of enabling environments at key times in a woman's life. The 3 pillars of enabling environments are as follows: a stable humanitarian government; a safe, secure, and clean environment; and a strong health system. Key times, and their associated specific issues, in a woman's life include prepregnancy, antenatal, birth and the postpartum period, childhood, adolescence and young womanhood, and the postchildbearing years. Accepted for publication September 8, 2017. Funding: None. The author declares no conflicts of interest. This review was undertaken as part of work completed by Associate Professor Dennis at the University of Sydney as part of the completion of her Master of International Public Health. Reprints will not be available from the author. Address correspondence to Alicia T. Dennis, MBBS, PhD, MIPH, PGDipEcho, FANZCA, Department of Anaesthesia, The Royal Women's Hospital, The University of Melbourne, Locked Bag 300, Corner Grattan St & Flemington Rd, Parkville, Victoria 3052, Australia. Address e-mail to alicia.dennis@thewomens.org.au. © 2017 International Anesthesia Research Society

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Alkalinized Lidocaine Preloaded Endotracheal Tube Cuffs Reduce Emergence Cough After Brief Surgery: A Prospective Randomized Trial

BACKGROUND: Alkalinized lidocaine in the endotracheal tube (ETT) cuff decreases the incidence of cough and throat pain on emergence after surgery lasting more than 2 hours. However, alkalinized lidocaine needs 60–120 minutes to cross the ETT cuff membrane; therefore, its usefulness in shorter duration surgery is unknown. This prospective double-blind randomized controlled trial tested the hypothesis that alkalinized lidocaine would reduce the incidence of emergence cough after surgeries lasting 90 minutes before intubation with either 2 mL of 2% lidocaine and 8 mL of 8.4% bicarbonate (group AL) or 10 mL of normal saline (group S). Cuffs were emptied immediately before intubation. After intubation, either 2 mL of 2% lidocaine (AL) or 2 mL of saline (S) were injected into the cuff. Additional 8.4% bicarbonate (AL) or saline (S) was injected into the cuff until there was no air leak. Anesthesia was maintained using desflurane, rocuronium, and either fentanyl or sufentanil to maintain vital signs within 20% of baseline values. Opioids administered in prophylaxis of extubation cough were proscribed. A standardized "no touch" emergence technique was used. A blinded assessor noted any cough above 0.2 minimum alveolar concentration (MAC) of expired desflurane. At 0.2 MAC, once every 30 seconds, the patient was instructed to open his eyes and extubation occurred once a directed response was noted. RESULTS: A total of 213 patients were randomized and 100 patients in each group completed the experimental protocol. The incidence of extubation cough in group AL was 12%, significantly lower (1-sided P = .045) than the 22% incidence in group S. The 1-tailed risk ratio for cough in group AL was 0.55 (0–0.94, P = .045). Total amount of opioids administered (P = .194), ETT cuff preloading times (P = .259), and extubation times (P = .331) were not significantly different between groups. The average duration of surgery was 59 ± 28 minutes in group AL and 52 ± 29 minutes in group S (P = .057). CONCLUSIONS: Alkalinized lidocaine in the ETT cuff significantly decreased general anesthesia emergence cough after surgeries with an average duration of slightly

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The Science of Local Anesthesia: Basic Research, Clinical Application, and Future Directions

Local anesthetics have been used clinically for more than a century, but new insights into their mechanisms of action and their interaction with biological systems continue to surprise researchers and clinicians alike. Next to their classic action on voltage-gated sodium channels, local anesthetics interact with calcium, potassium, and hyperpolarization-gated ion channels, ligand-gated channels, and G protein–coupled receptors. They activate numerous downstream pathways in neurons, and affect the structure and function of many types of membranes. Local anesthetics must traverse several tissue barriers to reach their site of action on neuronal membranes. In particular, the perineurium is a major rate-limiting step. Allergy to local anesthetics is rare, while the variation in individual patient's response to local anesthetics is probably larger than previously assumed. Several adjuncts are available to prolong sensory block, but these typically also prolong motor block. The 2 main research avenues being followed to improve action of local anesthetics are to prolong duration of block, by slow-release formulations and on-demand release, and to develop compounds and combinations that elicit a nociception-selective blockade. Accepted for publication October 16, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Markus W. Hollmann, MD, PhD, Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Address e-mail to m.w.hollmann@amc.uva.nl. © 2017 International Anesthesia Research Society

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Improvement of the Elevated Tryptase Criterion to Discriminate IgE- From Non–IgE-Mediated Allergic Reactions

BACKGROUND: Differentiating between immunoglobulin E (IgE)-dependent and IgE-independent hypersensitivity reactions may improve the etiologic orientation and clinical management of patients with allergic reactions in the anesthesia setting. Serum tryptase levels may be useful to discriminate the immune mechanism of allergic reactions, but the diagnostic accuracy and optimal cutpoint remain unclear. We aimed to compare the diagnostic accuracy of tryptase during reaction (TDR) alone and the TDR/basal tryptase (TDR/BT) ratio for discriminating IgE- from non–IgE-mediated allergic reactions, and to estimate the best cut point for these indicators. METHODS: We included 111 patients (45% men; aged 3–99 years) who had experienced an allergic reaction, even though the allergic reaction could be nonanaphylactic. Allergy tests were performed to classify the reaction as an IgE- or non–IgE-mediated one. The area under the curve (AUC) of the receiver operating characteristic analysis was performed to estimate the discriminative ability of TDR and TDR/BT ratio. RESULTS: An IgE-mediated reaction was diagnosed in 49.5% of patients, of whom 56% met anaphylaxis criteria. The median (quartiles) TDR for the IgE-mediated reactions was 8.0 (4.9–19.6) and 5.1 (3.5–8.1) for the non–IgE-mediated (P = .022). The median (quartiles) TDR/BT ratio was 2.7 (1.7–4.5) in IgE-mediated and 1.1 (1.0–1.6) in non–IgE-mediated reactions (P

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Anesthesia Medication Handling Needs a New Vision

No abstract available

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Effects of Increasing Airway Pressures on the Pressure of the Endotracheal Tube Cuff During Pelvic Laparoscopic Surgery

BACKGROUND: Tracheal tube cuff pressures exceeding the perfusion pressures of the tracheal mucosa have been associated with complications such as sore throat, tracheal mucosa ulcers, tracheal rupture, and subglottic stenosis. Despite appropriate inflation, many factors can increase the tracheal cuff pressure during mechanical ventilation. This prospective observational cohort study was designed to test the hypothesis that during a clinical model of decreasing respiratory compliance, the pressure within the endotracheal tube cuff will rise in direct relationship to increases in the airway pressures. METHODS: Twenty-eight adult obese patients (BMI ≥30 kg/m2) scheduled for elective laparoscopic gynecologic procedures were enrolled. All patients received general anesthesia utilizing endotracheal tubes with low-pressure high-volume cuffs. After baseline adjustment of the cuff pressure to 25 cm H2O, the airway pressures and endotracheal cuff pressures were continuously measured using pressure transducers connected to the anesthesia circuit and cuff pilot, respectively. Data on cuff and airway pressures, mechanical ventilation parameters, intraabdominal pressures, and degree of surgical table inclination were collected throughout the anesthetic procedure. General linear regression models with fixed and random effects were fit to assess the effect of increases in airway pressures on cuff pressure, after adjusting for covariates and the clustered structure of the data. RESULTS: The mean (standard deviation) age and body mass index were 42.2 (8.8) years and 37.7 (5.1) kg/m2, respectively. After tracheal intubation, the cuffs were overinflated (ie, intracuff pressures >30 cm H2O) in 89% of patients. The cuff pressures significantly changed after concomitant variations in the airway pressures from a mean (standard error) value of 29.6 (1.30) cm H2O before peritoneal insufflations, to 35.6 (0.68) cm H2O after peritoneal insufflation, and to 27.8 (0.79) cm H2O after peritoneal deflation (P

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Epidural Space Identification With Loss of Resistance Technique for Epidural Analgesia During Labor: A Randomized Controlled Study Using Air or Saline—New Arguments for an Old Controversy

BACKGROUND: The best technique to identify the epidural space for labor analgesia is still unclear despite the publication of various randomized controlled studies and meta-analyses. Our aim was to assess the superiority of the saline loss of resistance (SLOR) technique over the air loss of resistance (ALOR) technique with respect to the quality of the block. METHODS: Consenting parturients admitted to our obstetric suite for spontaneous or induced labor were randomized to receive epidural analgesia using either the ALOR or SLOR technique. Our primary outcome was to compare the impact of the SLOR and ALOR technique on pain score improvement measured 30 minutes after administration of epidural block. Our secondary outcomes included the density of motor blockade and analgesic efficacy measured at 30 minutes. Primary and secondary outcomes were compared using the Student t test and Mann-Whitney U test. Statistical significance was set at P

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Craniofacial Reconstruction by a Cost-Efficient Template-Based Process Using 3D Printing

Summary: Craniofacial defects often result in aesthetic and functional deficits, which affect the patient's psyche and wellbeing. Patient-specific implants remain the optimal solution, but their use is limited or impractical due to their high costs. This article describes a fast and cost-efficient workflow of in-house manufactured patient-specific implants for craniofacial reconstruction and cranioplasty. As a proof of concept, we present a case of reconstruction of a craniofacial defect with involvement of the supraorbital rim. The following hybrid manufacturing process combines additive manufacturing with silicone molding and an intraoperative, manual fabrication process. A computer-aided design template is 3D printed from thermoplastics by a fused deposition modeling 3D printer and then silicone molded manually. After sterilization of the patient-specific mold, it is used intraoperatively to produce an implant from polymethylmethacrylate. Due to the combination of these 2 straightforward processes, the procedure can be kept very simple, and no advanced equipment is needed, resulting in minimal financial expenses. The whole fabrication of the mold is performed within approximately 2 hours depending on the template's size and volume. This reliable technique is easy to adopt and suitable for every health facility, especially those with limited financial resources in less privileged countries, enabling many more patients to profit from patient-specific treatment. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Published online 17 November 2017. Received for publication July 19, 2017; accepted October 3, 2017. Drs. Jaquiéry and Thieringer contributed equally to this work. Presented at the 31st Annual Conference of the Swiss Society of Oral and Maxillo-Facial Surgery (SSOMFS) 2016, Solothurn, Switzerland. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors. Bilal Msallem, MD, DMD, Clinic for Oral and Cranio-Maxillofacial Surgery, University Hospital of Basel Spitalstrasse 21 4031 Basel, Switzerland, E-mail: bilal.msallem@usb.ch Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Vascular Occlusion in a Porcine Flap Model: Effects on Blood Cell Concentration and Oxygenation

Background: Venous congestion in skin flaps is difficult to detect. This study evaluated the ability of tissue viability imaging (TiVi) to measure changes in the concentration of red blood cells (CRBC), oxygenation, and heterogeneity during vascular provocations in a porcine fasciocutaneous flap model. Methods: In 5 pigs, cranial gluteal artery perforator flaps were raised (8 flaps in 5 pigs). The arterial and venous blood flow was monitored with ultrasonic flow probes. CRBC, tissue oxygenation, and heterogeneity in the skin were monitored with TiVi during baseline, 50% and 100% venous occlusion, recovery, 100% arterial occlusion and final recovery, thereby simulating venous and arterial occlusion of a free fasciocutaneous flap. A laser Doppler probe was used as a reference for microvascular perfusion in the flap. Results: During partial and complete venous occlusion, increases in CRBC were seen in different regions of the flap. They were more pronounced in the distal part. During complete arterial occlusion, CRBC decreased in all but the most distal parts of the flap. There were also increases in tissue oxygenation and heterogeneity during venous occlusion. Conclusions: TiVi measures regional changes in CRBC in the skin of the flap during arterial and venous occlusion, as well as an increase in oxygenated hemoglobin during venous occlusion that may be the result of reduced metabolism and impaired delivery of oxygen to the tissue. TiVi may provide a promising method for measuring flap viability because it is hand-held, easy to-use, and provides spatial information on venous congestion. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Published online 17 November 2017. Received for publication April 19, 2017; accepted August 23, 2017. Supported by the county council of Östergötland. Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors. Max Bergkvist, MD, Department of Clinical and Experimental Medicine, Linköping University, 58185 Linköping, Sweden, E-mail: max.bergkvist@regionostergotland.se Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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ASCT2 defined by enzyme-mediated activation of radical sources enhances malignancy of GD2-plus small cell lung cancer

Abstract

Ganglioside GD2 is specifically expressed in small cell lung cancer (SCLC) cells, leading to enhancement of malignant phenotypes, such as cell proliferation and migration. However, how GD2 promotes malignant phenotypes in SCLC cells is not well known. In this study, to reveal mechanisms by which GD2 increases malignant phenotypes in SCLC cells, we performed enzyme-mediated activation of radical sources combined with mass spectrometry in GD2 positive (+) SCLC cells. Consequently, we identified ASC amino-acid transporter 2 (ASCT2), a major glutamine transporter, which coordinately works with GD2. We showed that ASCT2 was highly expressed in glycolipid-enriched microdomain/rafts in GD2(+) SCLC cells, and co-localized with GD2 in proximity ligation assay and immunocytostaining, and bound with GD2 in immuneoprecipitation/TLC-immunostaining. Malignant phenotypes of GD2(+) SCLC cells were enhanced via glutamine uptake, and were suppressed by L-γ-glutamyl-p-nitroanilide, a specific inhibitor of ASCT2, via reduced phosphorylation of p70 S6K1 and S6. These results suggested that ASCT2 enhances glutamine uptake in GEM/rafts in GD2(+) SCLC cells, leading to the enhancement of cell proliferation and migration through increased phosphorylation of mTORC1 signaling axis.

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Detection of CTCs in cervical cancer using a conditionally replicative adenovirus targeting telomerase-positive cells

Abstract

Circulating tumor cells (CTCs) are newly discovered biomarkers of cancers. Although many systems detect CTCs, a gold standard has not yet been established. We analyzed CTCs in uterine cervical cancer patients using an advanced version of conditionally replicative adenovirus targeting telomerase-positive cells, which was enabled to infect coxsackievirus-adenovirus receptor-negative cells and to reduce false-positive signals in myeloid cells. Blood samples from cervical cancer patients were hemolyzed and infected with the virus and then labeled with fluorescent anti-CD45 and anti-pan cytokeratin antibodies. GFP (+)/CD45 (−) cells were isolated and subjected to whole-genome amplification followed by polymerase chain reaction analysis of human papillomavirus (HPV) DNA. CTCs were detected in 6 of 23 patients with cervical cancers (26.0%). The expression of CTCs did not correlate with the stage of cancer or other clinicopathological factors. In 5 of the 6 CTC-positive cases, the same subtype of HPV DNA as that of the corresponding primary lesion was detected, indicating that the CTCs originated from HPV-infected cancer cells. These CTCs were all negative for cytokeratins. The CTCs detected by our system were genetically confirmed. CTCs derived from uterine cervical cancers had lost epithelial characteristics, indicating that epithelial marker-dependent systems do not have the capacity to detect these cells in cervical cancer patients.

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Clinical significance of disease-specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma

Abstract

Recent sequencing studies demonstrated the MYD88 L265P mutation in more than 70% of primary central nervous system lymphomas (PCNSL), and the clinical significance of this mutation has been proposed as diagnostic and prognostic markers in PCNSL. On the other hand, mutational analyses using cell-free DNAs have been reported in a variety of systemic lymphomas. To investigate how sensitively the MYD88 L265P mutation can be identified in cell-free DNA from PCNSL patients, we performed droplet digital PCR (ddPCR) and targeted deep sequencing (TDS) in consecutive 14 PCNSL patients from whom paired tumor-derived DNA and cell-free DNA was available at diagnosis. The MYD88 L265P mutation was found in tumor-derived DNA from all 14 patients (14/14, 100%). In contrast, among 14 cell-free DNAs evaluated by ddPCR (14/14) and TDS (13/14), MYD88 L265P mutation was detected in eight out of 14 (ddPCR) and 0 out of 13 (TDS) samples, implying dependence on the detection method. After chemotherapy, the MYD88 L265P mutation in cell-free DNAs was traced in five patients; unexpectedly, the mutations disappeared after the chemotherapy was given, and they remained undetectable in all patients. These observations suggest that ddPCR can sensitively detect the MYD88 L265P mutation in cell-free DNA and could be used as non-invasive diagnostics, but may not be applicable for monitoring minimal residual diseases in PCNSL.

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Prospective evaluation of a nonsurgical device for rhinoplasty.

Prospective evaluation of a nonsurgical device for rhinoplasty.

Rhinology. 2017 Nov 18;:

Authors: Deggeller MA, Holzmann D, Soyka MB

Abstract
BACKGROUND: Rhinoplasty represents one of the most challenging and frequently performed procedures in plastic surgery and non-surgical rhinoplasty is rarely considered. The aim of this study was to investigate whether the Nasella Nose Former (NNF), a newly developed non-surgical rhinoplasty device, could improve objective and subjective results following surgical rhinoplasty and even correct the shape of the nose without any surgery at all.
METHODOLOGY: In this prospective, monocentric, two-armed, non-blinded randomized, controlled clinical trial, a total of 43 participants were included. In the Surgical group, 22 patients undergoing open or closed rhinoplasty with osteotomies were randomised based on their birth year; 15 of them got to wear the NNF over 8 weeks postoperatively and 7 patients getting surgery without the NNF formed the control group. In the Cosmetic group, 21 participants wore the NNF without surgery over 14 months. At every follow-up exam, angles for crookedness, nasal hump and width were measured, the investigator assessed the patients nose and asked for patient satisfaction using a Likert-scale.
RESULTS: Patients in the Surgical group wearing the NNF did not show any significant difference concerning objective measurements, investigator assessments and patient satisfaction compared to those not wearing the NNF. In the Cosmetic group, participants did not show objective improvements in measurements and investigator assessment. However, participants were significantly more satisfied after 14 months with their nasal back, nasal axis and outer nose in general.
CONCLUSIONS: Considering the results of this study, we conclude that this perfectly customised external device to enhance surgical rhinoplasty outcomes or correct the shape of the nose without surgery does not seem to be effective and that further investigations in this field are not meaningful.

PMID: 29150922 [PubMed - as supplied by publisher]

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