New-onset refractory status epilepticus (NORSE) and febrile infection–related epilepsy syndrome (FIRES): State of the art and perspectives

Summary

We report the proceedings of the First International new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) Symposium. To promote awareness of this condition and foster research efforts, we conveyed the First International new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) Symposium. The conference was supported by The NORSE Institute (http://www.norseinstitute.org). This article summarizes the discussions that were held during the Symposium and presents our strategy to unravel the cause of these disorders and to improve patient care. The standardized definitions for these disorders that have been developed, are required to improve communication and facilitate the development of multicenter registries and biobanks. A distinction between childhood- and adult-onset forms of the syndrome is not supported by strong scientific evidence and it is argued that both should be studied together. Although the pathophysiology remains elusive, nascent evidence suggests a role for a postinfectious cytokine-mediated mechanism, which should be further investigated. It also appears important to develop tools for their early recognition and prompt treatment. Recent evidence suggests that specific electroencephalography (EEG) features might be helpful. The optimal treatment options remain to be determined; immune therapies are usually disappointing, but the ketogenic diet has proved effective in uncontrolled trials. NORSE and FIRES represent a very delicate clinical situation with specific communication issues between physicians and with patients and families. Standardized consensus definitions and a multidisciplinary multicenter strategy will help research efforts and improve clinical care for patients with NORSE and FIRES.

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Neural Mechanisms of Swallowing Dysfunction and Apraxia of Speech in Acute Stroke

Abstract

Speech and swallowing utilize overlapping anatomy and are thus inherently related processes. We sought to identify common neural mechanisms between risk of swallowing dysfunction and apraxia of speech (AOS). This was a retrospective analysis using data from a prospectively collected cohort. Left hemisphere stroke patients (68 subjects) tested with the Apraxia Battery for Adults II, a swallow screen, and MRI were included in the study. Main outcome measure was the presence of AOS or aspiration risk after stroke. We identified a significant association between AOS measures and increased aspiration risk (defined by failed swallow screen; p = 0.04; OR 5.2). Lesions in pars opercularis of Broca's area (BA 44) were associated with both AOS (p = 0.044; OR 9.7) and increased aspiration risk (p = 0.04; OR 5) but deficits rarely co-occurred in the same cases. Lesions in left premotor cortex (BA 6) were not significantly associated with increased aspiration risk (p = 0.06; OR 3.3) but were significantly associated with AOS (p = 0.008; OR 7). Impaired swallowing function was also associated with lesions in Wernicke's area (BA 22; p = 0.05; OR 3.5) and pars triangularis (BA 45; p = 0.02; OR 6.8). AOS and risk of aspiration are associated in patients with acute left hemisphere stroke. Acute infarct in the pars opercularis of Broca's area is associated with both deficits, though they rarely co-occur in the same individual. The co-occurrence of AOS and risk of aspiration likely reflects dependence on closely related neural structures.

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Neural Mechanisms of Swallowing Dysfunction and Apraxia of Speech in Acute Stroke

Abstract

Speech and swallowing utilize overlapping anatomy and are thus inherently related processes. We sought to identify common neural mechanisms between risk of swallowing dysfunction and apraxia of speech (AOS). This was a retrospective analysis using data from a prospectively collected cohort. Left hemisphere stroke patients (68 subjects) tested with the Apraxia Battery for Adults II, a swallow screen, and MRI were included in the study. Main outcome measure was the presence of AOS or aspiration risk after stroke. We identified a significant association between AOS measures and increased aspiration risk (defined by failed swallow screen; p = 0.04; OR 5.2). Lesions in pars opercularis of Broca's area (BA 44) were associated with both AOS (p = 0.044; OR 9.7) and increased aspiration risk (p = 0.04; OR 5) but deficits rarely co-occurred in the same cases. Lesions in left premotor cortex (BA 6) were not significantly associated with increased aspiration risk (p = 0.06; OR 3.3) but were significantly associated with AOS (p = 0.008; OR 7). Impaired swallowing function was also associated with lesions in Wernicke's area (BA 22; p = 0.05; OR 3.5) and pars triangularis (BA 45; p = 0.02; OR 6.8). AOS and risk of aspiration are associated in patients with acute left hemisphere stroke. Acute infarct in the pars opercularis of Broca's area is associated with both deficits, though they rarely co-occur in the same individual. The co-occurrence of AOS and risk of aspiration likely reflects dependence on closely related neural structures.

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Inspissated cyst fluid in endoscopic ultrasound-guided fine needle aspiration of pancreatic cysts

Background

Inspissated cyst fluid may be identified on pancreatic cyst aspiration cytology. We report on the cytomorphologic characteristics of inspissated cyst fluid on EUS-FNA of pancreatic cysts and correlate this finding with histopathology or multimodal (cytology, cyst fluid analysis, molecular pathology, imaging) classification of cyst type.

Methods

The department archives were searched for pancreatic cyst fine-needle aspiration biopsies that contained dessicated, crystalline or inspissated material on cytologic preparations.

Results

Twenty-eight cases of pancreatic cysts containing inspissated material were identified. The cytomorphology of the inspissated material ranged from fibrillary fan-like structure (54%), ball-like structures (57%), and granular material (43%). When present, the fibrillary inspissated material was associated with neoplastic mucinous cysts in 11/15 (73%) cases, but was also seen in 2 pseudocysts, 1 serous cystadenoma, and 1 cyst of uncertain type (suggestive of mucinous cyst on EUS). The presence of fibrillary inspissated cyst material on cytology had a positive predictive value of 79% and a specificity of 63% for a neoplastic mucinous cyst.

Conclusion

Although not highly specific, the presence of inspissated cyst fluid with fibrillary architecture should be recognized by cytopathologists and interpreted as at least "atypical" given the potential association with neoplastic mucinous cysts of the pancreas.

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Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer

Background

Pembrolizumab was recently approved as a first line agent for metastatic NSCLC in patients with high programmed death-ligand 1 (PD-L1) expression.

Objectives

Since a significant portion of lung cancer is diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS TBNA); there is a need for PD-L1 testing in these specimens. However, to date few studies have evaluated performance of cytology specimens from EBUS TBNA for PD-L1 analysis.

Methods

Patients who had a diagnosis of NSCLC and in whom ancillary testing, i.e., next generation sequencing (NGS), anaplastic lymphoma kinase (ALK), and PD-L1 expression was requested between January and May 2017 were reviewed.

Results

Fifty of the 112 patients reviewed had the diagnosis of NSCLC for which ancillary testing was requested. Twelve patients (24%) had squamous cell carcinoma, twenty-seven had adenocarcinoma (54%), five had NSCLC favor adenocarcinoma (10%), two had NSCLC favor squamous cell cancer (4%), and four had NSCLC not otherwise specified (NOS) (8%). Size of the lymph nodes or lesion sampled ranged from 10 to 50 mm. Four (8%) patients had insufficient number of tumor cells in the cell block for any of the ancillary molecular testing. Forty-one (82%) patients had an adequate sample for all three ancillary tests. Satisfactory results for PD-L1 expression for all cases was 86% with 14 (32%) patients having levels of PD-L1 expression >50%.

Conclusion

EBUS TBNA is effective and has a high proportion of satisfactory results for testing PD-L1 expression on tumor cells in addition to NGS and ALK FISH.

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Variability of articulator positions and formants across nine English vowels

Publication date: May 2018
Source:Journal of Phonetics, Volume 68
Author(s): D.H. Whalen, Wei-Rong Chen, Mark K. Tiede, Hosung Nam
Speech, though communicative, is quite variable both in articulation and acoustics, and it has often been claimed that articulation is more variable. Here we compared variability in articulation and acoustics for 32 speakers in the X-ray microbeam database (XRMB; Westbury, 1994). Variability in tongue, lip and jaw positions for nine English vowels (/u, ʊ, æ, ɑ, ʌ, ɔ, ɛ, ɪ, i/) was compared to that of the corresponding formant values. The domains were made comparable by creating three-dimensional spaces for each: the first three principal components from an analysis of a 14-dimensional space for articulation, and an F1xF2xF3 space for acoustics. More variability occurred in the articulation than the acoustics for half of the speakers, while the reverse was true for the other half. Individual tokens were further from the articulatory median than the acoustic median for 40–60% of tokens across speakers. A separate analysis of three non-low front vowels (/ɛ, ɪ, i/, for which the XRMB system provides the most direct articulatory evidence) did not differ from the omnibus analysis. Speakers tended to be either more or less variable consistently across vowels. Across speakers, there was a positive correlation between articulatory and acoustic variability, both for all vowels and for just the three non-low front vowels. Although the XRMB is an incomplete representation of articulation, it nonetheless provides data for direct comparisons between articulatory and acoustic variability that have not been reported previously. The results indicate that articulation is not more variable than acoustics, that speakers had relatively consistent variability across vowels, and that articulatory and acoustic variability were related for the vowels themselves.



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Letter to the editor

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Does orthodontic treatment have a permanent effect on tooth color?

Abstract

Objectives

Aim of this systematic review was to assess the effect of orthodontic treatment with fixed appliances on the tooth color of patients.

Methods

Nine databases were searched up to May 2017 for clinical cohort studies on the effect of fixed appliance treatment on tooth color. After elimination of duplicate studies, data extraction, and risk of bias assessment according to the Cochrane guidelines, random effects meta-analyses of mean differences (MD) or means and their 95% confidence intervals (CIs) were performed, followed by GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment of the quality of evidence.

Results

Three nonrandomized and one randomized study with a total of 138 patients (46% male, 54% female) with average age of 15.7 years were included. Tooth color of treated patients was significantly altered during or after orthodontic treatment (4 studies; average of 3.2 ∆E units; 95% CI = 2.0–4.4 ∆E units), which was more than the variation among controls (1 study; MD = 1.9 ∆E units; 95% CI = 1.7–2.2 ∆E units). However, the quality of evidence was very low, due to the inclusion of nonrandomized studies, bias, and imprecision. Re-analysis of raw study data indicated that significant differences in clinically discernable treatment-induced color changes were seen between chemically and light-cured adhesives and among the various tooth categories.

Conclusion

Existing evidence of very low quality indicates that orthodontic treatment might be associated with alterations of tooth color, which are however not consistently clinically discernible. Treatment-induced color alterations might be dependent on bonding material and tooth type, but evidence supporting this is weak.

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Dentoalveolar characteristics in children with juvenile idiopathic arthritis

Abstract

Purpose

Juvenile idiopathic arthritis (JIA) is an autoimmune disease with multiple potential causal factors. In case of temporomandibular joint (TMJ) affection, the inflammatory reaction can result in restricted mandibular growth with implied skeletal and facial deformities. Aim of the present study was to examine dentoalveolar and occlusion characteristics in children with JIA.

Patients and methods

The sample consisted of 66 children (27 boys, 39 girls) with JIA. Thirty-three of them showed unilateral or bilateral condylar destruction, while the other half did not manifest any TMJ involvement. Corresponding dental casts of these patients were evaluated and Angle classification, overjet, overbite, crossbite, crowding, and ectopic teeth were registered. All dental casts were subsequently scanned and digitized to analyze 26 additional variables. Subgroups according to sex and condylar affection were formed. Statistical analysis was performed using Fisher's least significant difference (LSD) post hoc test of analysis of variance (ANOVA).

Results

The prevalence of Class II, division 1 malocclusion in this JIA sample was high (28.8%). Compared to girls, boys had significantly greater dental arch widths and lengths. The group with bilateral condylar affection had significantly decreased lower arch length and increased irregularity index (p < 0.035) compared to the non-affected group.

Conclusions

Bilateral condylar involvement in children with JIA seems to reduce the lower arch length, while increasing the irregularity index of the lower front teeth.

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Long-term effects of Class II orthodontic treatment on oral health

Abstract

Aim

To investigate the long-term (≥15 years) benefit of orthodontic Class II treatment (Tx) on oral health (OH).

Subjects and methods

All patients (Department of Orthodontics, University of Giessen, Giessen, Germany) who underwent Class II correction (Herbst-multibracket Tx, end of active Tx ≥ 15 years ago) and agreed to participate in a recall (clinical examination, interview, impressions, and photographs) were included. Records after active Tx were used to assess the long-term OH effects. Data were compared to corresponding population-representative age-cohorts as well as to untreated Class I controls without orthodontic Tx need during adolescence.

Results

Of 152 treated Class II patients, 75 could be located and agreed to participate at 33.7 ± 3.0 years of age (pre-Tx age: 14.0 ± 2.7 years). The majority (70.8%) were fully satisfied with their teeth and with their masticatory system. The Decayed, Missing, Filled Teeth Index (DMFT) was 7.1 ± 4.8 and, thus, almost identical to that of the untreated Class I controls (7.9 ± 3.6). In contrast, the DMFT in the population-representative age-cohort was 56% higher. The determined mean Community Periodontal Index (CPI) maximum score (1.6 ± 0.6) was also comparable to the untreated Class I controls (1.7 ± 0.9) but in the corresponding population-representative age-cohort it was 19–44% higher. The extent of lower incisor gingival recessions did not differ significantly between the treated Class II participants and the untreated Class I controls (0.1 ± 0.2 vs. 0.0 ± 0.1 mm).

Conclusion

Patients with orthodontically treated severe Class II malocclusions had a lower risk for oral health impairment than the general population. The risk corresponded to that of untreated Class I controls (without orthodontic Tx need during adolescence).

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Insertion torque values and success rates for paramedian insertion of orthodontic mini-implants

Abstract

Objectives

Orthodontic mini-implants (OMIs) are a reliable method to provide temporary orthodontic anchorage. We hypothesized that there is an optimal insertion torque (<10 Ncm) that can be used to ensure the success of self-drilling OMIs in the paramedian region.

Patients and methods

Included were 40 (26 females, 14 males) consecutive patients requiring palatal skeletal anchorage. Mean age was 17.3 years (range 11.0–44.6 years) for female patients and 15.7 years (range 10.6–36.9 years) for male patients. A total of 22 patients received a Beneslider according to Wilmes for the distalization of maxillary first molars, 10 patients received a Mesialslider for the mesialization of maxillary first molars, and 8 patients received a bone-borne rapid palatal expansion (RPE) appliance. Torque values of 10–15 Ncm were recorded in 46.3% of the OMIs and 15–20 Ncm in 35% of OMIs. OMIs that endured the orthodontic force applied for ≥6 months were considered as success.

Results

The overall success rate was 98.8%. No significant differences were found between insertion torque values with respect to the right and left sides, Jarabak's ratio, facial axis, and Frankfort to mandibular plane angle. There were no significant differences in the OMIs insertion torques with regard to the different appliances. No association was found between insertion torque and vertical skeletal morphology.

Conclusion

With an overall success rate of 98.8%, the study hypothesis that greater insertion torque (>10 Ncm) will decrease the success rate and increase palatal OMI failure was rejected.

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Mandibular fossa morphology during therapy with a fixed functional orthodontic appliance

Abstract

Objective

During therapy of distoclusion entailing a rigid, fixed orthodontic appliance, the mandibular fossa and condyle are ideally remodeled, while dentoalveolar effects occur through adaptive mechanisms. Adaptive processes, especially in the fossa region, have not been adequately investigated. Our magnetic resonance imaging (MRI) investigation aimed to assess the effects of therapy with a functional mandibular advancer (FMA) on mandibular fossa morphology.

Patients and methods

We monitored via MRI the therapeutic course of 25 patients at three time points. Visual findings and metric assessments were carried out in the sagittal plane. Three-dimensional (3D) reconstructions of the joint structure of two exemplary patients were also made.

Results

Visual examinations of the MRI slices at the three time points revealed no changes in fossa shape in any of the 50 temporomandibular joints. Lateral comparisons showed that the morphology of the fossae of all 25 patients was identical. Metric analysis demonstrated no significant alterations in width, depth, or in their ratio, not even laterally. Nine measurements of the distances between the porion, mandibular fossa, and articular eminence revealed no significant changes in total or on the left and right sides, or intralaterally.

Conclusion

The visual findings and metric analyses of parasagittal MRI slices did not indicate any morphological changes in the mandibular fossa or articular eminence in patients with distoclusion treated via a rigid, fixed orthodontic appliance. However, special reworking of the MRI data facilitated reconstruction of the surfaces of joint structures in 3D. This new method makes it possible to depict more accurately and noninvasively the adaptive mechanisms not ascertainable via metric methods and to assess them as 3D structures.

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Effect of EMD on the orthodontically induced root resorption repair process in rats

Abstract

Background

While different levels of root resorption may occur in orthodontic treatment, several preventive approaches have been reported. Nevertheless, little is known about the effect of enamel matrix derivative (EMD) on root repair during orthodontic tooth movement.

Objective

To evaluate the effect of EMD on root resorption repair following the application of orthodontic force.

Materials and methods

A force of 100 g was exerted for 14 days on the left maxillary first molars of twenty 10-week-old Sprague-Dawley rats divided into the EMD and control groups (n = 10 per group). In the EMD group, repeatedly injection of Emdogain® was administered after the appliance was removed, while phosphate-buffered saline was administered in the control group. In vivo microcomputed tomography (CT), haematoxylin and eosin (H&E) staining, and immunohistochemistry were then used to evaluate the effect of EMD on the process of root repair.

Results

In the EMD group, the observed decrease in root resorption crater volume and increase in both the bone volume fraction and trabecular thickness were significantly greater than those in the control group. H&E staining showed that the periodontal fibres were relatively regular in arrangement and that the surface of the cementum was smooth in the EMD group. Immunohistochemical analysis showed higher bone morphogenetic protein 2 (BMP-2) and bone sialoprotein (BSP) expression levels in the EMD group than in the control group. In addition, the osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) expression levels were similar in both groups.

Conclusion

EMD enhanced the repair process following orthodontically induced root resorption in rats.

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Pioglitazone and bladder cancer risk: a systematic review and meta-analysis

Abstract

Current evidence about the association between pioglitazone and bladder cancer risk remains conflict. We aimed to assess the risk of bladder cancer associated with the use of pioglitazone and identify modifiers that affect the results. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to 25 August 2016 for randomized controlled trials (RCTs) and observational studies that evaluated the association between pioglitazone and bladder cancer risk. Conventional and cumulative meta-analyses were used to calculate the odds ratio (OR) with 95% confidence interval (CI). A restricted spline regression analysis was used to examine the dose–response relationship with a generalized least-squares trend test. We included two RCTs involving 9114 patients and 20 observational studies (n = 4,846,088 individuals). An increased risk of bladder cancer in patients treated with pioglitazone versus placebo was noted from RCTs (OR, 1.84; 95%CI, 0.99 to 3.42). In observational studies, the increased risk of bladder cancer was slight but significant among ever-users of pioglitazone versus never-users (OR, 1.13; 95%CI, 1.03 to 1.25), which appeared to be both time- (P = 0.003) and dose-dependent (P = 0.05). In addition, we observed the association differed by region of studies (Europe, United States, or Asia) or source of funding (sponsored by industry or not). Current evidence suggests that pioglitazone may increase the risk of bladder cancer, possibly in a dose- and time-dependent manner. Patients with long-term and high-dose exposure to pioglitazone should be monitored regularly for signs of bladder cancer.

Current evidence about the association between pioglitazone and bladder cancer risk remains inconsistent. This meta-analysis of two randomized controlled trials and 20 observational studies showed that use of pioglitazone might increase risk of bladder cancer. Our findings suggest a close monitoring of bladder cancer in patients with long-term and high-dose exposure to pioglitazone.

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Reward Estimation for Dialogue Policy Optimisation

Publication date: Available online 24 February 2018
Source:Computer Speech & Language
Author(s): Pei-Hao Su, Milica Gašić, Steve Young
Viewing dialogue management as a reinforcement learning task enables a system to learn to act optimally by maximising a reward function. This reward function is designed to induce the system behaviour required for the target application and for goal-oriented applications, this usually means fulfilling the user's goal as efficiently as possible. However, in real-world spoken dialogue system applications, the reward is hard to measure because the user's goal is frequently known only to the user. Of course, the system can ask the user if the goal has been satisfied but this can be intrusive. Furthermore, in practice, the accuracy of the user's response has been found to be highly variable. This paper presents two approaches to tackling this problem. Firstly, a recurrent neural network is utilised as a task success predictor which is pre-trained from off-line data to estimate task success during subsequent on-line dialogue policy learning. Secondly, an on-line learning framework is described whereby a dialogue policy is jointly trained alongside a reward function modelled as a Gaussian process with active learning. This Gaussian process operates on a fixed dimension embedding which encodes each varying length dialogue. This dialogue embedding is generated in both a supervised and unsupervised fashion using different variants of a recurrent neural network. The experimental results demonstrate the effectiveness of both off-line and on-line methods. These methods enable practical on-line training of dialogue policies in real-world applications.



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Using a PCA-based Dataset Similarity Measure to Improve Cross-Corpus Emotion Recogniton

Publication date: Available online 24 February 2018
Source:Computer Speech & Language
Author(s): Ingo Siegert, Ronald Böck, Andreas Wendemuth
In emotion recognition from speech, huge amounts of training material are needed for the development of classification engines. As most current corpora do not supply enough material, a combination of different datasets is advisable. Unfortunately, data recording is done differently and various emotion elicitation and emotion annotation methods are used. Therefore, a combination of corpora is usually not possible without further effort. The manuscript's aim is to answer the question which corpora are similar enough to jointly be used as training material. A corpus similarity measure based on PCA-ranked features is presented and similar datasets are identified. To evaluate our method we used nine well-known benchmark corpora and automatically identified a sub-set of six most similar datasets. To test that the identified most similar six datasets influence the classification performance, we conducted several cross-corpora emotion recognition experiments comparing our identified six most similar datasets with other combinations. Our most similar sub-set outperforms all other combinations of corpora, the combination of all nine datasets as well as feature normalization techniques. Also influencing side-effects on the recognition rate were excluded. Finally, the predictive power of our measure is shown: increasing similarity score, expressing decreasing similarity, result in decreasing recognition rates. Thus, our similarity measure answers the question which corpora should be included into joint training.



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Functional lower lip reconstruction with the partial latissimus dorsi muscle free flap without nerve coaptation

Background

The repair of extensive lower lip defects is difficult due to the presence of both functional and esthetic requirements. This report describes functional lip repair using the partial latissimus dorsi free flap without nerve coaptation.

Methods

Reconstruction of the lower lip due to subtotal and total tissue defects was performed using latissimus dorsi free flap on twelve patients, between 2013 and 2017. The etiology was squamous cell carcinoma in six patients, malignant melanoma in one, firearm injury in three and microstomia in two. Following exposure of the lip defect, the partial latissumus dorsi muscle flap was harvested and transfered into the lower lip defect. The microvascular anastomoses was done and no nerve coaptation was performed. The muscle was covered with a skin graft taken from the thigh for mucosal and skin lining. Functional outcomes were assessed using physical examination, electromyography (EMG), electroneuromyography, cold/warm and pain sensation, two point discrimination (TPD), and Semmes Weinstein (SMW) tests.

Results

Postoperative course was uneventful for all of the flaps. Patients were followed for between fifteen months and four years (mean 28.2 months).Color match between the flap and the face and functional outcome was satisfactory. Reinnervation was detected at EMG in eleven patients undergoing surgery six months postoperatively.After 1 year, the patients demonstrated quite normal results of the test with SMW and TDP results. None of patients perceived both hot and cold sensation.

Conclusion

The technique is an alternative option in lower lip reconstruction since it provides satisfactory functional and esthetic results despite absence of any neural coaptation.

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Nivolumab in the treatment of microsatellite instability high metastatic colorectal cancer

Future Oncology, Ahead of Print.


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Lexical olfaction recruits olfactory orbitofrontal cortex in metaphorical and literal contexts

Publication date: April 2018
Source:Brain and Language, Volume 179
Author(s): Jennifer Pomp, Anne-Kathrin Bestgen, Patrick Schulze, Christina J. Müller, Francesca M.M. Citron, Boris Suchan, Lars Kuchinke
The investigation of specific lexical categories has substantially contributed to advancing our knowledge on how meaning is neurally represented. One sensory domain that has received particularly little attention is olfaction. This study aims to investigate the neural representation of lexical olfaction. In an fMRI experiment, participants read olfactory metaphors, their literal paraphrases, and literal olfactory sentences. Regions of interest were defined by a functional localizer run of odor processing. We observed activation in secondary olfactory areas during metaphorical and literal olfactory processing, thus extending previous findings to the novel source domain of olfaction. Previously reported enhanced activation in emotion-related areas due to metaphoricity could not be replicated. Finally, no primary olfactory cortex was found active during lexical olfaction processing. We suggest that this absence is due to olfactory hedonicity being crucial to understand the meaning of the current olfactory expressions. Consequently, the processing of olfactory hedonicity recruits secondary olfactory areas.



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Treatment of restless legs syndrome/Willis-Ekbom disease with the non-selective ENT1/ENT2 inhibitor dipyridamole: testing the adenosine hypothesis

Publication date: Available online 24 February 2018
Source:Sleep Medicine
Author(s): Diego Garcia-Borreguero, Xavier Guitart, Celia Garcia Malo, Irene Cano-Pumarega, Juan José Granizo, Sergi Ferré
ObjectivesRecent animal models of restless legs syndrome (RLS) suggest that brain iron deficiency is associated with a hypoadenosinergic state, with downregulation of adenosine A1 receptors (A1R) in the striatum and cortex. We hypothesized that an increase in extracellular adenosine induced by inhibitors of adenosine transporters, such as the non-selective ENT1/ENT2 inhibitor dipyridamole, would result in an improvement in RLS symptoms.MethodsIn a prospective two-month open-label, non-placebo controlled clinical trial, 15 untreated idiopathic RLS patients began treatment with 100 mg dipyridamole (with uptitration to 400 mg if necessary). Multiple Suggested Immobilization Tests and polysomnography were performed at baseline and at eight weeks. Severity was assessed at four and eight weeks using the IRLS, and the CGI scales. The primary endpoint was therapeutic response (50% improvement in IRLS total score).ResultsThirteen patients completed the study. IRLS score improved from a mean (±S.D.) of 23.4 ± 4.6 at baseline to 10.7 ± 4.5 at 8 weeks. Six out of 13 patients were full responders and four were partial responders. The mean (±S.D.) effective dose of dipyridamole at eight weeks was 281.8 ± 57.5 mg/day. Sleep variables also improved, and the mean (±S.D.) periodic leg movement index decreased from 26.7 ± 7.2 to 4.3 ± 1.9. Dipyridamole was generally well tolerated. Main side effects were abdominal cramps, diarrhea, dizziness, and flushing.ConclusionsThese preliminary results suggest that dipyridamole has significant therapeutic effects on both sensory and motor symptoms, as well as sleep. In addition, it provides evidence that hypoadenosinergic mechanisms play a central role in RLS.



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Maturation of the Coordination Between Respiration and Deglutition with and Without Recurrent Laryngeal Nerve Lesion in an Animal Model

Abstract

The timing of the occurrence of a swallow in a respiratory cycle is critical for safe swallowing, and changes with infant development. Infants with damage to the recurrent laryngeal nerve, which receives sensory information from the larynx and supplies the intrinsic muscles of the larynx, experience a significant incidence of dysphagia. Using our validated infant pig model, we determined the interaction between this nerve damage and the coordination between respiration and swallowing during postnatal development. We recorded 23 infant pigs at two ages (neonatal and older, pre-weaning) feeding on milk with barium using simultaneous high-speed videofluoroscopy and measurements of thoracic movement. With a complete linear model, we tested for changes with maturation, and whether these changes are the same in control and lesioned individuals. We found (1) the timing of swallowing and respiration coordination changes with maturation; (2) no overall effect of RLN lesion on the timing of coordination, but (3) a greater magnitude of maturational change occurs with RLN injury. We also determined that animals with no surgical intervention did not differ from animals that had surgery for marker placement and a sham procedure for nerve lesion. The coordination between respiration and swallowing changes in normal, intact individuals to provide increased airway protection prior to weaning. Further, in animals with an RLN lesion, the maturation process has a larger effect. Finally, these results suggest a high level of brainstem sensorimotor interactions with respect to these two functions.

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Maturation of the Coordination Between Respiration and Deglutition with and Without Recurrent Laryngeal Nerve Lesion in an Animal Model

Abstract

The timing of the occurrence of a swallow in a respiratory cycle is critical for safe swallowing, and changes with infant development. Infants with damage to the recurrent laryngeal nerve, which receives sensory information from the larynx and supplies the intrinsic muscles of the larynx, experience a significant incidence of dysphagia. Using our validated infant pig model, we determined the interaction between this nerve damage and the coordination between respiration and swallowing during postnatal development. We recorded 23 infant pigs at two ages (neonatal and older, pre-weaning) feeding on milk with barium using simultaneous high-speed videofluoroscopy and measurements of thoracic movement. With a complete linear model, we tested for changes with maturation, and whether these changes are the same in control and lesioned individuals. We found (1) the timing of swallowing and respiration coordination changes with maturation; (2) no overall effect of RLN lesion on the timing of coordination, but (3) a greater magnitude of maturational change occurs with RLN injury. We also determined that animals with no surgical intervention did not differ from animals that had surgery for marker placement and a sham procedure for nerve lesion. The coordination between respiration and swallowing changes in normal, intact individuals to provide increased airway protection prior to weaning. Further, in animals with an RLN lesion, the maturation process has a larger effect. Finally, these results suggest a high level of brainstem sensorimotor interactions with respect to these two functions.

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Editorial Board

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Administration of Hypoxia-Activated Prodrug Evofosfamide after Adjuvant Therapy Enhances Therapeutic Outcome and Targets Cancer-Initiating Cells in Colorectal Cancer

Purpose: Cancer-initiating cells (C-ICs) have been described in multiple cancer types, including colorectal cancer (CRC). C-ICs are defined by their capacity to self-renew, thereby driving tumor growth. C-ICs were initially thought to be static entities, however recent studies have determined these cells to be dynamic and influenced by microenvironmental cues such as hypoxia. If hypoxia drives the formation of C-ICs, then targeting hypoxia could represent a novel means to target C-ICs. Experimental Design: Patient-derived CRC xenografts were treated with evofosfamide (Evo), a hypoxia-activated prodrug (HAP), in combination with 5-Fluorouracil (5-FU) or chemoradiotherapy (5-FU and radiation; CRT). Treatment groups included both concurrent and sequential dosing regimens. Effects on the colorectal cancer-initiating cell (CC-IC) fraction were assessed by serial passage in vivo limiting dilution assays. FAZA-PET imaging was utilized as a non-invasive method to assess intratumoral hypoxia. Results: Hypoxia was sufficient to drive the formation of CC-ICs and cells surviving conventional therapy were more hypoxic and C-IC-like. Using a novel approach to combination therapy, we show that sequential treatment with 5-FU or CRT followed by Evo not only inhibits tumor growth of xenografts compared to 5-FU or CRT alone, but also significantly decreases the CC-IC fraction. Furthermore, non-invasive FAZA-PET hypoxia imaging was predictive of a tumor's response to Evo. Conclusions: Our data demonstrate a novel means to target the CC-IC fraction by adding a HAP sequentially after conventional adjuvant therapy, as well as the use of FAZA-PET as a biomarker for hypoxia to identify tumors that will benefit most from this approach.

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Introducing a New Series: Immunotherapy Facts and Hopes

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FDA Approval: Gemtuzumab ozogamicin for the treatment of adults with newly-diagnosed CD33-positive acute myeloid leukemia

On September 1, 2017, FDA granted approval for gemtuzumab ozogamicin (GO) (Mylotarg; Pfizer, Inc) in combination with daunorubicin and cytarabine (DA) and as a monotherapy for the treatment of adult patients with newly-diagnosed CD33-positive acute myeloid leukemia (AML). GO is a CD33-targeted antibody-drug conjugate joined to calicheamicin. Approval of GO combination treatment was based on a randomized trial of 271 patients with newly-diagnosed AML treated with DA with or without 3 mg/m2 fractionated GO, which resulted in an event-free survival (EFS) of 13.6 months for GO + DA and 8.8 months for DA alone (HR 0.68 [95% CI: 0.51-0.91]). Hemorrhage, prolonged thrombocytopenia, and veno-occlusive disease were serious toxicities that were more common in patients treated with GO + DA. Approval of GO monotherapy was based on a randomized trial of 237 patients with newly-diagnosed AML treated without curative intent. Median overall survival (OS) was 4.9 months with GO versus 3.6 months on best supportive care (HR 0.69, [95% CI 0.53-0.90]). Adverse events were similar on both arms. Post-approval, several studies are required including evaluation of fractionated GO pharmacokinetics, safety of combination GO in the pediatric population, of immunogenicity, and of the effects of GO on platelet function.

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Updated Results of Rituximab Pre- and Post-BEAM with or without 90Yttrium-Ibritumomab Tiuxetan during Autologous Transplant for Diffuse Large B-Cell Lymphoma

Purpose: We evaluated the effect on long-term survival of adding rituximab (R) to BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning with or without yttrium-90 ibritumomab tiuxetan (90YIT) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplant (ASCT). Experimental Design: Patients were enrolled on three consecutive phase 2 clinical trials. Patients received two doses of rituximab (375 mg/m2 and 1000 mg/m2) during mobilization of stem cells, followed by 1000 mg/m2 on days +1 and +8 after ASCT with R-BEAM or 90YIT-R-BEAM (90YIT dose of 0.4 mCi/kg) conditioning.  Results: One hundred thirteen patients were enrolled, with 73 receiving R-BEAM and 40 receiving 90YIT-R-BEAM. All patients had a prior exposure to rituximab. The median follow-up intervals for survivors were 11.8, 8.1, and 4.2 years in the three trials, respectively. The 5-year disease-free survival (DFS) rates were 62% for R-BEAM and 65% for 90YIT-R-BEAM (P =0.82). The 5-year overall survival rates were 73%, and 77%, respectively (P = 0.65). In patients with de novo DLBCL, survival outcomes of the germinal center/activated b-cell histologic subtypes were similar with 5-year OS rates (P = 0.52) and DFS rates (P = 0.64), irrespective of their time of relapse (< vs. > 1 year) after initial induction chemotherapy (P = 0.97).   Conclusions:Administering ASCT with rituximab during stem cell collection and immediately after transplantation induces long-term disease remission and abolishes the negative prognostic impact of cell-of-origin in patients with relapsed DLBCL. The addition of 90YIT does not confer a further survival benefit.

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Vitamin D-Binding Protein Enhances Epithelial Ovarian Cancer Progression by Regulating the Insulin-like Growth Factor-1/Akt Pathway and Vitamin D Receptor Transcription

Purpose: Malignant ascites of epithelial ovarian cancer (EOC) help identify prognostic biomarkers or mechanisms of tumor progression. Vitamin D-binding protein (DBP) was revealed to be upregulated in EOC ascites in our previous proteomic study. Here, we examined the role of DBP in EOC. Experimental Design: We analyzed ascites, serum, and tissue samples of patients with newly diagnosed EOC to determine the prognostic effects of DBP. We verified DBP function using orthotopic animal models and DBP regulation in ovarian cancer cell lines. Results: Elevated ascitic DBP was significantly associated with poor response to chemotherapy, short progression-free interval, increased cancer progression, and death. Ascitic DBP overexpression was an independent unfavorable biomarker for progression-free survival; DBP overexpression in cancerous tissue was significantly related to chemoresistance. In vivo and in vitro investigations demonstrated an important role for DBP in ovarian cancer progression. Orthotopic model mice inoculated with DBP-knockdown ovarian cancer cells displayed a significant reduction in tumor formation, malignant cell number, ascitic DBP levels, invasiveness, and metastasis, and increased survival compared with controls. In presence of vitamin D receptor (VDR), DBP promoted cell aggression (invasion and doubling time) via activation of the insulin-like growth factor-1/insulin-like growth factor binding protein-2/Akt axis, and induced suppression of vitamin D-responsive genes. A nuclear factor-kappa B p65-binding site in the VDR promoter was identified as a major determinant of DBP-dependent VDR promoter activation. Conclusions: This study highlights the importance of DBP in ovarian tumor progression and the potential application of DBP as a therapeutic target for EOC.

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Focal Irradiation And Systemic Transforming Growth Factor {beta} Blockade in Metastatic Breast Cancer

PURPOSE: This study examined the feasibility, efficacy (abscopal effect) and immune effects of TGFβ blockade during radiotherapy in metastatic breast cancer patients.EXPERIMENTAL DESIGN: Prospective randomized trial comparing two doses of TGFβ blocking antibody fresolimumab. Metastatic breast cancer patients with at least three distinct metastatic sites whose tumor had progressed after at least one line of therapy were randomized to receive 1 or 10 mg/kg of fresolimumab, every 3 weeks for 5 cycles, with focal radiotherapy to a metastatic site at week 1, (3 doses of 7.5 Gy), that could be repeated to a second lesion at week 7. Research bloods were drawn at baseline, week 2, 5 and 15 to isolate PBMCs, plasma and serum.RESULTS: Twenty-three patients were randomized, median age 57 (range 35 to 77). Seven grade 3/4 adverse events occurred in 5/11 patients in the 1mg/kg arm and in 2/12 patients in the 10mg/kg arm, respectively. Response was limited to 3 stable disease. At a median follow up of 12 months, 20/23 patients are deceased. Patients receiving the 10mg/kg had a significantly higher median overall survival than those receiving 1mg/kg fresolimumab dose (hazard ratio: 2.73 with 95% CI: 1.02, 7.30; p=0.039). The higher dose correlated with improved peripheral blood mononuclear cell counts and a striking boost in the CD8 central memory pool. CONCLUSIONS: TGFβ blockade during radiotherapy was feasible and well tolerated. Patients receiving the higher fresolimumab dose had a favorable systemic immune response and experienced longer median overall survival than the lower dose group.

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Acute Compartment Syndrome as a Complication of the Use of Intraoperative Neuromonitoring Needle Electrodes

Publication date: April 2018
Source:World Neurosurgery, Volume 112
Author(s): Ilyas M. Eli, Nicholas T. Gamboa, Jian Guan, Philipp Taussky
BackgroundThe use of intraoperative neurophysiologic monitoring (IOM) has become commonplace in many neurosurgical procedures as a tool to reduce the risk of complications through the early identification of reversible neurologic compromise. Although complications related to IOM itself are exceedingly rare, recognizing their clinical presentation in the postoperative neurosurgical patient is essential for the early identification and implementation of appropriate treatment.Case DescriptionThe authors present a case report of a patient who developed postoperative acute compartment syndrome in the right arm after placement of neuromonitoring needles for routine IOM during endovascular treatment of a left internal carotid artery aneurysm. Before the procedure, the patient received dual antiplatelet therapy and was noted to have a P2Y12 reaction unit value within therapeutic range. The patient had not received other anticoagulation therapy and had no family or personal history of hematologic or coagulopathic disorders. Immediately after an uncomplicated endovascular intervention, the patient began to develop symptoms of forearm swelling, tightness, and tenderness to palpation; pain with wrist flexion and extension; and paresthesias of the distal digits of the hand. She had eventual loss of a palpable radial pulse. The patient underwent emergent fasciotomies of multiple forearm compartments and had immediate return of a palpable radial pulse.ConclusionsThis case represents the first report of post-procedural compartment syndrome resulting from placement of neuromonitoring needles for routine IOM. Although it is a particularly rare complication of IOM, compartment syndrome represents a surgical emergency that carries significant morbidity if not immediately recognized and treated.



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Misclassification of Case-Control Studies in Neurosurgery and Proposed Solutions

Publication date: April 2018
Source:World Neurosurgery, Volume 112
Author(s): Ignatius Ngene Esene, Lawrence Mbuagbaw, Gilbert Dechambenoit, Wael Reda, Kazadi K. Kalangu
ObjectiveCase-control studies (CCS) and cohort studies (CS) are common research designs in neurosurgery. But the term case-control study is frequently misused in the neurosurgical literature, with many articles reported as CCS, even although their methodology does not respect the basic components of a CCS. We sought to estimate the extent of these discrepancies in neurosurgical literature, explore factors contributing to mislabeling, and shed some light on study design reporting.MethodsWe identified 31 top-ranking pure neurosurgical journals and searched them for articles reported as CCS, either in the title or in the abstract. The articles were read to determine if they really were CCS according to STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Article assessment was conducted in duplicate (agreement [κ statistics] = 99.82%).ResultsTwo hundred and twenty-four articles met our inclusion criteria, 133 of which (59.38%) correctly labeled the case-control design, whereas 91 (40.62%) misclassified this study design. Cohort studies (CS) were the most common design mislabeled as case-control studies in 76 articles (33.93%), 57 of which (25.45%) were retrospective CS. The mislabeling of CCS impairs the appropriate indexing, classification, and sorting of evidence. Mislabeling CS for CCS leads to a downgrading of evidence as CS represent the highest level of evidence for observational studies. Odds ratios instead of relative risk are reported for these studies, resulting in a distortion of the measurement of the effect size, compounded when these are summarized in systematic reviews and pooled in meta-analyses.ConclusionsMany studies reported as CCS are not true CCS. Reporting guidelines should include items that ensure that studies are labeled correctly. STROBE guidelines should be implemented in assessment of observational studies. Researchers in neurosurgery need better training in research methods and terminology. We also recommend accrued vigilance from reviewers and editors.



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Case of Spinal Osteoblastoma in Elderly: Is It Really a Young Patient's Disease?

Publication date: April 2018
Source:World Neurosurgery, Volume 112
Author(s): Pasquale Anania, Pietro Fiaschi, Paolo Merciadri, Nataniele Piol, Jean Louis Ravetti, Gianluigi Zona, Pier Filippo Sbaffi
BackgroundOsteoblastoma is a benign bone-forming tumor, sometimes locally invasive, that may involve any bone. The highest incidence is between 20 and 30 years of age, and there are no cases described in the elderly.MethodsWe report a case of an elderly patient with a lesion in the lumbar spine in which osteoblastoma diagnosis was made.ConclusionsOsteoblastoma is a rare tumor older than 50 years of age, but it should be considered in the differential diagnosis of bone lesions of the spine in adulthood and in the elderly, to avoid a delay in the treatment.



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Transnasal Transsphenoidal Elevation of Optic Chiasm in Secondary Empty Sella Syndrome Following Prolactinoma Treatment

Publication date: April 2018
Source:World Neurosurgery, Volume 112
Author(s): Mary In-Ping Huang Cobb, Rachael Mintz-Cole, Aatif M. Husain, Miles Berger, David Jang, Patrick Codd
BackgroundProlactinomas are typically treated nonsurgically with a dopamine agonist. Once the tumor shrinks, adjacent eloquent structures, such as the optic apparatus, can become skeletonized and herniate into the dilated parasellar space.Case DescriptionA 48-year-old man with a prolactin-secreting macroadenoma treated with cabergoline presented with progressive bitemporal hemianopsia. Magnetic resonance imaging showed no recurrence of disease and a stretched optic chiasm herniating into an empty sella. Elevation of the optic chiasm via a transnasal transsphenoidal approach with ALLODERM graft and septal cartilage strut was performed. The patient was discharged home the next day with significant improvement in vision; magnetic resonance imaging showed interval elevation of the optic chiasm.ConclusionsWe review secondary empty sella syndrome and discuss surgical strategies for optic chiasmapexy.



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Ultradense Middle Cerebral Artery: Specific Sign of Cerebral Lipiodol Embolization

Publication date: April 2018
Source:World Neurosurgery, Volume 112
Author(s): Mougnyan Cox, Robert Hurst, Arastoo Vossough
Cerebral lipiodol embolization is a rare but known complication of lymphatic embolization for plastic bronchitis. The classic imaging finding on a noncontrast head computed tomography is multiple small areas of hyperdensity within the cerebral hemispheres, which represent lipiodol deposition in the brain. We report a case of lipiodol deposition in the middle cerebral artery following lymphatic embolization, producing an "ultradense" vessel sign on noncontrast computed tomography.



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SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition

Doxorubicin is the preferred chemotherapeuticdrug for osteosarcoma treatment of which clinical efficacy is limited because of its chemo-resistance and cardiac toxicity. It is necessary to develop the combinati...

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Uro-oncology 2018: new horizons, new treatment options, improved patient outcomes

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Targeting angiogenesis in lung cancer

Summary

Angiogenesis inhibition is a promising way to inhibit and eradicate cancer. Many attempts have been made to use this tool for the treatment of lung cancer. Some success has been reported, and antiangiogenic drugs are actively being investigated in combination with other types of anticancer treatments.

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Antiangiogenic therapies in ovarian cancer

Summary

Antiangiogenic compounds were the first active targeted agents implemented in the treatment of ovarian cancer. Bevacizumab and tyrosine kinase inhibitors such as pazopanib, nintedanib and cediranib target the VEGF pathway, while trebananib was developed as an inhibitor of the angiopoietin pathway. All these compounds have been extensively evaluated and, in this review, we provide a structured overview of the randomized trials that have been performed in both primary and relapsed ovarian cancer. From this data, it is evident that antiangiogenic therapy has its place in ovarian cancer. If not during first-line treatment, then at least at some point for the treatment of relapsed disease. In addition, we address and summarize the trials designed to address the remaining issues related to treatment duration, continuation beyond progression and optimal combination. The future clinical development of angiogenesis inhibitors in ovarian cancer indeed looks at combinations with poly (ADP-ribose) polymerase (PARP) inhibitors, immune checkpoint inhibitors and vascular disrupting agents. Finally, an overview is given of the retrospective translational studies that were performed on the samples of the two pivotal first-line trials GOG(Gynecologic Oncology Group)-218 and ICON(International Collaborative Ovarian Neoplasm study)7, with initial evidence for the predictive value of the BRCA status, some molecular subtypes and histological assessment of microvessel density. If confirmed, these biomarkers could further improve the implementation of antiangiogenic therapy in ovarian cancer.

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Otolaryngology-Related Disorders in Underserved Populations, Otolaryngology Training and Workforce Considerations in North America

In North America, underserved and vulnerable populations experience poorer health outcomes despite greater per capita health care expenditures. Biologic, behavioral, and socioeconomic factors lead to more advanced disease presentation that may necessitate disparate treatment. Additionally, vulnerable populations are more likely to obtain care from low-volume providers, and are more likely to receive inappropriate care. Disparities in care are exacerbated by the distribution of the physician workforce and limited participation by physicians in the care of vulnerable populations. Multipronged strategies are needed to ameliorate observed disparities in care.

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Workforce Considerations, Training, and Diseases of the Asia-Pacific Region

The Asia-Pacific region has 60% of the world's population. There is a huge variability in ethnic groups, geography, diseases, and income. The otolaryngology workforce depends on the number of medical graduates, training programs, scope of practice, and available employment. Training has been influenced by the British, Russian, and US training systems, and by local influences and experience. Otolaryngologic diseases are similar to those seen in the United States but with ethnic and regional differences. There are opportunities for humanitarian service but the most sustainable projects will include repetitive visits with transfer of knowledge.

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The Pituitary-Thyroid Axis and Prolactin Secretion in Hemodialysis Patients in Two Endemic Regions of Eastern Germany

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-123184

Introduction Endocrine disorders of the pituitary axes are frequent in patients with hemodialysis (CKD5D). The aim of this multicenter study (Leipzig (L), Quedlinburg and Blankenburg in the Harz region (Hz)) in CKD5D patients was to evaluate influences of CKD5D related factors, morphological and biochemical parameters, and serum iodine and prolactin concentrations on the pituitary-thyroid axis. Patients and Methods 170 patients (L n=58; Hz n=112) were included in this prospective, non-interventional, cross-sectional study. Mann-Whitney-U-test and bivariate correlation analyses with Spearman-Rho test (r correlation coefficient) were used in statistical analysis. Results TSH was higher in patients with prolactin concentrations>370 mIU/l (p=0.013), in patients with high flux membranes (p=0.0013) and in patients with longer dialysis vintage (p=0.04). Median iodine serum concentrations were slightly elevated in the Leipzig cohort (p=0.001) and correlated with fT4 (p<0.001, r=0.43) and albumin (p=0.001, r=0.245) but not with morphological signs. Albumin was correlated with fT3 (p<0.001, r=0.339) and fT4 (p<0.001, r=0.421). Prolactin was correlated with residual excretion rate (p=0.001, r=- 0.303) and thyroid volume (p=0.027, r=0.217). Conclusions In the assessment of the thyroid status in CKD5D patients, the synopsis of the clinical and nutritional status, comorbidities, ultrasound of the thyroid gland and laboratory results is necessary for further intervention with hormone replacement. Standardized reference values of the pituitary-thyroid axis should be critically evaluated and are still lacking in CKD5D.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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A New Approach to Predict Daily pH in Rivers Based on the “à trous” Redundant Wavelet Transform Algorithm

Abstract

Prediction of pH is an important issue in managing water quality in surface waters (e.g., rivers, lakes) as well as drinking water. The capacity of artificial neural network (ANN), wavelet-artificial neural network (WANN), traditional multiple linear regression (MLR), and wavelet-multiple linear regression (WMLR) models to predict daily pH levels (1, 2, and 3 days ahead) at the Chattahoochee River gauging station (near Atlanta, GA, USA) was assessed. In the proposed WANN model, the original time series of pH and discharge (Q) were decomposed (after being split into training and testing series) into several sub-series by the the à trous (AT) wavelet transform algorithm. The wavelet coefficients were summed to obtain useful input time series for the ANN model to then develop the WANN model for pH prediction. The redundant à trous algorithm was used for data decomposition. Model implementation indicated the values of 1-day-ahead pH predicted by the WANN model closely matched the observed values (with a coefficient of determination, R² = 0.956; Root Mean Square Error, RMSE = 0.019; and Mean Absolute Error, MAE = 0.015). It is therefore possible that the WANN model's accuracy can be attributed to its better predictive ability (due to the use of the AT) to remove the noise caused by pH shifts (e.g., acid precipitation). Peak pH values predicted by the WANN model were also closer to observed values compared to the other machine learning models.

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Laser evoked potential amplitude and laser-pain rating reduction during high-frequency non-noxious somatosensory stimulation

The inhibition of pain by non-nociceptive cutaneous stimulation represents a well known phenomenon. Daily experience teaches us that rubbing a painful area can reduce pain. The underlying mechanism of the analgesia induced by non-painful somatosensory stimuli has been hypothesized by Melzack and Wall in 1965 (Melzack and Wall, 1965). According to the "gate control theory of pain", it is the balance between the small diameter (C and Aδ) and large diameter (Aβ) fibres at their entrance to the spinal cord to control pain.

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Pain-motor Integration and Chronic Pain: One Step Ahead

Pain-motor integration refers to physiological processes responsible for mutual interaction between nociceptive and motor information in the central nervous system. Two separate lines of evidence support the hypothesis that pain-motor integration mechanisms operate in the human cerebral cortex. First, epidural motor cortex stimulation (MCS), as well as non-invasive brain stimulation (NIBS) protocols delivered over the primary motor cortex (M1), can both improve pain in patients with drug-resistant chronic pain.

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Xolair®-induced recurrent anaphylaxis through sensitization to the excipient polysorbate

Omalizumab is an anti-IgE humanized IgG1 monoclonal antibody, indicated for the treatment of moderate-to-severe allergic and uncontrolled asthma. Anaphylaxis was found to occur in 0.1 to 0.2% of patients taking Xolair®, the commercialized form of omalizumab1, with no known underlying mechanism. Although it has been very difficult to develop a reliable assay to detect clinically significant anti-omalizumab IgE, a recent report suggested that Xolair®-induced anaphylaxis is not mediated by IgE sensitization to the monoclonal antibody (mAb) omalizumab itself2.

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Cow's milk-associated chronic food protein-induced enterocolitis syndrome (FPIES) exacerbated by extensively hydrolyzed formula

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy predominantly seen in infancy or early childhood. While its incidence has been steadily increasing over the past two decades, it is still often misdiagnosed due to lack of awareness.1 It presents in two forms: acute and chronic.

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Concurrent IgE-mediated NMBA-allergy in systemic mastocytosis

Mastocytosis is a rare clinical condition characterized by an abnormal increase in tissue mast cells, which can be limited to the skin (cutaneous mastocytosis) or infiltrate the bone marrow and other organs with or without skin involvement (systemic mastocytosis). Systemic mastocytosis (SM) is reported primarily in adulthood, where indolent SM is the most common form. We report an unusual case consistent with IgE-mediated neuromuscular blocking agent (NMBA) allergy evidenced in a patient with previously unsuspected mastocytosis.

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Evaporative coolers are not associated with dust mite or mold sensitization in large pediatric cohort

The primary species of house dust mites (HDM), Dermatophagoides farinae and Dermatophagoides pteronyssinus, are associated with asthma, atopic dermatitis, and allergic rhinitis1. Mold exposure is also implicated in allergic disease, most prominently with asthma2. HDM survival is dependent on a relative humidity of greater than 55-75%3, and most species of fungi grow at a relative humidity greater than 60% 4. Evaporative (or swamp) coolers (ECs) are used as a low-cost air conditioning alternative in arid and semi-arid climates.

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Relationship between traffic related air pollution particle exposure and asthma exacerbations: association or causation?

Clinicians are often asked about articles in the media proclaiming new and unexpected causes of disease. Often, these headlines are based not on randomized clinical trials but rather on associations discovered in observational studies. Most clinicians realize that a p-value less than 0.05 does not prove causation but do not necessarily know how to critically judge whether a reported association should be considered to be a true cause of the disease. In 1965, Austin Bradford Hill published "The Environment and Disease: Association or Causation?" 1.

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A case of neuropathic pain in monoclonal mast cell activation syndrome

Neuropathic pain is an uncommon symptom associated with mast cell disorders but can significantly impact quality of life. Mast cells are known to be gatekeepers of nociception and play an important role in the development of neuropathic pain in the central and peripheral nervous system1. Although musculoskeletal pain has been associated with mast cell disorders2, neuropathic pain associated with mast cell disorders and its management has not been well described in the literature. We present a patient with neuropathic pain associated with monoclonal mast cell activation syndrome (MMAS) and review the agents used in his treatment.

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Relying on allergy skin test results

We appreciate the comments related to our recent publication, "Reliability of allergy skin testing". The author writes, "Reliability (precision, repeatability) and validity (accuracy) are two completely different methodological issues". We agree that other titles such as, "Accuracy of allergy skin testing" may have fit more pedantic epidemiological definitions. However, this would not have emphasized the clinical concerns any greater. We had chosen to use the lay term for reliability as it appears in the Oxford English dictionary where it is defined as, "the degree to which the result of a measurement, calculation, or specification can be depended on to be accurate1."

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Intracholecystic papillary neoplasm of the gallbladder protruding into the common bile duct

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Treatment of restless legs syndrome/Willis-Ekbom disease with the non-selective ENT1/ENT2 inhibitor dipyridamole: testing the adenosine hypothesis

Recent animal models of restless legs syndrome (RLS) suggest that brain iron deficiency is associated with a hypoadenosinergic state, with downregulation of adenosine A1 receptors (A1R) in the striatum and cortex. We hypothesized that an increase in extracellular adenosine induced by inhibitors of adenosine transporters, such as the non-selective ENT1/ENT2 inhibitor dipyridamole, would result in an improvement in RLS symptoms.

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A Comparison of Two Stroke Cohorts Cared for by Two Different Specialties in a Practice-Based Tele-Stroke Population

Publication date: Available online 23 February 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Elias Atallah, Kimon Bekelis, Hassan Saad, Nohra Chalouhi, Sophia Dang, Jonathan Li, Ayan Kumar, Justin Turpin, Randa Barsoom, Stavropoula Tjoumakaris, David Hasan, Maureen Deprince, Giuliana LabellaRN, Robert H. Rosenwasser, Pascal Jabbour
ObjectivesNeurologists have continually led the assessment and management of Acute Ischemic Stroke(AIS) by use of IV-rtPA, anti-platelet therapy, antihypertensives, and other pharmacologic agents. Since the advent of mechanical thrombectomy(MT) and its proven efficacy, neurovascular surgeons(NS) are playing an increasingly important role in the management and overall care of AIS. We assessed outcomes of AIS patients managed by NS, who have been traditionally managed by neurologists.Patients and MethodsOutcomes of AIS patients who presented to the telestroke system, over a 5-year period, were assessed. NIHSS and mRS stroke scales were used as outcome metrics. Multivariate analysis was conducted to compare outcomes of patients treated by neurovascular surgeons and those treated by neurologists.Results1,353 AIS patients were identified. 21.6% received care from neurosurgeons and 78.4% received care from neurologists. Of the neurologist-managed group: 7.8% received MT and were followed by NS, 34% received IVrt-PA, average discharge NIHSS = 9.0 (SD = 8.42), latest follow-up mRS < 2 = 57.5% and mortality rate = 9.4%. Of the neurovascular surgeon-managed group: 7.4% patients received MT, 20% received IVrt-PA, average discharge NIHSS = 0.14(SD = 0.72), latest follow-up mRS ≤2 = 98.6% and mortality rate = 8.3%. There were no significant differences between groups in MT use (OR 1.22; CI95%, 0.971–2.09; p = 0.464), IVrt-PA administration (OR 0.98; CI95%, 0.70–1.38; p = 0.924), mortality rate (OR 1.21; 0.71–2.03; p = 0.483) and patients' latest mRS, p = 0.873.ConclusionsAIS requires multidisciplinary management. Care provided by neurosurgeons has similar efficacy and patient outcomes as the care provided by neurologists. These findings support the role and ability of neurosurgeons to manage and care for these patients.



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Wound irrigation and the lack of evidence-based-practice

Dear Editor,

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Evaluation of Surgical Strategies for Bilateral Vocal Fold Paralysis Using Excised Canine Larynges

The objective of this study was to provide a theoretical basis for the selection of optimal surgical procedures in ex vivo simulated bilateral vocal fold paralysis (BVFP).

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Allostatic load and subsequent all-cause mortality: which biological markers drive the relationship? Findings from a UK birth cohort

Abstract

The concept of allostatic load (AL) refers to the idea of a global physiological 'wear and tear' resulting from the adaptation to the environment through the stress response systems over the life span. The link between socioeconomic position (SEP) and mortality has now been established, and there is evidence that AL may capture the link between SEP and mortality. In order to quantitatively assess the role of AL on mortality, we use data from the 1958 British birth cohort including eleven year mortality in 8,113 adults. Specifically, we interrogate the hypothesis of a cumulative biological risk (allostatic load) reflecting 4 physiological systems potentially predicting future risk of death (N = 132). AL was defined using 14 biomarkers assayed in blood from a biosample collected at 44 years of age. Cox proportional hazard regression analysis revealed that higher allostatic load at 44 years old was a significant predictor of mortality 11 years later [HR = 3.56 (2.3 to 5.53)]. We found that this relationship was not solely related to early-life SEP, adverse childhood experiences and young adulthood health status, behaviours and SEP [HR = 2.57 (1.59 to 4.15)]. Regarding the ability of each physiological system and biomarkers to predict future death, our results suggest that the cumulative measure was advantageous compared to evaluating each physiological system sub-score and biomarker separately. Our findings add some evidence of a biological embodiment in response to stress which ultimately affects mortality.

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Repercusiones sociales de la disfagia

Publication date: Available online 23 February 2018
Source:Revista de Logopedia, Foniatría y Audiología
Author(s): Miguel Antonio Vargas García
ObjetivoValorar la realidad social y la percepción funcional que tienen los cuidadores principales acerca de la calidad de vida de los sujetos diagnosticados con disfagia.MétodosLa investigación se desarrolló partiendo de lineamientos de la resolución 008430 del 4 de octubre de 1993, que rige en Colombia las normas científica, técnica y administrativa para la investigación en salud. La elección de la muestra se realizó a partir del estudio de las historias clínicas y el diagnóstico de disfagia; el instrumento fue validado a través del Método Delphi, el cual busca dar confiabilidad a un instrumento a partir de la opinión de un panel de expertos.ResultadosLos cuidadores indican que el mejor dominio en la percepción de calidad de vida del sujeto con disfagia es el psicológico, sin embargo, este se encuentra por debajo del 80%, entendido como una percepción aceptable. Al analizar la individualidad, se detecta como porcentaje más bajo un 53.66% vs. el 84.15% que corresponde al más alto; el resultado promedio evidenció un 68.75% de percepción de calidad de vida, correspondiente según la propuesta de rangos de percepción, a una percepción aceptable; este valor equivale al promedio obtenido de 112.74 puntos de 164 posibles.ConclusionesDesde los aspectos terapéuticos, los profesionales no pueden olvidar al cuidador, ya que es un factor en la rehabilitación que también necesitará atención. No se puede permitir que el cuidador principal genere cansancio, estrés o despreocupación a causa de las largas cargas de trabajo en su labor de cuidar.PurposeTo assess the social reality and the functional perception that the main caregivers have about the quality of life of the subjects diagnosed with dysphagia.MethodsThe research was developed based on the guidelines of resolution 008430 of October 4, 1993, which governs the scientific, technical and administrative standards for health research in Colombia. The choice of the sample was made from the study of the clinical histories and the diagnosis of dysphagia; the instrument was validated through the Delphi method, which seeks to give reliability to an instrument based on the opinion of a panel of experts.ResultsCaregivers indicate that the best domain in the perception of quality of life of the subject with dysphagia is the psychological, but this is below 80%, understood as an acceptable perception. When analyzing the individuality, it is detected as a lower percentage 53.66%, versus 84.15% that corresponds to the highest. The average result showed a 68.75% perception of quality of life, corresponding to an acceptable perception according to the proposed ranges of perception. This value is equivalent to the average obtained of 112.74 points out of 164 possible.ConclusionsFrom the therapeutic aspects, professionals cannot forget the caregiver, since it is a factor in the rehabilitation that will also need attention. The primary caregiver cannot be allowed to create fatigue, stress, or unconcern because of the long workloads in their caring work.



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Oticon Improves Internet-Connected Hearing Aids with New ConnectClip

​Oticon (https://www.oticon.com/) has introduced ConnectClip, which turns Oticon's internet-connected hearing aids into wireless headsets for hands-free calls and listening to music or podcasts in stereo. It works with any smartphone, music player, or computer, and it serves as a remote control for Oticon's Opn hearing aids to adjust volume and change programs. Sound from mobile phones is streamed directly to the hearing aids via 2.4GHz Bluetooth Low Energy, and ConnectClip's directional microphones pick up the wearer's voice. ConnectClip can also function as a remote or partner microphone, providing improved intelligibility of the speaker wearing it at a distance of up to 65 feet, in very noisy environments, or a combination of both. ConnectClip can be paired with or connected directly to a computer's built-in Bluetooth or used with the BTD 800 USB dongle. 

Published: 2/23/2018 12:55:00 PM

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Commentary on “The Implications of Non-compliance for Endovascular Aneurysm Repair (EVAR)”

Publication date: Available online 23 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Klaas H.J. Ultee, Hence J.M. Verhagen




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Explanted Vascular and Endovascular Graft Analysis: Where Do We Stand and What Should We Do?

Publication date: Available online 23 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Anne Lejay, Benjamin Colvard, Louis Magnus, Delphine Dion, Yannick Georg, Julie Papillon, Fabien Thaveau, Bernard Geny, Lee Swanström, Fréderic Heim, Nabil Chakfé
Objective/BackgroundSince the late 1950s, major advances in vascular surgical practice have been closely associated with the introduction of novel vascular implants. These devices have been constructed from a variety of materials and have been designed to be implanted in several different ways. Despite a rigorous regulatory process, regular failures continue to be observed. A systematic review of the literature and of the Geprovas registry was performed in order to improve understanding of the failures.MethodsA systematic review was performed via a search of the MEDLINE and Embase databases. Full text, English, German, or French language studies without any chronological limit were included. The reference lists of included studies, as well as the first 20 related items, were scanned for other potentially relevant studies.ResultsData extraction allowed the evaluation of 184 publications; 72 publications met the inclusion criteria. Only 12 publications reported sufficient data for structural, histopathological, and epidemiological analysis. However, explant analysis allowed the understanding of degenerative phenomena: "warp knitted" replaced "weft knitted" polyethylene terephthalate grafts, decreasing the risk of dilatation or rupture; inter-nodal distance was modified in order to improve polytetrafluoroethylene graft incorporation capacities; and index of saturation, endograft fabric/stent interactions, and stent fatigue phenomena have been extensively studied in an attempt to improve endovascular device durability.ConclusionA general lack of depth of reporting of explants remains. Dedicated systematic explant analysis programs are the key to improving the performance of future generations of devices.



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Ten Year Mortality in Different Peripheral Arterial Disease Stages: A Population Based Observational Study on Outcome

Publication date: Available online 23 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Fredrik Sartipy, Birgitta Sigvant, Fredrik Lundin, Eric Wahlberg
ObjectiveThe aim was to determine long-term mortality rates and the underlying cause of death for subjects with different peripheral arterial disease (PAD) stages in a population based setting.MethodsA randomly selected population sample of 5080 subjects was enrolled in the study in 2004–2005. Participants completed health state questionnaires and underwent ankle brachial index (ABI) measurements for classification into PAD severity stages and reference subjects. A follow-up was conducted by the end of 2015 using data from Swedish governmental national registers for cause of death, which was then compared with PAD stage determined at baseline in 2005.ResultsThe 10 year all cause mortality was 27% for reference cases, 56% for asymptomatic PAD (APAD), 63% for intermittent claudication (IC), and 75% for severe limb ischaemia (SLI). Among all PAD subjects, cardiovascular (CV) causes were the most common main cause of death (45%) and a CV event was present as either the main or one of the three most common contributing causes of death in 64% of the cases. The age adjusted hazard ratios for a main cause of death by a CV event were 1.9 (95% CI 1.5–2.3) for APAD, 2.6 (95% CI 2.1–3.4) for IC, and 3.5 (95% CI 2.3–5.2) for SLI.ConclusionPAD subjects, including the APAD subjects, are still at high risk of CV death. The mortality risks are more than doubled in symptomatic PAD patients compared with reference subjects and increase by severity of PAD stage. Awareness and improved risk reduction management of PAD are still warranted.



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HYDration and Bicarbonate to Prevent Acute Renal Injury After Endovascular Aneurysm Repair With Suprarenal Fixation: Pilot/Feasibility Randomised Controlled Study (HYDRA Pilot Trial)

Publication date: Available online 23 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Athanasios Saratzis, Virginia Chiocchia, Ahmad Jiffry, Neelam Hassanali, Surjeet Singh, Christopher H. Imray, Matthew J. Bown, Asif Mahmood
Objective/BackgroundUp to 25% of patients undergoing elective endovascular aneurysm repair (EVAR) develop acute kidney injury (AKI), which is associated with short and long-term morbidity and mortality. There is no high quality randomised evidence regarding prevention of EVAR related AKI.MethodsA novel AKI prevention strategy for EVAR was devised, based on best evidence and an expert consensus group. This included a bolus of high dose sodium bicarbonate (NaHCO3) immediately before EVAR (1 mL/kg of 8.4% NaHCO3) and standardised crystalloid based hydration pre- and post-EVAR. A pilot/feasibility randomised controlled trial (RCT) was performed in two centres to assess the safety of the intervention, potential impact on AKI prevention, and feasibility of a national RCT; the primary end point was the proportion of eligible patients recruited into the study. AKI was defined using "Kidney Disease Improving Global Outcomes" and "Acute Kidney Injury Network" criteria based on National Institute for Health and Clinical Excellence AKI recommendations, using serum creatinine and hourly urine output.ResultsFifty-eight patients (84% of those screened; median age 75 years [range 57–89 years], 10% female) were randomised to receive the standardised intravenous hydration with (intervention) or without (control) NaHCO3. Groups were comparable in terms of AKI risk factors; 56 of 58 participants had a device with suprarenal fixation. Overall, 33% of patients in the control arm developed AKI versus 7% in the intervention arm (as treated analysis). None of the patients receiving NaHCO3 developed a serious intervention related adverse event; five patients did not attend their 30 day follow-up.ConclusionBolus high dose NaHCO3 and hydration is a promising EVAR related AKI prevention method. This trial has confirmed the feasibility of delivering a definitive large RCT to confirm the efficacy of this novel intervention, in preventing EVAR related AKI.



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An Individualised Strategy and Long-Term Outcomes of Endovascular Treatment of Budd–Chiari Syndrome Complicated by Inferior Vena Cava Thrombosis

Publication date: Available online 23 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): P.-X. Ding, X. He, X.-W. Han, Y. Zhang, Y. Wu, X.-X. Liang, C. Liu
ObjectivesThe aim was to evaluate individualised treatment and long-term outcomes of endovascular treatment of Budd–Chiari syndrome (BCS) complicated by inferior vena cava (IVC) thrombosis.MethodsBetween April 2005 and December 2015, 108 consecutive patients with BCS complicated by IVC thrombosis underwent endovascular treatment. According to the type, size, extent, and degree of organisation of the thrombus, agitation thrombolysis (n = 7), agitation thrombolysis combined with retrieval stent filter (n = 5), pre-dilation (n = 32), retrieval stent filter (n = 56), or direct large balloon dilation (n = 8) was performed. Peri- and post-operative follow-up data were recorded.ResultsThe endovascular treatment was technically successful in 107 of the 108 patients (99.1%). The incidence of thrombosis related complications was 7.4% (8/108). Major and minor complications occurred in four patients. The mean follow-up duration was 61.7 ± 39.3 months (range 3–140 months). The cumulative 1, 2, 5, and 10 year primary patency rates were 91%, 88%, 79%, and 79%, respectively, and the cumulative 1, 2, 5, and 10 year secondary patency rates were 100%, 100%, 97%, and 97%, respectively. The cumulative 1, 5, and 10 year survival rates were 95%, 86%, and 81%, respectively. Serum albumin and total bilirubin values were independent predictors of survival.ConclusionsFor patients with BCS complicated by IVC thrombosis, an individualised endovascular treatment strategy based on the type, size, extent, and degree of organisation of the thrombus is associated with long-term patency of the IVC and favourable survival and complication rates.



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To Hug or Not: Physicians Differ on What's the Right Behavior

Some physicians want to offer patients support; others say hugs have no business in the medical office. In today's environment, do doctors think hugs are appropriate?
Medscape Family Medicine

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Neural control of parental behaviors

Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49
Author(s): Johannes Kohl, Catherine Dulac
Parenting is a multicomponent social behavior that is essential for the survival of offspring in many species. Despite extensive characterization of individual brain areas involved in parental care, we do not fully understand how discrete aspects of this behavior are orchestrated at the neural circuit level. Recent progress in identifying genetically specified neuronal populations critical for parenting, and the use of genetic and viral tools for circuit-cracking now allow us to deconstruct the underlying circuitry and, thus, to elucidate how different aspects of parental care are controlled. Here we review the latest advances, outline possible organizational principles of parental circuits and discuss future challenges.



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NK-cell enteropathy: a case report with ten years of indolent clinical behavior

Abstract

NK-cell enteropathy is a recently described clinically indolent condition characterized by atypical NK-cell infiltrates in the gastrointestinal mucosa that mimics malignant lymphoma. We report the case of a 69-year-old female who clinically had long-standing abdominal pain and recurrent mucosal ulcerations associated with atypical NK-cell infiltrates. The clinical, morphologic, and immunophenotypic findings in this case were diagnostic of NK-cell enteropathy. Review of the patient's prior biopsies demonstrated that this persisted without clinical progression for ten years—confirming the clinical indolent course. Recognition of NK-cell enteropathy is important to avoid over-diagnosing this benign condition as an aggressive lymphoma.

This article is protected by copyright. All rights reserved.

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Motion and position shifts induced by the double-drift stimulus are unaffected by attentional load

Abstract

The double-drift stimulus produces a strong shift in apparent motion direction that generates large errors of perceived position. In this study, we tested the effect of attentional load on the perceptual estimates of motion direction and position for double-drift stimuli. In each trial, four objects appeared, one in each quadrant of a large screen, and they moved upward or downward on an angled trajectory. The target object whose direction or position was to be judged was either cued with a small arrow prior to object motion (low attentional load condition) or cued after the objects stopped moving and disappeared (high attentional load condition). In Experiment 1, these objects appeared 10° from the central fixation, and participants reported the perceived direction of the target's trajectory after the stimulus disappeared by adjusting the direction of an arrow at the center of the response screen. In Experiment 2, the four double-drift objects could appear between 6 ° and 14° from the central fixation, and participants reported the location of the target object after its disappearance by moving the position of a small circle on the response screen. The errors in direction and position judgments showed little effect of the attentional manipulation—similar errors were seen in both experiments whether or not the participant knew which double-drift object would be tested. This suggests that orienting endogenous attention (i.e., by only attending to one object in the precued trials) does not interact with the strength of the motion or position shifts for the double-drift stimulus.

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How to inhibit a distractor location? Statistical learning versus active, top-down suppression

Abstract

Recently, Wang and Theeuwes (Journal of Experimental Psychology: Human Perception and Performance, 44(1), 13–17, 2018a) demonstrated the role of lingering selection biases in an additional singleton search task in which the distractor singleton appeared much more often in one location than in all other locations. For this location, there was less capture and selection efficiency was reduced. It was argued that statistical learning induces plasticity within the spatial priority map such that particular locations that are high likely to contain a distractor are suppressed relative to all other locations. The current study replicated these findings regarding statistical learning (Experiment 1) and investigated whether similar effects can be obtained by cueing the distractor location in a top-down way on a trial-by-trial basis. The results show that top-down cueing of the distractor location with long (1,500 ms; Experiment 2) and short stimulus-onset symmetries (SOAs) (600 ms; Experiment 3) does not result in suppression: The amount of capture nor the efficiency of selection was affected by the cue. If anything, we found an attentional benefit (instead of the suppression) for the short SOA. We argue that through statistical learning, weights within the attentional priority map are changed such that one location containing a salient distractor is suppressed relative to all other locations. Our cueing experiments show that this effect cannot be accomplished by active, top-down suppression. Consequences for recent theories of distractor suppression are discussed.

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iSepsis – Sepsis 3.0- Flogging a dead horse!

qSOFA: Fails Once Again.

EMCrit Project by Paul Marik.

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Early toxicity and health-related quality of life results of high-dose-rate brachytherapy as monotherapy for low and intermediate-risk prostate cancer

Publication date: Available online 23 February 2018
Source:Brachytherapy
Author(s): Marc Gaudet, Mathieu Pharand-Charbonneau, Marie-Pierre Desrosiers, Debbie Wright, Alain Haddad
PurposeTo determine the acute toxicity and effect on health-related quality of life of a two-fraction regimen of high-dose-rate (HDR) prostate brachytherapy.Methods and materialsPatients with low- or intermediate-risk prostate cancer were treated with HDR brachytherapy as monotherapy in two implants of 13.5 Gy spaced 7–14 days apart. Patients completed International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC) questionnaires at 1, 3, 6, 9, 12, 16, 20, and 24 months after brachytherapy. Proportion of patients in each IPSS category (mild = 0–7, moderate = 8–18, severe = 19+) was evaluated at each of the intervals above. Paired t tests with baseline values were done for IPSS and EPIC scores.ResultsThirty patients were accrued to the study. Median prostate-specific antigen was 8,7 (range 4.1–17.5). T stages were T1c = 65%, T2a = 21%, and T2b = 14%. Twenty-seven percent of patients had a Gleason score of 6 and 73% had a Gleason score of 7. IPSS categories at baseline, 1, 3, 6, 12, and 24 months were mild (81%, 43%, 58%, 62%, 76%, 64%), moderate (19%, 32%, 29%, 30%, 20%, 29%), and severe (0%, 25%, 13%, 7%, 4%, 6%), respectively. There was a significant decrease in EPIC sexual summary scores at 1, 3, 6, and 12 months of 0 points (p < 0.001), 17 points (p = 0.01), 18 points (p = 0.02), and 17 points (p = 0.01), respectively.ConclusionsThis is the first report of this cohort of patients treated with two-fraction HDR monotherapy. This regimen shows rates of toxicity and health-related quality of life that appear acceptable as compared to other treatment modalities. These results are also comparable with other reports with similar treatment regimens.



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A Selection of Abstracts Presented at the 44th Annual Conference of the Anatomical Society of Southern Africa (ASSA), May 8–11, 2016, Bloem Spa Hotel and Conference Centre, Bloemfontein, Free State, South Africa

In memory of Professor Willie Vorster who was a long-standing member of ASSA and served on the Council for many years. He was a devoted teacher of Anatomy and Embryology at various tertiary institutions in South Africa, and the founding member of the School of Medicine at the University of Namibia where he served as the first Professor in Anatomy.

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[The innate immune system in oropharyngeal squamous cell carcinoma : Immune modulation by HPV].

Related Articles

[The innate immune system in oropharyngeal squamous cell carcinoma : Immune modulation by HPV].

HNO. 2018 Feb 15;:

Authors: Wagner S, Böckmann H, Gattenlöhner S, Klussmann JP, Wittekindt C

Abstract
Based on clinical and experimental data, oropharyngeal squamous cell carcinomas (OPSCC) associated with human papillomavirus (HPV) have been recognized as a distinct entity of head and neck cancers. However, outside of clinical trials, HPV status currently has no impact on treatment. The natural replication cycle of HPV takes place in epithelial cells, and is thus spatially separated from cytotoxic immune cells in the epidermis. Dendritic cells (Langerhans cells, LC), however, are frequent in this upper dermal layer. The ability of LC to process antigens, migrate, and, ultimately activate T cells is inhibited by the activity of the viral oncoproteins (E5-E7). Downregulation of functional human leukocyte antigen I (HLA-I) epithelial cell surface expression contributes to LC inhibition. However, due to their absence in upper skin layers, corresponding activation of natural killer (NK) cells via missing-self recognition is not relevant. Genome-wide analyses have revealed specific expression signatures for HPV-associated OPSCC that are distinct from HPV-negative cancers. Interestingly, aberrations in HLA-I genes were common in HPV-associated OPSCC. Our own findings indicate more frequent infiltration of HPV-associated OPSCC by CD56-positive (CD56+) NK cells, which might be related to HLA-I downregulation during HPV-associated carcinogenesis. In patients with OPSCC, CD56 positivity correlates with improved prognosis after conventional therapy. This could be evidence for HPV-associated OPSCC being especially eligible for novel immune-based therapies and an indication that immunological data should be included in the design of clinical trials.

PMID: 29468275 [PubMed - as supplied by publisher]

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[Selected otorhinolaryngological symptoms in functional disorders of the upper cervical spine and temporomandibular joints].

Related Articles

[Selected otorhinolaryngological symptoms in functional disorders of the upper cervical spine and temporomandibular joints].

HNO. 2018 Feb 21;:

Authors: Hölzl M, Behrmann R, Biesinger E, von Heymann W, Hülse R, Arens C

Abstract
This paper discusses otorhinolaryngological symptoms associated with functional disorders of the upper cervical spine. Hints aimed to avoid misdiagnoses of cross-organ otorhinolaryngological symptoms as phobic or psychogenic disorders are presented. Clinically relevant neuroanatomical convergence of the upper cervical spine (occiput to C3) is fundamental for the interpretation of functional otorhinolaryngological symptoms. Based thereon, evidence for the most common cervical differential diagnoses of dizziness, tinnitus, dysphagia, and craniomandibular dysfunction is presented separately. The corresponding therapeutic options and their contraindications are discussed in the concluding chapter. The importance of interdisciplinary cooperation in related fields is emphasized.

PMID: 29468274 [PubMed - as supplied by publisher]

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Treatment of benign thyroid nodules by high intensity focused ultrasound (HIFU) at different acoustic powers: a study on in-silico phantom

Abstract

Background

The non-surgical therapies of benign thyroid nodules are gaining momentum due to the possibility to reduce the nodule's volume and avoid surgery. As the last technique introduced, high intensity focused ultrasound allows the thermal tissue treatment by directing energy inside the targeted nodule with no invasive instruments. In the present study we applied the Food and Drug Administration high intensity focused ultrasound simulator to in-silico phantom to evaluate the effects obtained by different acoustic powers.

Methods

The simulated layers were water and thyroid tissue. The source was a spherically curved circular transducer with radius r   = 2.3 cm generating a continuous wave beam at a frequency of 3 MHz. The focal distance was 6.5 cm. The sequence included a pulse (8 s) with acoustic power at different value from 5 to 50 W, and a cooling-off interval (32 s).

Results

The use of acoustic power of 5 W allowed to achieve the threshold of temperature for coagulative necrosis (55 °C) at 1 s. The simulation with 50 W showed that temperature was significantly higher (above 300 °C) at 1 s and is maintained at high levels for a long interval.

Conclusion

Since 2016, we treated patients according to the present experience, and a significant reduction of nodule's volume was observed with good patent's comfort and no complications (unpublished data). Also, no anesthesia was practiced. We feel that the present data could contribute to develop a high intensity focused ultrasound therapy of benign thyroid nodules free from potential complications.

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