Publication date: Available online 29 November 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Young Chul Kim, Kyung Hyun Min, Jong Woo Choi, Kyung S. Koh, Tae Suk Oh, Woo Shik Jeong
BackgroundThe management of combined orbital floor and medial wall fractures involving the inferomedial strut is challenging due to absence of stable cornerstone. In this article, we proposed surgical strategies using customized 3D puzzle implant preformed with Rapid Prototype (RP) skull model.MethodsRetrospective review was done in 28 patients diagnosed with combined orbital floor and medial wall fracture. Using preoperative CT scans, original and mirror imaged RP skull models for each patient were prepared and sterilized. In all patients, porous polyethylene-coated titanium mesh was premolded onto RP skull model in two ways; Customized 3D jigsaw puzzle technique was used in 15 patients with comminuted inferomedial strut, whereas individual 3D implant technique was used in each fracture for 13 patients with intact inferomedial strut. Outcomes including enophthalmos, visual acuity, presence of diplopia were assessed and orbital volume was measured using OsiriX software preoperatively and postoperatively.ResultsSatisfactory results were achieved in both groups in terms of clinical improvements. Of 10 patients with preoperative diplopia, 9 improved in 6 months, except one with persistent symptom who underwent extraocular muscle rupture. 18 patient who had moderate to severe enophthalmos preoperatively improved, and one remained with mild degree. Orbital volume ratio, defined as volumetric ratio between affected and control orbit, decreased from 127.6% to 99.79% (p<0.05) in comminuted group, and that in intact group decreased from 117.03% to 101.3% (p<0.05).ConclusionOur surgical strategies using the jigsaw puzzle and individual reconstruction technique provide accurate restoration of combined orbital floor and medial wall fractures.
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Τετάρτη 29 Νοεμβρίου 2017
Patient-specific puzzle implant preformed with 3d-printed rapid prototype model for combined orbital floor and medial wall fracture
Option grids in melanoma - an underused tool
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Joseph Ward, Umar Butt, Barry Powell
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Effect of carpal tunnel release on median nerve epineurial flux
Publication date: Available online 29 November 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Zofia Bochen, Magdalena Murawska, Bartlomiej H. Noszczyk
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BranchAnalysis2D/3D automates morphometry analyses of branching structures
Source:Journal of Neuroscience Methods, Volume 294
Author(s): Aditya Srinivasan, Jesús Muñoz-Estrada, Justin R. Bourgeois, Julia W. Nalwalk, Kevin M. Pumiglia, Volney L. Sheen, Russell J. Ferland
BackgroundMorphometric analyses of biological features have become increasingly common in recent years with such analyses being subject to a large degree of observer bias, variability, and time consumption. While commercial software packages exist to perform these analyses, they are expensive, require extensive user training, and are usually dependent on the observer tracing the morphology.New methodTo address these issues, we have developed a broadly applicable, no-cost ImageJ plugin we call 'BranchAnalysis2D/3D', to perform morphometric analyses of structures with branching morphologies, such as neuronal dendritic spines, vascular morphology, and primary cilia.ResultsOur BranchAnalysis2D/3D algorithm allows for rapid quantification of the length and thickness of branching morphologies, independent of user tracing, in both 2D and 3D data sets.Comparison with existing methodsWe validated the performance of BranchAnalysis2D/3D against pre-existing software packages using trained human observers and images from brain and retina. We found that the BranchAnalysis2D/3D algorithm outputs results similar to available software (i.e., Metamorph, AngioTool, Neurolucida), while allowing faster analysis times and unbiased quantification.ConclusionsBranchAnalysis2D/3D allows inexperienced observers to output results like a trained observer but more efficiently, thereby increasing the consistency, speed, and reliability of morphometric analyses.
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Giant cell tumor of temporomandibular joint presenting as a parotid tumor: Challenges in the accurate subclassification of giant cell tumors in an unusual location
Abstract
Fine needle aspiration is frequently used as the initial diagnostic procedure in the work-up of head and neck lesions, including soft tissue masses and salivary gland neoplasms. Giant cell tumors (GCTs), both osseous and extraosseous, are benign tumors that occur, albeit rarely, in the head and neck region. Extraosseous GCTs may be further classified based on their tissue of origin and specific anatomic location. Regardless of location, giant cell tumors are morphologically similar and share cytologic and histologic diagnostic criteria. Evaluation of imaging is therefore essential to the correct classification of these tumors. Accurate diagnosis is crucial since the clinical behavior and treatment is significantly different among the subtypes of GCTs. The case presented herein illustrates the diagnostic dilemma between two uncommon entities in an unusual site: GCT of parotid gland and tenosynovial GCT.
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Primary cutaneous aspergillosis, mimicking malignancy, a rare presentation in an immunocompetent patient
Aspergillus species are ubiquitous opportunistic molds that cause both allergic and invasive syndromes. A 65-year-old female, farmer by occupation, presented with left upper limb and trunk swelling for one year, associated with pain, tightening of skin, and vesicles with watery discharge. Local examination showed a diffuse swelling extending from left arm to forearm and lateral chest wall associated with edema, induration, and raised temperature. The swelling was firm to hard with superficial skin ulcers and black eschar. Hematological investigations of the patient showed raised total WBC count and peripheral blood eosinophilia. Patient had no history suggesting immunosuppression. Clinico-radiological impression was left breast carcinoma with secondary skin involvement. fine-needle aspiration cytology (FNAC) from the swelling showed inflammatory cells, necrosis, epitheloid cell granulomas, and giant cells along with branching hyphae of variable thickness, confirmed on Gomori Methenamine Silver stain as fungal hyphae. Culture was advised which identified the species as Aspergillius fumigatus. Primary cutaneous infection by A. fumigatus in an immunocompetent patient is unheard of. FNAC has an important role in resolving diagnostic dilemma in primary cutaneous aspergillosis, which may mimic malignancy as in our case.
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Implementing noninvasive follicular thyroid neoplasm with papillary-like nuclear features may potentially impact the risk of malignancy for thyroid nodules categorized as AUS/FLUS and FN/SFN
Background
Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) has recently been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Implementation of the new terminology may alter the implied risk of malignancy (ROM) across the six categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).
Methods
The study cohort consisted of thyroid fine needle aspiration (FNA) cases which were assessed between January 2011 and June 2016 and led to surgical resections. For each case, patient demographics as well as cytologic and corresponding histologic diagnoses were recorded. The surgical specimens diagnosed as follicular variant of PTC (FVPTC) were re-reviewed to identify cases that met the diagnostic criteria for NIFTP. The ROM with and without exclusion of NIFTP from malignant categorization, as well as the relative change in ROM were calculated for individual categories of TBSRTC.
Results
A total of 908 FNA cases with surgical follow-up were retrieved and PTC was identified in 252 (27.8%) surgical specimens. Twenty-nine of 252 (11.5%) were initially classified as FVPTC, of which 17 (6.7%) were reclassified as NIFTP. The cytologic interpretations for the majority of NIFTP cases were atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS, n = 8) or follicular neoplasm/suspicious for neoplasm/(FN/SFN, n = 4). Excluding NIFTP from malignant categorization resulted in a relative decrease in ROM in AUS/FLUS (25.8%) and FN/SFN (22.3%) categories.
Conclusion
Our institutional data demonstrates that eliminating NIFTP from malignant categorization may result in a reduction of the implied ROM for AUS/FLUS and FN/SFN categories.
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Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC
Abstract
Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations affect comparable signaling pathways such as RB restriction of cell cycle progression or p53 inactivation. Despite its low incidence, MCC recently received much attention based on its exquisite immunogenicity and the resulting major success of immune modulating therapies. Here, we summarize current knowledge on epidemiology, biology and therapy of MCC as conclusion of the project 'Immune Modulating strategies for treatment of Merkel Cell Carcinoma', which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC.
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Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC
Abstract
Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations affect comparable signaling pathways such as RB restriction of cell cycle progression or p53 inactivation. Despite its low incidence, MCC recently received much attention based on its exquisite immunogenicity and the resulting major success of immune modulating therapies. Here, we summarize current knowledge on epidemiology, biology and therapy of MCC as conclusion of the project 'Immune Modulating strategies for treatment of Merkel Cell Carcinoma', which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC.
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Randomized Split-face, Controlled Comparison of Treatment with 1565 nm Non-ablative Fractional Laser for Enlarged Facial Pores
Abstract
Enlarged pores are common cosmetic concerns1. Though non-ablative fractional lasers (NAFLs) have been used reducing enlarged facial pores, a prospective, split-face, controlled study with objective assessment is still in blank. 1,565 nm NAFL (M22 ™ ResurFX™, Lumenis® Ltd, Yokneam, Israel), proved effective on skin elasticity and stretch marks2, was further aimed to assess for its safety and efficacy on enlarged facial pores.
This article is protected by copyright. All rights reserved.
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Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans
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Adipose Lipolysis Unchanged by Preexercise Carbohydrate regardless of Glycemic Index
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Biological/Genetic Regulation of Physical Activity Level: Consensus from GenBioPAC
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Strength, Affect Regulation, and Subcortical Morphology in Military Pilots
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Cardiometabolic Impact of Changing Sitting, Standing, and Stepping in the Workplace
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SoftHand at the CYBATHLON: a user’s experience
Roughly one-quarter of upper limb prosthesis users reject their prosthesis. Reasons for rejection range from comfort, to cost, aesthetics, function, and more. This paper follows a single user from training wit...
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The extent of surgery for benign parotid pathology and its influence on complications: A prospective cohort analysis
Source:American Journal of Otolaryngology
Author(s): Wai Keat Wong, Subhaschandra Shetty
BackgroundThe surgical management of benign parotid tumors is aimed at complete extirpation of the mass with preservation of facial nerve function. There is a relative paucity of literature pertaining to complications after benign parotid surgery and related risk factors. We aim to critically review the outcomes following treatment of benign parotid pathology when surgery entailed either complete superficial parotidectomy (CSP), partial superficial parotidectomy (PSP) or extracapsular dissection (ECD).Material and methodsThis is a review of prospectively collected data of all parotidectomies performed between June 2006 to June 2016 for histologically-proven benign pathology of the parotid. Median follow-up time was 31.6weeks.ResultsA total of 101 parotidectomies were carried out on 97 patients (40 CSP, 56 PSP and 5 ECD). Pleomorphic adenoma (48.4%) and Warthin tumors (32.7%) were the most common pathologies. Temporary facial weakness occurred after 7 operations (6.9%). Facial weakness was permanent in 4 cases (3.9%). The rates of sialocele and salivary fistula were 4.9% and 0.9%, respectively. Only one patient (0.9%) developed Frey Syndrome postoperatively. No significant associations between extent of parotid surgery and postoperative facial nerve dysfunction (p=0.674) or wound complications (p=0.433) were observed. Univariate analyses for potential contributing factors such as advanced age, smoking status, tumor location or histology did not demonstrate any increased risk with developing postoperative complications.ConclusionPartial superficial parotidectomy was associated with low rates of morbidity to the facial nerve and surgical wound. The results were comparable to complete superficial parotidectomy. We recommend offering patient partial superficial parotidectomy where appropriate and this is in line with the current trend of minimising surgical dissection, thereby potentially decreasing the risk of short-term and long-term complications.
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Acute Chest Syndrome: An Ongoing Challenge for Physicians Caring for Children with Sickle Cell Disease
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
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Diet, Lung Function, and Asthma Exacerbations in Puerto Rican Children
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
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Neutrophil–Lymphocyte Ratio in Children with Recurrent Wheezing
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
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Developing a Mobile Health Intervention for Low-Income, Urban Caregivers of Children with Asthma: A Pilot Study
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
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Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC
Abstract
Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations affect comparable signaling pathways such as RB restriction of cell cycle progression or p53 inactivation. Despite its low incidence, MCC recently received much attention based on its exquisite immunogenicity and the resulting major success of immune modulating therapies. Here, we summarize current knowledge on epidemiology, biology and therapy of MCC as conclusion of the project 'Immune Modulating strategies for treatment of Merkel Cell Carcinoma', which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC.
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Model of a bilateral Brown-type central pattern generator for symmetric and asymmetric locomotion
The coordinated activity of muscles is produced in part by spinal rhythmogenic neural circuits, termed central pattern generators (CPGs). A classical CPG model is a system of coupled oscillators that transform locomotor drive into coordinated and gait-specific patterns of muscle recruitment. The network properties of this conceptual model can be simulated by a system of ordinary differential equations with a physiologically-inspired coupling locus of interactions capturing the timing relationship for bilateral coordination of limbs in locomotion. While most similar models are solved numerically, it is intriguing to have a full analytical description of this plausible CPG architecture to illuminate the functionality within this structure and to expand it to include steering control. Here, we provided a closed-form analytical solution contrasted against the previous numerical method. The evaluation time of the analytical solution was decreased by an order of magnitude when compared to the numerical approach (relative errors, <0.01%). The analytical solution tested and supported the previous finding that the input to the model can be expressed in units of the desired limb locomotor speed. Furthermore, we performed parametric sensitivity analysis in the context of controlling steering and documented two possible mechanisms associated with either an external drive or intrinsic CPG parameters. The results identify specific propriospinal pathways that may be associated with adaptations within the CPG structure. The model offered several network configurations that may generate the same behavioral outcomes.
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The assessment of neurovascular coupling with the Addenbrooke's Cognitive Examination: a functional Transcranial Doppler Ultrasonographic Study
Cerebrovascular dysfunction occurs early in dementia and can be identified by Transcranial Doppler ultrasonography (TCD). Few studies have examined cerebral blood flow velocity (CBFv) responses to a detailed cognitive battery. This study aimed to characterise all CBFv responses, and the effect of hemispheric dominance, to the Addenbrooke's Cognitive Examination (ACE-III) in healthy volunteers. Forty volunteers underwent continuous bilateral TCD, beat-to-beat blood pressure (MAP) (Finapres), heart rate (HR) (electrocardiogram), and end-tidal CO2 (ETCO2) (capnography) monitoring. After 5 minutes baseline, all tasks from the ACE-III were performed in 3 sections (A: attention, fluency, memory, B: language, C: visuospatial, memory). Data are population mean normalised percentage (PM%) change from a twenty second baseline period prior to task initiation. Forty bilateral data sets were obtained (27 female, 37 right-hand dominant). All paradigms produced a sharp increase in CBFv in both dominant (PM% (range): 3.29 to 9.70%), and non-dominant (PM% (range): 4.34 to 11.63%), hemispheres at task initiation, with associated increases in (MAP) (PM% (range): 3.06 to 16.04%). ETCO2 did not differ significantly at task initiation (PM% (range): -1.1 to 2.4%, p>0.05). HR differed significantly across the A and C tasks at initiation (PM% (range): -1.1 to 2.4%, p<0.05), but not B tasks. In conclusion, all tasks resulted in increases in CBFv, differing significantly between paradigms. These results require further investigation in a cognitively impaired population.
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Ih Interacts with Somato-Dendritic Structure to Determine Frequency Response to Weak Alternating Electric Field Stimulation
Transcranial current stimulation (tCS) modulates brain dynamics using weak electric fields. Given the pathological changes in brain network oscillations in neurological and psychiatric illnesses, using alternating electric field waveforms that engage rhythmic activity has been proposed as a targeted, network-level treatment approach. Previous studies have investigated the effects of electric fields at the neuronal level. However, the biophysical basis of the cellular response to electric fields has remained limited. Here, we characterized the frequency-dependent response of different compartments in a layer V pyramidal neuron to exogenous electric fields to dissect the relative contributions of voltage-gated ion channels and neuronal morphology. Hyperpolarization-activated cation current (Ih) in the distal dendrites was the primary ionic mechanism shaping the model response to electric field stimulation and caused subthreshold resonance in the tuft at 20 ± 4 Hz. In contrast, subthreshold Ih-mediated resonance in response to local sinusoidal current injection was present in all model compartments at 11 ± 2 Hz. The frequencies of both resonance responses were modulated by Ih conductance density. We found that the difference in resonance frequency between the two stimulation types can be explained by the fact that exogenous electric fields simultaneously polarize the membrane potentials at the distal ends of the neuron (relative to field direction) in opposite directions. Our results highlight the role of Ih in shaping the cellular response to electric field stimulation and suggest that the common model of tCS as a weak somatic current injection fails to capture the cellular effects of electric field stimulation.
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Time course of functional recovery during first three months after surgical transection and repair of nerves to feline soleus and lateral gastrocnemius muscles
Locomotion outcomes after peripheral nerve injury and repair in cats have been described in the literature for the period immediately following the injury (muscle denervation period) and then again for an ensuing period of long-term recovery (at three months and longer) resulting in muscle self-reinnervation. Little is known about the changes in muscle activity and walking mechanics during mid-recovery, i.e. the early reinnervation period that takes place between 5 and 10 weeks of recovery. Here, we investigated hindlimb mechanics and EMG activity of ankle extensors in six cats during level and slope walking before and every two weeks thereafter in a 14-week period of recovery after the soleus (SO) and lateral gastrocnemius (LG) muscle nerves in one hindlimb were surgically transected and repaired. We found that the continued increase in SO and LG EMG magnitudes and corresponding changes in hindlimb mechanics coincided with the formation of neuromuscular synapses revealed in muscle biopsies. Throughout the recovery period, EMG magnitude of SO and LG during the stance phase and the duration of the stance-related activity were load-dependent, similar to those in the intact synergistic medial gastrocnemius and plantaris. These results and the fact that EMG activity of ankle extensors and locomotor mechanics during level and upslope walking recovered 14 weeks after nerve transection and repair suggest that loss of the stretch reflex in self-reinnervated muscles may be compensated by the recovered force-dependent feedback in self-reinnervated muscles, by increased central drive and increased gain in intermuscular motion-dependent pathways from intact ankle extensors.
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Clustering of Heading Selectivity and Perception-Related Activity in the Ventral Intraparietal Area
The ventral intraparietal area (VIP) of the macaque brain is a multimodal cortical region, with many cells tuned to both optic flow and vestibular stimuli. Responses of many VIP neurons also show robust correlations with perceptual judgments during a fine heading discrimination task. Previous studies have shown that heading tuning based on optic flow is represented in a clustered fashion in VIP. However, it is unknown whether vestibular self-motion selectivity is clustered in VIP. Moreover, it is not known whether stimulus- and choice-related signals in VIP show clustering in the context of a heading discrimination task. To address these issues, we compared the response characteristics of isolated single units (SUs) with those of the undifferentiated multiunit (MU) activity corresponding to several neighboring neurons recorded from the same microelectrode. We find that MU activity typically shows selectivity similar to that of simultaneously recorded SUs, for both the vestibular and visual stimulus conditions. In addition, the choice-related activity of MU signals, as quantified using choice-probabilities (CPs), is correlated with the choice-related activity of SUs. Overall, these findings suggest that both sensory and choice-related signals regarding self-motion are clustered in VIP.
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Complementary metrics of human auditory nerve function derived from compound action potentials
Declines in auditory nerve (AN) function contribute to suprathreshold auditory processing and communication deficits in individuals with normal hearing, hearing loss, hyperacusis, and tinnitus. Procedures to characterize AN loss or dysfunction in humans are limited. We report several novel complementary metrics using the compound action potential (CAP), a direct measure of summated AN activity. Together, these metrics may be used to characterize AN function noninvasively in humans. We examined how these metrics change with stimulus intensity, and interpreted these changes within a framework of known physiological properties of the basilar membrane and AN. Our results reveal how neural synchrony and the recruitment of AN fibers with longer first-spike latencies likely contribute to the CAP, affect auditory processing, and differ with noise exposure history in younger adults with normal pure-tone thresholds. Moving forward, this new battery of metrics provides a crucial step towards new diagnostics of AN function in humans.
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Implantable computer-controlled adaptive multi-electrode positioning system (AMEP)
Acute neuronal recordings performed with metal microelectrodes in non-human primates allow investigating the neural substrate of complex cognitive behaviors. Yet, the daily re-insertion and positioning of the electrodes prevents recording from many neurons simultaneously, limiting the suitability of these types of recordings for brain-computer-interface applications or for large-scale population statistical methods on a trial-by-trial basis. In contrast, chronically implanted multi-electrode arrays offer the opportunity to record from many neurons simultaneously, but immovable electrodes prevent optimization of the signal during and after implantation and cause the tissue response to progressively impair the transduced signal quality, thereby limiting the number of different neurons that can be recorded over the lifetime of the implant. Semi-chronically implanted matrices of electrodes, instead, allow individually movable electrodes in depth and achieve higher channel count compared to acute methods, hence partially overcome these limitations. Existing semi-chronic systems with higher channel count lack computerized control of electrode movements, leading to limited user-friendliness and uncertainty in depth-positioning. Here we demonstrate a chronically-implantable Adaptive Multi-Electrode Positioning (AMEP) system with detachable drive for computerized depth-adjustment of individual electrodes over several millimeters. This semi-chronic 16-channel system is designed to optimize the simultaneous yield of units in an extended period following implantation since the electrodes can be independently depth-adjusted with minimal effort and their signal quality continuously assessed. Importantly, the electrode array is designed to remain within a chronic recording chamber for a prolonged time, or can be used for acute recordings with high signal-to-noise ratio in the cerebral cortex of non-human primates.
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Quantitative relations between BOLD responses, cortical energetics and impulse firing
The blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal arises as a consequence of changes in blood flow (CBF) and oxygen usage (CMR$_{O_2}$) that in turn are modulated by changes in neural activity. Much attention has been given to both theoretical and experimental aspects of the energetics but not to the neural activity. Here we identify the best energetic theory for the steady-state BOLD signal on the basis of correct predictions of experimental observations. This theory is then used, together with the recently determined relationship between energetics and neural activity, to predict how the BOLD signal changes with activity. Unlike existing treatments, this new theory incorporates a non-zero baseline activity in a completely consistent way, and is thus able to account for both positive and negative BOLD signals. We also show that the increase in BOLD signal for a given increase in activity is significantly smaller the larger the baseline activity, as is experimentally observed. Furthermore, the decline of the BOLD signal arising from deeper cortical lamina in response to an increase in neural firing is shown to arise as a consequence of the larger baseline activity in deeper lamina. Finally, we provide quantitative relations integrating BOLD responses, energetics and impulse firing, which amongst other predictions, provides the same results as existing theories when the baseline activity is zero.
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Estimating properties of the fast and slow adaptive processes during sensorimotor adaptation
Experience of a prediction error recruits multiple motor learning processes: some that learn strongly from error but have weak retention, some that learn weakly from error but exhibit strong retention. These processes are not generally observable, but are inferred from their collective influence on behavior. Is there a robust way to uncover the hidden processes? A standard approach is to consider a state-space model where the hidden states change following experience of error, and then fit the model to the measured data by minimizing the squared error between measurement and model prediction. We found that this least-squares algorithm (LMSE) often yielded unrealistic predictions about the hidden states, possibly due to its neglect of the stochastic nature of error-based learning. We found that behavioral data during adaptation was better explained by a system in which both error-based learning and movement production were stochastic processes. To uncover the hidden states of learning, we developed a generalized Expectation Maximization (EM) algorithm. In simulation, we found that while LMSE tracked the measured data marginally better than EM, EM was far more accurate in unmasking the timecourses and properties of the hidden states of learning. In a power analysis designed to measure the effect of an intervention on sensorimotor learning, EM significantly reduced the number of subjects that were required for effective hypothesis testing. In summary, we developed a new approach for analysis of data in sensorimotor experiments. The new algorithm improved the ability to uncover the multiple processes that contribute to learning from error.
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Quantitative input: output relationships between human soleus muscle spindle afferents and motoneurons
A method is described which, for the first time, allows instantaneous estimation of the Ia fiber input to human soleus motoneurons following electrical stimulation of the tibial nerve. The basis of the method is to determine the thresholds of the most and least excitable 1a fibers to electrical stimulation, and to treat the intervening thresholds as having a normal distribution about the mean; the validity of this approach is discussed. It was found that, for the same Ia fibre input, the percentage of soleus motoneurons contributing to the H (Hoffmann)-reflex differed considerably among subjects; when the results were pooled, however, there was an approximately linear relationship between Ia input and motoneuron output. Weak extension of the great toe diminished the soleus motoneuron reflex discharge in all but 2 of 16 subjects; the results for weak ankle plantarflexion were less consistent but overall there was a reduction in soleus motoneuron output also. The methodology should provide new insights into disorders of movement and tone, especially as it permits estimates of motoneuron depolarization to be made.
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Effect of Sensory Attenuation on Cortical Movement-Related Oscillations
This study examined the impact of induced sensory deficits on cortical, movement-related oscillations measured using electroencephalography (EEG). We hypothesized that EEG patterns in healthy subjects with induced sensory reduction would be comparable to EEG found after chronic loss of sensory feedback. EEG signals from 64 scalp locations were measured from 10 healthy subjects. Participants dorsiflexed their ankle after prolonged vibration of the tibialis anterior (TA). Beta band time frequency decompositions were calculated using wavelets and compared across conditions. Changes in patterns of movement-related brain activity were observed following attenuation of sensory feedback. A significant decrease in beta power of event related resynchronization was associated with simple ankle dorsiflexion after prolonged vibration of the TA. Attenuation of sensory feedback in young, healthy subjects leads to a corresponding decrease in beta band synchronization. This temporary change in beta oscillations suggests that these modulations are a mechanism for sensorimotor integration. The loss of sensory feedback found in SCI patients contributes to changes in EEG signals underlying motor commands. Similar alterations in cortical signals in healthy subjects with reduced sensory feedback implies these changes reflect normal sensorimotor integration after reduced sensory input rather than brain plasticity.
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Modeling spatial navigation in the presence of dynamic obstacles: a differential games approach
Obstacle circumvention strategies can be shaped by the dynamic interaction of an individual (evader) and an obstacle (pursuer). We have developed a mathematical model with predictive and emergent components, using experimental data from seven healthy young adults walking towards a target while avoiding collision with a stationary or moving obstacle (approaching head-on, or diagonally 30° left or right) in a virtual environment. Two linear properties from the predictive component enable the evader to predict the minimum distance between itself and the obstacle at all times, including the future intersection of trajectories. The emergent component uses the classical differential games model to solve for an optimal circumvention while reaching the target, wherein the locomotor strategy is influenced by the obstacle, target, and the evader velocity. Both model components were fitted to a different set of experimental data obtained from five post-stroke and healthy participants to derive the minimum predicted distance (predictive component) and obstacle influence dimensions (emergent component) during circumvention. Minimum predicted distance between evader and pursuer was kept constant when the evader was closest to the obstacle in all participants. Obstacle influence dimensions varied depending on obstacle approach condition and preferred side of circumvention, reflecting differences in locomotor strategies between post-stroke and healthy individuals. Additionally, important associations between model outputs and observed experimental outcomes were found. The model, supported by experimental data, suggests that both predictive and emergent processes can shape obstacle circumvention strategies in healthy and post-stroke individuals.
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Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib
Purpose: Vandetanib is well-tolerated in patients with advanced medullary thyroid carcinoma (MTC). Long-term outcomes and mechanisms of MTC progression have not been reported previously. Experimental Design:We monitored toxicities and disease status in patients taking vandetanib for hereditary, advanced MTC. Tumor samples were analyzed for molecular mechanisms of disease progression. Results: Seventeen patients (8 male, age 13 (9-17)* years) enrolled; 16 had a RET p.Met918Thr germline mutation. The duration of vandetanib therapy was 6.1 (0.1-9.7+)* years with treatment ongoing in nine patients. Best response was partial response (PR) in ten, stable disease (SD) in six, and progressive disease (PD) in one patient. Duration of response was 7.4 (0.6-8.7+)* and 4.9 (0.6-7.8+)* years in patients with PR and SD, respectively. Six patients died 2.0 (0.4-5.7)* years after progression. Median progression free survival (PFS) was 6.7 years (95% CI: 2.3 years-undefined) and 5-year overall survival (OS) was 88.2% (95% CI 60.6-96.9%). Of 16 patients with a RET p.Met918Thr mutation, progression free survival was 6.7 years (95% CI 3.1-undefined) and 5-year overall survival was 93.8% (95% CI 63.2-99.1%). No patients terminated treatment because of toxicity. DNA sequencing of tissue samples (n=11) identified an increase in copy number alterations across the genome as a potential mechanism of drug resistance. Conclusions:This study demonstrates that vandetanib is safe and results in sustained responses in children and adolescents with hereditary MTC. Our preliminary molecular data suggest that an increase in copy number abnormalities may be associated with tumor progression in hereditary MTC patients treated with vandetanib.
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PTBP3-mediated regulation of ZEB1 mRNA stability promotes epithelial-mesenchymal transition in breast cancer
The RNA polypyrimidine tract binding protein PTBP3 is a little studied paralog of PTBP1 which has oncogenic properties. In this study, we demonstrate that PTBP3 induces epithelial-mesenchymal transition (EMT) in breast tumor cells and promotes their invasive growth and metastasis. Elevated expression of PTBP3 associated significantly with lymph node metastasis, advanced histology grade, TNM stage, and poor 5-year overall survival of patients. In human mammary epithelial cells, PTBP3 overexpression was sufficient to induce EMT and enhance cell migration, invasion, and cancer stem-like cell properties. PTBP3 regulated expression of the EMT regulatory transcription factor ZEB1 by binding the 3'UTR of its mRNA, thereby preventing its degradation. Conversely, ZEB1 ablation blocked the ability of PTBP3 to induce EMT. Overall, our findings define PTBP3 as a regulator of EMT that acts by governing expression of ZEB1, and they establish an oncogenic function of PTBP3 suggesting its candidacy as a theranostic target.
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Modeling the subclonal evolution of cancer cell populations
Increasing evidence shows that tumor clonal architectures are often the consequence of a complex branching process, yet little is known about the expected dynamics and extent to which these divergent subclonal expansions occur. Here we develop and implement more than 88,000 instances of a stochastic evolutionary model simulating genetic drift and neoplastic progression. Under different combinations of population genetic parameter values, including those estimated for colorectal cancer and glioblastoma multiforme, the distribution of sizes of subclones carrying driver mutations had a heavy right tail at the time of tumor detection, with only 1-4 dominant clones present at ≥10% frequency. In contrast, the vast majority of subclones were present at <10% frequency, many of which had higher fitness than currently dominant clones. The number of dominant clones (≥10% frequency) in a tumor correlated strongly with the number of subclones (<10% of the tumor). Overall, these subclones were frequently below current standard detection thresholds, frequently harbored treatment-resistant mutations and were more common in slow-growing tumors.
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HER2-driven Breast Tumorigenesis Relies upon Interactions of the Estrogen Receptor with Coactivator MED1
Studies of the estrogen receptor (ER) coactivator protein MED1 have revealed its specific roles in pubertal mammary gland development and potential contributions to breast tumorigenesis, based on co-amplification of MED1 and HER2 in certain breast cancers. In this study, we generated a mouse model of mammary tumorigenesis harboring the MMTV-HER2 oncogene and mutation of MED1 to evaluate its role in HER2-driven tumorigenesis. MED1 mutation in its ER-interacting LxxLL motifs was sufficient to delay tumor onset and impair tumor growth, metastasis and cancer stem-like cell formation in this model. Mechanistic investigations revealed that MED1 acted directly to regulate ER signaling through the downstream IGF-1 pathway but not the AREG pathway. Our findings show that MED1 is critical for HER2-driven breast tumorigenesis, suggesting its candidacy as a disease-selective therapeutic target.
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LSR antibody therapy inhibits ovarian epithelial tumor growth by inhibiting lipid uptake
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy but it still lacks effective treatment options. In this study, we utilized proteomic technology to identify lipolysis-stimulated lipoprotein receptor (LSR) as a new tumor antigen of EOC. Immunohistochemical analysis of EOC tissues in conjunction with survival analysis of EOC patients showed that high expression of LSR is associated with poor prognosis. High LSR expression also occurred in tumor metastases including to the lymph node and omentum. To evaluate the possible benefits of blocking this antigen in EOC, we raised a new monoclonal antibody (mAb) to human LSR (hLSR). In mouse xenograft models of hLSR-positive EOC (cell lines or patient-derived tumors), we found that administration of anti-hLSR mAb inhibited tumor growth in a manner independent of both antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity. Mechanistic investigations showed that hLSR expression increased incorporation of very low-density lipoprotein (VLDL) into EOC cells and that anti-hLSR mAb inhibited lipid uptake in vitro and in vivo. Moreover, VLDL promoted cell proliferation in hLSR-positive EOC cells in vitro and this effect was inhibited by anti-hLSR mAb. While the anti-hLSR mAb studied cross-reacted with the mouse antigen, we observed no adverse effects on normal organs and lipid metabolism in murine hosts. Our findings suggest that hLSR plays a key functional role in EOC development and that this antigen can be therapeutically targeted by specific mAb to improve EOC treatment.
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Photodynamic priming mitigates chemotherapeutic selection pressures and improves drug delivery
Physiological barriers to drug delivery and selection for drug resistance limit survival outcomes in cancer patients. In this study, we present preclinical evidence that a subtumoricidal photodynamic priming (PDP) strategy can relieve drug delivery barriers in the tumor microenvironment to safely widen the therapeutic window of a nanoformulated cytotoxic drug. In orthotopic xenograft models of pancreatic cancer, combining PDP with nanoliposomal irinotecan (nal-IRI) prevented tumor relapse, reduce metastasis and increase both progression-free survival and 1-year disease-free survival. PDP enabled these durable improvements by targeting multiple tumor compartments to (1) increase intratumoral drug accumulation by >10-fold, (2) increase the duration of drug exposure above a critical therapeutic threshold, and (3) attenuate surges in CD44 and CXCR4 expression which mediate chemoresistance often observed after multi-cycle chemotherapy. Overall, our results offer preclinical proof of concept for the effectiveness of PDP to minimize risks of tumor relapse, progression and drug resistance and to extend patient survival.
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The E3 ligase RING1 targets p53 for degradation and promotes cancer cell proliferation and survival
As a component of the transcriptional repression complex 1 (PRC1), the ring finger protein RING1 participates in the epigenetic regulation in cancer. However, the contributions of RING1 to cancer etiology or development are unknown. In this study, we report that RING1 is a critical negative regulator of p53 homeostasis in human hepatocellular and colorectal carcinomas. RING1 acts as an E3 ubiquitin (Ub) ligase to directly interact with and ubiquitinate p53, resulting in its proteasome-dependent degradation. The RING domain of RING1 was required for its E3 Ub ligase activity. RING1 depletion inhibited the proliferation and survival of the p53 wild-type cancer cells by inducing cell cycle arrest, apoptosis and senescence, with only modest effects on p53-deficient cells. Its growth inhibitory effect was partially rescued by p53 silencing, suggesting an important role for the RING1-p53 complex in human cancer. In clinical specimens of hepatocellular carcinoma, RING1 upregulation was evident in association with poor clinical outcomes. Collectively, our results elucidate a novel PRC1-independent function of RING1 and provide a mechanistic rationale for its candidacy as a new prognostic marker and/or therapeutic target in human cancer.
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Delivering type I interferon to dendritic cells empowers tumor eradication and immune combination treatments
An ideal generic cancer immunotherapy should mobilize the immune system to destroy tumor cells without harming healthy cells and remain active in case of recurrence. Furthermore, it should preferably not rely on tumor-specific surface markers, as these are only available in a limited set of malignancies. Despite approval for treatment of various cancers, clinical application of cytokines is still impeded by their multiple toxic side effects. Type I interferon (IFN) has a long history in the treatment of cancer, but its multifaceted activity pattern and complex side effects prevent its clinical use. Here we develop AcTakines (Activity-on-Target cytokines), optimized (mutated) immunocytokines that are up to 1000-fold more potent on target cells, allowing specific signaling in selected cell types only. Type I IFN-derived AcTaferon-targeting Clec9A+ dendritic cells (DC) displayed strong antitumor activity in murine melanoma, breast carcinoma, and lymphoma models and against human lymphoma in humanized mice without any detectable toxic side effects. Combined with immune checkpoint blockade, chemotherapy, or low-dose TNF, complete tumor regression and long-lasting tumor immunity were observed, still without adverse effects. Our findings indicate that DC-targeted AcTaferons provide a novel class of highly efficient, safe, and broad-spectrum off-the-shelf cancer immunotherapeutics with no need for a tumor marker.
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PPAR{delta} elicits ligand-independent repression of Trefoil Factor Family to limit prostate cancer growth
The nuclear receptor PPAR-β/δ (PPARD) has essential roles in fatty acid catabolism and energy homeostasis as well as cell differentiation, inflammation and metabolism. However, its contributions to tumorigenesis are uncertain and have been disputed. Here we provide evidence of tumor suppressive activity of PPARD in prostate cancer through a non-canonical and ligand-independent pathway. PPARD was downregulated in prostate cancer specimens. In murine prostate epithelium, PPARD gene deletion resulted in increased cellularity. Genetic modulation of PPARD in human prostate cancer cell lines validated the tumor suppressive activity of this gene in vitro and in vivo. Mechanistically, PPARD exerted its activity in a DNA binding-dependent and ligand-independent manner. We identified a novel set of genes repressed by PPARD that failed to respond to ligand-mediated activation. Among these genes, we observed robust regulation of the secretory trefoil factor family (TFF) members, including a causal and correlative association of TFF1 to prostate cancer biology in vitro and in patient specimens. Overall, our results illuminate the oncosuppressive function of PPARD and understanding of the pathogenic molecular pathways elicited by this nuclear receptor.
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Disparities in Prostate, Lung, Breast, and Colorectal Cancer Survival and Comorbidity Status among Urban American Indians and Alaskan Natives
Cancer is the second leading cause of death among American Indians and Alaskan Natives (AIAN), although cancer survival information in this population is limited, particularly among urban AIAN. In this retrospective cohort study, we compared all-cause and prostate, breast, lung, and colorectal cancer–specific mortality among AIAN (n = 582) and non-Hispanic white (NHW; n = 82,696) enrollees of Kaiser Permanente Northern California (KPNC) diagnosed with primary invasive breast, prostate, lung, or colorectal cancer from 1997 to 2015. Tumor registry and other electronic health records provided information on sociodemographic, comorbidity, tumor, clinical, and treatment characteristics. Cox regression models were used to estimate adjusted survival curves and hazard ratios (HR) with 95% confidence intervals (CI). AIAN had a significantly higher comorbidity burden compared with NHW (P < 0.05). When adjusting for patient, disease characteristics, and Charlson comorbidity scores, all-cause mortality and cancer-specific mortality were significantly higher for AIAN than NHW patients with breast cancer (HR, 1.47; 95% CI, 1.13–1.92) or with prostate cancer (HR, 1.87; 95% CI, 1.14–3.06) but not for AIAN patients with lung and colorectal cancer. Despite approximately equal access to preventive services and cancer care in this setting, we found higher mortality for AIAN than NHW with some cancers, and a greater proportion of AIAN cancer patients with multiple comorbid conditions. This study provides severely needed information on the cancer experience of the 71% of AIANs who live in urban areas and access cancer care outside of the Indian Health Services, from which the vast majority of AIAN cancer information comes. Cancer Res; 77(23); 1–7. ©2017 AACR.
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Which Preschool Children With Specific Language Impairment Receive Language Intervention?
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_LSHSS-17-0024/2665177/Which-Preschool-Children-With-Specific-Language
Re-irradiation for recurrent glioma- the NCI experience in tumor control, OAR toxicity and proposal of a novel prognostic scoring system
Despite mounting evidence for the use of re-irradiation (re-RT) in recurrent high grade glioma, optimal patient selection criteria for re-RT remain unknown. We present a novel scoring system based on radiobiol...
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Irinotecan and Oxaliplatin Might Provide Equal Benefit as Adjuvant Chemotherapy for Patients with Resectable Synchronous Colon Cancer and Liver-confined Metastases: A Nationwide Database Study
Background: Although irinotecan and oxaliplatin are both standard treatments for advanced colon cancer, it remains unknown whether either is effective for patients with resectable synchronous colon cancer and liver-confined metastasis (SCCLM) after curative surgery. Patients and Methods: A population-based cohort of patients diagnosed with de novo SCCLM between 2004 and 2009 was established by searching the database of the Taiwan Cancer Registry and the National Health Insurance Research Database of Taiwan. Patients who underwent curative surgery as their first therapy followed by chemotherapy doublets were classified into the irinotecan group or oxaliplatin group accordingly. Patients who received radiotherapy or did not receive chemotherapy doublets were excluded. Results: We included 6,533 patients with de novo stage IV colon cancer. Three hundred and nine of them received chemotherapy doublets after surgery; 77 patients received irinotecan and 232 patients received oxaliplatin as adjuvant chemotherapy. The patients in both groups exhibited similar overall survival (median: not reached vs. 40.8 months, p=0.151) and time to the next line of treatment (median: 16.5 vs. 14.3 months, p=0.349) in both univariate and multivariate analyses. Additionally, patients with resectable SCCLM had significantly shorter median overall survival than patients with stage III colon cancer who underwent curative surgery and subsequent adjuvant chemotherapy, but longer median overall survival than patients with de novo stage IV colon cancer who underwent surgery only at the primary site followed by standard systemic chemotherapy (p<0.001). Conclusion: Irinotecan and oxaliplatin exhibited similar efficacy in patients who underwent curative surgery for resectable SCCLM.
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Robotic-assisted Transperitoneal Infrarenal Para-aortic Lymphadenectomy for Gynecological Malignancies: Comparison with a Laparoscopic Approach
Background/Aim: We evaluated the clinical feasibility and surgical outcomes of robotic-assisted transperitoneal infrarenal para-aortic lymphadenectomy (TIPAL) in patients with gynecological malignancies. Patients and Methods: The perioperative outcomes in 90 patients with gynecological malignancies who underwent laparoscopic (n=43) or robotic-assisted (n=47) TIPAL were compared retrospectively. Results: The operative time for pelvic and total lymphadenectomy were significantly shorter in the robotic-assisted approach, whereas the time for infrarenal para-aortic lymphadenectomy did not differ statistically. In contrast, the number of infrarenal para-aortic lymph nodes was significantly higher in the robotic-assisted approach. We compared the time per retrieved lymph node in both approaches, and those for pelvic, infrarenal para-aortic, and total lymphadenectomy were significantly shorter in the robotic-assisted approach. Conclusion: In our study, the robotic-assisted TIPAL took less time to retrieve a lymph node than the laparoscopic approach. The robotic-assisted approach for TIPAL is feasible for the staging and treatment of patients with gynecological malignancies.
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Anastomotic Leakage Using Linear Stapling Device with Pre-attached Bioabsorbable Polyglycolic Acid Felt After Laparoscopic Anterior Resection
Aim: Many studies have evaluated the risk factors for anastomotic leakage after laparoscopic anterior resection. In this study in order to increase the tightness of anastomoses and prevent bleeding from their staple lines, a linear stapler with pre-attached bioabsorbable polyglycolic acid (PGA) felt was used for rectal transection, and the short-term surgical outcomes were evaluated. Patients and Methods: A prospective registry of 62 patients with rectosigmoidal or rectal carcinoma who initially underwent laparoscopic anterior resection using PGA felt for rectal transection was reviewed. Results: The overall frequency of anastomotic leakage was 1.6% (1/62), and none of the patients developed postoperative staple line bleeding or other adverse events related to the use of PGA felt. Conclusion: The frequency of anastomotic leakage was relatively low, and therefore the use of a linear stapler with pre-attached bioabsorbable PGA felt might reduce the risk of adverse events related to anastomosis, especially anastomotic leakage.
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A Glissonean Approach with Individual Isolation During Right Hemi-Hepatectomy After Portal Vein Embolization
Background/Aim: Although the Glissonean approach in hemi-hepatectomy is a very useful technique, right hemi-hepatectomy with Glissonean approach after portal vein embolization (PVE) is difficult because of the obstructing materials located at the right portal branch. The aim of this study was to evaluate the utility of the Glissonean approach with an individual isolation technique (GI technique) in right hemi-hepatectomies after PVE. Patients and Methods: We retrospectively analyzed 21 patients who underwent the GI technique between March 2007 and June 2012. Results: In one of the 21 patients, we could not perform the GI technique because of severe adhesions following previous operation; however, there were no troubles in the remaining 20 cases. In addition, none of the patients that were treated using this method developed massive ascites after right hemi-hepatectomy, despite 8 patients (40%) exhibiting severe fibrosis (F3 or F4). Conclusion: Even in right hemi-hepatectomy following PVE, our GI technique may be a useful procedures for patients.
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Mucinous Cystic Neoplasms Lined by Abundant Mucinous Epithelium Frequently Involve KRAS Mutations and Malignant Progression
Background: Pancreatic and hepatic mucinous cyst neoplasms (MCNs) have a malignant potential, but indolent MCNs are not uncommon. Materials and Methods: The pathological and genetic characteristics of resected MCNs (n=15) categorized by the amount of mucin of the lining epithelium were investigated. Results: MCNs were divided into two groups: (i) a rich (r)-MCN group (n=6), in which more than half of the epithelium was lined by abundant mucinous epithelium; and (ii) a poor (p)-MCN group (n=9), which consisted of the remaining cases. Three patients in the r-MCN group showed invasive carcinoma or high-grade dysplasia, whereas all patients in the p-MCN group showed low-grade dysplasia. Mutations of Kirsten rat sarcoma viral oncogene homolog (KRAS) were more frequent in the r-MCN group (83%) (p-MCN; 11%, p<0.05). Conclusion: Mucinous MCNs more frequently have KRAS mutations and higher risk of malignant progression.
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Outcome Evaluation of HER2 Breast Cancer Patients with Limited Brain Metastasis
Background/Aim: To appraise the outcome of limited brain metastasis (BMs) from HER2 breast cancer. Patients and Methods: The study cohort included sixty-six patients Treatments consisted of surgery followed by radiotherapy (RT), or radiosurgery (SRS/HSRS) or whole brain radiotherapy (WBRT). Results: Surgery followed by RT was performed in 25.8% of patients, SRS/HSRS alone in 48.5%, and WBRT alone in 25.7%. The median follow-up time was 23.4 months and 32.5 months for alive patients. Local recurrence occurred in 16 (24.2%) patients. The median, 1-, 2-, 3-year local control were (median not reached=nr), 87.5%, 71.2%, and 63.0%. The median 1-, 2-, 3-year overall survival were 30.7 months (95%CI: 18.9-42.6 months), 78.5%, 57.4%, 43.3%. Karnofsky Performance Scale (KPS), number of BMs, local treatment performed, the presence of extracranial (EC) metastases at the time of BMs diagnosis, and the administration of trastuzumab affected survival. Conclusion: HER2BC patients with good performance status, controlled EC disease and single BM had better outcome. In this long-term survivor patients, local BMs treatment can affect survival.
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Characterization of Prognostic Factors and the Efficacy of Adjuvant S-1 Chemotherapy in Patients with Post-surgery Extrahepatic Bile Duct Cancer
Background/Aim: There is no clear consensus on the type of adjuvant therapy that should be used for patients with extrahepatic bile duct cancer. Patients and Methods: Two hundred and seventy-one patients that had undergone surgical resection for extrahepatic bile duct cancer composed the study cohort. Demographics, treatments, and relationships between the potential prognostic factors and survival rates were analyzed. Results: The overall 3-year and 5-year survival rates for post-surgery extrahepatic bile duct cancer patients were 49.0% and 35.4%, respectively. Multivariate analysis revealed that regional lymph node metastasis was an independent negative prognostic factor. We observed a significant correlation between node-positive extrahepatic bile duct cancer and postoperative local recurrence, liver metastasis, peritoneal dissemination, and post-surgery lymph node metastasis. Adjuvant S-1 chemotherapy showed a favorable hazard ratio in patients with lymph node metastases or positive vascular invasion. Conclusion: We recommend the use of adjuvant S-1 therapy in patients with lymph node metastases or microvascular invasion.
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FOLFOX as First-line Therapy for Gastric Cancer with Severe Peritoneal Metastasis
Background/Aim: Severe peritoneal metastasis (PM) from advanced gastric cancer (AGC) causes massive ascites and inadequate oral intake. Because patients with severe PM are often not included in clinical trials, little is known regarding the efficacy and safety of oxaliplatin with l-leucovorin and bolus/continuous infusion of 5-fluorouracil (FOLFOX) for them. Patients and Methods: We retrospectively studied AGC patients with massive ascites and/or inadequate oral intake due to severe PM treated with FOLFOX as the first-line treatment. Results: Only 39 (10%) of 378 AGC patients had severe PM; 10 received FOLFOX. The median progression-free and overall survivals were 7.5 and 13.2 months, respectively. Ascites decreased in seven of nine patients with ascites, and oral intake improved in four of seven patients with an inadequate oral intake. Common grade 3-4 adverse events included neutropenia and anemia. Conclusion: This study suggests that FOLFOX is effective and manageable for AGC patients with severe PM.
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Incidence and Risk Factors of Symptomatic Hiatal Hernia Following Resection for Gastric and Esophageal Cancer
Background/Aim: Symptomatic hiatal hernia (HH) following resection for gastric or esophageal cancer is a potentially life-threatening event that may lead to emergent surgery. However, the incidence and risk factors of this complication remain unclear. Patients and Methods: Data of patients who underwent resection for gastric or esophageal cancer between 2005 and 2012 were assessed and the incidence of symptomatic HH was evaluated. Factors associated with an increased risk for HH were investigated. Results: Resection of gastric or esophageal cancer was performed in 471 patients. The primary tumor was located in the stomach, cardia and esophagus in 36%, 24%, and 40% of patients, respectively. The incidence of symptomatic HH was 2.8% (n=13). All patients underwent surgical hernia repair, 8 patients (61.5%) required emergent procedure, and 3 patients (23%) underwent bowel resection. Morbidity and mortality after HH repair was 38% and 8%, respectively. Factors associated with increased risk for symptomatic HH included Body-Mass-Index (median BMI with HH 27 (23-35) vs. BMI without HH 25 (15-51), p=0.043), diabetes (HH rate: with diabetes, 6.3% vs. without diabetes, 2%, p=0.034), tumor location (HH rate: stomach, 1.2% vs. esophagus, 1.1% vs. cardia, 7.9%, p=0.001), and resection type (HH rate: total/subtotal gastrectomy, 0.7% vs. transthoracic esophagectomy, 2.7% vs. extended gastrectomy, 6.1%, p=0.038). Conclusion: HH is a major adverse event after resection for gastric or esophageal cancer especially among patients undergoing extended gastrectomy for cardia cancer requiring a high rate of repeat surgery. Therefore, intensive follow-up examinations for high-risk patients and early diagnosis of asymptomatic patients are essential for selecting patients for elective surgery to avoid unpredictable emergent events with high morbidity and mortality.
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A Prospective Study of Intensity-modified Radiation Therapy in Comparison with Conventional 3D-RT for BR Pancreatic Cancer Patients with Arterial Involvement
Background/Aim: Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that allows accurate irradiation with reduced damage to surrounding tissues. Here, we analyzed borderline-resectable pancreatic cancer (BRPC) with arterial abutment (BR-A) patients with IMRT as neoadjuvant therapy and performed comparisons with patients with conventional RT to clarify the advantages of IMRT as a neoadjuvant therapy. Patients and Methods: Thirty BR-A patients treated at our hospital between January 2012 and December 2015 were divided into two groups: 12 patients underwent conventional 3D-RT before resection (RT group); and 18 patients underwent IMRT before resection (IMRT group). We analyzed safety, tumor resection rate, histological classification of the tumor and overall survival. Results: The R0 rate was 84% for the IMRT group and 83% for the RT group. Local therapeutic effects as assessed by Evans classification showed a higher local control rate in the IMRT group (Grade: 1, 0%; 2a, 25%; 2b, 41.6%; 3, 17%; 4, 8%) than in the RT group (Grade: 1, 17%; 2a, 50%; 2b, 17%; 3, 17%; 4, 0%). The cumulative dose of S1 treatment as adjuvant therapy was much smaller in the RT group (18.3%) compared to that in the IMRT group (57.1%, p=0.047), and with better subsequent overall survival rate (MST 32 months vs. 13.8 months, p=0.0273). Conclusion: The IMRT group showed a better control rate than the RT group. The neoadjuvant IMRT has advantages of higher completion rate of adjuvant chemotherapy with better nutritional status and better subsequent overall survival rate (OS).
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Pancreatic Mucinous Cystic Neoplasm Communicating with Main Pancreatic Duct: An Unrecognized Presentation of Pancreatic Mucinous Neoplasm?
Mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) are two well recognized entities of precursor cystic lesions of pancreatic duct adenocarcinoma. The characteristic features of MCNs are the lined mucinous epithelium with underlying ovarian-type stroma, but without communication with the ducts, while that for IPMNs are the communication with the ducts but without the underlying ovarian-type stroma. Here we report a case of MCN communicating with the main pancreatic duct in a 68-year-old woman. The initial radiographic diagnosis was pancreatic IPMN with main pancreatic involvement and this was also confirmed during gross examination. Histologically, the pancreatic cystic neoplasm was lined with mucinous epithelium with underlying ovarian-type of stroma. Immunohistochemical stains confirmed that the stroma cells were positive for ER, PR, alpha-inhibin and focally positive for CD10. The final pathologic diagnosis was pancreatic mucinous cystic neoplasm communicating with the main pancreatic duct. To the best of our knowledge, this is the second pathology confirmed case of MCN communicating with the main pancreatic duct. A careful gross examination and bivalvation of the main duct communicating with the cystic neoplasm helps render the correct diagnosis. If more cases are reported in the future, the MCN communicating with duct could become a new entity of pancreatic mucinous neoplasm.
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Predictive Factors and a Survival Score for Patients Irradiated for Metastatic Spinal Cord Compression from Carcinoma of the Salivary Glands
Aim: To our knowledge, this is the first study focusing on metastatic spinal cord compression (MSCC) from carcinoma of the salivary glands. Patients and Methods: Nine patients receiving radiation alone were evaluated for improvement of motor deficits, post-radiation gait function and survival. Results: Of nine characteristics (radiation program, age, sex, additional metastases to bone or to other organs, dynamic of motor deficits, pre-radiation gait function, number of vertebrae affected by MSCC, general condition), strong trends were found for associations between improved motor deficits and their dynamic (p=0.05), post-radiation gait function and pre-treatment ambulatory status (p=0.08) and between survival and additional metastases to other organs (p=0.07), dynamic of motor deficits (p=0.07) and general condition (p=0.07). In addition, a survival score was created. Patients with 2-3 points had a significantly better 6-month survival than those with 0-1 points (100% vs. 0%, p=0.027). Conclusion: Characteristics predicting outcomes identified in this study and the new survival score can guide physicians when making treatment decisions.
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Making and working of a new electronic resource for patients, carers and professionals: maxfacts.uk
Many maxillofacial patients have serious short, medium, or long-term problems, as well as having to make informed decisions about often life-changing interventions. Validated comprehensive information, at the right time and the right level for a diverse group of users (patients, carers, and professionals), is vital if patients are to make a serious contribution to their treatment. We describe the development of an online resource for this purpose. Maxfacts.uk aims to cover every aspect of oral and maxillofacial surgery and care, from neck dissection and ballistic wounds to physiotherapy and texture-modified foods.
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Nodular fasciitis of the temporomandibular joint: a case report
Nodular fasciitis is a relatively rare benign lesion of the soft tissue, which often presents in the fascia or deep subcutaneous tissues. It most commonly presents in the upper extremities and trunk and the head and neck region, particularly in younger patients. Its pathogenesis is poorly understood and it is predominantly thought to be a reactive lesion, although some have suggested that it may be a benign neoplasm. Advances in molecular testing and imaging have greatly assisted diagnosis. We discuss the benefits of ubiquitin-specific protease 6 (USP6) gene rearrangement testing and magnetic resonance imaging (MRI) to aid this uncommon diagnosis.
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Prognosis of oral cancer: a comparison of the staging systems given in the 7th and 8th editions of the American Joint Committee on Cancer Staging Manual
The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual introduces "depth of invasion" and "extranodal extension" into the head and neck section, and our aim was to find out if these changes have an impact on prognosis. We evaluated 174 patients who had had oral squamous cell carcinomas (SCC) resected between 2003 and 2012. The clinical records were reviewed, the patients' tumours restaged according to the 8th edition of the AJCC, and we analysed five-year survival to verify whether different correlations were made between the T and N stages and disease-specific survival using the 7th and 8th editions.
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Is it better to bend wires occlusally or apically during placement of arch bars for intermaxillary fixation?
We evaluated 78 patients who had intermaxillary fixation (IMF) of fractured mandibular condyles with arch bars and wires. Depending on whether the wires were bent apically or occlusally during placement of the arch bars, we randomly divided the patients into two groups (n=39 in each), then compared pain, satisfaction with oral hygiene, and complications between the groups at five to six weeks postoperatively when the arch bars were removed. Outcomes were significantly better in the occlusal group than in the apical group.
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Retroseptal transconjunctival approach for fractures of the zygomaticomaxillary complex: a retrospective study
We designed a retrospective study to evaluate the efficacy of retroseptal transconjunctival approaches in the management of fractures of the zygomaticomaxillary complex (ZMC). The patients were from a single institution, and had had three-point fixation of fractures of the ZMC between 2008 and 2016. A total of 77 patients (56 men and 21 women with a mean (range) age of 28 (18–54) years), were divided into two groups. Group I (n=51) had had reduction and fixation of the infraorbital rim using a retroseptal transconjunctival approach.
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Tracking the Growth of Tense and Agreement in Children With Specific Language Impairment: Differences Between Measures of Accuracy, Diversity, and Productivity
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_JSLHR-L-16-0427/2665179/Tracking-the-Growth-of-Tense-and-Agreement-in
Evaluation of an Automated Pipeline for Large Scale EEG Spectral Analysis: The National Sleep Research Resource
We present an automated sleep electroencephalogram (EEG) spectral analysis pipeline that includes an automated artifact detection step, and we test the hypothesis that spectral power density estimates computed with this pipeline are comparable to those computed with a commercial method preceded by visual artifact detection by a sleep expert (standard approach).
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Option grids in melanoma - an underused tool
It is not uncommon for patients faced with a new diagnosis of malignant melanoma to experience significant upset and confusion. During this distressing period, NICE guidance (NG14) recommends that patients with AJCC Stage IB-IIC disease should consider whether they wish to undergo sentinel lymph node biopsy (SLNB)1. The decision to undergo SLNB can be difficult and should ideally be reached following informed and considered discussion with patients guided as to the relative merits of SLNB by their plastic surgeon.
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Effect of carpal tunnel release on median nerve epineurial flux
It is believed that increased pressure that develops in the carpal tunnel syndrome (CTS) leads to nerve compression and a gradual decrease in neurovascular blood flow. Animal experiments showed that early nerve release restores neurovascular flow; however, late decompression has no effect.1 This finding raises the questions of whether carpal tunnel release increases blood flow in the median nerve and whether nerve ischemia may be associated with carpal tunnel etiology. The objective of this study was to evaluate the immediate effects of tunnel release and determine its influence on median nerve flux.
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Patient-specific puzzle implant preformed with 3d-printed rapid prototype model for combined orbital floor and medial wall fracture
The management of combined orbital floor and medial wall fractures involving the inferomedial strut is challenging due to absence of stable cornerstone. In this article, we proposed surgical strategies using customized 3D puzzle implant preformed with Rapid Prototype (RP) skull model.
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The extent of surgery for benign parotid pathology and its influence on complications: A prospective cohort analysis
The surgical management of benign parotid tumors is aimed at complete extirpation of the mass with preservation of facial nerve function. There is a relative paucity of literature pertaining to complications after benign parotid surgery and related risk factors. We aim to critically review the outcomes following treatment of benign parotid pathology when surgery entailed either complete superficial parotidectomy (CSP), partial superficial parotidectomy (PSP) or extracapsular dissection (ECD).
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Comparing Traditional Service Delivery and Telepractice for Speech Sound Production Using a Functional Outcome Measure
from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_AJSLP-16-0070/2665178/Comparing-Traditional-Service-Delivery-and
Effects of platelet-rich plasma on pain and muscle strength in patients with knee osteoarthritis
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The effect of stretching combined with ultrashort wave diathermy on joint function and it’s possible mechanism in a rabbit knee contracture model
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Uterus transplantation: A Rapidly Expanding Field
Categorizing coordination from the perception of joint actions
Abstract
The ability to perceive others' actions and coordinate our own body movements accordingly is essential for humans to interact with the social world. However, it is still unclear how the visual system achieves the remarkable feat of identifying temporally coordinated joint actions between individuals. Specifically, do humans rely on certain visual features of coordinated movements to facilitate the detection of meaningful interactivity? To address this question, participants viewed short video sequences of two actors performing different joint actions, such as handshakes, high fives, etc. Temporal misalignments were introduced to shift one actor's movements forward or backward in time relative to the partner actor. Participants rated the degree of interactivity for the temporally shifted joint actions. The impact of temporal offsets on human interactivity ratings varied for different types of joint actions. Based on human rating distributions, we used a probabilistic cluster model to infer latent categories, each revealing shared characteristics of coordinated movements among sets of joint actions. Further analysis on the clustered structure suggested that global motion synchrony, spatial proximity between actors, and highly salient moments of interpersonal coordination are critical features that impact judgments of interactivity.
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Phlebotomy as a preventive measure for crocidolite-induced mesothelioma in male rats
Summary
Malignant mesothelioma (MM) is a rare but socially important neoplasm due to its association with asbestos exposure. While MM is difficult to diagnose at an early stage, there are no particularly effective treatments available at the advanced stage, thus necessitating efficient strategies to prevent MM in individuals already exposed to asbestos. We previously showed that persistent oxidative damage caused by foreign body reaction and affinity of asbestos both to hemoglobin and histones is one of the major pathogeneses. Accordingly, as an effective strategy to prevent asbestos-induced MM, we undertook the use of an iron chelator, deferasirox, which decreased the epithelial-mesenchymal transition in a crocidolite-induced rat MM model. However, this agent may exhibit adverse effects. Here, we studied the effects of iron removal by phlebotomy as a realistic measure on the same rat model. We injected a total of 5 mg of crocidolite intraperitoneally to F1 hybrid rats between the Fischer-344 and Brown-Norway strains at the age of 6 weeks. We repeated weekly or biweekly phlebotomy of 6 to 8 ml/kg/time from 10 to 60 weeks of age. The animals were observed until 120 weeks. In male rats, phlebotomy significantly decreased the weight and nuclear grade of MM, and modestly reduced the associated ascites and the fraction of more malignant sarcomatoid subtype. Weekly phlebotomy prolonged the long-term survival. Our results indicate that appropriate phlebotomy may be a practical preventive measure to attenuate the initiation and promotion capacity of asbestos towards MM by reducing iron in individuals exposed to asbestos.
This article is protected by copyright. All rights reserved.
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Oral cancer databases: a comprehensive review
Abstract
Cancer database is a systemic collection and analysis of information on various human cancers at genomic and molecular level that can be utilized to understand various steps in carcinogenesis and for therapeutic advancement in cancer field. Oral cancer is one of the leading causes of morbidity and mortality all over the world. The current research efforts in this field are aimed at cancer etiology and therapy. Advanced genomic technologies including microarrays, proteomics, transcrpitomics and gene sequencing development have culminated in generation of extensive data and subjection of several genes and microRNAs that are distinctively expressed and this information is stored in the form of various databases. Extensive data from various resources has brought the need for collaboration and data sharing in order to make effective use of this new knowledge. The current review provides comprehensive information of various publicly accessible databases that contain information pertinent to oral squamous cell carcinoma (OSCC) and databases designed exclusively for OSCC. The databases discussed in the present paper are Protein-Coding Gene Databases and microRNA Databases. This paper also describes gene overlap in various databases, which will help researchers to reduce redundancy and focus on only those genes, which are common to more than one databases. We hope such introduction will promote awareness and facilitate the usage of these resources in the cancer research community and researchers can explore the molecular mechanisms involved in the development of cancer, which can help in subsequent crafting of therapeutic strategies.
This article is protected by copyright. All rights reserved.
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Frankophonie im Plural
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"Manuel des francophonies" published by De Gruyter
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Plurielles Francophonies
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EM Nerd-The Case of Corporeal Clock
How exactly do trialists proceed when deciding upon the appropriate acronyms for their soon-to-be blockbuster trial? Is the proper etiquette to follow a traditional prospective process, utilizing the first letter of each word in a trial's longer title? Or is the selection of an acronym based on its ability to inspire and only then, retrospectively […]
EMCrit by Rory Spiegel.
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A survival analysis using physique-adjusted tumor size of non-small cell lung cancer
Abstract
Background
Differences in individual body sizes have not been well considered when analyzing the survival of patients with non-small cell lung cancer (NSCLC). We hypothesized that physique-adjusted tumor size is superior to actual tumor size in predicting the prognosis.
Methods
Eight hundred and forty-two patients who underwent R0 resection of NSCLC between 2005 and 2012 were retrospectively reviewed, and overall survival (OS) was evaluated. The physique-adjusted tumor size was defined as: x-adjusted tumor size = tumor size × mean value of x/individual value of x [x = height, weight, body surface area (BSA), or body mass index (BMI)]. Tumor size category was defined as ≤2, 2–3, 3–5, 5–7, and >7 cm. The separation index (SEP), which is the weighted mean of the absolute value of estimated regression coefficients over the subgroups with respect to a reference group, was used to measure the separation of subgroups.
Results
The mean values of height, weight, BSA, and BMI were 160.7 cm, 57.6 kg, 1.59 m2, and 22.2 kg/m2, respectively. The 5-year survival rates ranged from 88−59% in the non-adjusted tumor size model (SEP 1.937), from 90−57% in the height-adjusted model (SEP 2.236), from 91−52% in the weight-adjusted model (SEP 2.146), from 90−56% in the BSA-adjusted model (SEP 2.077), and from 91−51% in the BMI-adjusted model (SEP 2.169).
Conclusions
The physique-adjusted tumor size can separate the survival better than the actual tumor size.
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