Reduced cerebral vascularisation in experimental neuronopathic Gaucher disease

Abstract

The glycosphingolipidosis of Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid β-glucocerebrosidase, with subsequent accumulation of β-glucocerebroside, its upstream substrates and the non-acylated congener, β-glucosylsphingosine. However, the mechanisms by which end-organ dysfunction arise are poorly understood. Here we report strikingly diminished cerebral microvascular density in a murine model of disease and provide a detailed analysis of the accompanying cerebral glycosphingolipidome in these animals, with marked elevations of β-glucosylsphingosine. Further in vitro studies confirmed a concentration dependent impairment of endothelial cytokinesis upon exposure to quasi-pathological concentrations of β-glucosylsphingosine. These findings support a premise for pathogenic disruption of cerebral angiogenesis as an end-organ effect, with potential for therapeutic modulation in neuronopathic Gaucher disease.

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Topical propranolol improves epistaxis in patients with hereditary hemorrhagic telangiectasia - a preliminary report

Severe epistaxis is often difficult to control in patients with hereditary hemorrhagic telangiectasia (HHT). Propranolol has been shown to have antiangiogenic properties in vitro and in vivo and is commonly us...

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Impact of Lipid-Inflammatory-Oxidative Metabolism on Auditory Skills after Hearing Aid Fitting in the Elderly

This study aimed to assess whether lipid-inflammatory-oxidative metabolism influences auditory processing skills, and whether they function in changing auditory performance after hearing aid fitting in the elderly. Twelve subjects with bilateral hearing loss were submitted to blood tests (to check their lipid-inflammatory-oxidative metabolism) and auditory processing skill tests. After 3 months of using the hearing aids, their auditory skills were re-evaluated and the data were correlated statistically. Oxidative stress levels mainly showed some impact on auditory temporal processing; such a relation and others should best be examined in further studies with larger populations.
Audiol Neurotol 2017;22:146-153

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Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study

Abstract

Ipilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab-related pulmonary toxicity are still scarce. Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with metastatic melanoma before and during treatment with ipilimumab were performed. A reduction from baseline of forced vital capacity (FVC) of ≥ 10%, or ≥ 15% of DLCO was defined as clinically meaningful and indicative for pulmonary toxicity. Of 71 patients included in this study, a clinically meaningful lung function decline was registered in 6/65 (9%), 5/44 (11%), and 9/38 (24%) patients after 3, 6, and 9 weeks of treatment initiation, respectively. Even after adjusting for age, concomitant melanoma treatment, progressive pulmonary metastases, and baseline pulmonary function values, mean ± SD DLCO decreased significantly during follow-up (−4.3% ± 13.6% from baseline, p = 0.033). Only 7% of patients reported respiratory symptoms. Clinically manifest ipilimumab-related pneumonitis was diagnosed only in one patient (1.4%). DLCO decline maybe an early indicator of subclinical pulmonary drug toxicity. Therefore, routine pulmonary function testing including DLCO measurement during treatment might help for risk stratification to screen for ipilimumab-related pneumonitis.

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Satzung der Deutschen Gesellschaft für Pathologie e. V.

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Satzung der Rudolf-Virchow-Stiftung für Pathologie

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Eustachian Tube Dysfunction-Related Symptoms in Chronic Nasal Obstruction Caused by Inferior Turbinate Enlargement.

Eustachian Tube Dysfunction-Related Symptoms in Chronic Nasal Obstruction Caused by Inferior Turbinate Enlargement.

Ann Otol Rhinol Laryngol. 2017 Oct 01;:3489417735538

Authors: Harju T, Kivekäs I, Numminen J, Rautiainen M

Abstract
OBJECTIVE: The aim of this study was to evaluate the relationship between chronic nasal obstruction caused by inferior turbinate enlargement and Eustachian tube dysfunction-related symptoms using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7) as an assessment method.
METHODS: A total of 80 adults were enrolled. Group 1 comprised consecutive patients with enlarged inferior turbinates and group 2 comprised healthy controls. The ETDQ-7 scores and tympanometry results of both groups were analyzed and compared.
RESULTS: The median total scores of the ETDQ-7 in groups 1 and 2 were 1.9 (interquartile range, 1.4-2.8) and 1.1 (interquartile range, 1.0-1.7), respectively ( P < .001). There was no significant difference in the abnormal tympanometry results between the groups. There was no significant difference in the ETDQ-7 total score between the patients with allergic sensitization and other patients in group 1.
CONCLUSIONS: Patients with inferior turbinate enlargement have more symptoms related to Eustachian tube dysfunction than healthy controls. Most patients with Eustachian tube dysfunction had normal tympanometry and normal otoscopy, which indicates a baro-challenge-induced Eustachian tube dysfunction. Whether the patient has allergic sensitization or not does not seem to cause a difference in symptoms related to Eustachian tube dysfunction.

PMID: 28975810 [PubMed - as supplied by publisher]

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A Real-time Prediction Model for Post-irradiation Malignant Cervical Lymph Nodes

Abstract

Objective

To establish a real-time predictive scoring model based on sonographic characteristics for identifying malignant cervical lymph nodes (LNs) in cancer patients after neck irradiation.

Methods

One-hundred-forty-four irradiation-treated patients underwent ultrasonography and ultrasound-guided fine needle aspirations (USgFNAs), and the resultant data were used to construct a real-time and computerized predictive scoring model. This scoring system was further compared with our previously proposed prediction model.

Results

A predictive scoring model, 1.35 x (L axis) + 2.03 x (S axis) + 2.27 x (Margin) + 1.48 x (Echogenic hilum) + 3.7, was generated by stepwise multivariate logistic regression analysis. Neck LNs were considered to be malignant when the score was ≥ 7, corresponding to a sensitivity of 85.5%, specificity of 79.4%, positive predictive value (PPV) of 82.3%, negative predictive value (NPV) of 83.1%, and overall accuracy of 82.6%. When this new model and the original model were compared, the areas under the receiver operating characteristic curve (c-statistic) were 0.89 and 0.81, respectively (p < 0.05).

Conclusions

A real-time sonographic predictive scoring model was constructed to provide prompt and reliable guidance for USgFNA biopsies to manage cervical LNs after neck irradiation.

This article is protected by copyright. All rights reserved.

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Incurable, progressive Merkel cell carcinoma: a single institution study of 54 cases

Abstract

The median overall survival, disease-free survival and survival from disease progression of patients with progressive disease was 15, 8 months and 5 months, respectively.

22 (96%) out of 23 individuals suffering from disease progression died of the disease. The overall mortality rate was 70%.

Patients with progressive MCC spend significantly more tumour related days in the hospital compared to patients without a progressive disease.

The rate of immunosuppression was significantly higher in the MCC progressive group and those patients received more often radio- and/or chemotherapy.

Despite an aggressive therapy approach and long hospitalization, survival among patients suffering from progressive MCC was very poor. Randomized clinical trials are required to assess whether aggressive systemic and local therapy is justified in Merkel cell carcinoma patients with progressive disease.

This article is protected by copyright. All rights reserved.

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Novel middle ear applications for a synthetic cerebrospinal fluid (CSF) sealant

Abstract

TissuePatchDural^™ is an easy to store and apply synthetic CSF sealant.

Its breakdown products are naturally occurring and non-toxic.

Its use appears safe in the middle ear.

It is shown to successfully close mastoid CSF leaks.

Its use as an adjunct in sealing middle ear fistulae is also demonstrated.

This article is protected by copyright. All rights reserved.

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Nodal factors predictive of recurrence and survival in patients with oral cavity squamous cell carcinoma

Abstract

Objectives

Lymph node (LN) metastasis of oral cavity squamous cell carcinoma (OSCC) is associated with survival outcomes. However, the relationship between different metastatic nodal factors and treatment outcomes require further elucidation. This study examined nodal factors predictive of recurrence and survival in patients with OSCC.

Methods

This prospective observational study included 157 patients with OSCC who underwent surgery between 2010 and 2015. Clinicopathological and follow-up information were recorded. Univariate and multivariate Cox proportional hazard models were performed to identify factors associated with recurrence-free survival, disease-specific survival and overall survival.

Results

Sixty-five of 157 patients (41.4%) had neck metastasis. During a median follow-up of 46 months, any recurrences and all deaths occurred in 43 (27.4%) and 43 (27.4%) of cases, respectively. All nodal factors (LN classification, size, number and ratio) and extra-nodal extension were significantly associated with all survival outcomes (P <0.001). Multivariate analyses indicated that a tumour size >2 cm and LN ratio were independentlyassociated with all survival (P <0.05). Patients with LN ratio >0.05 had six-fold higher recurrence and mortality rates than other patients (P <0.001).

Conclusion

LN ratio is an independent and predictive determinant of post-treatment recurrence and survival.

This article is protected by copyright. All rights reserved.

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Prospective multi-centre study on barbed reposition pharyngoplasty standing alone or as a part of multilevel surgery for sleep apnea

Abstract

Objectives

The aim of this study was to demonstrate in a prospective multi-centre study that Barbed Reposition Pharyngoplasty (BRP) procedure is safe and effective in management of obstructive sleep apnea/hypopnea syndrome (OSAHS) patients.

Design

prospective study.

Setting

multicenter study.

Participants

patients suffering from obstructive sleep apnea.

Main outcomes measures

values of post-operative apnea-hypopnea index(AHI), oxygen desaturation index (ODI), epworth sleepiness scale (ESS).

Results

111 BRP procedures standing alone or as a part of multilevel surgery for OSAHS, performed between January and September 2016, were analyzed in 15 different centers. The average hospitalization period was 2.5 ± 0.5 days. The mean patient age was 46.3 ± 10.5 years. The average BMI at the time of the procedure was 27.9 ± 3.2 and the majority of the patients were men (83%). The mean pre-operative and post-operative apnea/hypopnea index was 33.4 ± 19.5 and 13.5 ± 10.3, respectively (p < 0.001). The mean pre-operative and post-operative epworth sleepiness scale score was 10.2 ± 4.5 and 6.1 ± 3.6, respectively (p < 0.001). The mean pre- and post-operative oxygen desaturation index was 29.6 ± 20.7 and 12.7 ± 10.8, respectively (p < 0.001).

Conclusions

Patients undergoing BRP standing alone or as part of a multilevel approach for the treatment of OSAHS have a reasonable expectation for success with minimal morbidity.

This article is protected by copyright. All rights reserved.

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Adverse events during and after per-oral endoscopic myotomy: prevention, diagnosis, and management

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Efficacy and safety of endoscopic submucosal dissection for submucosal tumors of the colon and rectum

Endoscopic submucosal dissection (ESD) of colorectal submucosal tumors (SMTs) is becoming increasingly common; however, there have been few large consecutive studies analyzing its therapeutic efficacy and safety. The aim of this study was to evaluate the efficacy, safety, and long-term outcomes of ESD for colorectal SMTs.

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Endoscopy in Inflammatory Bowel Disease: Advances in Dysplasia Detection and Management

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Increase in female faculty in ASGE sponsored programming over time

Female representation in medicine is increasing across all levels of medical training yet women hold fewer senior leadership positions than men. National recognition, including participation as faculty in society-sponsored programs, is one component of academic advancement. The aim of this study was to characterize female representation among faculty in courses sponsored by the American Society for Gastrointestinal Endoscopy. (ASGE)

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Adenoma detection rate influences the risk of metachronous advanced colorectal neoplasia in low-risk patients

In individuals with either no or 1 to 2 nonadvanced adenomas, future risks of advanced colorectal neoplasia (AN) vary according to the clinical risk factors. However, little is known about the association between the adenoma detection rate (ADR) and the risk for metachronous AN in patients with low-risk adenomas.

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Impact of the staging method on the prognostic utility of the 8th AJCC staging system for non-small-cell lung cancer

Future Oncology, Ahead of Print.


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Selecting patients for gastrectomy in metastatic esophago-gastric cancer: clinics and pathology are not enough

Future Oncology, Ahead of Print.


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Epigenetic regulation by DNA methylation and miRNA molecules in cancer

Future Oncology, Ahead of Print.


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The SIRveNIB and SARAH trials and the role of SIR-Spheres® Y-90 resin microspheres in the management of hepatocellular carcinoma

Future Oncology, Ahead of Print.


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Neoantigens in the immuno-oncology space

Future Oncology, Ahead of Print.


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Avelumab and other recent advances in Merkel-cell carcinoma

Future Oncology, Ahead of Print.


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Dominant foot could affect the postural control in vestibular neuritis perceived by dynamic body balance

Publication date: Available online 4 October 2017
Source:Gait & Posture
Author(s): Tomoe Yoshida, Toshitake Tanaka, Yuya Tamura, Masahiko Yamamoto, Mitsuya Suzuki
During attacks of vestibular neuritis (VN), patients typically lose postural balance, with resultant postural inclination, gait deviation toward the lesion side, and tendency to fall. In this study, we examined and analyzed static and dynamic postural control during attacks of VN to characterize differences in postural control between right and left VN. Subjects were patients diagnosed with VN at the Department of Otolaryngology, Toho University Sakura Medical Center, and underwent in-patient treatment. Twenty-five patients who had spontaneous nystagmus were assessed within 3days after the onset; all were right-foot dominant. Right VN was detected in nine patients (men: 4, women: 5; mean age: 57.6±17.08years [range: 23–82]) and left VN in 16 patients (men: 10, women: 6; mean age: 58.4±14.08years [range: 23–85 years]); the percentages of canal paresis of right and left VN were 86.88±18.1% and 86.02±15.0%, respectively. Statistical comparisons were conducted using the independent t-test. In stabilometry, with eyes opened, no significant differences were found between patients with right and left VN. However, with eyes closed, the center of horizontal movement significantly shifted ipsilateral (p<0.01). The differences in the lateral and anteroposterior body tracking test (BTT) were statistically significant (p=0.0039 and p=0.0376, respectively), with greater changes in cases with right VN. Thus, the dominant foot might contribute to the postural control mechanism.



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The effects of real and artificial Leg Length Discrepancy on mechanical work and energy cost during the gait.

Publication date: Available online 4 October 2017
Source:Gait & Posture
Author(s): T.F. Assogba, S. Boulet, C. Detrembleur, P. Mahaudens




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Increased sensory noise and not muscle weakness explains changes in non-stepping postural responses following stance perturbations in healthy elderly

Publication date: Available online 4 October 2017
Source:Gait & Posture
Author(s): Maarten Afschrift, Friedl De Groote, Sabine Verschueren, Ilse Jonkers
The response to stance perturbations changes with age. The shift from an ankle to a hip strategy with increasing perturbation magnitude occurs at lower accelerations in older than in young adults. This strategy shift has been related to age-related changes in muscle and sensory function. However, the effect of isolated changes in muscle or sensory function on the responses following stance perturbations cannot be determined experimentally since changes in muscle and sensory function occur simultaneously. Therefore, we used predictive simulations to estimate the effect of isolated changes in (rates of change in) maximal joint torques, functional base of support, and sensory noise on the response to backward platform translations. To evaluate whether these modeled changes in muscle and sensory function could explain the observed changes in strategy; simulated postural responses with a torque-driven double inverted pendulum model controlled using optimal state feedback were compared to measured postural responses in ten healthy young and ten healthy older adults. The experimentally observed peak hip angle during the response was significantly larger (5°) and the functional base of support was smaller (0.04m) in the older than in the young adults but peak joint torques and rates of joint torque were similar during the recovery. The addition of noise to the sensed states in the predictive simulations could explain the observed increase in peak hip angle in the elderly, whereas changes in muscle function could not. Hence, our results suggest that strength training alone might be insufficient to improve postural control in elderly.



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DPYD genotype-guided fluoropyrimidines dose: is it ready for prime time?

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Whole-slide imaging at primary pathological diagnosis: Validation of whole-slide imaging-based primary pathological diagnosis at twelve Japanese academic institutes

Several reports have demonstrated the use of whole-slide imaging (WSI) for primary pathological diagnosis, but no such studies have been published from Asia. We retrospectively collected 1070 WSI specimens from 900 biopsies and small surgeries conducted in nine hospitals. Nine pathologists, who participated in this study, trained for the College of American Pathologists guidelines, reviewed the specimens and made diagnoses based on digitized, 20× or 40× optically magnified images with a WSI scanner. After a washout interval of over 2 weeks, the same observers reviewed conventional glass slides and diagnosed them by light microscopy. Discrepancies between microscopy- and WSI-based diagnoses were evaluated at the individual institutes, and discrepant cases were further reviewed by all pathologists. Nine diagnoses (0.9%) showed major discrepancies with significant clinical differences between the WSI- and microscopy-based diagnoses, and 37 (3.5%) minor discrepancies occurred without a clinical difference. Eight out of nine diagnoses with a major discrepancy were considered concordant with the microscopy-based diagnoses. No association was observed between the level of discrepancy and the organ type, collection method, or digitized optical magnification. Our results indicate the availability of WSI-based primary diagnosis of biopsies and small surgeries in routine daily practice.

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Abstracts of A − Presentation by the winners of The Japanese Society of Pathology; Pathology Research Award in 2017 (in program order)

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Surgical outcomes after laminoplasty for cervical spondylotic myelopathy: A focus on the dynamic factors and signal intensity changes in the intramedullary spinal cord on MRI

Publication date: Available online 4 October 2017
Source:Clinical Neurology and Neurosurgery
Author(s): Masashi Miyazaki, Naoki Notani, Toshinobu Ishihara, Shozo Kanezaki, Hiroshi Tsumura
ObjectiveWe aimed to analyze the relationship between the dynamic factors and signal intensity changes in the intramedullary spinal cord on MRI, and surgical outcomes, following double-door laminoplasty for cervical spondylotic myelopathy (CSM).Patients and methodsThis retrospective study included 100 consecutive patients who underwent double-door laminoplasty for CSM. The following factors were analyzed: JOA score recovery rate, age, duration from onset to surgery, intraoperative bleeding, signal intensity changes in the intramedullary spinal cord on MRI, pre and postoperative C2-7 lordotic angle (LA), changes in C2-7 LA, pre and postoperative C2-7 range of motion (ROM), and pre and postoperative segmental ROM. The Charlson Comorbidity Index (CCI) was also used for the assessment of complications.ResultsAge, CCI, preoperative segmental ROM, and pre and postoperative MRI grade significantly correlated with JOA score recovery rate (P<0.01), whereas number of expanded laminae, duration from onset to surgery, surgery time, intraoperative bleeding, preoperative and postoperative C2-7 LA, change in C2-7 LA, and preoperative C2-7 ROM did not. Multivariate analysis showed that the preoperative segmental ROM (OR=−0.988, P=0.017) and preoperative MRI grade (OR=−7.170, P=0.042) were significantly associated with JOA score recovery rate.ConclusionConsidering the dynamic factors, there was no correlation with C2-7 ROM and surgical outcome, but preoperative segmental ROM and a change in signal intensity of the intramedullary spinal cord on MRI were negatively correlated with surgical outcome. From these results, we suggest that preoperative segmental ROM is possibly associated with spinal cord damage due to repeated minor trauma and affects surgical outcome of laminoplasty.



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Why averaging multiple MUNIX measures in the longitudinal assessment of patients with ALS?

Amyotrophic lateral sclerosis (ALS), a terminal degenerative disease of the upper and lower motor neurons (LMN), lacks reliable lower motor neuron disease progression biomarker. Clinical assessment, functional scales, and routine electrophysiological parameters are insensitive in detecting subtle lower motor neuron degeneration as muscle strength and compound muscle action potential (CMAP) can remain stable despite progressive subclinical LMN loss and reinnervation (Neuwirth et al., 2017).

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Multiple spatial representations interact to increase reach accuracy when coordinating a saccade with a reach

Reaching is an essential behavior that allows primates to interact with the environment. Precise reaching to visual targets depends on our ability to localize and foveate the target. Despite this, how the saccade system contributes to improvements in reach accuracy remains poorly understood. To assess spatial contributions of eye movements to reach accuracy, we performed a series of behavioral psychophysics experiments in nonhuman primates (Macaca mulatta). We found that a coordinated saccade with a reach to a remembered target location increases reach accuracy without target foveation. The improvement in reach accuracy was similar to that obtained when the subject had visual information about the location of the current target in the visual periphery and executed the reach while maintaining central fixation. Moreover, we found that the increase in reach accuracy elicited by a coordinated movement involved a spatial coupling mechanism between the saccade and reach movements. We observed significant correlations between the saccade and reach errors for coordinated movements. In contrast, when the eye and arm movements were made to targets in different spatial locations, the magnitude of the error and the degree of correlation between the saccade and reach direction were determined by the spatial location of the eye and the hand targets. Hence, we propose that coordinated movements improve reach accuracy without target foveation due to spatial coupling between the reach and saccade systems. Spatial coupling could arise from a neural mechanism for coordinated visual behavior that involves interacting spatial representations.

NEW & NOTEWORTHY How visual spatial representations guiding reach movements involve coordinated saccadic eye movements is unknown. Temporal coupling between the reach and saccade system during coordinated movements improves reach performance. However, the role of spatial coupling is unclear. Using behavioral psychophysics, we found that spatial coupling increases reach accuracy in addition to temporal coupling and visual acuity. These results suggest that a spatial mechanism to couple the reach and saccade systems increases the accuracy of coordinated movements.

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Orthodontic treatment-induced temporal alteration of jaw-opening reflex excitability

The impairment of orofacial motor function during orthodontic treatment needs to be addressed, because most orthodontic patients experience pain and motor excitability would be affected by pain. In the present study, the temporal alteration of the jaw-opening reflex excitability was investigated to determine if orthodontic treatment affects orofacial motor function. The excitability of jaw-opening reflex evoked by electrical stimulation on the gingiva and recorded bilaterally in the anterior digastric muscles was evaluated at 1 (D1), 3 (D3), and 7 days (D7) after orthodontic force application to the teeth of right side; morphological features (e.g., osteoclast genesis and tooth movement) were also evaluated. To clarify the underlying mechanism of orthodontic treatment-induced alteration of orofacial motor excitability, analgesics were administrated for 1 day. At D1 and D3, orthodontic treatment significantly decreased the threshold for inducing the jaw-opening reflex but significantly increased the threshold at D7. Other parameters of the jaw-opening reflex were also evaluated (e.g., latency, duration and area under the curve of anterior digastric muscles activity), and only the latency of the D1 group was significantly different from that of the other groups. Temporal alteration of the jaw-opening reflex excitability was significantly correlated with changes in morphological features. Aspirin (300 mg·kg^–1·day^–1) significantly increased the threshold for inducing the jaw-opening reflex, whereas a lower dose (75–150 mg·kg^–1·day^–1) of aspirin or acetaminophen (300 mg·kg^–1·day^–1) failed to alter the jaw-opening reflex excitability. These results suggest that an increase of the jaw-opening reflex excitability can be induced acutely by orthodontic treatment, possibly through the cyclooxygenase activation.

NEW & NOTEWORTHY It is well known that motor function is affected by pain, but the effect of orthodontic treatment-related pain on the trigeminal motor excitability has not been fully understood. We found that, during orthodontic treatment, trigeminal motor excitability is acutely increased and then decreased in a week. Because alteration of trigeminal motor function can be evaluated quantitatively by jaw-opening reflex excitability, the present animal model may be useful to search for alternative approaches to attenuate orthodontic pain.

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Neuronal networks in the developing brain are adversely modulated by early psychosocial neglect

The brain's neural circuitry plays a ubiquitous role across domains in cognitive processing and undergoes extensive reorganization during the course of development in part as a result of experience. In this study we investigated the effects of profound early psychosocial neglect associated with institutional rearing on the development of task-independent brain networks, estimated from longitudinally acquired electroencephalographic (EEG) data from <30 to 96 mo, in three cohorts of children from the Bucharest Early Intervention Project (BEIP), including abandoned children reared in institutions who were randomly assigned either to a foster care intervention or to remain in care as usual and never-institutionalized children. Two aberrantly connected brain networks were identified in children that had been reared in institutions: 1) a hyperconnected parieto-occipital network, which included cortical hubs and connections that may partially overlap with default-mode network, and 2) a hypoconnected network between left temporal and distributed bilateral regions, both of which were aberrantly connected across neural oscillations. This study provides the first evidence of the adverse effects of early psychosocial neglect on the wiring of the developing brain. Given these networks' potentially significant role in various cognitive processes, including memory, learning, social communication, and language, these findings suggest that institutionalization in early life may profoundly impact the neural correlates underlying multiple cognitive domains, in ways that may not be fully reversible in the short term.

NEW & NOTEWORTHY This paper provides first evidence that early psychosocial neglect associated with institutional rearing profoundly affects the development of the brain's neural circuitry. Using longitudinally acquired electrophysiological data from the Bucharest Early Intervention Project (BEIP), the paper identifies multiple task-independent networks that are abnormally connected (hyper- or hypoconnected) in children reared in institutions compared with never-institutionalized children. These networks involve spatially distributed brain areas and their abnormal connections may adversely impact neural information processing across cognitive domains.

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The third-stimulus temporal discrimination threshold: focusing on the temporal processing of sensory input within primary somatosensory cortex

The somatosensory temporal discrimination threshold (STDT) has been used in recent years to investigate time processing of sensory information, but little is known about the physiological correlates of somatosensory temporal discrimination. The objective of this study was to investigate whether the time interval required to discriminate between two stimuli varies according to the number of stimuli in the task. We used the third-stimulus temporal discrimination threshold (ThirdDT), defined as the shortest time interval at which an individual distinguishes a third stimulus following a pair of stimuli delivered at the STDT. The STDT and ThirdDT were assessed in 31 healthy subjects. In a subgroup of 10 subjects, we evaluated the effects of the stimuli intensity on the ThirdDT. In a subgroup of 16 subjects, we evaluated the effects of S1 continuous theta-burst stimulation (S1-cTBS) on the STDT and ThirdDT. Results show that ThirdDT is shorter than STDT. We found a positive correlation between STDT and ThirdDT values. As long as the stimulus intensity was within the perceivable and painless range, it did not affect ThirdDT values. S1-cTBS significantly affected both STDT and ThirdDT, although the latter was affected to a greater extent and for a longer period of time. We conclude that the interval needed to discriminate between time-separated tactile stimuli is related to the number of stimuli used in the task. STDT and ThirdDT are encoded in S1, probably by a shared tactile temporal encoding mechanism whose performance rapidly changes during the perception process. ThirdDT is a new method to measure somatosensory temporal discrimination.

NEW & NOTEWORTHY To investigate whether the time interval required to discriminate between stimuli varies according to changes in the stimulation pattern, we used the third-stimulus temporal discrimination threshold (ThirdDT). We found that the somatosensory temporal discrimination acuity varies according to the number of stimuli in the task. The ThirdDT is a new method to measure somatosensory temporal discrimination and a possible index of inhibitory activity at the S1 level.

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{alpha}-Motoneurons maintain biophysical heterogeneity in obesity and diabetes in Zucker rats

Small-diameter sensory dysfunction resulting from diabetes has received much attention in the literature, whereas the impact of diabetes on α-motoneurons (MN) has not. In addition, the chance of developing insulin resistance and diabetes is increased in obesity. No study has examined the impact of obesity or diabetes on the biophysical properties of MN. Lean Zucker rats and Zucker diabetic fatty (ZDF) rats were separated into lean, obese (ZDF fed standard chow), and diabetic (ZDF fed high-fat diet that led to diabetes) groups. Glass micropipettes recorded hindlimb MN properties from identified flexor and extensor MN. MN were separated within their groups on the basis of input conductance, which created high- and low-input conductance subpopulations for each. A significant shorter (20%) afterhyperpolarization half-decay (AHP_1/2) was found in low-conductance MN for the diabetic group only, whereas AHP1/2 tended to be shorter in the obese group (19%). Significant positive correlations were found among rheobase and input conductance for both lean and obese animals. No differences were found between the groups for afterhyperpolarization amplitude (AHP_amp), input conductance, rheobase, or any of the rhythmic firing properties (frequency-current slope and spike-frequency adaptation index). MN properties continue to be heterogeneous in obese and diabetic animals. Obesity does not seem to influence lumbar MN. Despite the resistance of MN to the impact of diabetes, the reduced AHP_1/2 decay and the tendency for a reduction in AHP_amp may be the first sign of change to MN function.

NEW & NOTEWORTHY Knowledge about the impact of obesity and diabetes on the biophysical properties of motoneurons is lacking. We found that diabetes reduces the duration of the afterhyperpolarization and that motoneuron function is unchanged by obesity. A reduced afterhyperpolarization may impact discharge characteristics and may be the first sign of change to motoneuron function.

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Intra- and intersegmental influences among central pattern generating networks in the walking system of the stick insect

To efficiently move around, animals need to coordinate their limbs. Proper, context-dependent coupling among the neural networks underlying leg movement is necessary for generating intersegmental coordination. In the slow-walking stick insect, local sensory information is very important for shaping coordination. However, central coupling mechanisms among segmental central pattern generators (CPGs) may also contribute to this. Here, we analyzed the interactions between contralateral networks that drive the depressor trochanteris muscle of the legs in both isolated and interconnected deafferented thoracic ganglia of the stick insect on application of pilocarpine, a muscarinic acetylcholine receptor agonist. Our results show that depressor CPG activity is only weakly coupled between all segments. Intrasegmental phase relationships differ between the three isolated ganglia, and they are modified and stabilized when ganglia are interconnected. However, the coordination patterns that emerge do not resemble those observed during walking. Our findings are in line with recent studies and highlight the influence of sensory input on coordination in slowly walking insects. Finally, as a direct interaction between depressor CPG networks and contralateral motoneurons could not be observed, we hypothesize that coupling is based on interactions at the level of CPG interneurons.

NEW & NOTEWORTHY Maintaining functional interleg coordination is vitally important as animals locomote through changing environments. The relative importance of central mechanisms vs. sensory feedback in this process is not well understood. We analyzed coordination among the neural networks generating leg movements in stick insect preparations lacking phasic sensory feedback. Under these conditions, the networks governing different legs were only weakly coupled. In stick insect, central connections alone are thus insufficient to produce the leg coordination observed behaviorally.

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The strip method and the microelectrode technique in assessing dental plaque pH.

The strip method and the microelectrode technique in assessing dental plaque pH.

Minerva Stomatol. 2017 Oct 03;:

Authors: Cocco F, Cagetti MG, Lingström P, Camoni N, Campus G

Abstract
BACKGROUND: The pH strip method has been proposed for use in a clinical setting for the evaluation of dental plaque pH. The aim of this in vivo study was to compare the reliability of the pH-indicator strip method to the microelectrode technique in plaque pH measurement.
METHODS: 136 subjects (7-9 years) were enrolled and, for each subject, measurements of plaque pH were made at two interproximal sites; a total of 272 sites were analysed. Plaque pH was assessed in triplicate using pH-indicator strips (pH range of 4.0-7.0) and an iridium microelectrode with a diameter 0.1 mm. The caries status of 544 proximal surfaces between two primary molars, in proximity at the plaque-pH sites, was assessed. All measurements were performed before and 2, 5, 10, 15, 20 and 30 minutes after a mouth rinse with water solution of sucrose (10%). One-way ANOVA was performed to analyse statistically significant differences between the two techniques. Instrument reliability was measured by assessing the Intraclass Correlation Coefficient (ICC).
RESULTS: Comparable, not statistically significant pH values (p-values range from 0.98 to 1.00) were obtained by the two methods for AUC (area under curve )5.7, AUC6.2, maximum pH fall and minimum pH. High intraclass coefficients were recorded (Pearson's r = 0.96 and Yule's Q =0.99), implying an almost perfect association when the measurements were grouped as a carious lesion being present or not on the surface near the site of measurement.
CONCLUSIONS: The use of the pH strip method has high validity and may replace the traditional microtouch electrode technique for clinical use.

PMID: 28975774 [PubMed - as supplied by publisher]

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Molar incisor hypomineralization treatment with casein phosphopeptide and amorphous calcium phosphate in children.

Molar incisor hypomineralization treatment with casein phosphopeptide and amorphous calcium phosphate in children.

Minerva Stomatol. 2017 Oct 03;:

Authors: Pasini M, Giuca MR, Scatena M, Gatto R, Caruso S

Abstract
BACKGROUND: The purpose of this study was to evaluate the sensitivity of teeth with MIH in children before and after the use of a tooth mousse containing casein phosphopeptide and amorphous calcium phosphate (CPP-ACP).
METHODS: 40 patients, both males and females, aged from 8 to 13 years old that had a molar with MIH hypersensitivity were included in this study. In the test group (20 subjects), a tooth mousse with CPP-ACP was used while fluoride toothpaste was used in the control group. Dental sensitivity to mechanical and thermal stimuli was evaluated before (T0) and 120 days after the beginning of the treatment (T1).
RESULTS: In the test group, the thermal sensitivity decreased significantly (p <0.05) from T0 to T1 (2.4 ± 0.6 to 1.1 ± 0.4) while in the control group resulted very similar (from 2.3 ± 0.5 to 2.2 ± 0.4). Similarly, mechanical sensitivity decreased significantly (p <0.05) from 7.8 ± 1 to 3.8 ± 0.6 while in the control group decreased not significantly (from 7.5 ± 1.3 to 7.2 ± 0.8). No significant difference (p> 0.05) was observed by comparing males with females.
CONCLUSIONS: The use of the remineralizing agent containing CPP-ACP resulted in a significant improvement in dental sensitivity in patients with MIH.

PMID: 28975773 [PubMed - as supplied by publisher]

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Aspartate aminotransferase activity in peri-implant mucositis: experimental peri-implant mucositis model of 14 days.

Aspartate aminotransferase activity in peri-implant mucositis: experimental peri-implant mucositis model of 14 days.

Minerva Stomatol. 2017 Oct 03;:

Authors: Zeza B, Pilloni A, Angiullo G, Malatesta F, Mongardini C

Abstract
BACKGROUND: Experimental peri-implant mucositis has been studied from various prospective in a duration of 21 days. Given the higher sensitivity of peri-implant mucosa the aim of the present study was to evaluate if a duration of 14 days would be sufficient to establish a state of measurable inflammation.
MATERIALS AND METHODS: 20 patients of age 57 ± 11 years old contributed with 20 clinically healthy implants and teeth. They were instructed to use an individual stent in the selected elements prior to performing oral hygiene for 14 days. For each element plaque index (PlI), probing depth (PD), bleeding on probing (Bops) were reported at 0 days and 14 days of plaque accumulation. Aspartate aminotransferase activity was measure at both time points from the crevicular fluid.
RESULTS: Both implant and teeth developed similar increased response of inflammation at 14 days compared to day 0: BoPs of 4.2±1.8 (p=0.06) and BoPs of 3.1±2.2 (p=0.048) for implant and tooth, respectively. Implant presented deeper pocket depth at both time periods but less plaque accumulation. AST activity did not increased significantly, but it was significantly higher at implant level.
CONCLUSIONS: 14 days of plaque accumulation seemed to be sufficient for the establishment of peri- implant mucositis. However, AST did not resulted as a proper indicator of initial peri-implant inflammation.

PMID: 28975772 [PubMed - as supplied by publisher]

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A new multiple anti-infective non surgical therapy in the treatment of peri-implantitis: a case series.

A new multiple anti-infective non surgical therapy in the treatment of peri-implantitis: a case series.

Minerva Stomatol. 2017 Oct 03;:

Authors: Mensi M, Scotti E, Calza S, Pilloni A, Grusovin MG, Mongardini C

Abstract
BACKGROUND: Peri-implantitis is a frequent disease that may lead to implant loss. The aim of this case series was to evaluate the clinical results of a new non-surgical treatment protocol.
METHODS: Fifteen patients with dental implants affected by peri-implantitis were treated with a multiple anti-infective non-surgical treatment (MAINST) which included two steps: 1) supra-gingival decontamination of the lesion and sub-gingival treatment with a controlled-release topical doxycycline; 2) after one week, a session of supra and sub gingival air polishing with Erythritol powder and ultrasonic debridement (where calculus was present) of the whole oral cavity was performed along with a second application of topical doxycycline around the infected implant. Primary outcome measures were: implant failure; complications and adverse events; recurrence of peri-implantitis; secondary outcome measure were presence of Plaque (PI), Bleeding on Probing (BOP), Probing Pocket Depth (PPD). Recession (REC), Relative Attachment level (RAL).
RESULTS: Neither implant failure nor complications nor adverse events were reported. Statistically (p < 0.01) and clinically significant reductions between baseline and 1 year of PI (100% vs 13.9%, CI95% 72.4%; 93.7%); BOP (98.5% vs 4.5%, CI95% 85.4%; 98.5%) and PPD (7.89mm vs 3.16mm CI95% -5.67; -3.77), were detected. At baseline, all 15 patients had a PPD > 5 mm at the affected implant(s), whereas only 3.7% at 3 month follow-up a PPD> 5 mm, and none at 6 and 12 months.
CONCLUSIONS: Within the limits of this study, the MAINST protocol showed improvement of clinical parameters for the treatment of peri-implantitis, which were maintained for up to 12 months.

PMID: 28975771 [PubMed - as supplied by publisher]

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Treatment of hyperdivergent growth pattern and anterior open bite with posterior metallic bite planes (SOCIA).

Treatment of hyperdivergent growth pattern and anterior open bite with posterior metallic bite planes (SOCIA).

Minerva Stomatol. 2017 Oct 03;:

Authors: Ciavarella D, Lo Russo L, Nichelini J, Mastrovincenzo M, Barbato E, Laurenziello M, Montaruli G, Lo Muzio L

Abstract
INTRODUCTION: In the present paper, the authors analyze the effect of the "Swallowing Occlusal Contact Intercept Appliance" (SOCIA) in treatment of children with hyperdivergent Class II malocclusion. This functional appliance has no intra-oral anchorage, but induces a continuous periodontal, muscular, and articular stimulation.
METHODS: Twenty-six patients with hyperdivergent growth and class II malocclusion were selected and treated with "Swallowing Occlusal Contact Intercept Appliance" appliance. Cephalometric analysis was performed before treatment (T1) and immediately after the treatment (T2).
RESULTS: After 24 months treatment authors observed a modification of maxillary growth with a reduction of the divergence with an increase of the posterior facial height, a modification of condylar inclination and forward position of the a hyoid. No modifications was observed about the ANB angle. After treatment the open bite was resolved with a reduction of the inclination of the upper incisors.
CONCLUSIONS: SOCIA is a reliable functional appliance in growing age patients with a hyperdivergent pattern growth, anterior open bite and class II molar malocclusion.

PMID: 28975770 [PubMed - as supplied by publisher]

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Subcranial and orthognathic surgery for obstructive sleep apnea in achondroplasia: A case series

Obstructive sleep apnea (OSA) is a common problem in patients with achondroplasia. The purpose of this study was to assess changes in airway volumes following various degrees of facial skeletal advancement.

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Plastic surgical operative workload in major trauma centres (POW-MTC): a UK prospective national cohort study

Modern plastic surgery was born out of trauma during World War I and trauma is an essential part of the specialty. United Kingdom (U.K.) military and single-centre civilian data report plastic surgical operative involvement in 29 to 40% of major trauma patients requiring surgery,1,2 with a particularly high workload in lower limb trauma. The substantial role of plastic surgery in trauma has been reported in other settings, including a United States civilian Level I trauma centre3.

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Reduction of bone mineral density in native Chinese female idiopathic benign paroxysmal positional vertigo patients

This study aimed to investigate the clinical association between idiopathic benign paroxysmal positional vertigo (BPPV) and reduction of bone mineral density (BMD).

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Hearing aid silicone impression material as a foreign body in the middle ear.

Related Articles

Hearing aid silicone impression material as a foreign body in the middle ear.

Am J Otolaryngol. 2017 Jan - Feb;38(1):108-111

Authors: Lee HM, Yi KI, Jung JH, Lee IW

Abstract
We report an extremely rare case of hearing aid silicone impression material as a foreign body in the middle ear. Symptoms of the patient were otorrhea and vertigo after taking of a mold impression on his only hearing ear, and the symptoms mimicked chronic otitis media. A temporal bone CT scan revealed foreign body material in the middle ear and Eustachian tube. An intact canal wall mastoidectomy with a facial recess approach and type IV tympanoplasty was performed to remove the silicone impression material. In addition to the case report, we review the literature regarding impression material foreign bodies.

PMID: 27751620 [PubMed - indexed for MEDLINE]

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Palatal ancient schwannoma: optical, immunohistochemical and ultrastructural study with literature review.

Palatal ancient schwannoma: optical, immunohistochemical and ultrastructural study with literature review.

Eur Arch Otorhinolaryngol. 2017 Oct 03;:

Authors: Vera-Sirera B, Fernades-Ciacha L, Floria LM, Vera-Sempere F

Abstract
Schwannoma or neurilemmoma is a benign encapsulated slow-growing tumor that originates from a Schwann cell of a nerve, and is rare at intraoral locations. Different histological variants of schwannomas have been described, of these degenerative or ancient schwannoma is probably one of the least common in the oral cavity with only 16 previously reported cases, of which only one has been described in palatal location. Although ancient schwannoma shows particular characteristics, it is difficult to diagnose based on clinical and imaging appearance alone; as a result, morphological examination assisted by ancillary techniques is necessary to establish a definite diagnosis. We present a clinicopathological description of this rare variant of schwannoma, located in an unusual intraoral site, of a 26-year-old female. We illustrate the optical, immunohistochemical and ultrastructural characterization that aid diagnosis, as well as providing a review of the relevant published data of this unusual tumor.

PMID: 28975399 [PubMed - as supplied by publisher]

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Reduced upper obstructions in N3 and increased lower obstructions in REM sleep stage detected with manometry.

Reduced upper obstructions in N3 and increased lower obstructions in REM sleep stage detected with manometry.

Eur Arch Otorhinolaryngol. 2017 Oct 03;:

Authors: Wirth M, Schramm J, Bautz M, Hofauer B, Edenharter G, Ott A, Heiser C

Abstract
In obstructive sleep apnea (OSA), airway obstruction occurs at different anatomic levels. The frequency and location of obstructions play a crucial role in the planning of surgical treatment. The aim of this study was to evaluate the pharyngeal obstruction levels in different sleep stages with manometry in OSA patients. In addition, the manometry results were compared with drug-induced sleep endoscopy (DISE). Forty-one patients with OSA received manometry measurements during one night of sleep. All patients were simultaneously evaluated with polysomnography. The frequency of obstructions in different sleep stages was assessed. Twenty patients were additionally studied with DISE. Obstruction levels detected with manometry were compared with DISE. The frequency of upper and to a lesser extent lower obstructions decreased in sleep stage N3. In rapid eye movement (REM) sleep, lower obstructions increased. The overall proportion of upper and lower obstructions detected with manometry corresponded with DISE in 13 of 20 cases. A significant change in the obstruction levels was detected with manometry in N3 and REM sleep. The reduction of both upper and to a lesser extent lower obstructions in N3 suggests more stable airways in slow-wave sleep. Relevant lower obstructions were not detected in DISE compared to manometry in 5 out of 20 examinations. This could be a potential reason for treatment failure of site-specific surgical OSA treatment when only performing DISE preoperatively. Therefore, manometry could be a useful complementary tool in the preoperative evaluation for OSA.

PMID: 28975391 [PubMed - as supplied by publisher]

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Sudden Deafness during Antepartum versus Postpartum Periods

Objective: This study reviewed our experience in treating sudden deafness in antepartum (pregnant) and postpartum women during the past 2 decades. Methods: From 1997 to 2016, we have recorded sudden deafness in 16 antepartum (mean age, 32 years) and 3 postpartum (mean age, 31 years) women. Sudden deafness occurred during the 1st, 2nd, and 3rd trimesters in 5, 4, and 7 antepartum women, respectively. In contrast, the mean interval between giving birth and symptom onset in the 3 postpartum women was 18 days. Each patient underwent an inner ear test battery. Results: In 8 antepartum women treated by dextran infusion, the outcome as regards hearing was improved in 7 patients (88%) and unchanged in 1 patient. In contrast, the other 8 antepartum women selected no treatment, and only 1 patient (12%) achieved hearing improvement, exhibiting a significantly better outcome when receiving dextran treatment. For the postpartum women, 2 patients had hearing improvement when treated by antioxidants, while 1 patient retained unchanged hearing without treatment. Conclusion: Medication is needed in sudden deafness in antepartum or postpartum women rather than waiting for a natural course. No adverse effects have been identified in any of the mothers or offspring 1 year after delivery.
ORL 2017;79:274-281

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Task-based statistical image reconstruction for high-quality cone-beam CT.

Task-based statistical image reconstruction for high-quality cone-beam CT.

Phys Med Biol. 2017 Oct 04;:

Authors: Dang H, Stayman JW, Xu J, Zbijewski W, Sisniega A, Mow M, Wang X, Foos DH, Aygun N, Koliatsos VE, Siewerdsen JH

Abstract
Task-based analysis of medical imaging performance underlies many ongoing efforts in the development of new imaging systems. In statistical image reconstruction, regularization is often formulated in terms to encourage smoothness and/or sharpness (e.g., a linear, quadratic, or Huber penalty) but without explicit formulation of the task. We propose an alternative regularization approach in which a spatially varying penalty is determined that maximizes task-based imaging performance at every location in a 3D image. We apply the method to model-based image reconstruction (MBIR - viz., penalized weighted least-squares, PWLS) in cone-beam CT (CBCT) of the head, focusing on the task of detecting a small, low-contrast intracranial hemorrhage (ICH), and we test the performance of the algorithm in the context of a recently developed CBCT prototype for point-of-care imaging of brain injury. Theoretical predictions of local spatial resolution and noise are computed via an optimization by which regularization (specifically, the quadratic penalty strength) is allowed to vary throughout the image to maximize local task-based detectability index (d'). Simulation studies and test-bench experiments were performed using an anthropomorphic head phantom. Three PWLS implementations were tested: conventional (constant) penalty; a certainty-based penalty derived to enforce constant point-spread function, PSF; and the task-based penalty derived to maximize local detectability at each location. Conventional (constant) regularization exhibited a fairly strong degree of spatial variation in d', and the certainty-based method achieved uniform PSF, but each exhibited a reduction in detectability compared to the task-based method, which improved detectability up to ~15%. The improvement was strongest in areas of high attenuation (skull base), where the conventional and certainty-based methods tended to over-smooth the data. The task-driven reconstruction method presents a promising regularization method in MBIR by explicitly incorporating task-based imaging performance as the objective. The results demonstrate improved ICH conspicuity and support the development of high-quality CBCT systems.

PMID: 28976368 [PubMed - as supplied by publisher]

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[Rare, but important differential diagnosis of masses at the fronto-etmoidal/naso-pharyngeal basis of the skull].

Related Articles

[Rare, but important differential diagnosis of masses at the fronto-etmoidal/naso-pharyngeal basis of the skull].

Radiologe. 2016 Dec;56(12):1069-1071

Authors: Billich C, Vonend C, Schmitz B

PMID: 27796410 [PubMed - indexed for MEDLINE]

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18F-flortaucipir tau PET distinguishes established progressive supranuclear palsy from controls and Parkinson's disease: A multicenter study

ABSTRACT

Objective: ¹⁸F-flortaucipir (formerly ¹⁸F-AV1451 or ¹⁸F-T807) binds to neurofibrillary tangles in Alzheimer's disease (AD), but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo ¹⁸F-flortaucipir uptake in patients meeting clinical research criteria for PSP (N=33) to normal controls (N=46) and patients meeting criteria for Parkinson's disease (PD, N=26).

Methods: Participants underwent MRI and positron emission tomography for amyloid-β (¹¹C-PiB or ¹⁸F-florbetapir) and tau (¹⁸F-flortaucipir). ¹⁸F-flortaucipir Standardized Uptake Value Ratios were calculated (t=80-100 min, cerebellum gray matter reference). Voxelwise and region-of-interest group comparisons were performed in template space, with Receiver Operating Characteristic curve analyses to assess single-subject discrimination. Qualitative comparisons with postmortem tau are reported in one patient who died nine months after ¹⁸F-flortaucipir.

Results: Clinical PSP patients showed bilaterally elevated ¹⁸F-flortaucipir uptake in globus pallidus, putamen, subthalamic nucleus, midbrain and dentate nucleus relative to controls and PD patients (voxelwise p<0.05 family-wise-error-corrected). Globus pallidus binding best distinguished PSP patients from controls and PD (Area Under the Curve (AUC)=0.872 vs. controls, AUC=0.893 vs. PD). PSP clinical severity did not correlate with ¹⁸F-flortaucipir in any region. A patient with clinical PSP and pathological diagnosis of corticobasal degeneration had severe tau-pathology in PSP-related brain structures with good correspondence between in vivo ¹⁸F-flortaucipir and postmortem tau neuropathology.

Interpretation: ¹⁸F-flortaucipir uptake was elevated in PSP versus controls and PD patients in a pattern consistent with the expected distribution of tau pathology. This article is protected by copyright. All rights reserved.

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[Hearing rehabilitation with the cochlea implant following translabyrinthine CPA tumor removal ?]

[Hearing rehabilitation with the cochlea implant following translabyrinthine CPA tumor removal ?]

Laryngorhinootologie. 2017 Oct 04;:

Authors: Schipper J, Kristin J, Volpert S, Klenzner T

Abstract
We present a quality analysis of 10 patients with an individual treatment trial for a simultaneous or consecutive cochlea implantation after translabyrinthine removal of a neurinoma at the cerebellopontine angle. The results show that most of the patients benefit from the cochlea implantation after unilateral deafness. Through a careful surgical preparation technique at the inner ear canal and its surroundings the morphological and functional integrity of the neurovascular structures can be guaranteed.

PMID: 28977813 [PubMed - as supplied by publisher]

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Laryngopharyngeal Reflux Disease - LPRD.

Laryngopharyngeal Reflux Disease - LPRD.

Med Arch. 2017 Jun;71(3):215-218

Authors: Salihefendic N, Zildzic M, Cabric E

Abstract
INTRODUCTION: Laryngopharyngeal reflux disease (LPRD) referes to an inflammatory reaction of the mucous membrane of pharynx, larynx and other associated respiratory organs, caused by a reflux of stomach contents into the esophagus. LPRD is considered to be a relatively new clinical entity with a vast number of clinical manifestations which are treated through different fields of medicine, often without a proper diagnosis. In gastroenterology it is still considered to be a manifestation of GERD, which stands for gastroesophageal reflux disease. Patients suffering from LPRD communicate firstly with their primary physicians, and since further treatment might ask for a multidisciplinary approach, it is important to have a unified approach among experts when treating these patients.
GOAL: This paper is written with the intention to assess the frequency of symptoms of LPR in family medicine, possible diagnostics and adequate treatment in primary health care.
MATERIALS AND METHODS: This is a prospective, descriptive cohort study. Authors used "The Reflux Symptom Index" (RSI) questionnaire. Examinees were all patients who reported to their family medicine office in Gracanica for the first time with new symptoms during a period of one year. Patients with positive results for LPR (over 13 points) were treated in accordance with the suggested algorithm and were monitored during the next year.
RESULTS: Out of 2123 examinees who showed symptoms of LPR, 390 tested positive according to the questionnaire. This group of examinees were treated in accordance with all suggested protocols and algorithms. 82% showed signs of improvement as a response to basic treatment provided by their physicians.
CONCLUSION: Almost every fifth patient who reports to their family medicine physician shows symptoms of LPR. On primary health care levels it is possible to establish some form of prevention, diagnostics and therapy for LPR in accordance with suggested algorithms. Only a small number of patients requires procedures which fall under other clinical fields.

PMID: 28974837 [PubMed - in process]

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Optimization of Endotracheal Tube Cuff Pressure by Monitoring CO2 Levels in the Subglottic Space in Mechanically Ventilated Patients: A Randomized Controlled Trial.

Related Articles

Optimization of Endotracheal Tube Cuff Pressure by Monitoring CO2 Levels in the Subglottic Space in Mechanically Ventilated Patients: A Randomized Controlled Trial.

Anesth Analg. 2017 Oct;125(4):1309-1315

Authors: Efrati S, Bolotin G, Levi L, Zaaroor M, Guralnik L, Weksler N, Levinger U, Soroksky A, Denman WT, Gurman GM

Abstract
BACKGROUND: Many of the complications of mechanical ventilation are related to inappropriate endotracheal tube (ETT) cuff pressure. The aim of the current study was to evaluate the effectiveness of automatic cuff pressure closed-loop control in patients under prolonged intubation, where presence of carbon dioxide (CO2) in the subglottic space is used as an indicator for leaks. The primary outcome of the study is leakage around the cuff quantified using the area under the curve (AUC) of CO2 leakage over time.
METHODS: This was a multicenter, prospective, randomized controlled, noninferiority trial including intensive care unit patients. All patients were intubated with the AnapnoGuard ETT, which has an extra lumen used to monitor CO2 levels in the subglottic space.The study group was connected to the AnapnoGuard system operating with cuff control adjusted automatically based on subglottic CO2 (automatic group). The control group was connected to the AnapnoGuard system, while cuff pressure was managed manually using a manometer 3 times/d (manual group). The system recorded around cuff CO2 leakage in both groups.
RESULTS: Seventy-two patients were recruited and 64 included in the final analysis. The mean hourly around cuff CO2 leak (mm Hg AUC/h) was 0.22 ± 0.32 in the manual group and 0.09 ± 0.04 in the automatic group (P = .01) where the lower bound of the 1-sided 95% confidence interval was 0.05, demonstrating noninferiority (>-0.033). Additionally, the 2-sided 95% confidence interval was 0.010 to 0.196, showing superiority (>0.0) as well. Significant CO2 leakage (CO2 >2 mm Hg) was 0.027 ± 0.057 (mm Hg AUC/h) in the automatic group versus 0.296 ± 0.784 (mm Hg AUC/h) in the manual group (P = .025). In addition, cuff pressures were in the predefined safety range 97.6% of the time in the automatic group compared to 48.2% in the automatic group (P < .001).
CONCLUSIONS: This study shows that the automatic cuff pressure group is not only noninferior but also superior compared to the manual cuff pressure group. Thus, the use of automatic cuff pressure control based on subglottic measurements of CO2 levels is an effective method for ETT cuff pressure optimization. The method is safe and can be easily utilized with any intubated patient.

PMID: 28787340 [PubMed - indexed for MEDLINE]

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Open airway reconstruction in adults: Outcomes and prognostic factors.

Related Articles

Open airway reconstruction in adults: Outcomes and prognostic factors.

Am J Otolaryngol. 2017 Jan - Feb;38(1):7-12

Authors: Abouyared M, Szczupak M, Barbarite E, Sargi ZB, Rosow DE

Abstract
PURPOSE: The purpose was to assess the success of open tracheal resection and re-anastomosis for non-malignant tracheal stenosis in adults. Successful operations were defined as T-tube or tracheostomy-free status by 6months post-operatively.
MATERIALS AND METHODS: Retrospective chart review was performed and data were recorded in a de-identified manner. The primary outcome was T-tube or tracheostomy-free status by 6months following tracheal resection. Clinical and demographic characteristics were evaluated as potential prognostic variables.
RESULTS: Thirty-two patients met inclusion criteria, with a median age of 46. Seven patients underwent tracheal resection with primary closure, without stenting. Successful tracheal resection was defined as tracheostomy or T-tube free by 6months post-operation, and this was possible in 21 patients (66%). Eighty-two percent of patients with cricoid cartilage-sparing tracheal resection had a successful outcome, versus 30% of patients who underwent cricoid cartilage resection (HR 5.02, 95% CI 1.46-17.3; p=0.011). Patients with a history of tracheostomy-dependence were four times more likely to remain tube-dependent at 6months (HR 4.15, 95% CI 1.56-10.86; p=0.004).
CONCLUSIONS: Tracheal stenosis remains a very difficult problem to treat. In our series, we confirm that patients with cricoid involvement or with a history of tracheostomy were more likely to be tube dependent at 6-months post-operation.

PMID: 27776743 [PubMed - indexed for MEDLINE]

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A patient with a severe glottic stenosis and saddle nose.

Related Articles

A patient with a severe glottic stenosis and saddle nose.

Acta Clin Belg. 2017 Apr;72(2):130-132

Authors: Sabato V, Vanderveken OM, Van den Wyngaert T, Van Laer C, Ebo D

Abstract
We present the case of a 39-year-old man with a severe glottis stenosis. The saddle nose, images of laryngotracheal stenosis and the (FDG) positron-emission tomography/computed tomography lead to a final diagnosis of relapsing polychondritis. In the patient a coexistent myelodysplastic syndrome was diagnosed. Moreover, the elevated total IgG4 exceeding 135 ml/dl requested additional immunochemistry for detection of IgG4-bearing plasma cells in the biopsies. The patient underwent an allogenic stem cell transplantation and died on day 40 after the transplantation because of an acute steroid-resistent graft vs host.

PMID: 27075792 [PubMed - indexed for MEDLINE]

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The Swedish cause of death register

Abstract

Sweden has a long tradition of recording cause of death data. The Swedish cause of death register is a high quality virtually complete register of all deaths in Sweden since 1952. Although originally created for official statistics, it is a highly important data source for medical research since it can be linked to many other national registers, which contain data on social and health factors in the Swedish population. For the appropriate use of this register, it is fundamental to understand its origins and composition. In this paper we describe the origins and composition of the Swedish cause of death register, set out the key strengths and weaknesses of the register, and present the main causes of death across age groups and over time in Sweden. This paper provides a guide and reference to individuals and organisations interested in data from the Swedish cause of death register.

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Detection of generalized tonic–clonic seizures using surface electromyographic monitoring

Summary

Objective

A prospective multicenter phase III trial was undertaken to evaluate the performance and tolerability in the epilepsy monitoring unit (EMU) of an investigational wearable surface electromyographic (sEMG) monitoring system for the detection of generalized tonic–clonic seizures (GTCSs).

Methods

One hundred ninety-nine patients with a history of GTCSs who were admitted to the EMU in 11 level IV epilepsy centers for clinically indicated video-electroencephalographic monitoring also received sEMG monitoring with a wearable device that was worn on the arm over the biceps muscle. All recorded sEMG data were processed at a central site using a previously developed detection algorithm. Detected GTCSs were compared to events verified by a majority of three expert reviewers.

Results

For all subjects, the detection algorithm detected 35 of 46 (76%, 95% confidence interval [CI] = 0.61–0.87) of the GTCSs, with a positive predictive value (PPV) of 0.03 and a mean false alarm rate (FAR) of 2.52 per 24 h. For data recorded while the device was placed over the midline of the biceps muscle, the system detected 29 of 29 GTCSs (100%, 95% CI = 0.88–1.00), with a detection delay averaging 7.70 s, a PPV of 6.2%, and a mean FAR of 1.44 per 24 h. Mild to moderate adverse events were reported in 28% (55 of 199) of subjects and led to study withdrawal in 9% (17 of 199). These adverse events consisted mostly of skin irritation caused by the electrode patch that resolved without treatment. No serious adverse events were reported.

Significance

Detection of GTCSs using an sEMG monitoring device on the biceps is feasible. Proper positioning of this device is important for accuracy, and for some patients, minimizing the number of false positives may be challenging.

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Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency

Abstract

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non-infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches.

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Influenza Vaccination in Patients with Common Variable Immunodeficiency (CVID)

Abstract

Purpose of Review

Vaccination against influenza in patients with primary antibody deficiency is recommended. Common variable immunodeficiency (CVID) is the most frequent and clinically relevant antibody deficiency disease and is by definition characterized by an impaired vaccination response. The purpose of this review is to present the current knowledge of humoral and cellular vaccine response to influenza in CVID patients.

Recent Findings

Studies conducted in CVID patients demonstrated an impaired humoral response upon influenza vaccination. Data on cellular immune response are in part conflicting, with two out of three studies showing responses similar to healthy controls.

Summary

Available data suggest a benefit from influenza vaccination in CVID patients. Therefore, annual influenza vaccination in patients and their close household contacts is recommended.

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Somatic Hypermutation Defects in Common Variable Immune Deficiency

Abstract

Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by impaired antibody production and recurrent infections. In the last 20 years, several groups have reported that B cells from CVID patients have an impaired somatic hypermutation (SHM). The reported frequency of this defect among CVID patient cohorts is highly variable and so is the methodology used to evaluate this process. Interestingly, the low level of SHM on B cells from CVID patients has been correlated with the presence of infectious and non-infectious complications. In this review, an overview of the studies regarding SHM in CVID patients is presented. We highlight the importance of SHM studies in CVID patients as a clinical tool due to the reported association with clinical complications by several groups. We also considered SHM measurement useful to guide future investigations in order to identify genetic defects involved in the development of the disease.

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Electronic Cigarettes: Their Constituents and Potential Links to Asthma

Abstract

Purpose of Review

Vaping is gaining popularity in the USA, particularly among teens and young adults. While e-cigs are commonly represented as safer alternatives to tobacco cigarettes, little is known regarding the health effects of their short- or long-term use, especially in individuals with pre-existing respiratory diseases such as asthma. Flavored e-cig liquids (e-liquids) and e-cig aerosols contain airway irritants and toxicants that have been implicated in the pathogenesis and worsening of lung diseases. In this review, we will summarize existing data on potential health effects of components present in e-cig aerosols, such as propylene glycol, vegetable glycerin, nicotine, and flavorings, and discuss their relevance in the context of asthma.

Recent Findings

Recent survey data indicate that adolescents with asthma had a higher prevalence of current e-cig use (12.4%) compared to their non-asthmatics peers (10.2%) and conveyed positive beliefs about tobacco products, especially e-cigs. Similarly, a study conducted among high school students from Ontario, Canada, indicated a greater likelihood of e-cig use in asthmatics as compared to their non-asthmatic peers. Availability of different flavorings is often cited as the main reason among youth/adolescents for trying e-cigs or switching from cigarettes to e-cigs. Occupational inhalation of some common food-safe flavoring agents is reported to cause occupational asthma and worsen asthmatic symptoms. Moreover, workplace inhalation exposures to the flavoring agent diacetyl have caused irreversible obstructive airway disease in healthy workers. Additionally, recent studies report that thermal decomposition of propylene glycol (PG) and vegetable glycerin (VG), the base constituents of e-liquids, produces reactive carbonyls, including acrolein, formaldehyde, and acetaldehyde, which have known respiratory toxicities. Furthermore, recent nicotine studies in rodents reveal that prenatal nicotine exposures lead to epigenetic reprogramming in the offspring, abnormal lung development, and multigenerational transmission of asthmatic-like symptoms.

Summary

Comparisons of the toxicity and health effects of e-cigs and conventional cigarettes often focus on toxicants known to be present in cigarette smoke (CS) (i.e., formaldehyde, nitrosamines, etc.), as well as smoking-associated clinical endpoints, such as cancer, bronchitis, and chronic obstructive pulmonary disease (COPD). However, this approach disregards potential toxicity of components unique to flavored e-cigs, such as PG, VG, and the many different flavoring chemicals, which likely induce respiratory effects not usually observed in cigarette smokers.

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Are food allergic consumers ready for informative precautionary allergen labelling?

Precautionary allergen labelling (PAL) has resulted in consumer confusion. Previous research has shown that interpretive labels (using graphics, symbols, or colours) are better understood than the traditional ...

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Analgesia (mis)usage on a dental emergency service: a patient survey

Abstract

Objectives

Analgesics are one of the most frequently used medicines. Self-medication and misuse have been described in the literature. The purpose of this study was to document analgesic (mis)use in a population seeking emergency dental treatment.

Material and methods

Patients consulting a dental emergency service were randomly asked to complete a questionnaire on analgesic use, knowledge and information on the analgesics and on their pain history. A photobook was used as an aid to identify products used. Descriptive statistics were combined with chi-square and Mann-Whitney U testing.

Results

Ninety-eight patients were included. Acetaminophen (69.4%) and ibuprofen (65.3%) were the most frequently used products. Nearly half of the subjects (43.9%) combined at least two analgesics. Although 42.9% of subjects were aware of the maximum daily dose, 62.2% of the subjects exceeded this limit, specifically 76.6% of subjects using ibuprofen and 32.4% of subjects using acetaminophen overdosing. Females overdosed significantly more than males. Ingestion on medical advice did not affect the overdose rates significantly. No significant relation was found between the absence of knowledge on the maximum daily dose and actual overdosing. No higher pain reduction was found in patients overdosing analgesics. The average number of days patients experienced pain before consulting the emergency unit was 12. A significant relation was found between the lag time and overdosing.

Conclusions

A large portion of the patients overdosed analgesics. Even prior medical advice did not reduce significantly overdose rates.

Clinical relevance

Dentists treating emergency cases clearly need to be aware of the high risk and high rates of overdosing analgesics in their patients.

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Isocitrate dehydrogenase-mutant glioma: Evolving clinical and therapeutic implications

The metabolic genes isocitrate dehydrogenase 1 (IDH1) and IDH2 are commonly mutated in low-grade glioma and in a subset of glioblastoma. These mutations co-occur with other recurrent molecular alterations, including 1p/19q codeletions and tumor suppressor protein 53 (TP53) and alpha thalassemia/mental retardation (ATRX) mutations, which together help to define a molecular signature that aids in the classification of gliomas and helps to better predict clinical behavior. A confluence of research suggests that glioma development in IDH-mutant and IDH wild-type tumors is driven by different oncogenic processes and responds differently to current treatment paradigms. Herein, the authors discuss the discovery of IDH mutations and associated molecular alterations in glioma, review clinical features common to patients with IDH-mutant glioma, and highlight current understanding of IDH mutation-driven gliomagenesis with implications for emerging treatment strategies. Cancer 2017. © 2017 American Cancer Society.

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Efficacy and safety of retreatment with nivolumab in metastatic melanoma patients previously treated with nivolumab

Abstract

Background

Nivolumab is a monoclonal antibody directed against programmed death-1 that has been shown to improve survival in patients with metastatic melanoma. However, the efficacy of nivolumab and other agents in melanoma remains limited. The objective of this study was to evaluate the efficacy and safety of retreatment with nivolumab in metastatic melanoma patients who previously progressed on nivolumab.

Patients and methods

A retrospective review was performed on eight consecutive metastatic melanoma patients retreated with nivolumab who progressed on previous nivolumab. These patients received nivolumab 2 mg/kg every 3 weeks. Best responses to each treatment were assessed using RECIST 1.1.

Results

Of eight metastatic melanoma patients, three patients received chemotherapy before first nivolumab. The median first nivolumab treatment period was 4.1 months. During first nivolumab, 3 (37.5%) patients achieved a partial response and 3 (37.5%) patients achieved stable disease as their best response. First nivolumab was discontinued due to disease progression in seven patients and grade 3 colitis in 1 patient. Patients were subsequently treated with ipilimumab (n = 6), vemurafenib (n = 1), or no other medical treatment (n = 1). The median treatment period between first and second nivolumab was 3.0 months. Four patients received radiation therapy between first and second nivolumab. The median second nivolumab treatment period was 4.3 months. Among the eight patients who received second nivolumab, 2 (25%) patients achieved a partial response and 3 (37.5%) patients achieved stable disease as their best response. Second nivolumab was discontinued due to disease progression in seven patients. One patient continues to receive second nivolumab. Among the four patients treated with ipilimumab and radiotherapy between first and second nivolumab, the response rate was 50% and the disease control rate was 75%.

Conclusions

This study showed that retreatment with nivolumab is an option for select metastatic melanoma patients after previous nivolumab treatment.

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Analgesia (mis)usage on a dental emergency service: a patient survey

Abstract

Objectives

Analgesics are one of the most frequently used medicines. Self-medication and misuse have been described in the literature. The purpose of this study was to document analgesic (mis)use in a population seeking emergency dental treatment.

Material and methods

Patients consulting a dental emergency service were randomly asked to complete a questionnaire on analgesic use, knowledge and information on the analgesics and on their pain history. A photobook was used as an aid to identify products used. Descriptive statistics were combined with chi-square and Mann-Whitney U testing.

Results

Ninety-eight patients were included. Acetaminophen (69.4%) and ibuprofen (65.3%) were the most frequently used products. Nearly half of the subjects (43.9%) combined at least two analgesics. Although 42.9% of subjects were aware of the maximum daily dose, 62.2% of the subjects exceeded this limit, specifically 76.6% of subjects using ibuprofen and 32.4% of subjects using acetaminophen overdosing. Females overdosed significantly more than males. Ingestion on medical advice did not affect the overdose rates significantly. No significant relation was found between the absence of knowledge on the maximum daily dose and actual overdosing. No higher pain reduction was found in patients overdosing analgesics. The average number of days patients experienced pain before consulting the emergency unit was 12. A significant relation was found between the lag time and overdosing.

Conclusions

A large portion of the patients overdosed analgesics. Even prior medical advice did not reduce significantly overdose rates.

Clinical relevance

Dentists treating emergency cases clearly need to be aware of the high risk and high rates of overdosing analgesics in their patients.

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Reduced-dose C-arm computed tomography applications at a pediatric institution

Abstract

Background

Reduced-dose C-arm computed tomography (CT) uses flat-panel detectors to acquire real-time 3-D images in the interventional radiology suite to assist with anatomical localization and procedure planning.

Objective

To describe dose-reduction techniques for C-arm CT at a pediatric institution and to provide guidance for implementation.

Materials and methods

We conducted a 5-year retrospective study on procedures using an institution-specific reduced-dose protocol: 5 or 8 s Dyna Rotation, 248/396 projection images/acquisition and 0.1–0.17 μGy/projection dose at the detector with 0.3/0.6/0.9-mm copper (Cu) filtration. We categorized cases by procedure type and average patient age and calculated C-arm CT and total dose area product (DAP).

Results

Two hundred twenty-two C-arm CT-guided procedures were performed with a dose-reduction protocol. The most common procedures were temporomandibular and sacroiliac joint injections (48.6%) and sclerotherapy (34.2%). C-arm CT was utilized in cases of difficult percutaneous access in less common applications such as cecostomy and gastrostomy placement, foreign body retrieval and thoracentesis. C-arm CT accounted for between 9.9% and 80.7% of the total procedural DAP.

Conclusion

Dose-reducing techniques can preserve image quality for intervention while reducing radiation exposure to the child. This technology has multiple applications within pediatric interventional radiology and can be considered as an adjunctive imaging tool in a variety of procedures, particularly when percutaneous access is challenging despite routine fluoroscopic or ultrasound guidance.

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Efficient Removal of Lead(II) Ions from Aqueous Solutions Using Methyl-β-Cyclodextrin Modified Graphene Oxide

Abstract

Graphene oxide (GO) and graphene oxide modified with methyl-β-cyclodextrin denoted as GO-mβCD were prepared and applied as adsorbents to determine the adsorption characteristics of Pb(II) from aqueous solutions. The characteristic results of Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Raman spectroscopy, and scanning electron microscopy (SEM) showed that mβCD was successfully physically attached to GO to form the GO-mβCD nanocomposite. The adsorption equilibrium and kinetics of the adsorbents were well described by Langmuir isotherm and pseudo-second-order models, respectively. The maximum Pb(II) adsorption capacity of GO-mβCD (at pH = 6 and room temperature) was determined as 312.5 mg/g which was significantly higher than that of GO (217.39 mg/g). This indicates that the modification of GO with mβCD enhances the adsorption capacity of GO. The desorption studies show that the adsorbent GO-mβCD can be used for at least five cycles with non-significant loss of its initial adsorption capacity for Pb(II) ions.

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The oncogenic Golgi phosphoprotein 3 like overexpression is associated with cisplatin resistance in ovarian carcinoma and activating the NF-κB signaling pathway

Chemo-resistance is a leading cause of tumor relapse and treatment failure in patients with ovarian cancer. The identification of effective strategies to overcome drug resistance will have a significant clinic...

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Running Performance, $${\dot}{\bf O}_{\bf {2max}}$$ V ˙ O 2 max , and Running Economy: The Widespread Issue of Endogenous Selection Bias

Abstract

Studies in sport and exercise medicine routinely use samples of highly trained individuals in order to understand what characterizes elite endurance performance, such as running economy and maximal oxygen uptake ( \({\dot}{\rm O}_{\mathrm {2max}}\) ). However, it is not well understood in the literature that using such samples most certainly leads to biased findings and accordingly potentially erroneous conclusions because of endogenous selection bias. In this paper, I review the current literature on running economy and \({\dot}{\rm O}_{\mathrm {2max}}\) , and discuss the literature in light of endogenous selection bias. I demonstrate that the results in a large part of the literature may be misleading, and provide some practical suggestions as to how future studies may alleviate endogenous selection bias.

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Why averaging multiple MUNIX measures in the longitudinal assessment of patients with ALS?

Publication date: Available online 4 October 2017
Source:Clinical Neurophysiology
Author(s): Marcio Luiz Escorcio-Bezerra, Agessandro Abrahao, Denizart Santos-Neto, Nadia Iandoli de Oliveira Braga, Acary Souza Bulle Oliveira, Gilberto Mastrocola Manzano
ObjectiveTo assess the impact of averaging multiple MUNIX trials on the follow-up of patients with amyotrophic lateral sclerosis (ALS).MethodsWe determined the percent relative change (%RC) of MUNIX, in healthy subjects and patients with ALS, by subtracting the MUNIX value in the second visit from the first. Both the mean of a set of three MUNIX (mean-MUNIX) and the first MUNIX sample (single-MUNIX) were evaluated. Then, we studied the sensitivity to detect relative changes over time and the statistical dispersion of the%RC from these two parameters.ResultsWe found that the mean-MUNIX%RC has lower mean coefficient of variation than the single-MUNIX%RC in all muscles. The mean-MUNIX also resulted in more ALS patients with significant%RC, i.e., outside reference limits.ConclusionThe mean-MUNIX resulted in less dispersed values of%RC in patients with ALS and thus, increased the precision of the technique. The mean-MUNIX resulted also in an increase in the sensitivity to track changes over time in these patients.SignificanceThe mean-MUNIX should be considered in any ALS follow-up study as a more reliable approach and as a way of potentially reducing the sample size needed for the study.



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Development and validation of a childhood self-efficacy for functional constipation questionnaire

Abstract

Background

Children with functional constipation fear painful bowel movements leading to stool withholding behavior. Self-efficacy is the belief that an individual can accomplish a given goal. If children with constipation avoid defecation because they think that they are unable defecate comfortably, this low self-efficacy may prevent treatment success. The aim of the current study was to develop and validate a constipation specific self-efficacy scale.

Methods

The self-efficacy for functional constipation questionnaire (SEFCQ) was developed by the authors and evaluated by 10 children and seven experts. Ninety-nine healthy children and 122 children with functional constipation completed the SEFCQ and three other questionnaires measuring related constructs.

Key Results

Minor changes were made in wording based on feedback from experts and children. Factor analysis showed two scales, a 7 item Action scale (Cronbach's α = 0.88) and a 7 item Emotion scale (Cronbach α = 0.86). The SEFCQ total scale correlated positively with general self-efficacy (r = .32, P < .001) and quality of life (r = .20; P < .01) and negatively with anxiety (r = −.15; P < .05). Scores on the SEFCQ were higher in children without functional constipation compared to those with functional constipation (53.33 + 3.38 vs 39.34 + 7.19, P < .001).

Conclusions & Inferences

We developed a constipation specific self-efficacy questionnaire with good initial internal reliability, excellent face validity and adequate content validity. A low self-efficacy for defecation, may make the child resist their physical urge to defecate and hence, the need for further studies to assess its effect on treatment outcomes.

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The Correlation of Allergic Rhinitis with ABO Phenotype

Abstract

The aim of study the correlation of ABO phenotypes in patients of allergic rhinitis and controls and to compare our study with the previous studies to analyse the association of above. 100 patients with symptoms of allergic rhinitis and 100 controls individual were selected from same geographical region and paired by gender and age were enrolled in the study. Detailed history, examination and relevant radiological and hematological investigations were done. ABO phenotypes were identified in red blood cells using hemagglutination technique. This clinic-based observational study was conducted among the patients presenting with signs and symptoms of allergic rhinitis. Maximum no. of cases were seen in ABO phenotype O (52%), followed by A, B and AB (33, 12 and 3% respectively) and it was found to be statistically significant (p = 0.001). Also more number of male patients were found in B and O blood group which was statistically significant (OR 5.33, p = 0.017 and OR 3.63, p = 0.006 respectively). Controls showed marginalized difference in distribution among the basis of different ABO phenotypes. The O blood group phenotype of ABO histo-blood group system is associated with AR. This study contributes to the better understanding of the pathophysiology and clinical variability of this disease and may help to improve strategies towards its prevention and diagnosis. Additionally, ABO histo-blood group phenotyping, an inexpensive and easy to perform assay could be used to identify individuals at risk of developing allergic rhinitis.

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Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer

Abstract

Background

Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to first line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer.

Patients and Methods

83 patients on first line AI therapy for metastatic breast cancer were enrolled in a prospective study. Plasma samples were collected every 3 months to disease progression and ctDNA analysed by digital droplet PCR and enhanced tagged-amplicon sequencing (eTAm-Seq). Mutations identified in progression samples by sequencing were tracked back through samples prior to progression to study the evolution of mutations on therapy. The frequency of novel mutations were validated in an independent cohort of available baseline plasma samples in the SoFEA trial, which enrolled patients with prior sensitivity to AI.

Results

Of the 39 patients who progressed on first line AI, 56.4%(22/39) had ESR1 mutations detectable at progression, which were polyclonal in 40.9%(9/22) patients. In serial tracking, ESR1 mutations were detectable median 6.7 months (95%CI 3.7-NA) prior to clinical progression. Utilising eTAm-Seq ctDNA sequencing of progression plasma, ESR1 mutations were demonstrated to be sub-clonal in 72.2%(13/18) patients. Mutations in RAS genes were identified in 15.4%(6/39) of progressing patients (4 KRAS, 1 HRAS, 1 NRAS). In SoFEA, KRAS mutations were detected in 21.2%(24/113) patients, although there was no evidence that KRAS mutation status was prognostic for progression free or overall survival.

Conclusions

Cancers progressing on first line AI show high levels of genetic heterogeneity, with frequent sub-clonal mutations. Sub-clonal KRAS mutations are found at high frequency. The genetic diversity of AI resistant cancers may limit subsequent targeted therapy approaches.

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