Learning curve for endoscopic evaluation of vocal folds lesions with narrow band imaging

Publication date: Available online 4 August 2018

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Michał Żurek, Anna Rzepakowska, Ewa Osuch-Wójcikiewicz, Kazimierz Niemczyk

Abstract

Introduction

The endoscopic methods are progressing and becoming more common in routine clinical diagnosis in the field of otorhinolaryngology. Relatively large amount of researches have proved high accuracy of narrow band imaging endoscopy in differentiating benign and malignant lesions within vocal folds. However, little is known about learning curve in narrow band imaging evaluation of laryngeal lesions.

Objective

The aim of this study was to determine the learning curve for the narrow band imaging evaluation of vocal folds pathologies depending on the duration of the procedure.

Methods

Records of 134 narrow band imaging that were analyzed in terms of the duration of the procedure and the accuracy of diagnosis confirmed by histopathological diagnosis were enrolled in the study. The narrow band imaging examinations were performed sequentially by one investigator over a period of 18 months.

Results

The average duration of narrow band imaging recordings was 127.82 s. All 134 studies were divided into subsequent series of several elements. An evident decrease in time of investigation was noticed between 13th and 14th series, when the examinations were divided into 5 elements series, which corresponds to the difference between 65th and 70th subsequent narrow band imaging examination. Parallel groups of 67 examinations were created. Group 1 included 1st to 67th subsequent narrow band imaging examination; Group 2 – 68th to 134th narrow band imaging examinations. The non-parametric U Mann–Whitney test confirmed statistically significant difference between the mean duration of narrow band imaging examination in both groups 160.5 s and 95.1 s, respectively (p < 10⁻⁷). Sensitivity and specificity of narrow band imaging examination in the first group were respectively: 83.7% and 76.7%. In the second group, these indicators amounted 98.1% and 80% respectively.

Conclusions

A minimum of 65th–70th narrow band imaging examinations are required to reach a plateau phase of the learning process in assessment of glottis lesions. Analysis of learning curves is useful for the development of training programs and determination of a mastery level.

Resumo

Introdução

Os métodos endoscópicos estão progredindo e se tornando comuns no diagnóstico clínico de rotina também na otorrinolaringologia. Um número relativamente grande de pesquisas demonstrou alta precisão na endoscopia com imagem de banda estreita na diferenciação de lesões benignas e malignas nas pregas vocais. Entretanto, pouco se sabe sobre a curva de aprendizado na avaliação da de banda estreita de lesões laríngeas.

Objetivo

O objetivo do nosso estudo foi determinar a curva de aprendizado para a avaliação por imagem de banda estreita das afecções das pregas vocais, de acordo com a duração do procedimento.

Método

Foram incluídos no estudo 134 registros de imagens de banda estreita analisadas em termos da duração do procedimento e da acurácia do diagnóstico confirmado pelo diagnóstico histopatológico. Os exames com imagem de banda estreita foram realizados sequencialmente por um investigador por um período de 18 meses.

Resultados

A duração média dos registros de imagem de banda estreita foi de 127,82s. Todos os 134 estudos foram divididos em séries subsequentes de vários elementos. Uma evidente diminuição no tempo de investigação foi observada entre as séries 13 e 14, quando os exames foram divididos em séries de 5 elementos, o que corresponde à diferença entre o 65° e 70° exames de imagem de banda estreita subsequentes. Foram criados grupos paralelos de 67 exames. O grupo 1 incluiu o 1° ao 67° exame de imagem de banda estreita subsequente; Grupo 2 – o 68° ao 134° exame de imagem de banda estreita. O teste não-paramétrico U de Mann-Whitney confirmou uma diferença estatisticamente significante entre a duração média do exame de imagem de banda estreita em ambos os grupos de 160,5s e 95,1s, respectivamente (p < 10^-7). A sensibilidade e especificidade do exame de imagem de banda estreita no primeiro grupo foram, respectivamente: 83,7% e 76,7%. No segundo grupo, esses indicadores foram 98,1% e 80%, respectivamente.

Conclusões

Um mínimo de 65 a 70 exames de imagem de banda estreita são necessários para se atingir a fase de estabilização (plateau) do processo de aprendizado na avaliação de lesões de glote. A análise das curvas de aprendizado é útil para o desenvolvimento de programas de treinamento e determinar o n.

https://ift.tt/2MjlRiY

Otopalatodigital syndrome type I: New temporal bone CT-scan sign in a case with a de novo novel mutation

Publication date: Available online 4 August 2018

Source: Acta Otorrinolaringológica Española

Author(s): Marta Martínez-López, Ana Navedo, Reyes López De Mesa, Francisco Javier Cervera-Paz

https://ift.tt/2Mkg1Og

A long styloid process and Collet–Sicard syndrome

Publication date: Available online 4 August 2018

Source: Acta Otorrinolaringológica Española

Author(s): João Simões, Sofia Paiva, Jorge Miguéis, António Miguéis

https://ift.tt/2M0OYdX

Evaluación de la disfunción de la trompa de Eustaquio mediante el cuestionario de disfunción tubárica (ETDQ-7) y la tubomanometría

Publication date: Available online 4 August 2018

Source: Acta Otorrinolaringológica Española

Author(s): Mayte Herrera, Gustavo Eisenberg, Guillermo Plaza

Resumen

Objetivo

Evaluación del grado de severidad de la disfunción tubárica crónica mediante la adaptación al español del Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) y mediante el empleo de la tubomanometría (TMM).

Materiales y métodos

Validación española del cuestionario ETDQ-7. Muestra: Estudio prospectivo de cohortes compuesto por 125 pacientes, de ellos 75 con enfermedad ótica compatible con la existencia de disfunción tubárica crónica. Medidas de evaluación: administración de la versión española del ETDQ-7 tras traducción y retrotraducción y establecimiento de su fiabilidad y consistencia interna. Evaluación de la utilidad de la TMM junto con el ETDQ-7 en el estudio de una posible disfunción de la trompa de Eustaquio.

Resultados

La adaptación española del ETDQ-7 muestra fiabilidad y consistencia interna elevada. La unión de la TMM aumenta la sensibilidad y la especificidad en el diagnóstico de la disfunción de la trompa de Eustaquio.

Conclusión

La adaptación del ETDQ-7 al español es válida, fiable y puede ser utilizada en la evaluación clínica para cuantificar el impacto y la severidad de la disfunción tubárica crónica en el paciente. Un test nuevo formado por la suma del ETDQ-7 y la TMM podrían convertirse en un método exploratorio de rutina en el diagnóstico de la disfunción de la trompa de Eustaquio.

Abstract

Objective

Evaluation of the severity of Eustachian tube dysfunction using the Spanish validation of the Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) and tubomanometry (TMM).

Materials and methods

Spanish validation of the ETDQ-7. Patients: Prospective study with 125 patients, 75 of whom reported symptoms compatible with Eustachian tube dysfunction. Outcome measures: The Spanish version of the ETDQ-7 was administered after translation and back-translation. Internal consistency and reliability were established. Usefulness evaluation of TMM plus ETDQ-7 in the study of Eustachian tube dysfunction.

Results

The Spanish adaptation of the ETDQ-7 showed high reliability and internal consistency. TMM and ETDQ-7 together showed increased sensitivity and specificity in the diagnosis of Eustachian tube dysfunction.

Conclusions

The Spanish adaptation of the ETDQ-7 is valid, reliable and can be used in a clinical setting to quantify the impact and severity of chronic dysfunction on patients' lives. A new test formed by combining ETDQ-7 and TMM could be a routine test in the diagnosis of Eustachian tube dysfunction.

https://ift.tt/2MjaFD0

When attended and conscious perception deactivates fronto-parietal regions

Publication date: Available online 13 September 2017

Source: Cortex

Author(s): Ausaf Ahmed Farooqui, Tom Manly

Abstract

The finding of increased fronto-parietal activity during conscious and attended perception forms a key basis for theories of consciousness and attention. However, this finding comes largely from studies that required explicit detection of events in a way that made detection the goal of the ongoing task. This is an important confound because goal completion itself elicits fronto-parietal activity. In everyday life attended and conscious perception is instrumental in achieving our goals but rarely a goal in itself. Here we examined whether conscious perception that was instrumental to participants' current goals, but not a goal in itself, elicited increased fronto-parietal activity. In Experiments 1 and 2 participants attended to a stream of letters (1 per second) to detect occasional targets in their midst. We found that consciousness of, and attention to, these highly visible non-targets events deactivated fronto-parietal regions. In Experiment 3 participants heard a loud auditory cue that had to be retained in memory for up to 9 sec before being used to select the correct rule for completing the goal. No increased fronto-parietal activity was observed even for such salient, attended and remembered event. In contrast, robust fronto-parietal activation was observed across all the experiments for goal completion events. The results indicate that increased fronto-parietal activity is not a necessary correlate of conscious and attended perception. We speculate that fronto-parietal deactivation during non-target events may be related to the suppression of potential interference from salient, conscious, but non-goal stimuli.

https://ift.tt/2LXY637

Rule reactivation and capture errors in goal directed behaviour

Publication date: Available online 10 September 2017

Source: Cortex

Author(s): María Roca, Milagros García, María Juliana Torres Ardila, María Luz González Gadea, Teresa Torralva, Jesica Ferrari, Agustín Ibáñez, Facundo Manes, John Duncan

Abstract

In everyday life people may act automatically, following "unwanted" lines of action which are triggered by contextual cues and may interfere with current goals. Such occurrences are known as "capture errors" in reference to errors that occur when a more salient behaviour takes place when a similar, but less salient, action was intended. Clinical neuropsychological studies suggest that reactivation of previous rules may play an important role in behavioural interference, but such reactivation has been little studied in normal subjects and simple experimental tasks. In the present study we develop this theme, presenting data on 4 subjects who spontaneously showed capture errors in verbal fluency tasks, and developing a new experimental paradigm specifically designed to elicit such interference in normal subjects. In the new paradigm, 101 normal subjects performed a simple series of working memory tasks, including occasional stimuli whose answer matched both the current and the previous rule. We found that normal controls indeed tend to commit more mistakes after the presentation of a stimulus whose answer is consistent with a current and preceding rule. In this case, however, the errors produced are not necessarily associated with a shift back to the old rule, suggesting that rule reactivation leads to a more general interference effect. We discuss the importance of our data from both theoretical and clinical perspectives.

https://ift.tt/2Kv6J0a

Semantic dementia and the left and right temporal lobes

Publication date: Available online 31 August 2017

Source: Cortex

Author(s): Julie S. Snowden, Jennifer M. Harris, Jennifer C. Thompson, Christopher Kobylecki, Matthew Jones, Anna M. Richardson, David Neary

Abstract

Semantic dementia, a circumscribed disorder of semantic knowledge, provides a unique model for understanding the neural basis for semantic representation. The study addressed areas of contention: the relative roles of the left and right temporal lobe, the contribution of anterior versus posterior temporal cortex and the status of the anterior temporal lobes as amodal hub. Naming and word comprehension was examined in 41 semantic dementia patients, 31 with left-predominant and 10 right-predominant atrophy. In keeping with expectation, naming and comprehension were significantly poorer in left-predominant patients. Structural magnetic resonance image analysis, using a visual rating scale, showed strong inverse correlations between naming scores and severity of both left anterior and posterior temporal lobe atrophy. By contrast, comprehension performance was more strongly correlated with left posterior temporal atrophy. Analysis of naming errors revealed a correlation between anterior temporal atrophy and associative/functional descriptive responses, implying availability of semantic information. By contrast, 'don't know' responses, indicative of loss of semantic knowledge, were linked to left posterior temporal lobe atrophy. Semantic errors, the hallmark of semantic dementia, were linked to right hemisphere atrophy, especially the right posterior temporal lobe. Matched visual-verbal tasks (famous face and name identification, Pyramids and Palm trees pictures and words, animal knowledge from 3-D models and animal names) administered to nine patients elicited variable correspondence between performance on nonverbal and verbal versions of the task. Marked performance dissociations were demonstrated in some patients: poorer understanding of names/words in left-predominant patients and of faces/pictures/models in right-predominant cases. The findings are compatible with the notion of the anterior temporal lobes as areas of convergence, but are less easily accommodated within the framework of amodal conceptual representation. The data, which reconcile some apparent contradictions in the literature, are discussed in the light of the nature and distribution of degenerative change in semantic dementia.

https://ift.tt/2LZFMX7

Functional brain networks for learning predictive statistics

Publication date: Available online 18 August 2017

Source: Cortex

Author(s): Joseph Giorgio, Vasilis M. Karlaftis, Rui Wang, Yuan Shen, Peter Tino, Andrew Welchman, Zoe Kourtzi

Abstract

Making predictions about future events relies on interpreting streams of information that may initially appear incomprehensible. This skill relies on extracting regular patterns in space and time by mere exposure to the environment (i.e., without explicit feedback). Yet, we know little about the functional brain networks that mediate this type of statistical learning. Here, we test whether changes in the processing and connectivity of functional brain networks due to training relate to our ability to learn temporal regularities. By combining behavioral training and functional brain connectivity analysis, we demonstrate that individuals adapt to the environment's statistics as they change over time from simple repetition to probabilistic combinations. Further, we show that individual learning of temporal structures relates to decision strategy. Our fMRI results demonstrate that learning-dependent changes in fMRI activation within and functional connectivity between brain networks relate to individual variability in strategy. In particular, extracting the exact sequence statistics (i.e., matching) relates to changes in brain networks known to be involved in memory and stimulus-response associations, while selecting the most probable outcomes in a given context (i.e., maximizing) relates to changes in frontal and striatal networks. Thus, our findings provide evidence that dissociable brain networks mediate individual ability in learning behaviorally-relevant statistics.

https://ift.tt/2KuIzmt

Niraparib: A Review in Ovarian Cancer

Abstract

Niraparib (Zejula^®), a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for the maintenance treatment of recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy. Approval was based on the results of the randomized, double-blind, placebo-controlled phase III NOVA trial. In NOVA, niraparib significantly prolonged progression-free survival (primary endpoint), chemotherapy-free interval and time to first subsequent therapy compared with placebo in patients with recurrent, platinum-sensitive, high grade serous ovarian, fallopian tube or primary peritoneal cancer. The beneficial effects of niraparib were consistent regardless of BRCA mutation or homologous recombination deficiency (HRD) status. Niraparib had a manageable tolerability profile, with the majority of grade 3 or 4 adverse events being haematologic abnormalities (e.g. thrombocytopenia, anaemia, neutropenia). Adverse events were generally well managed with dose interruption or modification of niraparib. Current evidence suggests that niraparib is an effective new option with a manageable tolerability profile for the maintenance treatment of recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer in adults, with or without BRCA1/2 mutation or HRD.

https://ift.tt/2n8LrfG

Treatment of Advanced Merkel Cell Carcinoma: Current Therapeutic Options and Novel Immunotherapy Approaches

Abstract

Advanced Merkel cell carcinoma (MCC) is a very aggressive, rare neuroendocrine tumor of the skin with a high frequency of locoregional recurrence and metastasis, and a high mortality rate. Surgical resection, sentinel lymph node biopsy, and radiotherapy represent the gold standard of treatment in patients with localized disease, while chemotherapy has a significant role in the treatment of advanced disease. However, no definitive evidence on the survival impact of radiotherapy in the advanced stages has been provided to date, and response to chemotherapy remains brief in the majority of cases, indicating an urgent need for alternative approaches. Biological and genome sequencing studies have implicated multiple molecular pathways in MCC, thus leading to the development of new agents that target angiogenic factors, anti-apoptosis molecules, poly-ADP ribose polymerase, intracellular signal proteins such as the PI3K/AKT/mTOR pathway, and peptide receptors such as somatostatin receptors. More recently, immunotherapy agents such as avelumab, pembrolizumab, and nivolumab, which act by blocking the programmed cell-death (PD)-1/PD-L1 immune checkpoint, have shown promising results, especially in the advanced setting, and should now be considered standard of care for metastatic MCC. Current research is focusing on developing new immunotherapeutic strategies, identifying predictive biomarker to aid in the selection of patients responsive to immunotherapy, and defining combination approaches to increase efficacy in refractory patients.

https://ift.tt/2KlVNC9

Therapies Targeting the Tumor Stroma and the VEGF/VEGFR Axis in Pancreatic Ductal Adenocarcinoma: a Systematic Review and Meta-Analysis

Abstract

Abundant tumor stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and is suggested to play a role in the resistance of this deadly disease to systemic treatment. Despite promising results from preclinical studies, clinical trials with therapies targeting the tumor stroma and the vascular endothelial growth factor (VEGF) and its receptor VEGFR yielded conflicting results. With this systematic review and meta-analysis, we aim to summarize the existing evidence in this important field with a special focus on anti-VEGF/VEGFR therapy. A total of 24 clinical studies were included in the qualitative synthesis, and six randomized controlled trials (RCTs) investigating anti-VEGF/VEGFR agents were further included in the quantitative synthesis. The qualitative synthesis revealed a treatment advantage of combined therapy with nab-paclitaxel, while the meta-analysis on anti-VEGF/VEGFR drugs demonstrated marginal improvement of objective response rates and progression-free survival, but not overall survival. Stroma targeting is a promising and rapidly-developing treatment strategy in PDAC. However, novel drugs balancing stroma depletion and modulation are needed.

https://ift.tt/2Khf9bg

Constitutive activation of β-catenin in ameloblasts leads to incisor enamel hypomineralization

Abstract

Enamel is the hardest tissue with the highest degree of mineralization protecting the dental pulp from injury in vertebrates. The ameloblasts differentiated from ectoderm-derived epithelial cells are a single cell layer and are important for the enamel formation and mineralization. Wnt/β-catenin signaling has been proven to exert an important role in the mineralization of bone, dentin and cementum. Little was known about the regulatory mechanism of Wnt/β-catenin signaling pathway in ameloblasts during amelogenesis, especially in the mineralization of enamel. To investigate the role of β-catenin in ameloblasts, we established Amelx-Cre; β-catenin^∆ex3fl/fl (CA-β-catenin) mice, which could constitutive activate β-catenin in ameloblasts. It showed the delayed mineralization and eventual hypomineralization in the incisor enamel of CA-β-catenin mice. Meanwhile, the amelogenesis-related proteinases Mmp20 and Klk4 were decreased in the incisors of CA-β-catenin mice. These data indicated that β-catenin plays an essential role in differentiation and function of ameloblasts during amelogenesis.

https://ift.tt/2KdrPQo

Ewing-like Sarcoma: A Case of a Primary Cutaneous Primitive Neuroectodermal Tumor With Atypical Immunohistochemistry and Lack of Fusion Oncogene Detection

Abstract: We present a 25-year-old male patient with a primary cutaneous primitive neuroectodermal tumor (cPNET) with unusual immunohistochemistry and lack of fusion oncogene generation. The lesion expressed CD99 and WT-1, and the histological features were consistent with cPNET. Differential diagnoses such as rhabdomyosarcoma, desmoplastic small round blue cell tumor, hematolymphoid neoplasm, neuroblastoma, and CIC-DUX round cell sarcoma were ruled out based on immunohistochemistry, genetic studies, and histology. Previous cPNET cases have been published detailing abnormal immunochemistry and genetic expression. However, to our knowledge, fusion oncogene negativity in cPNET tumors has only been reported in one other published case series. These reports, including this study, reinforce the fact that a high index of suspicion should be used when diagnosing these tumors, regardless of immunohistochemical and genetic variability. This case highlights that the typical genetic and immunohistochemical features of cPNET may be more variable than previously thought. Future studies are needed to better understand these variations of cPNET. Correspondence: Jessica G. Labadie, MD, 676 N St Clair Street, Suite 1600, Chicago, IL 60611 (e-mail: Jessica.gandy13@gmail.com). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2AFFlwJ

Plexiform Xanthomatous Tumor, Variety of Xanthoma or Subtype of Fibrohistiocytic Tumors?

Abstract: Plexiform xanthomatous tumor was proposed as an independent neoplasm within fibrohistiocytic tumor group a few years ago. The arguments were based on their different clinical features as well as their own morphological and immunohistochemical findings. Nevertheless, it has not been widely studied yet, and there are few reports about this entity. Regarding a case, we reviewed the diagnostic characteristics of this underdiagnosed tumor. Correspondence: Francisco José Illán-Gambín, MD, Department of Pathology, University General Hospital of Alicante, Pintor Baeza 12, Alicante 03010, Spain (e-mail: fjig90@gmail.com). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2vhSIhq

A Rare Form of Acquired Telangiectasia With Distinctive Histopathologic Features: Challenge

No abstract available

https://ift.tt/2AJidxy

Telangiectatic Patches on Knees and Elbows of a 73-Year-Old Woman: Challenge

No abstract available

https://ift.tt/2vhlaQI

Retrospective Chart Review of Cutaneous Adverse Events Associated with Tremelimumab in 17 Patients

Abstract

Background and Objectives

Tremelimumab is a monoclonal human antibody that inhibits cytotoxic T-lymphocyte-associated antigen 4, giving rise to increased T cell activation and interleukin-2 release. While this activation of the immune system provides a mechanism to recognize and destroy cancer cells, it also leads to off-target immune-related adverse events. Ipilimumab is a US Food and Drug Administration-approved anti-cytotoxic T-lymphocyte-associated antigen 4 antibody, which has a high incidence of cutaneous adverse events. While cutaneous adverse events for ipilimumab have been extensively studied, there is a distinct lack of cutaneous adverse event data for tremelimumab.

Methods

We conducted a retrospective chart review of our institution's electronic medical records from January 2000 to March 2018 to characterize cutaneous adverse events induced by tremelimumab. Previous descriptions of tremelimumab cutaneous adverse events are limited to rash and pruritus.

Results

We found 17 patients treated with tremelimumab who had cutaneous adverse events including pruritus (12/17), eczematous dermatitis (8/17), morbilliform rash (5/17), vitiligo (2/17), xerosis (3/17), acneiform rash (2/17), and psoriasiform dermatitis (1/17).

Conclusions

This case series demonstrates that cutaneous adverse events seen in patients taking tremelimumab overlap with those of ipilimumab. While there are some differences between rash characterizations of the two drugs, such as time to onset and clearance, the sample size of this case series is too small to draw any definite conclusions. This study addresses a gap in the descriptive knowledge on tremelimumab cutaneous adverse events and highlights the need for further large cohort prospective studies. Awareness of expected cutaneous toxicities and how best to treat these can help patients continue on immunotherapy regimens without delays or interruptions and give patients the best quality of life while receiving treatment.

https://ift.tt/2AHAGdB

Piloting the Use of Smartphones, Reminders, and Accountability Partners to Promote Skin Self-Examinations in Patients with Total Body Photography: A Randomized Controlled Trial

Abstract

Objective

The aim of this study was to evaluate the use of a mobile application (app) in patients already using total body photography (TBP) to increase skin self-examination (SSE) rates and pilot the effectiveness of examination reminders and accountability partners.

Design

Randomized controlled trial with computer generated randomization table to allocate interventions.

Setting

University of Pennsylvania pigmented lesion clinic.

Participants

69 patients aged 18 years or older with an iPhone/iPad, who were already in possession of TBP photographs.

Intervention

A mobile app loaded with digital TBP photos for all participants, and either (1) the mobile app only, (2) skin examination reminders, (3) an accountability partner, or (4) reminders and an accountability partner.

Main Outcome Measure

Change in SSE rates as assessed by enrollment and end-of-study surveys 6 months later.

Results

Eighty one patients completed informed consent, however 12 patients did not complete trial enrollment procedures due to device incompatibility, leaving 69 patients who were randomized and analyzed [mean age 54.3 years, standard deviation 13.9). SSE rates increased significantly from 58% at baseline to 83% at 6 months (odds ratio 2.64, 95% confidence interval 1.20–4.09), with no difference among the intervention groups. The group with examination reminders alone had the highest (94%) overall satisfaction, and the group with accountability partners alone accounted for the lowest (71%).

Conclusion

A mobile app alone, or with reminders and/or accountability partners, was found to be an effective tool that can help to increase SSE rates. Skin examination reminders may help provide a better overall experience for a subset of patients.

Trial Registration

ClinicalTrials.gov Identifier: NCT02520622.

https://ift.tt/2OEYQse

IgE deficiency and prior malignancy: results of the 2005-2006 National Health and Nutrition Examination Survey (NHANES)

Publication date: Available online 4 August 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Denisa Ferastraoaru, David Rosenstreich

https://ift.tt/2vixdgC

Introducing the Transparency and Openness Promotion (TOP) Guidelines and Badges for Open Practices at Cortex

Publication date: Available online 4 August 2018

Source: Cortex

Author(s): Christopher D. Chambers

https://ift.tt/2AHMCMA

Removal of metronidazole by TiO 2 and ZnO photocatalysis: a comprehensive comparison of process optimization and transformation products

Abstract

The photodegradation of antibiotic metronidazole (MNZ) was systematically studied and compared by using aqueous suspensions of TiO₂ and ZnO catalysts under 100-W UV irradiation. The degradation conditions were optimized using the central composite design and response surface methodology. The optimal photodegradation conditions obtained were at pH 6.0 with 1.5 g L⁻¹ of TiO₂ (86.10% removal for 50 mg L⁻¹ MNZ) and at pH 9.5 with 0.5 g L⁻¹ of ZnO (60.32% removal for 30 mg L⁻¹ MNZ) after 60-min irradiation at 20 °C. The degradation efficiency in the presence of TiO₂ was higher than that of ZnO. The participation of active species such as hydroxyl radicals (OH·), holes (h⁺), and superoxide radicals (O₂⁻·) during MNZ photodegradation over TiO₂ and ZnO catalysts was also examined. Experimental results showed that MNZ oxidation was mainly driven by the presence of holes and superoxide radicals. Totally, 10 major intermediates were detected in UV/TiO₂ and UV/ZnO photocatalysis of MNZ using LC-QTof/MS system, in which 5 same intermediates were found. The remaining different intermediates led to the variations of degradation pathways of both processes. Moreover, some bigger transformation products than the parent MNZ were detected.

https://ift.tt/2M2toph

Comparación de la producción vocal en niños con hipoacusia prelocutiva con adaptación audioprotésica e implante coclear con normooyentes

Publication date: Available online 4 August 2018

Source: Acta Otorrinolaringológica Española

Author(s): Faustino Núñez-Batalla, Gabriela Vasile, Noelia Cartón-Corona, Daniel Pedregal-Mallo, Marta Menéndez de Castro, Maite Guntín García, Justo Gómez-Martínez, Pilar Carro Fernández, Jose Luis Llorente-Pendás

Resumen

Introducción y objetivos

La inadecuada retroalimentación auditiva en los niños con hipoacusia prelocutiva altera la articulación de consonantes y vocales.

El propósito de esta investigación es comparar la producción de vocales en niños hipoacúsicos hispanohablantes con implante coclear o adaptación audioprotésica con niños normooyentes por medio del análisis acústico de las frecuencias formánticas y el espacio vocal.

Método

Un total de 56 niños con hipoacusia prelocutiva (25 con implante coclear y 31 con audífonos) y 47 niños normooyentes participaron en el estudio. Los 2 primeros formantes (F1 y F2) de las 5 vocales del idioma español se midieron utilizando el programa Praat. Para analizar las diferencias entre los 3 grupos se aplicó el método ANOVA de análisis de la varianza y el test de Scheffé. También se calculó el área del espacio vocal.

Resultados

El valor medio del F1 en todas las vocales no mostró diferencias significativas en los 3 grupos de niños. Para las vocales /i/, /o/ y /u/ el valor medio del F2 fue significativamente diferente entre los 2 grupos de niños hipoacúsicos y el grupo de niños normooyentes.

Conclusión

Ambos grupos de niños con hipoacusia prelocutiva tienden a presentar sutiles desviaciones en la articulación de las vocales que pueden ser analizadas mediante un programa de análisis acústico.

Abstract

Introduction and objectives

Inadequate auditory feedback in prelingually deaf children alters the articulation of consonants and vowels.

The purpose of this investigation was to compare vowel production in Spanish-speaking deaf children with cochlear implantation, and with hearing-aids with normal-hearing children by means of acoustic analysis of formant frequencies and vowel space.

Methods

A total of 56 prelingually deaf children (25 with cochlear implants and 31 wearing hearing-aids) and 47 normal-hearing children participated. The first 2 formants (F1 and F2) of the five Spanish vowels were measured using Praat software. One-way analysis of variance (ANOVA) and post hoc Scheffé test were applied to analyze the differences between the 3 groups. The surface area of the vowel space was also calculated.

Results

The mean value of F1 in all vowels was not significantly different between the 3 groups. For vowels /i/, /o/ and /u/, the mean value of F2 was significantly different between the 2 groups of deaf children and their normal-hearing peers.

Conclusion

Both prelingually hearing-impaired groups tended toward subtle deviations in the articulation of vowels that could be analyzed using an objective acoustic analysis programme.

https://ift.tt/2n9Rctt

Características epidemiológicas de los pacientes con carcinomas escamosos de cabeza y cuello. Resultados de un registro hospitalario

Publication date: Available online 4 August 2018

Source: Acta Otorrinolaringológica Española

Author(s): Xavier León, Montserrat López, Jacinto García, Juan R. Montserrat, Juan R. Gras, Katarzyna A. Kolanczak, Miquel Quer

Resumen

Introducción y objetivos

A lo largo de las últimas décadas han aparecido una serie cambios con capacidad de modificar las características epidemiológicas de los pacientes con carcinomas escamosos de cabeza y cuello (CECC), como el incremento en las expectativas de vida, la modificación en los patrones de consumo de tabaco y alcohol, o la infección por virus del papiloma humano (HPV). El objetivo del presente estudio es analizar la existencia de modificaciones en las características epidemiológicas y clínicas de este tipo de pacientes a lo largo de un periodo de 30 años.

Métodos

Estudio retrospectivo de 5.123 pacientes con CECC tratados durante el periodo 1985-2017. Se evaluó la existencia de modificaciones en los patrones de edad, sexo, consumo de tóxicos, y localización y extensión del tumor a lo largo del periodo de estudio. Para los pacientes con carcinomas de orofaringe se evaluó el estatus HPV.

Resultados

A lo largo del periodo de estudio se incrementó de forma significativa el promedio de edad y el porcentaje de pacientes de sexo femenino, disminuyendo el porcentaje de pacientes con uso severo de tóxicos. A nivel del tumor, observamos una disminución en el porcentaje de pacientes con tumores de la laringe, incrementándose los pacientes con tumores iniciales cT1 y con afectación ganglionar cN2. Pudimos evidenciar un incremento progresivo en el porcentaje de pacientes con carcinomas de orofaringe HPV-positivos.

Conclusiones

Durante las últimas décadas se han producido modificaciones significativas en las características epidemiológicas y clínicas de los pacientes con CECC.

Abstract

Introduction and objectives

The epidemiological characteristics of patients with head and neck cancer squamous cell carcinoma (HNSCC) have changed over recent years. The increase in life expectancy of the population, changed patterns of tobacco and alcohol use, and human papillomavirus infection (HPV) have brought about significant changes. The objective of the present study is to analyze the changes in the epidemiological and clinical characteristics of these patients over a 30-year period.

Methods

Retrospective study of 5,123 patients with HNSCC treated over the period 1985-2017. We evaluated the existence of changes in the patterns of age, sex, tobacco and alcohol use, and location and extension of the tumours throughout the study period. HPV status was evaluated for patients with oropharyngeal carcinomas.

Results

Throughout the study period there was a significant increase in the mean age at presentation and in the percentage of women, and a decrease in the percentage of patients with history of high consumption of toxic substances. We observed a decrease in the proportion of patients with laryngeal cancer, and an increase of patients with early tumours cT1 and with neck disease cN2. We detected a progressive increase in the proportion of HPV-positive oropharyngeal carcinoma patients.

Conclusion

Over recent decades there have been significant changes in the epidemiological and clinical characteristics of patients with HNSCC.

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Physiological responses and metal uptake of Miscanthus under cadmium/arsenic stress

Abstract

The aim of this study is to explore the impact of cadmium (Cd) and arsenic (As) stress on physiological indexes and Cd/As uptake ability of Miscanthus, including Miscanthus sacchariflorus A0104, Miscanthus sinensis C0424 and C0640. Cd and As concentration showed significant hormesis effects on some physiological indexes, such as chlorophyll content, net photosynthetic rate, and MDA content. Compared with control group, Cd uptake can be most greatly enhanced by above fourfold with 150 mg/kg Cd treatment. As uptake of A0104 was increased by 3 ~ 33 folds with 200 mg/kg As treatment, C0424 was increased by 7–12 folds with 100 mg/kg As treatment, while C0640 was increased 1 ~ 6 folds with 250 mg/kg As treatment. The results also showed that C0640 was relatively better for the Cd remediation in the high Cd concentration (150 mg/kg) contaminated soil, while A0104 and C0424 were relatively better for the As remediation in the high As concentration (100 ~ 200 mg/kg) contaminated soil. Additionally, significantly (p < 0.05) close correlations were found among physiological indexes (except MDA content), while physiological indexes showed no significant relationship with the heavy metal contents in root, stem, and leaf.

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Dual intestinal anomalies in dizygotic twins

We report on the case of two digestive malformations in dizygotic/dichorionic/diamniotic twins born at 31 weeks of gestation. The mother (gravida 1 para 0) was treated by hydroxychloroquine for systemic lupus erythematosus during pregnancy. Twin A presented an arch-like dilatation on antenatal ultrasounds, characteristic of segmental volvulus. After birth, twin B presented repeated vomiting on feeding, leading us to diagnose ileal atresia despite normal antenatal ultrasounds. Both twins underwent surgery and the postoperative period was uneventful. After 1 year of follow-up, the twins are in excellent health without digestive sequelae. Genetic testing for cystic fibrosis was negative. The placenta showed diffuse signs of hypoxia and ischaemia, indicating that the root cause was vascular. The pathophysiology of intestinal atresia is hypothesised to derive from a vascular incident during fetal development. We are therefore led to believe that an intrauterine vascular event is the most likely cause of the dual malformation.

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Embolic stroke, left atrial myxoma and gigantism in a patient with Carney complex with additional features suggestive of Marfan syndrome

A 16-year-old boy presented to the emergency department with a sudden weakness on the right side of the body and was diagnosed as having embolic stroke. Later on, the patient was diagnosed as having Carney complex (CNC). The neurological complication might be caused by left atrial myxoma as a feature of CNC. Surprisingly, the patient showed some additional features such as positive wrist and thumb signs, pectus carinatum deformity and plain flat feet, suggestive of Marfan syndrome. This case demonstrated that both of these syndromes might coexist in the same patient, suggesting that proper diagnostic and management were key factors that affected prognosis. He showed an improved condition after he had received medical treatments, undergone tumour excision and physiotherapy. Further evaluation was needed to improve patient outcomes.

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Unexpected manifestation of cardiac amyloidosis

This report discusses an unusual case of cardiac amyloidosis. We report a patient who presented with unexplained ascites on a background of stable hypertension and mild left ventricular systolic dysfunction, cardiovascular complaints commonly associated with age. Due to the unspecific nature of his cardiovascular symptoms, it took 2 years of recurrent, unresolved ascites, numerous investigations, shifting differential diagnoses and significant cardiovascular deterioration before cardiac amyloidosis was recognised, by which the disease was at end stage. This case emphasises the need for more discriminating clinical features in the diagnosis of cardiac amyloidosis and advocates unexplained, recurrent ascites as a possible candidate.

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Uterine didelphys with one cervix obscured by blind hemivagina: a lesson in rarity

A 14-year-old girl presented with increasing cyclical pain, scanty menses, pelvic mass and absence of the left kidney. With both radiological and clinical examinations (examination under anaesthesia), diagnosis of bicornuate uterus with single cervix could be made while on laparotomy, and it turned out to be uterine didelphys, with one cervix obscured by blind hemivagina with haematometra and haematocolpos in the left horn, for which hemihysterectomy was done. Post procedure the patient was relieved of cyclical pain and is menstruating properly.

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Treatment of nasal myiasis with ivermectin irrigation

We describe a case of nasal myiasis due to Musca domestica in a 97-year-old Peruvian farmer with a previously undiagnosed mucocutaneous leishmaniasis. Initial attempts to remove the fly larvae using manual extraction with a toothed forceps and normal saline irrigation were unsuccessful. On subsequent nasal irrigation with ivermectin solution, the patient self-expulsed approximately 50 larvae within 15 min. He also received a course of oral ivermectin. A post-treatment CT scan revealed clear sinuses. Here, we propose that ivermectin irrigation is a simple and effective treatment for nasal myiasis.

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Acute intestinal ischaemia from a portal vein thrombosis in a young female smoker on an oral contraceptive

We report the case of a 23-year-old woman who presented with bloody diarrhoea and multiple syncopal events. While the initial diagnosis clinically appeared to be inflammatory bowel disease, she was found to have a portal vein thrombosis (PVT) on MR cholangiopancreatography and acute intestinal ischaemia on colonic biopsy. The aetiology of this patient's PVT is attributed to her acquired prothrombotic state from an estrogen-containing contraceptive pill in conjunction with regular tobacco use. Extensive mesenteric venous thrombosis from an acute PVT has been shown to cause intestinal ischaemia, likely from venous obstruction and reflexive arterial constriction; however, the diagnosis is often delayed until surgery or autopsy. Our case report highlights this patient's clinical presentation, workup and treatment, as part of a review for the risk factors and guidelines recommendations for management of an acute PVT.

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Appendiceal schwannoma: a rare cause of perforated appendicitis

Description 

An 82-year-old woman presented to the emergency department with an acute abdomen. CT imaging revealed a proximal appendiceal mass with distal appendicitis. She underwent a laparoscopic appendicectomy with partial caecectomy and subsequent histopathology confirmed an appendiceal schwannoma.

The woman presented with a 1-day history of acute abdominal pain localised to the lower quadrants, worse on mobilisation, loss of appetite and fever. She denied any previous abdominal pain, nausea or vomiting, bowel or bladder symptoms. There was no history of weight loss, generalised fatigue or other symptoms of chronic anaemia. She had been well in the preceding weeks. Her medical history was significant for a cerebrovascular accident, hypertension and hypercholesterolaemia. She had never had previous abdominal surgery.

On examination the patient had a temperature of 37.7°C. There were no signs of haemodynamic instability. Her abdomen was rigid with severe tenderness on palpation, worse in the right lower quadrant....

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Iliac bone tuberculosis with bicompartmental abscess

Description 

A 39-year-old man presented with insidious onset back pain and groin pain for 2 weeks, and limp for 7 days to orthopaedic outpatient department. He had anorexia for the past fortnight and had noticed weight loss of about 7 kg, though he remained afebrile. On examination, he had a pseudoflexion deformity of the right hip and tenderness in the right iliac fossa. An X-ray of the pelvis was done which showed an ill-defined lytic lesion in the anterior half of the right iliac blade with minimal periosteal reactions (figure 1). His laboratory investigation showed a high haemoglobin of 12 g/dL, erythrocyte sedimentation rate of 64 mm fall at the end of first hour, a raised total lymphocyte count of 13x10⁹/L with lymphocytosis 40%. His renal, liver and nutritional parameters were within normal range (albumin >3500 mg/dL, absolute lymphocyte count >1500/mm³). X-ray of the dorsolumbosacral region and chest was unremarkable. An MRI was done which...

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Sensory ganglionopathy associated with drug-induced hypersensitivity syndrome caused by mexiletine

Although various causes are reported for sensory ganglionopathy, drug-induced hypersensitivity syndrome (DIHS) has not been considered a possibility. We describe a 70-year-old woman, previously administered mexiletine hydrochloride for 4 weeks, who presented with systemic oedematous erythema and subacute progressive gait disturbance. Evaluation revealed lymphadenopathy with atypical lymphocytosis and eosinophilia, and human herpesvirus 6 (HHV-6) reactivation. Neurological examination indicated the almost complete loss of joint positional sense in her extremities; her tendon reflex was lost and there was marked pseudoathetosis and Romberg's sign. Skin biopsy revealed spongiosis with lymphocyte infiltration. Based on these findings, we diagnosed acute sensory ganglionopathy secondary to DIHS. Although her DIHS-induced symptoms subsided after methylprednisolone treatment, partial remission of sensory ganglionopathy occurred, even after subsequent intravenous immunoglobulin therapy. This case suggests the possibility that reactivation of HHV-6 may be involved in the pathomechanism of sensory ganglionopathy.

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Inflammatory myofibroblastic tumour mimicking a vocal cord polyp

Description 

A 9-year-old child presented with the complaint of voice change of 8 months in duration, which was gradually progressive, and a recent-onset noisy breathing at night noticed by the parents. There were no signs of airway distress or feeding issues on presentation, and the growth of the child was appropriate for her age.

On indirect laryngoscopic examination, a smooth, large polypoidal mass was seen arising from the anterior commissure, partially obscuring the laryngeal airway. Bilateral vocal cords were mobile. The initial impression was that of a benign vocal cord polyp (figure 1).

Figure 1

Laryngoscopic image showing smooth polypoidal mass arising from the anterior commissure.

The rest of the clinical examination was normal.

The patient was then planned for microlaryngoscopic laser-assisted excision of the polyp under general anaesthesia. Intraoperatively, the mass was engaged using a suspension laryngoscope and was seen  to arise from the anterior commissure and found to be firm on palpation....

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Analgesic effects of methadone and magnesium following posterior spinal fusion for idiopathic scoliosis in adolescents: a randomized controlled trial

Abstract

Purpose

To provide optimal conditions for neurophysiological monitoring and rapid awakening, remifentanil is commonly used during pediatric spinal surgery. However, remifentanil may induce hyperalgesia and increase postoperative opioid requirements. We evaluated the potential of methadone or magnesium to prevent remifentanil-induced hyperalgesia.

Methods

Using a prospective, randomized, blinded design, adolescents presenting for posterior spinal fusion to treat idiopathic scoliosis were assigned to receive desflurane with remifentanil alone (REMI), remifentanil + methadone (MET) (0.1 mg/kg IV over 15 min), or remifentanil + magnesium (MAG) (50 mg/kg bolus over 30 min followed by 10 mg/kg/h). Primary outcomes were opioid requirements and postoperative pain scores. Secondary outcomes included intraoperative anesthetic requirements, neurophysiological monitoring conditions, and emergence times.

Results

Data analysis included 60 patients. Total opioid requirement (hydromorphone) in the REMI group (received perioperatively and on the inpatient ward) was 0.34 ± 0.11 mg/kg compared to 0.26 ± 0.10 mg/kg in the MET group (95% confidence interval (CI) of difference: − 0.14, − 0.01; p = 0.035). The difference in opioid requirements between the REMI and MET group was related to intraoperative dosing (0.04 ± 0.02 mg/kg vs. 0.02 ± 0.01 mg/kg; 95% CI of difference: − 0.01, − 0.02; p = 0.003). No difference was noted in pain scores, and no differences were noted when comparing the REMI and MAG groups.

Conclusion

With the dosing regimens in the current study, the only benefit noted with methadone was a decrease in perioperative opioid requirements. However, given the potential for hyperalgesia with the intraoperative use of remifentanil, adjunctive use of methadone appears warranted.

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Frontiers of cancer imaging and guided therapy using ultrasound, light, and microwaves

Abstract

This review describes emerging techniques within the last 5 years that employ ultrasound for detecting and staging malignancy, tracking metastasis, and guiding treatment. Ultrasound elastography quantifies soft tissue elastic properties that change as a tumor grows and proliferates. Hybrid imaging modalities that combine ultrasound with light or microwave energy provide novel contrast for mapping blood oxygen saturation, transport of particles through lymphatic vessels and nodes, and real-time feedback for guiding needle biopsies. Combining these methods with smart nanoparticles and contrast agents further promotes new paradigms for cancer imaging and therapy.

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Measuring the frequency of consumer hair combing and magnitude of combing forces on individual hairs in a tress and the implications for product evaluation and claims substantiation

International Journal of Cosmetic Science, Volume 0, Issue ja, -Not available-.


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A Slow-Growing Fibrous Parapharyngeal Mass.

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A Slow-Growing Fibrous Parapharyngeal Mass.

JAMA Otolaryngol Head Neck Surg. 2018 Aug 02;:

Authors: Farlow JL, McHugh JB, Spector ME

PMID: 30073299 [PubMed - as supplied by publisher]

https://ift.tt/2Mg6Pu9

Association of Marijuana Use With Psychosocial and Quality of Life Outcomes Among Patients With Head and Neck Cancer.

Related Articles

Association of Marijuana Use With Psychosocial and Quality of Life Outcomes Among Patients With Head and Neck Cancer.

JAMA Otolaryngol Head Neck Surg. 2018 Aug 02;:

Authors: Zhang H, Xie M, Archibald SD, Jackson BS, Gupta MK

Abstract
Importance: Cannabis sativa, the most widely used illicit substance in Canada, has a unique ability to facilitate relaxation and relieve anxiety while reducing pain. However, no study to date has examined quality of life (QOL) and psychosocial issues in relation to the use of this drug among patients with newly diagnosed head and neck cancer (HNC).
Objective: To examine the differences in QOL and psychosocial outcomes between marijuana users and nonusers with newly diagnosed HNC.
Design, Setting, and Participants: This prospective cohort study was conducted at a tertiary care cancer center. Patients were enrolled consecutively and prospectively at the time of HNC diagnosis from January 1, 2011, to January 1, 2015. Seventy-four patients who were current marijuana users were case matched to 74 nonusers in a 1:1 scheme based on age, sex, and tumor subsite. All patient demographic and QOL data were collected prospectively, and data analysis was conducted from November 1 to December 1, 2017.
Main Outcomes and Measure: The QOL outcome was assessed using the EuroQol-5D (EQ5D) and the Edmonton Symptom Assessment System (ESAS) questionnaires.
Results: A total of 148 patients were included in this study: 74 in the marijuana user group (mean [SD] age, 62.3 [10.3] years; male sex, 61 patients [82%]) and 74 in the marijuana nonuser group (mean age, 62.2 years; male sex, 63 patients [85%]). There was no statistically significant difference in age, sex, tumor subsite, clinical TNM staging, treatment modality, or mean Karnofsky score between the 2 groups. On univariate analysis, there was no statistically significant difference in the mobility, self-care, and usual activities domains of the EQ5D. Marijuana users had significantly lower scores in the anxiety/depression (difference, 0.74; 95% CI, 0.557-0.930) and pain/discomfort (difference, 0.29; 95% CI, 0.037-1.541) domains. Wilcoxon rank sum test confirmed the results of the EQ5D with improvements in the pain/discomfort (z score, -2.60) and anxiety/depression (z score, -6.71) domains. Marijuana users had less pain, were less tired, were less depressed, were less anxious, had more appetite, were less drowsy, and had better general well-being according to the ESAS. A Wilcoxon rank sum test confirmed a statistically significant improvement in ESAS scores within the domains of anxiety (z score, -10.04), pain (z score, -2.36), tiredness (z score, -5.02), depression (z score, -5.96), drowsiness (z score, -5.51), appetite (z score, -4.17), and general well-being (z score, -4.43).
Conclusions and Relevance: This prospective case-matched study suggests that there may be significant QOL benefits, including decreased anxiety, pain, and depression and increased appetite and generalized feelings of well-being, associated with marijuana use among patients with newly diagnosed HNC.

PMID: 30073295 [PubMed - as supplied by publisher]

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Effect of Nitrous Oxide as a Treatment for Subjective, Idiopathic, Nonpulsatile Bothersome Tinnitus: A Randomized Clinical Trial.

Related Articles

Effect of Nitrous Oxide as a Treatment for Subjective, Idiopathic, Nonpulsatile Bothersome Tinnitus: A Randomized Clinical Trial.

JAMA Otolaryngol Head Neck Surg. 2018 Aug 02;:

Authors: Hong HY, Karadaghy O, Kallogjeri D, Brown FT, Yee B, Piccirillo JF, Nagele P

Abstract
Importance: The tinnitus research literature suggests that N-methyl-d-aspartate (NMDA) receptor antagonists may be useful in reducing tinnitus. Nitrous oxide, a member of the NMDA receptor antagonist class, is a widely used general anesthetic and sedative with a proven safety record.
Objective: To investigate whether nitrous oxide can reduce bothersome tinnitus.
Design, Setting, and Participants: Randomized, placebo-controlled crossover trial conducted between October 15, 2016, and June 22, 2017. Participants attended 2 interventional sessions separated by at least 14 days and were randomized to receive either placebo first or nitrous oxide first. Participants were followed up through completion of the second arm of the study. The setting was a clinical research unit at an academic medical center. Adults aged 18 to 65 years with subjective, idiopathic, nonpulsatile bothersome tinnitus of 6 months' duration or longer were recruited from 2 clinical research databases. Seventy-one individuals were screened, of whom 40 were enrolled. Of those enrolled, 37 participants completed all components of the study.
Interventions: The placebo session consisted of 50% nitrogen and 50% oxygen inhaled for 40 minutes, and the treatment session consisted of 50% nitrous oxide and 50% oxygen inhaled for 40 minutes.
Main Outcomes and Measures: Tinnitus was assessed before and after intervention, with the change in the Tinnitus Functional Index (TFI) as the primary outcome measure. Secondary outcome measures included the Patients' Global Impression of Change score and the change in the Global Bothersome Scale score.
Results: Among 40 participants in this intent-to-treat randomized clinical trial with 20 participants randomly assigned to each group, the mean (SD) age of participants was 52.9 (11.1) years, with equal numbers of male and female participants. The TFI after intervention was a mean (SD) of 1.8 (8.8) points lower than before intervention in the placebo arm and a mean (SD) of 2.5 (11.0) points lower than before intervention in the nitrous oxide arm. The within-participant mean difference in the change in the TFI of the placebo arm compared with the nitrous oxide arm was -1.1 points (95% CI, -5.6 to 3.4 points). The difference between the placebo and nitrous oxide arms was neither clinically meaningful nor statistically significant.
Conclusions and Relevance: Nitrous oxide was no more effective than placebo for the treatment of subjective, idiopathic tinnitus.
Trial Registration: ClinicalTrials.gov identifier: NCT03365011.

PMID: 30073285 [PubMed - as supplied by publisher]

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Dornase Alfa Ototoxic Effects in Animals and Efficacy in the Treatment of Clogged Tympanostomy Tubes in Children: A Preclinical Study and a Randomized Clinical Trial.

Related Articles

Dornase Alfa Ototoxic Effects in Animals and Efficacy in the Treatment of Clogged Tympanostomy Tubes in Children: A Preclinical Study and a Randomized Clinical Trial.

JAMA Otolaryngol Head Neck Surg. 2018 Aug 02;:

Authors: Chan KH, Allen GC, Kelley PE, Streubel SO, Friedman NR, Yoon P, Gao D, Ruiz AG, Jung TTK

Abstract
Importance: Many treatments for clogged tympanostomy tubes (TTs) have been proposed, but none have met scientific rigor for safety and efficacy, including the popular empirical use of ototopical antibiotic drops. Dornase alfa, a recombinant molecule with the unique property of cleaving DNA, may be ideal in treating clogged TTs because both middle-ear effusion and the plug are abundant with DNA.
Objective: To investigate the ototoxic effects of dornase alfa in a chinchilla model and its efficacy in a clinical trial in children with clogged TTs.
Design, Setting, and Participants: The safety profiles of dornase alfa (full-strength and 1:10 strength) were evaluated in chinchilla middle ears using serial auditory brainstem response. The efficacy of ototopical dornase alfa (full-strength) was evaluated in children with clogged TTs in a prospective, single-blind randomized clinical trial. The animal study included 21 chinchillas and was conducted at Loma Linda University, Loma Linda, California, and the clinical trial was conducted at Children's Hospital Colorado, Aurora. A total of 40 children (50 ears with tubes) were enrolled.
Interventions: In the animal study, chinchillas were assigned to 3 groups: controls (saline), full-strength dornase alfa, or 1:10 dornase alfa dilution. Children were randomly assigned to receive either topical dornase alfa or ofloxacin for clogged TT, 5 drops each ear twice a day for 7 days.
Main Outcomes and Measures: Animal study: Auditory brainstem responses. Randomized trial of children participants: The primary outcome was patency of TT at day 14 assessed by otoscopy and tympanometry.
Results: The chinchilla study showed similar auditory brainstem response degradation during a 6-hour period between the control (n = 5) and treatment groups (n = 21). In the clinical trial, a total of 40 clogged TTs (in 33 children, including 25 boys [76%]; mean age, 4.3 years; median [range] age, 3.4 [1.0-14.3] years) were analyzed. The number of unclogged TTs was higher in the dornase alfa group (13 [59%]) compared with the ofloxacin group (8 [44%]), with a difference of 15% (odds ratio, 1.8; 95% CI, 0.54-6.72).
Conclusions and Relevance: The chinchilla model suggests that dornase alfa is likely nonototoxic. The pilot clinical trial failed to show efficacy of dornase alfa to unclog TTs. With the difference seen between the treatment groups, a sample size estimate could be calculated for a future large-scale trial.
Trial Registration: ClinicalTrials.gov identifier: NCT00419380.

PMID: 30073253 [PubMed - as supplied by publisher]

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Cricopharyngeal Muscle Dysfunction Following Hypoglossal Nerve Stimulator Placement.

Related Articles

Cricopharyngeal Muscle Dysfunction Following Hypoglossal Nerve Stimulator Placement.

JAMA Otolaryngol Head Neck Surg. 2018 Aug 02;:

Authors: Stevens BJ, Geer AM, Dion GR, Laury AM, Scalzitti NJ

PMID: 30073244 [PubMed - as supplied by publisher]

https://ift.tt/2M3hc7G

Phase II trial of capecitabine plus oxaliplatin (CAPOX) as perioperative therapy for locally advanced rectal cancer

Abstract

Purpose

The standard strategy for locally advanced lower rectal cancer is chemoradiotherapy followed by total mesorectal excision (TME) in Western countries and TME followed by adjuvant chemotherapy without preoperative treatment in Japan.

Methods

This phase II trial evaluated the efficacy of a preoperative CAPOX chemotherapy regimen without radiation therapy for patients with locally advanced rectal cancer. The primary endpoint was 2-year disease-free survival.

Results

The trial enrolled 45 patients from 9 institutions between 2012 and 2014. The mean age was 63.5 (29–74) years; 31 patients were male. Most patients (n = 41) received preoperative chemotherapy (CTx), and the preoperative CTx completion rate was 95.2%. R0 resection after CTx was performed in 41 patients. The pathological complete response rate was 7.3% (3/41). After surgery, 35 patients (85.3%) received adjuvant CTx, and 22 of 35 completed the protocol treatment. The follow-up period ranged from 0.71 to 4.68 years (median 2.86 years). There was recurrence in 13 of 40 patients who underwent R0 resection, and the 2-year disease-free survival rate and overall survival rate were 71.6 and 92.7%, respectively.

Conclusions

Here we report the completion rates for neoadjuvant CTx and adjuvant CTx, the pathological complete response rate, and the mid-term prognosis. The results indicate that CAPOX followed by TME may be a safe treatment strategy for locally advanced rectal cancer.

https://ift.tt/2AFgbhU

Intranasal endoscopic prelacrimal recess approach for maxillary sinus inverted papilloma

Abstract

Purpose

This study aims to determine the indications and effectiveness of transnasal endoscopic prelacrimal recess approach (PLRA) in patients with maxillary sinus inverted papilloma (IP).

Methods

We retrospectively analyzed 71 patients treated in our institution for maxillary sinus IP between August 2008 and April 2015. 20 patients underwent endoscopic surgery via PLRA. All the patients who had postoperative follow-up for 3 years were enrolled. Demographic data, surgical technique, location of IP attachment, intra- and postoperative complications, follow-up duration and recurrence were recorded.

Results

The outpatient follow-up period was 3–10 years after surgery. Recurrence of IP was seen in 6 (8.5%) of 71 patients, including 1 patient in the PLRA group. The recurrence rate was 5% in the PLRA group. Six of 71 patients experienced postoperative complications, but none was observed in the PLRA group.

Conclusion

Transnasal endoscopic PLRA is a minimally invasive, safe and effective method for maxillary sinus IP. The indication for PLRA is tumor pedicle located on the antero-inferior or infero-lateral wall or at multiple attachment sites of the maxillary sinus.

https://ift.tt/2OJ0sBm

Association between CTLA-4 + 49A > G and – 318C > T single-nucleotide polymorphisms and susceptibility to thyroid neoplasm

Abstract

Purpose

Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4 or CD152) is among the immune checkpoint molecules and its abnormal expression in cancer predisposed individuals might make the person more susceptible to tumor initiation and progression. Considering the implication of single-nucleotide polymorphisms (SNPs) in CTLA-4 gene expression and probably protein function, one can assume the involvement of these SNPs in neoplastic diseases. rs5742909 ( − 318C > T) and rs231775 ( + 49 A > G) are among the most commonly studied SNPs and have been considered as genetic factors related to thyroid diseases. In this cross-sectional study, we aimed to elucidate the association between these SNPs and susceptibility to various types of thyroid cancers.

Methods

We investigated the genetic polymorphisms of − 318C > T and + 49 A > G in the CTLA-4 gene by means of ARMS-PCR and RFLP-PCR, respectively, in 167 patients with thyroid carcinomas (papillary, follicular, and anaplastic). The results were then compared with a group of 100 age-sex matched healthy individuals.

Results

A statistically significant association was observed between the presence of G allele in + 49 A > G locus and thyroid carcinoma, when comparing cases and controls (OR = 2.10; 95% CI = 1.35–3.28; P = 0.001) and the frequency of heterozygotes (AG) was higher than homozygotes for allele A (AA), in patients with and papillary thyroid carcinoma (PTC). Regarding Hashimoto's thyroiditis, the frequencies of A allele and AA genotype in PTC patients were higher than Hashimoto patients with no history of cancer (OR = 4.67, 95% CI = 2.70–8.08, P < 0.0001; and, OR = 4.68, 95% CI = 1.84–11.91, P = 0.0012; respectively). However; we observed no difference among allele/genotype frequencies in regards to locus – 318C > T.

Conclusion

In this study, we observed that G allele in + 49 A > G and possibly lower expression of mutated CTLA-4 molecule, is associated with higher susceptibility to thyroid carcinoma. Although the G allele frequency was higher in thyroid cancer patients, when justified for the presence of lymphocytic thyroiditis, the presence of A allele seemed to increase the odds for PTC in patients with Hashimoto's disease.

https://ift.tt/2MezQX9

Increased antitumor activities of glypican-3-specific chimeric antigen receptor-modified T cells by coexpression of a soluble PD1–CH3 fusion protein

Abstract

Our recent clinical study demonstrated that glypican-3 (GPC3)-specific chimeric antigen receptor-modified T (CAR-T) cells are a promising treatment for hepatocellular carcinoma (HCC). However, the interaction of programmed cell death 1 (PD-1) and PD-L1-mediated T-cell inhibition is involved in immune evasion in a wide range of solid tumors, including HCC. To overcome this problem, we introduced a fusion protein composed of a PD-1 extracellular domain and CH3 from IgG4 into GPC3-specific CAR-T cells (GPC3-28Z) to block the PD-1/PD-L1 pathway. GPC3-specific CAR-T cells carrying the PD-1–CH3 fusion protein (sPD1) specifically recognized and lysed GPC3-positive HCC cells. The proliferation capacity of GPC3-28Z-sPD1 T cells after weekly stimulation with target cells was much higher than that of control GPC3-28Z T cells. Additionally, the coexpression of sPD1 could protect CAR-T cells from exhaustion when incubated with target cells, as phosphorylated AKT and Bcl-xL expression levels were higher in GPC3-28Z-sPD1 T cells than in GPC3-28Z cells. Importantly, in two HCC tumor xenograft models, GPC3-28Z-sPD1 T cells displayed a significantly higher tumor suppression capacity than GPC3-28Z T cells. In addition, an increased number of CD3⁺ T cells in the circulation and tumors and increased granzyme B levels and decreased Ki67 expression levels in the tumors were observed in the mice treated with GPC3-28Z-sPD1 T cells. Together, these data indicated that GPC3-specific CAR-T cells carrying sPD1 show promise as a treatment for patients with HCC.

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Association between CTLA-4 + 49A > G and – 318C > T single-nucleotide polymorphisms and susceptibility to thyroid neoplasm

Abstract

Purpose

Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4 or CD152) is among the immune checkpoint molecules and its abnormal expression in cancer predisposed individuals might make the person more susceptible to tumor initiation and progression. Considering the implication of single-nucleotide polymorphisms (SNPs) in CTLA-4 gene expression and probably protein function, one can assume the involvement of these SNPs in neoplastic diseases. rs5742909 ( − 318C > T) and rs231775 ( + 49 A > G) are among the most commonly studied SNPs and have been considered as genetic factors related to thyroid diseases. In this cross-sectional study, we aimed to elucidate the association between these SNPs and susceptibility to various types of thyroid cancers.

Methods

We investigated the genetic polymorphisms of − 318C > T and + 49 A > G in the CTLA-4 gene by means of ARMS-PCR and RFLP-PCR, respectively, in 167 patients with thyroid carcinomas (papillary, follicular, and anaplastic). The results were then compared with a group of 100 age-sex matched healthy individuals.

Results

A statistically significant association was observed between the presence of G allele in + 49 A > G locus and thyroid carcinoma, when comparing cases and controls (OR = 2.10; 95% CI = 1.35–3.28; P = 0.001) and the frequency of heterozygotes (AG) was higher than homozygotes for allele A (AA), in patients with and papillary thyroid carcinoma (PTC). Regarding Hashimoto's thyroiditis, the frequencies of A allele and AA genotype in PTC patients were higher than Hashimoto patients with no history of cancer (OR = 4.67, 95% CI = 2.70–8.08, P < 0.0001; and, OR = 4.68, 95% CI = 1.84–11.91, P = 0.0012; respectively). However; we observed no difference among allele/genotype frequencies in regards to locus – 318C > T.

Conclusion

In this study, we observed that G allele in + 49 A > G and possibly lower expression of mutated CTLA-4 molecule, is associated with higher susceptibility to thyroid carcinoma. Although the G allele frequency was higher in thyroid cancer patients, when justified for the presence of lymphocytic thyroiditis, the presence of A allele seemed to increase the odds for PTC in patients with Hashimoto's disease.

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