71.
Int J Surg Case Rep. 2020 Mar 3;68:185-189. doi: 10.1016/j.ijscr.2020.02.062. [Epub ahead of print]
Gastric inflammatory myofibroblastic tumor in a 10-month-old girl: A case report.
Morales Prillwitz O1, Pérez Hurtado B2, Olaya Álvarez S3, Arevalo Sánchez NM3, Astudillo Palomino RE4.
Abstract
INTRODUCTION:
Inflammatory Myofibroblastic Tumors (IMTs) are rare mesenchymal tumors of unclear etiology and uncertain malignant potential that affect all age groups. IMTs are most often found in the lungs; although they do occur in a variety of other organs. IMTs have been reported in the mesentery, head and neck, omentum, retroperitoneum, limbs, genitourinary tract, and, extremely rarely, in the stomach. There is scant epidemiological data on IMTs, in part, due to the absence of national and international registries.
PRESENTATION OF CASE:
This is a case report of a 10-month-old girl who presented with clinical signs of fever and weight loss over a period of four months. The patient was initially diagnosed with a febrile syndrome of unknown origin. However, upon further investigation, a Gastric IMT was found, and the patient required a left hepatectomy and subtotal gastrectomy with Roux-en-Y reconstruction.
CONCLUSION:
In the pediatric population clinical findings are often nonspecific. Based on this case study, we conclude that, in children with palpable masses, IMT should always be considered as a diagnostic option.
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
KEYWORDS:
Biopsy; Case report; Infant; Inflammatory Pseudo Tumor; Stomach
72.
Eur J Radiol. 2020 Mar 5;126:108936. doi: 10.1016/j.ejrad.2020.108936. [Epub ahead of print]
Prediction of the human papillomavirus status in patients with oropharyngeal squamous cell carcinoma by FDG-PET imaging dataset using deep learning analysis: A hypothesis-generating study.
Abstract
PURPOSE:
To assess the diagnostic accuracy of imaging-based deep learning analysis to differentiate between human papillomavirus (HPV) positive and negative oropharyngeal squamous cell carcinomas (OPSCCs) using FDG-PET images.
METHODS:
One hundred and twenty patients with OPSCC who underwent pretreatment FDG-PET/CT were included and divided into the training 90 patients and validation 30 patients cohorts. In the training session, 2160 FDG-PET images were analyzed after data augmentation process by a deep learning technique to create a diagnostic model to discriminate between HPV-positive and HPV-negative OPSCCs. Validation cohort data were subsequently analyzed for confirmation of diagnostic accuracy in determining HPV status by the deep learning-based diagnosis model. In addition, two radiologists evaluated the validation cohort image-data to determine the HPV status based on each tumor's imaging findings.
RESULTS:
In deep learning analysis with training session, the diagnostic model using training dataset was successfully created. In the validation session, the deep learning diagnostic model revealed sensitivity of 0.83, specificity of 0.83, positive predictive value of 0.88, negative predictive value of 0.77, and diagnostic accuracy of 0.83, while the visual assessment by two radiologists revealed 0.78, 0.5, 0.7, 0.6, and 0.67 (reader 1), and 0.56, 0.67, 0.71, 0.5, and 0.6 (reader 2), respectively. Chi square test showed a significant difference between deep learning- and radiologist-based diagnostic accuracy (reader 1: P = 0.016, reader 2: P = 0.008).
CONCLUSIONS:
Deep learning diagnostic model with FDG-PET imaging data can be useful as one of supportive tools to determine the HPV status in patients with OPSCC.
Copyright © 2020 Elsevier B.V. All rights reserved.
KEYWORDS:
18F-fluorodeoxyglucose positron-emission tomography; Deep learning; Human papillomavirus; Oropharyngeal squamous cell carcinoma
73.
Neurosci Lett. 2020 Mar 11:134910. doi: 10.1016/j.neulet.2020.134910. [Epub ahead of print]
Nicotinamide riboside protects noise-induced hearing loss by recovering the hair cell ribbon synapses.
Abstract
OBJECTIVE:
Nicotinamide riboside (NR) has been proved to protect the hearing. To achieve animal models of temporary threshold shift (TTS) and permanent threshold shift (PTS) respectively, evaluate the dynamic change of ribbon synapse before and after NR administration METHODS: Mice were divided into control group, noise exposure (NE) group and NR group. The noise was exposed to NE and NR group, and NR was injected before noise exposure. Auditory brainstem response (ABR), ribbon synapse count and cochlear morphology were tested, as well as the concentration of hydrogen peroxide (H2O2) and ATP.
RESULTS:
Ribbon synapse count decrease with the intensity of noise exposure, and the cochlear morphology remains stable during TTS and was damaged during PTS. NR promotes the oxidation resistance to protect the synapse and the inner ear morphology.
CONCLUSION:
Our findings suggest that TTS mice are more vulnerable to noise, and NR can promote the recovery of the synapse count to protect the animals' hearing.
Copyright © 2020. Published by Elsevier B.V.
KEYWORDS:
cochlea; hidden hearing loss; nicotinamide ribose; noise; oxidative damage; ribbon synapse
74.
Magn Reson Imaging. 2020 Mar 11. pii: S0730-725X(19)30668-X. doi: 10.1016/j.mri.2020.03.004. [Epub ahead of print]
Feasibility of free-breathing T1-weighted 3D radial VIBE for fetal MRI in various anomalies.
Abstract
RATIONALE AND OBJECTIVES:
In magnetic resonance (MR) fetal imaging, the image quality acquired by the traditional Cartesian-sampled breath-hold T1-weighted (T1W) sequence may be degraded by motion artifacts arising from both mother and fetus. The radial VIBE sequence is reported to be a viable alternative to conventional Cartesian acquisition for both pediatric and adult MR, yielding better image quality. This study evaluated the role of radial VIBE in fetal MR imaging and compared its image quality and motion artifacts with those of the Cartesian T1W sequence.
MATERIALS AND METHODS:
We included 246 pregnant women with 50 lesions on 1.5-T MR imaging. Image quality and lesion conspicuity were evaluated by two radiologists, blinded to the acquisition schemes used, using a five-point scale, where a higher score indicated a better trajectory method. Mixed-model analysis of variance and interobserver variability assessment were performed.
RESULTS:
The radial VIBE sequence showed a significantly better performance than conventional T1W imaging in the head and neck, fetal body, and placenta region: 3.92 ± 0.88 vs 3 ± 0.74, p < 0.001, 3.8 ± 0.94 vs 3.15 ± 0.87, p < 0.001, and 4.17 ± 0.63 vs 3.12 ± 0.72, p < 0.001, respectively. Additionally, fewer motion artifacts were observed in all regions with the radial VIBE sequence (p < 0.01). Of 50 lesions, 49 presented better lesion conspicuity on radial VIBE images than on T1W images (4.34 ± 0.91 vs 3.48 ± 1.46, p < 0.001).
CONCLUSION:
For fetal imaging, the radial VIBE sequences yielded better image quality and lesion conspicuity, with fewer motion artifacts, than conventional breath-hold Cartesian-sampled T1W sequences.
Copyright © 2020. Published by Elsevier Inc.
KEYWORDS:
Artifact; Fetal diagnosis; Fetal magnetic resonance imaging; Image quality; Prenatal
75.
Oral Oncol. 2020 Mar 11:104636. doi: 10.1016/j.oraloncology.2020.104636. [Epub ahead of print]
Overcoming frailty in recurrent and metastatic head and neck cancer.
76.
J Craniomaxillofac Surg. 2020 Feb 24. pii: S1010-5182(20)30048-2. doi: 10.1016/j.jcms.2020.02.010. [Epub ahead of print]
Transoral resection with buccinator flap reconstruction vs. pull-through resection and free flap reconstruction for the management of T1/T2 cancer of the tongue and floor of the mouth.
Ferri A1, Perlangeli G2, Montalto N3, Carrillo Lizarazo JL1, Bianchi B1, Ferrari S1, Nicolai P3, Sesenna E1, Grammatica A3.
Abstract
AIM:
To compare the most important techniques usually used in these patients.
MATERIALS AND METHODS:
A multicentric retrospective evaluation on patients treated for cT1/2 N0 OTFOM SCC was conducted; patients in group A were treated by transoral approach and miomucosal local flap while those in group B were treated by pull-through and free flap reconstruction. Oncologic, functional and quality of life evaluation was assessed.
RESULTS:
55 patients were enrolled. Group A consisted of 35 patients and group B 20. At the 3-year follow-up 30 and 17 patients in group A and B were alive without disease. Tongue mobility index score was 23.3 in group A and 13.89 in group B (p < .001); Sydney swallowing mean score was 118.5 and 543.22 in group A and B (p < .001). EORTC QLC-C30 was of 33.57 in group A and 38.89 in group B (p = 0.057).
CONCLUSION:
T1/T2 cancers of the tongue and floor of the mouth can be equally treated with both techniques. Because of the fact that transoral resection with buccinators reconstruction provides better functional outcome, this technique should be preferred whenever appropriate.
Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
KEYWORDS:
Buccinator flap; Free flap; Oral cancer; Pull through resection; Transoral resection
77.
Eur J Cancer. 2020 Mar 11. pii: S0959-8049(20)30055-1. doi: 10.1016/j.ejca.2020.01.023. [Epub ahead of print]
A prospective multicentre REFCOR study of 470 cases of head and neck Adenoid cystic carcinoma: epidemiology and prognostic factors.
Atallah S1, Casiraghi O2, Fakhry N3, Wassef M4, Uro-Coste E5, Espitalier F6, Sudaka A7, Kaminsky MC8, Dakpe S9, Digue L10, Bouchain O11, Morinière S12, Hourseau M13, Bertolus C14, Jegoux F15, Thariat J16, Calugaru V17, Schultz P18, Philouze P19, Mauvais O20, Righini CA21, Badoual C22, Saroul N23, Goujon JM24, Marie JP25, Taouachi R26, Brenet E27, Aupérin A28, Baujat B29.
Abstract
BACKGROUND:
Adenoid cystic carcinoma (ACC) accounts for 1% of malignant head and neck tumours [1] and 10% of salivary glands malignant tumours. The main objective of our study is to investigate the prognostic factors influencing the event-free survival (EFS) of patients with ACC.
PATIENTS AND METHODS:
A multicentre prospective study was conducted from 2009 to 2018. All 470 patients with ACC whose survival data appear in the REFCOR database were included in the study. The main judgement criterion was EFS. Both a bivariate survival analysis using log-rank test and a multivariate using Cox model were performed using the R software.
RESULTS:
Average age was 55 years. Females accounted for 59.4% of the cohort. The body mass index (BMI) was normal in 86% of cases. Tumours were located in minor salivary glands in 60% of cases. T3/T4 stages represented 58%; 89% of patients were cN0. histological grade III was observed on 21% of patients. The EFS and overall 5-year survival rates were 50% and 85%, respectively. After adjustment, the most significant pejorative prognostic factors were age ≥65 years (hazard ratio [HR] = 1.67), BMI<16.5 (HR = 2.62), and lymph node invasion cN (HR = 2.08).
CONCLUSION:
Age, BMI and N stage are the three main clinical prognostic factors determining EFS identified in this prospective series of patients with ACC. Such findings open new research perspectives on the influence of these components on initial patient care.
Copyright © 2020 Elsevier Ltd. All rights reserved.
KEYWORDS:
Adenoid cystic carcinoma; Event-free survival; Prognostic factors; REFCOR
78.
J Endod. 2020 Mar 11. pii: S0099-2399(20)30071-6. doi: 10.1016/j.joen.2020.01.018. [Epub ahead of print]
3-year Outcome of Patients with Persistent Pain after Root Canal Treatment: The National Dental Practice-Based Research Network.
Daline IH1, Nixdorf DR2, Law AS3, Pileggi R4; National Dental Practice-Based Research Network Collaborative Group5.
Abstract
INTRODUCTION:
We measured the long-term outcomes of patients reporting persistent pain 6 months after root canal treatment (RCT) and assessed the characteristics differing patients with pain chronification from those with pain resolution.
METHODS:
Forty-five patients previously found to have persistent pain 6 months post-RCT from the National Dental Practice-Based Research Network were approached for a 3-year follow-up, and 27 participated in the survey. The frequency of self-reported pain, its impact on the ability to perform daily activities, and health care use were measured. The differences between patients whose persistent pain continued and those whose pain resolved were assessed.
RESULTS:
Five patients met criteria for pain at 3.4 years (range, 3.1-3.9 years) post-RCT, which was moderate in intensity, occurred for about 3 days in the preceding month, and kept 1 patient from usual activities. Additional health care was received by 4 of 5 patients whose pain continued compared with 7 of 22 patients whose pain resolved. A longer duration of preoperative pain and higher pain intensity and interference at 6 months were found among patients with pain chronification. Of 13 patients with specific diagnoses for the persistent pain derived at 65 ± 41 days (∼8 months) post-RCT, 10 improved regardless of the diagnosis or treatment, and 11 had a temporomandibular disorder and/or headache as comorbid diagnoses (6) or causes (6) of the persistent "tooth" pain.
CONCLUSIONS:
Progression of persistent post-RCT pain occurred in 19% of patients. The majority (56%) of patients improved without additional interventions. Both the group that improved and the group that continued to experience pain had a mixture of odontogenic and nonodontogenic etiologies.
Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Endodontics; health care use; observational study; patient outcome assessment; quality of life
79.
J Pediatr. 2020 Mar 11. pii: S0022-3476(20)30134-7. doi: 10.1016/j.jpeds.2020.01.061. [Epub ahead of print]
Differences in Tonsillectomy Use by Race/Ethnicity and Type of Health Insurance Before and After the 2011 Tonsillectomy Clinical Practice Guidelines.
Abstract
OBJECTIVE:
To evaluate whether differences in pediatric tonsillectomy use by race/ethnicity and type of insurance were impacted by the American Academy of Otolaryngology-Head and Neck Surgery's 2011 tonsillectomy clinical practice guidelines.
STUDY DESIGN:
We included children aged <15 years from Florida or South Carolina who underwent tonsillectomy in 2004-2017. Annual tonsillectomy rates within groups defined by race/ethnicity and type of health insurance were calculated using US Census data, and interrupted time series analyses were used to compare the guidelines' impact on utilization across groups.
RESULTS:
The average annual tonsillectomy rate was greater among non-Hispanic white children (66 procedures per 10 000 children) than non-Hispanic black (38 procedures per 10 000 children) or Hispanic children (41 procedures per 10 000 children) (P < .001). From the year before to the year after the guidelines' release, tonsillectomy use decreased among non-Hispanic white children (-11.1 procedures per 10 000 children), but not among non-Hispanic black (-0.9 procedures per 10 000 children) or Hispanic children (+3.9 procedures per 10 000 children) (P < .05). Use was greater among publicly than privately insured children (75 vs 52 procedures per 10 000 children, P < .001). The guidelines were associated with a reversal of the upward trend in use seen in 2004-2010 among publicly insured children (-5.5 procedures per 10 000 children per year, P < .001).
CONCLUSIONS:
Tonsillectomy use is greatest among white and publicly insured children. However, the American Academy of Otolaryngology-Head and Neck Surgery's 2011 clinical practice guideline statement was associated with an immediate decrease and change in use trends in these groups, narrowing differences in utilization by race/ethnicity and type of insurance.
Copyright © 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
clinical practice guidelines; ethnicity; healthcare disparities; insurance; race; tonsillectomy
80.
J Pediatr Surg. 2020 Feb 27. pii: S0022-3468(20)30168-8. doi: 10.1016/j.jpedsurg.2020.02.040. [Epub ahead of print]
Bilateral papillary thyroid cancer in children: Risk factors and frequency of postoperative diagnosis.
Baumgarten H1, Jenks CM2, Isaza A3, Bhatti T3, Mostoufi-Moab S3, Kazahaya K4, Adzick NS1, Bauer AJ5.
Abstract
BACKGROUND:
The recommendation for children with papillary thyroid cancer (PTC) is total thyroidectomy (TT) based on the incidence of bilateral disease. Evaluating this assumption, we reviewed the characteristics of bilateral PTC in a large cohort of children.
METHODS:
A retrospective chart review for patients surgically treated for PTC from 2009 to 2018 analyzing preoperative risk factors, ultrasound findings, and pathology results was performed. Bilateral disease was defined as pathologic PTC in the contralateral lobe, including microscopic disease.
RESULTS:
Of the 172 patients included, 38.4% had bilateral disease with 23% diagnosed postoperatively. Multifocal disease on ultrasound was associated with bilateral disease (OR 2.9, 95% CI 1.5-5.9, p = 0.002). Nodule dimension >2 cm was associated with increased risk for postoperative bilateral disease (OR 3.5, 95% CI 1.6-7.4, p = 0.001). Patients with bilateral disease were more likely to have extrathyroidal extension, lymphovascular invasion, positive central lymph nodes, and extranodal extension (p < 0.001 for all). Diffuse-sclerosing variant PTC was also associated with bilateral disease.
CONCLUSION:
Thirty-eight percent of children were diagnosed with PTC demonstrate bilateral disease. Nearly one in four have occult bilateral disease. The features that predicted bilateral disease were multifocality, widely invasive PTC on ultrasound, and the presence of lymphadenopathy. Thus, TT is the appropriate surgical approach for pediatric patients with PTC.
TYPE OF STUDY:
Clinical Research, Retrospective Review.
LEVEL OF EVIDENCE:
Level IV.
Copyright © 2020 Elsevier Inc. All rights reserved.
KEYWORDS:
Bilateral papillary thyroid cancer; Lobectomy; Multifocal; Occult disease; TI-RADS; Total thyroidectomy; Unifocal
81.
Int J Radiat Oncol Biol Phys. 2020 Apr 1;106(5):926-927. doi: 10.1016/j.ijrobp.2020.01.025.
Not So Fast: Deintensification Therapy for Locally Advanced Oral Cavity Cancer.
82.
Int J Radiat Oncol Biol Phys. 2020 Apr 1;106(5):893-899. doi: 10.1016/j.ijrobp.2019.12.015.
Four Influential Clinical Trials in Human Papilloma Virus-Associated Oropharynx Cancer.
83.
Acta Otorrinolaringol Esp. 2020 Mar 11. pii: S0001-6519(20)30011-X. doi: 10.1016/j.otorri.2019.10.001. [Epub ahead of print]
Versatility of the radial forearm free flap in head and neck reconstruction. A study of 58 cases.
[Article in English, Spanish]
Abstract
INTRODUCTION:
The radial forearm free flap (RFFF) is a widely used tool in head and neck reconstructive surgery. It stands out as a relatively simple flap to achieve; it is versatile and has features that enable the reconstruction of complex head and neck defects. The aim of the study was to present our results using the RFFF in the reconstruction of seated defects in the head and neck area.
MATERIAL AND METHODS:
A retrospective, observational and analytical study that included 58 cases of RFFF interventions, performed between January 2002 and July 2019. The data studied were the age and sex of the patients, location of the tumour, histological type, previous radiation therapy, number of venous anastomoses performed in the surgery and body temperature in the immediate postoperative period, at 24 and 48hours following surgery.
RESULTS:
The percentage of viable RFFF was 82.8%. None of the variables analysed appear to be a risk factor for flap failure. The most frequent cause of flap failure was venous thrombosis.
CONCLUSIONS:
Microvascularised flaps play an important role in reconstructive surgery, being the RFFF one of the most interesting for head and neck reconstruction. It is a very versatile tool that allows the reconstruction of many of the sites where the head and neck surgeon operates.
Copyright © 2020 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.
KEYWORDS:
Cabeza y cuello; Colgajo microvascularizado antebraquial radial; Factores de riesgo; Head and neck; Radial forearm free flap; Reconstrucción; Reconstruction; Risk factors
84.
Stem Cell Res Ther. 2020 Mar 14;11(1):117. doi: 10.1186/s13287-020-1576-3.
MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-β signaling pathway.
Abstract
BACKGROUND:
Oral squamous cell carcinoma (OSCC) is associated with high morbidity and ranks sixth among malignancies worldwide. Increasing evidence suggests that microRNAs (miRNAs or miRs) play a critical role in regulating cancer stem cells (CSCs), which drive the proliferation and spread of OSCC. Therefore, based on the alteration of aberrantly expressed miR-495 and homeobox C6 (HOXC6) by Gene Expression Omnibus (GEO) analysis, we subsequently explore the potential effect of miR-495 on the progression of CSCs in OSCC.
METHODS:
After the isolation of CSCs from the clinical tissue samples of OSCC patients, the expression of miR-495 and HOXC6 was determined, followed by the validation of the relationship between miR-495 and HOXC6. Subsequently, gain- and loss-function approach was performed to detect the role of miR-495 and HOXC6 in cell proliferation, migration, invasion, cell cycle entry, apoptosis, and epithelial-mesenchymal transition (EMT) of CSCs in OSCC, as well as the tumor growth in vivo.
RESULTS:
HOXC6 was highly expressed while miR-495 was poorly expressed in OSCC. HOXC6 was verified to be a target gene of miR-495, and miR-495 could inhibit the activation of the TGF-β signaling pathway. CSCs with miR-495 overexpression or HOXC6 silencing exhibited reversed EMT process; reduced abilities of proliferation, migration, and invasion; and promoted cell apoptosis in vitro. Moreover, inhibited tumor growth was observed in vivo after injection with miR-495 agomir or sh-HOXC6. In contrast, the downregulation of miR-495 showed an induced role in the progression of OSCC.
CONCLUSION:
These findings suggest that miR-495 may suppress HOXC6 to inhibit EMT, proliferation, migration, and invasion while promoting apoptosis of CSCs in OSCC by inhibiting the TGF-β signaling pathway.
KEYWORDS:
Cancer stem cells; Epithelial-mesenchymal transition; Homeobox C6; Invasion; Migration; Oral squamous cell carcinoma; TGF-β signaling pathway; microRNA-495
85.
BMC Cancer. 2020 Mar 14;20(1):218. doi: 10.1186/s12885-020-6692-z.
Evaluation of NID2 promoter methylation for screening of Oral squamous cell carcinoma.
Srisuttee R1, Arayataweegool A2, Mahattanasakul P3,4, Tangjaturonrasme N3, Kerekhanjanarong V3, Keelawat S5, Mutirangura A2, Kitkumthorn N6.
Abstract
BACKGROUND:
Oral squamous cell carcinoma (OSCC) is an aggressive human malignancy. Because of late diagnosis and recurrence of OSCC, the treatment of patients with OSCC is often ineffective. Thus, finding novel biomarkers of OSCC are essential. Here we derived a methylation marker by utilizing methylation microarray data and testing its capacity in cross-sectional study designed for OSCC detection and screening.
METHODS:
According to bioinformatics analysis of total of 27,578 cg sites, cg22881914 of Nidogen 2 (NID2) methylation was selected for evaluation. Next, we confirmed the methylation status by bisulfite sequencing from the microdissected OSCC cells in comparison with the microdissected oral epithelia. Subsequently, we developed a simple technique using real-time PCR with the specific probe to examine the ability for the detection of OSCC in the oral epithelial samples, which included 103 oral rinse and 82 oral swab samples.
RESULTS:
Based on the comparison of microdissected tissue, cg22881914 of NID2 was proved to be methylated in most OSCC cells but unmethylated in the normal oral epithelia. Furthermore, the methylated NID2-relied quantitative PCR approach has demonstrated that this marker assists in distinguishing among patients with OSCC from normal oral epithelia, smokers, and patients with oral lichen planus using the non-invasive oral rinse and swab samples.
CONCLUSIONS:
Specific methylation at cg22881914 of NID2 of OSCC could be used as an important potential marker for detecting OSCC. Thus, to certify the utility of this marker, further studies with a larger sample size are needed.
KEYWORDS:
Detection; Methylation; Nidogen2; Oral squamous cell carcinoma
86.
Medicine (Baltimore). 2020 Mar;99(10):e19329. doi: 10.1097/MD.0000000000019329.
Partial resection of hypertrophic torus tubarius for recurred snoring: Case series.
Abstract
Sleep-disordered breathing symptoms may recur in some children after successful adenoidectomy. A potential etiology that warrants consideration is torus tubarius hypertrophy (TTH) as well as residual or recurrent adenoid hypertrophy. Here, we report our experience and the treatment outcomes with microscopic coblator-assisted partial resection of TTH.Seven children who had undergone coblator-assisted partial resection of TTH under microscopy from April 2000 through January 2017 were retrospectively reviewed. The patient age at the time of initial adenotonsillectomy and the interval between the first operation and partial resection of TTH were identified. Lateral cephalometry and scores on the Korean version of the obstructive sleep apnea-18 (KOSA-18) questionnaire were reviewed.The median age at the time of the first operation was 3.0 years and the average time interval between the first operation and subsequent tubal tonsillectomy was 44.0 months. The average width between the torus tubarius was 2.1 mm preoperatively. Symptoms of sleep-disordered breathing were relieved in all patients after operation. Preoperative and postoperative KOSA-18 scores were 73.5 and 35.5, respectively (P = .024). On polysomnography, the preoperative and postoperative apnea-hypopnea index scores were 22.9 and 4.7, respectively (P = .068). The patients were followed up for an average of 1.3 years. One patient developed a recurrence of symptoms and underwent a revision operation. Complications such as bleeding and nasopharyngeal stenosis were not observed.Otorhinolaryngologists should keep TTH in mind as one of the differential diagnoses for recurrent upper airway obstruction symptoms after adenoidectomy. Microscopic coblator-assisted partial resection of TTH is likely to be safe and effective.
87.
Medicine (Baltimore). 2020 Feb;99(9):e19318. doi: 10.1097/MD.0000000000019318.
Increased risk of herpes zoster in patients with peptic ulcers: A longitudinal follow-up study using a national sample cohort.
Abstract
The purpose of this study was to investigate the association of herpes zoster infection with peptic ulcer disease in a Korean population.The Korean National Health Insurance Service selects samples directly from the entire Korean population database, and 1,125,691 participants with 114,369,638 medical claim codes were selected from the entire Korean population (50 million). A total of 127,802 peptic ulcer disease participants were matched with 127,802 control participants at a ratio of 1:1, considering age group, sex, income group, region of residence, hypertension, diabetes, and dyslipidemia. We analyzed stratified Cox proportional hazard models to calculate the hazard ratios of peptic ulcer with respect to herpes zoster. For subgroup analyses, we divided the participants by age, sex, and time periods after the index date.The rate of herpes zoster was higher in the peptic ulcer group (9.1% [11,669/127,802]) than in the control group (7.4% [9,397/127,802], P < .001). The adjusted hazard ratio of herpes zoster was 1.24 (95% CI = 1.21-1.28, P < .001). In subgroup analyses performed according to age and sex, all crude and adjusted hazard ratios of herpes zoster were higher in the peptic ulcer disease group than in the control group (each P < .05). In another subgroup analysis according to follow-up periods, the crude and adjusted hazard ratios of herpes zoster were higher in the peptic ulcer disease group than in the control group except for < 1 year periods after the index dates (each P < .001).The hazard ratios of herpes zoster were significantly increased in the peptic ulcer group compared with those in the control group in all age and sex groups.
88.
Medicine (Baltimore). 2020 Feb;99(9):e19294. doi: 10.1097/MD.0000000000019294.
Physical symptoms and mental health status in deep underground miners: A cross-sectional study.
Xie H1,2,3, Liu J1,4, Gao M1,3, Liu Y1, Ma T1,4, Lu Y2, Li C2, Wang M2, Zhang R2, Wu J1, Zou J1,4, Liu S1,4, Li W1.
Abstract
The aim of the present study was to reveal the physical symptom changes and their correlations with mental health status in deep underground miners.A total of 286 deep underground miners completed a cross-sectional questionnaire study at China Pingmei Shenma mine complex. The questionnaire included sociodemographics, self-reported physical symptoms, underground adverse environmental factors, and the Symptom Checklist-90-Revised (SCL-90-R). Five environmental parameters of 1 deep mine were also measured.Data from 266 valid questionnaires were analyzed. The 3 most frequent complaints about underground adverse conditions were moisture [62.03% (165/266)], dim light [45.86% (122/266)], and high temperature [42.11% (112/266)]. Fatigue [40.22% (107/266)], hearing loss [34.96% (93/266)], and tinnitus [31.58% (84/266)] were reported to be the three most common physical symptoms. Insomnia was reported in 204 participants (76.69%) mainly due to the difficulty of falling asleep [42.35% (84/204)] and dreams [39.70% (81/204)]. Mean scores of SCL-90-R subscales including somatization, anxiety, phobic anxiety, psychoticism, and paranoid ideation were elevated compared to Chinese norms, while there was diminished interpersonal sensitivity. Univariate analyses indicated that the 3 most common physical symptoms were associated with poorer SCL-90-R scores. With increasing depth below ground, air pressure, relative humidity, CO2 concentration and temperature rose, while total gamma radiation dose-rate decreased.The physical and mental health status of deep underground miners was poorer than the general Chinese male population. Some adverse environmental factors were identified that may have influenced health status. Measures are suggested to improve the deep underground working environment.
89.
Genes (Basel). 2019 Sep 24;10(10). pii: E744. doi: 10.3390/genes10100744.
The Prevalence and Clinical Characteristics of TECTA-Associated Autosomal Dominant Hearing Loss.
Yasukawa R1, Moteki H2, Nishio SY3,4, Ishikawa K5, Abe S6, Honkura Y7, Hyogo M8, Mihashi R9, Ikezono T10, Shintani T11, Ogasawara N12,13, Shirai K14, Yoshihashi H15, Ishino T16, Otsuki K17, Ito T18, Sugahara K19, Usami SI20,21.
Abstract
TECTA is well known as a causative gene for autosomal dominant mid-frequency hearing loss observed in various populations. In this study, we performed next-generation sequencing analysis of a large Japanese hearing loss cohort, including eight hundred and twelve (812) subjects from unrelated autosomal dominant hearing loss families, to estimate the prevalence and phenotype-genotype correlations in patients with TECTA mutations. The prevalence of TECTA mutations in Japanese autosomal dominant sensorineural hearing loss families was found to be 3.2%. With regard to the type of hearing loss, the patients with mutations in the nidogen-like domain or ZA domain of TECTA showed varied audiograms. However, most of the patients with mutations in the ZP domain showed mid-frequency hearing loss. The rate of hearing deterioration in TECTA-associated hearing loss patients and in the normal hearing Japanese control population were the same and regression lines for each group were parallel. We carried out haplotype analysis for four families which had one recurring missense variant, c.5597C>T (p.Thr1866Met). Our results revealed four different haplotypes, suggesting that this mutation occurred independently in each family. In conclusion, TECTA variants represent the second largest cause of autosomal dominant sensorineural hearing loss in Japan. The hearing loss progression observed in the patients with TECTA mutations might reflect presbycusis. The c.5597C>T mutation occurred in a mutational hot spot and is observed in many ethnic populations.
KEYWORDS:
DFNA8/12; TECTA; autosomal dominant; genotype-phenotype correlation; haplotype analysis; hearing progression; non-syndromic hearing loss; prevalence
90.
BMC Med Educ. 2019 Sep 23;19(1):363. doi: 10.1186/s12909-019-1789-2.
Examining the association of career stage and medical specialty with personality preferences - a cross-sectional survey of junior doctors and attending physicians from various specialties.
Abstract
BACKGROUND:
Personality preference research on medical students and physicians demonstrates that personality preferences may affect one's choice of specialty and transform over the course of one's academic career as well as during one's time spent in the clinical setting. The literature offers valuable methods for evaluating medical curricula, understanding medical specialties, and rethinking communication techniques between educators and learners. In line with this encompassing body of work, this study examines the personality preferences of junior doctors and attending physicians from various specialties to investigate how career stage and medical specialty are associated with personality preferences.
METHOD:
The Myers-Briggs Type Indicator (MBTI) was applied to assess the personality preferences of junior doctors (postgraduates year 1-3) and attending physicians from six major medical specialties. Participants completed a self-administered 93-item questionnaire, while a certified MBTI practitioner explained the personality dichotomies as well as facilitated the self-evaluation process and the questionnaire's interpretation. Contrasted dichotomous scores and radar plots were employed to illustrate the distinction between junior doctors and attending physicians' personality preferences. All analyses were performed using the SAS statistical software, while a Wilcoxon rank-sum test was used to quantify the polarisation of personality preferences between junior doctors and attending physicians.
RESULTS:
In total, 98 participants were recruited, of whom 59 were attending physicians and 39 were junior doctors. The most common personality types among the junior doctors were ESTJ (15.4%), INTP (12.8%), and ESFJ (10.3%), while among the attending physicians, the most common types were ISTJ (23.7%) and ESTJ (18.6%). Both junior doctors and attending physicians expressed personality preferences for sensing, thinking, and judging. However, compared to the junior doctors, more polarised personality preferences were noted among the attending physicians for sensing (p = 0.038), thinking (p = 0.032), and judging (p = 0.024). Moreover, junior doctors exhibited less distinct personality preferences in this study.
CONCLUSION:
Attending physicians and junior doctors exhibited greater personality inclinations for sensing, thinking, and judging, although the former expressed these personality preferences more strongly than the latter. These findings highlight that, amongst physicians, career stage is strongly associated with the expression of personality preferences.
KEYWORDS:
Career stage; Clinical training; Cross-sectional survey; Myers–Briggs type Indicator; Personality preference; Personality type; Specialty
- PMID:
- 31547826
- PMCID:
- PMC6757380
- DOI:
- 10.1186/s12909-019-1789-2
- [Indexed for MEDLINE]
91.
Genes (Basel). 2019 Sep 23;10(10). pii: E735. doi: 10.3390/genes10100735.
Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort.
Maekawa K1, Nishio SY2,3, Abe S4, Goto SI5, Honkura Y6, Iwasaki S7, Kanda Y8, Kobayashi Y9, Oka SI10, Okami M11, Oshikawa C12, Sakuma N13, Sano H14, Shirakura M15, Uehara N16, Usami SI17,18.
Abstract
Variants of the LOXHD1 gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8074 Japanese hearing loss patients utilizing massively parallel DNA sequencing to identify individuals with LOXHD1 variants and to assess their phenotypes. A total of 28 affected individuals and 21 LOXHD1 variants were identified, among which 13 were novel variants. A recurrent variant c.4212 + 1G > A, only reported in Japanese patients, was detected in 18 individuals. Haplotype analysis implied that this variation occurred in a mutational hot spot, and that multiple ancestors of Japanese population had this variation. Patients with LOXHD1 variations mostly showed early onset hearing loss and presented different progression rates. We speculated that the varying severities and progression rates of hearing loss are the result of environmental and/or other genetic factors. No accompanying symptoms, including vestibular dysfunction, with hearing loss were detected in this study. Few studies have reported the clinical features of LOXHD1-gene associated hearing loss, and this study is by far the largest study focused on the evaluation of this gene.
KEYWORDS:
DFNB77; LOXHD1; cochlear implantation; haplotype analysis; non-syndromic hearing loss; recurrent variation
92.
Ann Emerg Med. 2019 Oct;74(4):600-605. doi: 10.1016/j.annemergmed.2019.03.020.
Woman With Neck Mass.
93.
Pediatr Blood Cancer. 2019 Dec;66(12):e27974. doi: 10.1002/pbc.27974. Epub 2019 Sep 10.
Disseminated anaplastic pleomorphic xanthoastrocytoma with posttreatment fat necrosis during combined BRAF and MEK inhibitors therapy.
94.
Int J Dermatol. 2019 Nov;58(11):e210-e211. doi: 10.1111/ijd.14579. Epub 2019 Jul 8.
Tubular apocrine adenoma: dermoscopic and in vivo reflectance confocal microscopic aspects.
95.
J Bodyw Mov Ther. 2019 Apr;23(2):311-315. doi: 10.1016/j.jbmt.2019.02.011. Epub 2019 Feb 15.
Myofascial component of cancer pain review.
Abstract
BACKGROUND:
Pain is a common complaint of cancer patients, experienced by 38%-85% of patients. Some studies have shown a high incidence of myofascial pain syndrome (MPS) in cancer patients.
AIMS:
1) To estimate the prevalence of MPS in cancer patients; 2) to examine the efficacy of current treatment options for MPS in cancer patients.
METHODS:
Narrative review. PubMed, CINAHL, PEDro, and Google Scholar databases were searched from inception until November 2017, for the keywords: cancer; cancer pain; breast cancer; mastectomy; lumpectomy; myofascial pain; trigger points. Trials of any methodological quality were included. All published material with an emphasis on randomized control trials was analyzed.
RESULTS:
MPS is prevalent in cancer patients who suffer from pain, with a prevalence of between 11.9% and 44.8% in those diagnosed either with neck or head or breast cancer. Clinical studies showed conflicting results. Four interventional studies found that specific treatment for MPS may reduce the prevalence of active myofascial trigger points and therefore decrease pain level, sensitivity, and improve range of motion (in shoulder) in cancer patients. Two recent randomized control trials showed that pressure release of trigger points provides no additional beneficial effects to a standard physical therapy program for upper limb pain and function after breast cancer surgery.
CONCLUSIONS:
We recommend including the evaluation of myofascial pain in routine clinical examination of cancer patients suffering from pain. Future studies are needed to investigate the long- and short-term effect of MPS treatments in cancer patients.
Copyright © 2019 Elsevier Ltd. All rights reserved.
KEYWORDS:
Cancer; Myofascial pain; Myofascial release; Myofascial trigger points; Pain; Review
96.
Curr Opin Urol. 2019 Jul;29(4):364-370. doi: 10.1097/MOU.0000000000000640.
Genetics and penile cancer: recent developments and implications.
Abstract
PURPOSE OF REVIEW:
We summarize the recent developments in the molecular landscape of penile squamous cell carcinoma (PSCC).
RECENT FINDINGS:
Recent genomic studies have demonstrated a molecular convergence of PSCC with other squamous cell carcinomas (SCCs) from different organ sites. Similarly, human papillomavirus (HPV)-related PSCCs appear to have epigenetic and genomic similarities with other HPV-related cancers. This could have implications on future HPV-related cancer trial design. Growing efforts to characterize recurrent gene alterations in PSCC have expanded our understanding over the past years, showing a predominance of tumor suppressor gene alterations such as TP53 and NOTCH1. In addition, these studies have demonstrated that at least 30% of PSCC cases have targetable gene alterations. Further, the similar tumor mutational burden with other SCCs and the relatively high rates of programmed death-1 (PD-1) positive expression in PSCC constitute the rationale for investigation of PD-1 inhibition in ongoing clinical trials. Multiple studies have identified potential epigenetic and RNA signatures predictive of metastasis or survival, but these still require validation in larger cohorts.
SUMMARY:
PSCC appears to be genomicaly similar to other SCCs and HPV-related cancers. This provides the rationale and opportunity to include a rare tumor like PSCC in future 'basket type' trials using novel agents targeting multiple SCCs that may exhibit similar biology.
97.
J Speech Lang Hear Res. 2019 Feb 26;62(2):247-256. doi: 10.1044/2018_JSLHR-S-18-0316.
Laryngeal Neuromuscular Response to Short- and Long-Term Vocalization Training in Young Male Rats.
Abstract
Purpose Although vocal training is often purported to restore and rebalance laryngeal muscle function, little is known about the direct effects of vocal training on the laryngeal muscles themselves. Consequently, parameters of vocal exercise dose, such as training duration and intensity, have not been well defined. The goal of this study was to use a behavioral animal model to determine the effects of short- and long-term ultrasonic vocalization (USV) training on USV acoustics, thyroarytenoid (TA) muscle neuromuscular junctions (NMJs), and TA muscle fiber size in adult rats. Method Twenty-four young adult male Long-Evans rats were divided into 3 groups (untrained control, 4-week training, and 8-week training). Baseline and posttraining USVs were recorded and acoustically analyzed for fundamental frequency, frequency bandwidth, amplitude, and duration. Presynaptic and postsynaptic NMJ morphological features and muscle fiber size were measured in the TA. Results USV training had no effect on USV acoustics. Eight weeks of USV training, however, resulted in a lower NMJ motor endplate dispersion ratio, consistent with previous findings. USV training did not affect fiber size within the TA muscle. Conclusions This study demonstrated that 8 weeks of USV training can induce peripheral neural adaptations in the NMJ of the TA muscle in young rats. The observed adaptations suggest that vocal training is consistent with endurance-type exercise, but the adaptations occur on a longer time scale than similar adaptations in the limb muscles.
- PMID:
- 30950702
- PMCID:
- PMC6436889
- DOI:
- 10.1044/2018_JSLHR-S-18-0316
- [Indexed for MEDLINE]
98.
Am J Respir Crit Care Med. 2019 Sep 15;200(6):742-750. doi: 10.1164/rccm.201806-1178OC.
Driver Mutations in Normal Airway Epithelium Elucidate Spatiotemporal Resolution of Lung Cancer.
Kadara H1, Sivakumar S2,3, Jakubek Y2, San Lucas FA2, Lang W1, McDowell T1, Weber Z4, Behrens C5, Davies GE4, Kalhor N6, Moran C6, El-Zein R7, Mehran R8, Swisher SG8, Wang J9, Zhang J5, Fujimoto J1, Fowler J2, Heymach JV5, Dubinett S10, Spira AE11, Ehli EA4, Wistuba II1, Scheet P1,2,3.
Abstract
Rationale: Uninvolved normal-appearing airway epithelium has been shown to exhibit specific mutations characteristic of nearby non-small cell lung cancers (NSCLCs). Yet, its somatic mutational landscape in patients with early-stage NSCLC is unknown.Objectives: To comprehensively survey the somatic mutational architecture of the normal airway epithelium in patients with early-stage NSCLC.Methods: Multiregion normal airways, comprising tumor-adjacent small airways, tumor-distant large airways, nasal epithelium and uninvolved normal lung (collectively airway field), matched NSCLCs, and blood cells (n = 498) from 48 patients were interrogated for somatic single-nucleotide variants by deep-targeted DNA sequencing and for chromosomal allelic imbalance events by genome-wide genotype array profiling. Spatiotemporal relationships between the airway field and NSCLCs were assessed by phylogenetic analysis.Measurements and Main Results: Genomic airway field carcinogenesis was observed in 25 cases (52%). The airway field epithelium exhibited a total of 269 somatic mutations in most patients (n = 36) including key drivers that were shared with the NSCLCs. Allele frequencies of these acquired variants were overall higher in NSCLCs. Integrative analysis of single-nucleotide variants and allelic imbalance events revealed driver genes with shared "two-hit" alterations in the airway field (e.g., TP53, KRAS, KEAP1, STK11, and CDKN2A) and those with single hits progressing to two in the NSCLCs (e.g., PIK3CA and NOTCH1).Conclusions: Tumor-adjacent and tumor-distant normal-appearing airway epithelia exhibit somatic driver alterations that undergo selection-driven clonal expansion in NSCLC. These events offer spatiotemporal insights into the development of NSCLC and, thus, potential targets for early treatment.
KEYWORDS:
allelic imbalance; cancerization field; deep targeted sequencing; early-stage non–small cell lung cancer; normal airway
Comment in
- Sequencing Lung Cancer's Sequence. [Am J Respir Crit Care Med. 2019]
- PMID:
- 30896962
- PMCID:
- PMC6775870
- [Available on 2020-09-15]
- DOI:
- 10.1164/rccm.201806-1178OC
- [Indexed for MEDLINE]
99.
Int J Dermatol. 2019 Oct;58(10):1197-1198. doi: 10.1111/ijd.14380. Epub 2019 Jan 29.
Wooly hair nevus, Post's Type 2.
100.
J Allergy Clin Immunol. 2019 Mar;143(3):1058-1066.e6. doi: 10.1016/j.jaci.2018.12.1001. Epub 2019 Jan 15.
The SQ tree SLIT-tablet is highly effective and well tolerated: Results from a randomized, double-blind, placebo-controlled phase III trial.
Biedermann T1, Kuna P2, Panzner P3, Valovirta E4, Andersson M5, de Blay F6, Thrane D7, Jacobsen SH7, Stage BS7, Winther L8.
Abstract
BACKGROUND:
The SQ tree sublingual immunotherapy (SLIT)-tablet (ALK-Abelló, Hørsholm, Denmark) is developed for treatment of tree pollen-induced allergic rhinoconjunctivitis (ARC).
OBJECTIVE:
The aim of this pivotal phase III trial was to demonstrate the efficacy and safety of the SQ tree SLIT-tablet.
METHODS:
This was a randomized, double-blind, placebo-controlled trial with 634 subjects (12-65 years) with moderate-to-severe ARC despite use of symptom-relieving medication. Eligible subjects were randomized 1:1 to active or placebo treatment. The primary end point was the average daily ARC total combined score (TCS) during the birch pollen season (BPS) analyzed for subjects with diary data during the BPS. Secondary end points included average daily symptom scores (DSS) during the BPS, average TCS and DSS during the tree pollen season (TPS), and average daily medication scores (DMS) in the BPS and TPS.
RESULTS:
The primary and key secondary end points demonstrated statistically significant and clinically relevant effects of the SQ tree SLIT-tablet compared with placebo. For the BPS, absolute (relative) differences from placebo were 3.02 (40%) for TCS, 1.32 (37%) for DSS, and 1.58 (49%) for DMS (all P < .0001). For the TPS, absolute (relative) differences from placebo were 2.27 (37%) for TCS, 0.99 (33%) for DSS, and 1.20 (47%) for DMS (all P < .0001). Treatment was well tolerated. The most frequently reported treatment-related adverse events were mild or moderate local reactions related to sublingual administration.
CONCLUSION:
The trial demonstrated the efficacy and safety of the SQ tree SLIT-tablet compared with placebo during the BPS and TPS in adolescents and adults with birch pollen-induced ARC (EudraCT 2015-004821-15).
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Allergic rhinoconjunctivitis; allergy immunotherapy; birch pollen; clinical efficacy; clinical trial; safety; sublingual immunotherapy tablet; total combined score; tree pollen
101.
J Am Coll Surg. 2019 Apr;228(4):516-522. doi: 10.1016/j.jamcollsurg.2018.12.005. Epub 2018 Dec 23.
Remote-Access Thyroidectomy: A Multi-Institutional North American Experience with Transaxillary, Robotic Facelift, and Transoral Endoscopic Vestibular Approaches.
Abstract
BACKGROUND:
Many remote-access approaches (RAAs) to the thyroid have been described to circumvent anterior neck scarring, including the transaxillary, robotic facelift, and transoral endoscopic vestibular approaches. These techniques have been popularized in Asia, but adoption has been slow in North America. We aimed to examine multi-institutional North American outcomes with RAA thyroidectomy in the context of these institutions' transcervical approach (TCA) outcomes.
STUDY DESIGN:
Cases of lobectomy and total thyroidectomy via transaxillary, robotic facelift, and transoral endoscopic vestibular approaches were reviewed. Demographic characteristics, outcomes, and complications were compared with the same measures in patients undergoing lobectomy and total thyroidectomy via TCA by the primary RAA surgeons at each institution. Patients who underwent parathyroidectomy or other concomitant neck dissection procedures were excluded.
RESULTS:
Two hundred and sixteen RAA thyroidectomies were attempted (92 transoral endoscopic vestibular approaches, 70 transaxillary, and 54 robotic facelift) and 410 TCA thyroidectomies were performed. There was no difference in mean index nodule sizes between RAA (2.8 ± 1.6 cm) and TCA (2.9 ± 1.9 cm) cohorts (p = 0.72). Median operative times for lobectomy were 146 minutes (range 60 to 343 minutes) and 90 minutes (range 25 to 247 minutes) for the RAA and TCA cohorts, respectively (p < 0.0001). Median operative time for total thyroidectomy was 170 minutes (range 100 to 398 minutes) vs 126.5 minutes (range 51 to 260 minutes) for the RAA and TCA cohorts, respectively (p < 0.0001). There was no difference in the rates of permanent recurrent laryngeal nerve injury between the RAA (0 of 216 [0%]) and TCA (0 of 410 [0%]) cohorts (p = 0.99).
CONCLUSIONS:
Remote-access approach thyroidectomy can be performed in a select North American patient population with outcomes comparable with TCA.
Copyright © 2019. Published by Elsevier Inc.
Comment in
- Discussion. [J Am Coll Surg. 2019]
- PMID:
- 30586640
- PMCID:
- PMC6424630
- [Available on 2020-04-01]
- DOI:
- 10.1016/j.jamcollsurg.2018.12.005
- [Indexed for MEDLINE]
102.
J Allergy Clin Immunol. 2019 Mar;143(3):970-977. doi: 10.1016/j.jaci.2018.11.018. Epub 2018 Nov 30.
Sublingual allergen immunotherapy with a liquid birch pollen product in patients with seasonal allergic rhinoconjunctivitis with or without asthma.
Pfaar O1, Bachert C2, Kuna P3, Panzner P4, Džupinová M5, Klimek L6, van Nimwegen MJ7, Boot JD7, Yu D7, Opstelten DJE7, de Kam PJ7.
Abstract
BACKGROUND:
Sublingual allergen immunotherapy (SLIT) has been demonstrated to be both clinically efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, allergen immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal phase III trials for registration.
OBJECTIVE:
We sought to investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 allergy units native [AUN]/mL) in adults with birch pollen allergy.
METHODS:
A randomized, double-blind, placebo-controlled, parallel-group multicenter trial was conducted in 406 adult patients with moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis with or without mild-to-moderate controlled asthma. Treatment was started 3 to 6 months before the birch pollen season and continued during the season in 40 clinical study centers in 5 European countries. For primary end point assessment, the recommended combined symptom and medication score of the European Academy of Allergy and Clinical Immunology was used. Secondary end points included quality-of-life assessments, immunologic parameters, and safety.
RESULTS:
Primary efficacy results demonstrated a significant (P < .0001) and clinically relevant (32%) reduction in the combined symptom and medication score compared with placebo after 3 to 6 months of SLIT. Significantly better rhinoconjunctivitis quality-of-life scores (P < .0001) and the patient's own overall assessment of his or her health status, including the visual analog scale score (Euro Quality of Life Visual Analogue Scale; P = .0025), were also demonstrated. In total, a good safety profile of SLIT was observed.
CONCLUSION:
This study confirmed both the clinical efficacy and safety of a sublingual liquid birch pollen extract in adults with birch pollen allergy in a pivotal phase III trial (EudraCT: 2013-005550-30; ClinicalTrials.gov: NCT02231307).
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Birch pollen allergy; allergen immunotherapy; allergic rhinoconjunctivitis; combined symptom and medication score; efficacy; pivotal phase III trial; quality of life; safety; sublingual immunotherapy
103.
J Allergy Clin Immunol. 2019 Mar;143(3):990-1002.e6. doi: 10.1016/j.jaci.2018.10.056. Epub 2018 Nov 22.
Chronic rhinosinusitis in elderly patients is associated with an exaggerated neutrophilic proinflammatory response to pathogenic bacteria.
Morse JC1, Li P1, Ely KA2, Shilts MH3, Wannemuehler TJ1, Huang LC4, Sheng Q4, Chowdhury NI1, Chandra RK1, Das SR3, Turner JH5.
Abstract
BACKGROUND:
Potential effects of aging on chronic rhinosinusitis (CRS) pathophysiology have not been well defined but might have important ramifications given a rapidly aging US and world population.
OBJECTIVE:
The goal of the current study was to determine whether advanced age is associated with specific inflammatory CRS endotypes or immune signatures.
METHODS:
Levels of 17 mucus cytokines and inflammatory mediators were measured in 147 patients with CRS. Hierarchical cluster analysis was used to identify and characterize inflammatory CRS endotypes, as well as to determine whether age was associated with specific immune signatures.
RESULTS:
A CRS endotype with a proinflammatory neutrophilic immune signature was enriched in older patients. In the overall cohort patients 60 years and older had increased mucus levels of IL-1β, IL-6, IL-8, and TNF-α when compared with their younger counterparts. Increases in levels of proinflammatory cytokines were associated with both tissue neutrophilia and symptomatic bacterial infection/colonization in aged patients.
CONCLUSIONS:
Aged patients with CRS have a unique inflammatory signature that corresponds to a neutrophilic proinflammatory response. Neutrophil-driven inflammation in aged patients with CRS might be less likely to respond to corticosteroids and might be closely linked to chronic microbial infection or colonization.
Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
IL-1β; Rhinosinusitis; aging; bacteria; cytokine; endotype; inflammation; neutrophil
- PMID:
- 30468775
- PMCID:
- PMC6408962
- DOI:
- 10.1016/j.jaci.2018.10.056
- [Indexed for MEDLINE]
104.
J Allergy Clin Immunol. 2019 Mar;143(3):864-879. doi: 10.1016/j.jaci.2018.08.049. Epub 2018 Sep 29.
Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology.
Bousquet J, Hellings PW, Agache I, Amat F, Annesi-Maesano I, Ansotegui IJ, Anto JM, Bachert C, Bateman ED, Bedbrook A, Bennoor K, Bewick M, Bindslev-Jensen C, Bosnic-Anticevich S, Bosse I, Brozek J, Brussino L, Canonica GW, Cardona V, Casale T, Cepeda Sarabia AM, Chavannes NH, Cecchi L, Correia de Sousa J, Costa E, Cruz AA, Czarlewski W, De Carlo G, De Feo G, Demoly P, Devillier P, Dykewicz MS, El-Gamal Y, Eller EE, Fonseca JA, Fontaine JF, Fokkens WJ, Guzmán MA, Haahtela T, Illario M, Ivancevich JC, Just J, Kaidashev I, Khaitov M, Kalayci O, Keil T, Klimek L, Kowalski ML, Kuna P, Kvedariene V, Larenas-Linnemann D, Laune D, Le LTT, Carlsen KL, Lourenço O, Mahboub B, Mair A, Menditto E, Milenkovic B, Morais-Almeida M, Mösges R, Mullol J, Murray R, Naclerio R, Namazova-Baranova L, Novellino E, O'Hehir RE, Ohta K, Okamoto Y, Okubo K, Onorato GL, Palkonen S, Panzner P, Papadopoulos NG, Park HS, Paulino E, Pawankar R, Pfaar O, Plavec D, Popov TA, Potter P, Prokopakis EP, Rottem M, Ryan D, Salimäki J, Samolinski B, Sanchez-Borges M, Schunemann HJ, Sheikh A, Sisul JC, Rajabian-Söderlund R, Sooronbaev T, Stellato C, To T, Todo-Bom AM, Tomazic PV, Toppila-Salmi S, Valero A, Valiulis A, Valovirta E, Ventura MT, Wagenmann M, Wang Y, Wallace D, Waserman S, Wickman M, Yorgancioglu A, Zhang L, Zhong N, Zidarn M, Zuberbier T; Mobile Airways Sentinel Network (MASK) Study Group.
Erratum in
- Corrigenda. [J Allergy Clin Immunol. 2019]
Abstract
Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Allergic Rhinitis and Its Impact on Asthma; Change management; asthma; rhinitis
105.
Am J Otolaryngol. 2019 Jan - Feb;40(1):121-123. doi: 10.1016/j.amjoto.2018.09.008. Epub 2018 Sep 13.
Internal carotid artery dissection causing pulsatile tinnitus.
KEYWORDS:
Carotid artery dissection; Pulsatile tinnitus
106.
J Cell Physiol. 2019 Apr;234(4):4375-4384. doi: 10.1002/jcp.27223. Epub 2018 Sep 7.
Matrix metalloproteinase-13 is a target gene of high-mobility group box-containing protein 1 in modulating oral cancer cell invasion.
Abstract
Transcription factor high-mobility group box-containing protein 1 (HBP1) may function as a tumor suppressor in various types of cancer. In a previous study, we demonstrated that HBP1 suppressed cell invasion in oral cancer. To further understand the underlying mechanism, the current study is aimed at investigating how HBP1 exerts its antimetastatic potential in oral cancer. In a cell model, ectopic expression of HBP1 potently suppressed epithelial-mesenchymal transition, cellular migration, and invasion; conversely, HBP1 knockdown promoted these malignant phenotypes. The matrix metalloproteinase (MMP) family is highly implicated in tumor metastasis. Therefore, we examined the effect of HBP1 on the activation of the MMP members, MMP-2, -9, and -13 that are highly associated with the aggressiveness of oral cancer. Ectopic expression of HBP1 resulted in a mild reduction in the expression and activity of MMP-2 and -9, yet it had a potent inhibitory effect on MMP-13. In contrast, HBP1 knockdown strongly enhanced the activation of MMP-13. Further, we demonstrated that MMP-13 is a target of HBP1 transcription repression as evidenced by the identification of an HBP1 binding site in the cis proximal region of the MMP-13 promoter. More important, MMP-13 knockdown significantly alleviated HBP1 small interfering RNA-mediated promotion in cell invasion. Analysis of oral tumor specimens revealed that the low HBP1 (<0.3-fold)/high MMP-13 (>3-fold) status was associated with metastatic potential. All told, our study provides evidence supporting the idea that the HBP1-MMP-13 axis is a key regulator of the aggressiveness in oral cancer.
© 2018 Wiley Periodicals, Inc.
KEYWORDS:
HBP1; MMP-13; invasion; oral cancer
107.
J Allergy Clin Immunol. 2019 Mar;143(3):1163-1175.e15. doi: 10.1016/j.jaci.2018.07.006. Epub 2018 Jul 25.
Allergic conversion of protective mucosal immunity against nasal bacteria in patients with chronic rhinosinusitis with nasal polyposis.
Takeda K1, Sakakibara S2, Yamashita K3, Motooka D4, Nakamura S4, El Hussien MA5, Katayama J5, Maeda Y6, Nakata M7, Hamada S8, Standley DM9, Hayama M6, Shikina T6, Inohara H6, Kikutani H10.
Abstract
BACKGROUND:
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by eosinophilic inflammation and polyposis at the nose and paranasal sinus and a high concentration of IgE in nasal polyps (NPs). The causative antigen and pathogenesis of CRSwNP remain unknown.
OBJECTIVE:
We aimed to identify reactive allergens of IgE antibodies produced locally in NPs of patients with CRSwNP. We also attempted to unravel the differentiation pathway of IgE-producing B cells in NPs.
METHODS:
IgE reactivity of patients with CRSwNP was investigated by characterizing single cell-derived mAbs. T-cell response against identified allergens was investigated in vitro. NP-infiltrating lymphocytes were characterized by using flow cytometry. Immunoglobulins expressed in NPs were analyzed by using high-throughput DNA sequencing for immunoglobulin.
RESULTS:
About 20% of isolated IgE antibodies derived from NP-residing plasmablasts specifically recognized surface determinants of nasal bacteria, such as Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae. A TH2 response against S pyogenes was observed in patients with CRSwNP. Flow cytometric analysis revealed sizable germinal center B-like cell and plasmablast subsets expressing IgE on the cell surface in NPs. High-throughput DNA sequencing immunoglobulin analysis highlighted the clonal connectivity of IgE with IgG and IgA1. The Iε-Cα1 circle transcript was detected in NPs.
CONCLUSIONS:
In patients with CRSwNP, nasal bacteria-reactive B cells differentiate into IgE-producing B cells through IgG/IgA1-IgE class switching, suggesting that allergic conversion of the mucosal response against nasal bacteria underlies disease pathogenesis.
Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Chronic rhinosinusitis with nasal polyposis; IgE; T(H)2 inflammation; high-throughput immunoglobulin analysis; human mAb
108.
Telemed J E Health. 2019 Jun;25(6):477-484. doi: 10.1089/tmj.2018.0062. Epub 2018 Jul 24.
Smartphone Otoscopy Performed by Parents.
Abstract
Introduction: Implementation of pediatric telemedicine has been emphasized. We examined whether parents could perform smartphone otoscopy for the diagnosis of otitis media. Materials and Methods: We included children (6-35 months) attending day care with at least one episode of acute otitis media (AOM) within 90 days of the study entry. The timing for a teaching intervention was randomized. In the immediate teaching group, parents were taught smartphone otoscopy and cerumen was removed at the first visit. The delayed teaching group received the teaching intervention after 1 week's independent use. During the 60 study days, parents performed home examinations. The main outcome, the diagnostic quality of the tympanic membrane videos to determine healthy ear, otitis media with effusion (OME) and AOM diagnoses was measured with a structured video analysis independently by three physicians. Parents' experience was measured with a questionnaire. Results: AOM could be detected or excluded in 87% (609/699) of the videos during acute symptoms. After the teaching intervention, healthy ear, OME, or AOM could be diagnosed in 40% (521/1,293) of the videos. During the first week's intervention, one of the three diagnoses was attained in 33% (50/153) and in 12% (22/179) of the videos in the immediate and delayed teaching group, respectively (p < 0.001). The performance of the smartphone otoscopy examination was easy in 85% (35/41) of families. Discussion: After been taught, parents are able to perform smartphone otoscopy for the remote detection or exclusion of AOM. Conclusions: Future studies should assess the clinical usefulness of parent-performed smartphone otoscopy.
KEYWORDS:
109.
J Allergy Clin Immunol. 2019 Mar;143(3):1153-1162.e12. doi: 10.1016/j.jaci.2018.06.035. Epub 2018 Aug 23.
Human cystatin SN is an endogenous protease inhibitor that prevents allergic rhinitis.
Fukuoka A1, Matsushita K2, Morikawa T3, Adachi T4, Yasuda K4, Kiyonari H5, Fujieda S6, Yoshimoto T2.
Abstract
BACKGROUND:
Protease allergens disrupt epithelial barriers to exert their allergenicity. Cystatin SN (encoded by CST1) is an endogenous cysteine protease inhibitor upregulated in nasal epithelia in patients with allergic rhinitis (AR).
OBJECTIVE:
We sought to investigate the protective effect of human cystatin SN on AR symptoms using pollen-induced AR mouse models.
METHODS:
We performed an in vitro protease activity assay to evaluate the effect of recombinant human cystatin SN (rhCystatin SN) on Japanese cedar (JC) or ragweed proteases. A human nasal epithelial cell line, RPMI 2650, was used to examine tight junction (TJ) disruption in vitro. Mice were sensitized and nasally challenged with JC or ragweed pollens with or without rhCystatin SN to examine the effect of rhCystatin SN on AR symptoms and the epithelial barrier in vivo. Because mice lack CST1, we generated transgenic (Tg) mice expressing human CST1 under control of its genomic control region (hCST1-Tg mice) to examine the role of cystatin SN in physiologically expressed conditions.
RESULTS:
rhCystatin SN inhibited JC but not ragweed protease activities and prevented JC-induced but not ragweed-induced TJ disruption in vitro. Exogenous administration of rhCystatin SN ameliorated JC-induced but not ragweed-induced sneezing and nasal TJ disruption in vivo. Furthermore, hCST1-Tg mice showed decreased JC-induced but not ragweed-induced sneezing symptoms and nasal TJ disruption compared with wild-type mice.
CONCLUSION:
Human cystatin SN suppresses AR symptoms through inhibiting allergen protease activities and protecting the nasal TJ barrier in an allergen-specific manner. We propose that upregulation of nasal endogenous protease inhibitors, including cystatin SN, is a novel therapeutic strategy for protease allergen-induced AR.
Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
KEYWORDS:
Allergic rhinitis; cystatin SN; nasal epithelial cells; protease; tight junctions
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