Αρχειοθήκη ιστολογίου

Σάββατο 9 Ιουνίου 2018

Perineural Low-Dose Dexamethasone Prolongs Interscalene Block Analgesia With Bupivacaine Compared With Systemic Dexamethasone: A Randomized Trial

Background and Objectives Perineural dexamethasone and intravenous (IV) dexamethasone have been shown to prolong peripheral nerve block duration. The effects of perineural and IV dexamethasone have only been compared at doses of 4 mg or greater. This triple-blind, randomized trial examined the effect of 1 mg IV versus perineural dexamethasone on interscalene block (ISB) analgesia duration. Methods Patients undergoing ambulatory shoulder arthroscopy received an ultrasound-guided ISB with 15 mL bupivacaine 0.5% and 1 mg preservative-free dexamethasone that was administered perineurally (PeriD) or IV (IVDex). All patients received IV ketorolac and were discharged on naproxen 500 mg 2 times a day plus oxycodone/acetaminophen as needed. Peripheral nerve block duration, pain, opioid consumption, and block satisfaction were assessed via telephone follow-ups. Results There were 63 PeriD patients and 62 IVDex patients who completed the primary outcome follow-up. The median time until analgesia from the ISB completely wore off was 3.5 hours (95% confidence interval, 1.0–6.0 hours) longer in the PeriD versus IVDex groups; P = 0.007). Time until the pain relief from the ISB began to wear off was also longer in the PeriD versus IVDex group (5.5 hours [95% confidence interval, 2.1–9.0 hours]; P = 0.002). Other secondary outcomes, including opioid consumption, satisfaction, and pain scores, were not different between groups. Conclusions In patients undergoing shoulder arthroscopy, low-dose perineural dexamethasone (1 mg) in combination with 15 mL of 0.5% bupivacaine prolonged the median time until pain relief from the ISB completely wore off compared with 1 mg IV dexamethasone. However, the degree of prolongation was smaller than the a priori–defined minimal clinically meaningful difference of 5 hours. Clinical Trial Registration This study was registered at Clinicaltrials.gov, identifier NCT02506660. Accepted for publication February 12, 2018. Address correspondence to: Richard L. Kahn, MD, Hospital for Special Surgery, 535 E 70th St, New York, NY 10021 (e-mail: KahnR@HSS.edu). This study was funded by East River Medical Associates and the Research and Education Fund, Anesthesiology Department, Hospital for Special Surgery, New York, NY. REDCap use was supported by the National Center for Advancing Translational Science of the National Institutes of Health (UL1TR000457). This was presented in part at the Society for Ambulatory Anesthesia 32nd Annual Meeting (May 4–6, 2017) in Scottsdale, AZ. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Harnessing immune history to combat influenza viruses

Jenna J Guthmiller | Patrick C Wilson

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Editorial Board



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A novel punch biopsy technique without scissors or forceps



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Rituximab Treatment Of Pemphigus Foliaceus- A Retrospective Study Of 12 Patients



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Ocular abnormalities in congenital Zika syndrome: a case report, and review of the literature

As the number of children with Zika virus-related complications grows, the long-term developmental trajectory and its effects on families are unknown. We present the first known case of congenital Zika syndrom...

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Toward a new threshold for the P value?

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Publication date: Available online 8 June 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): O. Laccourreye, H. Maisonneuve




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Surgical treatment of enterovirus D68 brainstem encephalitis-induced dysphagia

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Takafumi Togashi, Hironori Baba, Meiko Kitazawa, Nao Takahashi, Yasuhiro Samejima, Eiji Yumoto, Arata Horii
Cluster of acute flaccid paralysis and cranial nerve dysfunction was associated with a 2014 outbreak of enterovirus D68 (EV-D68) respiratory illness in US. We describe a 33 year-old male patient of refractory dysphagia due to EV-D68-induced brainstem encephalitis successfully treated by surgery. Following acute upper respiratory tract infection, he developed dysphagia and bilateral facial paralysis. A coughing reflex was readily produced when the laryngopharyngeal fiberscope touched the epiglottis, however, water infusion induced only very weak and slow swallowing reflex, suggesting that only motor component was impaired but sensory function was preserved during swallowing. Despite eight months-conservative rehabilitations, Food Intake Level Scale (FILS) remained level 4. Therefore, corrective surgeries including cricopharyngeal myotomy, laryngeal suspension, and pharyngeal flap were performed. Thirty-six days after surgery, FILS rapidly and dramatically improved to level 8. This is the first report describing a successful surgical intervention for EV-D68-induced refractory dysphagia. Surgical treatment was suitable for EV-D68-induced dysphagia, perhaps because sensory function was preserved and only motor disturbance was present during the pharyngeal stage of swallowing.



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Music enjoyment with cochlear implantation

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Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Charlotte Prevoteau, Stephanie Y. Chen, Anil K. Lalwani
Since the advent of cochlear implant (CI) surgery in the 1960s, there have been remarkable technological and surgical advances enabling excellent speech perception in quiet with many CI users able to use the telephone. However, many CI users struggle with music perception, particularly with the pitch-based and melodic elements of music. Yet remarkably, despite poor music perception, many CI users enjoy listening to music based on self-report questionnaires, and prospective studies have suggested a disassociation between music perception and enjoyment. Music enjoyment is arguably a more functional measure of one's listening experience, and thus enhancing one's listening experience is a worthy goal. Recent studies have shown that re-engineering music to reduce its complexity may enhance enjoyment in CI users and also delineate differences in musical preferences from normal hearing listeners.



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Pyoderma gangrenosum on the nose

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Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Takuya Tomioka, Keiko Soma, Yoichiro Sato, Koshiro Miura, Ayako Endo
Pyoderma gangrenosum is a rare ulcerative condition associated with various systemic diseases. Lesions on the lower extremities and the trunk are common, but lesions on the nose are rare. Here we report a case of pyoderma gangrenosum on the nose. A 33-year-old woman presented with fever, nasal obstruction, and painful swelling on the nasal bridge. Physical examination revealed swellings on the nasal septal mucosa bilaterally. Computed tomography showed a septal abscess and a subcutaneous abscess on the nasal bridge. The lesions worsened despite treatment with intravenous antibiotics and abscess drainage. Meanwhile, the patient also complained of bloody stools and was diagnosed with ulcerative colitis. Therefore, pyoderma gangrenosum on the nose was suspected, and was diagnosed by exclusion of other diseases. Treatment with systemic corticosteroids was started and the nasal lesions improved rapidly. However, saddle nose deformity occurred. A review of the literature reveals that pyoderma gangrenosum on the nose can cause ulcerations, septal abscess, and sinusitis. Further, there is a high likelihood of nasal complications, including saddle nose deformity, septal perforation, and skin defects. Pyoderma gangrenosum should be included in the differential diagnosis when nasal ulceration, abscesses, and sinusitis do not improve with antibiotics and drainage.



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Surgical outcomes in the treatment of temporal bone cerebrospinal fluid leak: A systematic review

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Federico Maria Gioacchini, Ettore Cassandro, Matteo Alicandri-Ciufelli, Shaniko Kaleci, Claudia Cassandro, Alfonso Scarpa, Massimo Re




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Facial nerve palsy and laryngospasm as a complication of local anaesthesia during adenotonsillectomy

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Michał Lubszczyk, Anna Łuczyńska-Sopel, Dariusz Polaczkiewicz
Tonsil surgeries are the most frequently performed surgical procedures in ENT departments. We would like to present the case of a 5-year-old patient who suffered from unilateral peripheral facial nerve palsy and laryngeal spasm following adenotonsillectomy. Paresis was observed immediately after the transfer of the patient to the postoperative room. The activity of facial muscles was restored within 2 hours from the beginning of the surgery. We assume that this was the direct effect of an anaesthetic on the extracranial processes of the facial nerve.



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Cochlear implantation in patients with bilateral deafness caused by otitis media with ANCA-associated vasculitis (OMAAV): A report of four cases

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Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Takeshi Watanabe, Haruo Yoshida, Kan Kishibe, Yuka Morita, Naohiro Yoshida, Haruo Takahashi, Yasuaki Harabuchi
ObjectiveAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) without systemic symptoms but with initial symptoms related to the ear, such as hearing loss, otalgia, and dizziness, has recently been reported. We have categorized this condition as otitis media with AAV (OMAAV), and have recently proposed its diagnostic criteria.MethodsTo determine the effectiveness of cochlear implantation (CI) in patients with profound hearing loss due to OMAAV. We examined the language understanding ability of four patients with bilateral profound or total deafness due to OMAAV, who underwent CI.ResultsIn three of the four patients, the language understanding ability with CI was poor. These three patients with poor performance had characteristic features, including a short interval from the onset of ear symptoms to total deafness and clear enhancement of the cochlea on magnetic resonance imaging (MRI).ConclusionThe poor results observed in patients with a rapidly progressive history of hearing loss were attributed to possible severe and profuse intracochlear bleeding and/or destruction of structures, including the spiral ganglion. All the three patients showed contrast enhancement in the inner ear on MRI. We believe that preoperative evaluation of the history of hearing loss as well as the findings of contrast-enhanced MRI is important for predicting the prognosis after CI.



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Editorial Board

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Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5





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The protective effect of adrenocorticotropic hormone treatment against noise-induced hearing loss

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Ahmet Mutlu, Fatma Ceyda Akin Ocal, Seyra Erbek, Levent Ozluoglu
ObjectiveNIHL is a common problem, and steroids are the most effective treatment option. In this study, we aimed to evaluate the protective effects of the synthetic adrenocorticotropic hormone (ACTH) analogues, which induce endogenous steroid secretion, against noise-induced hearing loss (NIHL) and to compare their effectiveness with that of steroid treatment.MethodsTwenty-four male Sprague–Dawley albino rats were divided into four subgroups as follows: group 1 (n=6) control, group 2 (n=6) saline, group 3 (n=6) dexamethasone (2mg/kg/day intramuscularly [IM]), group 4 (n=6) ACTH analogue (0,4mg/kg/day IM), respectively. Three groups (groups 2–4) were exposed to white noise (105dB SPL, 12h). All the rats were evaluated for hearing thresholds of 10kHz, 20kHz, and 32kHz via acoustic brainstem responses (ABR) measurement. After the basal threshold measurements, measurements were repeated immediately after the noise and on day 7 and day 21.ResultsBoth steroid and ACTH analogue groups showed significantly better hearing outcomes than the saline group on day 7 (p<0.001) and day 21 (p<0.001) after the noise exposure. No superior treatment effect was demonstrated in either the steroid or ACTH analogue group. None of the related intervention groups reached the basal hearing thresholds.ConclusionSteroids were effective drugs for the treatment of NIHL. ACTH analogues also demonstrated promising therapeutic effects for NIHL. Further studies to establish ACTH analogues as an alternative NIHL treatment option to steroids are needed.



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Endoscopic cartilage versus temporalis fascia grafting for anterior quadrant tympanic perforations — A prospective study in a tertiary care hospital

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Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Sanjeev Mohanty, Vinoth Manimaran, Preethi Umamaheswaran, Shivapriya Jeyabalakrishnan, Sreenivas Chelladurai
ObjectiveManagement of anterior perforations of tympanic membrane is a surgical challenge. The objective of this study is to analyse and compare the results of composite cartilage perichondrium island (CCPI) graft and temporalis fascia graft by endoscopic technique in anterior quadrant perforations.MethodsA prospective study was conducted in a tertiary care centre from 2012–16. A total of 187 ear drums(n) in 168 patients with perforations involving anterior quadrant were included in the study. All the patients were operated completely by endoscopic technique. Tragal Composite cartilage perichondrium island (CCPI) graft was used in 87 ears and temporalis fascia in 100. Each group was categorised into A and B depending on perforation size. The outcome parameters assessed include graft success with regard to perforation size, pre- and postoperative ABG, mean improvement in ABG, ABG closure ratio and graft medialisation/lateralisation status.ResultsCartilage group had 91.95% (80/87) success rate overall, while fascia had 79% (79/100). In category 1, the success rate for cartilage and temporalis fascia were 89.6% (26/29) and 68.9% (20/29) respectively (p=0.51788). In category 2, the success rates were 93.1% (54/58) and 83.1% (59/71) respectively (p=0.86356). The mean improvement in ABG for both groups were 17.52±3.84dB and 15.26±5.56dB respectively (p=0.04). ABG closure ratio for both the groups were 62.84±11.87 % and 53.6±19.6 % respectively (p=0.0008).ConclusionEndoscopic composite cartilage perichondrium island graft is an effective technique in managing perforations of anterior quadrant barring the expertise required for endoscopic ear surgeries.



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Instrumental head impulse test changes after intratympanic gentamicin for unilateral definite Ménière’s disease: A systematic review and meta-analysis

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Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Pedro Santos Marques, Claudia Camila Dias, Nicolas Perez-Fernandez, Jorge Spratley
ObjectiveTo estimate how much could intratympanic gentamicin (ITG) interfere with the vestibular-ocular reflex (VOR) parameters on instrumental head impulse test (HIT), either with scleral search coil or video head impulse test and, eventually, foresee the control of vertigo crisis in unilateral intractable Ménière's disease (MD).MethodsA literature search was conducted in PubMed, Scopus, Web of Science and Cochrane search engines. The search terms used were "vestibular ocular reflex", "head impulse test", "gentamicin," and "Meniere's disease". Limitations included text availability to be full text, species to be humans and language to be English. All study types were included. 89 articles were screened identifying four eligible studies were identified. Studies were included after consensus of the authors. Meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data was analysed using Review Manager software.ResultsInstrumental HIT, after ITG for MD, demonstrated, in the treated ear, a decreased gain in the horizontal, posterior and superior semicircular canals (SCC), of 0.36 (0.26; 0.47; 95% CI), 0.35 (0.22; 0.48; 95% CI) and 0.28 (0.21; 0.35; 95% CI), respectively. Gain asymmetry increases between the treated and non-treated ear of 23.78 (7.22; 40.35; 95% CI), 32.01 (12.27; 51.76; 95% CI) and 17.49 (9.99; 24.99; 95% CI), were similarly detected in the horizontal, posterior and superior SCC, respectively. Significantly smaller gain values after the first treatment were observed for a single injection group versus multiple injection group in the horizontal (p=0.002) and superior SCCs (p=0.016).ConclusionsInstrumental HIT is effective in evaluating the SCC function after ITG for intractable unilateral MD. VOR gain changes in the direction of the treated ear in the three SCC have been clearly registered. An increased reduction of the VOR gain in the horizontal and anterior SCC also seemed to foresee the control of vertigo crisis. Still, after meta-analysis, the small number of patients' data available did not allow to define a treatment end-point value. This review also indicated that further and better-designed studies are warranted.



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Management of laryngeal cleft in mechanically ventilated children with severe comorbidities

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Rumi Ueha, Takao Goto, Asako Kaneoka, Tomonori Takano, Taku Sato, Yoichiro Hirata, Takaharu Nito, Tatsuya Yamasoba
Laryngeal clefts are rare congenital malformations of the posterior part of the larynx. The severities are correlated with the downward extension of the cleft and can involve numerous clinical symptoms including dysphagia and respiratory distress. As significant comorbidities may be present, individual treatments depend on the child's general condition and type of cleft involved. Herein, we describe two cases of children with laryngeal clefts and severe comorbidities requiring mechanical ventilation. One child with type III laryngeal cleft was successfully managed with the lateral pharyngotomy approach. The other child with type II laryngeal cleft has not been able to undergo cleft-closure surgery because of severe general conditions, therefore has continued training for feeding and swallowing.



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Analysis of chemosensory function in patients with chronic Eustachian tube dysfunction prior to and after balloon dilatation

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Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Walliczek-Dworschak Ute, Schmierer Lisa, Greene Brandon, Pellegrino Robert, Dworschak Philipp, Boris Alexander Stuck, Güldner Christian
ObjectiveEustachian tube dysfunction (ETD) affects approximately 1% of adults in the general population. Non treated Eustachian tube dysfunction can result in chronic middle ear diseases, which have been shown to significantly affect taste sensitivity. A promising treatment is balloon dilatation of the Eustachian tube. The primary aim of the present study was to investigate whether individuals with ETD had impairment in chemosensory functions, and the changes of the chemosensory function after balloon dilatation of the Eustachian tube.Methods26 patients (17 female, 9 male) (=56 ears) suffering from ETD with a mean age of 39±15years were included in the present study. 20 patients (76%) returned to be evaluated at the follow up (=40 ears) 51±22days after balloon dilatation. For pre- and post operation, gustatory function was measured with a lateralized gustatory test with the taste strips and olfactory function was tested by means of the Sniffin' Sticks test battery (threshold, discrimination and identification (ID)).ResultsPatients' baseline taste function (summed taste score 9.8±3.5 (mean±SD)) was significantly impaired compared to normative data (summed taste score 12.4±2.3; p=0.002). After balloon dilatation of the Eustachian tube, the taste function remained stable (summed taste score 9.4±4.3; p=0.814). Olfactory function (odor ID, summed score (TDI)) improved postoperatively (TDI 32.4±3.6) compared to pre-operative scores (TDI 33.6±4.0; p=0.012), but not to a clinically relevant extent.ConclusionThis study suggests, that patients suffering from ETD exhibit reduced taste scores. Balloon dilatation of the Eustachian tube does not seem to influence gustatory function, but olfactory function showed improvement.



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Conservative treatment for cutaneous fistula resulted from abscess formation in patients with tuberculous cervical lymphadenitis

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Bo Hae Kim, Yung Jin Jeon, Young Ju Jin, Woo-jin Jeong, Sung Joon Park, Soon-Hyun Ahn
ObjectiveThis study describes the clinical characteristics and course of conservative treatment using anti-Tb medication and dressing in patients with tuberculous cervical fistula resulting from abscess formation, and to investigate factors prognostic of dressing and treatment duration.MethodsThe medical records of patients with tuberculous cervical lymphadenitis were reviewed, and 38 of these patients who presented with cutaneous fistula that resulted from abscess formation were included in the study.ResultsThe mean duration of dressing until fistula closure was 3.7±2.0months (range 0.2–8.5), and the mean duration of treatment with anti-Tb medication was 10.6±2.6months (range 6.0–16.0). Patients with concomitant Tb, beyond the cervical lymph nodes showed significantly prolonged duration of dressing (4.6 months vs. 3.2 months, p=0.025) and anti-Tb medication (11.8 months vs. 9.8 months, p=0.015).ConclusionOur results indicate that about 3.7 months of dressing was required for fistula closure. Tuberculous cervical lymphadenitis patients with fistula who had Tb beyond the cervical lymph nodes could be expected to require dressing for 4.6 months and prolonged and anti-Tb medication treatment.



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Comparison of xerostomia incidence after three-dimensional conformal radiation therapy and contralateral superficial lobe parotid-sparing intensity-modulated radiotherapy for oropharyngeal and hypopharyngeal cancer

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Terufumi Kawamoto, Keiji Nihei, Yujiro Nakajima, Satoshi Kito, Keisuke Sasai, Katsuyuki Karasawa
ObjectiveIn the treatment of head–neck cancer, parotid-sparing intensity-modulated radiotherapy (IMRT) could reduce the incidence of xerostomia. When the parotid glands cannot be sufficiently spared because of the widespread tumor, contralateral superficial lobe parotid-sparing (CSLPS)-IMRT could be used to reduce marginal recurrence, however the success of this approach remains to be determined. The primary purpose of this study was to compare the incidence of xerostomia between three-dimensional conformal radiotherapy (3D-CRT) and CSLPS-IMRT for oropharyngeal and hypopharyngeal cancer. In a second aim, we also compared the clinical efficacy of 3D-CRT and CSLPS-IMRT.MethodsWe retrospectively reviewed the medical records of locally advanced oropharyngeal and hypopharyngeal cancer patients who were treated with definitive concurrent chemoradiotherapy between June 2007 and April 2014. We estimated the average mean dose delivered to the parotid glands, the incidence of xerostomia≥Grade 2, patterns of failure, and survival outcomes.ResultsSeventeen patients received 3D-CRT and 21 received CSLPS-IMRT. The average mean dose delivered to the superficial lobe of the contralateral parotid gland was 45.3Gy and 26.6Gy (p<0.001), and the incidence of xerostomia≥Grade 2 following treatment was 75% and 26% at 12 months (p=0.012) and 67% and 18% at 24 months (p=0.018) in the 3D-CRT and CSLPS-IMRT groups, respectively. Patterns of failure did not differ between the two groups. The 2-year progression-free survival was 59% and 62% (p=0.73), and the 2-year overall survival rate was 71% and 71% in the 3D-CRT and CSLPS-IMRT groups, respectively (p=0.76).ConclusionIncidence of xerostomia was significantly lower in patients receiving CSLPS-IMRT compared with 3D-CRT, while clinical efficacy did not differ between two treatment strategies.



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Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Hiroshi Matsuyama, Keisuke Yamazaki, Ryuichi Okabe, Yushi Ueki, Ryusuke Shodo, Jo Omata, Yuichiro Sato, Hisayuki Ota, Takeshi Takahashi, Masahiko Tomita, Yusuke Yokoyama, Takafumi Togashi, Hidefumi Aoyama, Eisuke Abe, Yasuo Saijo, Kouji Katsura, Marie Soga, Tadashi Sugita, Yasuo Matsumoto, Emiko Tsuchida, Arata Horii
ObjectiveRecent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese.MethodsPatients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II–IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70mg/m2 for level 0, 80mg/m2 for level 1, and 100mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200mg/m2, response rate, and incidences of adverse events.ResultsA CDDP dose of 100mg/m2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m2. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200mg/m2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event.ConclusionThe present phase I study indicated that a CDDP dose of 80mg/m2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80mg/m2 as compared with a dose of 100mg/m2, and a dose of 80mg/m2 is therefore recommended in CCRT for the Japanese.This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).



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Pneumolabyrinth, intracochlear and vestibular fluid loss after cochlear implantation

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Hideaki Moteki, Yasunari Fujinaga, Tetsuya Goto, Shin-ichi Usami
The present case was a 38-year-old male who presented with progressive hearing loss, resulting in profound bilateral hearing loss. He had a past history of childhood medulloblastoma, which was treated with posterior fossa craniotomy and radiotherapy. A ventriculoperitoneal (VP) shunt was put in place to manage the hydrocephalus. Cochlear implantation (CI) was carried out on his right ear by a standard procedure. At CI activation, the electric impedance of the electrode was very high, and computed tomography revealed that there was no area of liquid density, suggesting depletion of the perilymph in the cochlea and vestibule. Eight months later, the impedance improved gradually, and the cochlea was filled with perilymph. Consequently, one of the causes of the pneumolabyrinth in the present case was that a scarred stenotic cochlear canaliculus secondary to surgery or radiation therapy might have prevented the CSF from filling the scala. In addition, it is also possible that the VP shunt might have altered the CSF pressure, leading to depletion of the perilymph.



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Transoral videolaryngoscopic surgery for papillary carcinoma arising in lingual thyroid

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Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Chisato Mogi, Hirotaka Shinomiya, Natsumi Fujii, Tomoyuki Tsuruta, Naruhiko Morita, Tatsuya Furukawa, Masanori Teshima, Maki Kanzawa, Mitsuyoshi Hirokawa, Naoki Otsuki, Ken-ichi Nibu
Carcinoma arising in lingual thyroid is an extremely rare entity accounting for only 1% of all reported ectopic thyroids. Here, we report a case of carcinoma arising in lingual thyroid, which has been successfully managed by transoral resection and bilateral neck dissections.A lingual mass 4-cm in diameter with calcification was incidentally detected by computed tomography at medical check-up. No thyroid tissue was observed in normal position. Ultrasound examination showed bilateral multiple lymphadenopathies. Fine needle aspiration biopsy from lymph node in his right neck was diagnosed as Class III and thyroglobulin level of the specimen was 459ng/ml. Due to the difficulty in performing FNA of the lingual masses, right neck dissection was performed in advance for diagnostic purpose. Pathological examination showed existence of large and small follicular thyroid tissues in several lymph nodes, suggesting lymph node metastasis from thyroid carcinoma. Two months after the initial surgery, video-assisted transoral resection of lingual thyroid with simultaneous left neck dissection was performed. Postoperative course was uneventful. Papillary carcinoma was found in the lingual thyroid and thyroid tissues were also found in left cervical lymph nodes.Video-assisted transoral resection was useful for the treatment of thyroid cancer arising in lingual thyroid.



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Does drug-induced sleep endoscopy predict surgical success of limited palatal muscle resection in patients with obstructive sleep apnea?

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Jae-Wook Kim, Deok Soo Kim, Sung-Dong Kim, Sue Jean Mun, Soo-Kweon Koo, Kyu-Sup Cho
ObjectiveThe aims of this study were to determine the associated factors affecting the success rate of limited palatal muscle resection (LPMR), and to investigate whether drug-induced sleep endoscopy (DISE) could predict the therapeutic response to LPMR in patients with obstructive sleep apnea obstructive sleep apnea (OSA).MethodsTwenty-one consecutive OSA patients underwent LPMR were enrolled. All patients received routine ENT examination, preoperative DISE, and polysomnography (PSG). Clinical, polysomnographic, cephalometric variables, and DISE findings were evaluated. The measurements were related to the success or failure of LPMR based on the results of preoperative and postoperative PSG.ResultsThe overall success rate of LPMR was 66.6%. Postoperative AHI and minimal oxygen saturation were significantly decreased after LPMR (p<0.001). Comparison between success and failure groups revealed no significant differences in BMI, Friedman stage, preoperative AHI, minimal oxygen saturation, and all cephalometric parameters. However, the success of LPMR was significantly correlated with site, degree, and configuration of obstruction in DISE. In the velopharynx, complete obstruction (p=0.006) with anterolateral or concentric pattern (p=0.044) had significantly better success rate than partial obstruction with lateral pattern.ConclusionDISE was only predictive method for identifying the success in OSA patients undergoing LPMR. Patients with anteroposterior or concentric total obstruction in the velopharynx might be suitable candidate for LPMR.



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High frequency jet ventilation during endolaryngeal surgery: Risk factors for complications

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Demet Altun, Emre Çamcı, Mukadder Orhan-Sungur, Nükhet Sivrikoz, Bora Başaran, Tülay Özkan-Seyhan




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A retrospective study of treatment for curative synchronous double primary cancers of the head and neck and the esophagus

Publication date: October 2018
Source:Auris Nasus Larynx, Volume 45, Issue 5
Author(s): Tabito Okamoto, Chikatoshi Katada, Shouko Komori, Keishi Yamashita, Shunsuke Miyamoto, Koichi Kano, Yutomo Seino, Hiroshi Hosono, Hiroki Matsuba, Hiromitsu Moriya, Mitsuhiro Sugawara, Mizutomo Azuma, Hiromichi Ishiyama, Satoshi Tanabe, Kazushige Hayakawa, Wasaburo Koizumi, Makito Okamoto, Taku Yamashita
ObjectiveCurative synchronous double primary cancers of the head and neck and the esophagus (CSC-HE) are frequently detected, but a standard treatment remains to be established. We studied the clinical course to explore appropriate treatment strategies.MethodsWe retrospectively studied consecutive 33 patients who had CSC-HE. The disease stage was classified into 4 groups: group A, early head and neck cancer (HNC) and early esophageal cancer (EC); group B, early HNC and advanced EC; group C, advanced HNC and early EC; and group D, advanced HNC and advanced EC. As induction chemotherapy, the patients received 3 courses of TPF therapy (docetaxel 75mg/m2 on day 1, cisplatin 75mg/m2 on day 1, and 5-fluorouracil 750mg/m2 on days 1–5) at 3-week intervals. The clinical courses and treatment outcomes were studied according to the disease stage of CSC-HE.ResultsThe disease stage of CSC-HE was group A in 1 patient (3%), group B in 9 patients (27.3%), group C in 3 patients (9.1%), and group D in 20 patients (60.6%). The median follow-up was 26months, and the 2-year overall survival rate was 67.4%. In groups A, B, and C, the 2-year overall survival rate was 83.3%. In group D, the 2-year overall survival rate was 62.6%. Ten of 20 patients in group D received induction chemotherapy with TPF, and 6 patients were alive and disease free at the time of this writing.ConclusionThe treatment outcomes of patients with CSC-HE were relatively good. TPF induction chemotherapy might be an effective treatment for patients with advanced HNC and advanced EC.



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Dexmedetomidine facilitates extubation in children who require intubation and respiratory support after airway foreign body retrieval: a case–cohort analysis of 57 cases

Abstract

Purpose

This study aimed to investigate whether dexmedetomidine had sedative weaning advantage for extubation after airway foreign body (FB) removal in children.

Methods

A retrospective case–cohort comparison study with total of 57 critical children who required mechanical ventilation after rigid bronchoscopy was performed. After tracheal intubation, group D (received dexmedetomidine 1 µg/kg over 10 min, followed by an infusion of 0.8 µg/kg/h), and group RP (received remifentanil–propofol 6–10 µg/kg/h and 1–3 mg/kg/h, respectively). The primary outcome was successful extubation rate on first weaning trial. The minor outcomes included weaning time, emergency agitation, coughing score and the incidence of respiratory adverse complications on emergency.

Main results

All 57 patients were included in the analysis, with 30 patients in group D and 27 controlled cases in group RP. The success rate of first weaning trial in the D group was 96.7 vs 77.8% in the RP group, risk ratio (RR) 1.56, 95% CI [0.78–1.98]. Time for resuming spontaneous breathing after termination infusion was shorter in the D group (median 8 min, IQR 15 min) vs RP group (median 12 min, IQR 19 min, P = 0.02, RR 0.56, 95% CI 0.14–6.57).

Conclusions

In mechanical ventilation of pediatric patients following rigid bronchoscopy, in comparison to remifentanil–propofol, dexmedetomidine is proved to have high success rate for weaning strategy.

What is already known?

Remifentanil is proved to be effective for weaning in ICU patients. Dexmedetomedine can provide similar rates of smooth extubation for pediatric patients who underwent airway surgery.

What this article adds?

Invasive ventilation is used for patients with severe comorbidity after airway surgery, but the correct strategy for pediatric extubation after removal of airway foreign body remains unclear. For these patients with short-term mechanical ventilation, dexmedetomedine may improve the extubation rate, when compared with remifentanil–propofol.



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Airway evaluation in children with single ventricle cardiac physiology

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Publication date: August 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 111
Author(s): Jose Ting, Soham Roy, Sriram Navuluri, Robert Hanfland, Lauren Mulcahy, Sancak Yuksel, Zhen Huang, Zi Yang Jiang
ObjectiveChildren with single ventricle cardiac physiology (SVC) often require airway procedures as an adjunct to their care. Descriptive analysis with a focus on outcomes of airway procedures in SVC patients have not been fully described in the literature.MethodsRetrospective, single-center cohort review of 270 patients born between Aug-2007 and Jan-2017. Patients were identified by cardiac database for single ventricle pathophysiology. A subset of these patients were identified to have been evaluated by otolaryngology with airway evaluations and/or interventions.Results88/270 patients (32.6%) required investigation or intervention for airway pathology. The most frequent procedure was flexible fiberoptic laryngoscopy (58/88 patients); it was the only procedure performed in 40 patients. Seventeen patients required tracheostomies with an associated increased length of stay (p < 0.001). Patients with cardiac procedures involving dissection around the aortic arch were considered higher airway risk due to the threat of recurrent laryngeal nerve injury, and were more likely to have vocal cord paralysis (58%) compared to patients with lower risk procedures (21%; p < 0.001). However, on multivariate logistic regression, vocal cord paralysis did not statistically impact the odds for tracheostomy placement, although the presence of subglottic stenosis increased the odds ratio of tracheostomy by 14.7 (p = 0.02).ConclusionsChildren with SVC often require airway evaluation and intervention. Patients with high risk cardiac procedures had a higher risk of recurrent laryngeal nerve injury but the presence of subglottic stenosis was the best predictor for a tracheostomy. This study represents one of the largest series of SVC children evaluated for airway pathology.



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A novel use of coblation in the treatment of subglottic stenosis

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Publication date: August 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 111
Author(s): Craig A. Bollig, Eliav Gov-Ari
Bipolar radiofrequency plasma ablation (Coblation) technology has recently been described in the treatment of airway stenosis. In these small case series and case reports, the mucosal and submucosal tissues have been removed. We describe a novel use of coblation technology, in which a coblation needle was used to submucosally ablate subglottic stenosis in a 9 month-old girl with grade II subglottic stenosis who had previously undergone multiple balloon dilations. This technique spared the overlying mucosa, similar to that utilized in coblation turbinoplasty. She experienced objective clinical improvement after the intervention and has not required additional airway interventions to date.



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Auditory brainstem response in very preterm, moderately preterm and late preterm infants

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Publication date: August 2018
Source:International Journal of Pediatric Otorhinolaryngology, Volume 111
Author(s): Jayashree Seethapathy, Prakash Boominathan, Ajith Kumar Uppunda, Binu Ninan
BackgroundAuditory brainstem response across preterm infants help in understanding difference if any in auditory maturation. Objective: To analyze and compare absolute and interpeak latencies of ABR in very preterm, moderate preterm and late preterm infants at term age.MethodABR traces were obtained from 148 ears of preterm infants (52 of very preterm, 44 of moderately preterm & 52 of late preterm) at term age. ABR was recorded with 11.1/s clicks at different intensity levels.ResultsAbsolute latencies of peak I, III, V and interpeak latencies of peak I-V, I-III and III-V were analyzed and compared between three preterm groups. One way ANOVA was used to compare ABR parameters between three groups of preterm infants and also to compare ABR parameters across various gestation ages. There were no overall differences in absolute latencies, interpeak latencies and amplitude of ABR between preterm groups and across various gestation ages (P>0.05). Pearson correlation was used to find the correlation between gestation age and ABR parameters. However, no correlation was found. ABRs were similar among preterm groups at term age which reflects that the brainstem maturation is similar among preterm groups.ConclusionGestational age at birth does not seem to influence absolute and interpeak latencies of ABR at term age. In preterm neonates, the findings lead to suggest that maturation of auditory pathway occurs in a similar manner in preterm infants regardless of gestational age at birth.We conclude that preterm birth alone as a risk factor does not appear to have any marked effect on the development of ABR at term age.



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Does CoolSculpting work?

CoolSculpting is a noninvasive cosmetic procedure to reduce stubborn areas of fat using cold temperatures. Plastic surgeons make bold claims about its benefits, but does it really work? In this article, we take a close look at what the research says about how effective and safe CoolSculpting is for removing body fat.

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What are the side effects of laser hair removal?

Removing unwanted hair from the body and face is usually done safely and effectively using laser hair removal therapy. Some people may experience mild redness, swelling, and irritation of the treated area. Here, we look at how safe laser hair removal is, possible side effects, and some of the myths about the process.

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Insulin decreases expression of the pro-inflammatory receptor Proteinase-Activated Receptor-2 on human airway epithelial cells

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Publication date: Available online 8 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Vivek D. Gandhi, Nami Shrestha Palikhe, Shereen M. Hamza, Jason R.B. Dyck, Jean Buteau, Harissios Vliagoftis

Teaser

The authors show that insulin, a hormone with anti-inflammatory properties, decreases the expression of a pro-inflammatory receptor on airway epithelial cells. This observation may explain the heightened respiratory inflammation seen in patients with metabolic syndrome.


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GM-CSF Therapy in Human CARD9 Deficiency

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Publication date: Available online 8 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Rebecca A. Drummond, Fatema Tuz Zahra, Mukil Natarajan, Muthulekha Swamydas, Amy P. Hsu, L. Joseph Wheat, Christina Gavino, Donald C. Vinh, Steven H. Holland, Constantinos M. Mikelis, Michail S. Lionakis

Teaser

CARD9 deficiency is associated with life-threatening fungal infections of the CNS. This work shows that the H-RAS/RASGRF1/ERK pathway is intact in the c.170G>A (p.R57H) CARD9 missense mutation, a finding that correlates with the clinical outcome of GM-CSF therapy.


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Midostaurin in indolent systemic mastocytosis patients: an open-label phase 2 trial

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Publication date: Available online 8 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Bjorn van Anrooij, Joanne N.G. Oude Elberink, L.F. Span, Jan G.R. de Monchy, Stefano Rosati, André B. Mulder, Johanna C. Kluin-Nelemans

Teaser

This is the first report on a trial using a Kit D816V targeting drug in indolent systemic mastocytosis. The results indicate midostaurin to be effective in reducing symptom severity and improving quality of life.


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A trial of P2Y12 receptor inhibition with prasugrel identifies a potentially distinct endotype of patients with aspirin-exacerbated respiratory disease

Publication date: Available online 8 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Tanya M. Laidlaw, Katherine N. Cahill, Juan Carlos Cardet, Katherine Murphy, Jing Cui, Brittney Dioneda, Parul Kothari, Benjamin A. Raby, Elliot Israel, Joshua Boyce
BackgroundAspirin-exacerbated respiratory disease (AERD) is characterized by asthma, recurrent nasal polyposis, and respiratory reactions upon ingestion of cyclooxygenase-1 inhibitors. Increased numbers of platelet-leukocyte aggregates are present in the sinus tissue and blood of patients with AERD, compared to aspirin-tolerant patients, and platelet activation may contribute to aspirin-induced reactions.ObjectiveWe sought to determine whether treatment with prasugrel, which inhibits platelet activation by blocking the P2Y12 receptor, would attenuate the severity of sinonasal and respiratory symptoms induced during aspirin challenge in subjects with AERD.Methods40 subjects with AERD completed a 10-week, double-blinded, placebo-controlled crossover trial of prasugrel. All subjects underwent oral aspirin challenges after 4 weeks of prasugrel and after 4 weeks of placebo. The primary outcome was a change in the provocative dose of aspirin that would elicit an increase in total nasal symptom score of 2 points (PD2). Changes in lung function, urinary eicosanoids, plasma tryptase, platelet-leukocyte aggregates, and platelet activation were also recorded.ResultsPrasugrel did not significantly change the mean PD2 (79 ±15 on placebo and 139 ±32 on prasugrel, P = 0.10), platelet-leukocyte aggregates, or increases in urinary leukotriene E4 (LTE4) and prostaglandin D2 metabolite (PGD-M) levels during aspirin-induced reactions in the study population as a whole. Five subjects ("responders") reacted to aspirin while on placebo but did not develop any reaction to aspirin challenge after the prasugrel arm. In contrast to prasugrel nonresponders (35 subjects), the prasugrel responders had smaller reaction-induced increases in TNSS, did not show significant aspirin-induced increases in urinary LTE4, PGD-M, or thromboxane B2 levels, and failed to display increases in serum tryptase levels during the aspirin reactions on the placebo arm, all of which were observed in the nonresponders.ConclusionIn the overall study population, prasugrel did not attenuate aspirin-induced symptoms, possibly because it failed to decrease the frequencies of platelet-adherent leukocytes, or to diminish aspirin-induced mast cell activation. In a small subset of patients with AERD who had higher baseline platelet activation and milder upper respiratory symptoms during aspirin reactions, P2Y12 antagonism with prasugrel completely inhibited all aspirin-induced reaction symptoms, suggesting a contribution from P2Y12 signaling in this subset.Clinical ImplicationsP2Y12 antagonism with prasugrel prevents aspirin-induced reactions in only a subset of AERD patients with a component of P2Y12-dependent mechanisms of reaction to aspirin.

Teaser

Platelet activation increased in AERD. In a randomized placebo-controlled cross-over trial, platelet inhibition through P2Y12 antagonism with prasugrel neither prevented nor lessened aspirin-induced reactions in most patients with AERD, though did identify a small subset of responders who may have a distinct P2Y12-dependent mechanism of reaction to aspirin.


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A bispecific antibody strategy to target multiple type 2 cytokines in asthma

Publication date: Available online 8 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Marie Godar, Kim Deswarte, Karl Vergote, Michael Saunders, Hans de Haard, Hamida Hammad, Christophe Blanchetot, Bart N. Lambrecht
BackgroundAsthma is a chronic inflammatory airway disease in which innate and adaptive immune cells act together to cause eosinophilic inflammation, goblet cell metaplasia (GCM) and bronchial hyperreactivity (BHR). In clinical trials employing biologicals against interleukin (IL)-4Rα or IL-5, only a subset of moderate-to-severe asthmatics responded favorably, suggesting that distinct pathophysiological mechanisms are at play in subgroups of patients, called endotypes. However, the effect of multiple cytokine blockade using bispecific antibodies (Ab) has not been tested.ObjectiveTo target simultaneously IL-4, IL-13 and IL-5 signaling pathways with a novel IL-4Rα/IL-5 bispecific Ab in a murine house dust mite (HDM) model of asthma.MethodsTwo monoclonal Abs neutralizing IL-4Rα and IL-5 were generated using a llama-based Ab platform. Their heavy (HC) and light chains (LC) where then co-transfected in mammalian cells, resulting in a heterogeneous Ab mixture from which the bispecific Ab was isolated using a dual anti-idiotypic purification process. C57BL/6J mice were finally sensitized and challenged to HDM extracts and treated during challenge with the Abs.ResultsWe successfully generated and characterized the monospecific and bispecific Abs targeting IL-4Rα and IL-5. The monospecific Abs could suppress eosinophilia and/or IgE synthesis whereas only the IL-4Rα/IL-5 bispecific Ab and the combination of monospecific Abs additionally inhibited GCM and BHR.ConclusionType 2 cytokines act synergistically to cause GCM and BHR in HDM-exposed mice.

Teaser

Current asthma biologicals include IL-4Rα and IL-5 monospecific Abs. Here we show the feasibility of producing an anti-IL-4Rα/IL-5 bispecific Ab that neutralizes both targets and demonstrates superior effectiveness in a murine house dust mite model.


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Blood cell count indexes as predictors of outcomes in advanced non-small-cell lung cancer patients treated with Nivolumab

Abstract

Lung cancer is the most common malignancy worldwide. Despite significant advances in diagnosis and treatment, mortality rates remain extremely high, close to incidence rates. Several targeted therapies have been recently introduced for the treatment of non-small cell lung cancer (NSCLC), the most common type of lung cancer. Nivolumab, a monoclonal antibody that targets programmed death-1 (PD-1), was the first immune checkpoint inhibitor approved for the treatment of patients with advanced/metastatic NSCLC not responding to platinum-based chemotherapy. Biomarkers predicting response to these therapies would allow early identification of non-responders and timely implementation of appropriate combination strategies, avoiding inadequate and expensive therapies. The role of the neutrophil to lymphocyte ratio and other blood cell count indexes as possible biomarkers of response has been recently investigated. We discuss the encouraging results reported on the topic, provide new data from our personal experience, and discuss opportunities for further research.



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Next-Generation of Allergen-Specific Immunotherapies: Molecular Approaches

Abstract

Purpose of Review

The aim of this article is to discuss how allergen-specific immunotherapy (AIT) can be improved through molecular approaches. We provide a summary of next-generation molecular AIT approaches and of their clinical evaluation. Furthermore, we discuss the potential of next generation molecular AIT forms for the treatment of severe manifestations of allergy and mention possible future molecular strategies for the secondary and primary prevention of allergy.

Recent Findings

AIT has important advantages over symptomatic forms of allergy treatment but its further development is limited by the quality of the therapeutic antigen preparations which are derived from natural allergen sources. The field of allergy diagnosis is currently undergoing a dramatic improvement through the use of molecular testing with defined, mainly recombinant allergens which allows high-resolution diagnosis. Several studies demonstrate that molecular testing in early childhood can predict the development of symptomatic allergy later on in life.

Summary

Clinical studies indicate that molecular AIT approaches have the potential to improve therapy of allergic diseases and may be used as allergen-specific forms of secondary and eventually primary prevention for allergy.



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Durable clinical remission of a skull metastasis under intralesional Viscum album extract therapy: Case report

Head &Neck, EarlyView.


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Vanderbilt head and neck symptom survey, version 2.0: Clinical and research utility for identification of symptom clusters and changes in symptoms over time

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Publication date: August 2018
Source:Oral Oncology, Volume 83
Author(s): Sheila H. Ridner, Bethany A. Rhoten, Kenneth J. Niermann, Barbara A. Murphy, Mary S. Dietrich
ObjectivesThe symptoms and functional defects following treatment for head and neck cancer (HNC) have been poorly defined. The purpose of this study was to examine the utility of the Vanderbilt Head and Neck Symptom Survey (VHNSS) version 2.0 to identify symptom clusters experienced by patients with HNC as well as assess reliability and sensitivity to change.Materials and methodsThe VHNSS 2.0 questionnaire was completed by 150 patients over three studies. Two studies utilized the survey at multiple time points.ResultsCluster analysis identified ten multi-item clusters and three single items. The internal consistency was good to excellent, with Cronbach's alpha coefficient above 0.90 in five symptom clusters and above 0.70 in remaining clusters. Clusters demonstrated convergent and divergent validity with other measures. Symptom burden was lowest at baseline, peaked at the end of treatment then subsided over the following months.ConclusionsThe VHNSS 2.0 is a reliable and valid measure of acute and late toxicities in patients treated for HNC. The tool may be used in research and clinical practice to screen, to evaluate treatments, and to compare side effects of treatment regimens.



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Frequent HPV-independent p16/INK4A overexpression in head and neck cancer

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Publication date: August 2018
Source:Oral Oncology, Volume 83
Author(s): Matt Lechner, Ankur R. Chakravarthy, Vonn Walter, Liam Masterson, Andrew Feber, Amrita Jay, Paul M. Weinberger, Richard A. McIndoe, Cillian T. Forde, Kerry Chester, Nicholas Kalavrezos, Paul O'Flynn, Martin Forster, Terry M. Jones, Francis M. Vaz, D. Neil Hayes, Tim R. Fenton
Objectivesp16INK4A (p16) is the most widely used clinical biomarker for Human Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a favourable prognostic marker in HNSCC and is used for patient stratification. While p16 is a relatively accurate marker for HPV within the oropharynx, recent reports suggest it may be unsuitable for use in other HNSCC subsites, where a smaller proportion of tumors are HPV-driven.Materials and methodsWe integrated reverse phase protein array (RPPA) data for p16 with HPV status based on detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and other pathway genes to investigate possible drivers of p16 expression.ResultsWhile p16 levels as measured by RPPA were significantly different by HPV status, there were multiple HPV (−) samples with similar expression levels of p16 to HPV (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16 overexpression in HPV (−) tumors could not be explained by mutation or amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV (−)/p16-high tumors.ConclusionsRPPA data suggest high p16 protein expression in many HPV (−) non-oropharyngeal HNSCCs, limiting its potential utility as an HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild-type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of chromatin state by inactivating mutations in NSD1.



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Palynology of the Palaeocene and early Eocene of the London Basin

Allen, Lynn Olive; (1982) Palynology of the Palaeocene and early Eocene of the London Basin. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Immediate effects of a rhino-pharyngeal clearance protocol in nasal obstruction and middle ear condition of children under 3 years of age with upper respiratory infections: A randomized controlled trial

Publication date: Available online 8 June 2018
Source:Acta Otorrinolaringológica Española
Author(s): Ana Silva Alexandrino, Rita Santos, Cristina Melo, David Tomé, José Mesquita Bastos, Guy Postiaux
Introduction and objectivesChildren up to 2 years old are at high risk of respiratory infections and nasal irrigation is often prescribed. Yet, to date there is no sufficient knowledge about its immediate effects on the nasopharynx and middle ear. Therefore, this study aimed to analyze the effect of a rhino-pharyngeal clearance intervention protocol on nasal obstruction and middle ear condition in children under 3 years of age with URTI.Materials and methodsRandomized controlled trial in a day-care centre of Porto, including 44 children randomized to Intervention Group (IG) and Control Group (CG). Nasal auscultation and tympanometry were performed at baseline (M0) as well as after the intervention (M1), which consisted of nasal irrigation (NaCl .9%) followed by a forced nasal inspiration in the IG, and after 30min of normal activities, in the CG.ResultsIn M1 there was a lower frequency of children classified as having an obstructed nasal sound in the IG when compared to the CG (IG=33.3%; CG=68.4%; p=0.042). We also observed an improvement of mean peak pressure (PP) in the IG (Left ear: M0=−124daPa; M1=−92daPa; p=0.022. Right ear: M0=−102daPa; M1=−77daPa; p=0.021), which was not observed in the CG (Left ear: M0=−105daPa; M1=−115daPa; p=0.485. Right ear: M0=−105daPa; M1=−131daPa; p=0.105). There were no significant results concerning the compliance of the tympanic membrane.ConclusionsThe rhino-pharyngeal clearance improved the nasal obstruction and PP of the middle ear of children under 3 years of age with URTI.



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Manejo del absceso de la glándula tiroides

Publication date: Available online 9 June 2018
Source:Acta Otorrinolaringológica Española
Author(s): Javier García Callejo, Jaume Redondo Martínez, Miguel Civera, José Verdú Colomina, Verónica Pellicer Zoghbi, M. Paz Martínez Beneyto
IntroducciónLa enfermedad supurativa de la glándula tiroides-absceso de tiroides o tiroiditis supurativa aguda– supone una infrecuente situación clínica. Presentamos nuestra experiencia en los casos asistidos durante 41 años.Materiales y métodosEstudio longitudinal retrospectivo anotando características epidemiológicas, conducta diagnóstico-terapéutica y resultado clínico, detectando 14 casos –9 varones y 5 mujeres, entre 19 y 68 años, con una media de edad de 40,6±15,4 años– con 22 episodios. En 2 pacientes la condición se había reproducido hasta en 4 ocasiones.ResultadosSupusieron el 0,29% de todos los abscesos cervicales atendidos. La punción-aspiración fue efectuada en 13 de ellos para su tratamiento e identificación del agente causal. Los agentes más habitualmente implicados fueron Mycobacterium tuberculosis y Staphylococcus aureus. Se realizó un estudio de imagen mediante ecografía en 9 casos y de tomografía computarizada en 7. En 10 pacientes el tratamiento definitivo fue quirúrgico, efectuándose drenaje del absceso en 7 de ellos, tiroidectomía total en 4 y hemitiroidectomía en 2. Otros tratamientos admitidos fueron la antibioterapia sistémica o mediante irrigación intralesional y la esclerosis. Aunque en un caso la fase aguda comenzó con hipertiroidismo y tirotoxicosis, a los 6 meses del alta existió hipotiroidismo definitivo en 5 casos. Las opciones terapéuticas adoptadas consiguieron la curación en el 100% de los casos.ConclusiónLa supuración de la glándula tiroidea es una circunstancia extremadamente rara en el contexto de la enfermedad cervical, variando las opciones terapéuticas desde alternativas conservadoras al drenaje con tiroidectomía según los hallazgos microbiológicos y radiológicos.BackgroundThyroid abscess or acute suppurative thyroiditis is an unusual clinical condition. We present our experience with cases attended over 41 years.Materials and methodsA retrospective study was performed on these patients reviewing their epidemiological characteristics and the diagnostic and therapeutic manoeuvres chosen for them all, as well as their clinical outcome. A group of 9 males and 5 females was studied, with ages ranging from 19 to 68 (mean of 40.6±15.4). These patients suffered 22 acute episodes, and 2 patients each had 4 episodes.ResultsSuppurative thyroiditis comprised 0.29% of the neck abscesses. Fine needle aspiration was performed in 13 cases to evacuate the collection and isolate the aetiological agent. Mycobacterium tuberculosis and Staphylococcus aureus were the most frequently identified. Nine patients underwent ultrasound and 7 computed tomography imaging studies. Surgery was the option for 10 patients, including drainage for 7, thyroidectomy for 4 and hemithyroidectomy for the remaining 2. Systemic or intralesional antibiotics and sclerosis of the gland were also carried out. Although one case presented with hyperthyroidism and thyrotoxicosis in the acute phase, definitive hypothyroidism was observed in 5 patients at 6 months following discharge. The rate of success was 100%.ConclusionThyroid gland suppuration is a very infrequent circumstance in neck pathology, and the options for its treatment are varied, from conservative to invasive techniques according to the microbial and radiologic findings.



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