The Role of Palliative Care in Oral Cavity Carcinoma

Abstract

Purpose of Review

The purpose of this study is to review the current and future role of palliative care in relation to oral cavity carcinoma (OCC).

Recent Findings

Palliative care for patients with OCC has traditionally been reserved for patients with advanced disease, recurrent disease, or poor performance status who are unable to undergo surgical or adjuvant treatments. Patients with early- or mid-stage disease were not typically offered palliative services. However, patients at all stages face quality of life issues including disruption of speech, eating, pain, mood, self-image, social interactions, work, and daily activities. This can directly affect performance status and has been shown to increase length of hospitalizations and decrease overall survival. Recent evidence suggests that involving palliative care earlier may decrease rates of depression, decrease cost, improve communication, and increase overall survival outcomes. Furthermore, new applications and innovations in radiation therapy, immunotherapy, and chemotherapy have broadened the palliative therapies available to patients with incurable disease.

Summary

Given the impact that OCC has on quality of life during all stages of disease, a paradigm shift is occurring to involve palliative care at earlier stages. Recent evidence has shown that upstream palliative care increases quality of life and ultimately overall survival.

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Book review—Diagnostic pathology: intraoperative consultation, 2nd edition

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Treatment of penile actinomycosis

Dermatologic Therapy, EarlyView.


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The clinical, biochemical, and ultrasonographic characteristics of patients with hidradenitis suppurativa in Northern Peninsular Malaysia: a multicenter study

International Journal of Dermatology, EarlyView.


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Mammalian meat allergy

International Journal of Dermatology, EarlyView.


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Shared decision making and decisional conflict in the Management of Vestibular Schwannoma: a prospective cohort study

Patients with vestibular schwannomas (VS) are faced with complex management decisions. Watchful waiting, surgical resection, and radiation are all viable options with associated risks and benefits. We sought t...

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Effectiveness of skull X-RAY to determine cochlear implant insertion depth

Cochlear implant (CI) insertion depth can affect residual hearing preservation, tonotopic range coverage, and Mapping. Therefore, determining insertion depth has the potential to maximize CI performance. A pos...

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Re-visiting the ATA 2015 sonographic guidelines - who are we missing?: A retrospective review

The American Thyroid Association published revised guidelines in 2015 on the management of differentiated thyroid cancer in adults. One of the key changes introduced in the revision proposes that diagnostic bi...

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Peri‐implant diseases

European Journal of Oral Sciences, Volume 126, Issue S1, Page 88-94, October 2018.


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Current concepts on Sjögren's syndrome – classification criteria and biomarkers

European Journal of Oral Sciences, Volume 126, Issue S1, Page 37-48, October 2018.


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Mediators between oral dysbiosis and cardiovascular diseases

European Journal of Oral Sciences, Volume 126, Issue S1, Page 26-36, October 2018.


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Oral manifestations of human papillomavirus infections

European Journal of Oral Sciences, Volume 126, Issue S1, Page 49-66, October 2018.


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From understanding tooth development to bioengineering of teeth

European Journal of Oral Sciences, Volume 126, Issue S1, Page 67-71, October 2018.


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Tooth formation and eruption – lessons learnt from cleidocranial dysplasia

European Journal of Oral Sciences, Volume 126, Issue S1, Page 72-80, October 2018.


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Issue Information

European Journal of Oral Sciences, Volume 126, Issue S1, Page 1-2, October 2018.


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From body‐on‐frame to unibody constructions and designs mimicking biological structures – an overview

European Journal of Oral Sciences, Volume 126, Issue S1, Page 95-101, October 2018.


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Dental implants – are they better than natural teeth?

European Journal of Oral Sciences, Volume 126, Issue S1, Page 81-87, October 2018.


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The oral microbiome – friend or foe?

European Journal of Oral Sciences, Volume 126, Issue S1, Page 5-12, October 2018.


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Optimizing quality and safety of dental materials

European Journal of Oral Sciences, Volume 126, Issue S1, Page 102-105, October 2018.


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Prevention of dental caries as a non‐communicable disease

European Journal of Oral Sciences, Volume 126, Issue S1, Page 19-25, October 2018.


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Nordic contribution to dental and orofacial sciences

European Journal of Oral Sciences, Volume 126, Issue S1, Page 3-4, October 2018.


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Biofilms and their properties

European Journal of Oral Sciences, Volume 126, Issue S1, Page 13-18, October 2018.


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Bilateral Central Giant Cell Granuloma of the mandibular angle in three females from the same family

In literature there are few reports about multiple CGCG. But this is the first report of bilateral CGCG of the mandibular angles in three females from the same family.

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Announcements

Dear Colleagues,

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EACMFS Awards

The Council of EACMFS wishes to ensure that all members of the Association are aware of the current awards and prizes that are available. These are designed to provide educational support and also allow the opportunity for trainees and those who have recently achieved specialist status to visit units outside their own departments.

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When designing vaccines, consider the starting material: the human B cell repertoire

Colin Havenar-Daughton | Robert K. Abbott | William R. Schief | Shane Crotty

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Dysmorphic features and cochlear implantation outcome in children with sensorineural hearing loss; the headmost study

Susan Amirsalari, Shahla Afsharpayman, Mohammad Ajalloueyan, Jaber Rasuli, Amin Saburi, Mohammad Torkaman

Indian Journal of Otology 2018 24(2):75-79

Introduction: Recently, treatment of children with severe-to-profound sensorineural hearing loss (SNHL) has been influenced by diagnostic improvements and technological treatment advances, specifically new cochlear implant prospects. Multiple handicaps children and children with syndromes and conditions resulting disabilities, such as dual sensory loss, cerebral palsy, somatic abnormalities, and autistic spectrum disorder, are now not routinely precluded from receiving a cochlear implant. The primary aim of this study was to determine the effects of dysmorphic feature on cochlear implant outcome. Materials and Methods: In this cohort study, we evaluated 336 cochlear implanted children from 2007 to 2009. The case group consists of 53 patients (15/7%) with dysmorphic features and control group consisted at 53 patients with normal features and without behavioral and developmental disorders. All patients received auditory and speech rehabilitation and we evaluated their speech and auditory outcome. One year after cochlear implantation, the patient was assessed by categories of auditory perception (CAP) and speech intelligibility rating (SIR) tests. Results: We included 106 out of 336 cochlear implanted children, with the mean age of 30.42 ± 12.16 (maximum 48 months), 52 cases (49.1%) were girls and 54 (50.9%) were boys. There was a significant difference in SIR between case and control groups (3.26 ± 0.98) versus (4.06 ± 0.94) (P < 0.001), and a significant difference in CAP (4.09 ± 1.26) versus (5.43 ± 1.23) as well (P < 0.001). Conclusion: In this study, the prevalence of dysmorphic feature in children with severe-to-profound SNHL is 15.7%. One year after cochlear implant SIR and categories of auditory perception in these patients are significantly lower than children without dysmorphic feature, but cochlear implant will help these children.

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A prospective, observational study of incidence of sensory neural hearing loss in diabetes mellitus patients

Swati Dadhich, Sushil G Jha, Vikas Sinha, TU Samanth

Indian Journal of Otology 2018 24(2):80-82

Aims and Objective: To find out the incidence of hearing loss among the type 2 diabetes mellitus patients. Materials and Methods: Study included 100 diabetic mellitus patients at least for 3 years. It is an observational study carried out for 1 year. Fasting blood sugar, PP2BS, random blood sugar, pure tone audiogram were done. Results: In this study, 100 diabetic patients were studied; out of them, 73 patients were having sensorineural hearing loss (SNHL). Out of 73 SNHL diabetic patients, 48 patients are having mild SNHL (65.75%), 21 patients are having moderate SNHL (28.76%), one patient of mod severe SNHL (1.37%), and three patients of severe SNHL (4.11%). Conclusion: The diabetic individuals had higher hearing threshold with bilateral mild to moderate degree SNHL. Gender of diabetic patient had no significant correlation with hearing loss. Duration of diabetes had significant correlation with hearing loss. Blood glucose level had strong association with SNHL.

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Papular mycosis fungoides: Three case reports and a comprehensive literature review

Jingcheng Zhang, Mingzhe Zhao, Huixian Hu

Indian Journal of Otology 2018 24(2):120-122

This study was to investigate the clinicopathological characteristics, treatments, and prognoses of papillary mycosis fungus (PMF). From May 2004 to September 2015, three cases of papular mycosis fungoides were analyzed at Jinhua Municipal Central Hospital. Diagnostic criteria refer to the World Health Organization 2005 Classification of Cutaneous Lymphoma. Factors that influenced patient survival and prognoses were analyzed. Skin papules were reduced, and skin color was lightened in three patients after a short treatment regimen. Follow-up for 4–7 years revealed few changes in pigmentation, no increase in skin papules, and neither organ nor lymph node involvement. Skin papular mycosis fungal disease can heal itself, and there is no need for excessive intervention.

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Determinants of holistic outcome in traumatic tympanic membrane perforation

Hemant Ahluwalia, Prem Narain, Arunabh Ahluwalia, Jaypal Singh, Ajay Singh

Indian Journal of Otology 2018 24(2):83-87

Objective: The goal of this study is to understand the perforation closure dynamics and to elucidate the factors playing vital role in closure of traumatic tympanic membrane perforation (TMP). Study Design: This was a prospective, sequential allocation, three armed, January 2015–June 2017 (30 months). Setting: This study was conducted at university teaching tertiary hospital. Sample Size: A sample size was 309 (291 patients and 294 ears). Results: The total number of patients included was 291 and the total ears were 294 being bilateral traumatic TMPs in three patients. The mean age of the patients was 27.9 years. Hearing loss and bleeding from ear were the most common presentation. In majority, the hearing loss was conductive. Slap being the most common etiology. Posteroinferior quadrant was the most common site of injury. The overall mean closure time of this study was 13.32 days. Three patients were lost to follow-up. Perforation healing rate in this study was 98.98% at 1 month, and there was a significant difference in healing rate for small and large perforations. We have studied all the three variables together, i.e., the impact of time of initiating treatment after injury, grade of perforation, and their closure time to understand the closure dynamics of traumatic TMPs which is unique and is first of its kind in literature. Conclusion: The carbolic acid to the edge and paper patch with soframycin is a noninvasive, patient-friendly and low-cost office procedure for traumatic TMP's and if performed within 72 h of injury gives 99%–100% closure rate.

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Osteomyelitis of temporal bone: A case report of a rare disease

Bigyan Raj Gyawali, Pabina Rayamajhi

Indian Journal of Otology 2018 24(2):114-116

Osteomyelitis of temporal bone affecting the squamous portion is a very rare entity. We present here a case of osteomyelitis affecting the squamous portion of temporal bone following blunt trauma to the head.

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Effectiveness of multitalker babble over speech noise and its implications: A comparative study

Archana Gundmi, P Himaja, Alisha Dhamani

Indian Journal of Otology 2018 24(2):88-90

Introduction: Speech perception is a complex process. Many variables can affect speech perception; among that, background noise is one of the important factors where maximum interference for the speech perception happens. Perception of speech varies also with types of noise the individual is encountering. Aim: The present study was concentrated on effect of multitalker babble over speech noise in perceiving speech signal. Method: Twenty-four normal-hearing individuals participated in the present study were tested in two different conditions in different signal-to-noise ratio ratios. Result and Conclusion: Results revealed multitalker babble is more effective than speech noise thus can be used more relevantly in clinical practice.

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A therapeutic approach of isolated suppurative labyrinthitis complicated by meningitis

Erika Celis-Aguilar, Lucero Escobar-Aispuro, Jose M Alarid-Coronel, Alan Burgos-Paez

Indian Journal of Otology 2018 24(2):125-128

Suppurative labyrinthitis (SL), a major complication of otitis media, results from a bacterial infection spread through the round window to the inner ear. The most frequent symptoms are hearing loss, vertigo, nystagmus, nausea, and vomiting. This infection poses a significant risk of meningitis due to direct communication of the perilymph to the cerebrospinal fluid through the cochlear aqueduct. There are scarce data in the literature documenting isolated SL as the only cause of meningitis. There are no data describing which treatment is more effective, how often this complication occurs, or when to expect this fatal outcome. We report a case that developed from a labyrinthine suppurative infection to a late-onset meningeal infective disease. This case highlights the importance of correct and timely treatment of SL with early mastoidectomy. The indications of mastoidectomy in these cases are discussed, with a brief review of the literature.

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Clinical features of preauricular sinus and recurrence rate of supra-auricular approach

O Song-Hwan, In-Kyo So, Jin-Ho Kim

Indian Journal of Otology 2018 24(2):91-94

Objective: The objective of this study was to analyze the clinical features of preauricular sinus and the recurrence rate of supra-auricular approach. Materials and Methods: A total of 87 patients (96 ears) treated for preauricular sinus at the Department of Otolaryngology-Head and Neck Surgery, Pyongyang Medical College Hospital, Kim Il Sung University, between January 2007 and December 2016 were enrolled in this study. Results: The prevalence of preauricular sinus was more common in teenage group (55.2%). Preauricular sinus occurred more frequently in male (1.4 times). The most common type of preauricular sinus was marginal helicine type with 86.5%. The recurrence rate with supra-auricular approach was found to be 3.3% whereas simple sinusectomy was 17.1%. Conclusion: The most common type in the preauricular sinus was marginal helicine type and supra-auricular approach was a reliable technique which had significantly less recurrence rate.

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Measurement of speech in noise abilities in laboratory and real-world noise

Bhanu Shukla, B Srinivasa Rao, Udit Saxena, Himanshu Verma

Indian Journal of Otology 2018 24(2):109-113

Aim: The present study aimed to investigate speech in noise perception abilities in normal-hearing adults using different types of noise (i.e., speech babble, traffic noise, and speech spectrum noise) and at different signal-to-noise ratios (SNRs) (i.e., +5 dB, 0 dB, −5 dB, and −10 dB). Methods: A total of 109 individuals with mean age of 23 years were participated in the study. All participants had English as second language and Telugu as native and first language. English disyllabic words (Hrish et al.) were used as speech stimuli under different noises and different SNRs. Results: Results have shown that for any type of noise the speech perception scores changed with the variance in SNRs, the scores have decreased when the SNRs were decreased from 0 dB to −10 dB SNR, and the scores have increased when SNRs increased from 0 dB to +5 dB SNR. Conclusion: From this study, it can be concluded that speech perception score in noise depends on the type of noise used in testing the speech in noise abilities. This factor is very important in the selection of the noise type when measuring speech perception in the presence of noise. It was also seen that change in noise level also had a different impact on speech perception in noise abilities.

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Influence of mastoid drilling on otoacoustic emissions of the nonoperated ear

Sherien Badarudeen, Mubeena , Gangadhara Somayaji

Indian Journal of Otology 2018 24(2):95-97

Introduction: Drilling in mastoid surgeries can affect the nonoperated normal ear by transcranial transmission. This transient hearing loss can be assessed using distortion-product otoacoustic emissions (DPOAE). Objectives: To determine the effect of drilling on the DPOAE in the contralateral normal ear following mastoid surgeries and its relation with the duration of drilling. Study Design: This was a comparative, prospective, and case–control study. Materials and Methods: DPOAE was obtained for 20 patients who underwent mastoid surgery. DPOAE was measured at frequencies of 2, 3, 4, and 5 kHz with frequency ratio maintained at 1.22. DPOAE was recorded during the preoperative, immediate postoperative, 1st and 7th postoperative days. Twenty controls that underwent tympanoplasty were also analyzed pre- and post-operatively. Results: Significant deterioration in the DPOAE amplitudes was noticed during immediate postoperative period in all the four frequencies studied. No correlation was obtained between the duration of drilling and the change in amplitudes. Conclusion: A transient hearing loss is seen in the nonoperated ear following mastoid surgeries due to a drill-induced noise exposure.

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Double-Peak tympanometry in keratosis obturans

Azliana Aziz, Mohd Khairi Md Daud

Indian Journal of Otology 2018 24(2):117-119

Tympanometry is an effective objective tool used to identify problems in the middle ear. Keratosis obturans (KO) is a rare condition but may cause bony erosion and gradual expansion of the bony external auditory canal (EAC). We report a case of 32-year-old woman with KO who presented with bilateral hearing loss for a few years and right ear pain and discharge for 3 months before visit to an otorhinolaryngology clinic. She was treated by ear drops antibiotic and repeated ear toilet. Tympanometry done revealed a large EAC volume with a double-peak admittance. Double-peak tympanometry with an intact tympanic membrane may indicate diseases causing severe erosion in the EAC.

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Effect of below-damage-risk criteria environmental noise on auditory perception and working memory

Sandeep Maruthy, G Nike Gnanateja, Preethi C Chengappa, Sam A Publius, Varsha M Athreya

Indian Journal of Otology 2018 24(2):98-104

Background: The current research finding is the first in reporting impaired auditory and cognitive abilities consequent to chronic exposure to below-damage-risk criteria (DRC) environmental noise in humans. Objective: The objective of this study is to assess the chronic effects of occupational noise below DRC on auditory and cognitive abilities. Methods: A static-group comparison design was used, with three groups with varying levels of noise exposure below DRC. Shopkeepers working in busy areas exposed daily to environmental noise below DRC and shopkeepers working in quiet residential areas and college students in quiet environments. Speech perception in noise, acceptable noise levels, and concurrent vowel identification were used to assess auditory abilities, while Operation SPAN and Backward Digit Span were used to assess cognitive abilities. The data were analyzed using multivariate analysis of variance, Pearson's product-moment correlation, discriminant function analysis, and mediation analysis. Results: The results showed significantly poor auditory stream segregation abilities and working memory abilities in the shopkeepers exposed to environmental noise below DRC when compared to the other two groups with very low levels of occupational noise. The findings of the study are discussed in light of the deleterious effect of the supposedly safe (below DRC) levels of environmental noise on auditory and cognitive abilities. Conclusions: The novel results of affected auditory and cognitive abilities resulting from below-DRC occupational noise exposure as observed in the current study will have a great impact on the applicability to the general populace and also open up new avenues of research in ecological acoustics.

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The inferior “transposition flap” in meatal nevus

Manish Munjal, Archana Arora, Amanjeet Singh, Porshia Rishi

Indian Journal of Otology 2018 24(2):123-124

Nevi and benign lesions of the epithelium of the cartilaginous meatus and refractory to multiple sessions of laser resections are ideal candidates for composite resection with transposition flap reconstitution, retaining thereby the esthetic appearance and dimensional configuration of the cartilaginous meatus. An inferiorly based flap transposed anteriorly and utilized in nevus of the floor and posterior wall gave excellent results.

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Role of cervical vestibular-evoked myogenic potentials in evaluating vestibular dysfunction in patients with Type II diabetes mellitus: A prospective institutional study

Sitaramaraju Kanumuri, Krishna Vemuru Chaitanya, Janardhan Nara, K Vasu Kumar Reddy

Indian Journal of Otology 2018 24(2):105-108

Introduction: Cervical Vestibular Evoked Myogenic Potentials (C VEMP) is new dimension of non-invasive investigation to evaluate integrity of Saccule and inferior vestibular nerve by means of sacculo-collic reflex. In this study, we intend to use cervical vestibular evoked Myogenic potential as tool to investigate prevalence of vestibular dysfunction in patients with type II diabetes mellitus. Objectives: To study the prevalence of vestibular dysfunction as measured by cervical Vestibular Evoked Myogenic Potentials in patients with type 2 diabetes mellitus. Results: Prospective study performed on patients presenting in Otorhinolaryngology department during 2013-2016. Patients in study with type 2 diabetes mellitus of greater than 5 years underwent vestibular assessment by using Cervical Vestibular Evoked Myogenic Potentials. It was observed that 4 (10.0%) patients had absent bilateral Cervical Vestibular Evoked Myogenic Potentials responses, 8(20.0%) patients had delayed Cervical Vestibular Evoked Myogenic Potentials responses with delayed p1 and n1 latencies. Discussion and Conclusion: In diabetic individuals who are asymptomatic in patients who never complained of giddiness, Cervical Vestibular Evoked Myogenic Potentials identified vestibular dysfunction in 25% of patients. In symptomatic diabetic mellitus individuals, Cervical Vestibular Evoked Myogenic Potentials was able to identify 33.3% of vestibular dysfunction, however in another 33.3% of patients where Cervical Vestibular Evoked Myogenic Potentials failed to identify.

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Management of unsafe type of chronic suppurative otitis media with extracranial complications at a tertiary care center

Vinod Tukaram Kandakure, Pradipkumar Digambarrao Khokle, Udit Rohit Shah

Indian Journal of Otology 2018 24(2):129-134

Chronic suppurative otitis media (CSOM) is a common disease in the developing countries and the complications associated with it still pose a major problem. Despite the reduction in the incidence of CSOM-related complications with the introduction of antibiotics, Gradenigo's syndrome, mastoid abscess, labyrinthine fistula, and other complications still do occur. Computed tomography scan is an inevitable part of diagnostic algorithm rendered when a patient with CSOM presents with complications. Otitis media although a common pathology,complications are rare and should be suspected when the picture is of torpid evolution with clinical worsening and manifestation of neurological signs. There is a need to emphasize the importance of accurate and early diagnosis followed by adequate surgical therapy with a multidisciplinary approach. Here, we look at such cases encountered at our institute and their management.

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Management of seborrhoeic keratosis and actinic keratosis with an erbium:YAG laser—experience with 547 patients

Seborrhoeic keratosis and actinic keratosis are common skin lesions, and the latter is a precursor for skin malignancy. The treatment regime can be lesion-directed or field-directed. Current lesion-directed treatments include cryotherapy, shave excision, and laser ablation. Field-directed treatment typically encompasses multiple topical agents. This article presents the authors' experience of lesion- and field-directed erbium:YAG laser treatment of 547 patients (Fotona Dualis XS Laser). In this series of patients, those who had resurfacing as field therapy showed no recurrence during the 12-month review period.

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Subsets of CD4+, CD8+, and CD25hi Lymphocytes Are in General Not Influenced by Isolation and Long-Term Cryopreservation [NOVEL IMMUNOLOGICAL METHODS]

Several key factors can affect the outcome of immunological studies; isolation/cryopreservation can possibly alter T, B, NK, and T-regulatory (Treg) cell marker expression patterns. Blood samples from 50 blood donors supplemented with Na-heparin or K₂EDTA were handled within 4 and 24 h after blood sampling. PBMC were isolated with different density gradients. Flow cytometric analysis of intracellular and extracellular CD markers was performed on blood samples freshly isolated PBMC, and PBMC was thawed 6 and 12 mo post-cryopreservation for the purpose of identifying B, NK, Th, T-cytotoxic, and Treg cells. No differences were observed in the percentages for CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD19⁺, or CD56⁺CD16⁺ cells within 24 h of sampling regardless of which supplement or isolation techniques were used. Differentiated (diff) CD4⁺ cells were in general less affected by isolation and cryopreservation than diff CD8⁺ cells. Terminally diff effector CD4⁺ and CD8⁺ cells were not affected by either isolation of lymphocytes or cryopreservation. In contrast, naive and early-diff effector memory CD4⁺ and CD8⁺ cells were affected by isolation and cryopreservation. The percentages of Treg cells defined as CD4⁺CD25^hi expressing CD101 or CD129, CD4⁺CD25^hiCD127^–, and CD4⁺CD25^hiCD127^–FOXP3⁺, respectively, remained stable after isolation and cryopreservation. Subsets expressing CD127, with or without FOXP3, were not affected by isolation/cryopreservation. Subsets expressing CD39, contrary to CD45RA, on CD4⁺CD25⁺CD127^– cells with or without FOXP3 were not affected by either isolation or cryopreservation. In conclusion, subsets of CD4⁺, CD8⁺, and CD25^hi lymphocytes are in general not influenced by isolation and long-term cryopreservation.

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Sweaty feet in adolescents—Early use of botulinum type A toxin in juvenile plantar hyperhidrosis

Pediatric Dermatology, EarlyView.


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Melanotic neuroectodermal tumor of infancy: A rare pediatric head and neck lesion

Pediatric Dermatology, EarlyView.


https://ift.tt/2Na99a3

Type 1 IFN and PD-L1 Coordinate Lymphatic Endothelial Cell Expansion and Contraction during an Inflammatory Immune Response [INNATE IMMUNITY AND INFLAMMATION]

Lymph node (LN) expansion during an immune response is a complex process that involves the relaxation of the fibroblastic network, germinal center formation, and lymphatic vessel growth. These processes require the stromal cell network of the LN to act deliberately to accommodate the influx of immune cells to the LN. The molecular drivers of these processes are not well understood. Therefore, we asked whether the immediate cytokines type 1 IFN produced during viral infection influence the lymphatic network of the LN in mice. We found that following an IFN-inducing stimulus such as viral infection or polyI:C, programmed cell death ligand 1 (PD-L1) expression is dynamically upregulated on lymphatic endothelial cells (LECs). We found that reception of type 1 IFN by LECs is important for the upregulation of PD-L1 of mouse and human LECs and the inhibition of LEC expansion in the LN. Expression of PD-L1 by LECs is also important for the regulation of LN expansion and contraction after an IFN-inducing stimulus. We demonstrate a direct role for both type 1 IFN and PD-L1 in inhibiting LEC division and in promoting LEC survival. Together, these data reveal a novel mechanism for the coordination of type 1 IFN and PD-L1 in manipulating LEC expansion and survival during an inflammatory immune response.

https://ift.tt/2NfUtWR

Discovery of the IL-23/IL-17 Signaling Pathway and the Treatment of Psoriasis [TRANSLATING IMMUNOLOGY]

Psoriasis vulgaris is a common, heterogeneous, chronic inflammatory skin disease characterized by thickened, red, scaly plaques and systemic inflammation. Psoriasis is also associated with multiple comorbid conditions, such as joint destruction, cardiovascular disease, stroke, hypertension, metabolic syndrome, and chronic kidney disease. The discovery of IL-17–producing T cells in a mouse model of autoimmunity transformed our understanding of inflammation driven by T lymphocytes and associations with human inflammatory diseases, such as psoriasis. Under the regulation of IL-23, T cells that produce high levels of IL-17 create a self-amplifying, feed-forward inflammatory response in keratinocytes that drives the development of thickened skin lesions infiltrated with a mixture of inflammatory cell populations. Recently, the Food and Drug Administration approved multiple highly effective psoriasis therapies that disrupt IL-17 (secukinumab, ixekizumab, and brodalumab) and IL-23 (guselkumab and tildrakizumab) signaling in the skin, thus leading to a major paradigm shift in the way that psoriatic disease is managed.

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Progression from the Common Lymphoid Progenitor to B/Myeloid PreproB and ProB Precursors during B Lymphopoiesis Requires C/EBP{alpha} [IMMUNE SYSTEM DEVELOPMENT]

The C/EBPα transcription factor is required for myelopoiesis, with prior observations suggesting additional contributions to B lymphopoiesis. Cebpa expression is evident in common lymphoid progenitor (CLP) and preproB cells but is absent in proB and preB cells. We previously observed that marrow lacking the Cebpa +37 kb enhancer is impaired in producing B cells upon competitive transplantation. Additionally, a Cebpa enhancer/promoter-hCD4 transgene is expressed in B/myeloid CFU. Extending these findings, pan-hematopoietic murine Cebpa enhancer deletion using Mx1-Cre leads to expanded CLP, fewer preproB cells, markedly reduced proB and preB cells, and reduced mature B cells, without affecting T cell numbers. In contrast, enhancer deletion at the proB stage using Mb1-Cre does not impair B cell maturation. Further evaluation of CLP reveals that the Cebpa transgene is expressed almost exclusively in Flt3⁺ multipotent CLP versus B cell–restricted Flt3^– CLP. In vitro, hCD4⁺ preproB cells produce both B and myeloid cells, whereas hCD4^– preproB cells only produce B cells. Additionally, a subset of hCD4^– preproB cells express high levels of RAG1-GFP, as seen also in proB cells. Global gene expression analysis indicates that hCD4⁺ preproB cells express proliferative pathways, whereas B cell development and signal transduction pathways predominate in hCD4^– preproB cells. Consistent with these changes, Cebpa enhancer–deleted preproB cells downmodulate cell cycle pathways while upregulating B cell signaling pathways. Collectively, these findings indicate that C/EBPα is required for Flt3⁺ CLP maturation into preproB cells and then for proliferative Cebpa^int B/myeloid preproB cells to progress to Cebpa^lo B cell–restricted preproB cells and finally to Cebpa^neg proB cells.

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The Intestinal Virome and Immunity [BRIEF REVIEWS]

The composition of the human microbiome is considered a major source of interindividual variation in immunity and, by extension, susceptibility to diseases. Intestinal bacteria have been the major focus of research. However, diverse communities of viruses that infect microbes and the animal host cohabitate the gastrointestinal tract and collectively constitute the gut virome. Although viruses are typically investigated as pathogens, recent studies highlight a relationship between the host and animal viruses in the gut that is more akin to host–microbiome interactions and includes both beneficial and detrimental outcomes for the host. These viruses are likely sources of immune variation, both locally and extraintestinally. In this review, we describe the components of the gut virome, in particular mammalian viruses, and their ability to modulate host responses during homeostasis and disease.

https://ift.tt/2NQfvZ0

Conventional Dendritic Cells Impair Recovery after Myocardial Infarction [SYSTEMS IMMUNOLOGY]

Ischemic myocardial injury results in sterile cardiac inflammation that leads to tissue repair, two processes controlled by mononuclear phagocytes. Despite global burden of cardiovascular diseases, we do not understand the functional contribution to pathogenesis of specific cardiac mononuclear phagocyte lineages, in particular dendritic cells. To address this limitation, we used detailed lineage tracing and genetic studies to identify bona fide murine and human CD103⁺ conventional dendritic cell (cDC)1s, CD11b⁺ cDC2s, and plasmacytoid DCs (pDCs) in the heart of normal mice and immunocompromised NSG mice reconstituted with human CD34⁺ cells, respectively. After myocardial infarction (MI), the specific depletion of cDCs, but not pDCs, improved cardiac function and prevented adverse cardiac remodeling. Our results showed that fractional shortening measured after MI was not influenced by the absence of pDCs. Interestingly, however, depletion of cDCs significantly improved reduction in fractional shortening. Moreover, fibrosis and cell areas were reduced in infarcted zones. This correlated with reduced numbers of cardiac macrophages, neutrophils, and T cells, indicating a blunted inflammatory response. Accordingly, mRNA levels of proinflammatory cytokines IL-1β and IFN- were reduced. Collectively, our results demonstrate the unequivocal pathological role of cDCs following MI.

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Cutting Edge: Glycolytic Metabolism and Mitochondrial Metabolism Are Uncoupled in Antigen-Activated CD8+ Recent Thymic Emigrants [CUTTING EDGE]

Recent thymic emigrants (RTEs) are peripheral T cells that have most recently completed selection and thymic egress and constitute a population that is phenotypically and functionally distinct from its more mature counterpart. Ag-activated RTEs are less potent effectors than are activated mature T cells, due in part to reduced aerobic glycolysis (correctable by exogenous IL-2), which in turn impacts IFN- production. Mitochondria serve as nodal regulators of cell function, but their contribution to the unique biology of RTEs is unknown. In this study, we show that activated mouse RTEs have impaired oxidative phosphorylation, even in the presence of exogenous IL-2. This altered respiratory phenotype is the result of decreased CD28 signaling, reduced glutaminase induction, and diminished mitochondrial mass in RTEs relative to mature T cells. These results suggest an uncoupling whereby IL-2 tunes the rate of RTE glycolytic metabolism, whereas the unique profile of RTE mitochondrial metabolism is "hard wired."

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CBLB Constrains Inactivated Vaccine-Induced CD8+ T Cell Responses and Immunity against Lethal Fungal Pneumonia [INFECTIOUS DISEASE AND HOST RESPONSE]

Fungal infections in CD4⁺ T cell immunocompromised patients have risen sharply in recent years. Although vaccines offer a rational avenue to prevent infections, there are no licensed fungal vaccines available. Inactivated vaccines are safer but less efficacious and require adjuvants that may undesirably bias toward poor protective immune responses. We hypothesized that reducing the TCR signaling threshold could potentiate antifungal CD8⁺ T cell responses and immunity to inactivated vaccine in the absence of CD4⁺ T cells. In this study, we show that CBLB, a negative regulator of TCR signaling, suppresses CD8⁺ T cells in response to inactivated fungal vaccination in a mouse model of CD4⁺ T cell lymphopenia. Conversely, Cblb deficiency enhanced both the type 1 (e.g., IFN-) and type 17 (IL-17A) CD8⁺ T cell responses to inactivated fungal vaccines and augmented vaccine immunity to lethal fungal pneumonia. Furthermore, we show that immunization with live or inactivated vaccine yeast did not cause detectable pathologic condition in Cblb^–/– mice. Augmented CD8⁺ T cell responses in the absence of CBLB also did not lead to terminal differentiation or adversely affect the expression of transcription factors T-bet, Eomes, and RORt. Additionally, our adoptive transfer experiments showed that CBLB impedes the effector CD8⁺ T cell responses in a cell-intrinsic manner. Finally, we showed that ablation of Cblb overcomes the requirement of HIF-1α for expansion of CD8⁺ T cells upon vaccination. Thus, adjuvants that target CBLB may augment inactivated vaccines and immunity against systemic fungal infections in vulnerable patients.

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Cutting Edge: Proper Orientation of CTCF Sites in Cer Is Required for Normal J{kappa}-Distal and J{kappa}-Proximal V{kappa} Gene Usage [CUTTING EDGE]

Ig locus contraction and V gene usage are controlled by Cer, a cis-acting sequence in the V–J intervening region. This effect is attributed to two CTCF-binding sites within Cer that are oriented toward the V gene region. However, the importance of Cer CTCF orientation in regulating VJ rearrangement is unknown. We used CRISPR/Cas9 editing to delete and invert Cer in murine Abl pro–B cell lines. This revealed that Cer orientation is critical because clones with either an inverted or deleted Cer element show skewing toward J-proximal V gene usage. However, only Cer deletion increased J-proximal V germline transcription, suggesting an insulating function of Cer. Lastly, circularized chromosome conformation capture interaction data show that Cer CTCF orientation regulates long-range interactions with inversion clones displaying fewer interactions with regions in the middle and distal parts of the V locus and more interactions to downstream regions compared with wild-type or deletion clones.

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Nucleotide Composition of Human Ig Nontemplated Regions Depends on Trimming of the Flanking Gene Segments, and Terminal Deoxynucleotidyl Transferase Favors Adding Cytosine, Not Guanosine, in Most VDJ Rearrangements [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

The formation of nontemplated (N) regions during Ig gene rearrangement is a major contributor to Ab diversity. To gain insights into the mechanisms behind this, we studied the nucleotide composition of N regions within 29,962 unique human V_HDJ_H rearrangements and 8728 unique human DJ_H rearrangements containing exactly one identifiable D gene segment and thus two N regions, N1 and N2. We found a distinct decreasing content of cytosine (C) and increasing content of guanine (G) across each N region, suggesting that N regions are typically generated by concatenation of two 3' overhangs synthesized by addition of nucleoside triphosphates with a preference for dCTP. This challenges the general assumption that the terminal deoxynucleotidyl transferase favors dGTP in vivo. Furthermore, we found that the G and C gradients depended strongly on whether the germline gene segments were trimmed or not. Our data show that C-enriched N addition preferentially happens at trimmed 3' ends of V_H, D, and J_H gene segments, indicating a dependency of the transferase mechanism upon the nuclease mechanism.

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Cutting Edge: Dysregulated CARD9 Signaling in Neutrophils Drives Inflammation in a Mouse Model of Neutrophilic Dermatoses [CUTTING EDGE]

Mice homozygous for the Y208N amino acid substitution in the carboxy terminus of SHP-1 (referred to as Ptpn6^spin mice) spontaneously develop a severe inflammatory disease resembling neutrophilic dermatosis in humans. Disease in Ptpn6^spin mice is characterized by persistent footpad swelling and suppurative inflammation. Recently, in addition to IL-1α and IL-1R signaling, we demonstrated a pivotal role for RIPK1, TAK1, and ASK1 in promoting inflammatory disease in Ptpn6^spin mice. In the current study we have identified a previously unknown role for CARD9 signaling as a critical regulator for Ptpn6^spin-mediated footpad inflammation. Genetic deletion of CARD9 significantly rescued the Ptpn6^spin-mediated footpad inflammation. Mechanistically, enhanced IL-1α–mediated signaling in Ptpn6^spin mice neutrophils was dampened in Ptpn6^spinCard9^–/– mice. Collectively, this study identifies SHP-1 and CARD9 cross-talk as a novel regulator of IL-1α–driven inflammation and opens future avenues for finding novel drug targets to treat neutrophilic dermatosis in humans.

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In This Issue [IN THIS ISSUE]

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Cutting Edge: IL-1R1 Mediates Host Resistance to Mycobacterium tuberculosis by Trans-Protection of Infected Cells [CUTTING EDGE]

IL-1R1 deficiency in mice causes severe susceptibility to Mycobacterium tuberculosis. Mice and macrophage cultures lacking IL-1R1 display increased bacterial growth, suggesting that phagocytes may require IL-1R1–dependent antimicrobial signals to limit intracellular M. tuberculosis replication directly. However, the myeloid-cell–intrinsic versus –extrinsic requirements for IL-1R1 to control M. tuberculosis infection in mice have not been directly addressed. Using single-cell analysis of infected cells, competitive mixed bone marrow chimeras, and IL-1R1 conditional mutant mice, we show in this article that IL-1R1 expression by pulmonary phagocytes is uncoupled from their ability to control intracellular M. tuberculosis growth. Importantly, IL-1R1–dependent control was provided to infected cells in trans by both nonhematopoietic and hematopoietic cells. Thus, IL-1R1–mediated host resistance to M. tuberculosis infection does not involve mechanisms of cell-autonomous antimicrobicidal effector functions in phagocytes but requires the cooperation between infected cells and other cells of hematopoietic or nonhematopoietic origin to promote bacterial containment and control of infection.

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The Phagocyte Oxidase Controls Tolerance to Mycobacterium tuberculosis Infection [INFECTIOUS DISEASE AND HOST RESPONSE]

Protection from infectious disease relies on two distinct strategies: antimicrobial resistance directly inhibits pathogen growth, whereas infection tolerance protects from the negative impact of infection on host health. A single immune mediator can differentially contribute to these strategies in distinct contexts, confounding our understanding of protection to different pathogens. For example, the NADPH-dependent phagocyte oxidase (Phox) complex produces antimicrobial superoxide and protects from tuberculosis (TB) in humans. However, Phox-deficient mice display no sustained resistance defects to Mycobacterium tuberculosis, suggesting a more complicated role for NADPH Phox complex than strictly controlling bacterial growth. We examined the mechanisms by which Phox contributes to protection from TB and found that mice lacking the Cybb subunit of Phox suffered from a specific defect in tolerance, which was caused by unregulated Caspase-1 activation, IL-1β production, and neutrophil influx into the lung. These studies imply that a defect in tolerance alone is sufficient to compromise immunity to M. tuberculosis and highlight a central role for Phox and Caspase-1 in regulating TB disease progression.

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Syndecan-1 Regulates Psoriasiform Dermatitis by Controlling Homeostasis of IL-17-Producing {gamma}{delta} T Cells [ALLERGY AND OTHER HYPERSENSITIVITIES]

IL-17 is a potent proinflammatory cytokine that drives pathogenesis of multiple autoimmune diseases, including psoriasis. A major source of pathogenic IL-17 is a subset of T cells (T17) that acquires the ability to produce IL-17 while developing in the thymus. The mechanisms that regulate homeostasis of T17 cells and their roles in psoriasis, however, are not fully understood. In this paper, we show that the heparan sulfate proteoglycan syndecan-1 (sdc1) plays a critical role in regulating homeostasis of T17 cells and modulating psoriasis-like skin inflammation in mice. sdc1 was predominantly expressed by T17 cells (but not IL-17^– T cells) in the thymus, lymph nodes, and dermis. sdc1 deficiency significantly and selectively increased the frequency and absolute numbers of T17 cells by mechanisms that included increased proliferation and decreased apoptosis. Adoptive transfer experiments ruled out a significant role of sdc1 expressed on nonhematopoietic cells in halting expansion and proliferation of sdc1-deficient T17 cells. When subjected to imiquimod-induced psoriasiform dermatitis, T17 cells in sdc1KO mice displayed heightened responses accompanied by significantly increased skin inflammation than their wild-type counterparts. Furthermore, transferred sdc1-deficient T cells caused more severe psoriasiform dermatitis than their sdc1-sufficient counterparts in TCR–β KO hosts. The results uncover a novel role for sdc1 in controlling homeostasis of T17 cells and moderating host responses to psoriasis-like inflammation.

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Glatiramer Acetate Enhances Myeloid-Derived Suppressor Cell Function via Recognition of Paired Ig-like Receptor B [INNATE IMMUNITY AND INFLAMMATION]

Glatiramer acetate (GA; Copaxone) is a copolymer therapeutic that is approved by the Food and Drug Administration for the relapsing-remitting form of multiple sclerosis. Despite an unclear mechanism of action, studies have shown that GA promotes protective Th2 immunity and stimulates release of cytokines that suppress autoimmunity. In this study, we demonstrate that GA interacts with murine paired Ig-like receptor B (PIR-B) on myeloid-derived suppressor cells and suppresses the STAT1/NF-B pathways while promoting IL-10/TGF-β cytokine release. In inflammatory bowel disease models, GA enhanced myeloid-derived suppressor cell–dependent CD4⁺ regulatory T cell generation while reducing proinflammatory cytokine secretion. Human monocyte-derived macrophages responded to GA by reducing TNF-α production and promoting CD163 expression typical of alternative maturation despite the presence of GM-CSF. Furthermore, GA competitively interacts with leukocyte Ig-like receptors B (LILRBs), the human orthologs of PIR-B. Because GA limited proinflammatory activation of myeloid cells, therapeutics that target LILRBs represent novel treatment modalities for autoimmune indications.

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Identification and Analysis of Islet Antigen-Specific CD8+ T Cells with T Cell Libraries [CLINICAL AND HUMAN IMMUNOLOGY]

Type 1 diabetes (T1D) is most likely caused by killing of β cells by autoreactive CD8⁺ T cells. Methods to isolate and identify these cells are limited by their low frequency in the peripheral blood. We analyzed CD8⁺ T cells, reactive with diabetes Ags, with T cell libraries and further characterized their phenotype by CyTOF using class I MHC tetramers. In the libraries, the frequency of islet Ag–specific CD45RO⁺IFN-⁺CD8⁺ T cells was higher in patients with T1D compared with healthy control subjects. Ag-specific cells from the libraries of patients with T1D were reactive with ZnT8_186–194, whereas those from healthy control recognized ZnT8_186–194 and other Ags. ZnT8_186–194-reactive CD8⁺ cells expressed an activation phenotype in T1D patients. We found TCR sequences that were used in multiple library wells from patients with T1D, but these sequences were private and not shared between individuals. These sequences could identify the Ag-specific T cells on a repeated draw, ex vivo in the IFN-⁺ CD8⁺ T cell subset. We conclude that CD8⁺ T cell libraries can identify Ag-specific T cells in patients with T1D. The T cell clonotypes can be tracked in vivo with identification of the TCR gene sequences.

https://ift.tt/2NNxXBL

A Fundamental Role of Myh9 for Neutrophil Migration in Innate Immunity [INNATE IMMUNITY AND INFLAMMATION]

Neutrophils are the first leukocytes to arrive at sites of injury during the acute inflammatory response. To maintain the polarized morphology during migration, nonmuscle myosins class II are essential, but studies using genetic models to investigate the role of Myh9 for neutrophil migration were missing. In this study, we analyzed the functional role of Myh9 on neutrophil trafficking using genetic downregulation of Myh9 in Vav-iCre⁺/Myh9^wt/fl mice because the complete knockout of Myh9 in the hematopoietic system was lethal. Migration velocity and Euclidean distance were significantly diminished during mechanotactic migration of Vav-iCre⁺/Myh9^wt/fl neutrophils compared with Vav-iCre^–/Myh9^wt/fl control neutrophils. Similar results were obtained for transmigration and migration in confined three-dimensional environments. Stimulated emission depletion nanoscopy revealed that a certain threshold of Myh9 was required to maintain proper F-actin dynamics in the front of the migrating cell. In laser-induced skin injury and in acute peritonitis, reduced Myh9 expression in the hematopoietic system resulted in significantly diminished neutrophil extravasation. Investigation of bone marrow chimeric mice in the peritonitis model revealed that the migration defect was cell intrinsic. Expression of Myh9-EGFP rescued the Myh9-related defects in two-dimensional and three-dimensional migration of Hoxb8-SCF cell–derived neutrophils generated from fetal liver cells with a Myh9 knockdown. Live cell imaging provided evidence that Myh9 was localized in branching lamellipodia and in the uropod where it may enable fast neutrophil migration. In summary, the severe migration defects indicate an essential and fundamental role of Myh9 for neutrophil trafficking in innate immunity.

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SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells [IMMUNE REGULATION]

Clinical application of Ag-specific T regulatory cells (Tregs) offers promise for the treatment of undesirable immune diseases. To achieve this goal, long-term expansion of Tregs is required to obtain sufficient numbers of cells. However, human Tregs are not stable ex vivo. Therefore, we previously developed an innovative Treg expansion protocol using 25mer-phosphorothioated random oligonucleotides (ODNps25). The addition of ODNps25 successfully resulted in the stabilization of engineered Ag-specific Tregs; however, the mechanism is not fully characterized. We first identified sterile α motif histidine-aspartate–domain containing protein 1 (SAMHD1) as an ODNps25-binding protein using a UV–cross-linking pull-down strategy. SAMHD1 physically interacted with the 3' untranslated region of Foxp3 mRNA and was translocated from nucleus to cytoplasm after ODNps25 treatment. Importantly, addition of ODNps25 enhanced the interaction of SAMHD1 and Foxp3 mRNA significantly, and this interaction was increased by TCR stimulation. Because ODNps25 binds to the nuclease (HD) domain of SAMHD1, we then established that overexpression of a dNTPase-deficient mutant (D137N) in Tregs significantly stabilized the expression level of the Foxp3 protein. Furthermore, we found that TCR stimulation upregulates phosphorylation of the threonine residue (Thr592), which is a regulatory site to control SAMHD1 activity, and phosphorylation of Thr592 is critical to control SAMHD1 activity to stabilize the expression of Foxp3 and Helios in Tregs. Taken together, we suggest that the interaction of ODNPs25 in HD or phosphorylation of Thr592 by TCR stimulation interferes with nuclease activity of SAMHD1, thereby stabilizing 3' untranslated region of Foxp3 and Helios mRNAs in long-term culture.

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Airway Epithelial Cell Peroxisome Proliferator-Activated Receptor {gamma} Regulates Inflammation and Mucin Expression in Allergic Airway Disease [MUCOSAL IMMUNOLOGY]

Airway epithelial cells (AECs) orchestrate inflammatory responses to airborne irritants that enter the respiratory system. A viscous mucus layer produced by goblet cells in the airway epithelium also contributes to a physiological defense mechanism through the physical and chemical barriers it provides. Dysregulation or impairment in these functions has been implicated as a cause of the chronic inflammation and tissue remodeling that constitute major pathological features of asthma. In particular, mucus hypersecretion leading to airway obstruction and impaired pulmonary function is associated with morbidity and mortality in asthma patients. Peroxisome proliferator–activated receptor (PPAR) is a ligand-activated transcription factor involved in a variety of cellular processes. Accumulating evidence indicates that PPAR agonists antagonize exaggerated inflammatory responses, yet PPAR's precise role in airway remodeling/mucus hypersecretion has yet to be defined. In this study, we created an AEC-specific PPAR (AEC-PPAR) deletion to investigate PPAR's functions in a murine model of allergic airway disease. AEC-PPAR deficiency exaggerated airway hyperresponsiveness, inflammation, cytokine expression, and tissue remodeling. We also found that PPAR directly bound to a PPAR response element found in MUC5AC and repressed gene expression. Likewise, PPAR regulated mucin and inflammatory factors in primary human bronchial epithelial cells. In light of the current standard therapies' limited and inadequate direct effect on airway mucus hypersecretion, our study showing AEC-PPAR's role as a transcriptional repressor of MUC5AC highlights this receptor's potential as a pharmacological target for asthma.

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ERK Signaling Controls Innate-like CD8+ T Cell Differentiation via the ELK4 (SAP-1) and ELK1 Transcription Factors [IMMUNE SYSTEM DEVELOPMENT]

In mouse thymocyte development, signaling by the TCR through the ERK pathway is required for positive selection of conventional naive T cells. The Ets transcription factor ELK4 (SAP-1), an ERK-regulated cofactor of the SRF transcription factor, plays an important role in positive selection by activating immediate-early genes such as the Egr transcription factor family. The role of ELK4–SRF signaling in development of other T cell types dependent on ERK signaling has been unclear. In this article, we show that ELK4, and its close relative ELK1, act cell autonomously in the thymus to control the generation of innate-like αβ CD8⁺ T cells with memory-like characteristics. Mice lacking ELK4 and ELK1 develop increased numbers of innate-like αβ CD8⁺ T cells, which populate the periphery. These cells develop cell autonomously rather than through expansion of PLZF⁺ thymocytes and concomitantly increased IL-4 signaling. Their development is associated with reduced TCR-mediated activation of ELK4–SRF target genes and can be partially suppressed by overexpression of the ELK4–SRF target gene EGR2. Consistent with this, partial inhibition of ERK signaling in peripheral CD8⁺T cells promotes the generation of cells with innate-like characteristics. These data establish that low-level ERK signaling through ELK4 (and ELK1) promotes innate-like αβ CD8⁺ T cell differentiation, tuning conventional versus innate-like development.

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Anaphylaxis triggers in a large tertiary care hospital in Qatar: a retrospective study

Anaphylaxis is a serious allergic disease that may lead to death if not immediately recognized and treated. Triggers of anaphylaxis including food, drugs, and insect stings can vary widely. The incidence of an...

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Correction to: Effect of Stimulus Polarity on Detection Thresholds in Cochlear Implant Users: Relationships with Average Threshold, Gap Detection, and Rate Discrimination

The middle initial of Julie G. Arenberg's name was incorrect in the original publication; it is correct as displayed here.

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The first line of defence: insights into mechanisms and relevance of phagocytosis in epithelial cells

Abstract

Epithelial tissues cover most of the external and internal surfaces of the body and its organs. Inevitably, these tissues serve as first line of defence against inorganic, organic, and microbial intruders. Epithelial cells are the main cell type of these tissues. Besides their function as cellular barrier, there is growing evidence that epithelial cells are of particular relevance as initial sensors of danger and also as executers of adequate defence responses. These cells feature various essential functions to maintain tissue integrity in health and disease. In this review, we survey some of the different innate immune functions of epithelial cells in mucosal tissues being constantly exposed to a plethora of harmless contaminants but also of pathogens. We discuss how epithelial cells avoid inadequate immune responses in such conditions. In particular, we will focus on the diverse types and mechanisms of phagocytosis used by epithelial cells to not only maintain homeostasis but to also harness the host response against invading pathogens.

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Correction to: Effect of Stimulus Polarity on Detection Thresholds in Cochlear Implant Users: Relationships with Average Threshold, Gap Detection, and Rate Discrimination

The middle initial of Julie G. Arenberg's name was incorrect in the original publication; it is correct as displayed here.

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Congenital Syphilis—Still a Shadow on the Land

The US Surgeon General, Thomas Parran, chose an ominous phrase—Shadow on the Land—as the title of his best-selling book about syphilis, published in 1937. It was not without reason. At the time, according to Parran, nearly 700 000 Americans were being treated for syphilis, constituting only a fraction of the approximately 1.7 million that he estimated needed treatment. At least 500 000 new infections occurred in the United States each year, Parran stated, including 60 000 cases of congenital syphilis. Cardiovascular syphilis claimed 40 000 lives each year. The arsenic-containing compound salvarsan, supplemented with mercury or bismuth, was the most effective treatment. Syphilis, Parran wrote, was "the most urgent public health problem in this country today."^(p52)

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Druckdolenter, subkutaner Tumor an der Handinnenfläche

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Effects of double‐dose intranasal corticosteroid for allergic rhinitis: a systematic review and meta‐analysis

International Forum of Allergy &Rhinology, EarlyView.


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Ultrasonographic assessment of the lens

Description 

B scan ultrasonography is the most commonly used modality for the assessment of posterior segment pathologies.1–3 On placing the probe along the lateral longitudinal axis, the nasal aspect of the retina, ciliary body, the lens in its entirety, iris, angle and peripheral cornea can be appreciated easily. Using this technique, the anatomy of the lens can be studied in terms of its width along the horizontal and anteroposterior extent; similarly, by placing the probe along the inferior longitudinal axis, the vertical width of the lens can be defined, along with the anteroposterior thickness. This technique helps in the assessment of lens in its entirety, from the anterior capsule to the posterior capsule. Herein few pathologies of the lens and its capsule are illustrated using B scan ultrasound (Sonomed, New York, USA).

After making the patient lie down in a comfortable supine...

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First report of concomitant pheochromocytoma and duodenal neuroendocrine tumour in a sporadic multiple endocrine neoplasia type 1

A 77-year-old woman was diagnosed with pheochromocytoma followed by adrenalectomy at age 57. Hyperparathyroidism without osteoprosis was diagnosed at age 58. At age 75, Dual Energy X-ray Absoptiometry (DEXA) revealed osteoporosis and sestamibi scan showed a left parathyroid adenoma. Criteria for parathyroidectomy were met, and she underwent parathyroidectomy. Furthermore, she presented with haematochezia at age 75. An abdominal CT demonstrated a mass in the second portion of the duodenum. Additionally, octreoscan revealed somatostatin receptor positive tissue in the duodenum and Gallium 68 dotatate scan also showed a well-differentiated duodenal neuroendocrine tumour (NET). Genetic testing for MEN1, MEN2 and MEN4 was negative. Diagnosis of sporadic MEN1 syndrome was made. The patient underwent resection of the duodenal NET at age 76. She is in good health 21 years after her first presentation of MEN1. In summary, we present the first sporadic case of MEN1 with concomitant pheochromocytoma and duodenal NET which occurred 20 years apart.

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Mumps presenting with unilateral, synchronous parotid and submandibular gland swelling

A previously healthy 22-year-old woman presented with acute, unilateral facial and neck swelling, associated with fever and malaise. She was initially treated with intravenous antibiotics; however, CT imaging showed unilateral, synchronous swelling and inflammation of the parotid and submandibular glands, and a PCR swab from the parotid duct was positive for mumps. She was fully immunised and had no contact in the preceding period with anyone diagnosed with mumps. She responded to supportive management and her symptoms resolved over the course of her admission. Unilateral, synchronous swelling and severe inflammation of both the parotid and submandibular glands in mumps is a very unusual presentation, and not one previously reported in the literature.

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Management of a giant uterine leiomyoma

Uterine leiomyomas are the most common tumours arising from the female reproductive tract. However, giant myomas, which are greater than 11.4 kg in weight, are exceedingly rare. They may cause a pressure effect on surrounding organs, heart and lungs, which can be potentially life threatening. We present a case of a 53-year-old woman with a massive uterine mass complicated by restrictive lung disease. She underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy with frozen section and reconstruction of the abdominal wall by the gynaecologists and plastic surgeons. The excised specimen weighed 27.8 kg, which included a benign subserosal leiomyoma measuring 64 by 50.5 by 15 cm. Intraoperative blood loss was 7 L and her postoperative recovery was complicated by coagulopathy and haemorrhagic shock. This case illustrates the pivotal role of multidisciplinary care in the management of complicated surgical patients and the need for careful perioperative care.

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Vacuum-assisted right atrial infected clot extraction due to persistent bacteraemia: a percutaneous approach for the management of right-sided endocarditis

A 56-year-old woman with non-ischaemic cardiomyopathy with implantable cardioverter defibrillator (ICD) presented to the hospital with progressive dyspnoea of 4 weeks' duration. She soon spiralled down to develop septic shock with methicillin-sensitive Staphylococcus aureus bacteraemia. A transoesophageal echocardiogram revealed a 2.4x2.1 cm large mobile echodensity in the right atrium likely attached to the ICD lead and to the interatrial septum. Although the ICD along with its leads was extracted, bacteraemia persisted despite appropriate antibiotic therapy. Because of her worsening condition, she underwent a right atrial infected clot extraction by the AngioVac system. Her clinical condition noticeably improved soon after evacuation of the infected clot.

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Laryngopyocoele with contralateral laryngocoele: a rare cause of respiratory distress

We present the case of a 76-year-old patient who attended our emergency department with signs of sepsis and severe respiratory distress. She had stridor, type 1 respiratory failure and a left-sided neck swelling. On CT, it was initially misdiagnosed as parapharyngeal abscess. When the imaging was reviewed, it was found to be a left-sided mixed laryngopyocoele obstructing the larynx with an asymptomatic contralateral laryngocoele. The internal component of the left laryngopyocoele was excised through a microlaryngoscopy approach while the external component was approached through a transcervical incision. The patient recovered well despite a postoperative myocardial infarction. Both laryngocoeles and laryngopyocoeles are rare, with the latter being the rarer of the two, however, extensive literature review could not identify any previous cases where both have coexisted in the same patient.

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Hereditary sensory and autonomic neuropathy in a male child: 'The other side of not feeling pain

Description 

A 1-year-old boy was brought to our outpatient department with complaints of whitish opacity in both eyes noticed 3 months ago. The mother also gave a history of self-mutilating behaviour in the child. There was a history of absence of crying during vaccination. There was no history of consanguinity and a similar disease in the family. The child was following light binocularly. On anterior segment examination, bilateral corneal scarring secondary to keratitis was seen (figure 1A). Corneal sensations were absent. An ocular ultrasonography was done for posterior segment evaluation, which revealed no abnormalities. There were signs of self-mutilation in the perioral area in form of damage to both upper and lower lips that caused as a result of repeated insults in form of tooth bite (figure 1B). Apart from this, similar injuries were present in fingers of hands (figure 1C) as...

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Atypical presentation of acute aortic dissection in a young competitive rower

A 27-year-old man (who is also the lead author) presented with dull pain deep to the suprasternal notch, following a period of intense exercise (rowing). He was initially sent home with no diagnosis, but 24 hours later returned to a different Accident & Emergency (A&E), due to continued discomfort and an increasingly altered mental state, and was diagnosed with an extensive type A aortic dissection extending from the aortic root to the iliac bifurcation of the aorta, with an ~8 cm aneurysm on the ascending aorta and a diseased aortic valve. Following emergency surgery to replace the aortic valve and the aorta from the aortic root to the middle of the aortic arch (hemiarch), the patient recovered well.

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Missed ureteral injury in a young man with stab injury

Description 

An 18-year-old man was referred to us from the department of emergency surgery for management of his ureteric injury. The patient underwent exploratory laparotomy for bowel injury that he had sustained due to a stab wound to his left flank 1 month ago. At that time his ureteric injury was missed. Two weeks after being discharged he developed fever and his ultrasonogram was suggestive of a large left retroperitoneal collection with mild left hydronephrosis. A contrast-enhanced CT (CECT) scan was done that demonstrated leak of contrast from left ureter into the collection (figure 1A). The patient then underwent insertion of a percutaneous nephrostomy tube into the left kidney along with placement of a drain into the retroperitoneal collection. The drain placed into the collection had purulent output suggesting an infected urinoma. Two weeks later another CECT scan was done, which showed persistent retroperitoneal urinoma, and ureter...

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Typhoid fever with isolated left lateral rectus palsy

A 17-year-old young woman presented to Patan Hospital, Kathmandu, Nepal, with high-grade fever and headache for 4 days and non-projectile vomiting for 1 day. She also had blurred vision with dizziness on and off. There was no abnormal physical finding. Enteric fever was suspected, and she was empirically started on azithromycin (20 mg/kg) for 7 days. She became afebrile after 2 days and was followed up in 7 days with diplopia since 5 days. At this time, the blood culture was positive for Salmonella serovar typhi. On examination, there was isolated left lateral rectus palsy which accounted for her diplopia. Methylprednisolone (1 mg/kg) was prescribed which was tapered over 1 month and gradually her diplopia subsided. We hypothesise that vasculitic change in the blood vessel supplying the left abducens nerve could be causing the diplopia.

https://ift.tt/2MMVB4U

Clear cell chondrosarcoma of the larynx

Chondrosarcomas represent a group of malignant tumours composed of cells producing cartilage, and clear cell chondrosarcomas (CCC) represent a variant of these. A rare case of a laryngeal CCC is presented. The patient was a 70-year-old man who presented with a 6-week history of throat pain, worsening dysphonia and a lump in the neck. Examination revealed a level 3 neck mass and positron emission tomography imaging revealed a metabolically active right laryngeal mass. Biopsies revealed a cartilaginous neoplasm. The patient underwent total laryngectomy, and the pathology confirmed CCC of the larynx. Chondrosarcomas are the most common type of sarcoma in the larynx but the CCC variant is rare. CCC are usually low-grade tumours affecting long bones, with a male predominance. Less than six cases have been described in the literature affecting the larynx. Management of these malignancies is complete surgical excision given the high risk of local recurrence.

https://ift.tt/2wKOgbg

Double pylorus

Description 

A 69-year-old man with a past medical history of asthma, chronic back pain and hypertension presented with symptoms of light headedness, epigastric pain and blood-mixed bowel movement of 2 days duration. Since the past 9 months the patient had been taking two to three pills of ibuprofen almost on a daily basis for his back pain. He had also received short courses of prednisone tablets frequently in the last 6 months for his poorly controlled asthma. On arrival in the emergency room, his blood pressure was 84/48 mm Hg, heart rate 121/min, respiratory rate 18/min, temperature 36°C and oxygen saturation was 94% on room air. His haemoglobin (Hb) was 7.2 mg/dL. The patient was given proton pump inhibitor (PPI) therapy, volume resuscitated and was admitted to the intensive care unit. After 2 units of packed red blood cell transfusion his Hb was 9.1 mg/dL. He underwent upper gastrointestinal (GI) endoscopy which showed two openings into...

https://ift.tt/2MLf85r

Incidentally detected adrenocortical carcinoma in familial adenomatous polyposis: an unusual presentation of a hereditary cancer syndrome

Description 

A 30-year-old woman presented to us with complaints of intermittent bleeding per rectum, vague abdominal pain and altered bowel habits for last 3 months. There was no history of headache, palpitations, diarrhoea, weight loss, skin lesions, haematuria and hypertension. Her grandmother had history of colostomy for acute intestinal obstruction and died of unexplained cause at age of 55 years. Her laboratory investigations were normal. On digital rectal examination, multiple polypoidal firm masses were felt approximately 1–5 cm from anal verge. On colonoscopy, number of polyps were seen in the colon around 40–50 in number, ranging from few millimetres to largest measuring around 3 cm. These polyps spread over ascending to sigmoid colon and rectum in increasing number. The biopsy from these polyps was suggestive of tubular adenomas. A definitive diagnosis of familial adenomatous polyposis (FAP) was made. FAP is associated with a myriad of presentations, and hence, a thorough work...

https://ift.tt/2LZucXY

Atypical giant prolactinoma with frontal lobe manifestations

Description 

Prolactinomas having the diameter above 4 cm are termed 'giant prolactinomas'.1 2 Their incidence is approximately 2%–3% of all prolactinomas1. These are associated with very high prolactin concentration and numerous neurological sequelae, arising from their extension into surrounding structures. However, frontal lobe symptoms have not been reported frequently in the literature.3 These are more common in males with the male-to-female ratio of 9:1.1 We report an atypical case of a giant prolactinoma that presented with frontal lobe symptoms but responded remarkably well to dopamine agonist treatment.

We present a case of a 65-year-old woman who presented with progressively worsening short-term memory loss, confusion, mild intermittent headaches, increased somnolence, difficulty in walking due to unsteadiness and urine incontinence of 2 months' duration. There was a major change in behaviour and personality. On examination, she was confused with Montreal Cognitive Assessment...

https://ift.tt/2MLeXqN

Bronchobiliary fistula: a rare complication after pancreaticoduodenectomy

Biliary anatomic pathologies are rare disease occurrences that can result from a number of causes, most commonly iatrogenic, infectious and malignant aetiologies. Communications between the biliary and bronchial systems are even rarer and few cases have been documented in the literature. The present study describes a case of a 70-year-old man who underwent a pancreaticoduodenectomy (Whipple Procedure) as a curative procedure for an early stage neuroendocrine tumour. He presented nearly a decade after surgery with a communication between the biliary and bronchial tree initially manifesting as bilioptysis. His underlying medical conditions and poor clinical picture made treatment options limited. Therefore, he was treated conservatively with percutaneous biliary balloon dilation of the anastomotic stricture followed by temporary percutaneous internal/external drain and made a full recovery.

https://ift.tt/2LWj3qM

Innovative use of a stereolithographic model together with the mirror image technique to reconstruct a defect in mandibular continuity

Publication date: Available online 3 September 2018

Source: British Journal of Oral and Maxillofacial Surgery

Author(s): A.J. Abbasi, M. Parvin, S. Bashiri

https://ift.tt/2wG3YUO

Orthodromic transfer of the temporalis tendon with extension of the fascia lata to reanimate the smile in facial palsy

Publication date: Available online 3 September 2018

Source: British Journal of Oral and Maxillofacial Surgery

Author(s): Anson Jose, Shakil Ahmed Nagori, Indranil D. Roy, Ajoy Roychoudhury

https://ift.tt/2Q4N6A4

Molecular pathogenesis of proliferative verrucous leucoplakia: a systematic review

Publication date: Available online 3 September 2018

Source: British Journal of Oral and Maxillofacial Surgery

Author(s): E.M. Okoturo, J.M. Risk, A.G. Schache, R.J. Shaw, M.T. Boyd

Abstract

Proliferative verrucous leucoplakia (PVL) is a potentially premalignant lesion that undergoes malignant transformation in over 40% of cases. Its clinical homogeneity suggests that a single or a small number of molecular pathogenic pathways may exist. Using the Cochrane protocol for systematic reviews, we have looked at the reported evidence of the molecular aetiology and pathogenesis of PVL and compared it with that of conventional oral epithelial dysplasia (OED). Of the 43 papers studied, 19 met the inclusion criteria including 13 proteins assayed in 344 tissues, and genes investigated were TP53, p14ARF, and p16INK4A. In all studies the research objectives were defined and outcomes were clearly stated. This review has shown that the transformation of PVL does not follow the same pathway as that of OED. There was weak evidence to suggest possible correlations between DNA aneuploidy, loss of heterozygosity at locus 9p21, and specific expression of MCM (mini chromosome maintenance) protein, to transformation of PVL. To show important or distinct pathways of this condition, further studies are needed to access the somatic genomic alterations that are found in malignancies.

https://ift.tt/2LQPYgF

Mitral Valve Endocarditis due to Lactobacillus

Lactobacillus species are Gram-positive, facultative anaerobic, rod-shaped bacteria. They belong to the lactic acid bacteria group and are also known as a usual part of the normal flora of the gastrointestinal tract as well as of the urinary and genital tracts. They are an infrequent human pathogen but can induce several infections such as bacteremia and infectious endocarditis. We report the case of an 81-year-old woman with Lactobacillus bacteremia and mitral valve endocarditis as well as splenic abscesses.

https://ift.tt/2NLHUzA

International Symposium: Trailblazing in Cancer Immunotherapy, October 29–31, 2017, Pamplona, Spain

https://ift.tt/2PYhZWV

PET/MR in Locally Advanced Nasopharyngeal Carcinoma

Conditions:   Nasopharyngeal Carcinoma;   PET/MR
Intervention:   Diagnostic Test: PET/MR
Sponsor:   Zhejiang Cancer Hospital
Recruiting

https://ift.tt/2Nh5qYb

Use of a Proliferation Saturation Index to Determine Personalized Radiotherapy for HPV + Oropharyngeal Cancers

Condition:   Oropharyngeal Cancer
Intervention:   Radiation: Radiotherapy fractionation
Sponsor:   H. Lee Moffitt Cancer Center and Research Institute
Recruiting

https://ift.tt/2LV0Mu5

Assessment of Treatment Response of Nasopharyngeal Cancer Using Simultaneous 18F-FDG-PET and MRI

Condition:   Nasopharyngeal Cancer
Intervention:   Diagnostic Test: PET/CT scans
Sponsor:   New York University School of Medicine
Recruiting

https://ift.tt/2Nh5h75

Prediction of permanent hypoparathyroidism by parathyroid hormone and serum calcium 24 h after thyroidectomy

Publication date: Available online 3 September 2018

Source: American Journal of Otolaryngology

Author(s): Wenlong Wang, Fada Xia, Chaoyang Meng, Zhejia Zhang, Ning Bai, Xinying Li

Abstract

Purpose

To assess the value of 24-hour intact parathyroid hormone (iPTH), serum calcium, and decreases in both were evaluated against preoperative values (iPTH and serum calcium decline) and used to determine the existence of permanent hypoparathyroidism (pHPP) after total thyroidectomy (TT).

Materials and methods

The clinical data of patients who underwent total thyroidectomy in our hospital between September 2014 and July 2015 were retrospectively analyzed.

Results

There were 42 cases with normal parathyroid function, 58 cases with temporary HPP, and 10 cases with pHPP. When iPTH and serum calcium were administered at 24 h after surgery, iPTH decline and calcium decline differed significantly among the three groups above (P < .01). The accuracy and positive predictive value of 24 h iPTH for pHPP were higher than any one of the others. The sensitivity, specificity, false positive rate, and accuracy were 100%, 95%, 33.33%, and 94.45%, respectively. The AUC was 0.982 when 24-hour iPTH was equal to or <3.15 pg/mL. The use of blood calcium equal to or <2.03 mmol/L (8.12 mg/dL) pointed to a diagnosis of pHPP, with a sensitivity of 100%, specificity of 63%, false positive rate of 78.72%, and accuracy of 66.36%.

Conclusions

Measurement of the postoperative 24-h intact parathyroid hormone and serum calcium concentration can predict the occurrence of permanent hypoparathyroidism and the former is more advantageous. Postoperative 24-h intact parathyroid hormone equal to or <3.15 pg/mL is a reliable index, and it is suitable for the prediction of postoperative permanent hypoparathyroidism.

https://ift.tt/2oEaOGI

The influence of orbital decompression on objective nasal function in patients with graves’ orbitopathy

Abstract

Purpose

To determine the influence of anatomical changes after orbital decompression to nasal function.

Methods

We examined postoperative nasal function after orbital decompression in patients with GO in a prospective study. 25 patients were enrolled between 2014 and 2016. Sense of smell (Sniffin' Test) and nasal airflow (anterior rhinomanometry) were tested pre- and 6 weeks postoperatively. In addition, postoperative incidence of sinus infections, persistent pressure pain, and infraorbital hypoesthesia were assessed by means of a questionnaire.

Results

The olfactory performance showed a significant increase (p < 0.05) after surgery, while the nasal airflow significantly decreased (p < 0.05). Acute sinus infection occurred in three, infraorbital sensibility disorders in eight cases within the first 6 weeks after surgery. No persistent pain was recorded.

Conclusion

We demonstrate that decompression of the medial orbital wall leads to a decrease in nasal airflow, whereof patients should be informed before the procedure. This is most likely due to a medialization of the medial turbinate and the prolapse of orbital content into the nasal cavity. The increase of the olfactory performance is, in our opinion, more likely due to variation within the standard deviation than to anatomical changes.

https://ift.tt/2Nglqtn

Correlation of sleep-disordered breathing and laryngopharyngeal reflux: a two-channel triple-sensor pHmetry catheter study

Abstract

Purpose

To investigate the relationship between sleep-disordered breathing with gastroesophageal reflux (GER) and laryngopharyngeal reflux (LPR) using a two-channel triple-sensor pHmetry catheter.

Methods

The study was carried out on a total of 34 people with complaints of snoring, witnessed apnea and daytime sleepiness. 24-h pH monitoring with a two-channel, triple-sensor antimony pH catheter was applied to individuals simultaneously with polysomnography (PSG) on the day they would sleep in the sleep laboratory. Obstructive sleep apnea syndrome (OSAS) severity and reflux grade were compared with each other. Data obtained from PSG and pHmetry results were numerically compared with each other. The relationship between apnea, hypopnea, and arousal periods and reflux episodes was then examined by overlaying pHmetry graphics for each patient.

Results

A total of 34 individuals (18 males—52.9% and 16 females—47.1%), age ranging from 27 to 71 years (mean 50.5 ± 11.0) participated in the study. GER was detected in 52.9% and LPR in 85.3% of the patients. In 35.3% of cases, pathologic GER was not observed despite LPR detection. No statistically significant relationship was found between the numerical values of apnea–hypopnea index (AHI) and arousal numbers and reflux parameters of individuals and between OSAS severity and LPR and GER (p > 0.05). There was no statistically significant correlation between respiratory events and reflux episodes with regard to timing (p > 0.05).

Conclusion

The prevalence of GER and LPR is found to be high in patients with sleep-disordered breathing. There is no significant relationship between OSAS severity and GER and LPR grade or respiratory events and reflux episodes with regard to timing.

https://ift.tt/2LUAlVw

Correction to: Increased incidence of Warthin tumours of the parotid gland: a 42-year evaluation

In the original publication, in Table 2, the last value of third column, referring to `Number of cases' has been misprint. It should read "265" instead of the "235". The corrected table 2 is given below.

https://ift.tt/2NeYGtW

Unilateral congenital malformations of middle ear with intact external ear: a review of 64 cases

Abstract

Objective

To describe the operative findings and surgical results of unilateral congenital middle ear malformations with intact external ear.

Methods

A retrospective review was performed on 64 patients with unilateral congenital middle ear malformations and intact external ear who underwent exploratory tympanotomy from 2011 to 2016. Demographic data, clinical data, high-resolution computed tomography findings, audiometric data and intraoperative findings were collected. Audiological evaluations before and 6 months after surgery were analyzed in 47 patients.

Results

The most common malformation were mobile stapes with missing incus long process and stapes suprastructure. The air conduction pure tone average was 58.9 ± 10.5 dB HL (range 34.4–78.1 dB HL) preoperatively and 28.8 ± 10.6 dB HL (range 9.4–55.6 dB HL) postoperatively (P = 0.000). Twenty-five cases (53.2%) acquired an air conduction hearing gain exceeding 30 dB. Mean air-bone gap (ABG) was 44.5 ± 9.4 dB (range 22.5–66.4 dB HL) before surgery and 15.6 ± 9.3 dB (range 0–35.6 dB) after surgery (P = 0.000) for an average gain of 28.8 ± 11.5 dB. Thirty-four cases (72.3%) showed a postoperative ABG of less than 20 dB, 15 had an ABG within 10 dB, and 4 had 0 dB ABG after operation. No significant difference was observed for air conduction hearing gain regarding age (P = 0.261) or types of malformations (mobile stapes footplate with or without a suprastructure anomaly, P = 0.058).

Conclusion

Unilateral congenital middle ear malformations with intact external ear can be complex and diverse. Functional ossiculoplasty for patients with unilateral congenital middle ear malformations can achieve good hearing outcomes.

https://ift.tt/2LTg0jb

Vocal fold paresis: Medical specialists’ opinions on standard diagnostics and laryngeal findings

Abstract

Purpose

There is still no clear consensus on the diagnostic value of specific laryngeal findings in patients with suspected vocal fold paresis (VFP). The aim of the study was to establish expert opinion on criteria for the diagnosis of VFP in Europe.

Methods

A cross-sectional survey using the questionnaire introduced by Wu and Sulica for US American experts was addressed to laryngeal experts in Germany, Austria, and Switzerland and in a second survey wave to members of the European Laryngological Society.

Results

100 respondents returned survey 1 (response rate 47.2%). 26% worked at a university department. 28% regularly used laryngeal electromyography (LEMG). A pathologic test results in LEMG was considered to have the strongest positive predictive value for VFP (79 ± 23%), followed by a decreased vocal fold abduction (70 ± 29%), decreased vocal fold adduction (61 ± 34%), and atrophy of the hemilarynx (61 ± 31%). The multivariate analysis showed the predictive value of LEMG was estimated lower by respondents from non-university hospital (β = − 16.33; confidence interval (CI) = − 25.63 to − 7.02; p = 0.001) and higher in hospitals with higher frequency of VFP patients per months (β = 1.57; CI = − 0.98 to 2.16; p < 0.0001). 30 ELS members returned survey 2 (response rate, 8.4%). Their answers were not significantly different to survey 1.

Conclusions

The laryngology experts in Europe rely on LEMG for diagnosis of VFP like the US American experts, but paradoxically only a minority uses LEMG frequently. Next to LEMG, motion abnormities were considered to have the best predictive value for the diagnosis of VFP.

https://ift.tt/2NhbcZU

Simultaneous acquisition of 40- and 80-Hz auditory steady-state responses for a direct comparison of response amplitude, residual noise and signal-to-noise ratio

Abstract

Purpose

The purpose of this study was to establish a paradigm that allows for the simultaneous recording of auditory steady-state responses (ASSRs) to two largely different modulation rates.

Methods

In 21 normal-hearing adults, ASSRs for 40- and 80-Hz modulation rates were recorded in (1) a classical monotic single-stimulus condition, (2) a monotic simultaneous condition, where 40 Hz was paired with a 1-kHz carrier and 80 Hz with a 2-kHz carrier, and (3) a dichotic simultaneous condition with the same modulation rate/carrier pairing. Response amplitudes, residual noises, and signal-to-noise ratios were compared across conditions.

Results

Whereas the multiple-stimulus paradigms reduced the 40-Hz ASSR amplitude compared to the single condition, there was hardly any change for the 80-Hz ASSR. In all conditions, the 40-Hz ASSR was considerably larger than the 80-Hz ASSR. The residual noise was only 1.4 times larger for 40 Hz than for the 80 Hz.

Conclusion

The proposed procedure using multiple stimuli with largely different modulation rates can be used to study differences in their responses and residual noise under identical states of vigilance. The amplitude reduction caused by the interaction between multiple stimuli has to be taken into account when interpreting the results.

https://ift.tt/2LWYfiX

The ameliorative effect of berberine and coenzyme Q10 in an ovalbumin-induced allergic rhinitis model

Abstract

Purpose

Berberine and coenzyme Q10 (CoQ10) are agents with anti-inflammatory and antioxidant characteristics. The purpose of this study was to investigate the effectiveness of berberine and CoQ10 on allergic rhinitis.

Methods

This study involved 30 Sprague–Dawley rats, and allergic rhinitis model was established with induction of ovalbumin. Rats were randomized into five groups. The first represented the control group, in which no allergy was established. The second represented the allergy group, in which allergy was induced but no treatment was given. In the remaining three groups, following induction of allergy, desloratadine at a dose of 10 mg/kg was given to Group 3, 100 mg/kg dose of berberine to Group 4, and 20 mg/kg dose of CoQ10 to Group 5. Nasal symptom scores, and plasma immunoglobulin-E, interleukin (IL)-4, IL-13, malondialdehyde (MDA) and nitric oxide (NO) levels were examined at the end of the study. Rats' nasal tissues were also subjected to histopathological immunohistochemical examination.

Results

Nasal symptom scores, and plasma immunoglobulin-E, IL-4, IL-13, MDA and NO levels increased significantly in rats with induced allergic rhinitis. Berberine and CoQ10 significantly reduced these elevated levels. CoQ10 was also found as effective as desloratadin in terms of nasal symptom scores and biochemical parameters. At histopathological examination, severe allergic inflammation was observed in rats from allergic rhinitis group. At all treatment groups, the histopathological changes were significantly improved and only a mild inflammation was determined. Also, immunochemistry showed a significant improvement in all three treatment groups. Coenzyme Q10 and berberine were both effective in suppressing allergy symptoms.

Conclusion

We think that berberine and coenzyme Q10 can usefully be employed as therapy due to their antioxidant and anti-inflammatory effects in an experimentally induced allergic rhinitis model.

https://ift.tt/2NfaL1X

Electroglottography in the diagnosis of functional dysphonia

Abstract

Introduction

Electroglottography (EGG) is the most commonly used method of indirect visual examination of vocal fold vibration.

Aim

The study was conducted with an aim of assessing EGG quasi open quotient (QOQ_EGG) in different functional dysphonias to develop a differential diagnosis. The second aim was to check the influence of articulation on QOQ_EGG values.

Material and methods

There were 20 people without voice problems, 20 patients with hypofunctional dysphonia and 20 patients with hyperfunctional dysphonia included in the study. Electroglottography was recorded during comfortable sustained phonation of [a], [e], [i], [o], [u].

Results

There were no statistically significant differences in QOQ_EGG observed during phonation of different vowels in the control group and patients with hyperfunctional dysphonia. In patients with hypofunctional dysphonia, significantly higher values of QOQ_EGG were observed during [a] and [e]. Both in the control and in studied groups vowel [i] was vocalized significantly quieter.

Conclusions

To conclude, EGG can be useful in differential diagnosis of functional dysphonia. QOQ_EGG is a parameter differentiating hypofunctional dysphonia from hyperfunctional dysphonia. Dissimilarities in articulation of different vowels in patients with various types of dysphonia influence values of QOQ_EGG. EGG study protocol in cases of functional dysphonia should include a comparison of [a], [e], [i] vowels.

https://ift.tt/2LV4wfj

Increased incidence of Warthin tumours of the parotid gland: a 42-year evaluation

Abstract

Aim

To evaluate the frequency of Warthin tumours among parotid neoplasms over the past 42 years in a population in rural Germany and to identify potential risk factors.

Methods

We conducted a retrospective case note evaluation from all patients who underwent parotid surgery between 1975 and 2017. The 42-year time period was evenly split into four quartiles.

Results

A Warthin tumour was diagnosed in 265 out of 806 patients (32.9%). The frequency of Warthin tumour increased steadily from 20.6% in the first decade between 1975 and 1986 to 44.9% in the fourth decade between 2008 and 2017. The age of the patients decreased from 68 years in the first to 62 years in the fourth decade. The male-to-female ratio in Warthin tumour was reduced from 1:5.3 in the first to 1:2.1 in the fourth decade.

Conclusion

A Warthin tumour was the most common histological tumour type in the period from 1997 to 2017. We also found a high incidence of multiple tumours, a growing incidence in women and a decreasing age of patients. We propose a re-evaluation of the existing view of the epidemiology of benign parotid tumours, which proposes that pleomorphic adenoma is the most common benign parotid tumour.

https://ift.tt/2NhpPMC

The impact of rehabilitation on quality of life after hearing loss: a systematic review

Abstract

Purpose

Hearing loss is a major health problem and is associated with several negative outcomes such as difficulties in communicating and poor quality of life. The aim of this study was to conduct a systematic literature review to evaluate the impact of different types of hearing rehabilitation after hearing loss and their impact on quality of life.

Methods

A systematic literature search was conducted on Pubmed which retrieved 549 articles. Of these, 29 articles regarding cochlear implants, bone anchored hearing devices and traditional amplification hearing aids have been systematically reviewed. The search was limited to articles published from 1960/01/01 to 2017/05/22, included human participants and available in English.

Results

The main finding was that hearing rehabilitation is beneficial in all types of hearing loss and treatment regarding quality of life. However, bone-anchored hearing devices and cochlear implants were shown to produce greater improvements in terms of quality of life than conventional hearing aids.

Conclusion

From these findings, we concluded that hearing rehabilitation does have a positive impact on quality of life after hearing loss.

https://ift.tt/2LV4mVf

Gaviscon® Advance alone versus co-prescription of Gaviscon® Advance and proton pump inhibitors in the treatment of laryngopharyngeal reflux

Abstract

Objectives

Management of laryngopharyngeal reflux (LPR) typically comprises alginates and proton pump inhibitors (PPIs) alone or in combination, yet evidence to support any particular treatment regimen is lacking. We sought to evaluate the efficacy of Gaviscon® Advance alone versus co-prescription with a PPI in treating LPR.

Methods

One hundred consecutive LPR patients with a reflux symptom index (RSI) score > 10 attending our joint voice clinic (JVC) were studied prospectively. All were treated with Gaviscon® Advance four times daily. If patients had been started on a PPI prior to their JVC attendance, this was optimised to a twice-daily dosing regimen and continued. RSI scores were recorded at first attendance and 3 months post-treatment via postal questionnaire. Scores were analysed using t tests and Levene's test for equality of variances.

Results

Follow-up RSI scores were returned by 72 patients, 39 of whom were treated with Gaviscon® Advance only (group A) and 33 with Gaviscon® Advance + PPI (group B). Mean pre-treatment RSI scores were similar between groups [group A: 19.2, 95% confidence interval (CI) ± 2.4; group B: 21.3, 95% CI ± 3.2 (p = 0.65)]. No significant differences were observed with respect to 3-month post-treatment RSI scores [group A: 9.9, 95% CI ± 2.8; group B: 12.6, 95% CI ± 4.2 (p = 0.82)] and change in RSI scores [group A: 9.3, 95% CI ± 3.0; group B: 8.7, 95% CI ± 2.9 [p = 0.75]).

Conclusions

Gaviscon® Advance alone is effective in treating symptoms of LPR, while co-prescription with a high-dose PPI offers no additional benefit.

https://ift.tt/2NeYECk

Expression and functional characterization of collection-K1 from Nile tilapia (Oreochromis niloticus) in host innate immune defense

Publication date: November 2018

Source: Molecular Immunology, Volume 103

Author(s): Liangliang Mu, Xiaoxue Yin, Xia Bian, Liting Wu, Yanjian Yang, Xiufang Wei, Zheng Guo, Jianmin Ye

Abstract

Collectin-K1 (CL-K1), a multifunctional Ca²⁺-dependent lectin, is able to bind carbohydrates on pathogens and inhibit infection by direct neutralization, agglutination, opsonization and killing, which plays an important role in innate immunity. In this study, a CL-K1 homolog (OnCL-K1) was identified from Nile tilapia (Oreochromis niloticus) and characterized at expression and agglutination functional levels. The open reading frame of OnCL-K1 is 720 bp of nucleotide sequence encoding a polypeptide of 239 amino acids. The deduced amino acid sequence has two characteristic structures, containing a collagen-like region and a carbohydrate recognition domain. Expression analysis revealed that the OnCL-K1 was highly expressed in the liver, and widely exhibited in other tissues including kidney, intestine and spleen. In addition, the OnCL-K1 expression was significantly up-regulated in spleen and anterior kidney following challenges with a Gram-positive bacterial pathogen (Streptococcus agalactiae) and a Gram-negative bacterial pathogen (Aeromonas hydrophila). The up-regulation of OnCL-K1 expression was also demonstrated in hepatocytes and monocytes/macrophages in vitro stimulation with S. agalactiae and A. hydrophila. Recombinant OnCL-K1 protein was able to agglutinate both S. agalactiae and A. hydrophila in vitro, and participate in the regulation of inflammatory, migration reaction and promote the phagocytosis by monocytes/macrophages. Taken together, the results of this study indicated that OnCL-K1, possessing apparent agglutination, opsonization and killing ability to bacterial pathogens and participating in the regulation mechanisms of the non-specific cellular immune, might be involved in host defense of innate immunity against bacterial infection in Nile tilapia.

https://ift.tt/2Cd9AvG

Effect of a dairy diet on nasopharyngeal mucus secretion

The Laryngoscope, EarlyView.


https://ift.tt/2CgBjf5

Up-regulated lipocalin-2 in pediatric thyroid cancer correlated with poor clinical characteristics

Abstract

Background

The incidence of thyroid cancer is fast increasing in both adults and children. The pediatric thyroid cancer had often already progressed to a more advanced stage of the disease at diagnosis. Early detection of pediatric thyroid cancer has been a problem for many years. Lipocalin-2 (Lcn2) has been reported to be over-expressed in cancers of diverse histological origin and it facilitates tumorigenesis by promoting survival, growth, and metastasis.

Methods

The plasma Lcn2 concentration of 28 Chinese papillary thyroid cancer (PTC) children and 24 healthy controls was measured. Immunostaining for Ki-67 of tumor tissue from PTC children was performed. The expression levels of Lcn2 and NFκB in PTC tissue and peri-carcinoma tissue of PTC children were measured through Western blot.

Results

The plasma concentration of Lcn2 was significantly elevated in pediatric PTC patients compared with healthy controls. Besides, the plasma Lcn2 concentration significantly correlated with clinical characteristics, NFκB level, and Ki-67 positive rate of nucleus in tissue of PTC.

Conclusion

This is the first study to evaluate the plasma Lcn2 in pediatric PTC patients. It is possible that the plasma Lcn2 may be a new biomarker of pediatric thyroid cancer. Further studies are needed to explore the definite role and mechanism of Lcn2 in thyroid cancer, which will help to explore novel diagnostic or therapeutic strategies.

https://ift.tt/2Q4xDQi

Treatment of Atopic Dermatitis with Biologic Drugs

Abstract

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease which predominately affects children and usually clears up during infancy or childhood. However, AD may persist with a chronic relapsing course until adulthood or develop at a later age. AD treatment can often be complicated. Treating moderate-to-severe AD can be challenging: only a few therapeutic options are available, with cyclosporine being the only approved and labeled systemic drug. In the last few years, advances in the knowledge of AD pathogenesis have been made that can provide the basis for developing new topical and systemic drugs. Among them, biologic drugs targeting specific cytokines involved in the development of the disease will probably revolutionize AD therapy. Currently, dupilumab, a monoclonal antibody that binds to the shared alpha chain subunit of the receptors for IL-4 and IL-13, is the only biologic drug licensed for the treatment of AD in adults. However, other biologic drugs that selectively target some key cytokines in AD pathogenesis (IL-13, IL-31, and IL-22) are also being studied. In this review, we discuss all of the biologic drugs that have been studied for AD treatment.

https://ift.tt/2oENSra

Erythropoietin (rhEPOa) promotes endothelial transdifferentiation of stem cells of the apical papilla (SCAP)

Publication date: Available online 3 September 2018

Source: Archives of Oral Biology

Author(s): Anastasios Koutsoumparis, Angelina Vassili, Athina Bakopoulou, Argyro Ziouta, Asterios S. Tsiftsoglou

Abstract

Objective

Mesenchymal stem cells (MSCs) have attracted worldwide attention for their capacity to repair damaged tissue, immunosuppression, ability to differentiate into several cell types and their secretome. Earlier studies have demonstrated their angiogenic potential in vitro and in vivo. However, little is known regarding pro-angiogenic inducers of stable endothelial transdifferentiation of MSCs. Here, we employed human MSCs from the Apical Papilla (SCAP) and investigated whether recombinant human erythropoietin-alpha (rhEPOa) could act as such inducer.

Design

Cultured SCAP cells were exposed to rhEPOa and assessed for cell growth kinetics, viability and morphology, as well as their capacity to form capillary tubule structures in selected microenvironments. RT-PCR was used to monitor endothelial markers and activation of EPO/EPOR pathway signaling components; while gelatin zymographies to assess activation of MMP-2.

Results

rhEPOa treatment initially (48 h) accelerated cell proliferation and allowed SCAP to sprout micro-tubular structures. Morphological and biochemical differentiation was accompanied by activation of MMP-2 and upregulation of PECAM-1, VEGFR2, vWF and VE-cadherin/CDH5. SCAP expressed the cognate EPO-R, while rhEPOa-treated SCAP exhibited higher expression of molecules involved in EPO/EPOR pathway (EPOR and JAK2).

Conclusion

rhEPOa is capable of promoting endothelial transdifferentiation of SCAP which may be of clinical value in treating of ischemic disorders.

Graphical abstract

https://ift.tt/2NJgoCE