Surgery- vs Radiation-Based Therapy for p16+/HPV-Related Oropharyngeal Cancers

Abstract

Purpose of Review

Oropharyngeal cancer (OPC) has traditionally been managed by radiotherapy (RT)-based approaches. Minimally invasive surgery [transoral robotic surgery (TORS)/transoral laser microsurgery (TLMS)] is gaining popularity in T1-T2 HPV+ OPC. However, there is lack of high level evidence to guide practice. We summarize ongoing research regarding outcomes and investigational strategies for TORS/TLM- and RT-based treatments for this disease.

Recent Findings

Literature published in 2012–2017 demonstrated comparable exemplary outcomes with TORS/TLM and IMRT for selected HPV+ T1-T2 OPC. However, many TORS/TLM-treated patients also require adjuvant treatment, which impacts quality of life. Emerging RT-based de-intensification trial data suggest promising results. Ongoing investigation include indications for postoperative (chemo-)radiotherapy following TORS/TLM- and optimal RT-based de-intensification strategies.

Summary

A contemporary literature review demonstrates equal efficacy for TORS/TLM and IMRT as primary treatment for selected HPV+ T1-T2 OPC. TORS/TLM is an attractive approach when the opportunity for single modality treatment is high.

https://ift.tt/2A4MOFz

Relations between epidermal barrier dysregulation and staphylococci-dominated microbiome dysbiosis in atopic dermatitis

Publication date: Available online 24 July 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Can Altunbulakli, Matthias Reiger, Avidan U. Neumann, Natalie Garzorz-Stark, Megan Fleming, Claudia Huelpuesch, Francesc Castro-Giner, Kilian Eyerich, Cezmi A. Akdis, Claudia Traidl-Hoffmann

https://ift.tt/2LhZ4Yu

Biological profile and jaw distribution of ameloblastoma among 1,246 Nigerians

Publication date: Available online 24 July 2018

Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

Author(s): Agbaje Jimoh. Olubanwo, Adisa Akinyele. Olumuyiwa, Petrova Mariya Ivanova, Olusanya Adeola. Adenike, Osayomi Tolulope, Effiom Olajumoke. Ajibola, Soyele Olujide. Oladele, Omitola Olufemi. Gbenga, Olawuyi Adetokunbo. Babajide, Okiti Robinson. Obos, Saiki Thelma. Eziafa, Fomete Benjamin, Ibikunle Adebayo. Aremu, Okwuosa Chuckwubuzor, Olajide Mofoluwaso. Abimbola, Ladeji Adeola. Mofoluwake, Adebiyi Kehinde. Emmanuel, Emmanuel Mubarak. Mobola, Lawal Hammed. Sikiru, Uwadia Emeke

Abstract

Objectives

Ameloblastoma is a benign, slow-growing, locally invasive epithelial tumor of odontogenic origin with unlimited growth capacity and a strong tendency to recur. This multicentric study analyzed ameloblastoma diagnosed in Nigeria among different ethnic groups.

Materials and methods

This retrospective study included ameloblastoma cases diagnosed from 1964 to 2017 at 10 hospitals/medical centers in Nigeria. Age, gender, tribe, and location of the ameloblastoma in the jaw were analyzed. Associations between variables were tested using chi-squared and Fisher exact test.

Results

A total of 1,246 ameloblastoma cases were recorded (mean patient age 32.51±14.54 years, range 4-86 years; male to female ratio 1.2:1). Approximately 60% of ameloblastoma cases occurred in young adults (18-40 years old). Ninety-eight lesions were located in the maxilla and 1103 in the mandible; the posterior mandible was the most common site (31.3% on the right and 26.5% on the left, respectively), followed by the anterior (26.0%) mandible. No significant differences were noted in the distribution of ameloblastoma within the tribes with respect to age (p = 0.92) and gender (p = 0.71).

Conclusion

The mandible is a common site of ameloblastoma in Nigeria, and most cases occur in young adults. Early presentation, diagnosis, and treatment are important to reduce post-operative disfigurement and morbidity.

https://ift.tt/2Lj7fUm

Temporomandibular joint involvement in children with juvenile idiopathic arthritis – Preliminary Report

Publication date: Available online 24 July 2018

Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

Author(s): Shelly Abramowicz, Joshua M. Levy, Sampath Prahalad, Curtis D. Travers, Sheila T. Angeles-Han

ABSTRACT

Background

Children with juvenile idiopathic arthritis (JIA) are at risk for temporomandibular joint (TMJ) arthritis. This can lead to pain, limited mouth opening, facial asymmetry, and malocclusion. Our objective was to characterize patients with JIA and TMJ involvement in a single center.

Methods

This was a retrospective study of children with JIA evaluated at Children's Healthcare of Atlanta. Inclusion criteria were confirmed JIA and jaw complaints. Medical records were reviewed to document demographics, JIA information, age at first TMJ complaint, and involvement of other joints. Descriptive statistics were computed.

Results

Majority of patients were white (mean age 13 years, range 5-18) with polyarticular RF negative or oligoarticular persistent JIA. Some were ANA positive, RF positive, and/or HLA-B27 positive. Patients had involvement of other joints (e.g. fingers, knees, wrists). Of those with TMJ symptoms, 6 (10%) had TMJ arthritis.

Conclusions

In our cohort, 60 patients only 10% of patients were diagnosed with TMJ arthritis. In this population, patients who are female, white, RF negative, HLA-B27 negative, ANA negative, poly RF negative subtype, and have involvement of other joints have a higher likelihood of having TMJ symptoms. If a patient meets these criteria, careful evaluation of TMJs should take place.

https://ift.tt/2LLNAZc

Investigation of the mtDNA mutations in Syrian Families With Non-Syndromic Sensorineural Hearing Loss

Publication date: Available online 24 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Faten Moassass, Bassel AL-Halabi, Mohamad Sayah Nweder, Walid AL-Achkar

Abstract

Objective

Hearing loss is a common sensory disorder, and at least 50% of cases are due to a genetic etiology. Several mitochondrial DNA mutations (mtDNA) have been reported to be associated with nonsyndromic hearing loss (NSHL) in different population. However, There is no previous available data about the frequency of mtDNA mutations as etiology for deafness in Syrian. The aim of present study is to investigate the incidence of common mt DNA mutations in our families with congenital hearing loss and not related to the ototoxicity or aminoglycosides.

Methods

A total of 50 deaf families were enrolled in the present study. Direct sequencing and PCR-RFLP methods were employed to detect seven mt DNA mutations, including A1555G, A3243G, C1494T, G3316A, T7510C, A7445G, and 7472insC.

Results

Our results revealed a high prevalence of mt DNA mutation (10%) in deaf families (5/50). In surprising, the unexpected mutations were observed. The G3316A mutation was found in 2 families as homoplasmic genotype. Also, we found the homoplasmic and heteroplasmic genotype for the C1494T mutation in two families. in one family the heteroplasmic genotype for T7510C mutation was observed; this family harbor 35delG mutation in GJB2 gene. None of the common mtDNA mutations (A1555G, A3243G,) and other mutations (A7445G, 7472insC) were detected here.

Conclusion

Our findings indicate to significant contribution of the mt DNA mutations in our families with NSHL. The presented data is the first report about mt DNA and it will improve the genetic counseling of hearing impaired in Syrian families.

https://ift.tt/2mCCPxx

In utero drug exposure and hearing impairment in 2-year-old children A case-control study using the EFEMERIS database

Publication date: Available online 24 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Caroline Foch, Mélanie Araujo, Alexandra Weckel, Christine Damase-Michel, Jean-Louis Montastruc, Justine Benevent, Geneviève Durrieu, Isabelle Lacroix

https://ift.tt/2uUD36S

Association of Plasma Pentraxin-3 Levels with Retinopathy and Systemic Factors in Diabetic Patients

Metabolic Syndrome and Related Disorders, Ahead of Print.


https://ift.tt/2LvSU6g

Decreasing Disease-Specific Mortality of Differentiated Thyroid Cancer in Korea: A Multicenter Cohort Study

Thyroid, Ahead of Print.


https://ift.tt/2v0S3QH

Cardiovascular Morbidity and Mortality After Treatment of Hyperthyroidism with Either Radioactive Iodine or Thyroidectomy

Thyroid, Ahead of Print.


https://ift.tt/2LwzFJK

Comparison between patient specific implants and conventional mini-plates in Le Fort I osteotomy with regard to infections: No differences in up to 3-year follow-up

Publication date: Available online 23 July 2018

Source: Journal of Cranio-Maxillofacial Surgery

Author(s): Juho Suojanen, Sanna Järvinen, Karoliina Kotaniemi, Justus Reunanen, Tuula Palotie, Patricia Stoor, Junnu Leikola

Summary

Individually designed osteotomies and milled or printed patient-specific osteosynthesis materials are rapidly becoming a standard in maxillofacial reconstructive surgery. The benefits of using patient-specific implants (PSIs) in orthognathic surgery are especially clear in complex cases, and for this reason they are rapidly becoming common practice. We have earlier reported the benefits related to the use of PSIs as reposition and fixation system in Le Fort I osteotomy. The aim of this study was to compare complications associated with fixation with PSIs (31 patients) versus conventional mini-plates (37 patients) in Le Fort I osteotomy. No statistically significant differences in infection, reoperations or soft tissue problems were observed between the two systems used. Interestingly, three of the 37 patients in the mini-plate group underwent reoperation due to insufficient advancement or malocclusion, whereas none of the patients in the PSI group needed reoperation. In conclusion, PSIs are reliable for use in orthognathic surgery, with no signs of infection associated complications.

https://ift.tt/2uY10Kt

Pseudohyperkalemia: Hyperkalemia Cocktail or Alternative Diagnosis

Introduction. Hyperkalemia is a commonly encountered clinical problem. Pseudohyperkalemia is believed to be an in vitro phenomenon that does not reflect in vivo serum potassium and therefore should not be treated. Here, we present a case who unfortunately underwent unnecessary treatment because of failure to detect the common lab abnormality of pseudohyperkalemia. Case Presentation. A 91-year-old female with a history of chronic lymphocytic leukemia presented to the emergency with nausea and vomiting 24 hours after her first chemotherapy with chlorambucil. Physical examination was overall unremarkable. She had a leukocytosis of 210 × 103/µL with 96% lymphocytes along with chronic anemia with hemoglobin of 8.1 g/dL. Her initial sodium and potassium levels were normal. During the clinical course, her potassium progressively worsened and failed to improve despite standard medical treatment. Patient ultimately underwent dialysis. Conclusions. Differentiating true hyperkalemia from pseudohyperkalemia is very important in selected group of patients to avoid unnecessary medications, higher level of care, and unnecessary procedure including dialysis. We want to emphasize the importance of simple yet profound knowledge of technique of blood draws and basic metabolic panel processing for every clinician in day-to-day practice.

https://ift.tt/2Oe5RA3

Cardiac Involvement by HIV-Associated DLBCL

Non-Hodgkin's lymphoma (NHL) is a common AIDS-defining malignancy among people living with HIV. Of the different types of NHLs, diffuse large B-cell lymphoma (DLBCL) is the most common. Prognosis of DLBCL has improved over the years in the general population but remains relatively poor in HIV-positive individuals. Almost any organ system can be affected by DLBCL; however, cardiac involvement remains rare and suggests aggressive disease. We present a case of DLBCL in an HIV-positive patient, who had cardiac involvement, with the only clue to cardiac involvement being symptom being tachycardia and dysphagia.

https://ift.tt/2NBaT8C

Störungen des Kalziumhaushalts

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 516-528
DOI: 10.1055/s-0043-121655

Störungen des Kalziumhaushalts sind weit verbreitet. Ihre pathophysiologischen Ursachen sind sehr heterogen und die klinischen Symptome häufig unspezifisch. Daher ist eine genaue Diagnostik unerlässlich und ein schneller Ausgleich der Kalziumhomöostase essenziell. Dieser Artikel erörtert die pathophysiologischen, diagnostischen und therapeutischen Pfeiler von Hypo- und Hyperkalzämie sowie ihre Auswirkungen auf Anästhesie und Intensivmedizin.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2LvGY4s

Videolaryngoskopie – Ende der Fiberoptik beim erwartet schwierigen Atemweg?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 487-488
DOI: 10.1055/a-0643-3504

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2v09YqC

Störungen des Natriumhaushalts

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 492-502
DOI: 10.1055/s-0043-121662

Störungen des Natriumhaushalts sind häufig auftretende Elektrolytimbalancen. Sowohl sie selbst als auch ihre unsachgemäße Therapie können schwerwiegende Komplikationen nach sich ziehen. Der vorliegende Artikel informiert über die Ätiologie von Störungen des Natriumhaushalts und stellt wichtige therapeutische Prinzipien dar.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2LvGg7i

Vollelektrolyt- versus NaCl-Lösung in der Therapie kritisch kranker Erwachsener

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 488-488
DOI: 10.1055/a-0643-3479

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2v09TTQ

Orale Antikoagulanzien: Management von elektiven und Notfalleingriffen

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 543-550
DOI: 10.1055/s-0043-111006

Orale Antikoagulation bei chirurgischen Patienten erfolgt meistens mit Vitamin-K-Antagonisten (VKA) oder nicht-Vitamin-K-antagonistischen oralen Antikoagulanzien (NOAK). Während VKA wegen ihrer langen Halbwertszeit über die INR gesteuert werden, ist bei NOAK in der Regel keine Gerinnungskontrolle notwendig. Die Gabe erfolgt in festen Dosierungen. Spezifische Gerinnungswerte zur Bestimmung der Wirkung von NOAK können über die Anti-Faktor-Xa(FXa)-Aktivität (für FXa-Inhibitoren: Apixaban, Edoxaban, Rivaroxaban) und die verdünnte Thrombinzeit (für Dabigatran) erfolgen. Es gibt aktuell keine validierten Grenzwerte, die mit einem erhöhten Risiko für perioperative Blutungen einhergehen. Während VKA perioperativ auf eine parenterale Antikoagulation (z. B. niedermolekulares Heparin) umgestellt werden („Bridging"), werden NOAK pausiert. Ebenso ist nach ausreichendem Sicherheitsabstand die Durchführung von rückenmarksnahen Regionalanästhesieverfahren möglich. Falls erforderlich können NOAK auch auf ein parenterales Verfahren umgestellt werden („Switching"). Lebensbedrohliche Blutungskomplikationen können sowohl unter VKA als auch unter NOAK mit Prothrombinkomplex (PPSB) behandelt werden. Für Dabigatran steht ein Antidot zur Verfügung.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2LvGewc

Glukokortikoid-Therapie im septischen Schock – ja oder nein?

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 489-489
DOI: 10.1055/a-0643-3451

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2v09Pn4

Störungen des Kaliumhaushalts

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 504-514
DOI: 10.1055/s-0043-121654

Störungen des Kaliumhaushalts sind perioperativ und beim Intensivpatienten häufig anzutreffen – sie können sich schnell zu einer akuten Lebensbedrohung entwickeln. Dieser Beitrag geht auf die physiologischen Grundlagen des Kaliumhaushalts ein und zeigt auf, wie akute Störungen behandelt werden können.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2LzcQVU

Elektrolytstörungen

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 490-491
DOI: 10.1055/a-0631-0160

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2uWbgDd

Neue Antibiotika für die Therapie von multiresistenten gramnegativen Bakterien

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 529-542
DOI: 10.1055/s-0043-110504

Die stetige Zunahme an bakteriellen Resistenzen und von multiresistenten Erregern (MRE) – vor allem im gramnegativen Bereich – ist ein weltweites Problem. Die Entwicklung neuer Wirkstoffe gegen Infektionen mit multiresistenten gramnegativen Erregern (MRGN) besitzt daher höchste Priorität. Im Folgenden werden kürzlich zugelassene oder in der fortgeschrittenen klinischen Prüfung befindliche Antibiotika mit Wirksamkeit gegen MRGN vorgestellt.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2LwYPrC

Versorgung von Traumapatienten mit dem „REBEL“-Set

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 551-558
DOI: 10.1055/s-0044-102122

Die zunehmende Terrorbedrohung und ein verändertes Einsatzspektrum für den Rettungsdienst erfordern eine Anpassung und Erweiterung von Notfallrettungsmitteln und Einsatztaktik. Ein Beispiel hierfür ist die bayerische „Handlungsempfehlung für Rettungsdienst bei besonderen Einsatzlagen (REBEL)". Es werden 3 Fälle vorgestellt, bei denen „neue Hilfsmittel" wie Hämostyptika, Thoraxverschlusspflaster und Tourniquet aus dem REBEL-Set bei Rettungsdiensteinsätzen angewandt wurden.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2v0On1p

Gefährliche Patientenübergaben!

Anästhesiol Intensivmed Notfallmed Schmerzther 2018; 53: 486-487
DOI: 10.1055/a-0643-3517

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2LsXpyx

FcεRI cross-linking and IL-3 protect human basophils from intrinsic apoptotic stress

Publication date: Available online 23 July 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Lionel Rohner, Ramona Reinhart, Björn Hagmann, Andrea Odermatt, Annet Babirye, Thomas Kaufmann, Michaela Fux

https://ift.tt/2JTZa2Y

Autologous dermis-fat grafts in head and neck patients: Indications and evaluation in reconstructive surgery

The aim of this study was to examine the indications and results of autologous dermis-fat grafts in the reconstruction of maxillofacial soft-tissue defects.

https://ift.tt/2v0l9zF

Comparison between patient specific implants and conventional mini-plates in Le Fort I osteotomy with regard to infections: No differences in up to 3-year follow-up

Individually designed osteotomies and milled or printed patient-specific osteosynthesis materials are rapidly becoming a standard in maxillofacial reconstructive surgery. The benefits of using patient-specific implants (PSIs) in orthognathic surgery are especially clear in complex cases, and for this reason they are rapidly becoming common practice. We have earlier reported the benefits related to the use of PSIs as reposition and fixation system in Le Fort I osteotomy. The aim of this study was to compare complications associated with fixation with PSIs (31 patients) versus conventional mini-plates (37 patients) in Le Fort I osteotomy.

https://ift.tt/2uYfYAk

Fractures of the mandibular condyle: A comparison of patients, fractures and treatment characteristics between Groningen (The Netherlands) and Dresden (Germany)

To explore differences in patient, fracture, accident and treatment characteristics between patients treated for a mandibular condyle fracture in the University Centres of Dresden and Groningen, as an explanation for differences treatment results.

https://ift.tt/2Lu3zhD

Hypoxia disrupts aryl hydrocarbon receptor signaling and the Th17 response in allergic rhinitis patients

Publication date: September 2018

Source: Molecular Immunology, Volume 101

Author(s): Wei Kou, Xuelei Li, Hongbing Yao, Cheng Zhang, Ping Wei

Abstract

Background

Hypoxic conditions area key feature of allergic rhinitis (AR), however, the role of hypoxia in AR remains to be fully understood. The aim of this study was to survey the effect of hypoxia on the Th17 response in AR patients by investigating the action of hypoxia-influenced signaling pathways on Th17 differentiation.

Methods

23 AR patients and 15 healthy controls were recruited for this study. Under normoxia and hypoxic conditions, the expression of HIF-1α, AhR, CYP1A1 and CYP1B1 and the presence of Th17 cells in CD4⁺T cells were measured. Furthermore, the amount of ARNT combined with either HIF-1α or AhR was determined after the exposure of 2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl easter (ITE) with normoxia and hypoxia.

Results

HIF-1α and AhR expression were higher in CD4⁺T cells from AR patients than in those from healthy controls. In a hypoxic environment, the expression of HIF-1α was elevated in CD4⁺T cells of both AR patients and healthy controls. Meanwhile, the suppressive effects of a non-toxic AhR ligand (ITE) on the Th17 response and its positive effects on IL-10 production were suppressed in the cells of AR patients and healthy controls under hypoxia. These effects were arisen from HIF-1α out-competing AhR for ARNT binding which limited the activity of the AhR pathway.

Conclusions

The present results suggest that hypoxia is capable of promoting the Th17 response by reducing AhR activity via HIF-1α activity. Thus hypoxia may be intimately involved in the pathogenesis of AR.

https://ift.tt/2v0Ezo7

Nail photography tricks for pediatric and geriatric patients

https://ift.tt/2NECRjI

Methods for Decreasing the Incidence of Moist Desquamation in Patients Undergoing Radiotherapy

https://ift.tt/2OcKDTe

Lightening Becker’s Nevus with Topical Glycolic Acid

https://ift.tt/2NEj8ko

Sirolimus for treatment of verrucous venous malformation: A retrospective cohort study

https://ift.tt/2O6kgOR

Small oral tongue cancers (≤ 4 cm in diameter) with clinically negative neck: from the 7th to the 8th edition of the American Joint Committee on Cancer

Abstract

One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (≤ 4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12–4.99) and disease-free survival (HR 2.12, 95% CI 1.09–4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27–7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.

https://ift.tt/2mDOVGN

Simple and secure intra-articular infiltration during arthroscopy of the temporomandibular joint

Arthroscopy is commonly used to treat various anomalies of the temporomandibular joint (TMJ) such as internal derangements, osteoarthrosis, osteoarthritis, and chronic luxation of the jaw.1 It has been improved during the last decades, and operative arthroscopy includes biopsy, discopexy, synovectomy, and coagulation of tissues.2 Recently, some substances have had exceptional benefits when infiltrated inside the joint, including hyaluronic acid, platelet-rich plasma and growth factors, and steroids.

https://ift.tt/2NE9TR5

Is the removal of osteosynthesis plates after orthognathic surgery necessary? Retrospective long-term follow-up study

The removal of titanium miniplates is a controversial topic in oral and maxillofacial surgery. This retrospective study examined the timing of and reasons for titanium plate removal after orthognathic surgery. The study included 240 orthognathic surgery patients (71 male, 169 female; age range 16–55 years, mean 25.0±8.8 years) who had maxillofacial osteosynthesis plates inserted or inserted and then removed at the Division of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital, between April 2003 and March 2017.

https://ift.tt/2Lh3Xkz

Is there a correlation between arthroscopic findings and the clinical signs and symptoms of patients with internal derangement of the temporomandibular joint? A prospective study

The aim of this study was to evaluate the correlation between clinical signs and symptoms of patients with internal derangement of the temporomandibular joint (TMJ) and arthroscopic findings. The study included a sample of 67 patients who underwent TMJ arthroscopy. The variables evaluated were the arthroscopic findings of synovitis, chondromalacia, adhesion, and roofing. The Spearman correlation index was used to correlate these findings with the clinical signs and symptoms of internal derangement of the TMJ, namely maximum mouth opening, pain (visual analogue scale, VAS), and the Wilkes classification.

https://ift.tt/2JNKIZW

Neck stiffness in a post-irradiated nasopharyngeal carcinoma adult: An unusual diagnosis

Nasopharyngeal carcinoma is a neoplasm commonly found in population of South East Asia. The mainstay of treatment is high dose irradiation. Complications from radiotherapy are not uncommon especially to those nearby structures such as vertebrae and spinal cord. A 57 year-old gentleman with nasopharyngeal carcinoma (NPC) who was treated with chemo-radiation (total of 35 fractions,70Gy) presented to us 6 months post therapy with bilateral nasal discharge and progressive neck stiffness. Nasoendoscopy showed inflamed nasophayngeal mucosa and Computed Tomography (CT) brain and cervical spine showed retropharyngeal and anterior epidural collection with extension into atlantoaxial bone and spinal cord compression.

https://ift.tt/2JNIjyo

Collagen VI Contains Multiple Host Defense Peptides with Potent In Vivo Activity [INNATE IMMUNITY AND INFLAMMATION]

Collagen VI is a ubiquitous extracellular matrix component that forms extensive microfibrillar networks in most connective tissues. In this study, we describe for the first time, to our knowledge, that the collagen VI von Willebrand factor type A–like domains exhibit a broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria in human skin infections in vivo. In silico sequence and structural analysis of VWA domains revealed that they contain cationic and amphipathic peptide sequence motifs, which might explain the antimicrobial nature of collagen VI. In vitro and in vivo studies show that these peptides exhibited significant antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa through membrane disruption. Our findings shed new light on the role of collagen VI–derived peptides in innate host defense and provide templates for development of peptide-based antibacterial therapies.

https://ift.tt/2mBX4vd

Leishmania donovani Exploits Tollip, a Multitasking Protein, To Impair TLR/IL-1R Signaling for Its Survival in the Host [INFECTIOUS DISEASE AND HOST RESPONSE]

IL-1R/TLR signaling plays a significant role in sensing harmful foreign pathogens and mounting effective innate and adaptive immune responses. However, the precise mechanism by which Leishmania donovani, an obligate intramacrophagic pathogen, breaches IL-1R/TLR signaling and host-protective immunity remains obscure. In this study, we report the novel biphasic role of Toll-interacting protein (Tollip), a negative regulator of the IL-1R/TLR pathway, in the disease progression of experimental visceral leishmaniasis. We observed that during early hours of infection, L. donovani induced phosphorylation of IRAK-1, resulting in the release of Tollip from the IL-1R–associated kinase (IRAK)-1 complex in J774 macrophages, which then acted as an endocytic adaptor on cell surface IL-1R1 and promoted its lysosomal degradation. In the later stage, Tollip shuttled back to IRAK-1, thereby inhibiting IRAK-1 phosphorylation in association with IRAK-M to neutralize downstream TLR signaling in infected macrophages. Moreover, during late infection, L. donovani enhanced nuclear translocation and recruitment of transcription factors early growth response protein 2, NF erythroid 2–related factor 2, and Ahr on Tollip promoter for its induction. Small interfering RNA–mediated silencing of Tollip in infected macrophages significantly enhanced NF-B activation and induced host-defensive IL-12 and TNF-α synthesis, thereby reducing amastigote multiplication. Likewise, abrogation of Tollip in L. donovani–infected BALB/c mice resulted in STAT-1–, IRF-1–, and NF-B–mediated upregulation of host-protective cytokines and reduced organ parasite burden, thereby implicating its role in disease aggravation. Taken together, we conclude that L. donovani exploited the multitasking function of Tollip for its own establishment through downregulating IL-1R1/TLR signaling in macrophages.

https://ift.tt/2mBpp4J

From Cancer Immune Surveillance to Cancer Immunoediting: Birth of Modern Immuno-Oncology [PILLARS OF IMMUNOLOGY]

https://ift.tt/2mAVr0G

Widespread Effects of Chemokine 3' Untranslated Regions on mRNA Degradation and Protein Production in Human Cells [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

Chemokines are a large family of chemotactic cytokines that play critical roles in inflammation, development, and diseases. Chemokine expression is highly regulated during development and in response to environmental stimuli. The 3' untranslated regions (3'-UTRs) of mRNA are believed to be important in the control of chemokine gene expression. However, the regulatory effects of most chemokine 3'-UTRs have not been characterized previously. In this work, we systematically studied the effects of 43 CC and CXC chemokine 3'-UTRs on gene expression in eight human cell lines and two types of human primary cells. We found that chemokine 3'-UTRs had a wide spectrum of regulatory effects on mRNA abundance and protein production that were tightly correlated with the effects on mRNA stability. In general, 3'-UTRs had remarkably similar effects across all cell types studied. The presence of AU-rich elements, microRNA targets, and Pumilio binding sites were associated with chemokine 3'-UTR activity but did not fully account for all 3'-UTR activity detected using the reporter assay. Mutational analysis illustrated how specific cis-regulatory elements contributed to the regulatory effect of chemokine 3'-UTRs. These findings bring new insights into the mechanisms by which chemokine expression is regulated by 3'-UTRs.

https://ift.tt/2mCjBIk

Pillars Article: IFN{gamma} and Lymphocytes Prevent Primary Tumour Development and Shape Tumour Immunogenicity. Nature. 2001. 410: 1107-1111 [PILLARS OF IMMUNOLOGY]

https://ift.tt/2uXQm6E

Ebola Immunity: Gaining a Winning Position in Lightning Chess [BRIEF REVIEWS]

Zaire ebolavirus (EBOV), one of five species in the genus Ebolavirus, is the causative agent of the hemorrhagic fever disease epidemic that claimed more than 11,000 lives from 2014 to 2016 in West Africa. The combination of EBOV's ability to disseminate broadly and rapidly within the host and its high pathogenicity pose unique challenges to the human immune system postinfection. Potential transmission from apparently healthy EBOV survivors reported in the recent epidemic raises questions about EBOV persistence and immune surveillance mechanisms. Clinical, virological, and immunological data collected since the West Africa epidemic have greatly enhanced our knowledge of host–virus interactions. However, critical knowledge gaps remain in our understanding of what is necessary for an effective host immune response for protection against, or for clearance of, EBOV infection. This review provides an overview of immune responses against EBOV and discusses those associated with the success or failure to control EBOV infection.

https://ift.tt/2mEzYUW

Multiplexed Division Tracking Dyes for Proliferation-Based Clonal Lineage Tracing [NOVEL IMMUNOLOGICAL METHODS]

The generation of cellular heterogeneity is an essential feature of immune responses. Understanding the heritability and asymmetry of phenotypic changes throughout this process requires determination of clonal-level contributions to fate selection. Evaluating intraclonal and interclonal heterogeneity and the influence of distinct fate determinants in large numbers of cell lineages, however, is usually laborious, requiring familial tracing and fate mapping. In this study, we introduce a novel, accessible, high-throughput method for measuring familial fate changes with accompanying statistical tools for testing hypotheses. The method combines multiplexing of division tracking dyes with detection of phenotypic markers to reveal clonal lineage properties. We illustrate the method by studying in vitro–activated mouse CD8⁺ T cell cultures, reporting division and phenotypic changes at the level of families. This approach has broad utility as it is flexible and adaptable to many cell types and to modifications of in vitro, and potentially in vivo, fate monitoring systems.

https://ift.tt/2mDDXB7

Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism [CUTTING EDGE]

Recent studies suggest that autism is often associated with dysregulated immune responses and altered microbiota composition. This has led to growing speculation about potential roles for hyperactive immune responses and the microbiome in autism. Yet how microbiome–immune cross-talk contributes to neurodevelopmental disorders currently remains poorly understood. In this study, we report critical roles for prenatal microbiota composition in the development of behavioral abnormalities in a murine maternal immune activation (MIA) model of autism that is driven by the viral mimetic polyinosinic-polycytidylic acid. We show that preconception microbiota transplantation can transfer susceptibility to MIA-associated neurodevelopmental disease and that this is associated with modulation of the maternal immune response. Furthermore, we find that ablation of IL-17a signaling provides protection against the development of neurodevelopmental abnormalities in MIA offspring. Our findings suggest that microbiota landscape can influence MIA-induced neurodevelopmental disease pathogenesis and that this occurs as a result of microflora-associated calibration of gestational IL-17a responses.

https://ift.tt/2uXQcfy

Rhabdovirus-Inducible MicroRNA-210 Modulates Antiviral Innate Immune Response via Targeting STING/MITA in Fish [INFECTIOUS DISEASE AND HOST RESPONSE]

Viral infection induces type I IFN production, which plays critical roles in orchestrating the antiviral defense by inducing direct antiviral activities. To establish a persistent infection, viruses have evolved numerous strategies to specifically interfere with IFN production or its downstream mediators, thereby evading the immune responses. MicroRNAs (miRNAs) are a family of small noncoding RNAs that posttranscriptionally regulate the expressions of specific target genes. Although accumulating evidence demonstrates that miRNAs play vital roles in regulating viral infection, miRNAs that target intracellular sensors and adaptors of innate immunity have not been fully uncovered. In this paper, we identify fish miR-210 as a robust regulator involved in regulating virus–host interactions. We found that rhabdovirus significantly upregulated the expression of fish miR-210. Inducible miR-210 modulates virus-triggered type I IFN and inflammatory cytokine production by targeting stimulator of IFN genes (STING), thereby promoting viral replication. Furthermore, we demonstrated that miR-210 regulates innate immune response through NF-B, IFN regulatory factor 3, and JAK/STAT signaling pathways. The collective findings indicate that inducible miR-210 plays a regulatory role in virus–host interactions through STING-mediated singling pathway by targeting STING.

https://ift.tt/2mBpoxH

Repeated Allergen Exposure in A/J Mice Causes Steroid-Insensitive Asthma via a Defect in Glucocorticoid Receptor Bioavailability [ALLERGY AND OTHER HYPERSENSITIVITIES]

The importance of developing new animal models to assess the pathogenesis of glucocorticoid (GC)-insensitive asthma has been stressed. Because of the asthma-prone background of A/J mice, we hypothesized that asthma changes in these animals would be or become resistant to GCs under repeated exposures to an allergen. A/J mice were challenged with OVA for 2 or 4 consecutive d, starting on day 19 postsensitization. Oral dexamethasone or inhaled budesonide were given 1 h before challenge, and analyses were done 24 h after the last challenge. Airway hyperreactivity, leukocyte infiltration, tissue remodeling, and cytokine levels as well as phosphorylated GC receptor (p-GCR), p-GATA-3, p-p38, MAPK phosphatase-1 (MKP-1), and GC-induced leucine zipper (GILZ) levels were assessed. A/J mice subjected to two daily consecutive challenges reacted with airway hyperreactivity, subepithelial fibrosis, and marked accumulation of eosinophils in both bronchoalveolar lavage fluid and peribronchial space, all of which were clearly sensitive to dexamethasone and budesonide. Conversely, under four provocations, most of these changes were steroid resistant. A significant reduction in p-GCR/GCR ratio following 4- but not 2-d treatment was observed, as compared with untreated positive control. Accordingly, steroid efficacy to transactivate MKP-1 and GILZ and to downregulate p-p38, p-GATA-3 as well as proinflammatory cytokine levels was also seen after two but not four provocations. In conclusion, we report that repeated allergen exposure causes GC-insensitive asthma in A/J mice in a mechanism associated with decrease in GCR availability and subsequent loss of steroid capacity to modulate pivotal regulatory proteins, such as GATA-3, p-p38, MKP-1, and GILZ.

https://ift.tt/2mEv0Yk

Ligation of the CD44 Glycoform HCELL on Culture-Expanded Human Monocyte-Derived Dendritic Cells Programs Transendothelial Migration [INNATE IMMUNITY AND INFLAMMATION]

The success of dendritic cell (DC)–based immunotherapeutics critically hinges on the capacity of the vascularly administered cells to enter tissues. Transendothelial migration (TEM) is dictated by an ordered cascade of receptor/ligand interactions. In this study, we examined the key molecular effectors of TEM of human monocyte-derived DCs (mo-DCs) generated by clinically relevant methods: CD14 selection (CD14-S) and plastic adherence selection (PA-S). Without chemokine input, CD14-S cells undergo greater TEM than PA-S cells over TNF-α–stimulated HUVECs. TEM of CD14-S mo-DCs is E-selectin/very late Ag-4 (VLA-4) dependent, and engagement of E-selectin ligands activates VLA-4 on CD14-S mo-DCs but not on PA-S mo-DCs. E-selectin binding glycoforms of P-selectin glycoprotein ligand-1 (PSGL-1) (i.e., cutaneous lymphocyte Ag [CLA]) and CD44 (i.e., hematopoietic cell E-selectin/L-selectin ligand [HCELL]) are both expressed on CD14-S mo-DCs, but only CLA is expressed on PA-S mo-DCs. To elucidate the effect of CD44 or PSGL-1 engagement, mo-DCs were pretreated with their ligands. Ligation of CD44 on CD14-S mo-DCs triggers VLA-4 activation and TEM, whereas PSGL-1 ligation does not. HCELL expression on CD14-S mo-DC can be enforced by cell surface exofucosylation, yielding increased TEM in vitro and enhanced extravasation into bone marrow in vivo. These findings highlight structural and functional pleiotropism of CD44 in priming TEM of mo-DCs and suggest that strategies to enforce HCELL expression may boost TEM of systemically administered CD14-S mo-DCs.

https://ift.tt/2mBpohb

Anti-Insulin B Cells Are Poised for Antigen Presentation in Type 1 Diabetes [AUTOIMMUNITY]

Early breaches in B cell tolerance are central to type 1 diabetes progression in mouse and man. Conventional BCR transgenic mouse models (VH125.Tg NOD) reveal the power of B cell specificity to drive disease as APCs. However, in conventional fixed IgM models, comprehensive assessment of B cell development is limited. To provide more accurate insight into the developmental and functional fates of anti-insulin B cells, we generated a new NOD model (V_H125^SD.NOD) in which anti-insulin VDJH125 is targeted to the IgH chain locus to generate a small (1–2%) population of class switch–competent insulin-binding B cells. Tracking of this rare population in a polyclonal repertoire reveals that anti-insulin B cells are preferentially skewed into marginal zone and late transitional subsets known to have increased sensitivity to proinflammatory signals. Additionally, IL-10 production, characteristic of regulatory B cell subsets, is increased. In contrast to conventional models, class switch–competent anti-insulin B cells proliferate normally in response to mitogenic stimuli but remain functionally silent for insulin autoantibody production. Diabetes development is accelerated, which demonstrates the power of anti-insulin B cells to exacerbate disease without differentiation into Ab-forming or plasma cells. Autoreactive T cell responses in V_H125^SD.NOD mice are not restricted to insulin autoantigens, as evidenced by increased IFN- production to a broad array of diabetes-associated epitopes. Together, these results independently validate the pathogenic role of anti-insulin B cells in type 1 diabetes, underscore their diverse developmental fates, and demonstrate the pathologic potential of coupling a critical β cell specificity to predominantly proinflammatory Ag-presenting B cell subsets.

https://ift.tt/2uXQbIw

Kidney Proximal Tubular TLR9 Exacerbates Ischemic Acute Kidney Injury [TRANSPLANTATION]

The role for kidney TLR9 in ischemic acute kidney injury (AKI) remains unclear. In this study, we tested the hypothesis that renal proximal tubular TLR9 activation exacerbates ischemic AKI by promoting renal tubular epithelial apoptosis and inflammation. To test this hypothesis, we generated mice lacking TLR9 in renal proximal tubules (TLR9^fl/fl PEPCK Cre mice). Contrasting previous studies in global TLR9 knockout mice, mice lacking renal proximal tubular TLR9 were protected against renal ischemia/reperfusion (IR) injury, with reduced renal tubular necrosis, inflammation (decreased proinflammatory cytokine synthesis and neutrophil infiltration), and apoptosis (decreased DNA fragmentation and caspase activation) when compared with wild-type (TLR9^fl/fl) mice. Consistent with this, a selective TLR9 agonist oligonucleotide 1668 exacerbated renal IR injury in TLR9^fl/fl mice but not in renal proximal tubular TLR9-null mice. Furthermore, in cultured human and mouse proximal tubule cells, TLR9-selective ligands induced NF-B activation, proinflammatory cytokine mRNA synthesis, as well as caspase activation. We further confirm in the present study that global TLR9 deficiency had no impact on murine ischemic AKI. Taken together, our studies show that renal proximal tubular TLR9 activation exacerbates ischemic AKI by promoting renal tubular inflammation, apoptosis as well as necrosis, after IR via NF-B and caspase activation. Our studies further suggest the complex nature of TLR9 activation, as renal tubular epithelial TLR9 promotes cell injury and death whereas TLR9 signaling in other cell types may promote cytoprotective effects.

https://ift.tt/2mC0DkY

Breakdown of Immune Tolerance in AIRE-Deficient Rats Induces a Severe Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy-like Autoimmune Disease [AUTOIMMUNITY]

Autoimmune regulator (AIRE) deficiency in humans induces a life-threatening generalized autoimmune disease called autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), and no curative treatments are available. Several models of AIRE-deficient mice have been generated, and although they have been useful in understanding the role of AIRE in central tolerance, they do not reproduce accurately the APECED symptoms, and thus there is still a need for an animal model displaying APECED-like disease. We assessed, in this study, the potential of the rat as an accurate model for APECED. In this study, we demonstrate that in rat, AIRE is expressed by MHC class II (MCH-II)⁺ and MHC-II^– medullary thymic epithelial cells in thymus and by CD4^int conventional dendritic cells in periphery. To our knowledge, we generated the first AIRE-deficient rat model using zinc-finger nucleases and demonstrated that they display several of the key symptoms of APECED disease, including alopecia, skin depigmentation, and nail dystrophy, independently of the genetic background. We observed severe autoimmune lesions in a large spectrum of organs, in particular in the pancreas, and identified several autoantibodies in organs and cytokines such as type I IFNs and IL-17 at levels similar to APECED. Finally, we demonstrated a biased Ab response to IgG1, IgM, and IgA isotypes. Altogether, our data demonstrate that AIRE-deficient rat is a relevant APECED animal model, opening new opportunity to test curative therapeutic treatments.

https://ift.tt/2mBpw09

In This Issue [IN THIS ISSUE]

https://ift.tt/2A4cmCF

A Diverse Lipid Antigen-Specific TCR Repertoire Is Clonally Expanded during Active Tuberculosis [CLINICAL AND HUMAN IMMUNOLOGY]

Human T cells that recognize lipid Ags presented by highly conserved CD1 proteins often express semi-invariant TCRs, but the true diversity of lipid Ag–specific TCRs remains unknown. We use CD1b tetramers and high-throughput immunosequencing to analyze thousands of TCRs from ex vivo–sorted or in vitro–expanded T cells specific for the mycobacterial lipid Ag, glucose monomycolate. Our results reveal a surprisingly diverse repertoire resulting from editing of germline-encoded gene rearrangements analogous to MHC-restricted TCRs. We used a distance-based metric (TCRDist) to show how this diverse TCR repertoire builds upon previously reported conserved motifs by including subject-specific TCRs. In a South African cohort, we show that TCRDist can identify clonal expansion of diverse glucose monomycolate–specific TCRs and accurately distinguish patients with active tuberculosis from control subjects. These data suggest that similar mechanisms govern the selection and expansion of peptide and lipid Ag–specific T cells despite the nonpolymorphic nature of CD1.

https://ift.tt/2uXQ9jS

Immune Checkpoint Blockade Restores HIV-Specific CD4 T Cell Help for NK Cells [INFECTIOUS DISEASE AND HOST RESPONSE]

Immune exhaustion is an important feature of chronic infections, such as HIV, and a barrier to effective immunity against cancer. This dysfunction is in part controlled by inhibitory immune checkpoints. Blockade of the PD-1 or IL-10 pathways can reinvigorate HIV-specific CD4 T cell function in vitro, as measured by cytokine secretion and proliferative responses upon Ag stimulation. However, whether this restoration of HIV-specific CD4 T cells can improve help to other cell subsets impaired in HIV infection remains to be determined. In this study, we examine a cohort of chronically infected subjects prior to initiation of antiretroviral therapy (ART) and individuals with suppressed viral load on ART. We show that IFN- induction in NK cells upon PBMC stimulation by HIV Ag varies inversely with viremia and depends on HIV-specific CD4 T cell help. We demonstrate in both untreated and ART-suppressed individuals that dual PD-1 and IL-10 blockade enhances cytokine secretion of NK cells via restored HIV-specific CD4 T cell function, that soluble factors contribute to these immunotherapeutic effects, and that they depend on IL-2 and IL-12 signaling. Importantly, we show that inhibition of the PD-1 and IL-10 pathways also increases NK degranulation and killing of target cells. This study demonstrates a previously underappreciated relationship between CD4 T cell impairment and NK cell exhaustion in HIV infection, provides a proof of principle that reversal of adaptive immunity exhaustion can improve the innate immune response, and suggests that immune checkpoint modulation that improves CD4/NK cell cooperation can be used as adjuvant therapy in HIV infection.

https://ift.tt/2A4JKJm

B7-H4 Modulates Regulatory CD4+ T Cell Induction and Function via Ligation of a Semaphorin 3a/Plexin A4/Neuropilin-1 Complex [IMMUNE REGULATION]

The potent immune regulatory function of an agonistic B7-H4-Ig fusion protein (B7-H4Ig) has been demonstrated in multiple experimental autoimmune models; however, the identity of a functional B7-H4 receptor remained unknown. The biological activity of B7-H4 is associated with decreased inflammatory CD4⁺ T cell responses as supported by a correlation between B7-H4–expressing tumor-associated macrophages and Foxp3⁺ T cells within the tumor microenvironment. Recent data indicate that members of the semaphorin (Sema)/plexin/neuropilin (Nrp) family of proteins both positively and negatively modulate immune cell function. In this study, we show that B7-H4 binds the soluble Sema family member Sema3a. Additionally, B7-H4Ig–induced inhibition of inflammatory CD4⁺ T cell responses is lost in both Sema3a functional mutant mice and mice lacking Nrp-1 expression in Foxp3⁺ T cells. These findings indicate that B7-H4Ig binds to Sema3a, which acts as a functional bridge to stimulate an Nrp-1/Plexin A4 heterodimer to form a functional immunoregulatory receptor complex resulting in increased levels of phosphorylated PTEN and enhanced regulatory CD4⁺ T cell number and function.

https://ift.tt/2mBzMFJ

Blocking TIR Domain Interactions in TLR9 Signaling [INNATE IMMUNITY AND INFLAMMATION]

Interaction of TLR9 with ligands activates NF-B, leading to proinflammatory cytokine production. Excessive TLR activation is a pathogenic factor for inflammatory diseases. This study has examined cell-permeating decoy peptides (CPDPs) derived from the TLR9 Toll/IL-1R resistance (TIR) domain. CPDP 9R34, which included AB loop, β-strand B, and N-terminal BB loop residues, inhibited TLR9 signaling most potently. CPDPs derived from α-helices C, D, and E (i.e., 9R6, 9R9, and 9R11) also inhibited TLR9-induced cytokines but were less potent than 9R34. 9R34 did not inhibit TLR2/1, TLR4, or TLR7 signaling. The N-terminal deletion modification of 9R34, 9R34-N, inhibited TLR9 as potently as the full length 9R34. Binding of 9R34-N to TIR domains was studied using cell-based Förster resonance energy transfer/fluorescence lifetime imaging approach. Cy3-labeled 9R34-N dose-dependently decreased fluorescence lifetime of TLR9 TIR–Cerulean (Cer) fusion protein. Cy3–9R34-N also bound TIRAP TIR, albeit with a lesser affinity, but not MyD88 TIR, whereas CPDP from the opposite TIR surface, 9R11, bound both adapters and TLR9. i.p. administration of 9R34-N suppressed oligonucleotide-induced systemic cytokines and lethality in mice. This study identifies a potent, TLR9-specific CPDP that targets both receptor dimerization and adapter recruitment. Location of TIR segments that represent inhibitory CPDPs suggests that TIR domains of TLRs and TLR adapters interact through structurally homologous surfaces within primary receptor complex, leading to formation of a double-stranded, filamentous structure. In the presence of TIRAP and MyD88, primary complex can elongate bidirectionally, from two opposite ends, whereas in TIRAP-deficient cells, elongation is unidirectional, only through the αE side.

https://ift.tt/2A4JIBe

Active mTORC2 Signaling in Naive T Cells Suppresses Bone Marrow Homing by Inhibiting CXCR4 Expression [IMMUNE REGULATION]

Recirculation of naive T cells between secondary lymphoid organs to receive survival cues and scan for signs of infection or other pathologic conditions is important for immune homeostasis and effective immune responses. Although the mechanisms that specifically guide the entry of naive T cells into secondary lymphoid organs are well studied, the mechanisms that keep them from fluxing into inappropriate or undesirable compartments, such as healthy tissues or bone marrow, are less well understood. In this study, we report an unexpected finding that under steady state, bone marrow homing of naive T cells is actively suppressed by mTORC2 signaling. We found that in mice, T cell–specific deletion of an essential mTORC2 component Sin1 results in increased accumulation of naive T cells in the bone marrow. Mechanistically, we show that loss of mTORC2 signaling in naive T cells results in enhanced FOXO1 activity, which leads to increased CXCR4 expression and chemotactic response to CXCL12, a key chemokine that promotes bone marrow homing and retention of T cells. Together, the results of our study reveal a novel role of mTORC2 in T cell homeostasis via active suppression of naive T cell bone marrow homing by the mTORC2–FOXO1–CXCR4 axis.

https://ift.tt/2uXQ7Zi

Simple and secure intra-articular infiltration during arthroscopy of the temporomandibular joint

Publication date: Available online 23 July 2018

Source: British Journal of Oral and Maxillofacial Surgery

Author(s): R. Martín-Granizo

https://ift.tt/2uMDzEE

Neck stiffness in a post-irradiated nasopharyngeal carcinoma adult: An unusual diagnosis

Publication date: Available online 23 July 2018

Source: Auris Nasus Larynx

Author(s): Kang Ni Lorna Ting, Yew Toong Liew, Zulkiflee Abu Bakar, Prepageran Narayanan

Abstract

Nasopharyngeal carcinoma is a neoplasm commonly found in population of South East Asia. The mainstay of treatment is high dose irradiation. Complications from radiotherapy are not uncommon especially to those nearby structures such as vertebrae and spinal cord. A 57 year-old gentleman with nasopharyngeal carcinoma (NPC) who was treated with chemo-radiation (total of 35 fractions,70 Gy) presented to us 6 months post therapy with bilateral nasal discharge and progressive neck stiffness. Nasoendoscopy showed inflamed nasophayngeal mucosa and Computed Tomography (CT) brain and cervical spine showed retropharyngeal and anterior epidural collection with extension into atlantoaxial bone and spinal cord compression. Histopathological specimen revealed features of chronic inflammations with multiple actinomycetes colonies. Our patient suffered severe neck stiffness and loss of sensations on both upper limbs. He was treated conservatively with Halo vest and intravenous antibiotics for 8 weeks and recovered fully.

Irradiation in NPC is known to cause devastating complications to cervical spine such as osteoradionecrosis, osteomyelitis. It also renders tissues hypoxic and risk of getting rare infection like actinomycosis. This report can represent a great diagnostic and therapeutic challenge with differentials of tumor recurrence, osteoradionecrosis or osteomyelitis. Patients must be regularly followed up to look for possible cervical complications as a result from irradiation, to prevent devastating outcome or prognosis.

https://ift.tt/2LhJThD

Corrigendum to “From periodontal mechanoreceptors to chewing motor control: A systematic review” [Arch. Oral Biol. 78 (2017) 109–121]

Publication date: Available online 23 July 2018

Source: Archives of Oral Biology

Author(s): Grazia Piancino Maria, Isola Gaetano, Cannavale Rosangela, Cutroneo Giuseppina, Vermiglio Giovanna, Bracco Pietro, Pio Anastasi Giuseppe

https://ift.tt/2NAWlGg

Corrigendum to “From periodontal mechanoreceptors to chewing motor control: A systematic review” [Arch. Oral Biol. 78 (2017) 109–121]

Publication date: Available online 23 July 2018

Source: Archives of Oral Biology

Author(s): Grazia Piancino Maria, Isola Gaetano, Cannavale Rosangela, Cutroneo Giuseppina, Vermiglio Giovanna, Bracco Pietro, Pio Anastasi Giuseppe

https://ift.tt/2NAWlGg

Is the removal of osteosynthesis plates after orthognathic surgery necessary? Retrospective long-term follow-up study

Publication date: Available online 23 July 2018

Source: International Journal of Oral and Maxillofacial Surgery

Author(s): S. Sukegawa, T. Kanno, Y. Manabe, K. Matsumoto, Y. Sukegawa-Takahashi, M. Masui, Y. Furuki

Abstract

The removal of titanium miniplates is a controversial topic in oral and maxillofacial surgery. This retrospective study examined the timing of and reasons for titanium plate removal after orthognathic surgery. The study included 240 orthognathic surgery patients (71 male, 169 female; age range 16–55 years, mean 25.0 ± 8.8 years) who had maxillofacial osteosynthesis plates inserted or inserted and then removed at the Division of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital, between April 2003 and March 2017. During the study period, a total of 717 miniplates were inserted in the 240 patients, and 71 of the patients (29.6%) had 236 plates (32.9%) removed. Ten patients (14.1%) had their plates removed within a year due to early complications. Although no patient had their plate removed due to complications at 1–5 years postoperative, a further 14 patients (19.7%) had their plates removed after more than 5 years of long-term follow-up due to plate-related complications. Complications requiring plate removal were evidently biphasic, occurring within 1 year after the operation and at ≥5 years after the operation. Therefore, after confirming postoperative bone healing, it is necessary to explain to patients the risks of plate removal and the importance of long-term follow-up.

https://ift.tt/2mBAOS4

Measurement of oral health quality of life among patients who underwent haematopoietic stem-cell transplantation

Abstract Oral mucositis is a painful condition that occurs in patients who have undergone haematopoietic stem-cell transplantation (HSCT) and has a huge impact on their quality of life. The objective of this study was to examine the extent to which interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) are associated with oral health quality of life among patients who underwent HSCT. A. C. Camargo Cancer Center patients were evaluated over 20 months at 4 different time-points: a) at patient admission (M1); b) on the day of infusion of HSC (M2); c) 12 and 20 days after the first day of the conditioning regimen for autologous and allogeneic transplantation, respectively (M3); and d) 30 days after the first day of the conditioning regimen (M4). Mucositis clinical evaluations were performed using World Health Organization (WHO) criteria. Oral health quality of life was measured using the Oral Health Impact Profile short form (OHIP-14), Oral Mucositis Quality of Life (OMQoL) and Patient-Reported Oral Mucositis Symptom (PROMS) scales. Correlations between clinical data and quality of life scores were examined. STATA 11.0 was used to perform the statistical analyses (5% level of significance). Eighty-two patients participated in the study; 62.2% were male, 28.05% had multiple myeloma, and the mean age was 48.49 years (SD 13.76). Higher scores (worse quality of life) were observed as mucositis scores increased, but the results were not significant. The OMQoL had a high correlation with OHIP-14 (0.8377), but the correlation between the PROMS scale and the OHIP-14 was lower (0.6643). Higher concentrations of IL-6 and TNF-α were associated with worse quality of life, according to all indices (p < 0.05). Oral mucositis was associated with quality of life scores (p < 0.01).

https://ift.tt/2uHRbRG

Systemic diseases and other painful conditions in patients with temporomandibular disorders and migraine

Abstract Temporomandibular disorders (TMD) are a highly prevalent, painful musculoskeletal condition affecting the masticatory system, and are frequently associated with migraines (M) and other diseases. This study aimed to investigate the association between painful TMD and M with other painful conditions and systemic diseases, such as cervicalgia, body pain (BP), ear-nose-throat disorders, musculoskeletal disorders, diabetes, cardiopulmonary diseases and gastritis/peptic ulcer. Methods: This was a cross-sectional study conducted in a sample of 352 individuals. Participants were stratified into three groups according to the presence of painful TMD and M: controls [individuals free of TMD and any headache (HA)]; TMD only (presence of painful TMD, but free of any HA); and TMD+M (presence of painful TMD and M). TMD was classified according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) - Axis I. Nonspecific physical symptoms (NSPS) were assessed by RDC/TMD - Axis II. The International Classification of Headache Disorders - II criteria, second edition, were applied to identify and classify primary HA. Other painful conditions and systemic diseases were assessed by volunteers' self-report. The prevalence of all assessed conditions was higher in the TMD+M group. Multiple regression models showed that cervicalgia was associated with the TMD only group (p<0.05), whereas gender (p<0.05), cervicalgia (p<0.05), BP (p<0.05) and NSPS (p<0.05) were significantly associated with the TMD+M group. Our results suggest that individuals with a comorbidity (TMD associated with M) have a more severe condition than those presenting only painful TMD.

https://ift.tt/2A2vcKh

Erratum: Inorganic filler content of resin-based luting agents and the color of ceramic veneers. Braz Oral Res. 2018;32:e49. https://ift.tt/2Aa17Zw

Abstract The aim of the present study was to evaluate the association between metabolic syndrome (MS) and periodontitis (PD), through a systematic review and meta-analysis. Original observational studies assessing the association between MS and PD in adults, published before May 11th (2017), were identified through electronic searches of MEDLINE, EMBASE and Cochrane Library databases. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was used. For studies to be included, they had to mention the criteria used to diagnose MS and to have used at least one clinical measure to diagnose PD. There was no language restriction. Three reviewers independently identified eligible studies for possible inclusion in the systematic review and meta-analysis. The quality of the studies was evaluated by the Newcastle-Ottawa scale for observational studies. A random model meta-analysis was conducted. The strategies used to investigate heterogeneity were sequential analysis, subgroup analysis, univariate meta-regression and sensitivity analysis. Thirty-three studies met the inclusion criteria for the systematic review, and 26 had enough information to be included in the meta-analysis, totaling 52,504 patients. MS and PD were associated with an odds ratio of 1.38 (95%CI 1.26–1.51; I2 = 92.7%; p < 0.001). Subgroup analysis showed that complete periodontal examination (I2 = 70.6%; p < 0.001) partially explained the variability between studies. The present findings suggest an association between MS and PD. Individuals with MS are 38% more likely to present PD than individuals without this condition. Prospective studies should be conducted to establish cause and effect relations between MS and PD.

https://ift.tt/2uKhlmJ

Analysis of the audiogram shape in patients with idiopathic sudden sensorineural hearing loss using a cluster analysis

Tetsuo Watanabe, MD, PhD; Masashi Suzuki, MD, PhD

Abstract

We performed a cluster analysis to classify the audiogram shape in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). We also investigated whether the audiogram shape is a prognostic indicator in the management of ISSNHL. A total of 115 inpatients with ISSNHL treated between 2001 and 2010 were analyzed. The data collected included age, sex, duration of hearing loss at the time of treatment, and the presence or absence of tinnitus, vertigo, diabetes, nystagmus, and canal paresis. A hierarchical cluster analysis was performed using the hearing threshold for each frequency on audiograms as variables. A logistic regression model was used for the prognostic analysis. The audiogram shape was classified into four clusters: (1) crossing horizontally pattern of all tones; (2) up-sloping pattern of low-tone loss; (3) deaf pattern; and (4) down-sloping pattern of high-tone loss. The age of the patient, presence of canal paresis, and audiogram shape showed statistically significant relationships with hearing improvement. The audiogram shape based on the cluster analysis demonstrated a significant relationship with hearing improvement in patients with ISSNHL. Further studies are needed to elucidate the underlying etiology of each audiogram shape.

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Analyzing Medicare payments to otologists

T. Edward Imbery, MD; Brian D. Nicholas, MD; Parul Goyal, MD, MBA

Abstract

The study objective was to analyze Medicare payment data to otologists compared to otolaryngologists, using the publicly released Centers for Medicare and Medicaid Services dataset. Charges, payments, and common Current Procedural Terminology codes were obtained. Otology providers were selected from the roster of the American Otological Society. Descriptive statistics and unequal variance two-tailed t tests were used for comparisons between otologists (n = 147) and otolaryngologists (n = 8,318). The mean overall submitted charge was $204,851 per otology provider and was $211,209 per other otolaryngology providers (non-otologists) (p = 0.92). The mean payment to otologists was $56,191 (range: $297 to $555,274, standard deviation [SD] ±$68,540) and significantly lower (p = 0.005) than $77,275 to otolaryngologists (range: $94 to $2,123,900, SD ±$86,423). The mean submitted charge-to-payment ratio (fee multiplier) per otology provider was 3.87 (range 1.50 to 9.10, SD ±1.70), which was significantly higher (p < 0.0001) than the ratio for otolaryngologists (mean 2.91; range: 1.25 to 17.51, SD ±1.22). Office visit evaluation and management (E&M) codes made up the majority in terms of use and payments. Interestingly, allergy-based services comprised a substantial amount of repeat use among a small subset of otologists. Audiology services were billed by a similar percentage of otologists and other otolaryngologists (52%), but otologists received a significantly higher overall payment for these services.

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Ocular vestibular evoked myogenic potentials and intravestibular intralabyrinthine schwannomas

Massimo Ralli, MD, PhD; Giuseppe Nola, MD; Massimo Fusconi, MD; Luca Sparvoli, MD; Giovanni Ralli, MD

Abstract

Intravestibular intralabyrinthine schwannomas (ILSs) are uncommon benign tumors that arise from the saccular, utricular, and lateral and superior ampullary nerves. According to the literature, there is an average delay of 8 years between the onset of symptoms and diagnosis. The diagnosis is based on an audiovestibular examination and magnetic resonance imaging (MRI). We describe a case of intravestibular ILS in which we included the ocular vestibular evoked myogenic potentials (oVEMPs) test in the diagnostic workup. The oVEMPs test is a relatively new neurophysiologic diagnostic modality that evaluates the superior vestibular pathway and the ascending contralateral pathway through the vestibulo-ocular reflex. In our case, a 65-year-old man presented with progressive right-sided sensorineural hearing loss, dizziness, and tinnitus and fullness in his right ear. Audiovestibular examination and MRI detected an intravestibular ILS on the right. We found that oVEMPs were absent on the contralateral side, which contributed to the diagnostic process. The detection of oVEMPs can provide detailed information on the functionality of the macula of the utricle and the lateral and superior ampullary nerves, with a precise identification of the affected area. Based on our findings, we discuss the role of oVEMPs in the diagnosis of an intravestibular ILS.

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Warthin tumor of the larynx: A case report and review of the literature

Irit Duek, MD; Miki Paker, MD; Ziv Gil, MD, PhD; Jacob T. Cohen, MD

Abstract

Warthin tumor (papillary cystadenoma lymphomatosum) is a benign salivary gland tumor that occurs almost exclusively in the parotid gland. As far as we know, only 15 cases of laryngeal Warthin tumor have been previously reported worldwide. We describe the case of a 75-year-old woman with a supraglottic tumor that mimicked a mucoepidermoid carcinoma. The tumor was completely excised via a transcervical approach. Pathology identified it as a Warthin tumor. At follow-up, the patient maintained good oral intake. Computed tomography 3 months postoperatively confirmed complete tumor resection and detected no evidence of residual disease or recurrence. We also discuss our review of the literature on benign laryngeal salivary gland tumors, which included an analysis of 112 cases. The most common tumors were oncocytic cystadenomas (n = 65), pleomorphic adenomas (n = 28), and Warthin tumors (n = 15); we also found 2 cases each of basal cell adenomas and myoepitheliomas. The most common single tumor site was the glottis (n = 25), followed by the supraglottis (n = 24), and the subglottis (n = 22); 5 cases occurred in multiple sites, and the specific site was not reported in 36 cases. Benign laryngeal neoplasms of salivary gland origin should be carefully evaluated. Distinguishing these tumors from malignant lesions and establishing the correct diagnosis are crucial for treatment planning. Large lesions with extralaryngeal extension can be resected completely via an open external approach.

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Endoscopic view of a sinonasal osteoma

Dewey A. Christmas, MD; Joseph P. Mirante, MD, MBA, FACS; Eiji Yanagisawa, MD, FACS

Surgical intervention is indicated only in the event of symptoms or complications caused by the osteoma.

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Inflammatory myofibroblastic tumor of the larynx

Yu-Hsuan Wang, MD; Yi-Shing Leu, MD; Wei-Chin Chang, MD

Inflammatory myofibroblastic tumor usually involves the lungs, bronchopulmonary tree, and abdominal viscera.

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Accessory submandibular duct sialolithiasis identified during sialendoscopy

Andrew J. Thomas, MD; Kevin F. Wilson, MD

Abstract

We describe a unique case of a 62-year-old patient with recurrent right submandibular sialadenitis. He initially appeared to have extensive sialolithiasis of the right submandibular duct on computed tomography imaging and examination, but sialendoscopy demonstrated a normal-appearing right submandibular duct. An accessory duct posterior and parallel to the normal duct was identified at the time of sialendoscopy and was found to have extensive sialolithiasis, which required removal by both an endoscopic and intraoral technique. To the best of our knowledge, this is the first report of sialolithiasis of an accessory submandibular duct identified at the time of sialendoscopy; the other few reported cases in the literature are based primarily on findings from traditional sialography or magnetic resonance sialography. Identification of accessory salivary ducts requires intraoperative consideration of this entity during sialendoscopy. Open approaches to sialolithiasis, however, may be aided by appropriate preoperative imaging.

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Esophageal perforation as a complication of the Heimlich maneuver in a pediatric patient: A case report

Shira L. Koss, MD; William E. Karle, MD; Gregory Dibelius, MD; Ameet Kamat, MD; Craig Berzofsky, MD

Abstract

We report a case of cervical esophageal perforation caused by the Heimlich maneuver in a healthy 16-year-old boy. The patient reported a short coughing episode while eating rice, and his mother performed the Heimlich maneuver on him. Five days later, he presented to the emergency department with throat pain, odynophagia, secretion intolerance, muffled voice, and neck stiffness. He was admitted to the pediatric intensive care unit for conservative management. The next day he underwent transcervical incision and drainage of purulence, but the esophageal perforation could not be visualized at that time. The perforation was identified several days later and successfully repaired surgically. Esophageal perforation as a complication of the Heimlich maneuver is exceedingly rare, but the clinician should be aware of this entity in the differential diagnosis, as it is associated with a high mortality rate and warrants multidisciplinary care, including timely surgical intervention.

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HPV-related sinonasal carcinoma with adenoid cystic-like features with intracranial invasion

Yuntsung Hung, MD; Yu-Yen Chung, MD; Mei-Ling Chen, MD; Jyun-Ying Guo, MD

HPV-related sinonasal carcinoma with adenoid cystic-like features is a recently described tumor with less than 10 cases reported in the literature to date.

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Tympanometric volume as a useful tool for the evaluation of middle ear status in chronic otitis media

Shin Hye Kim, MD, PhD; Hyun Sook Hong, MD, PhD; Jong Dae Lee, MD, PhD; Moo Kyun Park, MD, PhD

Abstract

Tympanometric volume is a useful tool for evaluating middle ear status in otitis media. However, its usefulness in chronic otitis media (COM) has not been well evaluated. This study aimed to investigate whether tympanometric volume reflects the status of the middle ear and mastoid or can provide clinical information about patients with COM and subsequent tympanic membrane perforation. A prospective cohort study including 50 adult patients with COM and subsequent tympanic membrane perforation was performed. The volumes of the middle ear and mastoid were preoperatively calculated using tympanometry and three- dimensional computed tomography (CT) reconstruction of the temporal bone, respectively. During surgery for COM, the patency of the middle ear and mastoid antrum was evaluated. The volumes of the middle ear and mastoid measured by tympanometry and CT were compared with the surgical findings. When the mastoid antrum was patent, the volumes of the middle ear and mastoid measured by tympanometry and CT were well correlated. Moreover, the difference in the volumes measured by tympanometry between the affected and unaffected ears was large. However, when the mastoid antrum was poorly aerated, the difference in the volumes measured by tympanometry between the affected and unaffected ears was small. Middle ear status can be evaluated according to the difference in tympanometric volume between the two ears. If the tympanometric volume suggests poor aeration of the middle ear and mastoid, clinicians should consider procedures for mastoid aeration.

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Prevalence of food allergy in Vietnam: comparison of web-based with traditional paper-based survey

Web-based surveys (WBS) are increasingly applied in epidemiological studies as an appealing alternative to traditional survey methods. Rapid data collection, reduced expenditure and ease of access to large pop...

https://ift.tt/2NFsblh

The Detection of Barrett's Esophagus by Gastrointestinal Endoscopy Prevents Esophageal Carcinoma in Morbid Obese After Sleeve Gastrectomy

Condition:   Gastroesophageal Reflux
Intervention:  
Sponsor:   Centre Hospitalier Universitaire de Nice
Recruiting

https://ift.tt/2uZGmtq

Nomograms to Precisely Predict Conditional Risk of Recurrence for Patients With Laryngeal Cancer

Condition:   Recurrent Laryngeal Cancer
Intervention:   Other: Recurrence laryngeal cancer
Sponsor:   First Affiliated Hospital, Sun Yat-Sen University
Recruiting

https://ift.tt/2LCnN9i

Giftschlangen in Deutschland und Europa

Zusammenfassung

Schätzungen gehen von weltweit mehr als 5.000.000 Schlangenbissen pro Jahr aus; 2.500.000 von diesen führen zu Vergiftungserscheinungen, knapp 400.000 hinterlassen dauerhafte Folgen, und ca. 125.000 verlaufen tödlich. In Deutschland gibt es nur 2 Giftschlangen, die Kreuzotter und die Aspisviper. Bisse durch giftige Schlangen sind aber nicht nur in Deutschland, sondern auch auf dem gesamten Gebiet des geografischen Europa bis zum Beweis des Gegenteils stets als bedrohlicher Notfall einzuordnen. Jeder dieser Bisse sollte, selbst bei fehlender Symptomatik, für mindestens 24 Stunden überwacht werden, möglichst in einer mit der medizinischen Versorgung von Schlangenbissen vertrauten Einrichtung. Reisenden sollte dringend geraten werden, sich vor Reiseantritt über das am Reiseziel übliche Aufkommen giftiger Schlangen zu informieren

https://ift.tt/2zYQM2e

Ex vivo expanded tumour-infiltrating lymphocytes from ovarian cancer patients release anti-tumour cytokines in response to autologous primary ovarian cancer cells

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of gynaecological cancer-related death in Europe. Although most patients achieve an initial complete response with first-line treatment, recurrence occurs in more than 80% of cases. Thus, there is a clear unmet need for novel second-line treatments. EOC is frequently infiltrated with T lymphocytes, the presence of which has been shown to be associated with improved clinical outcomes. Adoptive T-cell therapy (ACT) using ex vivo-expanded tumour-infiltrating lymphocytes (TILs) has shown remarkable efficacy in other immunogenic tumours, and may represent a promising therapeutic strategy for EOC. In this preclinical study, we investigated the efficacy of using anti-CD3/anti-CD28 magnetic beads and IL-2 to expand TILs from freshly resected ovarian tumours. TILs were expanded for up to 3 weeks, and then subjected to a rapid-expansion protocol (REP) using irradiated feeder cells. Tumours were collected from 45 patients with EOC and TILs were successfully expanded from 89.7% of biopsies. Expanded CD4⁺ and CD8⁺ subsets demonstrated features associated with memory phenotypes, and had significantly higher expression of key activation and functional markers than unexpanded TILs. Expanded TILs produced anti-tumour cytokines when co-cultured with autologous tumour cells, inferring tumour cytotoxicity. Our findings demonstrate that it is possible to re-activate and expand tumour-reactive T cells from ovarian tumours. This presents a promising immunotherapy that could be used sequentially or in combination with current therapeutic strategies.

https://ift.tt/2uVFu9b

Primary Nasopharyngeal Kaposi Sarcoma as Index Diagnosis of AIDS in a Previously Healthy Man

Abstract

A 38-year-old, previously healthy man presented with blood-stained saliva and epistaxis. A 3 mm nasopharyngeal lesion was found. A biopsy was performed and microscopic examination revealed a Kaposi sarcoma. The patient was subsequently found to be positive for human immunodeficiency virus (HIV). The diagnosis of Kaposi sarcoma in the presence of HIV infection advanced his disease to Acquired Immunodeficiency Syndrome (AIDS). Primary manifestation of Kaposi sarcoma in the nasopharynx is extremely rare. The histologic differential diagnosis of Kaposi sarcoma in this unusual site, especially without the clinical history of immunosuppression, is broad. Awareness that nasopharynx can be a primary involvement site of Kaposi sarcoma and serves as index diagnosis of AIDS is important given its serious clinical implication.

https://ift.tt/2JMawpm

ASCO – vom amerikanischen Krebskongress 2018

https://ift.tt/2uXFXb7

Leveraging Quality Improvement and Patient Safety Initiatives to Enhance Value and Patient-Centered Care in Otolaryngology

Abstract

Purpose of Review

Patient safety and quality improvement (PS/QI) initiatives have rapidly proliferated through all fields of healthcare including otolaryngology. Harnessing these initiatives provides an opportunity to systematically evaluate and disseminate best practices and to evaluate their effect in improving value for patients.

Recent Findings

New data registries and disease-specific quality improvement collaboratives provide opportunities for otolaryngologists to use data to enhance quality. We describe PS/QI measures that enhance value by improving quality and controlling costs. These include data registries that allow "big data" approaches, the benefits of multidisciplinary teams and care coordination, subspecialty-specific initiatives, use of M&M conference as a launchpad for PS/QI activity, and barriers to implementation of PS/QI strategies.

Summary

As changes in healthcare continue to accelerate, otolaryngologists who embrace opportunities to optimize value in their respective subspecialties will see improved outcomes for their patients and will reap the benefits of thriving, fulfilling clinical practices.

https://ift.tt/2Ab4tvl

Primary Nasopharyngeal Kaposi Sarcoma as Index Diagnosis of AIDS in a Previously Healthy Man

Abstract

A 38-year-old, previously healthy man presented with blood-stained saliva and epistaxis. A 3 mm nasopharyngeal lesion was found. A biopsy was performed and microscopic examination revealed a Kaposi sarcoma. The patient was subsequently found to be positive for human immunodeficiency virus (HIV). The diagnosis of Kaposi sarcoma in the presence of HIV infection advanced his disease to Acquired Immunodeficiency Syndrome (AIDS). Primary manifestation of Kaposi sarcoma in the nasopharynx is extremely rare. The histologic differential diagnosis of Kaposi sarcoma in this unusual site, especially without the clinical history of immunosuppression, is broad. Awareness that nasopharynx can be a primary involvement site of Kaposi sarcoma and serves as index diagnosis of AIDS is important given its serious clinical implication.

https://ift.tt/2JMawpm

Primary Nasopharyngeal Kaposi Sarcoma as Index Diagnosis of AIDS in a Previously Healthy Man

Abstract

A 38-year-old, previously healthy man presented with blood-stained saliva and epistaxis. A 3 mm nasopharyngeal lesion was found. A biopsy was performed and microscopic examination revealed a Kaposi sarcoma. The patient was subsequently found to be positive for human immunodeficiency virus (HIV). The diagnosis of Kaposi sarcoma in the presence of HIV infection advanced his disease to Acquired Immunodeficiency Syndrome (AIDS). Primary manifestation of Kaposi sarcoma in the nasopharynx is extremely rare. The histologic differential diagnosis of Kaposi sarcoma in this unusual site, especially without the clinical history of immunosuppression, is broad. Awareness that nasopharynx can be a primary involvement site of Kaposi sarcoma and serves as index diagnosis of AIDS is important given its serious clinical implication.

https://ift.tt/2JMawpm

Circumflex retroesophageal right aortic arch: rare differential of mediastinal widening

Description 

A 48-year-old man presented to the outpatient department with complaints of inspiratory stridor and occasional dysphagia. Chest radiograph revealed bilateral symmetric widening of the superior mediastinum at the level of aortic arch with the descending aorta seen to the left of spine. No lateral displacement of tracheal air column was noted (figure 1A). The patient was referred to us for a CT angiography (CTA) with a provisional diagnosis of an aneurysm or a mediastinal mass. Review of CTA images revealed a right-sided aortic arch crossing the midline posterior to the trachea and the oesophagus in the upper mediastinum and further descending on the left side of spine (figure 1B–E). A Kommerell's diverticulum arising from the anterosuperior aspect of aorta, on the left side, gave rise to an aberrant left subclavian artery (LSCA). The circumflex arch was ectatic and measured 37 mm in its maximum...

https://ift.tt/2LDNjYd

Fixation of femoral attachment: anterior cruciate ligament avulsion fracture with arthroscopy suture loop technique

Anterior cruciate ligament (ACL) avulsion fracture is rare and mostly occur in tibial attachment. Avulsion fracture of femoral attachment of ACL was uncommon and mostly reported in skeletally immature patient. This article aims to report an interesting case of femoral attachment–ACL avulsion fracture in skeletally mature patient with arthroscopic suture loop fixation.

A 32-year-old man, with no significant medical-surgical history, sustained a right non-contact pivoting knee injury during soccer competition. Plain radiographs of knee joint demonstrated intra-articular bone fragment in the intercondylar notch space. The MRI confirmed femoral attachment–ACL avulsion fracture. Then, we planned to perform fixation of femoral attachment–ACL avulsion fracture with arthroscopy suture loop technique. At 5 months after surgery, patient had no pain and swelling knee. The physical examination demonstrated negative Lachman test, anterior drawer test, pivot shift test and patient can return to preinjury daily activity and sport activities.

https://ift.tt/2uIMl6H

Laryngopyocoele in an adult female mimicking an infected branchial cyst

The incidence of laryngopyocoele is very unusual and only 41 cases have been documented in the world literature. Although hoarseness and stridor are the predominant symptoms associated with laryngocoele,patient can present with a recurrent neck abscess misleading to an infected branchial cyst. Complete excision of the cyst can be effectively achieved by the transcervical approach, especially in case of a large lateral cyst in a stable patient.

https://ift.tt/2LFlnDu

Pericardial calcification: an uncommon presentation of rheumatic heart disease

Description 

A 42-year-old man presented to cardiology outpatient department with complaints of gradually progressive dyspnoea on exertion, easy fatigability and mild intermittent atypical chest pain for the past 9 months. Chest radiograph revealed mild cardiomegaly, enlarged left atrium and presence of multiple focal calcific specks along right inferior and upper left cardiac border (figure 1A). Transthoracic echocardiography showed thickened mitral valve leaflets with restricted mobility of posterior leaflet and mitral stenosis with mitral regurgitation.

Figure 1

Frontal chest radiograph (A) shows cardiomegaly with enlarged left atrium along with linear calcific foci (black arrows) along cardiac borders, which were confirmed to be involving the pericardium (white arrows) on coronal reconstructed maximum intensity projection images of CT angiography (B, C). Short-axis (D) and long-axis (E) reconstructions reveal thickening of mitral valve (MV) leaflets along with speck of calcification involving the anterior MV leaflet (dotted black arrow) along with...

https://ift.tt/2uIMjM7

Laparoscopic management of an unusual case of small bowel obstruction: appendiculoileal knotting

Appendicitis presenting at small bowel obstruction due to the formation of encircling loop around a bowel segment is a rare occurrence. We report such case managed with the laparoscopic approach. A 45-year-old woman presented to emergency services with severe pain in abdomen and bilious vomiting in the past 2 days, having a history of abdominal hysterectomy 10 years ago. The abdominal examination was suggestive of bowel obstruction. A CT showed dilated bowel loops with complete cut-off at the level of the terminal ileum. The patient was taken for diagnostic laparoscopy. The inspection of the small bowel revealed an appendicular looping around the small bowel lumen. After separating, the appendix obstruction was relieved. Then, the tip of the appendix was dissected free from the parietal wall along with approximately 5 mL purulent fluid. Appendectomy was completed and based looped doubly using catgut endoloop. The patient had an uneventful recovery and was discharged on the second postoperative day.

https://ift.tt/2LGDfxK

The anteromedial thigh free flap: a primary reconstructive option or second best?

Purpose of review This article reviews the recent literature on the anteromedial thigh free flap. Recent findings The anteromedial thigh (AMT) free flap is an excellent reconstructive option for head and neck defects. It is often overshadowed by the anterolateral thigh (ALT) free flap. Lack of familiarity with the anatomy of the AMT likely deters many surgeons from considering it as a reliable option. However, as many as one in 20 patients may not have anatomy suitable for ALT free-flap harvest, and in these cases the AMT provides an ideal alternative as it can be harvested through the same incision without added morbidity. Current areas of research include clinical, anatomic, cadaveric, and radiographic studies evaluating the AMT flap anatomy and utility. Summary The AMT flap has been successfully used to reconstruct the same types of soft tissue head and neck defects as the ALT. However, given that approximately 95% of patients appear to have anatomy favorable to harvest an ALT, the utility of the AMT should be reserved for patients with unfavorable lateral thigh anatomy or when when a chimeric flap is indicated and anatomy permits. Correspondence to Arnaud F. Bewley, Department of Otolaryngology – Head and Neck Surgery, UC Davis Medical Center, California, USA. E-mail: abewley@ucdavis.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2uHe5Zz

A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia

Abstract

In elderly acute myeloid leukemia (AML) patients post-remission treatment options are associated with high comorbidity rates and poor survival. Dendritic cell (DC)-based immunotherapy is a promising alternative treatment strategy. A novel allogeneic DC vaccine, DCP-001, was developed from an AML-derived cell line that uniquely combines the positive features of allogeneic DC vaccines and expression of multi-leukemia-associated antigens. Here, we present data from a phase I study conducted with DCP-001 in 12 advanced-stage elderly AML patients. Patients enrolled were in complete remission (CR1/CR2) (n = 5) or had smoldering disease (n = 7). All patients were at high risk of relapse and ineligible for post-remission intensification therapies. A standard 3 + 3 dose escalation design with extension to six patients in the highest dose was performed. Patients received four biweekly intradermal DCP-001 injections at different dose levels (10, 25, and 50 million cells DCP-001) and were monitored for clinical and immunological responses. Primary objectives of the study (feasibility and safety) were achieved with 10/12 patients completing the vaccination program. Treatment was well tolerated. A clear-cut distinction between patients with and without detectable circulating leukemic blasts during the vaccination period was noted. Patients with no circulating blasts showed an unusually prolonged survival [median overall survival 36 months (range 7–63) from the start of vaccination] whereas patients with circulating blasts, died within 6 months. Long-term survival was correlated with maintained T cell levels and induction of multi-functional immune responses. It is concluded that DCP-001 in elderly AML patients is safe, feasible and generates both cellular and humoral immune responses.

https://ift.tt/2Lrydbw

The anteromedial thigh free flap: a primary reconstructive option or second best?

Purpose of review This article reviews the recent literature on the anteromedial thigh free flap. Recent findings The anteromedial thigh (AMT) free flap is an excellent reconstructive option for head and neck defects. It is often overshadowed by the anterolateral thigh (ALT) free flap. Lack of familiarity with the anatomy of the AMT likely deters many surgeons from considering it as a reliable option. However, as many as one in 20 patients may not have anatomy suitable for ALT free-flap harvest, and in these cases the AMT provides an ideal alternative as it can be harvested through the same incision without added morbidity. Current areas of research include clinical, anatomic, cadaveric, and radiographic studies evaluating the AMT flap anatomy and utility. Summary The AMT flap has been successfully used to reconstruct the same types of soft tissue head and neck defects as the ALT. However, given that approximately 95% of patients appear to have anatomy favorable to harvest an ALT, the utility of the AMT should be reserved for patients with unfavorable lateral thigh anatomy or when when a chimeric flap is indicated and anatomy permits. Correspondence to Arnaud F. Bewley, Department of Otolaryngology – Head and Neck Surgery, UC Davis Medical Center, California, USA. E-mail: abewley@ucdavis.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2uHe5Zz