Applying artificial intelligence to assess the impact of orthognathic treatment on facial attractiveness and estimated age

Publication date: Available online 4 August 2018

Source: International Journal of Oral and Maxillofacial Surgery

Author(s): R. Patcas, D.A.J. Bernini, A. Volokitin, E. Agustsson, R. Rothe, R. Timofte

Abstract

This observational study aimed to use artificial intelligence to describe the impact of orthognathic treatment on facial attractiveness and age appearance. Pre- and post-treatment photographs (n = 2164) of 146 consecutive orthognathic patients were collected for this longitudinal retrospective single-centre study. Every image was annotated with patient-related data (age; sex; malocclusion; performed surgery). For every image, facial attractiveness (score: 0–100) and apparent age were established with dedicated convolutional neural networks trained on >0.5 million images for age estimation and with >17 million ratings for attractiveness. Results for pre- and post-treatment photographs were averaged for every patient separately, and apparent age compared to real age (appearance). Changes in appearance and facial attractiveness were statistically examined. Analyses were performed on the entire sample and subgroups (sex; malocclusion; performed surgery). According to the algorithms, most patients' appearance improved with treatment (66.4%), resulting in younger appearance of nearly 1 year [mean change: −0.93 years (95% confidence interval (CI): −1.50; −0.36); p = 0.002), especially after profile-altering surgery. Orthognathic treatment had similarly a beneficial effect on attractiveness in 74.7% [mean difference: 1.22 (95% CI: 0.81; 1.63); p < 0.001], especially after lower jaw surgery. This investigation illustrates that artificial intelligence might be considered to score facial attractiveness and apparent age in orthognathic patients.

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

Publication date: Available online 4 August 2018

Source: Brazilian Journal of Otorhinolaryngology

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

Abstract

Introduction

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

Objective

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

Methods

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

Results

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

Conclusions

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

Resumo

Introdução

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

Objetivo

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

Método

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

Resultados

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

Conclusões

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

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

Publication date: Available online 4 August 2018

Source: Acta Otorrinolaringológica Española

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

https://ift.tt/2Mkg1Og

A long styloid process and Collet–Sicard syndrome

Publication date: Available online 4 August 2018

Source: Acta Otorrinolaringológica Española

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

https://ift.tt/2M0OYdX

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

Publication date: Available online 4 August 2018

Source: Acta Otorrinolaringológica Española

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

Resumen

Objetivo

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

Materiales y métodos

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

Resultados

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

Conclusión

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

Abstract

Objective

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

Materials and methods

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

Results

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

Conclusions

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

https://ift.tt/2MjaFD0

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

Publication date: Available online 4 August 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Denisa Ferastraoaru, David Rosenstreich

https://ift.tt/2vixdgC

Plasma rich in growth factors (PRGF) for the promotion of bone cell proliferation and tissue regeneration

Abstract

Objectives

Over the past few years, studies about growth factors have been increasingly developed and the knowledge of their role in stimulating cell proliferation and differentiation used for therapeutic purposes. This study aims to compare a platelets concentrate, the plasma rich in growth factors (PRGF) to a control, consisting of cellulose membranes, to evaluate in vitro the cellular adhesion and migration of human osteoblasts (hOb) and understand if the use of platelets concentrates could be an advantage in view of bone tissue regeneration.

Study design

Twenty-seven human donors provided 27 blood samples used to make 54 samples: 27 for PRGF and 27 for the control group. PRGFs and controls were incubated for 48 h in sterility in 1 ml of culture with 10⁵ hOb and hOb in the scaffolds were then quantified.

Results

In PRGF samples, hObs were more numerous than in controls. (T = 6.6964, p < 0.0001).

Conclusions

Human osteoblasts are driven to colonize PRGFs with a greater efficacy than negative controls, probably due to the presence of chemokines and growth factors in PRGFs.

https://ift.tt/2vfbC8Q

Diplopia—an unheralded consequence of neck dissection: case report

Abstract

Introduction

Neck dissection is a part of the standard surgical procedure in the management of head and neck malignancy. Diplopia following neck dissection is a rare entity; hence, its diagnosis and management strategies needed to be discussed for prevention of its grave consequences.

Case report

A 30-year-old male patient presented with binocular horizontal diplopia following total thyroidectomy and neck dissection. On evaluation, there was internal jugular vein (IJV) thrombosis followed by cerebral venous sinus thrombosis (CVST). After meticulous medical management with diuretics and antiplatelet drugs, diplopia resolved completely and normal vision was restored.

Conclusion

Therapeutic ligation of internal jugular vein during neck dissection may result in IJV thrombosis followed by CVST leading to raised intracranial tension (ICT). It has to be anticipated and addressed as early as possible to prevent its grave consequences like blindness and death.

https://ift.tt/2MkD4ID

Psychometric properties of Hindi version of child oral impact on daily performances (C-OIDP) index amongst school children in North India

Publication date: Available online 4 August 2018

Source: Journal of Oral Biology and Craniofacial Research

Author(s): Preeti Dhawan, Aditi Singh, Anubha Agarwal, Himanshu Aeran

Abstract

Aim

To assess validity and reliability of Hindi version of Child Oral impact on daily performances (C-OIDP) index among school children in North India.

Material and methodology

Descriptive cross sectional study was conducted amongst 250, 11–12 year old school children in primary schools of Rishikesh, Uttarakhand, India. The study was done in two phases: first phase included assessment of Psychometric and linguistic properties of hindi version of C-OIDP index which was then pilot tested on study subjects. Phase two comprised of the actual main study which included the re-assessment of Hindi C-OIDP index on the entire study population. The pilot study comprised of 40 school children while the main study was conducted on 250 school children.

Results

The inter-item correlation coefficient ranged from 0.1 to 0.786 while corrected item total correlation coefficient ranged from 0.176 (smiling) to 0.843 ((cleaning). The standardised Cronbach's Alpha coefficient was 0.88. Moreover, the alpha coefficients didn't increase upon deleting any of the items. Weighted kappa was 0.85 & ICC was 0.9. Children with higher scores were less satisfied with their mouth (p- 0.001) in case of concurrent validity.

Conclusion

Hindi Child Oral Impact on Daily Performances index can be used as a valid and reliable instrument in measuring OHRQoL. of Paediatric North Indian population.

https://ift.tt/2Oc60Dd

Effect of sodium chloride on gene expression of Streptococcus mutans and zeta potential of demineralized dentin

Publication date: Available online 4 August 2018

Source: Journal of Oral Biology and Craniofacial Research

Author(s): Ali Akbar Nagavi-alhoseiny, Maryam Torshabi, Morteza Rasoulianboroujeni, Lobat Tayebi, Fahimeh Sadat Tabatabaei

Abstract

Purpose

In this work, the effects of sodium chloride (NaCl) on gene expression of planktonic Streptococcus mutans cells are investigated. Also assessed are the effects of NaCl on zeta potential of sound and demineralized dentin.

Methods

The relative level of glucosyltransferase B (gtfB), gtfC and gtfD transcription of S. mutans in the presence of NaCl was evaluated by quantitative polymerase chain reaction (qPCR). The osmolality of varying salt (NaCl) concentrations and their influence on the zeta potential of sound and demineralized dentin was investigated as well.

Results

NaCl significantly reduced the expression of gtfB and C genes in planktonic S. mutans; whereas, gtf D gene expression significantly increased in the presence of NaCl (P < 0.05). NaCl at concentrations of 37.5 mg/ml reduced zeta potential of demineralized dentin, while no significant decrease of zeta potential was found when sound dentin was exposed to this concentration.

Conclusion

NaCl reduces the expression of some gtfs in S. mutans and increases negative potential charge of demineralized dentin.

https://ift.tt/2LShkYA

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

Publication date: Available online 4 August 2018

Source: Acta Otorrinolaringológica Española

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

Resumen

Introducción y objetivos

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

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

Método

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

Resultados

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

Conclusión

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

Abstract

Introduction and objectives

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

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

Methods

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

Results

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

Conclusion

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

https://ift.tt/2n9Rctt

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

Publication date: Available online 4 August 2018

Source: Acta Otorrinolaringológica Española

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

Resumen

Introducción y objetivos

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

Métodos

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

Resultados

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

Conclusiones

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

Abstract

Introduction and objectives

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

Methods

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

Results

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

Conclusion

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

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Dual intestinal anomalies in dizygotic twins

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

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

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

https://ift.tt/2vB2jPY

Unexpected manifestation of cardiac amyloidosis

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

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

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

https://ift.tt/2vBkdSt

Treatment of nasal myiasis with ivermectin irrigation

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

https://ift.tt/2ndRkbb

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

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

https://ift.tt/2vDoViy

Appendiceal schwannoma: a rare cause of perforated appendicitis

Description 

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

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

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

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Iliac bone tuberculosis with bicompartmental abscess

Description 

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

https://ift.tt/2vBk1CJ

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

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

https://ift.tt/2n9NHmL

Inflammatory myofibroblastic tumour mimicking a vocal cord polyp

Description 

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

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

Figure 1

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

The rest of the clinical examination was normal.

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

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

Abstract

Purpose

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

Methods

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

Results

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

Conclusion

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

https://ift.tt/2M3fUK3

Maxillomandibular Advancement Improves Multiple Health-Related and Functional Outcomes in Patients With Obstructive Sleep Apnea: A Multicenter Study

Publication date: Available online 4 August 2018

Source: Journal of Oral and Maxillofacial Surgery

Author(s): Scott B. Boyd, Radhika Chigurupati, Joseph E. Cillo, Gail Eskes, Reginald Goodday, Tina Meisami, Christopher F. Viozzi, Peter Waite, James Wilson

Purpose

To comprehensively determine the effectiveness and safety of maxillomandibular advancement (MMA) for the treatment of obstructive sleep apnea (OSA).

Patients and Methods

We designed and implemented a prospective multicenter cohort study to evaluate OSA patients who underwent MMA. The primary outcome measures and associated instruments included sleepiness (Epworth Sleepiness Scale [ESS]), quality of life (QOL) (Functional Outcomes of Sleep Questionnaire [FOSQ]), sleep-disordered breathing (apnea-hypopnea index), cardiovascular risk (office blood pressure and levels of high-sensitivity C-reactive protein), and neurocognitive performance (psychomotor vigilance testing [PVT]). The outcomes were measured preoperatively and approximately 6 months postoperatively. Other variables were grouped into the following categories: demographic and pre-MMA use of continuous positive airway pressure. Descriptive and bivariate statistics were computed.

Results

The sample was composed of 30 adult patients (63% men; mean age, 45.9 ± 9.8 years). The median length of follow-up was 6.7 months (range, 4.3 to 12.7 months). The ESS score decreased from a mean of 13.3 to 4.9 (P < .001). The FOSQ score increased from a mean of 14.1 to 18.3 (P < .001). The apnea-hypopnea index decreased from a mean of 39.6 to 7.9 events per hour (P < .001). Mean diastolic blood pressure decreased from 83 to 79.7 mm Hg (P = .025). PVT response times improved after MMA (P = .04). Few treatment-related adverse events occurred, which had minimal impact on the QOL. Additional improvements in sleepiness (mean ESS score change, –7.6; P < .001), QOL (mean FOSQ score change, 3.9; P < .001), and PVT (mean change, 0.5; P = .004) occurred after MMA for patients using continuous positive airway pressure before surgery.

Conclusions

MMA is a highly effective and safe treatment for OSA, which predictably leads to significant improvements in sleepiness, QOL, sleep-disordered breathing, and neurocognitive performance, as well as a reduction in cardiovascular risk (blood pressure).

https://ift.tt/2KprHO4

A Slow-Growing Fibrous Parapharyngeal Mass.

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A Slow-Growing Fibrous Parapharyngeal Mass.

JAMA Otolaryngol Head Neck Surg. 2018 Aug 02;:

Authors: Farlow JL, McHugh JB, Spector ME

PMID: 30073299 [PubMed - as supplied by publisher]

https://ift.tt/2Mg6Pu9

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

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

JAMA Otolaryngol Head Neck Surg. 2018 Aug 02;:

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

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

PMID: 30073295 [PubMed - as supplied by publisher]

https://ift.tt/2LTOLtC

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

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

JAMA Otolaryngol Head Neck Surg. 2018 Aug 02;:

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

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

PMID: 30073285 [PubMed - as supplied by publisher]

https://ift.tt/2vkCDHS

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

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

JAMA Otolaryngol Head Neck Surg. 2018 Aug 02;:

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

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

PMID: 30073253 [PubMed - as supplied by publisher]

https://ift.tt/2Oe0al1

Cricopharyngeal Muscle Dysfunction Following Hypoglossal Nerve Stimulator Placement.

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Cricopharyngeal Muscle Dysfunction Following Hypoglossal Nerve Stimulator Placement.

JAMA Otolaryngol Head Neck Surg. 2018 Aug 02;:

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

PMID: 30073244 [PubMed - as supplied by publisher]

https://ift.tt/2M3hc7G

Intranasal endoscopic prelacrimal recess approach for maxillary sinus inverted papilloma

Abstract

Purpose

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

Methods

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

Results

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

Conclusion

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

https://ift.tt/2OJ0sBm

Impact of Temporomandibular Disorders and Sleep Bruxism on Oral Health-Related Quality of Life of Individuals With Complete Cleft Lip and Palate

The temporomandibular disorders (TMDs) and sleep bruxism (SB) affect the quality of life (QoL) of the individuals in general. However, the literature lacks studies on individuals with cleft lip and palate (CLP). Thus, this study aimed to evaluate the impact of TMD and SB on the oral health-related quality of life (OHRQoL) of individuals with CLP. Thirty-six individuals, both genders, aged between 30 and 50 years, at routine treatment in the Dental Prosthesis Sector of Hospital for Rehabilitation of Craniofacial Anomalies—University of São Paulo were selected and divided into the following groups: G1—unilateral complete CLP (n = 22) and G2—bilateral complete CLP (n = 14). Three questionnaires were applied: Oral Health Impact Profile (OHIP-14), SB self-report and Research Diagnosis Criteria for TMD. Fisher test, Mann–Whitney test, and t test were applied to verify values between TMD, SB, gender, and OHIP-14 (P 

https://ift.tt/2vj70hX

Complications After Scalp Suturing Posttraumatic Avulsion

Scalp avulsion is a rare but severe trauma. Most cases of this injury happened as a result of hair entrapment in a high-speed rotating machine. Treatment of scalp avulsion can be challenging. Nowadays, microsurgical scalp replantation has become the treatment of choice. However, there are situations in which replantation or even usage of scalp as composite grafts is not possible. The aim of this paper is to present 2 cases of scalp avulsion, which needed split-thickness skin graft for covering posttraumatic scalp loss. Closing large scalp defects after its avulsion by skin graft is still a viable option, especially when replantation and even usage of scalp as a composite graft is not achievable. Scalp shaving is mandatory before any surgical procedures. Address correspondence and reprint requests to Marta Fijałkowska, MD, PhD, Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital No 1, Kopcińskiego Street 22, 90-153 Lodz, Poland; E-mail: fijalkowska.m@wp.pl Received 5 April, 2018 Accepted 23 May, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

https://ift.tt/2O9Avtu

Staged Raising of a Coronal Flap for Fronto-Orbital Advancement and Remodeling in Saethre–Chotzen Syndrome Complicated by Sinus Pericranii

This article reports the surgical management of a 3-month-old girl with Saethre–Chotzen syndrome, who presented with bicoronal synostosis and a large midline sinus pericranii with abnormal cerebral venous drainage via scalp veins. Raised intracranial pressure was demonstrated on monitoring, indicating the need for calvarial expansion necessitating a coronal access incision. A 2-staged delayed raising of the coronal flap was performed to reduce the potential risk of cerebral venous infarction. Monitoring for clinical sequelae and a computerised tomography venogram followed each of these procedures, demonstrating successful redirection of the venous drainage of the brain posteriorly. Finally, a successful fronto-orbital advancement and remodeling procedure was performed with no complications. Address correspondence and reprint requests to David Johnson, DM, MA, BMBCh, FRCS (Plast), Oxford Craniofacial Unit, West Wing, John Radcliffe Hospital, Headington, OX3 9DU, UK; E-mail: davidjohnson@doctors.org.uk Received 14 January, 2018 Accepted 1 June, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

https://ift.tt/2M7kLKs

Surgical Correction of Proptosis in Craniofacial Benign Bone Lesions Involving the Orbit

Craniofacial bone lesions involving the orbit are often associated with symptoms, including proptosis, orbital dystopia, and overall facial asymmetry. Fibrous dysplasia and osteoma are the 2 most commonly observed bone tumors in the craniofacial area. Nine patients with either craniofacial fibrous dysplasia or osteoma and an unacceptable aesthetic appearance were treated from January 2015 to July 2016. All patients underwent preoperative craniofacial 3-dimensional computed tomographic (CT) scanning, and standard photographs were obtained. Proptosis measurements were performed on CT images using an annotation ruler provided by the imaging system both pre- and postoperatively. All patients were treated surgically, and a coronal incision was used. Outcomes were assessed by CT scans, and photographs were obtained during routine follow-ups at 1 week, 3 to 6 months, and 1 year after surgery. The Likert scale was used to investigate patients' postoperative satisfaction rate. Favorable outcomes were achieved in all patients. The mean difference between eyeball proptosis was reduced from 3.6 mm before surgery to 1.6, 0.6, and 0.3 mm after the surgery at 1 week, 3 to 6 months, and 1 year, respectively. No complications, such as facial and/or optic nerve injury, recurrence, and malignant degeneration, were noted. This study demonstrated that surgical treatment of craniofacial bone lesions involving the orbit achieved acceptable results shortly after the surgery, and more prominently, starting from 3 to 6 months. Address correspondence and reprint requests to Dejun Cao, MD, PhD, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, China 200011; E-mails: dejuncao@sjtu.edu.cn, dejuncao@163.com Received 1 November, 2017 Accepted 1 June, 2018 This study was supported by Medical-Engineering Cross Foundation of Shanghai Jiao Tong University (award number: YG2015QN06; grant recipient: Dr Zheyuan Yu). The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

https://ift.tt/2Mizz5F

A Shift in the Orbit: Immediate Endoscopic Reconstruction After Transnasal Orbital Tumors Resection Response

No abstract available

https://ift.tt/2vhVXpr

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

Abstract

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

https://ift.tt/2OIFH92