Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Πέμπτη 9 Μαΐου 2019

Autoimmunity

Chaperones of the class I peptide-loading complex facilitate the constitutive presentation of endogenous antigens on HLA-DP84GGPM87

Publication date: Available online 8 May 2019

Source: Journal of Autoimmunity

Author(s): Mark Anczurowski, Kenji Sugata, Yukiko Matsunaga, Yuki Yamashita, Chung-Hsi Wang, Tingxi Guo, Kenji Murata, Hiroshi Saijo, Yuki Kagoya, Kayoko Saso, Marcus O. Butler, Naoto Hirano

Abstract

Recent work has delineated key differences in the antigen processing and presentation mechanisms underlying HLA-DP alleles encoding glycine at position 84 of the DPβ chain (DP84GGPM87). These DPs are unable to associate with the class II-associated Ii peptide (CLIP) region of the invariant chain (Ii) chaperone early in the endocytic pathway, leading to continuous presentation of endogenous antigens. However, little is known about the chaperone support involved in the loading of these endogenous antigens onto DP molecules. Here, we demonstrate the proteasome and TAP dependency of this pathway and reveal the ability of HLA class I to compete with DP84GGPM87 for the presentation of endogenous antigens, suggesting that shared subcellular machinery may exist between the two classes of HLA. We identify physical interactions of prototypical class I-associated chaperones with numerous DP alleles, including TAP2, tapasin, ERp57, calnexin, and calreticulin, using a conventional immunoprecipitation and immunoblot approach and confirm the existence of these interactions in vivothrough the use of the BioID2 proximal biotinylation system in human cells. Based on immunological assays, we then demonstrate the ability of each of these chaperones to facilitate the presentation of endogenously derived, but not exogenously derived, antigens on DP molecules. Considering previous genetic and clinical studies linking DP84GGPM87 to disease frequency and severity in autoimmune disease, viral infections, and cancer, we suggest that the above chaperones may form the molecular basis of these observable clinical differences through facilitating the presentation of endogenously derived antigens to CD4+ T cells.



The role of protein SUMOylation in rheumatoid arthritis

Publication date: Available online 8 May 2019

Source: Journal of Autoimmunity

Author(s): Sajad Dehnavi, Mahvash Sadeghi, Thomas P. Johnston, George Barreto, Mojtaba Shohan, Amirhossein Sahebkar

Abstract

Small ubiquitin-like modifier (SUMO) proteins, as a subgroup of post-translational modifiers, act to change the function of proteins. Through their interactions with different targets, immune pathways, and the responses they elicit, can be affected by these SUMO conjugations. Thus, both a change to protein function and involvement in immune pathways has the potential to promote an efficient immune response to either a pathogenic challenge, or the development of an imbalance that could lead to an autoimmune-based disease. Also, a variety of changes such as mutations and polymorphisms can interfere with common functions of these modifications and move an effective immune response in the direction of an autoimmune disease. The present review discusses the general characteristics of SUMO proteins and focuses on their involvement in rheumatoid arthritis as an autoimmune disease.



Chronic inflammatory demyelinating polyneuropathy as an autoimmune disease

Publication date: Available online 6 May 2019

Source: Journal of Autoimmunity

Author(s): Yhojan Rodríguez, Nikhil Vatti, Carolina Ramírez-Santana, Christopher Chang, Oscar Mancera-Páez, M. Eric Gershwin, Juan-Manuel Anaya

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease characterized by neurological symptoms and signs of progressive weakness, paresthesias, and sensory dysfunction. Other symptoms include reduced or absent tendon reflexes, cranial nerve involvement, autonomic symptoms, ataxia, and neuropathic pain. Unlike other autoimmune diseases, CIDP generally affects older individuals and has a male predominance. The onset is generally insidious and can take up to 8 weeks with a relapsing-recovery pattern. Like all autoimmune diseases, the etiology is multifactorial, with both genetic and environmental factors contributing to it. Case reports of CIDP have found associations with multiple pathogenic organisms including Hepatitis B and C viruses, Bartonella henselaeMycoplasma pneumoniae, Human immunodeficiency virus, Cytomegalovirus and Epstein-Barr virus. Possible antigenic self-targets include myelin protein 0, myelin protein 2, peripheral myelin protein 22, Connexin 32, and myelin basic protein. Antibodies targeting the Ranvier node proteins such as contactin-1, contactin-associated protein 1, and neurofascin 155 have been described. CIDP is treated with rehabilitation and pharmacological modalities. Pharmacological treatments target autoimmune dysfunction and include corticosteroids, intravenous immunoglobulin, subcutaneous immunoglobulin, plasma exchange, immunosuppressive and immunomodulatory agents such as methotrexate, cyclophosphamide, rituximab, and mycophenolate mofetil. Although there are few observational studies and randomized clinical trials with limited evidence supporting the use of immunosuppressive drugs, they are widely used in clinical practice. A comprehensive review of CIDP is presented herein in light of the autoimmune tautology.



Myelin oligodendrocyte glycoprotein revisited—sensitive detection of MOG-specific T-cells in multiple sclerosis

Publication date: Available online 1 May 2019

Source: Journal of Autoimmunity

Author(s): Mattias Bronge, Sabrina Ruhrmann, Claudia Carvalho-Queiroz, Ola B. Nilsson, Andreas Kaiser, Erik Holmgren, Caterina Macrini, Stephan Winklmeier, Edgar Meinl, Lou Brundin, Mohsen Khademi, Tomas Olsson, Guro Gafvelin, Hans Grönlund

Abstract

Autoreactive CD4+ T-cells are believed to be a main driver of multiple sclerosis (MS). Myelin oligodendrocyte glycoprotein (MOG) is considered an autoantigen, yet doubted in recent years. The reason is in part due to low frequency and titers of MOG autoantibodies and the challenge to detect MOG-specific T-cells. In this study we aimed to analyze T-cell reactivity and frequency utilizing a novel method for detection of antigen-specific T-cells with bead-bound MOG as stimulant.

Peripheral blood mononuclear cells (PBMCs) from natalizumab treated persons with MS (n = 52) and healthy controls (HCs) (n = 24) were analyzed by IFNγ/IL-22/IL-17A FluoroSpot. A higher number of IFNγ (P = 0.001), IL-22 (P = 0.003), IL-17A (P < 0.0001) as well as double and triple cytokine producing MOG-specific T-cells were detected in persons with MS compared to HCs. Of the patients, 46.2–59.6% displayed MOG-reactivity. Depletion of CD4+ T-cells or monocytes or blocking HLA-DR completely eliminated the MOG specific response. Anti-MOG antibodies did not correlate with T-cell MOG-responses.

In conclusion, we present a sensitive method to detect circulating autoreactive CD4+ T-cells producing IFNγ, IL-22 or IL-17A using MOG as a model antigen. Further, we demonstrate that MOG-specific T-cells are present in approximately half of persons with MS.

Graphical abstract

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Primary immunodeficiency and autoimmunity: A comprehensive review

Publication date: May 2019

Source: Journal of Autoimmunity, Volume 99

Author(s): Laura Amaya-Uribe, Manuel Rojas, Gholamreza Azizi, Juan-Manuel Anaya, M. Eric Gershwin

Abstract

The primary immunodeficiency diseases (PIDs) include many genetic disorders that affect different components of the innate and adaptive responses. The number of distinct genetic PIDs has increased exponentially with improved methods of detection and advanced laboratory methodology. Patients with PIDs have an increased susceptibility to infectious diseases and non-infectious complications including allergies, malignancies and autoimmune diseases (ADs), the latter being the first manifestation of PIDs in several cases. There are two types of PIDS. Monogenic immunodeficiencies due to mutations in genes involved in immunological tolerance that increase the predisposition to develop autoimmunity including polyautoimmunity, and polygenic immunodeficiencies characterized by a heterogeneous clinical presentation that can be explained by a complex pathophysiology and which may have a multifactorial etiology. The high prevalence of ADs in PIDs demonstrates the intricate relationships between the mechanisms of these two conditions. Defects in central and peripheral tolerance, including mutations in AIRE and T regulatory cells respectively, are thought to be crucial in the development of ADs in these patients. In fact, pathology that leads to PID often also impacts the Treg/Th17 balance that may ease the appearance of a proinflammatory environment, increasing the odds for the development of autoimmunity. Furthermore, the influence of chronic and recurrent infections through molecular mimicry, bystander activation and super antigens activation are supposed to be pivotal for the development of autoimmunity. These multiple mechanisms are associated with diverse clinical subphenotypes that hinders an accurate diagnosis in clinical settings, and in some cases, may delay the selection of suitable pharmacological therapies. Herein, a comprehensively appraisal of the common mechanisms among these conditions, together with clinical pearls for treatment and diagnosis is presented.



Ischemic stroke in giant-cell arteritis: French retrospective study

Publication date: May 2019

Source: Journal of Autoimmunity, Volume 99

Author(s): Aaron Pariente, Alexis Guédon, Sonia Alamowitch, Sara Thietart, Fabrice Carrat, Stephen Delorme, Jean Capron, Carlotta Cacciatore, Michael Soussan, Azeddine Dellal, Olivier Fain, Arsene Mekinian

Abstract

Acute cerebrovascular ischemic events are a rare and severe complication of giant cell arteritis (GCA). We aimed to determine the prevalence of GCA-related stroke, the overall survival and the relapse-free survival in patients with GCA.

A multicentric retrospective analysis was performed on 129 patients with GCA diagnosed between September 2010 and October 2018 in two University Hospitals. Among 129 GCA patients, 18 (16%) presented an acute ischemic cerebrovascular event. Patients with stroke were older (83 [67–96] years versus 76 [58–96]; p = 0.014) and more frequently males (61% versus 30%; p = 0.014) than those without stroke. The frequency of anterior ischemic optic neuropathy was higher in patients with stroke (n = 6, 33%) than patients without stroke (n = 12, 11%)(p = 0.02). Overall survival was significantly decreased in GCA patients with stroke (4.4 months), comparatively to patients without stroke (221.7 months; log rank test = 0.006). The 3-years relapse-free survival was decreased in patients with stroke (8.42 versus78.0 months; log rank = 0.0001), as well as the time with sustained remission (78 versus 139 months; log rank test = 0.0004). This study shows the prevalence and risk factors of ischemic stroke in GCA.



Autophagy promotes aortic adventitial fibrosis via the IL-6/Jak1 signaling pathway in Takayasu's arteritis

Publication date: May 2019

Source: Journal of Autoimmunity, Volume 99

Author(s): Rongyi Chen, Ying Sun, Xiaomeng Cui, Zongfei Ji, Xiufang Kong, Sifan Wu, Qingrong Huang, Xiaoming Dai, Si Zhang, Lili Ma, Lindi Jiang

Abstract
Background

Autophagy is a ubiquitous and evolutionarily conserved self-rescue process. Studies have shown that autophagy is involved in the pathogenesis of multiple diseases; however, whether autophagy is associated with the pathogenesis of Takayasu's arteritis (TA), a large vessel idiopathic inflammatory disease characterized by vascular fibrosis, remains unclear. Moreover, although IL-6 is believed to be a direct target for TA treatment, anti-IL-6 treatment could not block TA-associated fibrosis in some cases, which impairs the aortic function of patients and can result in death. Thus, identify the mechanisms associated with TA is extremely important. Based on the relationship between autophagy and IL-6, we investigated the role of autophagy in the vascular fibrosis of TA induced by IL-6.

Methods

Autophagy proteins (LC3 and Atg3), IL-6, and markers of fibrosis (collagen 1 and α-SMA) were detected in tissues with TA lesions via immunochemistry, immunofluorescence, and Western blot, respectively. Different stages of autophagy were analyzed by the specific inhibitors, 3-methyladenosine (early stage), hydroxychloroquine sulfate (late stage), and bafilomycin A1 (late stage). Autophagosomes were detected using electron microscopy and a viral-vector transfection assay. The fibrosis profiles induced by IL-6-dependent autophagy was assessed with an ELISA.

Results

The expression of autophagy, IL-6, and fibrosis markers were elevated and correlated with each other in the adventitia tissues of TA patients. Furthermore, exogenous IL-6/IL-6Rα could significantly increase autophagy and fibrosis in vitro. An autophagy inhibitor was found to significantly block both autophagy and fibrosis induced by IL-6. Finally, IL-6 was found to significantly promote autophagy-induced fibrosis through the activation of the Jak1 pathway.

Conclusions

IL-6-induced autophagy plays an important role in vascular fibrosis of TA. Targeting autophagy pathways might represent a novel therapeutic option for the treatment of TA.



Histologically proven AMA positive primary biliary cholangitis but normal serum alkaline phosphatase: Is alkaline phosphatase truly a surrogate marker?

Publication date: May 2019

Source: Journal of Autoimmunity, Volume 99

Author(s): Chunyan Sun, Xiao Xiao, Li Yan, Li Sheng, Qixia Wang, Pan Jiang, Min Lian, Yanmei Li, Yiran Wei, Jun Zhang, Yong Chen, Bo Li, You Li, Binyuan Huang, Yikang Li, Yanshen Peng, Xiaoyu Chen, Jingyuan Fang, Dekai Qiu, Jing Hua

Abstract
Background and aims

The most highly directed and specific autoantibody in human immunopathology is the serologic hallmark of primary biliary cholangitis (PBC), antimitochondrial antibodies (AMAs). However the clinical significance of finding a positive AMA, with normal alkaline phosphatase (ALP) remains enigmatic.

Methods

We took advantage of 169 consecutive outpatients who were identified as having a positive AMA, but normal ALP levels between January 2012 and January 2018. A liver biopsy was performed on 67/169 of these AMA positive normal ALP patients.

Results

In all 169 patients we reconfirmed the AMA and also performed anti-gp210 and anti-sp100, liver stiffness (LSM) assessed by vibration-controlled transient elastography (VCTE), an abdominal computed tomography (CT) scan, and either a magnetic resonance imaging (MRI) or ultrasound. The liver biopsies were reviewed by two unbiased observers. 87.6% of the 169 patients were females with a mean age of 46; the median AMA titer 1:320; an elevated serum IgM was found in 53.3%. Importantly, in patients with a liver biopsy, 55(82.1%)out of 67 had varying degrees of cholangitis activity, diagnostic of PBC.

Conclusion

In patients who were AMA-positive but had normal ALP levels, more than 80% were associated with histological classic PBC. These data emphasize the importance of a positive AMA, even with a normal ALP and also question the role of ALP as a sole surrogate marker of cholangitis.



PAM3 supports the generation of M2-like macrophages from lupus patient monocytes and improves disease outcome in murine lupus

Publication date: May 2019

Source: Journal of Autoimmunity, Volume 99

Author(s): Begum Horuluoglu, Defne Bayik, Neslihan Kayraklioglu, Emilie Goguet, Mariana J. Kaplan, Dennis M. Klinman

Abstract

Systematic Lupus Erythematosus (SLE) is an autoimmune syndrome of unclear etiology. While T and B cell abnormalities contribute to disease pathogenesis, recent work suggests that inflammatory M1-like macrophages also play a role. Previous work showed that the TLR2/1 agonist PAM3CSK4 (PAM3) could stimulate normal human monocytes to preferentially differentiate into immunosuppressive M2-like rather than inflammatory M1-like macrophages. This raised the possibility of PAM3 being used to normalize the M1:M2 ratio in SLE. Consistent with that possibility, monocytes from lupus patients differentiated into M2-like macrophages when treated with PAM3 in vitro. Furthermore, lupus-prone NZB x NZW F1 mice responded similarly to weekly PAM3 treatment. Normalization of the M2 macrophage frequency was associated with delayed disease progression, decreased autoantibody and inflammatory cytokine synthesis, reduced proteinuria and prolonged survival in NZB x NZW F1 mice. The ability of PAM3 to bias monocyte differentiation in favor of immunosuppressive macrophages may represent a novel approach to the therapy of SLE.



Elevated autoimmunity in residents living near abandoned uranium mine sites on the Navajo Nation

Publication date: May 2019

Source: Journal of Autoimmunity, Volume 99

Author(s): Esther Erdei, Chris Shuey, Bernadette Pacheco, Miranda Cajero, Johnnye Lewis, Robert L. Rubin

Abstract

Specific autoantibodies were assessed among residents of the Navajo Nation in New Mexico chronically exposed to metal mixtures from uranium mine wastes and in drinking water supplies. Age and the extent of exposure to legacy waste from 100 abandoned uranium mine and mill sites were associated with antibodies to denatured DNA, previously known to be an early indicator of medication-induced autoimmunity. Surprisingly, autoantibodies to native DNA and/or chromatin were also linked to environmental exposure, specifically uranium consumption through drinking water for both men and women, while urinary arsenic was negatively associated with these autoantibodies in women. These findings suggest that contaminants derived from uranium mine waste enhanced development of autoantibodies in some individuals, while arsenic may be globally immunosuppressive with gender-specific effects. Specific autoantibodies may be a sensitive indicator of immune perturbation by environmental toxicants, an adverse effect not considered in current drinking water standards or regulatory risk assessment evaluations.



EJNMMI Radiopharmacy and Chemistry

Endorsement of International Consensus Radiochemistry Nomenclature Guidelines


Open letter to journal editors on: International Consensus Radiochemistry Nomenclature Guidelines


Molecular imaging of multiple sclerosis: from the clinical demand to novel radiotracers
Brain PET imaging with different tracers is mainly clinically used in the field of neurodegenerative diseases and brain tumors. In recent years, the potential usefulness of PET has also gained attention in the...

Automated synthesis of [11C]L-glutamine on Synthra HCN plus synthesis module
L-Glutamine (L-Gln) is the most abundant amino acid present in the human body and is involved in numerous metabolic pathways. Glutaminolysis is the metabolic process deployed by many aggressive cancers such as...

Radiosynthesis and in vivo evaluation of 11C-labeled BMS-193885 and its desmethyl analog as PET tracers for neuropeptide Y1 receptors
Neuropeptide Y (NPY) has been implicated in a wide variety of physiological processes, including feeding, learning, memory, emotion, cardiovascular homeostasis, hormone secretion, and circadian rhythms. NPY Yl...

Pediatric Surgery Case Reports

Melanotic neuroectodermal tumor of infancy

Publication date: July 2019

Source: Journal of Pediatric Surgery Case Reports, Volume 46

Author(s): Hao Tran Kiem, Kim Hoa Nguyen Thi, Phu Tran Xuan, Loi Nguyen Hong, Son Nguyen Huu, Duy Phan Canh, Carlos Rodriguez Galindo, McKay McKinnon

Abstract
Introduction

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, rapidly growing pigmented neoplasm of neural crest origin generally arising in infants during the first year of life.

Case

We report a 15-month old male who presented with a 2-month history of a rapidly growing mass in the anterior. A biopsy showed melanotic neuroectodermal tumor, and complete resection with negative margins was subsequently achieved. The patient is in remission at 11 months from surgery.

Conclusion

Due to its rapid growth potential and locally destructive behaviour, early diagnosis is extremely important to limit local expansion. The treatment of choice for melanotic neuroectodermal tumor of infancy (MNTI) is surgical excision.



Robot-assisted Heller myotomy for achalasia

Publication date: June 2019

Source: Journal of Pediatric Surgery Case Reports, Volume 45

Author(s): Giulia Fusi, Francesco Molinaro, Francesco Ferrara, Edoardo Bindi, Chiara Pellegrino, Chiara Calani, Mario Messina, Rossella Angotti

Abstract

Achalasia is a rare neuromuscular esophageal disorder in children. There are many surgical options to treatment including botulinum toxin (Botox) injections, oral pharmacologic therapies with nitrates and calcium channel blockers, pneumatic dilation (PD), and surgical myotomy (open surgery, endoscopy, laparoscopy and recently robotic approach). In pediatric age, usually, Heller's myotomy is the main choice. Laparoscopic approach is known and standardized. Few robotic have been published. We decided to report our first case to share our experience with scientific community.



Unexpected finding of an intra-peritoneal toothpick during laparoscopic appendectomy

Publication date: June 2019

Source: Journal of Pediatric Surgery Case Reports, Volume 45

Author(s): Mohamad El Mahmoud, Mohammad Al Onazi, Saad H. Aldosari, Sarah A. Hadi, Reema Alsadhan



Bilateral chest wall mesenchymal hamartomas treated with sclerotherapy and cryoablation

Publication date: June 2019

Source: Journal of Pediatric Surgery Case Reports, Volume 45

Author(s): Kristen A. Calabro, John McGrath, Elizabeth Bowdish

Abstract

Mesenchymal hamartoma of the chest wall is a rare disorder, traditionally treated with mutilating radical excision. We report a case of an infant with bilateral mesenchymal hamartomas (MH) complicated with aneurysmal bone cyst (ABC) features. We subsequently describe a novel technique combining sclerotherapy and cryoablation to achieve non-operative tumor burden reduction in an effort to minimize disfigurement making the MH amenable to less morbid resection.

A 3.5-month-old male presented with bilateral, complex, mixed cystic and solid, chest wall masses consistent with a chest wall mesenchymal hamartoma. Under ultrasound and fluoroscopic guidance, the aneurysmal bone cyst components were aspirated and contrast studies performed to exclude venous drainage. Doxycycline sclerotherapy was performed using dwelling volumes approximately 50–60% of the estimated cyst cavity size. Repeat sclerotherapy was performed on days 85, 147, 229 and 267, with interval imaging guiding timing and location of therapy.

The ABC components responded well to sclerotherapy with significant size decrease of the cystic components. Overall lesion size decreased significantly, with new bone formation noted in response to treatment. The first treatment of computer tomographic (CT)-guided cryoablation was then performed on day 329 to attempt further reduce the size of the solid components. Multiple cryoablation probes were advanced into the mass under CT fluoroscopy. Deep components were treated initially with a series of freeze/thaw cycles. Cryoprobes were then retracted to treat the more superficial portions of the lesion. CT guided cryoablation was repeated on day 601.



Urethral mucosa prolapse in a post-partum patient

Publication date: June 2019

Source: Journal of Pediatric Surgery Case Reports, Volume 45

Author(s): Godwin Turyasingura

Abstract

A 23 year old Ugandan, Black, Mukiga, mother of two presented to us one year after delivery with severe lower abdominal pain, failure to pass urine, slight vaginal bleeding and a mass protruding from her vagina. Vaginal examination revealed she had a prolapsed urethral mucosa which was undergoing ischemic necrosis. Her condition was successfully treated by surgical excision of the prolapsed mucosa. The patient had no urinary, genital or other symptoms at 6 weeks, 6 months and at one and half years follow up.



Pediatric pulmonary mucormycosis in a diabetic patient treated with extended pleurectomy and Clagett procedure

Publication date: June 2019

Source: Journal of Pediatric Surgery Case Reports, Volume 45

Author(s): Rebecca C. Gologorsky, Sora Ely, Kara A. Rothenberg, Carol Glaser, Jeffrey B. Velotta

Abstract

Mucor is a ubiquitous fungus that is non-pathogenic in healthy people. In immunocompromised hosts, nonfunctional or absent neutrophils and macrophages result in fungal invasion and infection [1]. Invasive mucor (mucormycosis) most commonly involves the sinuses, brain, or lungs. Pulmonary mucormycosis typically presents in patients with a history of organ transplantation or hematologic malignancy [2], and is rare in patients with diabetes alone. The epidemiology and management of pediatric pulmonary mucormycosis is poorly described. We report an unusual occurrence of this disease, complicated by segmental pulmonary artery thrombus in a 15-year-old with poorly controlled diabetes. His severe, medication-resistant infection was ultimately treated successfully with antifungal medication combined with aggressive surgical debridement. The pulmonary artery segmental thrombus resolved after treatment of the underlying infection without anticoagulation.



Segmental dilatation of colon detected on prenatal ultrasound

Publication date: June 2019

Source: Journal of Pediatric Surgery Case Reports, Volume 45

Author(s): Naoko Uga, Tatsuya Suzuki, Kouhei Sakurai, Tetsuya Tsukamoto, Tomonori Tsuchiya, Yasuhiro Kondo, Atsuki Naoe, Shunsuke Watanabe, Toshihiro Yasui, Fujio Hara

Abstract

Segmental dilatation of the colon is a rare condition in which there is an abrupt segment of dilated colon between regions of normal colon, without obstruction. The condition causes bilious vomiting and abdominal distention in the neonate, and causes constipation or anemia in infants and adults. We herein report a case of segmental dilatation of the descending colon detected on prenatal sonography. The patient was born at 39 weeks' gestation, weighing 3720 g. At 10 months, he developed constipation and enterocolitis. At 1 year of age, the patient underwent laparoscopic-assisted resection of dilated colon with end-to-end anastomosis. Resection of the dilated segment alone was not sufficient, according to frozen biopsy. Therefore, we resected an additional 3 cm both proximally and distally, where teniae coli were grossly evident. Histological examination of the dilated segment showed muscular layer hypertrophy with hyperplasia and widening of Auerbach's plexus. The patient's 7-month follow-up was unremarkable. With improved quality of prenatal sonography, more patients will be diagnosed with segmental dilatation of the intestine. This is the first report in the English literature of segmental dilatation of the colon detected on prenatal ultrasound.



Intrabronchial valves for persistent pulmonary air leaks in children

Publication date: June 2019

Source: Journal of Pediatric Surgery Case Reports, Volume 45

Author(s): Faisal G. Qureshi, Ahmed Abdelrahman, Mirza Zain Baig, Stephen Megison, Muhanned Abu-Hijleh

Abstract
Background

Surgery to address parenchymal lung disease in children is rare. One of the complications of the surgery is a persistent air leak (PAL). Intrabronchial valves (IBV), which received FDA approval for treating PAL in recent years, limit or exclude the inflow of air towards the pleura and allow air and secretions to flow towards central airways. The valves have been effective in adults with PAL but little has been published on their use in children.

Methods

Retrospective chart review was performed after IRB approval on patients treated with IBV after surgical excision of lung parenchyma. A literature review was then performed.

Results

2 pediatric patients are presented. Patient 1, a 10 year old girl underwent excision of a lung mass that developed persistent air leak. Traditional conservative methods did not seal the air leak for 23 days but an IBV sealed the leak in 24 h. Patient 2, a 6 year old boy underwent a pneumonectomy with post-operative bronhical leak. The bronchus was repaired but a leak persisted for 36 days. An IBV sealed the leak immediately.

Conclusion

Intrabronchial valves can be used for the management of persistent pulmonary air leaks. We propose a tentative algorithm for using the devices in children with PAL.



Urachal cyst and enteric duplication in a pediatric patient

Publication date: June 2019

Source: Journal of Pediatric Surgery Case Reports, Volume 45

Author(s): Allen K. Chen, Michael J. Allshouse

Abstract

Here we present an unusual case of a 3-year-old male with multiple congenital developmental abnormalities discovered during laparotomy: an urachal cyst and enteric duplication. This combination of anomalies has not been described before.



Sleeve lobectomy for an arteriovenous malformation in the bronchus intermedius in a child

Publication date: June 2019

Source: Journal of Pediatric Surgery Case Reports, Volume 45

Author(s): Aditya Sengupta, Othman Aljohani, Howaida El-Said, Aparna Rao, Matthew Brigger, Raghav Murthy

Abstract

Arteriovenous malformations within the tracheobronchial tree in pediatric patients uncommonly present as hemoptysis, and can usually be treated with percutaneous transcatheter embolization. When this fails, parenchymal-sparing operations are needed. While these have been popularized for the management of bronchial neoplasms in children and adults, such bronchoplastic techniques are not commonly performed in children with tracheobronchial vascular malformations and acute hemoptysis. Here, we present a patient with recurrent hemoptysis who was found to have an arteriovenous malformation in the bronchus intermedius, and had failed numerous attempts at coil embolization. Via a right thoracotomy approach, we successfully performed a right middle lobectomy and sleeve resection of the bronchus intermedius. The post-operative recovery was uneventful, and there were no further episodes of hemoptysis. Thus, by applying the principles of bronchoplastic resection, such parenchymal-preserving surgery can be successfully used to manage symptomatic bronchial arteriovenous malformations with hemoptysis.



Τετάρτη 8 Μαΐου 2019

Otolaryngology

Research articleAbstract only
Clinicopathological features of papillary thyroid microcarcinoma with a diameter less than or equal to 5 mm
Lei Yan, Jayjay Blanco, Vijaya Reddy, Samer Al-Khudari, ... Paolo Gattuso
In Press, Accepted Manuscript, Available online 8 May 2019
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Abstract
Abstract
Purpose
This retrospective study was conducted to assess the epidemiological, clinical and histologic characteristics of incidentally identified and presurgically diagnosed papillary thyroid microcarcinomas less than or equal to 5 mm in size (small PTMC).

Materials and methods
Cases from October 2003 to February 2018 were retrieved from pathology databases, and their clinicopathological features were reviewed.

Results
There were a total of 182 cases of small PTMCs, 141 women and 41 men. The mean age at diagnosis was 53.5. Most of the small PTMCs were not detected on clinical examination and workup and were diagnosed incidentally during pathologic examination. 21.4% of small PTMCs showed multifocality, with 21 cases of unilateral multifocal lesions and 18 cases with bilateral multifocal tumors. Small PTMCs were most often follicular variant (51.9%) followed by classic type (47.5%). The average size of follicular variants appeared to be larger than that of the classic type PTMCs (2.84 ± 1.43 mm vs 2.26 ± 1.51 mm, P = 0.01). A total of 66 cases (36.3%) had regional lymph node sampling or selective neck dissection and 15 of these cases identified lymph node metastasis (22.7%). 46.7% of patients with node positive microcarcinomas were male compared with 16% male in group with negative lymph nodes (P = 0.03).

Conclusions
Small PTMCs (≤5 mm) are often multifocal and bilateral and histology is commonly both the classical and follicular variant of PTC. While often diagnosed incidentally small PTMC can lead to regional lymph node involvement in a significant portion of cases and evaluation of the regional lymph nodes should be considered in the clinical management of these patients.

select article An unusual case of sudden sensorineural hearing loss after cycling class
Case reportAbstract only
An unusual case of sudden sensorineural hearing loss after cycling class
Vivian F. Kaul, Sarah Kidwai, Adam Lupicki, Maura Cosetti
In Press, Accepted Manuscript, Available online 25 April 2019
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Abstract
Abstract
In this case report, our patient developed sudden sensorineural hearing loss (SSNHL) after loud noise exposure during a popular cardiovascular group exercise cycling class. To increase awareness among all healthcare professionals of the effects of these modern-day group fitness classes on hearing loss, we describe this case and review the current literature on SSNHL and its management. A 35-year old man developed SSNHL in the setting of loud noise exposure during a high intensity aerobic exercise class. After a short course of oral steroids with no improvement, intratympanic steroids were administered weekly for three weeks. The patient showed minimal improvement; thus, hyperbaric oxygen therapy was conducted. Serial audiograms continued to show severe to profound mixed hearing loss in the right ear. In conclusion, individuals who participate in loud, high-intensity aerobic group-exercise classes should be careful of the potential for noise-induced hearing loss. Aerobic exercise may make these individuals more susceptible to noise-induced hearing loss. Early intervention is critical for any chance of recovery.

select article Practice patterns and knowledge among California pediatricians regarding human papillomavirus and its relation to head and neck cancer
Research articleAbstract only
Practice patterns and knowledge among California pediatricians regarding human papillomavirus and its relation to head and neck cancer
Michael H. Berger, Yarah M. Haidar, Benjamin Bitner, Monica Trent, Tjoson Tjoa
In Press, Corrected Proof, Available online 25 April 2019
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Abstract
Abstract
Objective
To identify practice patterns regarding human papillomavirus (HPV) vaccination efforts and vaccination rates in context of head and neck cancer prevention, identify barriers to vaccination, and identify gaps in knowledge regarding the link between HPV and head and neck cancer in the pediatrician population.

Study design/Methods
A 27-question cross-sectional survey was distributed to members of the four California chapters of the American Academy of Pediatrics.

Results
Of the completed responses, 89.4% identified as "always" recommending the HPV vaccine to patients, but only 19.5% of pediatricians estimated that >75% of their eligible patients had completed the HPV vaccination series. 71.5% of respondents felt that further education about HPV's link to head and neck cancer them more comfortable discussing vaccination. Physicians who were in practice longer were less likely to respond that additional education about HPV and its link to head and neck cancer would make them more comfortable discussing vaccination with patients (p = 0.043). Physicians who were in practice longer were more likely to correctly respond that HPV type 16 is the most common strain linked to head and neck cancer (p = 0.021).

Conclusion
There is need to improve both the knowledge base and comfort level of pediatricians in counseling their patients during vaccine recommendations. Otolaryngologists have a critical role in providing education to physicians, trainees, and the general public in the effort to combat the epidemic of HPV-associated head and neck cancer.

select article The molecular differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma: A bioinformatics study
Research articleAbstract only
The molecular differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma: A bioinformatics study
Jiaming Wang, Xiaoxi Xi, Wei Shang, Aneesha Acharya, ... Xianda Hu
In Press, Corrected Proof, Available online 23 April 2019
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Abstract
Abstract
Objective
To investigate the genetic and epigenetic differences between human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) and HPV-negative OPSCC.

Methods
Microarray data of HPV-positive and -negative OPSCC were retrieved from NCBI GEO datasets. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were identified by performing differential expression analysis. A functional enrichment analysis was performed to explore the biological processes and signaling pathways that DEGs and DE-miRNAs were involved in, respectively. A protein-protein interaction (PPI) network of DEGs was constructed to identify hub genes. miRNA-target network and miRNA-miRNA functional synergistic network were each constructed in order to identify risk-marker miRNAs. An miRNA-target-pathway network was constructed in order to explore the function of identified risk-marker miRNAs.

Results
Microarray data from 3 datasets (GSE39366, GSE40774, and GSE55550) was included and analyzed. The PPI network identified 3 hub genes (VCAM1, UBD, and RPA2). MiR-107 and miR-142-3p were found to play the most significant role in both the DE-miRNA-target network as well as in the miRNA-miRNA functional synergistic network. MiR-107 was involved in HPV-induced tumorigenesis by targeting many genes (CAV1, CDK6, MYB, and SERPINB5) and regulating the p53 signaling pathway, the PI3K-Akt signaling pathway, and the autophagy pathway. In addition, miR-142-3p was implicated in HPV-induced tumorigenesis by targeting the PPFIA1 gene and regulating transcriptional dysregulation and other cancerous pathways.

Conclusion
Three genes (VCAM1, UBD, and RPA2), two miRNAs (miR-107 and miR-142-3p), and four pathways (p53, PI3K-Akt, autophagy, and transcription dysregulation in cancer) were identified to play critical roles in distinguishing HPV-positive OPSCC from HPV-negative OPSCC.

select article Vitamin D deficiency and its relationship to cancer stage in patients who underwent thyroidectomy for papillary thyroid carcinoma.
Research articleAbstract only
Vitamin D deficiency and its relationship to cancer stage in patients who underwent thyroidectomy for papillary thyroid carcinoma.
Anita Sulibhavi, Matthew L. Rohlfing, Scharukh M. Jalisi, David B. McAneny, ... J. Pieter Noordzij
In Press, Corrected Proof, Available online 22 April 2019
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Abstract
Abstract
Purpose
As imaging technology improves and more thyroid nodules and malignancies are identified, it is important to recognize factors associated with malignancy and poor prognosis. Vitamin D has proven useful as a prognostic tool for other cancers and may be similarly useful in thyroid cancer. This study explores the relationship of Vitamin D to papillary thyroid carcinoma stage while accounting for socioeconomic covariates.

Materials and methods
The medical records of all patients who underwent thyroidectomy at one institution between 2000 and 2015 were reviewed. Subjects with non-papillary thyroid cancer pathology, prior malignancy, and without Vitamin D levels were excluded. The remaining 334 patient records were examined for cancer stage, Vitamin D levels, Vitamin D deficiency listed in history, and demographic and comorbid factors.

Results
Vitamin D laboratory values showed no significant relationship to cancer stage (p = 0.871), but patients with Vitamin D deficiency documented in the medical record were more likely to have advanced disease (28.6% versus 14.7%; p = 0.028). The patients with documented Vitamin D deficiency also had lower 25-hydroxyvitamin D nadirs (21.5 ng/mL versus 26.5 ng/mL, p = 0.008) and were more likely to be on Vitamin D supplementation (92.6% versus 41.8%, p < 0.001).

Conclusions
The results suggest that Vitamin D deficiency may have value as a negative prognostic indicator in papillary thyroid cancer and that pre-operative laboratory evaluation may be less useful. This is important because Vitamin D deficiency is modifiable. While different racial subgroups had different rates of Vitamin D deficiency, neither race nor socioeconomic status showed correlation with cancer stage.

select article Failed larynx preservation and survival in patients with advanced larynx cancer
Research articleAbstract only
Failed larynx preservation and survival in patients with advanced larynx cancer
Cheryl C. Nocon, Jessica Yesensky, Gaurav S. Ajmani, Mihir K. Bhayani
In Press, Corrected Proof, Available online 22 April 2019
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Abstract
Abstract
Purpose
To evaluate the survival benefit of total laryngectomy (TL) after induction chemotherapy in locally advanced laryngeal cancer patients.

Materials and methods
This is a retrospective study utilizing the National Cancer Database, which captures >80% of newly diagnosed head and neck squamous cell carcinoma cases in the United States. We included patients diagnosed with advanced stage laryngeal squamous cell carcinoma between 2004 and 2013 (n = 5649) who received either TL (n = 4113; 72.8%) or induction chemotherapy followed by either radiation therapy (n = 1431) or TL (n = 105). Kaplan-Meier curves and Cox proportional hazards regression were used to evaluate overall survival. A Cox regression model was computed to examine how the prognostic impact of treatment differed by clinical stage.

Results
In multivariable analysis, when compared to patients receiving TL alone, those receiving induction chemotherapy followed by TL experienced no significant difference in survival (HR 0.85, 95% CI 0.63–1.13), while those receiving induction chemotherapy followed by radiation experienced poorer survival (HR 1.15, 95% CI 1.06–1.26). Induction chemotherapy followed by TL was associated with improved survival compared to induction chemotherapy and radiation (P = .042). Among patients with T4a tumors, TL (P < .001) and induction chemotherapy followed by TL (P = .002) were both associated with improved survival compared to induction chemotherapy and radiation. There were no survival differences between TL and induction chemotherapy followed by TL (HR 0.76, 95% CI 0.52–1.10).

Conclusions
Larynx preservation may be attempted without compromising survival in patients with locally advanced larynx cancer who fail induction chemotherapy and undergo TL.

select article Improving efficiency in epistaxis transfers in a large health system: Analyzing emergency department treatment variability as pretext for a clinical care pathway
Research articleAbstract only
Improving efficiency in epistaxis transfers in a large health system: Analyzing emergency department treatment variability as pretext for a clinical care pathway
Clare Richardson, Anish Abrol, Chelsea S. Hamill, Nicole Maronian, ... Brian D'Anza
In Press, Corrected Proof, Available online 16 April 2019
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Abstract
Abstract
Introduction
Epistaxis is a common condition with an estimated $100 million in health care costs annually. A significant portion of this stems from Emergency Department (ED) management and hospital transfers. Currently there is no data in the literature clearly depicting the differences in treatment of epistaxis between Emergency Medicine (EM) physicians and Otolaryngologists. Clinical care pathways (CCP) are a way to standardize care and increase efficiency. Our goal was to evaluate the variability in epistaxis management between EM and Otolaryngology physicians in order to determine the potential impact of a system wide clinical care pathway.

Materials and methods
A retrospective case study was conducted of all patients transferred between emergency departments for epistaxis over an 18-month period. Exclusion criteria comprised patients under 18 years old, recent sinonasal surgery, bleeding disorders, and recent facial trauma.

Results
73 patients met inclusion criteria. EM physicians used nasal cautery in 8%, absorbable packing in 1% and non-absorbable packing in 92% (with 33% being bilateral). In comparison, Otolaryngologists used nasal cautery in 37%, absorbable packing in 34%, and non-absorbable packing in 23%. Eighty percent of patients treated by an Otolaryngology physician required less invasive intervention than previously performed by EM physicians prior to transfer.

Conclusions
Epistaxis management varied significantly between Emergency Medicine and Otolaryngology physicians. Numerous patients were treated immediately with non-absorbable packing. On post-transfer Otolaryngology evaluation, many of these patients required less invasive interventions. This study highlights the variability of epistaxis treatment within our hospital system and warrants the need for a standardized care pathway.

select article Predicting transient hypocalcemia in patients with unplanned parathyroidectomy after thyroidectomy
Research articleAbstract only
Predicting transient hypocalcemia in patients with unplanned parathyroidectomy after thyroidectomy
Ramez Philips, Phillip Nulty, Nolan Seim, Yubo Tan, ... Garth Essig
In Press, Corrected Proof, Available online 16 April 2019
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Abstract
Abstract
Objective
To assess the utility of rapid parathyroid hormone (PTH) values in predicting transient post-operative hypocalcemia in patients with unplanned parathyroidectomy during total or completion thyroidectomy.

Methods
All patients who underwent total or completion thyroidectomy between January 2010 and January 2015 were reviewed. Incidences of post-operative hypocalcemia were compared in patients with and without unplanned parathyroidectomy. Unplanned parathyroidectomy was defined as intra-operative incidental or intentional parathyroidectomy. Logistic regression assessed for predictors of hypocalcemia and optimum amount of calcium supplementation.

Results
Thirty-eight (13.6%) patients had evidence of incidental parathyroidectomy and 39/280 (13.9%) patients had parathyroid autotransplantation intra-operatively. Central neck dissection and malignancy were identified as risk factors for unplanned parathyroidectomy (p = 0.001, p = 0.060). Patients with unplanned parathyroidectomy were more likely to have hypocalcemia (p = 0.002) and hypoparathyroidism (p < 0.0005). PTH value was the only significant predictor of hypocalcemia in these patients. In patients with a post-operative PTH of ≤15, initial calcium supplementation ≥ 1000 mg decreased the risk of hypocalcemia (p < 0.05).

Conclusion
Post-operative PTH value predicts hypocalcemia in patients undergoing total and completion thyroidectomy with unplanned parathyroidectomy. In patients with a post-operative PTH < 15, initial calcium supplementation with ≥1000 mg of elemental calcium is recommended.

select article Clinical practice patterns in laryngeal cancer and introduction of CT lung screening
Research articleAbstract only
Clinical practice patterns in laryngeal cancer and introduction of CT lung screening
Krzysztof Piersiala, Lee M. Akst, Alexander T. Hillel, Simon R. Best
In Press, Corrected Proof, Available online 12 April 2019
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Abstract
Abstract
Objectives
After the publication of large clinical trials, in January 2014 The U.S. Preventive Services Task Force (USPSTF) recommended annual lung cancer screening with low-dose CT in a well-defined group of high-risk smokers. A significant proportion of patients with laryngeal cancer (LC) meet the introduced criteria, and we hypothesized that clinical practice would change as a result of these evidence-based guidelines.

Methods
Retrospective chart review of patients diagnosed with LC and treated at Johns Hopkins Hospital who met USPSTF criteria for annual chest screening and were followed for at least 3 consecutive years in the years surrounding the introduction of screening guidelines (January 2010 to December 2017) was performed to identify those who had recommended screening CT chest.

Results
A total of 151 patients met the inclusion criteria of the study and were followed for a total of 746 patient-years. 184/332 (55%) patient-years in the pre-guidelines period and 246/414 (59%) in the post-guidelines period included at least one recommended chest imaging (CT or PET-CT; p = 0.27). 248/332 (75%) patient-years in the pre-guidelines period and 314/414 (76%) in the post-guidelines period included any radiological chest imaging (X-ray, CT or PET-CT; p = 0.72). Screening scans were ordered by OHNS (45%), Medical Oncology (31%), Radiation Oncology (8%), and primary care (14%) with 70% of patients missing at least one year of indicated screening.

Conclusions
The implementation of new lung cancer screening guidelines did not change clinical practice in the management of patients with LC and many patients do not receive recommended screening. Further study concerning potential barriers to effective evidence-based screening and coordination of care is warranted.

select article Wideband Tympanmetry Results of Bone Cement Ossiculoplasty
Research articleAbstract only
Wideband Tympanmetry Results of Bone Cement Ossiculoplasty
O. Yigit, S. Tokgoz-Yilmaz, E. Tahir, M.D. Bajin, ... L. Sennaroglu
In Press, Corrected Proof, Available online 12 April 2019
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Abstract
Abstract
Objective
We aim to investigate hearing sensitivity and wideband tympanometry results in bone cement ossiculoplasty cases in present study.

Study design
A prospective study.

Setting
Ossiculoplasty patients were grouped according to the anatomical location of bone cement application by surgery note. Ossiculoplasty and tympanoplasty patients were retrospectively invited to the clinic and evaluated. 30 bone cement ossiculoplasty cases as well as 30 Type I tympanoplasty cases (intact ossicular chain) and 30 healthy controls were included in the study and Wideband Tympanometry was performed. Tympanometric peak pressure, equivalent middle ear volume, static admittance, tympanogram width, resonance frequency, average wideband tympanometry and absorbance measurements were analyzed.

Results
A statistically significant improvement was observed in the hearing levels of all ossiculoplasty and type I tympanoplasty patients (p < 0.05). Bone cement ossiculoplasty groups demonstrated the remarkable differences than the type I tympanoplasty and control group in Wideband Tympanometry test parameters. In some parameters, malleus-stapes and manubriostapedioplasty groups demonstrated similarities to Type I tympanoplasty and control groups.

Conclusion
Bone cement is an effective application for ossiculoplasty. Wideband tympanometry is a promising method for the evaluation of the middle ear dynamics.

select article Intracapsular hemorrhage rates in non-fixated nylon sheet orbital implants for orbital fracture management
Research articleAbstract only
Intracapsular hemorrhage rates in non-fixated nylon sheet orbital implants for orbital fracture management
Mark A. Prendes, Brett Gudgel, Enoch B. Kassa, Amelia M. Todd, ... H.B. Harold Lee
In Press, Corrected Proof, Available online 9 April 2019
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Abstract
Abstract
Purpose
To examine the incidence of intracapsular hemorrhage in orbital fracture repair with non-fixated nylon sheet implants.

Methods
A retrospective chart review of 227 patients presenting from January 2013 to December 2016 for orbital fracture repair with nylon sheet implants.

Results
Of the 331 orbital fractures repaired over 4 years, a total of 227 met inclusion criteria. The average implant thickness was 0.38 mm and no implants were fixated. Four total implants (1.8%) were removed due to complications; one each secondary to exploration for ongoing postoperative diplopia, immediate post-operative orbital hemorrhage, a cystic mass anterior to the implant, and pain. There were no cases of intracapsular hemorrhage nor infection for any of the 227 patients over 4 years.

Conclusions
To the authors knowledge, this represents the largest case series to date to assess the rate of intracapsular hemorrhage in non-fixated nylon sheet orbital implants. In the 227 cases reviewed over a 4-year period, there were no cases of intracapsular hemorrhage. This suggests a much lower complication rate than previously reported.

Précis
A case series of 227 patients who underwent orbital fracture repair with non-fixated nylon sheet implants.

select article Atypical thyroglossal duct cyst with intra-laryngeal and para-glottic extension
Case reportAbstract only
Atypical thyroglossal duct cyst with intra-laryngeal and para-glottic extension
Adele Chin Wei Ng, Heng Wai Yuen, Xin Yong Huang
In Press, Corrected Proof, Available online 8 April 2019
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Abstract
Abstract
Thyroglossal duct cysts (TDC) are the most common congenital neck masses. Although they are anatomically closely related to the larynx, intra-laryngeal extension is very rare. We present a case, review the literature and discuss the challenges of intra-laryngeal TDC. A 55-year-old man presented with a neck mass associated with dysphagia. Computer Tomography neck scan showed a midline cyst extending to the pre-epiglottic space with partial obliteration of the right pyriform sinus and narrowing of the larynx. The cyst was excised en-bloc via Sistrunk procedure. Intra-laryngeal TDC are surgically challenging due to risk of perforation into the aerodigestive tract.

select article The etiology, pathogeneses, and treatment of objective tinnitus: Unique case series and literature review
Case reportAbstract only
The etiology, pathogeneses, and treatment of objective tinnitus: Unique case series and literature review
Parsa P. Salehi, David Kasle, Sina J. Torabi, Elias Michaelides, Douglas M. Hildrew
In Press, Corrected Proof, Available online 5 April 2019
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Abstract
Abstract
We present two unique cases of myoclonus-induced objective tinnitus (OT), along with a comprehensive literature review on the topic. Primary goals include: explore the relationship between palatal myoclonus (PM) and middle ear myoclonus (MEM), highlight the embryologic, neurologic, and anatomical relationship between the involved peri-tubular muscles, exemplify the first case of OT which documents video evidence demonstrating the link between objective tinnitus and eustachian tube movement. Also, we discuss available treatment interventions and why they often do not fully resolve patients' symptoms. Finally we introduce a novel way to objectively quantify the severity of OT. Ultimately, our series hopes to inform future diagnostic and treatment guidelines.

select article Expression of vimentin (VIM) and metastasis-associated 1 (MTA1) protein in laryngeal squamous cell carcinoma are associated with prognostic outcome of patients
Research articleAbstract only
Expression of vimentin (VIM) and metastasis-associated 1 (MTA1) protein in laryngeal squamous cell carcinoma are associated with prognostic outcome of patients
Sotirios Karamagkiolas, Ioannis Giotakis, Efthimios Kyrodimos, Evangelos I. Giotakis, ... Andreas M. Lazaris
In Press, Corrected Proof, Available online 3 April 2019
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Abstract
Abstract
Purpose
Laryngeal squamous cell carcinoma (LSCC), a common type of head and neck cancer, is associated with high rates of metastasis and recurrence. In this study, we investigated the potential combinatorial prognostic value of NOTCH1, Vimentin (VIM), and Metastasis-associated 1 (MTA1) protein in LSCC, using immunohistochemistry.

Materials and methods
Tissue specimens from 69 patients with LSCC were immunohistochemically evaluated for the protein expression of NOTCH1, VIM, and MTA1. Then, biostatistical analysis was performed, in order to assess the prognostic value of the expression of each one of these proteins.

Results
NOTCH1 expression status was not a significant prognosticator in LSCC, as shown in Kaplan-Meier survival analysis. On the contrary, both VIM and MTA1 seem to have an important prognostic potential, independently of TNM staging and histological grade of the tumor. In fact, positive VIM expression was shown to predict patients' relapse and poor outcome regarding patients' overall survival, in contrast with MTA1, the positive expression of which predicts higher disease-free survival (DFS) and overall survival (OS) rates in LSCC.

Conclusions
VIM and MTA1 constitute potential tumor biomarkers in LSCC and could be integrated into a multiparametric prognostic model. Undoubtedly, their prognostic value needs further validation in larger cohorts of LSCC patients.

select article Spontaneous cervical chyle fistula: A case report
Case reportAbstract only
Spontaneous cervical chyle fistula: A case report
Swathi Appachi, Joseph B. Meleca, Paul C. Bryson
In Press, Corrected Proof, Available online 2 April 2019
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Abstract
Abstract
Background
Cervical chylous fistulae are rare complications usually occurring from iatrogenic injury to the thoracic duct. There have been no reported cases of spontaneous chyle leaks in surgical naïve necks.

Methods
Case report.

Results
A 50 year-old female presented with progressive left neck swelling without fever, dyspnea, or dysphagia. Imaging demonstrated extensive infiltrative changes of the left neck with retropharyngeal fluid extending into strap musculature and the mediastinum. Flexible laryngoscopy revealed posterior pharyngeal wall edema. Differential diagnosis included abscess versus necrotizing fasciitis. Broad-spectrum antibiotics were initiated and she was taken to the OR for neck exploration. Intra-operatively, milky fluid was present around the carotid sheath and in the retropharyngeal space. Fluid analysis demonstrated chylomicrons and triglycerides >2400 mg/dL. Repeat imaging of the neck, chest, and abdomen did not reveal malignancy or obstructive masses. A lymphangiogram showed dilated lymphatic vessels near the cervical thoracic duct. On post-operative day four, the patient was taken back to the OR for thoracic duct ligation and biopsy of nearby tissue. Pathology demonstrated benign lymph nodes with dilated sinusoids. A low-fat diet was started and she was discharged home on hospital day nine. She has followed up regularly with no signs of recurrence.

Conclusion
A cervical chylous fistula usually results from iatrogenic injury to the thoracic duct. To our knowledge, this is the first reported case of a spontaneous cervical chyle leak.

select article Does cervical range of motion affect the outcomes of canalith repositioning procedures for posterior canal benign positional paroxysmal vertigo?
Research articleAbstract only
Does cervical range of motion affect the outcomes of canalith repositioning procedures for posterior canal benign positional paroxysmal vertigo?
Salvatore Martellucci, Giuseppe Attanasio, Massimo Ralli, Vincenzo Marcelli, ... Andrea Gallo
In Press, Corrected Proof, Available online 2 April 2019
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Abstract
Abstract
Purpose
Canalith repositioning procedure (CRP) for posterior canal benign positional paroxysmal vertigo (BPPV), also known as Epley maneuver, is a common procedure for the treatment of BPPV. This maneuver entails flexion, extension and rotation of the patient's neck. This study aims to investigate the impact of cervical range of motion (C-ROM) on CRP efficacy.

Materials and methods
The study included 47 patients with posterior canal BPPV treated by CRP. The procedure was considered successful if vertigo and nystagmus disappeared at the post-treatment evaluation. If CRP resulted ineffective, it was repeated up to three times per session. C-ROM was measured at BPPV diagnosis before treatment. Patients were followed up for 30 days.

Results
The first CRP was successful in 29 patients (61.7%), while it was ineffective in 18 patients (38.3%) requiring multiple repositioning maneuvers. Patients who needed two or more CRP showed lower C-ROM in extension (p = .003) and flexion (p = .042), and earlier recurrences (p = .006). Univariate regression analysis showed that lower cervical extension was significantly associated with the failure of the first CRP (OR: 0.899, 95% CI 0.831–0.973, p = .008).

Conclusions
Our data suggest that a reduced C-ROM can require multiple CRPs to successfully treat BPPV and increase the risk of early recurrences.

select article Total vs hemithyroidectomy for intermediate risk papillary thyroid cancer: A 23 year retrospective study in a tertiary center
Research articleAbstract only
Total vs hemithyroidectomy for intermediate risk papillary thyroid cancer: A 23 year retrospective study in a tertiary center
Kwan Pok Tsui, Wai Yin Kwan, Tam Lin Chow
In Press, Corrected Proof, Available online 2 April 2019
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Abstract
Abstract
Background
There is much debate in the literature over the extent of surgery for patients with intermediate risk papillary thyroid cancer. We herein report our results in a local tertiary hospital.

Method
We identify from our database patients with papillary thyroid cancer who underwent surgery in our hospital and were stratified to be of intermediate risk from the GAMES stratification system. Patients' demographic data, surgical and pathological details were recorded. Primary end points were disease specific survival (DSS) and recurrence free survival (RFS).

Results
From January 1993 to December 2016, 231 patients with papillary thyroid cancer underwent surgery of which 137 (59%) were of intermediate risk. 45 (33%) patients had hemithyroidectomy and 92 (67%) patients had total thyroidectomy. In the total thyroidectomy group, patients had a higher tumor (T) (p value = 0.009) and nodal (N) staging (p value = 0.001). They were also predicted to have a higher risk of recurrence according to the American Thyroid Association (ATA) classification (p value = 0.005). The 5 year DSS in both groups were 100%. The 5 year RFS in the total thyroidectomy and hemithyroidectomy groups were 92% and 100% respectively and were significantly different by the log rank test (p value = 0.02). The median follow up time was 54 months (range 4–276 months).

Conclusion
The 5 year survival in intermediate risk papillary thyroid cancer is favorable. Hemithyroidectomy is an acceptable choice of operation in intermediate risk patients with a better risk profile.

select article Translation and validation of the Parotidectomy Outcome Inventory 8 (POI-8) to Spanish
Research articleAbstract only
Translation and validation of the Parotidectomy Outcome Inventory 8 (POI-8) to Spanish
Carlos Miguel Chiesa-Estomba, Elizabeth Ninchritz, Teresa Rivera-Schmitz, Jose Angel González-García, ... Xabier Altuna-Mariezcurrena
In Press, Corrected Proof, Available online 2 April 2019
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Abstract
Abstract
Introduction
There are >400 million of native Spanish speakers around the world, being the second most spoken language in regard to the number of native speakers. For this reason, a valid questionnaire to access the quality of our patients after parotidectomy is necessary.

Material and methods
Validation and cross-cultural adaptation of the POI-8 questionnaire to the Spanish language. Internal consistency of Sp-POI 8 measured with Cronbach α.

Results
35 patients met the inclusion criteria during the mentioned period. Mean age was 59 ± 15,37 (Min: 18/Max: 87). 20 patients (57,1%) were male and 15 (42,9%) were female. Internal consistency with Cronbach α was 0.868. The intraclass correlation coefficient was 0.830 [CI] (95%: 0,791–925). Hypoesthesia was the most severely weighted problem (0,91) and xerostomia was the second (0,89). However, the high score was for fear of revision surgery (1,26).

Conclusion
The Spanish Language is the second most spoken language with regard to the number of native speakers and the Sp-POI 8 translation represents a valid option for the Spanish-speaking medical community, from which a large number of patients can benefit.

select article Sex-specific enlarged vestibular aqueduct morphology and audiometry
Research articleAbstract only
Sex-specific enlarged vestibular aqueduct morphology and audiometry
Jeremy Ruthberg, Mustafa S. Ascha, Armine Kocharyan, Amit Gupta, ... Todd D. Otteson
In Press, Corrected Proof, Available online 29 March 2019
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Abstract
Abstract
Objective
Enlargement of the vestibular aqueduct (EVA) is one of the most common congenital malformations in pediatric patients presenting with sensorineural or mixed hearing loss. The relationship between vestibular aqueduct (VA) morphology and hearing loss across sex is not well characterized. This study assesses VA morphology and frequency-specific hearing thresholds with sex as the primary predictor of interest.

Materials and methods
A retrospective, longitudinal, and repeated-measures study was used. 47 patients at an academic tertiary care center with hearing loss and a record of CT scan of the internal auditory canal were candidates, and included upon meeting EVA criteria after confirmatory measurements of vestibular aqueduct midpoint and operculum widths. Audiometric measures included pure-tone average and frequency-specific thresholds.

Results
Of the 47 patients (23 female and 24 male), 79 total ears were affected by EVA; the median age at diagnosis was 6.60 years. After comparing morphological measurements between sexes, ears from female patients were observed to have a greater average operculum width (3.25 vs. 2.70 mm for males, p = 0.006) and a greater average VA midpoint width (2.80 vs. 1.90 mm for males, p = 0.004). After adjusting for morphology, male patients' ears had pure-tone average thresholds 17.6 dB greater than female patients' ears (95% CI, 3.8 to 31.3 dB).

Conclusions
Though females seem to have greater enlargement of the vestibular aqueduct, this difference does not extend to hearing loss. Therefore, our results indicate that criteria for EVA diagnoses may benefit from re-evaluation. Further exploration into morphological and audiometric discrepancies across sex may help inform both clinician and patient expectations.

select article Clinical and audiometric outcomes of palisade cartilage myringoplasty under local anesthetic in an office setting
Research articleAbstract only
Clinical and audiometric outcomes of palisade cartilage myringoplasty under local anesthetic in an office setting
Nael M. Shoman
In Press, Corrected Proof, Available online 29 March 2019
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Abstract
Abstract
Objective
Assess clinical and functional outcomes of a modified palisade cartilage-perichondrium graft myringoplasty under local in an office setting.

Study design
Retrospective case series.

Setting
Tertiary care facility.

Patients
Patients with a tympanic membrane perforation presenting between March 2013 and October 2017. Inclusion criteria included age ≥ 7 years, entire perforation margin visualized through a transcanal view, and the ability to lie supine for up to 45 min. Exclusion criteria included a conductive hearing loss larger than expected, and presence of active infection.

Intervention
In-office modified myringoplasty technique under local anesthesia without sedation.

Main outcome measures
Complete perforation closure rate and audiometric outcomes.

Results
250 patients underwent the procedure, of whom 13 had bilateral sequential procedures (total 263 ears). Of those, 197 were primary and 66 revision. Average age was 46.3 years. Perforation sizes were categorized as small (32), moderate (109), large (78), and subtotal (44). Complete perforation closure was evident in 219 of the 250 cases (88%). Preoperative mean air pure tone average (PTA) was 56.7 dB and mean bone PTA was 27.5 dB (pre-operative ABG 29.2 dB). AC-PTA significantly improved to 35.0 dB (p < 0.0001), and ABG to 9.6 dB (p < 0.0001). Only subtotal perforations showed a statistically significant negative relationship with outcome (p = 0.04).

Conclusion
The modified palisade cartilage-perichondrium graft myringoplasty under local anesthetic is a highly successful procedure well tolerated by adult and pediatric patients with variable perforation sizes. This may have significant potential patient benefits, as well as cost savings to the health care system.

Oral Oncology

  1. The interest of sequential treatment with immune check point inhibitors followed chemotherapy: A case report

    In Press, Corrected Proof, Available online 8 May 2019
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  2. Myoepithelial carcinoma with rhabdoid features in the maxillary sinus: Immunohistochemical and in situ hybridization analysis of a rare case

    In Press, Corrected Proof, Available online 30 April 2019
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    Abstract

    Myoepithelial carcinomas of the head and neck are often located in the major salivary glands, notably in the parotid glands, being less frequent in the minor salivary glands. Noteworthy, myoepithelial carcinoma in the maxillary sinus is extremely rare. In fact, only five cases have been previously published to date. Here, we present, for the first time, a detailed immunohistochemical and in situ hybridization analysis of a SMARCB1 (INI-1)-intact myoepithelial carcinoma with rhabdoid features, expanding the histopathological spectrum of high-grade sinonasal carcinomas.

  3. Corrigendum to "Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma" [Oral Oncol. 86 (2018) 278–287]

    In Press, Corrected Proof, Available online 30 April 2019
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  4. Regression and long-term control after radiotherapy of carotid body paraganglioma – Are these still issues?

    In Press, Corrected Proof, Available online 30 April 2019
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  5. Concurrent oropharyngeal squamous cell carcinomas in couples

    In Press, Corrected Proof, Available online 25 April 2019
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  6. Tooth mobility: A plausible predictor of bony margins

    In Press, Corrected Proof, Available online 24 April 2019
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  7. Sanctuary site central nervous system relapse-refractory DLBCL responding to nivolumab and lenalidomide

    In Press, Corrected Proof, Available online 19 April 2019
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    Abstract

    Despite improvement in survival in diffuse large B-cell lymphoma (DLBCL) with the introduction of rituximab, central nervous system (CNS) relapse continues to represent a clinical challenge. In diffuse large B-cell lymphoma (DLBCL), the incidence of CNS relapse is only ∼5% in unselected cohorts. Immunotherapy is the treatment that either boosts the patient's own immune system or uses man-made versions of the normal parts of the immune system to kill lymphoma cells or slow their growth. We are presenting a thirty-eight year old man who, presented with neck nodes, axillary nodes, altered sensorium, abnormal body movements, unconsciousness, weight loss and, fever, with a past history of DLBCL in May 2008, treated with 6 cycles of CHOP and completed in November 2008. After 9 years in April 2018, the patient developed similar symptoms and treated with salvage chemotherapy with R-DHAP which was completed in September 2018. Post-treatment PET-CT showed partial metabolic response and we started external beam radiotherapy to initial bulky disease. After completion of radiotherapy, the patient was very reluctant for any type of therapy and went home. After one month he presented to us with persistent vomiting, abnormal body movements and, altered sensorium. On examination, his Glasgow Coma Scale (GCS) was E2V3M2 and he was admitted in Intensive Care Unit. The patient was managed with mannitol, dexamethasone, antiepileptics, antibiotics and other supportive care medicines. His brain magnetic resonance imaging (MRI) was showing multiple heterogeneously enhancing lesions with surrounding vasogenic oedema and his cerebrospinal fluid analysis was positive for malignant cells. He was managed with triple intrathecal chemotherapy with methotrexate 12 mg, Cytarabine 50 mg, and Hydrocortisone 50 mg along with other supportive care medicines, and after 4–5 days he regained consciousness and he was able to talk and understand verbal commands. In view of improvement in general condition and performance status, we started biweekly triple intra-thecal therapy, and Inj. Nivolumab 3 mg per kg q 2 weekly. From the second cycle, we started Lenalidomide 10 mg once a day for 21 days with 7 days gap along with 2 weekly nivolumab and biweekly triple IT chemotherapy. After one month his CSF analysis was negative for malignant cells. Now he is on regular treatment with weekly IT chemotherapy, 2 weekly nivolumab and 3 weeks on and one week off lenalidomide. After 2 months of treatment, his MRI Brain was showing. At the time of submission of this article, he has completed the fifth cycle of immunotherapy and two cycles of lenalidomide. He was able to manage his daily ADL and able to walk with a stick. The patient tolerated immunotherapy, triple IT therapy and lenalidomide very well without much intolerable side effects. Therefore, we concluded that nivolumab and lenalidomide was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory sanctuary site CNS B- cell lymphomas. Additional studies of Nivolumab and lenalidomide in these diseases are ongoing.

  8. Human papillomavirus (HPV) vaccine and HPV-related head and neck cancer: What's next?

    In Press, Corrected Proof, Available online 5 April 2019
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