Αρχειοθήκη ιστολογίου

Κυριακή 16 Δεκεμβρίου 2018

Rates of sialoendoscopy and sialoadenectomy in 5,111 adults with private insurance

Objective

To determine frequencies and trends in sialoendoscopy and sialoadenectomy for the treatment of obstructive, nonneoplastic submandibular gland disease in the United States.

Methods

Epidemiologic study of insurance claims from 2006 to 2013 in a large, private insurance claims database. Rates were calculated for patients undergoing one or both index procedures.

Results

A total of 5,111 adults with sialadenitis who underwent sialoendoscopy or submandibular gland excision were included. Mean age was 47.6 years, and patients undergoing sialoendoscopy were less likely to be male (relative risk [RR] = 0.84; 95% confidence interval [CI], 0.78–0.89), more likely to have sialoadenitis without stones (RR = 1.60; 95% CI, 1.53–1.66), and had a similar number of comorbidities (RR = 1.00; 95% CI, 0.91–1.06) compared to patients undergoing sialoadenectomy. The most common complication after sialoadenectomy was surgical site infection (1.4%; 95% CI, 1.1–1.8%), and complications after sialoendoscopy were rare. From 2007 to 2013, use of sialoendoscopy increased from 0.13 (95% CI, 0.08–0.18) to 0.42 (95% CI, 0.40–0.45) per 100 thousand people, and sialoadenectomy decreased from 2.41 (95% CI, 2.39–2.42) to 1.43 (95% CI, 1.40–1.44) per 100 thousand. The highest mean rate of sialadenectomy was seen in the south (2.15 per 100,000; 95% CI, 2.13–2.16), the lowest was in the west (1.6 per 100,000; 95% CI, 1.57–1.62), and it decreased in all regions over time.

Conclusion

Utilization of sialoendoscopy has increased over time, and the overall rate of sialoadenectomy is decreasing. Both procedures are safe for treatment of patients with sialadenitis and sialolithiasis. Future research should examine whether availability of sialoendoscopy leads to a decreased rate of sialoadenectomy in patients with salivary gland disease.

Level of Evidence

2c. Laryngoscope, 2018



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The use of dermoscopy in differentiating Sister Mary Joseph nodule and cutaneous endometriosis



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Dermoscopic pre‐ and posttreatment evaluation in patients with androgenetic alopecia on platelet‐rich plasma—A prospective study

Summary

Background

Platelet‐rich plasma is rich in growth factors that promote differentiation and growth of dermal papilla cells by various signaling pathways. Dermoscopy is handy, bedside tool that helps to improve diagnostic accuracy in various hair disorders.

Objectives

To evaluate and study the role of dermoscopy in patients with androgenetic alopecia (AGA) pre‐ and posttreatment with platelet‐rich plasma (PRP).

Methods

It is a prospective comparative study. Twenty male patients with AGA, aged 18‐45 years with modified Norwood‐Hamilton classification grade II‐VI were included in this study. Patients were given platelet‐rich plasma injections every 3 week for a period of 3 months. Dermoscopy was performed with 10 x magnifications in polarized mode at baseline and at 3 months from the baseline and photographs were taken. Patients were evaluated based on following dermoscopic findings (a) hair count, (b) hair density, (c) hair diameter diversity, perifollicular pigmentation, yellow dots, multi‐hair follicular units, honeycomb pigment pattern and white dots, (d) patient's hair growth assessment score.

Results

Posttherapy, patients showed significant improvement in hair count (27.4%), hair diversity (84.2%), increase in number of thick, terminals hairs, reduction in yellow dots (60%), perifollicular pigmentation (92.3%) was appreciated. Hair pull test negative after treatment in 10 patients (50%). Patient's hair growth assessment score showed 50%‐75% improvement in 7 (35%) patients.

Conclusion

Dermoscopy helps to easily evaluate and compare the therapeutic response pre‐ and posttreatment which can be easily documented and visualized at every visit.



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Initial experience with image‐guided surgical navigation in transoral surgery

Abstract

Background

Surgical navigation using image guidance may improve the safety and efficacy of transoral surgery (TOS); however, preoperative imaging cannot be accurately registered to the intraoperative state due to deformations resulting from placement of the laryngoscope or retractor. This proof of concept study explores feasibility and registration accuracy of surgical navigation for TOS by utilizing intraoperative imaging.

Methods

Four patients undergoing TOS were recruited. Suspension laryngoscopy was performed with a CT‐compatible laryngoscope. An intraoperative contrast enhanced CT scan was obtained and registered to fiducials placed on the neck, face, and laryngoscope.

Results

All patients were successfully scanned and registered. Registration accuracy within the pharynx and larynx was 1 mm or less. Target registration was confirmed by localizing endoscopic and surface structures to the CT images. Successful tracking was performed in all 4 patients.

Conclusion

For surgical navigation during TOS, although a high level of registration accuracy can be achieved by utilizing intraoperative imaging, significant limitations of the existing technology have been identified. These limitations, as well as areas for future investigation, are discussed.



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PI3‐kinase pathway biomarkers in oral cancer and tumor immune cells

Abstract

Background

This study investigated the hypothesis that phosphoinositide 3‐kinase (PI3‐kinase) pathway dysregulation in either head and neck cancer cells and/or tumor infiltrating immune cells would influence outcomes of patients with surgically treated oral tongue squamous cell carcinomas (SCC).

Methods

We constructed tissue microarrays containing 123 oral tongue SCC samples and performed immunohistochemistry using antibodies against 7 PI3‐kinase pathway markers: phosphatase and tensin homolog (PTEN), Akt, p‐Akt, mammalian target of rapamycin (mTOR), phosphorylated‐mammalian target of rapamycin (p‐mTOR), survivin, and Ki‐67). Expression levels in cancer cells or tumor infiltrating immune cells were correlated with outcomes.

Results

Higher levels of PTEN expression in immune cells were significantly associated with improved recurrence‐free survival (heart rate (HR) = 0.45, 95% confidence interval (CI) 0.23‐0.90, P = .03), and overall survival (HR = 0.34, 95% CI 0.15‐0.76, P = .01) on univariate and multicovariate models.

Conclusions

We identified a novel, negative prognostic role of PI3‐kinase activation (as determined by PTEN loss) in oral SCC infiltrating immune cells. These findings could be relevant for clinical development of PI‐3 kinase inhibitors for this disease.



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Outcome of patients following neo-adjuvant chemotherapy for unresectable cervical nodes in head and neck squamous cell carcinomas

Abstract

Background

This study was undertaken to assess the effects of neo-adjuvant chemotherapy (NACT) on patients with head and neck squamous cell carcinoma (HNSCC) having advanced unresectable cervical nodal metastasis.

Methodology

A retrospective cohort study was conducted to assess the response of unresectable nodes to NACT in a pragmatic manner. Patients were grouped according to the response noted and the treatment offered after chemotherapy. The median survival amongst the patients in these groups was compared.

Results

The study included 51 patients. Oral cavity was the commonest site (67.2%). Favourable nodal response was seen in 64.7% of the patients. Up to 87.9% of the nodal responders were amenable to curative intent therapy. The overall survival of patients undergoing surgery, definitive chemoradiotherapy, palliative chemotherapy and palliative radiotherapy was 24, 13, 10 and 9 months, respectively.

Conclusion

NACT may be utilized in HNSCC with advanced inoperable nodal disease to make them amenable to definitive therapy.



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“Slime” dermatitis, a fad‐associated chronic hand dermatitis

Abstract

"Slime" is the colloquial name for a non‐Newtonian viscoelastic putty‐like substance that is currently a popular plaything among pre‐teens and adolescents. Several ingredients in homemade slime recipes may cause irritant or allergic contact dermatitis. We report two children who developed slime‐associated chronic hand dermatitis, more prominently on their dominant hand. We review the potential for irritant and allergic contact dermatoses as the causes of dermatitis associated with homemade slime.



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The impact of pediatric atopic dermatitis on families: A review

Abstract

Background

Atopic dermatitis (AD) is an extremely common childhood disease, with considerable impact on the quality of life of affected children and their families. While pruritus is the hallmark symptom of this disease, AD has been well‐documented to impact patients beyond physical symptoms, resulting in behavior problems, mood disorders, and sleep disturbance.

Objective

This literature review outlines how atopic dermatitis impacts the quality of life of families of children affected by AD.

Methods

A total of 3436 articles were identified via an online search of the MEDLINE health literature database and were screened for relevance to quality of life impacts on families with children affected by AD.

Results

Caring for children affected by AD can be an extremely time‐consuming task that can impair personal relationships, decrease psychosocial functioning, and cause sleep loss among family members of affected patients. Additionally, AD may result in work absence or decreased work productivity for caregivers. Special diets, irritant and allergen avoidance strategies, and alternative therapies are commonly used by patients to manage their disease and require large amounts of family involvement.

Conclusions

Atopic dermatitis can greatly decrease quality of life of families of affected children in various domains, including sleep, finances, and relationships. Early intervention and psychotherapy may be needed in some patients to address these quality of life impairments.



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Hereditary cardiac amyloidosis associated with Pro24Ser transthyretin mutation: a case report

Transthyretin amyloidosis is a systemic disorder caused by extracellular deposition of insoluble amyloid fibrils in peripheral and autonomic nerves, heart, kidney, gastrointestinal tract, and other organs. Her...

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Clinical and histopathologic prognostic implications of the expression of cytokeratins 8, 10, 13, 14, 16, 18 and 19 in oral and oropharyngeal squamous cell carcinoma

Publication date: Available online 16 December 2018

Source: Archives of Oral Biology

Author(s): Rima-A. Safadi, Niveen-I. Abdullah, Rolla-F. Alaaraj, Dima H. Bader, Darshan D. Divakar, Abed H. Hamasha, Maher A. Sughayer

ABSTRACT
Objectives

To identify cytokeratins (CK) of significant correlations with clinical and histopathologic prognostic parameters in oral and oropharyngeal squamous cell carcinoma (SCC).

Design

The sample consisted of 100 cases retrieved from the archives of the Pathology Department/ King Hussein Cancer Center/Amman/ Jordan. Recorded data included: age, gender, location, grade, depth of invasion, the presence of epithelial dysplasia, tumor size, lymph node metastasis, number of positive lymph nodes, distant metastases, clinical stage, local recurrence, treatment modalities and 5-year survival rate. Immunohistochemical staining of 6 cytokeratins: 8, 10, 13, 14, 16, 18, and 19 was performed using standard protocols. Stained sections were digitized and analyzed using ImageJ-color deconvolution to identify the percentage of cytokeratin-positive area (score). Statistical tests used were: student t-test, analysis of variance, bivariate analysis and logistic regression.

Results

Lower CK8,18, 19 scores correlated with lower 5-year survival rate. Higher CK19 and lower CK 10, 14, 16 scores were associated with distant metastasis. Increased CK8, 18, 19 scores correlated with higher stage and with higher depth of invasion. The higher CK18 score was associated with local recurrence. Higher CK10, 13, 16 scores correlated with well-differentiated grade. Higher CK19 and lower CK16 scores were associated with adjacent epithelial dysplasia. Regression analysis showed that better 5-year survival rate was significantly correlated with increased CK16, decreased CK18 and 19 scores.

Conclusion

Expression scores of a panel of cytokeratin are potential prognostic indicators for 5-year survival and correlates with other prognostic parameters.



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UV‐B‐activated B16 melanoma cells or HaCaT keratinocytes increase melanogenesis via ANGPTL2 induction, an activity antagonized by Chrysanthemum extract

Abstract

Sunburn causes inflammation, which increases melanin production in skin and causes hyperpigmentation. Angiopoietin‐like protein (ANGPTL) 2 is an inflammatory mediator induced in sun‐exposed skin areas. However, whether ANGPTL2 functions in melanin production remains unclear. To assess this possibility, we overexpressed Angptl2 in the melanoma line B16 and in the keratinocyte line HaCaT. Relative to controls, Angptl2‐expressing B16 cells produced higher melanin levels via tyrosinase induction. Accordingly, Angptl2‐expressing HaCaT cells secreted relatively high levels of both endothelin‐1 (ET‐1) and α‐melanocyte stimulating hormone (α‐MSH). Moreover, treatment with an extract from Chrysanthemum indicum x Erigeron annuus (CE) suppressed ANGPTL2 expression and repressed tyrosinase induction in melanocytes and of α‐MSH and ET‐1 in keratinocytes. Our data suggests that ANGPTL2 expression in keratinocytes and melanin‐producing cells accelerates pigment production and that treatment of skin with a CE extract could prevent melanin accumulation.

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Salivary opiorphin in dental pain: a potential biomarker for dental disease

Publication date: Available online 15 December 2018

Source: Archives of Oral Biology

Author(s): Mahmut Sertac Ozdogan, Mustafa Gungormus, Selen Ince Yusufoglu, Sinan Yasin Ertem, Cigdem Sonmez, Metin Orhan

Abstract
Objectives

Opiorphin is a recently discovered peptide shown to inhibit the enkephalin-degrading enzymes and prolong the effects of enkephalins. Although opiorphin is found in high concentrations in saliva, the relationship between salivary opiorphin and orofacial pains is not yet fully understood. We aimed to determine salivary opiorphin concentrations in dental pain related to symptomatic irreversible pulpitis (SIP), and symptomatic periapical periodontitis (SAP).

Design

39 patients participated in this study. The participants were categorized into SIP and SAP based on their diagnosis. All the patients were treated with root canal treatment. Saliva specimens were collected, and pain levels were recorded at pre-treatment, 7 days post-treatment and 30 days post-treatment. Saliva opiorphin levels were measured using a commercially available ELISA kit. Pre-treatment and post-treatment opiorphin levels were evaluated using repeated measures ANOVA. Correlations between VAS scores, opiorphin levels and age were evaluated using Spearman's Rank Correlation.

Results

The average saliva opiorphin level pre-treatment, 7 days post-treatment and 30 days post-treatment were 31.28 ± 7.10 ng/ml, 20.41 ± 2.67 ng/ml and 18.61 ± 2.05 ng/ml respectively. Significantly higher pre-treatment opiorphin levels were observed in the SIP group compared to the SAP group. A strong correlation was observed between the pre-treatment pain levels and the saliva opiorphin concentrations.

Conclusions

Our findings indicate that saliva opiorphin levels increase in inflammation related dental pain. The level of salivary opiorphin is strongly correlated with the reported level of pain. The extent of the inflammation (pulpal vs. periodontal) also affects the opiorphin level.



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Next-generation sequencing reveals new insights about gene usage and CDR-H3 composition in the horse antibody repertoire

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Taciana Conceição Manso, Michele Groenner-Penna, João Carlos Minozzo, Bruno Cesar Antunes, Gregory C. Ippolito, Franck Molina, Liza F. Felicori

Abstract

Horse serum antibodies have been used for greater than a century for the treatment and prophylaxis of infectious diseases and envenomations. Little is known, however, about the immunogenetic diversity that produces horse serum antibodies. Here, we employed next-generation sequencing for a first-in-kind comprehensive analysis of the equine B-cell repertoire. Nearly 45,000 and 30,000 clonotypes were obtained for the heavy-chain (IGH) and lambda light-chain (IGL) loci, respectively. We observed skewed use of the common subgroups IGHV2 (92.49%) and IGLV8 (82.50%), consistent with previous reports, but also novel use of the rare genes IGHV6S1 and IGLV4S2. CDR-H3 amino acid composition revealed different amino acid patterns at positions 106 and 116 compared to human, rabbit, and mouse, suggesting that an extended conformation predominates among horse CDR-H3 loops. Our analysis provides new insights regarding the mechanisms employed to generate antibody diversity in the horse, and could be applicable to the optimized design of synthetic antibodies intended for future therapeutic use.



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Evaluation of Epstein-Barr virus-specific antibodies in Cypriot multiple sclerosis patients

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Elie Deeba, Dana Koptides, Efthychia Gaglia, Astero Constantinou, Anastasia Lambrianides, Marios Pantzaris, Georges Krashias, Christina Christodoulou

Abstract

Multiple Sclerosis (MS) is a chronic, demyelinating, inflammatory disease of the central nervous system (CNS) with a strong autoimmune component. Several genetic and environmental factors have been suggested to contribute in MS. The Epstein-Barr virus (EBV) is one pathogenic candidate proposed to be involved in the onset of MS and/or induction of subsequent exacerbations. The possible involvement of EBV in MS is highlighted by a number of national epidemiological studies showing a higher percentage of EBV seropositivity. This study aims to evaluate for the first time the seroprevalence of EBV in Cypriot MS patients. The serum of 133 MS patients and 101 healthy controls (HCs) was used to determine the positivity index of the EBV nuclear antigen-1 (EBNA-1) IgG, viral capsid antigen (VCA) IgG, and early antigen-D (EA-D) IgG, using ELISA. All MS patients were seropositive for both EBNA-1 IgG and VCA IgG as compared to 94.1% (Fisher's exact test, p = 0.0059) and 93.1% (Fisher's exact test, p = 0.0025) of HCs respectively. Furthermore, the positivity indexes of both antibodies were significantly higher in MS patients. There was no significant difference in the presence/absence of EA-D IgG between the two groups nor in the corresponding P.I. levels. The results obtained, revealing higher seropositivity of EBNA-1 IgG and VCA IgG in MS patients, seem to concur with previous findings of studies in other countries, thereby further asserting the theory of EBV involvement in MS.



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IL-17A contributes to myocardial ischemic injury by activating NLRP3 inflammasome in macrophages through AMPKα/p38MAPK/ERK1/2 signal pathway in mice

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Lisha Zhang, Peining Liu, Wen Wen, Xiaofang Bai, Yan Zhang, Mengping Liu, Lijun Wang, Yue Wu, Zuyi Yuan, Juan Zhou

Abstract
Background

Acute myocardial infarction (AMI) is followed by an acute inflammation involving inflammasome activation, thereby inducing cardiac dysfunction. Interleukin-17A (IL-17A) involves in many inflammatory diseases, but its roles in inflammation following AMI are still obscure. The aim of this study is to investigate the roles of IL-17A in the inflammatory response following AMI and its underlying mechanisms.

Methods and results

NLRP3 inflammasome and AMPKα/p38MAPK/ERK1/2 signaling pathway were significantly activated under the induction of IL-17A in mouse peritoneal macrophages, which could be inhibited by AMPK inhibitor compound C (CC). Both p38MAPK and ERK1/2 inhibitors could partially inhibit the activation of NLRP3 inflammasome in macrophages treated by IL-17A. In vivo, IL-17A knockout not only decreased the infiltration of macrophages and the activation of NLRP3 inflammasome and AMPKα/p38MAPK/ERK1/2 signaling pathway in ischemic myocardium, but also improved cardiac function and reduced infarction size after the ligation of descending segment from left coronary artery for 3 days in mice, while IL-17A administration further aggravated the myocardial ischemic injury, which were prevented by CC administration.

Conclusion

IL-17A aggravates inflammatory response during AMI by inducing macrophages infiltration and activating NLRP3 inflammasome through AMPKα/p38MAPK/ERK1/2 pathway.



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Antifungal activities of surfactant protein D in an environment closely mimicking the lung lining

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Soledad R. Ordonez, Martin van Eijk, Natalia Escobar Salazar, Hans de Cock, Edwin J.A. Veldhuizen, Henk P. Haagsman

Abstract

At the lung lining innate defenses protect our lungs against inhaled fungal cells that could pose a threat to our health. These defenses are comprised of mucociliary clearance, soluble effector molecules and roaming phagocytic cells, such as macrophages and neutrophils. How important each of these defenses is during fungal clearance depends on the specific fungal pathogen in question and on the stage of infection. In this study the localization and antifungal activity of the lung surfactant protein D (SP-D) was studied in an environment mimicking the lung lining. To this end Calu-3 cells were grown on an air-liquid interface allowing them to polarize and to produce mucus at their apical surface. Additionally, neutrophils were added to study their role in fungal clearance. Two fungal pathogens were used for these experiments: Candida albicans and Aspergillus fumigatus, both of clinical relevance. During fungal infection SP-D localized strongly to both fungal surfaces and stayed bound through the different stages of infection. Furthermore, SP-D decreased fungal adhesion to the epithelium and increased fungal clearance by neutrophils from the epithelial surface. These findings suggest that SP-D plays an important role at the different stages of pulmonary defense against fungal intruders.



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Evaluating the effect of nasal septoplasty on atrial electromechanical features

Publication date: Available online 15 December 2018

Source: American Journal of Otolaryngology

Author(s): Osman Kayapinar, Adnan Kaya, Cem Ozde, Derya Cebeci, Ilhan Unlu

Abstract
Background

Recent studies have demonstrated that right ventricular (RV) dysfunction and increased pulmonary artery pressure may be frequent in patients with upper airway obstruction. In this study, we evaluated atrial conduction delays in patients with upper airway obstruction secondary to nasal septum deviation (NSD).

Methods

A total of 32 patients with upper airway obstruction secondary to NSD undergoing a septoplasty procedure were enrolled in this study. Preoperative electrocardiography and transthoracic echocardiography were performed in all patients who underwent surgery. The mean pulmonary artery pressure (mPAP) and atrial conduction time (ACT) were recorded before and 6 months after the surgical procedures.

Results

The PAP was significantly lower postoperatively than preoperatively (20.75 ± 4.83 vs. 24.68 ± 5.26; P < 0.001). The postoperative Electromechanical Delay of Mitral septal wall (EMD-MS) value was significantly lower than that preoperatively (46.20 ± 8.5 vs. 40.5 ± 9.9; P < 0.001). The postoperative Electromechanical Delay of Mitral lateral wall (EMD-ML) value decreased significantly compared to the preoperative period (46.3 ± 7.4 vs. 40.6 ± 9.3; P < 0.001). The postoperative Electromechanical Delay of Tricuspit lateral wall (EMD-TL) value was significantly lower than that preoperatively (43.8 ± 7.0 vs. 38.1 ± 9.1; P < 0.001). There was no significant change in pre- or postoperative measurements of inter- and intra-atrial conduction delays.

Conclusions

We demonstrated that upper airway obstruction secondary to NSD causes a significant increase in mPAP and a significant delay in ACT, which improved after nasal septoplasty. According to these results, we conclude that upper airway obstruction may be an important risk factor for pulmonary arterial hypertension, RV dysfunction, and atrial arrhythmias, especially in unoperated cases.



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Obesity and genes related to lipid metabolism predict poor survival in oral squamous cell carcinoma

Publication date: February 2019

Source: Oral Oncology, Volume 89

Author(s): Qinchao Hu, Jianmin Peng, Xijuan Chen, Huan Li, Ming Song, Bin Cheng, Tong Wu

Abstract
Objectives

Obesity is an important risk factor for several malignancies, but its effect on oral squamous cell carcinoma (OSCC) prognosis is controversial. We aimed to disclose the association between obesity and the OSCC outcome, and explore the potential of some lipid metabolism-related genes as biomarkers for prognostic prediction.

Materials and methods

A total of 576 patients diagnosed as T1/2N0M0 OSCC without prediagnosis weight loss was included in this retrospective study. These patients were grouped according to body mass index (BMI). The univariate and multivariate analysis were used to compare the progression-free survival (PFS) and disease specific survival (DSS) between groups. Propensity score matching (PSM) was adopted to minimize confounders. Data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were employed to analyze the potential of some lipid metabolism-related genes for OSCC prognosis prediction.

Results

The PFS (P = 0.023) and DSS (P = 0.047) were poorer in obese patients than in normal weight ones. Obesity was an independent risk factor for PFS (Hazard Ratio = 2.016, 95% Confidence Interval 1.101–3.693, P = 0.023) and DSS (Hazard Ratio = 2.022, 95% Confidence Interval 1.040–3.932, P = 0.038). Furthermore, the PSM matched cohort analysis revealed that obesity was associated with poor prognosis of OSCC patients. Finally, 72 dysregulated lipid metabolism-related genes were identified in OSCC, and a combining signature of TGFB1, SPP1, and SERPINE1 was defined as a biomarker for prognostic prediction.

Conclusions

Obesity is an independent risk factor for T1/2N0M0 OSCC, and a combining signature of TGFB1, SPP1, and SERPINE1 may be applied to predict prognosis of OSCC patients.



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Prevalence of voice disturbances in pediatric airway patients: Are we missing anything?

Publication date: Available online 16 December 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Anne Hseu, Nohamin Ayele, Natasha Dombrowski, Alex Irace, Kosuke Kawai, Geralyn Woodnorth, Karen Watters, Roger Nuss, Reza Rahbar

Abstract
Objective

To report on the prevalence of voice disturbances in pediatric airway patients.

Methods

Consecutive patients seen in a specialized Center for Airway Disorders at a tertiary children's hospital from February 2017 to September 2017 were included. Patients' families were invited to complete a pediatric voice health handicap index (pVHI) questionnaire. Patients underwent evaluation including flexible laryngoscopy and/or direct laryngoscopy and bronchoscopy.

Results

146 patients were included. Of these children, 73 patients (50.3%) presented with swallowing difficulty and 44 patients (30.3%) presented with respiratory complaints. Only 7 patients (4.8%) reported hoarseness initially. The median age at referral was 2.7 years of age (interquartile range: 1.4-4.3). The mean total pVHI score was 9.5 (± 12.9). Sixty-seven patients (45.9%) had abnormal pVHI findings of score > 4. Six patients (4.1%) had pVHI > 40. The mean pVHI score was 26.0 (± 21.1) among 12 patients with a history of tracheostomy, 12.0 (± 14.3) among 30 patients with laryngeal cleft, and 9.0 (± 9.9) among 19 patients with laryngomalacia.

Conclusion

Voice disturbances are not uncommon in pediatric patients evaluated for airway disorders. Although patients may present with primary concerns for breathing or swallowing difficulties, many of these patients may need further work-up and treatment for dysphonia.



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House dust mite drives pro‐inflammatory eicosanoid reprogramming and macrophage effector functions

Abstract

Background

Eicosanoid lipid mediators play key roles in type 2 immune responses, e.g. in allergy and asthma. Macrophages represent major producers of eicosanoids and they are key effector cells of type 2 immunity. We aimed to comprehensively track eicosanoid profiles during type 2 immune responses to house dust mite (HDM) or helminth infection and to identify mechanisms and functions of eicosanoid reprogramming in human macrophages.

Methods

We established an LC‐MS/MS workflow for the quantification of 52 oxylipins to analyze mediator profiles in human monocyte derived macrophages (MDM) stimulated with HDM and during allergic airway inflammation (AAI) or nematode infection in mice. Expression of eicosanoid enzymes was studied by qPCR and western blot and cytokine production was assessed by multiplex assays.

Results

Short (24h) exposure of alveolar‐like MDM (aMDM) to HDM suppressed 5‐LOX expression and product formation, while triggering prostanoid (thromboxane and prostaglandin D2 and E2) production. This eicosanoid reprogramming was p38‐dependent, but Dectin‐2‐independent. HDM also induced pro‐inflammatory cytokine production, but reduced granulocyte recruitment by aMDM. In contrast, high levels of cysteinyl leukotrienes (cysLTs) and 12‐/15‐LOX metabolites were produced in the airways during AAI or nematode infection in mice.

Conclusion

Our findings show that a short exposure to allergens as well as ongoing type 2 immune responses are characterized by a fundamental reprogramming of the lipid mediator metabolism with macrophages representing particularly plastic responder cells. Targeting mediator reprogramming in airway macrophages may represent a viable approach to prevent pathogenic lipid mediator profiles in allergy or asthma.

This article is protected by copyright. All rights reserved.



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Orf virus infection of human keratinocytes and dermal fibroblasts: limited virus detection and interference with intercellular adhesion molecule‐1 up‐regulation

Abstract

Orf virus (Parapoxvirus ovis, ORFV) is a dermatotropic virus causing pustular dermatitis in small ruminants and humans. We analyzed isolated human primary keratinocytes (KC) and dermal fibroblasts (FB) for cell death and virus replication by infection with a patient‐derived ORFV isolate. ORFV infection was associated with rapid induction of cell death in KC allowing for considerable virus removal. Upon infection with ORFV, KC and FB harbored intracytoplasmic ORFV and showed viral protein presence, however missing virus spread indicated an abortive infection. Upon ORFV exposure, KC but not FB secreted the pro‐inflammatory cytokine interleukin (IL)‐6. ORFV infection enhanced the frequency of KC expressing intercellular adhesion molecule (ICAM)‐1 which was independent of IL‐6. Interestingly, ORFV inhibited ICAM‐1 up‐regulation on infected but not on non‐infected KC. Even interferon‐γ, a potent inducer of ICAM‐1, upregulated ICAM‐1 only on non‐infected KC. Transfer of ORFV‐free supernatant from infected to non‐infected KC induced ICAM‐1 on non‐infected KC pointing to the involvement of soluble mediator(s). Similarly as in KC, in FB interference with ICAM‐1 up‐regulation by ORFV infection was also observed. In conclusion, we shed light on epidermal and dermal defense mechanisms to ORFV infection and point to a novel ICAM‐1‐related immune evasion mechanism of ORFV in human skin.

This article is protected by copyright. All rights reserved.



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Efficacy of calcium excretion and calcium/creatinine clearance ratio in the differential diagnosis of familial hypocalciuric hypercalcemia and primary hyperparathyroidism

Abstract

Background

Twenty‐four‐hour renal calcium‐excretion (CE) and calcium/creatinine‐clearance‐ratio (CCCR), respectively, are widely used to rule out familial hypocalciuric hypercalcemia (FHH) in patients with suspected primary hyperparathyroidism before surgery. The aim was to evaluate the practicability of CE compared to CCCR.

Patients and Methods

We analyzed biochemical parameters, surgical treatment, gene mutation results, and long‐term follow‐up data of 198 patients (including 14 patients with FHH) and the discriminative power of CE and CCCR.

Results

Twenty four patients (12.1%) had a low CE and 35 patients (20.2%) had a CCCR indicating FHH. However, eight patients with FHH (57.1%) had a normal or increased CE. Correspondingly, only eight cases of FHH (57.1%) were correctly predicted by CCCR. Sensitivity/specificity were 42.9%/89.9% for CE and 64.3%/79.9% for CCCR, showing no statistical differences (P = 0.482) between both methods.

Conclusion

Neither CE nor CCCR was able to distinguish between PHPT and FHH but may help to narrow down potential FHH patients.



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Plasma circulating tumor DNA as a potential tool for disease monitoring in head and neck cancer

Abstract

Background

Recommendations for perioperative therapy in head and neck cancer are not explicit and recurrence occurs frequently. Circulating tumor DNA is an emerging cancer biomarker, but has not been extensively explored for detection of recurrence in head and neck cancer.

Methods

Patients diagnosed with head and neck squamous cell carcinoma were recruited into the study protocol. Tumors were sequenced to identify patient‐specific mutations. Mutations were then identified in plasma circulating tumor DNA from pre‐treatment blood samples and longitudinally during standard follow‐up. Circulating tumor DNA status during follow‐up was correlated to disease recurrence.

Results

Samples were taken from eight patients. Tumor mutations were verified in seven patients. Baseline circulating tumor DNA was positive in six patients. Recurrence occurred in four patients, two of whom had detectable circulating tumor DNA prior to recurrence.

Conclusion

Circulating tumor DNA is a potential tool for disease and recurrence monitoring following curative therapy in head and neck cancer, allowing for better prognostication, and/or modification of treatment strategies.



https://ift.tt/2Bsc99A

Shoulder symptoms and quality of life impact of limited neck dissection after de‐intensified chemoradiotherapy: Secondary analysis of two prospective trials

Abstract

Background

We investigated the quality of life (QOL) impact of post‐radiation therapy (RT) superselective/selective neck dissection after de‐intensified chemoradiation for human papillomavirus‐associated oropharynx cancer.

Methods

A total of 147 patients received 60 Gy and weekly low‐dose cisplatin on two phase 2 trials with planned post‐RT neck dissection or surveillance positron emission tomography with neck dissection reserved for salvage. UW‐QOL Shoulder Score, EORTC H&N‐35, and EAT‐10 were assessed.

Results

In all, 48 of 147 patients had post‐RT neck dissection. At 2 years, 37% and 13% of patients receiving post‐RT neck dissection had Shoulder Score ≥ 1 (any shoulder symptoms) and ≥ 2 (symptoms affecting work/hobbies), respectively, versus only 16% and 3% of patients not receiving post‐RT neck dissection. Post‐RT neck dissection was associated with Shoulder Score ≥ 1 (P = 0.005) and Shoulder Score ≥ 2 (P = 0.03) at 2 years, but not H&N‐35 or EAT‐10 scores.

Conclusions

Post‐RT superselective/selective neck dissection was associated with modest but persistent shoulder symptoms. These toxicities should be weighed against the probability of persistent disease when evaluating patients for post‐RT neck dissection.



https://ift.tt/2Bm9zlK

Novel ANO5 mutation c.1067G>T (p.C356F) identified by whole genome sequencing in a big family with atypical gnathodiaphyseal dysplasia

Abstract

Background

Gnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied.

Methods

Sanger sequencing, whole‐genome sequencing (WGS), and bioinformatics and structural modeling analyses were performed.

Results

A family with patients with fibro‐osseous lesions of the jawbones were initially diagnosed with cherubism. Sequencing of SH3BP2, which is the causal gene of cherubism, revealed no pathogenic mutation. Through WGS, we identified a novel mutation c.1067G>T (p.C356F) in ANO5, and bioinformatics analyses and structural modeling showed that the mutation was deleterious. Because ANO5 is the gene responsible for GDD, we reappraised the clinical data of the patients, and the diagnosis was corrected to atypical GDD. A review of the literature showed that 67% of GDD cases confirmed by molecular testing were initially misdiagnosed.

Conclusions

The novel mutation c.1067G>T (p.C356F) in ANO5 is responsible for the atypical GDD observed in our patients. GDD should be included in the differential diagnosis for patients with fibro‐osseous lesions.



https://ift.tt/2A16zv7

Origin site‐based staging system of sinonasal inverted papilloma for application to endoscopic sinus surgery

Abstract

Background

We aimed to assess the recurrence risk of sinonasal inverted papillomas (SNIPs), based on a staging system developed according to the originating site of SNIP.

Methods

A total of 200 patients with SNIP were enrolled, and a staging system was developed based on the originating sites and corresponding recurrence rates of tumor in the patients. In the verification phase, 675 patients with SNIPs were enrolled as above, and the originating sites of the SNIPs were confirmed by an endoscopic sinus surgery. Cluster analysis was performed to determine the stage for each SNIP.

Results

Overall, 608 patients completed the study. SNIP recurrence rates for stages 1‐4 were 0 (n = 43), 4.0% (n = 420), 13.4% (n = 134), 36.4% (n = 11), respectively (total = 6.4%).

Conclusions

The origin site‐based classification of SNIP may aid surgeons in selecting appropriate endoscopic surgical approaches to minimize the risk of recurrence.



https://ift.tt/2BkSM2b

In vitro and in vivo evidence of tyrosinase inhibitory activity of a synthesized (Z)‐5‐(3‐hydroxy‐4‐methoxybenzylidene)‐2‐thioxothiazolidin‐4‐one (5‐HMT)

Abstract

Tyrosinase is a key enzyme that catalyzes the initial rate‐limiting steps of melanin synthesis. Due to its critical role in melanogenesis, various attempts were made to find potent tyrosinase inhibitors although many were not safe and effective in vivo. We evaluated tyrosinase inhibitory activity of six compounds. Among them, (Z)‐5‐(3‐hydroxy‐4‐methoxybenzylidene)‐2‐thioxothiazolidin‐4‐one (5‐HMT) had the greatest inhibitory effect and potency as the IC50 value of 5‐HMT was lower than that of kojic acid, widely‐known tyrosinase inhibitor. Based on in silico docking simulation, 5‐HMT had a greater binding affinity than kojic acid with a different binding conformation in the tyrosinase catalytic site. Furthermore, its skin depigmentation effect was confirmed in vivo as 5‐HMT topical treatment significantly reduced UVB‐induced melanogenesis in HRM2 hairless mice. In conclusion, our study demonstrated that 5‐HMT has a greater binding affinity and inhibitory effect on tyrosinase and may be a potential candidate for a therapeutic agent for preventing melanogenesis.

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