Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τρίτη 17 Οκτωβρίου 2017
Plasmacytoid dendritic cells drive acute exacerbations of asthma
Publication date: Available online 17 October 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Aikaterini-Dimitra Chairakaki, Maria-Ioanna Saridaki, Katerina Pyrillou, Marios-Angelos Mouratis, Ourania Koltsida, Ross P. Walton, Nathan W. Bartlett, Athanasios Stavropoulos, Louis Boon, Nikoletta Rovina, Nikolaos G. Papadopoulos, Sebastian L. Johnston, Evangelos Andreakos
BackgroundAlthough acute exacerbations, mostly triggered by viruses, account for the majority of hospitalizations in asthma, there is still very little known about the pathophysiological mechanisms involved. Plasmacytoid DCs (pDCs), prominent cells of antiviral immunity, exhibit pro-inflammatory or tolerogenic functions depending on the context, yet their involvement in asthma exacerbations remains unexplored.ObjectivesWe sought to investigate the role of pDCs in allergic airway inflammation and acute exacerbations of asthma.MethodsAnimal models of allergic airway disease (AAD) and virus-induced AAD exacerbations were employed to dissect pDC function in vivo and unwind potential mechanisms involved. Sputum from asthma patients with stable disease or acute exacerbations was further studied to determine pDC presence and correlation with inflammation.Results: pDCs were key mediators of the immuno-inflammatory cascade that drives asthma exacerbations. In animal models of AAD and RV-induced AAD exacerbations, pDCs were recruited to the lung during inflammation and migrated to the draining lymph nodes to boost Th2-mediated effector responses. Accordingly, pDC depletion post-allergen challenge or during RV infection abrogated exacerbation of inflammation and disease. Central to this process was IL-25, induced by allergen challenge or RV infection that conditioned pDCs for pro-inflammatory function. Consistently, in asthma patients pDCs were markedly increased during exacerbations, and correlated with the severity of inflammation and the risk for asthmatic attacks.ConclusionsOur studies uncover a previously unsuspected role of pDCs in asthma exacerbations with potential diagnostic and prognostic implications. They also propose the therapeutic targeting of pDCs and IL-25 for the treatment of acute asthma.
Graphical abstract
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Dynamic Risk Stratification in Stage I Papillary Thyroid Cancer Patients Younger Than 45 Years of Age
http://ift.tt/2gpDKlp
Extensive nail changes in a toddler with multisystemic Langerhans cell histiocytosis
Abstract
Langerhans cell histiocytosis (LCH) is a multisystem disorder involving various organs. Nail changes in LCH are extremely rare. We present this case report of extensive nail changes in an 18-month-old child with multisystem LCH.
http://ift.tt/2yvzw1T
Methotrexate treatment in a case of juvenile pityriasis rubra pilaris
Abstract
An 8-year-old boy who was initially diagnosed with plaque psoriasis failed management with topical therapies and skin biopsy confirmed the suspected diagnosis of juvenile pityriasis rubra pilaris (PRP). Pityriasis rubra pilaris is a rare inflammatory disorder of the skin characterized by follicular keratotic papules coalescing into plaques, along with palmoplantar keratoderma. Treatment modalities include topical and systemic therapies, although previous studies have not shown much benefit with methotrexate in children. We present a case in which methotrexate led to significant improvement of the skin findings in a child with type IV juvenile pityriasis rubra pilaris.
http://ift.tt/2xMPOQp
Latent Autoimmune Diabetes in Adults in North Indian Region: Assessment of β-Cell Function, Metabolic and Immunological Features
Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.
http://ift.tt/2gr8Adz
Inherited and acquired clinical phenotypes associated with neuroendocrine tumors.
Purpose of review: Overview of neuroendocrine neoplasms in the context of their associations with primary and secondary immunodeficiency states. Recent findings: Malignancies of neuroendocrine origin are well known to be associated with hereditary syndromes, including multiple endocrine neoplasia type 1, von Hippel-Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis. This review includes the X-linked form of hyper-IgM syndrome (XHIGM), due to mutations in the CD40Ligand gene (CD40LG), as an additional inherited disorder with susceptibility to such malignancies, and discusses neuroendocrine tumors (NETs) arising in other immunocompromised states. Of all primary immune deficiency diseases, NETs appear to be unique to XHIGM patients. Outcomes for XHIGM patients with NETs is poor, and the mechanism behind this association remains unclear. In secondary immune deficiency states, NET occurrences were primarily in patients with HIV or AIDS, the autoimmune disease systemic lupus erythematosus and solid organ transplant recipients. Gastroenteropancreatic NETs were most frequent in XHIGM patients, whereas nongastroenteropancreatic-NETs, like Merkel cell carcinoma and small-cell lung carcinoma, affected HIV/AIDS patients. Possible mechanisms as to the nature of these associations are discussed, including chronic infections and inflammation, and CD40-CD40L interactions. Many questions remain, and further studies are needed to clarify the predisposition of patients with XHIGM to the development of NETs. Given that many of these patients present late in their disease state and have poor outcomes, it is imperative to keep a high index of suspicion at the advent of early signs and symptoms. Regular monitoring with laboratory or imaging studies, including tumor markers, may be warranted, for which further studies are needed. Summary: Of all primary immunodeficiency diseases, NETs appear to be unique to XHIGM, and the mechanism behind this association remains unclear. Outcome for XHIGM patients with NETs is poor, and it is imperative to keep a high index of suspicion at the advent of early signs and symptoms. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2gq1pSD
http://ift.tt/2gq1pSD
An update on gain-of-function mutations in primary immunodeficiency diseases.
Purpose of review: Most primary immunodeficiencies described since 1952 were associated with loss-of-function defects. With the advent and popularization of unbiased next-generation sequencing diagnostic approaches followed by functional validation techniques, many gain-of-function mutations leading to immunodeficiency have also been identified. This review highlights the updates on pathophysiology mechanisms and new therapeutic approaches involving primary immunodeficiencies because of gain-of-function mutations. Recent findings: The more recent developments related to gain-of-function primary immunodeficiencies mostly involving increased infection susceptibility but also immune dysregulation and autoimmunity, were reviewed. Updates regarding pathophysiology mechanisms, different mutation types, clinical features, laboratory markers, current and potential new treatments on patients with caspase recruitment domain family member 11, signal transducer and activator of transcription 1, signal transducer and activator of transcription 3, phosphatidylinositol-4,5-biphosphate 3-kinase catalytic 110, phosphatidylinositol-4,5-biphosphate 3-kinase regulatory subunit 1, chemokine C-X-C motif receptor 4, sterile [alpha] motif domain containing 9-like, and nuclear factor [kappa]-B subunit 2 gain-of-function mutations are reviewed for each disease. Summary: With the identification of gain-of-function mutations as a cause of immunodeficiency, new genetic pathophysiology mechanisms unveiled and new-targeted therapeutic approaches can be explored as potential rescue treatments for these diseases. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2ywnF4a
http://ift.tt/2ywnF4a
Anticholinergics for asthma: a long history.
Purpose of review: To provide a fast overview about the introduction and development of anticholinergic drugs in Western medicine to their current indications particularly in asthma. Recent findings: Although short-acting muscarinic antagonists have been positioned in the last 15 years for the treatment of adults and children with moderate-to-severe acute asthma in the emergency setting (reducing the risk of hospital admissions and improving lung function), a growing body of evidence has recently emerged that positions the long-acting muscarinic anticholinergic tiotropium bromide as add-on therapy to at least inhaled corticosteroids (ICS) maintenance therapy in adults, adolescents, and children with symptomatic asthma. Thus, the addition of tiotropium bromide to ICS alone or ICS and another controller was associated with significant improvements in spirometric measures and asthma control, and a significantly decrease in the rate of asthma exacerbations. Summary: Short-acting muscarinic antagonists and tiotropium bromide have a well established role in the treatment of different phases of asthma. Further data are needed to provide more evidence on other selective long-acting muscarinic antagonists in addition to tiotropium as potential treatment options. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2gq8bYX
http://ift.tt/2gq8bYX
Delafloxacin an Effective Option for Acute Bacterial Skin Infections
Delafloxacin is non-inferior to vancomycin plus aztreonam for treating acute bacterial skin and skin-structure infections (ABSSSI), according to a new phase 3 trial.
Reuters Health Information
http://ift.tt/2xOnHVX
Inherited and acquired clinical phenotypes associated with neuroendocrine tumors.
Purpose of review: Overview of neuroendocrine neoplasms in the context of their associations with primary and secondary immunodeficiency states. Recent findings: Malignancies of neuroendocrine origin are well known to be associated with hereditary syndromes, including multiple endocrine neoplasia type 1, von Hippel-Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis. This review includes the X-linked form of hyper-IgM syndrome (XHIGM), due to mutations in the CD40Ligand gene (CD40LG), as an additional inherited disorder with susceptibility to such malignancies, and discusses neuroendocrine tumors (NETs) arising in other immunocompromised states. Of all primary immune deficiency diseases, NETs appear to be unique to XHIGM patients. Outcomes for XHIGM patients with NETs is poor, and the mechanism behind this association remains unclear. In secondary immune deficiency states, NET occurrences were primarily in patients with HIV or AIDS, the autoimmune disease systemic lupus erythematosus and solid organ transplant recipients. Gastroenteropancreatic NETs were most frequent in XHIGM patients, whereas nongastroenteropancreatic-NETs, like Merkel cell carcinoma and small-cell lung carcinoma, affected HIV/AIDS patients. Possible mechanisms as to the nature of these associations are discussed, including chronic infections and inflammation, and CD40-CD40L interactions. Many questions remain, and further studies are needed to clarify the predisposition of patients with XHIGM to the development of NETs. Given that many of these patients present late in their disease state and have poor outcomes, it is imperative to keep a high index of suspicion at the advent of early signs and symptoms. Regular monitoring with laboratory or imaging studies, including tumor markers, may be warranted, for which further studies are needed. Summary: Of all primary immunodeficiency diseases, NETs appear to be unique to XHIGM, and the mechanism behind this association remains unclear. Outcome for XHIGM patients with NETs is poor, and it is imperative to keep a high index of suspicion at the advent of early signs and symptoms. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2gq1pSD
http://ift.tt/2gq1pSD
An update on gain-of-function mutations in primary immunodeficiency diseases.
Purpose of review: Most primary immunodeficiencies described since 1952 were associated with loss-of-function defects. With the advent and popularization of unbiased next-generation sequencing diagnostic approaches followed by functional validation techniques, many gain-of-function mutations leading to immunodeficiency have also been identified. This review highlights the updates on pathophysiology mechanisms and new therapeutic approaches involving primary immunodeficiencies because of gain-of-function mutations. Recent findings: The more recent developments related to gain-of-function primary immunodeficiencies mostly involving increased infection susceptibility but also immune dysregulation and autoimmunity, were reviewed. Updates regarding pathophysiology mechanisms, different mutation types, clinical features, laboratory markers, current and potential new treatments on patients with caspase recruitment domain family member 11, signal transducer and activator of transcription 1, signal transducer and activator of transcription 3, phosphatidylinositol-4,5-biphosphate 3-kinase catalytic 110, phosphatidylinositol-4,5-biphosphate 3-kinase regulatory subunit 1, chemokine C-X-C motif receptor 4, sterile [alpha] motif domain containing 9-like, and nuclear factor [kappa]-B subunit 2 gain-of-function mutations are reviewed for each disease. Summary: With the identification of gain-of-function mutations as a cause of immunodeficiency, new genetic pathophysiology mechanisms unveiled and new-targeted therapeutic approaches can be explored as potential rescue treatments for these diseases. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2ywnF4a
http://ift.tt/2ywnF4a
Anticholinergics for asthma: a long history.
Purpose of review: To provide a fast overview about the introduction and development of anticholinergic drugs in Western medicine to their current indications particularly in asthma. Recent findings: Although short-acting muscarinic antagonists have been positioned in the last 15 years for the treatment of adults and children with moderate-to-severe acute asthma in the emergency setting (reducing the risk of hospital admissions and improving lung function), a growing body of evidence has recently emerged that positions the long-acting muscarinic anticholinergic tiotropium bromide as add-on therapy to at least inhaled corticosteroids (ICS) maintenance therapy in adults, adolescents, and children with symptomatic asthma. Thus, the addition of tiotropium bromide to ICS alone or ICS and another controller was associated with significant improvements in spirometric measures and asthma control, and a significantly decrease in the rate of asthma exacerbations. Summary: Short-acting muscarinic antagonists and tiotropium bromide have a well established role in the treatment of different phases of asthma. Further data are needed to provide more evidence on other selective long-acting muscarinic antagonists in addition to tiotropium as potential treatment options. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2gq8bYX
http://ift.tt/2gq8bYX
Antibacterial activity against cariogenic bacteria and cytotoxic and genotoxic potential of Anacardium occidentale L. and Anadenanthera macrocarpa (Benth.) Brenan extracts
Source:Archives of Oral Biology, Volume 85
Author(s): Josenildo Segundo Chaves de Araújo, Aline Rogéria Freire de Castilho, Andressa Brito Lira, Andréia Vieira Pereira, Tatiane Kelly Barbosa de Azevêdo, Edja Maria de Melo de Brito Costa, Maria do Socorro Vieira Pereira, Hilzeth Freire Luna Pessoa, Jozinete Vieira Pereira
ObjectivesThe present study aimed to assess the antibacterial activity against bacteria with cariogenic relevance, toxic and genotoxic potential of the plants Anacardium occidentale L. and Anadenanthera macrocarpa (Benth.) Bernam.DesignUsing a microdilution technique, the extracts were submitted to minimum inhibitory concentration (MIC) testing against Streptococcus mitis (ATCC 903), Streptococcus mutans (ATCC 25175), Streptococcus oralis (ATCC 10557), Streptococcus salivarius (ATCC 7073), Streptococcus sanguinis (ATCC 15300) and Streptococcus sobrinus (ATCC 27609). The toxicity of the extracts was then verified against eukaryotic cells. Additionally, a micronucleus assay was performed to investigate the potential mutagenic effects of the extracts on rat erythrocytes. The Student's t-test, Bonferroni test, and one-way ANOVA followed by Tukey's tests were used for statistical analysis, at a significance level of 5%.ResultsWhile the A. occidentale extract was able to inhibit all of the tested strains, with S. mutans and S. mitis being the most susceptible to that extract́s action, the A. macrocarpa did not show antimicrobial activity. Interestingly, the hemolytic, oxidant and antioxidant activities were slightly observed for either extract, even at high concentrations (1000mg/mL). The micronucleus assay showed no significant changes in the cells exposed to the extracts.ConclusionThe A. occidentale extract has potential as an antimicrobial agent with low eukaryotic cell toxicity or mutagenic activity. The A. macrocarpa extract, although absent of antibacterial activity might as well be a safe and effective phytotherapeutic alternative.
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Elderly patients affected by head and neck squamous cell carcinoma unfit for standard curative treatment: Is de-intensified, hypofractionated radiotherapy a feasible strategy?
Source:Oral Oncology, Volume 74
Author(s): Pierluigi Bonomo, Isacco Desideri, Mauro Loi, Monica Lo Russo, Emanuela Olmetto, Virginia Maragna, Giulio Francolini, Camilla Delli Paoli, Roberta Grassi, Donato Pezzulla, Daniela Greto, Icro Meattini, Lorenzo Livi
ObjectivesThe aim of our work was to report on the clinical outcome of a moderately hyprofractionated radiotherapy regimen in elderly patients affected by head and neck squamous cell carcinoma (HNSCC).Material and methodsHNSCC aged ≥65 deemed unsuitable for curatively-intended concurrent chemo-radiotherapy or high-dose radiotherapy by clinical judgement were further evaluated with the Geriatric 8 (G8) questionnaire and Charlson comorbidity index (CCI). In case of a G8 score ≤14, a de-intensified radiation schedule of 40 Gy delivered in 16 fractions was prescribed.ResultsThirty-six patients were treated between 2011 and 2016. The median age of the cohort was 77.5 (range: 65–91 years) with a combined ECOG PS of 2–3 in 77.8% and CCI of ≥8 in 25% patients, respectively. At a median follow-up of 13 months (range 2–62 months), the 6-month and 1-year rates of loco-regional control and progression-free survival were 42%, 28% and 36% and 20%, respectively. At univariate analysis, log-rank test showed that age >75 years (p=0.036), worse PS (ECOG≥2; p=0.027), lower G8 score (<9; p=0.027) and PTV volume greater than 200 cc (p=0.038) had a significant correlation with PFS. The negative impact of the PTV volume on PFS was the only parameter confirmed in the multivariate analysis (HR 2.68; 95% CI: 1.24–5.81, p=0.013). No grade 4–5 toxicity was observed, while 13/36 patients (36%) had G3 acute side effects.ConclusionThe hypofractionated radiation schedule evaluated provides clinical benefit with low toxicity in frail, elderly patients affected by locally advanced HNSCC.
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A high ratio of IL-12Rβ2-positive tumor-infiltrating lymphocytes indicates favorable prognosis in laryngeal cancer
Source:Oral Oncology, Volume 74
Author(s): Ye Tao, Neil Gross, Yehai Liu, Liyong Zhang, Guojun Li, Zhigang Huang, Jianming Yang
BackgroundThe purpose of this study was to elucidate IL-12Rβ2's roles as a tumor-associated immunological molecule, delineate the complex roles of IL-12Rβ2+ tumor-infiltrating lymphocytes (TILs) and tumor cell IL-12Rβ2 expression in the tumor microenvironment, and determine the correlation of IL-12Rβ2+ TILs and tumor cell IL-12Rβ2 expression with clinical prognosis.MethodsWe assessed mRNA and protein levels in matched laryngeal cancer tissues (LTs) and adjacent normal mucous membrane tissues (ANMMTs) from 3 laryngeal cancer (LC) patients and ratios of IL-12Rβ2+ TILs in matched LTs and ANMMTs from 61 LC patients. We used the Kaplan-Meier log-rank test and Cox regression hazard ratios to analyze survival.ResultsComparative proteomic and transcriptomic assays revealed that matched LTs and ANMMTs from the 3 patients had significantly different IL-12Rβ2 and IFN-γ expression; the ratio of IL-12Rβ2+ TILs decreased with lower degrees of tumor differentiation. Among all 61 LC patients, the IL-12Rβ2+ TIL ratio in ANMMTs (38.5% ± 22.8%) was significantly higher than that in LTs (29.7% ± 19%; p<.001). Kaplan-Meier analysis revealed that patients with an IL-12Rβ2+ TIL ratio ≥35% had significantly better survival than those with an IL-12Rβ2+ TIL ratio <35% (log rank p=0.041). Multivariable analysis showed a significant association between a high IL-12Rβ2+ TIL ratio and overall survival (hazard ratio, 0.14; 95% confidence interval, 0.03–0.77).ConclusionTumor cell differentiation is associated with TILs' expression of IL-12Rβ2, and an IL-12Rβ2+ TIL ratio ≥35%) indicates favorable prognosis in LC.
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Patient, disease, and treatment factors associated with overall survival in esthesioneuroblastoma
Background
Esthesioneuroblastomas (ENB) are uncommon and data regarding outcomes are often limited to single-institution series. The National Cancer Database (NCDB), which contains outcomes information from treatment centers across the United States, represents an opportunity to evaluate outcomes for rare diseases such as ENB across multiple institutions.
Methods
The NCDB was queried for location codes corresponding to the nasal cavity and paranasal sinuses and the histology code for ENB. Multivariate analyses were performed to evaluate for contributing factors to overall survival.
Results
A total of 1225 patients with ENB met the inclusion criteria. The 5-year overall survival was 76.2% (95% confidence interval [CI], 73.4-79.0%). Overall survival was associated with Kadish stage, grade, treatment sequence, margin status, Charlson/Deyo score, age, and gender (p < 0.05). Multivariate analysis demonstrated that, compared with surgery alone, surgery followed by radiation without chemotherapy had improved all-cause mortality (odds ratio [OR], 0.61; 95% CI, 0.40-0.95). Surgery with chemotherapy alone was associated with increased odds of all-cause mortality (OR, 4.86; 95% CI, 2.31-10.25). Multivariate subanalysis for Kadish stages A and B demonstrated no difference in survival between surgery and surgery followed by radiation, but surgery followed by chemoradiation had worse overall survival (OR, 3.03; 95% CI, 1.07-8.56). For Kadish stage C, surgery followed by radiation had improved overall survival compared with surgery alone (OR, 0.44; 95% CI, 0.24-0.81).
Conclusion
The most common treatment for ENB is surgery followed by radiation, which is associated with the highest overall survival. The role of adjunctive chemotherapy needs to be re-evaluated in further studies.
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Laparoscopic Supracervical Hysterectomy with In-Bag Morcellation in Very Large Uterus
Laparoscopic supracervical hysterectomy (LASH) is a safe and fast minimally invasive approach in hysterectomy. In order to extract the uterine body from the abdominal cavity, one condition for LASH is the morcellation of the tissue. The intra-abdominal dissemination of benign and occult malignant uterine cells is a possible risk of this method, which can be avoided by the use of special bags for laparoscopic in-bag morcellation. We present a case of laparoscopic supracervical hysterectomy with in-bag morcellation in a uterus of more than 1400 g. and describe that this minimal-access surgery is safe and feasible even in very large uteri. This case report is registered in Research Registry under the UIN researchregistry1810.
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Real world treatment patterns and outcomes among metastatic cutaneous melanoma patients treated with ipilimumab
Abstract
Background
There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011.
Objective
To evaluate ipilimumab and post-ipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain following regulatory approval.
Methods
Retrospective multicentre, multinational, observational chart review study. Data were extracted from the start of ipilimumab therapy until the end of at least 40 weeks of follow-up, or death.
Results
Data from 371 patients (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was 65 years; 62% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second-line or later therapy. Patients received on average 3.4 ipilimumab doses. The ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in Australia, 47% in Germany, 29% in Italy and 14% in Spain received another anti-melanoma treatment after ipilimumab including chemotherapy in 26% and BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received post-ipilimumab treatment showed a 40% reduced hazard of dying than those not receiving treatment after ipilimumab (HR 0.60; 95% CI 0.43-0.83), after adjustment for potential confounders.
Conclusion
During the time observed, ipilimumab was mainly used as second-line or later therapy. A significant proportion of patients received post-ipilimumab therapy, most of which was chemotherapy. Nevertheless, overall survival following progression on ipilimumab treatment remained poor, highlighting the need for research to develop more effective end-of-life treatment options.
This article is protected by copyright. All rights reserved.
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Determination of the impact of melanoma surgical timing on survival using the National Cancer Database
The ideal timing for melanoma treatment, predominantly surgery, remains undetermined. Patient concern for receiving immediate treatment often exceeds surgeon or hospital availability, requiring establishment of a safe window for melanoma surgery.
http://ift.tt/2zhvKqp
A Study of DSP-7888 Dosing Emulsion in Combination With Immune Checkpoint Inhibitors in Adult Subjects With Advanced Solid Tumors
Conditions: Neoplasms; Melanoma; Non Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Renal Cell Carcinoma; Urothelial Neoplasm
Interventions: Drug: DSP-7888 Dosing Emulsion; Drug: Nivolumab; Drug: Atezolizumab
Sponsor: Boston Biomedical, Inc
Not yet recruiting
http://ift.tt/2x0G853
Interventions: Drug: DSP-7888 Dosing Emulsion; Drug: Nivolumab; Drug: Atezolizumab
Sponsor: Boston Biomedical, Inc
Not yet recruiting
http://ift.tt/2x0G853
Is there a relationship between melanocytes and sensorineural hearing loss? clinical evaluation of fifthy-one alopecia areata patients
Abstract
Melanocytes are located in both the cochlea and vestibular organ of the inner ear. They are present in the hearing organ, in the intermediate layer of stria vascularis in the cochlea.
The most important task of the stria vascularis is to provide the endolymph production necessary for normal hearing levels, especially high K+ concentration, and to protect the positive endocochlear potential.
Specifically, intermediate layer melanocytes express ionic channels, such as inwardly rectifying K+ channels and voltage-dependent outwardly rectifying K+.
The underlying mechanisms of the damage to melanocytes in the skin can also affect other organs, including inner ear.
Coexistence of cochlear dysfunction in alopecia areata patients suggest that presumed autoimmunity against follicular melanocytes in AA might also effect the melanocytes in the inner ear. This could strengthen the relationship between sensorineural hearing loss and autoimmunity.
This article is protected by copyright. All rights reserved.
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Aretrospective review of six-hundred nineteen cases to determine the prevalence and factors associated with revision endoscopic sinus surgery in AFRS vs non-AFRS patients
Abstract
Patients undergoing revision functional endoscopic sinus surgery (rFESS) for refractory chronic rhinosinusitis (CRS) are more likely to be older, have worse pre-operative Lund-Mackay CT scores, and poorer quality-of-life scores than primary FESS patients.
Patients with more aggressive forms of CRS such as CRS with nasal polyposis (CRSwNP) or allergic fungal rhinosinusitis (AFRS) may fare worse in the long term with residual disease and be more likely to seek out tertiary institutions for treatment including rFESS.
Computed tomography (CT) findings most frequently associated with failure of primary FESS were frontal sinus/recess residual bony partitions (91.8%), remnant ethmoid sinus shelves (88.2%) and unopened pneumatized ethmoid cells (77.7%).
Patients with a diagnosis of allergic fungal rhinosinusitis (AFRS) who required rFESS presented with significantly fewer frontal sinus residual bony partitions, residual uncinate process, and ethmoid sinus residual unopened pneumatized cells, than non-AFRS patients, suggesting that intrinsic biological factors were the major contributors to failure of primary FESS.
The factors associated with rFESS are numerous and should be explored further. Other factors that may be important to consider when assessing causes of primary FESS failure may include surgeon skill level as well as the availability of proper instrumentation and support staff in the setting in which the procedure is performed (e.g. tertiary vs community level hospital).
This article is protected by copyright. All rights reserved.
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Diagnostic Accuracy of Nasal Endoscopy as Compared to Computed Tomography in Chronic Rhinosinusitis
Abstract
The study was done with the aims to evaluate the accuracy of nasal endoscopy as compared to computed tomography (CT) in diagnosing chronic rhinosinusitis (CRS) and to evaluate the correlation between Endoscopy Score and CT Score. It was a cross sectional study. Every consecutive, symptomatic patient of CRS who fulfilled the criteria of American Academy of Otolaryngology—Head and Neck Surgery Task Force were included in the study. Rigid diagnostic nasal endoscopy (DNE) was done and Lund-Kennedy scoring system was used. Plain CT of paranasal sinuses was done on the same day and severity was assessed using Lund-Mackay scoring system. Results were analysed considering CT as a gold standard. Out of 54 study patients, 45 (83.33%) had abnormal endoscopic examination while 50 (92.59%) were showing positive CT scan. Sensitivity and specificity of DNE against CT scan were 94% (95% CI 81.43–98.33%) and 75% (95% CI 42–99.24%), respectively. The positive predictive value was 98% and negative predictive value was 67%. Correlation between Lund-Mackay overall CT and Lund-Kennedy Endoscopy Score was high [Pearson's correlation coefficient (r) = 0.881, p value < 0.0001]. The conclusion was drawn that, endoscopy is valuable in individuals with symptoms consistent with CRS and can be used to confirm the diagnosis and to know the severity of the disease. CT scan can be advised in those with high clinical suspicion of CRS but negative endoscopy and in those having persistent symptoms after optimum medical management requiring Functional Endoscopic Sinus Surgery.
http://ift.tt/2ikFjlq
Does omalizumab modify a course of recalcitrant chronic spontaneous urticaria?: A retrospective study in Asian patients
Abstract
Omalizumab has been approved for the treatment of recalcitrant chronic spontaneous urticaria (CSU). However, it remains unanswered whether omalizumab modifies a CSU course. We aimed to study a course of CSU after omalizumab treatment in an Asian population. Medical records of recalcitrant CSU patients who attended Siriraj Hospital between 2013 and 2017 were reviewed. All patients receiving omalizumab treatment were followed after the first injection for at least 1 year. Of 15 patients receiving omalizumab treatment, 11 patients (73.3%) responded well to 150 mg while the rest required 300 mg. The median follow-up period was 18 months (range, 13.5–25.3). Three patterns of response were proposed and measured: excellent (disease remission over than 6 months) was found in 20%; good (injection interval extended longer than 6 months) was found in 27%; and modest (frequently required injections) was found in 53%. The mean duration of complete remission was 33 weeks (range, 26–38). Two-thirds of patients had disease relapse and required omalizumab injections to control symptoms. The other third did not show relapses for at least 69 weeks of the follow-up period. After 1 year of treatment, Kaplan–Meier curves estimated that a higher percentage (86.7%) of recalcitrant CSU patients receiving omalizumab treatment would be free of symptoms (weekly Urticaria Activity Score = 0) without prednisolone and/or cyclosporin as compared with 42% of patients not receiving omalizumab treatment. In conclusion, patients seem to be easily and safely manageable with omalizumab. Prednisolone and cyclosporin could be discontinued in all patients. Further studies are needed to conclude whether omalizumab can exactly modify CSU.
http://ift.tt/2ynBjqn
Possible pro-inflammatory role of heparin-binding epidermal growth factor-like growth factor in the active phase of systemic sclerosis
Abstract
Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family growth factors, which affects multiple aspects of the wound healing process such as epithelialization, wound contraction and angiogenesis. In our study, we measured the serum HB-EGF levels of 51 systemic sclerosis (SSc) patients, which showed a significant increase compared with those of 20 normal subjects. Further analysis revealed a positive correlation between the HB-EGF level and pulmonary ground-glass score but no correlation between the former and pulmonary fibrosis score. Other findings include: a significant increase of serum sialylated carbohydrate antigen KL-6 levels and significant shortness of disease duration in the diffuse cutaneous SSc patients with elevated HB-EGF levels; and significantly higher HB-EGF levels in the presence of Raynaud's phenomenon, in that of telangiectasia, and in the absence of contracture of phalanges in all SSc patients. We then evaluated HB-EGF mRNA levels of fibroblasts harvested from skin samples of the SSc patients and those of foreskin-derived fibroblasts treated with transforming growth factor-β, both of which were significantly higher than each control. In conclusion, we speculate that HB-EGF plays a pro-inflammatory role in the active skin and lung lesions of SSc.
http://ift.tt/2geZTzb
Cover Image
The cover image, by Amy J. Hobbs et al., is based on the Original Article rimary treatment for oropharyngeal squamous cell carcinoma in Alberta, Canada: A population-based study, DOI: 10.1002/hed.24889.
http://ift.tt/2yrWzc5
Effect of matrix metalloproteinase inhibitor on disrupted E-cadherin after acid exposure in the human nasal epithelium
Objective
Laryngopharyngeal reflux disease (LPRD) is one of potential factors in recalcitrant chronic rhinosinusitis with or without polyps. An increase in junctional permeability in the nasal mucosa in LPRD may be due to disrupted protein bridge formation with cell-to-cell adhesion molecules such as E-cadherin. Despite the relationship between nasal mucosal inflammation and LPRD, the clear mechanism by which acid reflux affects the nasal epithelium remains unclear.
Methods
The expression levels and distribution patterns of E-cadherin in primary culture of nasal epithelial cells after acid exposure with or without dexamethasone and matrix metalloproteinase (MMP) inhibitor were determined using Western blot and immunocytochemistry. The functional roles of MMP inhibitor in maintaining junctional permeability in the nasal epithelium were elucidated by transepithelial permeability test.
Results
By acid exposure to nasal epithelial cells, mature E-cadherin was decreased and cleaved E-cadherin was increased. This was thought to be caused by cleavage of mature E-cadherin between cells and was confirmed by the increment of E-cadherin inside a cell in immunocytochemical evaluation. Whereas disruption of E-cadherin was not recovered by steroid medication with various treatments of dexamethasone, disrupted E-cadherin was restored to normal by inhibition of MMPs with actinonin, a broad MMP inhibitor. This recovery was functionally demonstrated by transepithelial permeability test.
Conclusion
Our results suggest that altered expression of E-cadherin in the nasal epithelium by acid exposure may be a possible mechanism for nasal tissue injury in chronic nasal inflammation with LPRD, and that MMP inhibition is a potential treatment.
Level of Evidence
NA. Laryngoscope, 2017
http://ift.tt/2yxwhHP
Frailty, hospital volume, and failure to rescue after head and neck cancer surgery
Objectives/Hypothesis
We previously reported that high-volume hospital head and neck cancer (HNCA) surgical care is associated with decreased mortality, largely explained by reduced rates of failure to rescue. Frailty is an independent predictor of mortality, but is significantly less likely in patients receiving high-volume care. We investigate whether differences in frailty rates explain the relationship between volume and outcomes in HNCA patients and whether frailty confounds the relationship between failure to rescue and mortality.
Study Design
Cross-sectional analysis.
Methods
Discharge data from the Nationwide Inpatient Sample for 159,301 patients who underwent ablative surgery for a malignant oral cavity, laryngeal, hypopharyngeal, or oropharyngeal neoplasm in 2001 to 2010 were analyzed using cross-tabulations and multivariate regression. Failure to rescue was defined as death after a major complication. Frailty was defined using frailty-defining diagnosis clusters from the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator.
Results
High-volume hospital care was associated with a lower odds of frailty (odds ratio [OR]: 0.7 [95% confidence interval [CI]: 0.5-1.0]). Frail patients had higher odds of postoperative complications (OR: 4.1 [95% CI: 3.4-4.9]) and mortality (OR: 2.0 [95% CI: 1.3-3.2]), but no difference in failure to rescue rates (OR: 1.0 [95% CI: 0.6-1.6]). High-volume care was not associated with differences in odds of complications (OR: 1.0 [95% CI: 0.8-1.2]), but was associated with significantly decreased odds of mortality (OR: 0.6 [95% CI: 0.5-0.9]) and failure to rescue (OR: 0. 6 [95% CI: 0.3-1.0]), which was not attenuated by adjusting for frailty.
Conclusions
High-volume HNCA surgical care is associated with a significantly lower odds of mortality, which appears to be associated with differences in the response to and management of complications rather than differences in frailty or complication rates.
Level of Evidence
2c. Laryngoscope, 2017
http://ift.tt/2xLiol8
Investigating the effects of laryngotracheal stenosis on upper airway aerodynamics
Objective
Very little is known about the impact of laryngotracheal stenosis (LTS) on inspiratory airflow and resistance, especially in air hunger states. This study investigates the effect of LTS on airway resistance and volumetric flow across three different inspiratory pressures.
Methods
Head-and-neck computed tomography scans of 11 subjects from 2010 to 2016 were collected. Three-dimensional reconstructions of the upper airway from the nostrils to carina, including the oral cavity, were created for one subject with a normal airway and for 10 patients with LTS. Airflow simulations were conducted using computational fluid dynamics modeling at three different inspiratory pressures (10, 25, 40 pascals [Pa]) for all subjects under two scenarios: 1) inspiration through nostrils only (MC), and 2) through both nostrils and mouth (MO).
Results
Volumetric flows in the normal subject at the three inspiratory pressures were considerably higher (MC: 11.8–26.1 L/min; MO: 17.2–36.9 L/min) compared to those in LTS (MC: 2.86–6.75 L/min; MO: 4.11–9.00 L/min). Airway resistances in the normal subject were 0.051 to 0.092 pascal seconds per milliliter (Pa.s)/mL (MC) and 0.035–0.065 Pa.s/mL (MO), which were approximately tenfold lower than those of subjects with LTS: 0.39 to 0.89 Pa.s/mL (MC) and 0.45 to 0.84 Pa.s/mL (MO). Furthermore, subjects with glottic stenosis had the greatest resistance, whereas subjects with subglottic stenosis had the greatest variability in resistance. Subjects with tracheal stenosis had the lowest resistance.
Conclusion
This pilot study demonstrates that LTS increases resistance and decreases airflow. Mouth breathing significantly improved airflow and resistance but cannot completely compensate for the effects of stenosis. Furthermore, location of stenosis appears to modulate the effect of the stenosis on resistance differentially.
Level of Evidence
NA. Laryngoscope, 2017
http://ift.tt/2ywrV3x
Diagnostic Accuracy of Nasal Endoscopy as Compared to Computed Tomography in Chronic Rhinosinusitis
Abstract
The study was done with the aims to evaluate the accuracy of nasal endoscopy as compared to computed tomography (CT) in diagnosing chronic rhinosinusitis (CRS) and to evaluate the correlation between Endoscopy Score and CT Score. It was a cross sectional study. Every consecutive, symptomatic patient of CRS who fulfilled the criteria of American Academy of Otolaryngology—Head and Neck Surgery Task Force were included in the study. Rigid diagnostic nasal endoscopy (DNE) was done and Lund-Kennedy scoring system was used. Plain CT of paranasal sinuses was done on the same day and severity was assessed using Lund-Mackay scoring system. Results were analysed considering CT as a gold standard. Out of 54 study patients, 45 (83.33%) had abnormal endoscopic examination while 50 (92.59%) were showing positive CT scan. Sensitivity and specificity of DNE against CT scan were 94% (95% CI 81.43–98.33%) and 75% (95% CI 42–99.24%), respectively. The positive predictive value was 98% and negative predictive value was 67%. Correlation between Lund-Mackay overall CT and Lund-Kennedy Endoscopy Score was high [Pearson's correlation coefficient (r) = 0.881, p value < 0.0001]. The conclusion was drawn that, endoscopy is valuable in individuals with symptoms consistent with CRS and can be used to confirm the diagnosis and to know the severity of the disease. CT scan can be advised in those with high clinical suspicion of CRS but negative endoscopy and in those having persistent symptoms after optimum medical management requiring Functional Endoscopic Sinus Surgery.
http://ift.tt/2ikFjlq
Clinical Characteristics of Children With Single-Sided Deafness Presenting for Candidacy Assessment for Unilateral Cochlear Implantation
Abstract
Purpose of Review
Children with unilateral deafness may experience challenges with language development, educational progress, and social interaction. Rehabilitation with a cochlear implant (CI) may minimize these impacts. This review examines the characteristics of children with unilateral deafness presenting for candidacy assessment.
Recent Findings
Forty-nine children with unilateral deafness were assessed. Many (15/49) did not meet candidacy criteria due to cochlear nerve aplasia/hypoplasia (12/49), while 17/49 elected not to pursue CI. The most common etiologies in those 17/49 (35%) who met candidacy and consented to CI were congenital cytomegalovirus (cCMV) (41%) and trauma (26%).
Summary
Many children with unilateral deafness who present for assessment do not go on to receive an implant due to anatomic contraindications or their desire for non-intervention. This review highlights the high prevalence of cCMV amongst children with unilateral deafness presenting for CI where the potential for progression to bilateral hearing loss may influence decision for implantation.
http://ift.tt/2gKTSuy
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