In this article, we look at the process of breast reconstruction surgery, the reasons for choosing this surgery, alternative options, and recovery outlook.
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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 2 Σεπτεμβρίου 2017
Breast reconstruction surgery: Options and what to expect
Long-term results of a phase II study of gemcitabine and cisplatin chemotherapy combined with intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma
Source:Oral Oncology, Volume 73
Author(s): Mingyao Wu, Dan Ou, Xiayun He, Chaosu Hu
http://ift.tt/2wteYGj
Chemotherapy in head and neck osteosarcoma: Adjuvant chemotherapy improves overall survival
Source:Oral Oncology, Volume 73
Author(s): YiMing Chen, Sandhya Gokavarapu, QingCheng Shen, Feng Liu, Wei Cao, YueHua Ling, Tong Ji
BackgroundOsteosarcoma is an aggressive bone malignancy presenting uncommonly in head and neck sites. Surgery is mainstay in treatment. However; trials show an improved survival with addition of chemotherapy in the treatment of extremity osteosarcoma. The head and neck osteosarcomas(HNOs) were excluded in these trials because of atypical presentation and disease course. Further; sufficient numbers were not possible for a trial. We present the largest retrospective study from single institute investigating the role of chemotherapy in the management of HNOs.Patients and methodsThe retrospective cohort of HNOs treated from 2007 to 2015 of a tertiary hospital were charted. The therapeutic and prognostic factors were analyzed for overall survival(OS), disease free survival(DFS), local control(LC) and metastasis(MT) in univariate and multivariate analysis. The minimum and median period of follow up was 12months and 56.04months respectively.ResultsThere was a total of 157 patients definitively treated with surgery in the time period. 7 patients had positive margins and all were maxillary or skull base tumors. The multivariate cox regression showed significance of tumor site(p=0.034), margin status (p=0.006), chemotherapy(p=0.025), histological subtype(p=0.012) as predictors of overall survival. The margin status(p=0.002), Radiotherapy(p=0.005) were significant predictors for local recurrence. The age and histology subtype(p=0.058) were borderline significant predictors of metastasis(p=0.065). The KM method for OS of different chemotherapy groups(p=0.013), and survival with and without chemotherapy(p=0.007) was significant. The OS was significantly better with adjuvant chemotherapy among various treatment plans(p=0.034).ConclusionAdjuvant chemotherapy improved OS while adjuvant radiotherapy improved local control of HNOs.
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Pre-diagnostic dynamic HPV16 IgG seropositivity and risk of oropharyngeal cancer
Source:Oral Oncology, Volume 73
Author(s): Karen S. Anderson, Garrick Wallstrom, Hilde Langseth, Marshall Posner, Julia N. Cheng, Rizwan Alam, Diego Chowell, Ingegerd E. Furre, Jon Mork
ObjectiveThe aim of this study was to determine the association of HPV16 antibodies (Abs) and oropharyngeal cancer (OPC) risk in sera obtained prior to clinical diagnosis.MethodsWe identified 92 participants with incident OPC and 460 matched controls from the Janus Serum Bank Cohort in Norway. Archived tumor specimens were requested for a subset of the cases. Serum samples were collected from cases, on average, 9.3years before diagnosis (range, 0.1–14.9years). Ten cases had serum samples from multiple time points. IgG seropositivity to 8 HPV16 antigens was determined, and a logistic regression classifier of a panel of all early-antigen (EA) Abs for the predictive diagnosis of OPC was applied.ResultsHPV16 EA seropositivity was present in 25.0% of patients with OPC and 7.6% of controls (odds ratio (OR), 4.1; 95% CI, 2.3–7.2, p<0.0001). Abs to E2 were strongly associated with cases 0–2years pre- diagnosis (OR, 150.1; 95% CI, 27.4–1040.0, p<0.0001), and the probability of seropositivity was inversely associated with time to diagnosis (OR, 0.7 per additional year; 95% CI, 0.6–0.9, p=0.0002). Abs to E2 were also strongly associated with tumor HPV status (OR, 35.6; 95% CI, 8.7–200.0, p<0.0001). A positive score on the binary classifier was associated with an overall OR of 15.8 (95% CI, 5.6–53.4) compared with controls (p<0.05), and was strongly associated with tumor HPV status (OR, 27.4; 95% CI, 8.6–99.6, p<0.001).ConclusionsHPV16 Abs are detectable years prior to diagnosis of OPC, and the probability of seropositivity increases closer to diagnosis.
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A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator’s choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141
Source:Oral Oncology, Volume 73
Author(s): Naomi Kiyota, Yasuhisa Hasegawa, Shunji Takahashi, Tomoya Yokota, Chia-Jui Yen, Shigemichi Iwae, Yasushi Shimizu, Ruey-Long Hong, Masahiro Goto, Jin-Hyoung Kang, Wing Sum Kenneth Li, Robert L. Ferris, Maura Gillison, Yoshinobu Namba, Manish Monga, Mark Lynch, Makoto Tahara
ObjectivesTo assess efficacy and safety of nivolumab versus investigator's choice of therapy (IC) in Asian patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).Materials and methodsThirty-four patients from Japan, Taiwan, Hong Kong, and Korea received nivolumab 3mg/kg (n=23) every 2weeks or IC (n=11), as part of a global trial (n=361), until intolerable toxicity or disease progression. The primary endpoint was overall survival (OS).ResultsMedian OS was 9.5months (95% confidence interval [CI] 9.1–NR) with nivolumab and 6.2months (95% CI 2.6–NR) with IC. Seven (30.4%) patients receiving nivolumab and six (54.5%) receiving IC died. The hazard ratio (HR) for risk of death (nivolumab vs. IC) was 0.50 (95% CI 0.17–1.48). Median progression-free survival was 1.9months (95% CI 1.6–7.5) with nivolumab and 1.8months (95% CI 0.4–6.1) with IC (HR 0.57 [95% CI 0.25–1.33]). Objective response rates (complete+partial responses) were 26.1% (6/23 patients; 95% CI 10.2–48.4) for nivolumab and 0% (0/11 patients; 95% CI 0.0–28.5) for IC. Sixteen (69.6%) nivolumab-treated patients and 10 (90.9%) patients receiving IC had a treatment-related adverse event, most commonly decreased appetite (21.7%), pruritus, rash, and fatigue (17.4% each) with nivolumab, and nausea, stomatitis, and decreased appetite (27.3% each) with IC.ConclusionNivolumab demonstrated a survival advantage compared with conventional treatments in Asian patients with platinum-refractory recurrent or metastatic SCCHN, and was well tolerated.Clinical trial registration NCT02105636.
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Assessing hypoxia risk during air travel after a severe asthma exacerbation in children
Source:Annals of Allergy, Asthma & Immunology
Author(s): Jose Antonio Peña-Zarza, Borja Osona, Sebastian Sailer, Jose Antonio Gil-Sanchez, Joan Figuerola Mulet
http://ift.tt/2vAIsmC
Nasal interleukin 25 as a novel biomarker for patients with chronic rhinosinusitis with nasal polyps and airway hypersensitiveness
Source:Annals of Allergy, Asthma & Immunology
Author(s): Fenghong Chen, Haiyu Hong, Yueqi Sun, Xianting Hu, Jia Zhang, Geng Xu, Weidong Zhao, Huabin Li, Jianbo Shi
BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airway and is tightly linked with airway hyperresponsiveness (AHR) and asthma. However, the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP remain elusive.ObjectiveTo investigate the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP.MethodsIn this study, sinonasal tissues were collected from 42 patients with CRSwNP (asthma, n = 17; asymptomatic AHR, n = 11; non-AHR, n = 14), 11 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 13 controls. The protein and messenger RNA levels of interleukin (IL) 25 and other cytokines in nasal polyp (NP) and control sinonasal tissues were determined by quantitative real-time polymerase chain reaction and multiplex immunoassay, respectively. Multivariate logistic regression and receiver operating characteristic curve analysis were performed to assess the clinical relevance of IL-25.ResultsWe found that the protein and messenger RNA levels of IL-25 were significantly increased in NP tissues compared with the control sinonasal tissues from patients with CRSwNP, patients with CRSsNP, and controls. Multivariate logistic regression revealed that the nasal IL-25 protein level and nasal and blood eosinophil counts were independent risk factors for AHR in patients with CRSwNP. According to receiver operating characteristic curve analysis, nasal tissue IL-25 had a sensitivity of 91.4% and a specificity of 62.8% (area under the curve, 0.845) at the cutoff level of 5 pg/μL for indicating AHR in this CRSwNP cohort.ConclusionOur findings indicated that IL-25 was significantly increased in NP tissues and may be considered as the molecular indicator for AHR in patients with CRSwNP.Trial RegistrationClinicalTrials.gov Identifier: NCT02110654.
http://ift.tt/2wwVGOM
Three new cases of bullous pemphigoid during anti-PD-1 antibody therapy
Abstract
Anti-programmed death 1 (PD-1) antibodies are revolutionizing the treatment of many cancers, including melanoma 1. Cutaneous adverse events (AE) of anti-PD-1 antibodies are common (20%) and mainly non-specific. Bullous pemphigoids (BP) are very rare immune-related AEs induced by anti-PD-1 antibodies, with only 12 cases previously published. We report here three new cases of BP during anti PD-1 therapy with nivolumab.
This article is protected by copyright. All rights reserved.
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Differential regulation of PD-1 and its ligands in allergic asthma
Abstract
Background
Targeting PD-1/PD-1 ligand signalling is an established treatment option for cancer. The role of these molecules in allergic asthma has been investigated in several mouse studies yielding conflicting results. However, human studies investigating the expression and regulation of PD-1 and its ligands in allergic inflammation are lacking.
Objective
To analyse the expression and regulation of PD-1 and its ligands in human allergic asthma.
Methods
The well-established human asthma model of segmental allergen challenge (SAC) was used to analyse the regulation of PD-1 and its ligands PD-L1 and PD-L2 on T lymphocytes and dendritic cells by flow cytometry. The impact of immunoglobulin E (IgE)-mediated signalling on PD-L1 expression was analysed on isolated plasmacytoid dendritic cells (pDCs).
Results
PD-1 expression by blood CD4+ T cells was negatively associated with total and specific (against the allergen used for provocation) IgE serum concentrations. 24 hours after SAC, a small decrease in endobronchial PD-1+CD4+ T cells was accompanied by an increase of PD-L1 expression on endobronchial myeloid dendritic cells (mDCs) and pDCs. The PD-L1 up-regulation on pDCs was not induced by IgE-mediated mechanisms. In contrast, PD-L2 was only detected on endobronchial mDCs and was significantly down-regulated 24 hours after SAC.
Conclusion and Clinical Relevance
This study shows, for the first time, an association of a low PD-1 expression by circulating CD4+ T cells with high total and specific (against the allergen used for provocation) IgE concentrations in allergic asthma. In addition, we demonstrate a differential regulation of PD-1 ligands on endobronchial DCs after allergen challenge which may favour Th2-inflammation. Therefore, modulating PD-1 ligand-mediated pathways might be a promising target in allergic asthma.
This article is protected by copyright. All rights reserved.
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Hen's egg allergen in house and bed dust is significantly increased after hen's egg consumption – a pilot study
Abstract
Environmental exposure to food allergens may be a risk factor for cutaneous sensitization. Previous studies could detect peanut allergen in house dust. In this pilot study, we wanted to investigate whether hen's egg allergen is detectable in house dust collected from different household areas and whether levels are increased after intentional hen's egg consumption. Hen's egg protein levels of dust samples were measured using ELISA. In 8/8 households, hen's egg was detectable in dust samples of eating area and bed. 48 hours after intentional hen's egg consumption, hen's egg protein levels were significantly increased in both. Still, further research is necessary to investigate whether hen's egg allergen in house and bed dust plays a role in sensitization via skin.
This article is protected by copyright. All rights reserved.
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Validation of a Portuguese version of the health-related quality of life measure for active chronic otitis media (COMQ-12)
Publication date: Available online 1 September 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Anna Carolina Oliveira Fonseca, Pedro Ramos, Fernando A. Balsalobre, Edson L. Freitas, Ricardo F. Bento, John S. Phillips, Matthew W. Yung
IntroductionMeasuring the impact on quality of life, especially after the beginning of the treatment, is becoming increasingly important in healthcare.ObjectiveThe aim of this study was to translate the Chronic Otitis Media Questionnaire-12 (COMQ-12) into Portuguese language and validate this version in a group of patients with chronic otitis media.MethodsThe Portuguese version of COMQ-12 was obtained by translation and back translation. Portuguese speaking patients with a history of active chronic otitis media were asked to complete the COMQ-12 Portuguese version. Cronbach's α coefficient was calculated for an estimation of the internal consistency of the questionnaire.ResultsA total of 100 patients were included in the study; 49 women and 51 men, with a mean age of 39 years (range 12–77 years, median 40 years). The average COMQ-12 score was 29, out of a maximum score of 60. Cronbach's α result for the Portuguese version of the COMQ-12 was 0.85, indicating a high internal consistency. The participants presented with different forms of chronic otitis media, and almost all domains of the COMQ-12 questionnaire were able to differentiate between patients with healed chronic otitis media and patients with cholesteatoma or wet tympanic membrane perforation. Showing that patients with healed chronic otitis media have a better quality of life, measured by the COMQ-12, is a first step to guarantee the questionnaire's validity. The next step will consist on routinely using the questionnaire in patients undergoing surgery for chronic otitis media in order to evaluate their quality of life after treatment.ConclusionThe COMQ-12 Portuguese version showed high reliability, and may be used as an assessment of quality of life in patients with chronic otitis media.
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Platelet to lymphocyte ratio and red cell distribution width as prognostic factors for survival and recurrence in patients with oral cancer
Abstract
Although platelet to lymphocyte ratio (PLR) and red cell distribution width (RDW) have been reported as good predictors for survival outcomes in various cancers, there is limited data supporting these as reliable predictors in oral cancer. This study thus aimed to assess the prognostic value of PLR and RDW markers in predicting survival and recurrence rates in patients with oral cancer. The records of 374 oral cancer patients treated with curative intent over a 7-year period (2009–2015) were reviewed. Survival and recurrence outcomes were compared between those with low and high PLR (≤135 vs. >135) and those with low and high RDW (≤14.05 vs. >14.05) using hazard ratios (HR). The 5-year disease-specific survival was significantly higher and recurrence rate significantly lower among the low PLR group compared to the high PLR group (65.7 vs. 37.6%; p < 0.001 and 34.4 and 57.5%; p < 0.001), respectively. There were no significant differences between the low and high RDW groups for disease-specific survival (53.6 vs. 54.7%, p = 0.408) and recurrence (40.0% vs. 53.8%, p = 0.079). Multivariate analysis showed that PLR was associated with disease-specific survival (HR = 2.05, p < 0.001) and recurrence (HR = 1.69, p < 0.005) after adjusting for other factors, but not RDW. High PLR shows promise as a prognostic predictor for poor survival and recurrence in patients with oral cancer, but further studies are required. RDW has no prognostic value on any outcome.
http://ift.tt/2vTEAIN
SYK protects cardiocytes against anoxia and hypoglycemia-induced injury in ischemic heart failure
Source:Molecular Immunology, Volume 91
Author(s): Guotian Yin, Xiuli Yang, Qiong Li, Zhikun Guo
Spleen tyrosine kinase (SYK), a non-receptor protein tyrosine kinase, is reported to be related to cell survival after A/H (anoxia/hypoglycemia) insult. However, the role of SYK in cardiocyte survival under A/H injury remains unclear. In this study, we aimed to gain insight into the role and molecular mechanism of SYK in cardiocytes exposed to A/H stress. The mRNA and protein expressions of SYK in H9c2 cardiocytes exposed to A/H injury, separately detected by real-time quantitative PCR and Western blot, were both robustly up-regulated. Then we overexpressed SYK in H9c2 with A/H injury, and found that cell viability was significantly increased and LDH leakage was decreased. Moreover, apoptosis measured by annexin V–fluorescein isothiocyanate/propidium iodide and reactive oxygen species (ROS) identified by 2′, 7′-dichlorofluorescin diacetate were markedly inhibited in H9c2 with A/H injury following SYK overexpression. Furthermore, we observed that SYK could induce HO-1 expression by regulating the Akt phosphorylation level in H9c2 with A/H injury, protecting H9c2 from the injury induced by A/H treatment.
http://ift.tt/2wsi7Gs
Identification and verification of hybridoma-derived monoclonal antibody variable region sequences using recombinant DNA technology and mass spectrometry
Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Lmar Babrak, Jeffery A. McGarvey, Larry H. Stanker, Robert Hnasko
Antibody engineering requires the identification of antigen binding domains or variable regions (VR) unique to each antibody. It is the VR that define the unique antigen binding properties and proper sequence identification is essential for functional evaluation and performance of recombinant antibodies (rAb). This determination can be achieved by sequence analysis of immunoglobulin (Ig) transcripts obtained from a monoclonal antibody (MAb) producing hybridoma and subsequent expression of a rAb. However the polyploidy nature of a hybridoma cell often results in the added expression of aberrant immunoglobulin-like transcripts or even production of anomalous antibodies which can confound production of rAb. An incorrect VR sequence will result in a non-functional rAb and de novo assembly of Ig primary structure without a sequence map is challenging. To address these problems, we have developed a methodology which combines: 1) selective PCR amplification of VR from both the heavy and light chain IgG from hybridoma, 2) molecular cloning and DNA sequence analysis and 3) tandem mass spectrometry (MS/MS) on enzyme digests obtained from the purified IgG. Peptide analysis proceeds by evaluating coverage of the predicted primary protein sequence provided by the initial DNA maps for the VR. This methodology serves to both identify and verify the primary structure of the MAb VR for production as rAb.
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Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues
Source:Clinical Immunology
Author(s): Zejun Zhou, Lumin Zhang, Miao Ding, Zhenwu Luo, Shao Yuan, Meena B. Bansal, Gary Gilkeson, Ren Lang, Wei Jiang
Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability.
http://ift.tt/2iQ0mvH
The sneaking ligand approach for cell type-specific modulation of intracellular signalling pathways
Source:Clinical Immunology
Author(s): Bettina Sehnert, Harald Burkhardt, Stephanie Finzel, Stefan Dübel, Reinhard E. Voll
Small molecules interfering with intracellular signalling pathways are used in the treatment of multiple diseases including RA. However, small molecules usually affect signalling in most cell types, not only in those which need to be targeted. This general inhibition of signalling pathways causes often adverse effects, which could be avoided by cell type-specific inhibitors. For cell-type specific modulation of signal transduction, we developed the sneaking ligand fusion proteins (SLFPs). SLFPs contain three domains: (1) the binding domain mediating cell type-specific targeting and endocytosis; (2) the endosomal release sequence releasing the effector domain into the cytoplasm; (3) the effector domain modulating signalling. Using our SLFP NF-kappaB inhibitor termed SLC1 we demonstrated that cell-type-specific modulation of intracellular signalling pathways is feasible, that endothelial NF-kappaB activation is critical for arthritis and peritonitis and that SLFPs help to identify disease-relevant pathways in defined cell types. Hence, SLFPs may improve risk-benefit ratios of therapeutic interventions.
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Laser Assisted Double-Layer Endoscopic Repair of Laryngeal Clefts: Our Experience in 11 Cases
Abstract
Laryngeal cleft is a rare congenital malformation of the respiratory tract leading to a high level of morbidity and mortality, recently being diagnosed with increased frequency. Management throughout the years included medical and surgical. The open surgical technique is more commonly used although it has higher risk and need longer post-operative care. Recently surgical endoscopic repair was introduced using different techniques. To evaluate the clinical features of infants and children presenting with laryngeal clefts, and review endoscopic management modality especially the technique and results of repair using double-layer (2 layers) technique. Outlining our experience with the surgical technique, complications arising from surgery as well as surgical outcome by evaluating the decannulation rate and cessation of the assisted feeding by the end of treatment. Retrospective case series study. Review of infant and children seen in our clinic with the diagnosis of laryngeal cleft from January 2012 till June 2014., and treated by CO2 laser assisted double-layer endoscopic closure. The presenting symptoms, patient demographics, diagnostic procedure, cleft type, surgical outcome and complications all were evaluated. We revised the case notes of 34 patients with a workable diagnosis of Laryngeal cleft. A total of 11 patients met our criteria and were included in the study. Clefts typing was according to modified Benjamin–Ingles classification, type 1 (n = 9) and type 2 (n = 2). All clefts were closed endoscopically by CO2 laser incision of the mucosa and two-layer endoscopic closure of the cleft without postoperative intubation or tracheotomy. They accepted oral feeding within 5 postoperative days (range 3–11 days). 5 out of 6 patients (83.3%) successfully stopped nasogastric feeding and 1 out of 2 patients successfully weaned from nasal cannula. One patient deceased few months after surgery due to other medical problems. Two patients needed redo after burst of the upper cleft stitches immediately after repair by iatrogenic cause during suctioning. The repair was stable in all patients during the second look 6 weeks after surgery with no recurrence or fistula formed. There were no clinically significant observed complications with this technique. After a mean follow up of 24 months, all children have a good voice, have no sign of residual aspiration, and less hospital admissions. Laryngeal cleft should be suspected in children presenting with recurrent pneumonia and difficulties during feeding. Endoscopic repair is a successful and safe technique for treating laryngeal clefts, and has short post-operative recovery without postoperative intubation or tracheotomy. Using the double-layer technique appeared to be promising but needs more comparative studies in the future.
http://ift.tt/2iR4ZFN
Sequential pediatric bilateral cochlear implantation: The effect of time interval between implants
Source:International Journal of Pediatric Otorhinolaryngology, Volume 102
Author(s): Giovanni Bianchin, Lorenzo Tribi, Patrizia Formigoni, Carmela Russo, Valeria Polizzi
ObjectiveTo examine speech intelligibility in children subjected to sequential bilateral cochlear implants (CI) surgery and to assess the influence of the inter-stage interval duration.IntroductionBinaural hearing recovery can have additional benefits, especially in speech and language development in patients with congenital profound sensorineural hearing loss; so recently there has been an increase in the number of children receiving bilateral CI.MethodsTwenty-seven children who underwent sequential bilateral cochlear implant (SBCI) with a short (1–3 yrs), medium (4–6 yrs) and long (7–12 yrs) range interval between both implantations, respectively, were evaluated. All patients underwent periodic speech perception test in quiet and noise after second implant activation in three conditions: with the first or second implant alone and with both implants. Results were examined according to the inter-stage interval.ResultsSpeech intelligibility in noise was significantly better under bilateral conditions than either ear alone, in all three groups. Small improvements were seen in quiet, especially in the third group (6–12 yrs).ConclusionBenefits of second implant in the early-implanted children and after a short inter-implant delay are more evident. However our study support that, even after a long period of deafness and despite a prolonged inter-stage interval, sequential bilateral cochlear implantation should be considered.Level of Evidence: Level 4.
http://ift.tt/2wsdvjA
Laser Assisted Double-Layer Endoscopic Repair of Laryngeal Clefts: Our Experience in 11 Cases
Abstract
Laryngeal cleft is a rare congenital malformation of the respiratory tract leading to a high level of morbidity and mortality, recently being diagnosed with increased frequency. Management throughout the years included medical and surgical. The open surgical technique is more commonly used although it has higher risk and need longer post-operative care. Recently surgical endoscopic repair was introduced using different techniques. To evaluate the clinical features of infants and children presenting with laryngeal clefts, and review endoscopic management modality especially the technique and results of repair using double-layer (2 layers) technique. Outlining our experience with the surgical technique, complications arising from surgery as well as surgical outcome by evaluating the decannulation rate and cessation of the assisted feeding by the end of treatment. Retrospective case series study. Review of infant and children seen in our clinic with the diagnosis of laryngeal cleft from January 2012 till June 2014., and treated by CO2 laser assisted double-layer endoscopic closure. The presenting symptoms, patient demographics, diagnostic procedure, cleft type, surgical outcome and complications all were evaluated. We revised the case notes of 34 patients with a workable diagnosis of Laryngeal cleft. A total of 11 patients met our criteria and were included in the study. Clefts typing was according to modified Benjamin–Ingles classification, type 1 (n = 9) and type 2 (n = 2). All clefts were closed endoscopically by CO2 laser incision of the mucosa and two-layer endoscopic closure of the cleft without postoperative intubation or tracheotomy. They accepted oral feeding within 5 postoperative days (range 3–11 days). 5 out of 6 patients (83.3%) successfully stopped nasogastric feeding and 1 out of 2 patients successfully weaned from nasal cannula. One patient deceased few months after surgery due to other medical problems. Two patients needed redo after burst of the upper cleft stitches immediately after repair by iatrogenic cause during suctioning. The repair was stable in all patients during the second look 6 weeks after surgery with no recurrence or fistula formed. There were no clinically significant observed complications with this technique. After a mean follow up of 24 months, all children have a good voice, have no sign of residual aspiration, and less hospital admissions. Laryngeal cleft should be suspected in children presenting with recurrent pneumonia and difficulties during feeding. Endoscopic repair is a successful and safe technique for treating laryngeal clefts, and has short post-operative recovery without postoperative intubation or tracheotomy. Using the double-layer technique appeared to be promising but needs more comparative studies in the future.
http://ift.tt/2iR4ZFN
Epidemiology and survival outcomes of sinonasal verrucous carcinoma in the United States
Introduction
Verrucous carcinoma (VC) is a rare, variant of squamous cell carcinoma with benign cytohistopathologic features and a generally favorable prognosis. Epidemiologic and clinical outcomes data are lacking as a result of limited cases of sinonasal VC.
Objective
To describe the incidence and determinants of survival of patients with verrucous carcinoma of the sinonasal tract between the years of 1973 to 2014 using the Surveillance, Epidemiology, and End Results (SEER) database.
Methods
The SEER registry was utilized to calculate survival trends for patients with verrucous carcinoma of the sinonasal tract between 1973 and 2014. Patient data then was analyzed with respect to age, sex, race, and treatment modalities (surgery and radiation therapy). Overall survival (OS) and disease-specific survival (DSS) were calculated.
Results
A total of 86 cases of VC of the sinonasal tract were identified. The cohort was comprised of 69.8% males. The mean age at diagnosis was 67.4 years. The nasal cavity was the most common primary site (51.2%), followed by the maxillary sinus (40.7%) and nasopharynx (5.8%). The median OS was 97.6 months. 89.5% of cases underwent surgery and 20.9% received both surgery and radiation therapy. Overall survival at 2, 5, and 10 years was 73%, 59%, and 36%, respectively. On multivariate analysis, advanced age (P < 0.05) and primary site (P < 0.05) were associated with worse OS and DSS, respectively. Primary nasopharyngeal tumor site was associated with reduced DSS (P < 0.05). Surgery improved OS (P < 0.001) and DSS (P < 0.001).
Conclusion
Verrucous carcinoma of the sinonasal tract is associated with a generally favorable prognosis. Age, primary site, and surgical therapy are independent predictors of OS and DSS, respectively. We present the first population-based analysis of sinonasal VC, thus clarifying the prognosis and reinforcing the management of this malignancy.
Level of Evidence
4. Laryngoscope, 2017
http://ift.tt/2vSZlEJ
Untreated oral cavity cancer: Long-term survival and factors associated with treatment refusal
Objective
Oral cavity cancer is the most common malignant disease of the head and neck. The natural course of the disease is poorly characterized and unavailable for patient consideration during initial treatment planning. Our primary objective was to outline this natural history, with a secondary aim of identifying predictors of treatment refusal.
Study Design
Retrospective review of adult patients with oral cavity cancer who refused surgery that was recommended by their physician in the National Cancer Database.
Methods
Demographic, tumor, and survival variables were included in the analyses. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted.
Results
Patients who were older, uninsured, had government insurance, or had more advanced disease were more likely to go untreated. Survival among untreated patients was poor, but there was a small proportion of patients surviving long term. Five-year survival rates ranged from 31.1% among early-stage patients to 12.6% among stage 4 patients.
Conclusion
Although the natural course of oral cavity cancer carries a poor prognosis, there are a number of patients with longer-than-expected survival. The survival estimates may provide supplemental information for patients deciding whether to pursue treatment. In addition to age and extent of disease, system factors such as insurance status and facility case volume are associated with a patient's likelihood of refusing treatment.
Level of Evidence
4. Laryngoscope, 2017
http://ift.tt/2wsiGQr
Sinonasal quality of life after endoscopic resection of malignant sinonasal and skull base tumors
Objectives
Improvement in sinonasal quality of life (QoL) following sinus surgery has been well-documented across the literature. To our knowledge, only one series has evaluated long-term QoL in patients undergoing tumor resection, and that study demonstrated no improvement in rhinologic QoL following malignant tumor resection at 2-year follow-up. The objective of the present study was to evaluate QoL in the 2 years following endoscopic malignant tumor resection.
Methods
A prospective cohort study was performed, including patients with both malignant and benign sinonasal tumors in a tertiary academic medical center. Patients undergoing endoscopic tumor resection who had completed Sinonasal Outcome Test 22 (SNOT-22) questionnaires were included in the cohort. SNOT-22 questionnaires were administered preoperatively and over a 2-year follow-up period at clinic visits. Longitudinal linear mixed-effects regression was used to compare preoperative QoL to QoL over the 2 years following surgery.
Results
Among 145 patients included in this study, 64 had malignant tumors. There was a statistically significant improvement in SNOT-22 score from baseline to 2 years for patients with both malignant tumors (37.0, 95% confidence Interval [CI] 32.0–42.1 at baseline; 26.5 95% CI 20.8–32.2 at 2 years; P < 0.001) and benign tumors (26.5, 95% CI 21.4–30.4 at baseline; 12.9 95% CI 7.6–18.2 at 2 years; P < 0.001).
Conclusion
In contrast to previously reported series, in this cohort endoscopic resection of sinonasal tumors appears to be followed by an improvement in QoL, which is sustained over a 2-year period.
Level of Evidence
2b. Laryngoscope, 2017
http://ift.tt/2wsmgKy
Eosinophilic esophagitis in children under the age of 5 years: Clinical characteristics
Objectives/Hypothesis
To delineate clinical characteristics and treatment outcomes of eosinophilic esophagitis (EoE) in the youngest of children.
Study Design
Retrospective chart review.
Methods
A 7-year retrospective chart review of children with clinicopathologic diagnosis of EoE was performed with specific analysis of patients under 5 years old. EoE was defined as the presence of symptoms of esophageal dysfunction with pathologically proven eosinophilic inflammation (≥15 eosinophils per high-power field [EOS/HPF]) unresponsive to reflux therapy. Patient parameters and clinical results were systematically reviewed.
Results
Of 558 children diagnosed with EoE, 127 (22.8%) were younger than 5 years old (mean age 2.5 years). This subgroup presented with reflux symptoms (90.1%), vomiting (86.2%), diarrhea (55.3%), liquid dysphagia (52.0%), and constipation (50.0%), whereas food impaction (1.6%) was rare. Liquid dysphagia was present at all ages but significantly more common in younger children (P = .0101). The most common food and environmental allergens were egg whites (39.7%), cow's milk (36.5%), peanuts (34.9%), animal dander (15.1%), and weed pollen (11.1%). Patients were managed with antireflux medication (100%), elimination diet (83.5%), and steroid medication (68.5%). After treatment, 86% of parents reported symptom improvement. Mean reduction of EOS in pos-treatment biopsy was 33.5 EOS/HPF (P < .0001), and 67 patients showed histologic resolution of EoE (56.8%, P < .0001).
Conclusions
Approximately one-quarter of children with EoE present under 5 years of age with multiple esophageal symptoms, comorbidities, and allergen-sensitization profiles. These patients demonstrate substantial clinicohistologic improvement following therapy.
Level of Evidence
4 Laryngoscope, 2017
http://ift.tt/2vThcLv
Accuracy of preoperative MRI to assess lateral neck metastases in papillary thyroid carcinoma
Abstract
Primary treatment of papillary thyroid carcinoma (PTC) with lateral lymph node metastasis is surgery, but the extent of lateral neck dissection remains undefined. Preoperative imaging is used to guide the extent of surgery, although its sensitivity and specificity for defining the number and level of affected lymph nodes on the lateral neck is relatively modest. Our aim was to assess the role of preoperative magnetic resonance imaging (MRI) in predicting the requisite levels of neck dissection in patients with regionally metastatic PTC, with a focus on Levels II and V. All patients with PTC and lateral neck metastasis who had undergone neck dissection at the Department of Otorhinolaryngology—Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland from 2013 to 2016 and had a preoperative MRI available were retrospectively reviewed. A head and neck radiologist re-evaluated all MRIs, and the imaging findings were compared with histopathology after neck dissection. In the cohort of 39 patients, preoperative MRI showed concordance with histopathology for Levels II and V as follows: sensitivity of 94 and 67%, specificity of 20 and 91%, positive predictive value of 56 and 75%, and negative predictive value of 75 and 87%, respectively. In PTC, MRI demonstrated fairly high specificity and negative predictive value for Level V metastasis, and future studies are needed to verify our results to omit prophylactic dissection of this level. Routine dissection of Level II in patients with regionally metastatic PTC needs to be considered, as MRI showed low specificity.
http://ift.tt/2gx4dgI
Validating the Physiologic Model HumMod as a Substitute for Clinical Trials Involving Acute Normovolemic Hemodilution.
BACKGROUND: Blood conservation strategies and transfusion guidelines remain a heavily debated clinical topic. Previous investigational trials have shown that acute isovolemic hemodilution does not limit adequate oxygen delivery; however, a true critical hemoglobin level has never been investigated or defined due to safety concerns for human volunteers. Validated physiologic modeling may be useful to investigate hemodilution at critical hemoglobin levels without the ethical or safety hazards of clinical trials. Our hypothesis is that HumMod, an integrative physiological model, can replicate the cardiovascular and metabolic findings of previous clinical studies of acute isovolemic hemodilution and use coronary blood flow and coronary oxygen delivery in extreme hemodilution to predict a safety threshold. METHODS: By varying cardiovascular and sizing parameters, unique individuals were generated to simulate a population using HumMod, an integrative mathematical model of human physiology. Hemodilution was performed by simultaneously hemorrhaging 500 mL aliquots of blood while infusing equal volumes of hetastarch, 5% albumin balanced salt solution, or triple volumes of lactated Ringer's solution over 10 minutes. Five hemodilution protocols reported over 3 studies were directly replicated with HumMod to compare and validate essential cardiovascular and metabolic responses to hemodilution in moderately healthy, awake adults. Cardiovascular parameters, mental status, arterial and mixed venous oxygen content, and oxyhemoglobin saturation were recorded after the removal of each aliquot. The outputs of this simulation were considered independent variables and were stratified by hemoglobin concentration at the time of measurement to assess hemoglobin as an independent predictor of hemodynamic and metabolic behavior. RESULTS: The published reports exhibited discrepancies: Weiskopf saw increased heart rate and cardiac index, while Jones and Ickx saw no change in these variables. In HumMod, arterial pressure was maintained during moderate hemodilution due to decreases in peripheral resistance opposing increases in cardiac index. HumMod showed preserved ventilation through moderate hemodilution, compensated for by an increased oxygen extraction similar to the studies of Jones and Ickx. The simulation results qualitatively followed the clinical studies, but there were statistical differences. In more extreme hemodilution, HumMod had a lesser increase in cardiac index, which led to deficiencies in oxygen delivery and low venous saturation. In the simulations, coronary blood flow and oxygen delivery increase up to a critical hemoglobin threshold of 55-75 g/L in HumMod. In this range, coronary blood flow and oxygen delivery fell, leading to cardiac injury. The allowable amount of hemodilution before reaching the critical point is most closely correlated with nonmuscle mass (r = 0.69) and resting cardiac output (r = 0.67). CONCLUSIONS: There were significant statistical differences in the model population and the clinical populations, but overall, the model responses lay within the clinical findings. This suggests our model is an effective replication of hemodilution in conscious, healthy adults. A critical hemoglobin range of 5.5-7.5 g/L was predicted and found to be highly correlated with nonmuscle mass and resting cardiac output. (C) 2017 International Anesthesia Research Society
http://ift.tt/2wrJG2s
http://ift.tt/2wrJG2s
The Effect of Head Position on the Cross-sectional Area of the Subclavian Vein.
In 41 healthy volunteers, we investigated the cross-sectional area (CSA) of the subclavian vein (SCV) in the following head positions: neutral and 30[degrees] head rotation toward the contralateral or ipsilateral sides. Significant differences were observed in the CSA of the SCV at 3 different head positions: contralateral 30[degrees] versus neutral, -0.05 cm2 (95% confidence interval, -0.08 to -0.03); contralateral 30[degrees] versus ipsilateral 30[degrees], -0.15 cm2 (-0.19 to -0.12); neutral versus ipsilateral 30[degrees], -0.10 cm2 (-0.13 to -0.07); all Pcorrected
http://ift.tt/2vSI8eu
http://ift.tt/2vSI8eu
Evaluation of the Augmented Infant Resuscitator: A Monitoring Device for Neonatal Bag-Valve-Mask Resuscitation.
BACKGROUND: Annually, 6 million newborns require bag-valve-mask resuscitation, and providing live feedback has the potential to improve the quality of resuscitation. The Augmented Infant Resuscitator (AIR), a real-time feedback device, has been designed to identify leaks, obstructions, and inappropriate breath rates during bag-valve-mask resuscitation. However, its function has not been evaluated. METHODS: The resistance of the AIR was measured by attaching it between a ventilator and a ventilator tester. To test the device's reliability in training and clinical-use settings, it was placed in-line between a ventilation bag or ventilator and a neonatal manikin and a clinical lung model simulator. The lung model simulator simulated neonates of 3 sizes (2, 4, and 6 kg). Leaks, obstructions, and respiratory rate alterations were introduced. RESULTS: At a flow of 5 L/min, the pressure drop across the AIR was only 0.38 cm H2O, and the device had almost no effect on ventilator breath parameters. During the manikin trials, it was able to detect all leaks and obstructions, correctly displaying an alarm 100% of the time. During the simulated clinical trials, the AIR performed best on the 6-kg neonatal model, followed by the 4-kg model, and finally the 2-kg model. Over all 3 clinical models, the prototype displayed the correct indicator 73.5% of the time, and when doing so, took 1.6 +/- 0.9 seconds. CONCLUSIONS: The AIR is a promising innovation that has the potential to improve neonatal resuscitation. It introduces only marginal resistance and performs well on neonatal manikins, but its firmware should be improved before clinical use. (C) 2017 International Anesthesia Research Society
http://ift.tt/2vSIphr
http://ift.tt/2vSIphr
Neurologic Injury With Severe Adult Respiratory Distress Syndrome in Patients Undergoing Extracorporeal Membrane Oxygenation: A Single-Center Retrospective Analysis.
This retrospective single-center study investigated the incidence of neurologic injury as determined by autopsy or cerebral imaging in 74 patients undergoing extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome. Seventy-three percent of patients were treated with venovenous and 27% with venoarterial ECMO. ECMO-associated intracerebral hemorrhage was diagnosed in 10.8% of patients. There were no cases of ischemic stroke. Clinical characteristics did not differ between patients with and without neurologic injury. Six-month survival was 13% (Wilson confidence interval, 2%-47%) in patients with severe intracerebral hemorrhage compared to an overall survival rate of 57% (Wilson confidence interval, 45%-67%). (C) 2017 International Anesthesia Research Society
http://ift.tt/2wsbqEp
http://ift.tt/2wsbqEp
Transfusion of Older Red Blood Cells Increases the Risk of Acute Kidney Injury After Orthotopic Liver Transplantation: A Propensity Score Analysis.
BACKGROUND: Acute kidney injury (AKI) is a common and serious complication of orthotopic liver transplantation (OLT). Transfusion of older red blood cells (RBCs) has been implicated in poor outcomes in trauma, cardiac surgery, and critically ill patients. However, whether transfusion of older RBCs plays any role in post-OLT AKI remained unknown. The aim of this study was to investigate the effect of the age of transfused RBCs on post-OLT AKI. METHODS: The clinical data of consecutive adult patients who received donation after cardiac death and underwent OLT from December 2011 to December 2015 were analyzed. These patients were divided into 2 groups: the newer blood group, who received exclusively RBCs that had been stored for
http://ift.tt/2wrVMIW
http://ift.tt/2wrVMIW
Pediatric Anesthesiology Fellows' Perception of Quality of Attending Supervision and Medical Errors.
BACKGROUND: Appropriate supervision has been shown to reduce medical errors in anesthesiology residents and other trainees across various specialties. Nonetheless, supervision of pediatric anesthesiology fellows has yet to be evaluated. The main objective of this survey investigation was to evaluate supervision of pediatric anesthesiology fellows in the United States. We hypothesized that there was an indirect association between perceived quality of faculty supervision of pediatric anesthesiology fellow trainees and the frequency of medical errors reported. METHODS: A survey of pediatric fellows from 53 pediatric anesthesiology fellowship programs in the United States was performed. The primary outcome was the frequency of self-reported errors by fellows, and the primary independent variable was supervision scores. Questions also assessed barriers for effective faculty supervision. RESULTS: One hundred seventy-six pediatric anesthesiology fellows were invited to participate, and 104 (59%) responded to the survey. Nine of 103 (9%, 95% confidence interval [CI], 4%-16%) respondents reported performing procedures, on >1 occasion, for which they were not properly trained for. Thirteen of 101 (13%, 95% CI, 7%-21%) reported making >1 mistake with negative consequence to patients, and 23 of 104 (22%, 95% CI, 15%-31%) reported >1 medication error in the last year. There were no differences in median (interquartile range) supervision scores between fellows who reported >1 medication error compared to those reporting 1 mistake with negative patient consequences, 3.3 (3.0-3.7), compared with those who did not report mistakes with negative patient consequences (3.4 [3.3-3.7]; median difference, 0.1; 99% CI, -0.2 to 0.6; P = .35). CONCLUSIONS: We detected a high rate of self-reported medication errors in pediatric anesthesiology fellows in the United States. Interestingly, fellows' perception of quality of faculty supervision was not associated with the frequency of reported errors. The current results with a narrow CI suggest the need to evaluate other potential factors that can be associated with the high frequency of reported errors by pediatric fellows (eg, fatigue, burnout). The identification of factors that lead to medical errors by pediatric anesthesiology fellows should be a main research priority to improve both trainee education and best practices of pediatric anesthesia. (C) 2017 International Anesthesia Research Society
http://ift.tt/2vSDf5d
http://ift.tt/2vSDf5d
Changing Patterns of Foreigner Transplants in Korea and Overseas Organ Transplants among Koreans.
Background: This study aimed to estimate the numbers of foreign patients seeking organ transplantation (OT) in Korea, and to examine the relationship between the trend of deceased donors in Korea and number of Korean patients seeking OT overseas since 2000. Methods: Data on foreigners who received a transplant in Korea were obtained from the Korean Network for Organ Sharing. Data on overseas transplants were obtained from 42 transplant centers surveyed through transplant coordinators. Results: A total of 336 foreigners underwent OT (kidney transplantation [KT]: 174; liver transplantation [LT]: 162) in Korea between 2006 and 2016. The Mongolians were the most common foreigners who undergo KTs (32%), followed by the Chinese (18%), Americans (9%), and Emiratis (7%). Among foreigners undergoing LTs, the most common country of origin was Mongolia (39%), followed by United Arab Emirates (23%), China (13%), and the United States (6%). A total of 2206 Korean patients underwent overseas OT (KT: 977; LT: 1229) between 2000 and 2016. In 97% of overseas KT cases (n=942) and 98% (n=1205) of overseas LT cases, the transplantations were performed in China. The relationship between the number of deceased donors in Korea and the number of overseas transplants after 2006 indicates a highly negative correlation. ([rho]= -0.988, p
http://ift.tt/2vz5tqa
http://ift.tt/2vz5tqa
Efficacy and safety of 4 months of sublingual immunotherapy with recombinant Mal d 1 and Bet v 1 in patients with birch pollen-related apple allergy
Source:Journal of Allergy and Clinical Immunology
Author(s): Tamar Kinaciyan, Birgit Nagl, Sandra Faustmann, Florian Frommlet, Stephan Kopp, Martin Wolkersdorfer, Stefan Wöhrl, Katharina Bastl, Hans Huber, Uwe Berger, Barbara Bohle
BackgroundBirch pollen-related apple allergy is among the most prevalent food allergies in adolescent/adult individuals and mainly results from sensitization to the major birch pollen allergen Bet v 1 and subsequent cross-reaction with the apple protein Mal d 1. However, specific immunotherapy with birch pollen has inconsistent effects on apple allergy.ObjectiveTo compare the safety and efficacy of sublingual immunotherapy (SLIT) with two formulations containing either recombinant (r) Mal d 1 or Bet v 1 on birch pollen-related apple allergy.MethodsSixty participants with birch pollen-related apple allergy were randomized to daily sublingual application of placebo (n=20), 25 μg of rMal d 1 (n=20) or rBet v 1 (n=20) for 16 weeks. Adverse events were regularly recorded. Sublingual challenges with standardized doses of rMal d 1, skin prick testing with recombinant allergens and measurements of allergen-specific IgE and IgG4 antibodies were performed before and after treatment.ResultsBoth formulations caused comparable, mainly local adverse events. No systemic reactions occurred. Compared to the placebo and the rBet v 1-treated group SLIT with rMal d 1 reduced rMal d 1-induced oral symptoms (P=0.001 and P=0.038), accompanied by longitudinally reduced rMal d 1-specific cutaneous reactions (P=0.022) and enhanced IgG4/IgE ratios (P=0.012). SLIT with rBet v 1 neither improved the clinical reactivity to rMal d 1 nor enhanced rMal d 1-specific IgG4/IgE ratios. Participants receiving placebo showed no allergen-specific changes.ConclusionSublingual treatment with a recombinant food allergen was safe and clinically effective as determined by standardized challenges. We present a promising approach for the effective treatment of birch pollen-related apple allergy.
Teaser
SLIT with recombinant Mal d 1 is a promising approach for the effective treatment of birch pollen-related apple allergy.http://ift.tt/2wsasIg
Food diversity during the first year of life and allergic diseases until 15 years
Source:Journal of Allergy and Clinical Immunology
Author(s): Iana Markevych, Marie Standl, Irina Lehmann, Andrea von Berg, Joachim Heinrich
Teaser
Higher food diversity during the first year of life appears to decrease the risk of allergic sensitization to aeroallergens up to 15 years only among children with early skin symptoms in German birth cohort.http://ift.tt/2vTbx8b
IL-12 and IL-7 synergise to control MAIT cell cytotoxic responses to bacterial infection
Publication date: Available online 1 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Joshua C. Wallington, Anthony P. Williams, Karl J. Staples, Tom M.A. Wilkinson
BackgroundBacterial respiratory tract infections and exacerbations of chronic lung diseases are commonly caused by nontypeable Haemophilus influenzae (NTHi). Cell-mediated cytotoxicity may be key to controlling infection, but the responses of NTHi-specific T cell populations are not well understood. Mucosal-associated invariant T (MAIT) cells are a recently-discovered, innate-like subset of T cells with cytotoxic function, whose role in lung immunity is unclear.ObjectiveThe aim of this study was to determine the mechanisms behind conventional T and MAIT cell cytotoxic responses to NTHi.MethodsHuman ex vivo lung explants were infected with a clinical strain of NTHi. Monocyte-derived macrophages were also infected with NTHi in vitro and co-cultured with autologous T cells. Cytotoxic responses of T cell subsets were measured by flow cytometry.ResultsWe found significant upregulation of the cytotoxic markers, CD107a and granzyme B, in lung CD4+, CD8+ and MAIT cell populations. We show that MAIT cell cytotoxic responses were upregulated by a combination of both time-dependent antigen presentation and through a novel mechanism by which IL-12 and IL-7 synergistically control granzyme B through upregulation of the IL-12 receptor.ConclusionsOverall our data provide evidence for a cytotoxic role of MAIT cells in the lung and highlight important differences in the control of adaptive and innate-like T cell responses. Understanding these mechanisms may lead to new therapeutic opportunities to modulate the anti-bacterial response and improve clinical outcome.
Graphical abstract
Teaser
The mechanisms controlling the cytotoxic response of MAIT cells to NTHi infection are unknown. Our observations provide a new understanding of protective immune mechanisms and also potential new therapeutic opportunities to improve clinical outcome.http://ift.tt/2wrvpms
Elevated IgE levels are linked to faster relapse in omalizumab-discontinued chronic spontaneous urticaria patients
Source:Journal of Allergy and Clinical Immunology
Author(s): Ragip Ertas, Kemal Ozyurt, Emin Ozlu, Yilmaz Ulas, Atil Avci, Mustafa Atasoy, Tomasz Hawro, Marcus Maure
http://ift.tt/2wrOPrb
Enhanced Plasmacytoid Dendritic Cell Antiviral Responses After Omalizumab
Source:Journal of Allergy and Clinical Immunology
Author(s): Michelle A. Gill, Andrew H. Liu, Agustin Calatroni, Rebecca Z. Krouse, Baomei Shao, Allison Schiltz, James E. Gern, Alkis Togias, William W. Busse
BackgroundAtopy and viral respiratory infections synergistically promote asthma exacerbations. IgE cross-linking inhibits critical viral-induced IFNα responses of plasmacytoid dendritic cells (pDCs), which can be deficient in allergic asthma.ObjectiveTo determine whether reducing IgE in vivo with omalizumab treatment increases pDC antiviral IFNα responses in inner city children with asthma.MethodsPBMCs and pDCs isolated from children with exacerbation-prone asthma before and during omalizumab treatment were stimulated ex vivo with rhinovirus and influenza in the presence or absence of IgE cross-linking. IFNα was measured in supernatants and mRNA of IFNα pathway genes determined by qRT-PCR in cell pellets. FcεRIα protein and mRNA expression were measured in unstimulated cells by flow cytometry and qRT-PCR respectively. Changes in these outcomes and associations with clinical outcomes were analyzed and statistical modeling utilized to identify risk factors for asthma exacerbations.ResultsOmalizumab treatment increased rhinovirus and influenza-induced PBMC and rhinovirus-induced pDC IFNα responses in the presence of IgE cross-linking, and reduced pDC surface FcεRIα expression. Omalizumab-induced reductions in pDC FcεRIα were significantly associated with lower asthma exacerbation rate during the outcome period and correlated with increases in PBMC IFNα responses. PBMC FcεRIα mRNA measured upon study entry significantly improved an existing model of exacerbation prediction.ConclusionsThese findings indicate that omalizumab treatment augments pDC IFNα responses and attenuates pDC FcεRIα protein expression, and provide evidence that these effects are related. These results support a potential mechanism underlying clinical observations that allergic sensitization is associated with increased susceptibility to virus-induced exacerbations of asthma.
Teaser
Omalizumab enhanced ex vivo antiviral IFNα responses and reduced pDC surface FcεRIα. Both effects were significantly associated with lower asthma exacerbation rate, highlighting a potential mechanism underlying the atopy-virus connection in promoting exacerbations of asthma.http://ift.tt/2vSEdyi
Serum periostin, IgE and SE-IgE can be used as biomarkers to identify moderate to severe chronic rhinosinusitis with nasal polyps
Source:Journal of Allergy and Clinical Immunology
Author(s): Karin Jonstam, Marit Westman, Gabriële Holtappels, Cecile T.J. Holweg, Claus Bachert
http://ift.tt/2wrX3zQ
Intestinal Microbiota in Infants at High-risk for Allergy: Effects of Prebiotics and Role in Eczema Development
Publication date: Available online 1 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Harm Wopereis, Kathleen Sim, Alexander Shaw, John O. Warner, Jan Knol, J. Simon Kroll
BackgroundThe development of gut microbiota in infancy is important in the maturation of the immune system. Deviations in colonization patterns have been associated with allergic manifestations (e.g. eczema), but exact microbiome dysfunctions underlying allergies remain unclear. We studied the gut microbiota of 138 infants at increased risk of developing allergy, participating in a clinical trial investigating the effectiveness of a partially hydrolyzed protein formula supplemented with non-digestible oligosaccharides (pHF-OS) on the prevention of eczema.ObjectiveThe effects of the interventions and breastfeeding on fecal microbiota were investigated. Additionally, we aimed to identify microbial patterns associated with the onset of eczema.MethodsBacterial taxonomic compositions in the first 26 weeks of life were analyzed using 16S rRNA-gene sequencing. Additionally, fecal pH and microbial metabolites were measured.ResultsFecal microbial composition, metabolites and pH of infants receiving pHF-OS was closer to breastfed infants than to infants receiving standard cow's milk formula. Infants developing eczema by 18 months showed temporal differences that were marked by decreased relative abundances of Parabacteroides and Enterobacteriaceae at 4 weeks, and decreased relative abundances of lactate-utilizing bacteria producing butyrate at 26 weeks, namely Eubacterium and Anaerostipes spp., supported by increased lactate and decreased butyrate levels.ConclusionsWe showed that a pHF with specific prebiotics modulated the gut microbiota closer to that of breastfed infants. Additionally, we identified a potential link between the microbial activity and onset of eczema, which may reflect a suboptimal implementation of gut microbiota at specific developmental stages in infants at high-risk for allergy.
Graphical abstract
Teaser
This study investigated the factors influencing the assembly of the intestinal microbiome and reveals links between the functionality of key microbial taxa in the gut and eczema development in infants at high-risk of developing allergy.http://ift.tt/2vT9Ur0
Allergen sensitization in a birth cohort at mid-childhood: focus on food component IgE and IgG4 responses
Source:Journal of Allergy and Clinical Immunology
Author(s): Jeffrey M. Wilson, Lisa Workman, Alexander J. Schuyler, Sheryl L. Rifas-Shiman, Emily C. McGowan, Emily Oken, Diane R. Gold, Robert G. Hamilton, Thomas A.E. Platts-Mills
Teaser
Among 616 eight year old children in an unselected birth cohort the authors found strikingly different IgG4/IgE ratios to milk and peanut components. This finding was additionally related to discordant results between an extract and microchip component IgE assay.http://ift.tt/2vSZ5W4
Natural protective immunity against grass pollen allergy is maintained by a diverse spectrum of response types
Source:Journal of Allergy and Clinical Immunology
Author(s): Almedina Kurtaj, Christoph Hillebrand, Gerda Fichtinger, Eva Hattinger, Melanie Lietzenmayer, Yoan Machado, Sandra Scheiblhofer, Angelika Stoecklinger, Theresa Thalhamer, Susanne Suessner, Martin Danzer, Sabine Keplinger, Johannes Weinberger, Susanne Schaller, Stephan Winkler, Christian Gabriel, Josef Thalhamer, Richard Weiss
Naturally acquired immunity against allergens utilizes a broad spectrum of response types besides T regulatory cells. Therapeutic concepts should not be limited to T regulatory cell induction, but take advantage of the diversity found in natural responses.
http://ift.tt/2wrOLaV
T cell receptor sequencing reveals decreased diversity 18 years after early thymectomy
Source:Journal of Allergy and Clinical Immunology
Author(s): Judith Gudmundsdottir, Christina Lundqvist, Hanna IJspeert, Eva van der Slik, Sólveig Óskarsdóttir, Susanne Lindgren, Vanja Lundberg, Martin Berglund, Jenny Lingman-Framme, Esbjörn Telemo, Mirjam van der Burg, Olov Ekwall
Teaser
Next generation T and B cell receptor sequencing in individuals 18 years after early thymectomy (n=11) due to congenital cardiac malformation reveals decreased diversity in both helper and cytotoxic T cell receptor repertoires whereas the B cell repertoire remains unaffected.http://ift.tt/2vSNNRT
Primary osteoporosis in children
Osteoporosis in childhood is uncommon, and it may be secondary to a spectrum of diverse conditions. Idiopathic juvenile osteoporosis is a primary osteoporosis of unknown aetiology present in previously well children and is a diagnosis of exclusion. We describe a 10-year-old prepubertal boy who presented with back pain of 1-week duration. His spinal X-ray showed generalised loss of vertebral body heights in keeping with osteoporosis. Endocrine and haematological work-up were normal. He was treated with vitamin D supplement and intravenous pamidronate. This case illustrates the general work-up and causes for paediatric osteoporosis, and the management for idiopathic juvenile osteoporosis.
http://ift.tt/2eOaEs0
Strategies to reduce line infections in a small child with homozygous familial hypercholesterolaemia who cannot yet receive LDL apheresis
Patients with homozygous familial hypercholesterolaemia are optimally treated with low-density lipoprotein apheresis. Young patients who do not meet a weight threshold (25 kg) receive regular plasmapheresis. This approach may remove excessive immunoglobulins and vascular access set-up can be challenging. We report the case of a 4 year-old child who exhibited repeated septic infections (5 in 6 months) and had recurrent access issues before two interventions were implemented: (1) the percutaneous central venous line was modified to two implanted paediatric ports, and (2) the patient started receiving two bags of Octaplasma at the end of each plasmapheresis treatment to account for the excessive loss of immunoglobulins. For the paediatric plasmapheresis access port, a 19-gauge Huber needle had to be used for the arterial port to prevent the collapse of the extension. These two simple changes have left the patient infection-free for 9 months.
http://ift.tt/2gycfG0
Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement
Abstract
Background
Guidelines discourage the use of systemic corticosteroids for atopic dermatitis but their use remains widespread.
Objective
To reach consensus among an international group of atopic dermatitis experts on the use of systemic corticosteroids for atopic dermatitis.
Methods
A survey consisting of statements accompanied by visual analog scales ranging from "strongly disagree" to "neutral" to "strongly agree" was distributed to the International Eczema Council (IEC). Consensus was reached in agreement on a statement if <30% of respondents marked to the left of "neutral" towards "strongly disagree."
Results
Sixty of 77 (79%) IEC members participated. Consensus was reached on 12 statements, including that systemic corticosteroids should generally be avoided but can be used rarely for severe atopic dermatitis under certain circumstances, including a lack of other treatment options, as a bridge to other systemic therapies or phototherapy, during acute flares in need of immediate relief, in anticipation of a major life event or in the most severe cases. If used, treatment should be limited to short-term. Most respondents agreed that systemic corticosteroids should never be used in children, but consensus was not reached on that statement. The conclusions of our expert group are limited by a dearth of high-quality published evidence. If more stringent consensus criteria were applied (e.g., requiring <20% of respondents marking towards "strongly disagree," consensus would have been reached on fewer statements.
Conclusions
Based on expert opinion from the IEC, routine use of systemic corticosteroids for atopic dermatitis is generally discouraged and should be reserved for special circumstances.
This article is protected by copyright. All rights reserved.
http://ift.tt/2wrOlRT
Laser Nd:YAG to treat primary pilonidal cysts: an alternative treatment
Abstract
A pilonidal cyst is an acquired inflammatory disease that affects young adults. Many treatments have been described, although no clear consensus has been reported. At present, surgical intervention is the first line of treatment. The main problem after treatment is the high recurrence of the pilonidal sinus (PNS).
We treated six patients with clinical PNS in the natal cleft (with different time of evolution) and 1.5 cm diameter approximately with Nd:YAG (1064nm). It took 3-4 treatments to resolve the sinus. It is important to remove the residual hairs into the cyst. All of our patients healed. Six lesions were eradicated, and no symptoms were described after the treatment. The mean follow-up period was 52 months (12 to 100 months) without any recurrences.
The early management of pilonidal cysts, with Nd:YAG (1064nm) could be an interesting way of treatment versus conventional surgery, because it causes few side effects and the clinical and aesthetic results are optimal.
This article is protected by copyright. All rights reserved.
http://ift.tt/2vT9AbM
Sunburn and ambient temperature
Abstract
On days during the summer months when high temperatures are expected, weather forecasters frequently warn about the dangers of UV and high UV indices. It is not surprising, therefore, that it is a common belief that high ambient air temperatures are a major risk factor for burning. Although the UV index is generally higher on cloudless, hot days compared with cloudy, cool days, reliance should not be placed on ambient temperature alone as a guide to the need for sun protection.
This article is protected by copyright. All rights reserved.
http://ift.tt/2wsxej7
Acquired erythropoietic uroporphyria secondary to myelodysplastic syndrome with chromosome 3 alterations. A case report
Abstract
Congenital erythropoietic porphyria (CEP) is a rare, autosomal recessive disease caused by a deficiency of uroporphyrinogen III synthase (UROS), due to mutations in the UROS gene in chromosome 10. On occasion, patients show a mild late-onset disease, without germline UROS mutations, associated with hematologic malignancies. We report a 65-year-old patient with photosensitivity, porphyrins overexcretion and thrombocytopenia. Bone marrow analysis gave a diagnosis of myelodysplastic syndrome (MDS) with the presence of a derivative chromosome 3, possible due to an inversion including 3q21 and 3q26 breakpoints. After allogeneic stem cell transplantation a complete remission of MDS and uroporphyria was achieved. To our knowledge, this is the first reported case of acquired erythropoietic uroporphyria associated with MDS, with chromosome 3 alterations.
This article is protected by copyright. All rights reserved.
http://ift.tt/2vSEv8h
Minimally-invasive and targeted therapeutic cell delivery to the skin using microneedle devices
Summary
Background
Translation of cell therapies to the clinic is accompanied by numerous challenges, including controlled and targeted delivery of the cells to their site of action, without compromising cell viability and functionality.
Objectives
To explore the use of hollow microneedle devices (to date only used for the delivery of drugs and vaccines into the skin and for the extraction of biological fluids) to deliver cells into skin in a minimally-invasive, user-friendly and targeted fashion.
Methods
Melanocyte, keratinocyte and mixed epidermal cell suspensions were passed through various types of microneedles and subsequently delivered into the skin.
Results
Cell viability and functionality is maintained after injection through hollow microneedles with a bore size ≥75 μm. Healthy cells are delivered into skin at clinically relevant depths.
Conclusions
Hollow microneedles provide an innovative and minimally-invasive method for delivering functional cells into the skin. Microneedle cell delivery represents a potential new treatment option for cell therapy approaches including skin re-pigmentation, wound repair, scar and burn remodelling, immune therapies, and cancer vaccines.
This article is protected by copyright. All rights reserved.
http://ift.tt/2ws8l7h
Oral mucosa is a useful substrate for detecting autoantibodies of mucous membrane pemphigoid
Abstract
Mucous membrane pemphigoid (MMP) is a rare autoimmune blistering disease targeting various autoantigens, including the C-terminus of collagen XVII (COL17) and laminin332. Bullous pemphigoid (BP) is the most common autoimmune blistering disease, affecting the mucosae in 10-20% of cases. COL17, particularly, the non-collagenous (NC)16A domain is the pathogenic epitope for BP.
This article is protected by copyright. All rights reserved.
http://ift.tt/2vSEt09
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