Rhomboid Intercostal and Subserratus Plane Block: A Cadaveric and Clinical Evaluation

Background and Objectives Fascial plane blocks are rapidly emerging to provide safe, feasible alternatives to epidural analgesia for thoracic and abdominal pain. We define a new option for chest wall and upper abdominal analgesia, termed the rhomboid intercostal and subserratus plane (RISS) block. The RISS tissue plane extends deep to the erector spinae muscle medially and deep to the serratus anterior muscle laterally. We describe a 2-part proof-of-concept study to validate the RISS block, including a cadaveric study to evaluate injectate spread and a retrospective case series to assess dermatomal coverage and analgesic efficacy. Methods For the cadaveric portion of the study, bilateral ultrasound-guided RISS blocks were performed on 6 fresh cadavers with 30 mL of 0.5% methylcellulose with india ink. For the retrospective case series, we present 15 patients who underwent RISS block or RISS catheter insertion for heterogeneous indications including abdominal surgery, rib fractures, chest tube–associated pain, or postoperative incisional chest wall pain. Results In the cadaveric specimens, we identified staining of the lateral branches of the intercostal nerves from T3 to T9 reaching the posterior primary rami deep to the erector spinae muscle medially. In the clinical case series, dermatomal coverage was observed in the anterior hemithorax with visual analog pain scores less than 5 in patients who underwent both single-shot and continuous catheter infusions. Conclusions Our preliminary cadaveric and clinical data suggest that RISS block anesthetizes the lateral cutaneous branches of the thoracic intercostal nerves and can be used in multiple clinical settings for chest wall and upper abdominal analgesia. Accepted for publication March 10, 2018. Address correspondence to: Hesham Elsharkawy, MD, MBA, MSc, Department of General Anesthesia and Outcomes Research, Anesthesiology Institute, Cleveland Clinic, 9500 Euclid Ave, Mail Code E31, Cleveland, OH 44195 (e-mail: elsharh@ccf.org). H.E. has received unrestricted educational funding from PAJUNK (Norcross, GA) and consultant fees from Pacira Pharmaceuticals, Inc. Those companies had no input into any aspect of the present project design or manuscript preparation. The authors declare no conflict of interest. All images are created and used with permission of Cleveland Clinic Center for Medical Art and Photography. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.rapm.org). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Editorial introductions

No abstract available

https://ift.tt/2N975ii

Noninvasive measures in atopic dermatitis

Purpose of review To summarize the current knowledge on the morphology, functionality and biochemical composition of the skin in allergic reactions. We address novel noninvasive techniques that promise to disclose intimate mechanisms of skin allergy in vivo. Epidermal barrier is not just a static wrap of the organism but rather a dynamic field for immunological, biophysical and biochemical processes and serves as a bio-sensor for exogenous danger signals. Recent findings Classical biophysical methods are amended by novel in-vivo techniques, such as Raman spectroscopy, analysing the skin microcomposition and develop epidermal profiles. Visualization techniques, such as reflectance spectroscopy and optical coherence tomography (OCT) are employed in studying the micro-morphological changes in the skin of allergic patients. Summary The noninvasive assessment of skin functions, micro-morphology and biochemical as well as immunological pathways will help to better understand skin allergies. They will allow to detect subtypes, for example in atopic dermatitis and to develop specific treatment modalities.

https://ift.tt/2NIZmEA

Globalization and anaphylaxis

Purpose of review To understand the impact of globalization in the management of anaphylaxis and identify potential strategies to improve patients' care and prevention. Recent findings Developments in the field of anaphylaxis have been consistently following these globalization trends offering possibilities of collaborations of the allergy community and integrated international initiatives to reach quality care of allergic patients worldwide. Summary Globalization is the process of interaction and integration between people, companies, and governments worldwide. Developments in the field of anaphylaxis have been following these globalization trends offering possibilities of collaborations and integrated international initiatives to reach quality care of allergic patients worldwide. Complex disorders, such as anaphylaxis, have called for complex integrative strategies, leading to a new acceptance of outside traditions. Allergy is encouraging us to accept holistic and integrative medical practices as viable options. With the dissolution of multinational boundaries and the universal free access to information, the notion of holistic and global-based care is emerging as the new reality of the medicine. We strongly believe that the integrated action plan to the management and prevention of anaphylaxis, just possible through the globalization, is a key health, political and economical move that advocates for the best practice of allergology.

https://ift.tt/2N6VrEx

Cosmetics and ocular allergy

Purpose of review The purpose of this review was to explore recent developments in the study of ocular cosmetics, as they pertain to adverse reactions that can be attributed to them. Recent findings Immunologically mediated adverse reactions to cosmetics are most commonly the result of sensitization to preservatives, fragrances and dyes used in these products. Metals such as nickel, cobalt, chromium and lead are used in products such as eye shadows and eye liners as well as toy makeup sets in amounts greater than the recommended amount of 1 ppm. Cosmetics make up the majority of fragrance-induced contact dermatitis. Recently, a free smartphone app was developed by American Contact Dermatitis Society that holds promise in better enabling patients to utilize their patch test data while shopping for cosmetics. Summary Both immediate and delayed hypersensitivity reactions linked to cosmetics are often the result of sensitization to preservatives, fragrances and additives in the products themselves. Despite significant advances in our understanding of these reactions, further research will be necessary to elucidate the mechanisms behind these reactions and bring this knowledge to the bedside as to improve patient care with potential cosmetic-based related allergic disorders.

https://ift.tt/2PpKRpY

Phenotypes, endotypes and biomarkers in anaphylaxis: current insights

Purpose of review The aim of the review is to describe the different clinical pictures of anaphylaxis (phenotypes), in relation to the underlying mechanisms and potential biomarkers, to describe anaphylaxis endotypes. This may aid in achieving a better understanding, management and outcomes of such severe reactions. Recent findings Different anaphylaxis phenotypes have been outlined, ranging from the classical type-I-like to those suggestive of cytokine-storm-like or complement-mediated reactions. Underlying mechanisms differ and biomarkers of cells and systems involved are being identified (tryptase, IL-6, bradykinin etc.) Summary Identifying specific phenotypes/endotypes will allow the application of precision medicine in patients with anaphylaxis, providing insights to the most appropriate approach in each case.

https://ift.tt/2N9pSde

Novel systemic drugs in treatment of atopic dermatitis: results from phase II and phase III studies published in 2017/2018

Purpose of review The present review will give an update of recently published clinical studies on novel systemic treatment approaches in atopic dermatitis. Recent findings Until 2017 immunosuppressive drugs such as cyclosporine had to be used in atopic dermatitis when the disease could not sufficiently be treated with topical drugs. Several new substances specifically targeting inflammation in atopic dermatitis are currently studied. In 2017, dupilumab was approved in the United States and in Europe for first-line biologic treatment of moderate to severe atopic dermatitis in adults. The antibody blocks a subunit of the interleukin (IL)-4 and IL-13 receptor, thus inhibiting effects of two key cytokines in type 2 polarized inflammation. In addition to the studies on dupilumab recent clinical investigations on the effects on anti-IL-13 (lebrikizumab, tralokinumab), anti-IL-31 receptor (nemolizumab), anti-IL-22 (fezakinumab), and on small molecules targeting the histamine-4-receptor (ZPL389) and the Janus kinase inhibitor baricitinib have been published as full papers in the last 2 years. Summary A couple of promising novel therapeutical targets have recently been investigated and published in clinical trials on atopic dermatitis.

https://ift.tt/2NIZhAM

Adults and children with anaphylaxis in the emergency room: why it is not recognized?

Purpose of review Despite many international guidelines have been published in the last 10 years, anaphylaxis continues to be underdiagnosed, undernotified, and undertreated. Anaphylactic reactions in adults and children in emergency departments are frequently not recognized, leading to underutilization of epinephrine, and a higher risk of death. Recent findings A few studies have been recently published showing that educational intervention for both physicians and other healthcare professionals improve diagnosis and treatment of anaphylaxis. Moreover, the new International Classification of Diseases, 11th edition improved classification of anaphylaxis, making it easier to be notified. Summary Anaphylaxis is a life-threatening hypersensitivity reaction that is most frequently seen by emergency physicians and nurses than allergists or immunologists. Education seems to be best strategy to improve management of this severe condition.

https://ift.tt/2N4TaK5

Ocular allergy as a risk factor for dry eye in adults and children

Purpose of review To provide an overview of the pathogenic mechanisms underlying the correlation between ocular allergy and dry eye disease (DED), highlighting how the first condition may be a risk factor for the second one. Recent findings Recent advances in our comprehension of the pathogenesis of ocular allergy and DED allow identifying several pathways of interaction between these two conditions. A growing body of evidence supports the role of ocular allergy as a risk factor for DED. Ocular allergy, particularly the severe forms of keratoconjunctivitis, can impact on different key mechanisms of the DED vicious cycle, including tear film instability, ocular surface inflammation and damage, and neurosensory abnormalities. Summary Ocular allergy and DED are two common, relevant, symptomatic, not mutually exclusive conditions affecting the ocular surface. They share some clinical and biochemical features. To better understand the complex interactions between these two conditions, it's essential to consider the very wide spectrum of clinical conditions included in the term ocular allergy and the still largely unexplored peculiarities of the pediatric ocular surface physio-pathology and DED.

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Pitfalls in anaphylaxis

Purpose of review Anaphylaxis is an acute medical emergency characterized by sudden presentation of life-threatening respiratory and cardiovascular symptoms. Rapid diagnosis of anaphylaxis is crucial to implement an appropriate treatment and management plan. However, mistakes in the diagnosis of anaphylaxis may occur because of the limited time during which the diagnosis must be made, the stressful environment of the emergency room, the often aspecific or incomplete clinical features of early anaphylaxis and the lack of useful laboratory markers. Recent findings Several disorders may mimick anaphylaxis and cause wrong or delayed diagnosis increasing chances of fatal outcomes. In addition, certain clinical situations, like general anesthesia, may complicate detection of early signs of anaphylaxis. Drugs like beta-blockers, angiotensin converting enzyme-inhibitors, antihistamines or steroids may hide or blunt initial clinical manifestations of anaphylaxis. Summary A careful evaluation of clinical signs in all organs is mandatory to quickly establish and confirm a diagnosis of anaphylaxis. Alternative diagnosis should be considered, particularly in the case of unresponsive patients. Avoiding pitfalls in anaphylaxis diagnosis will help to establish rapidly effective treatments and would further reduce the rate of fatal events.

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Topical antihistamines, mast cell stabilizers, and dual-action agents in ocular allergy: current trends

Purpose of review To address the current trends of therapeutic mechanisms for treatment of allergic conjunctivitis (AC), based on topical antihistamines and mast cell stabilizers (MCS). Recent findings The antihistamine drug alcaftadine has H4 receptor inverse agonism, anti-inflammatory and MCS activities. The antihistamines levocabastine and azelastine are more effective than placebo in treatment of AC symptoms in randomized controlled trials (RCTs). The topical dual-action antihistamines/MCS olopatadine, azelastine, ketotifen, and epinastine are commonly used in Europe and in the United States for mild subtypes of AC. For the main symptoms of AC, ocular itch and conjunctival hyperemia, epinastine 0.05% was superior to placebo, but equal or more effective than olopatadine 0.1%, while the later was more effective than ketotifen. High concentration olopatadine 0.77% had longer duration of action, better efficacy on ocular itch, and a similar safety profile to low-concentration olopatadine 0.2%. The new formulas of topical dual-action agents present longer duration of action, leading to a decreased frequency of use. Summary The topical dual-action agents are the most effective agents treating signs and symptoms of mild forms of AC. There is superiority to the high-concentration olopatadine drug over other agents on ocular itch, with prolonged effect when used once-daily.

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Seasonal ocular allergy and pollen counts

Purpose of review The purpose of the article is to provide a historical overview of literature regarding pollen sensitization and ocular allergy with an emphasis on developments that have occurred over the past 5 years. Recent findings Currently, pollen studies have examined the molecular and cellular pathways involved in initiating allergic conjunctivitis to find targets for therapeutics. Studies have also documented the threshold, linear increase and plateau point in the relationship between pollen levels and allergic conjunctivitis symptoms. Summary Traditionally, intact pollen grains are counted as a means of correlating patient symptoms to allergen exposure. However, establishing a dose–response relationship between pollen grain exposure and allergic conjunctivitis has proven to be difficult. It has been observed that ocular allergies induce a two-fold response including early-phase and late-phase IgE-mediated reactions. Sensitization itself is a combination of pollen exposure over time in genetically predisposed individual. However, symptoms appear to reach an asymptotic point at which clinical severity plateaus. More studies are needed to clearly define differences in pollen sensitization by plant species.

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New biologics in the treatment of urticaria

Purpose of review Symptomatic management of chronic spontaneous urticaria (CSU) basically depends on second-generation H1 antihistamines and omalizumab. Omalizumab is a game changer in the management, but still there is a need for new targets and new biologics targeting new pathways in the treatment which will provide long-lasting remission, which will be given orally and which will be cheaper. This review will focus on new biologics that are underway of production or are already under use for different disorders but could be beneficial for the treatment of Chronic urticaria. Recent findings In this review, the treatment targets are classified according to the cells which are involved in the pathogenesis of CSU. Those are mast cells/basophils, B cells, T cells and eosinophils. The treatments that are under clinical trials for CSU are anti-IgE treatments such as ligelizumab, molecules targeting intracellular signaling pathways such as spleen tyrosine kinase inhibitors, surface inhibitory molecules such as siglec-8, anti-IL-1s such as canakinumab, Bruton kinase (BTK) inhibitors such as GDC-0853 and anti-IL-5s such as benralizumab and mepolizumab. Summary The ongoing clinical trials on new targets of treatment hold new hopes not only for a better care of the disease but also a better understanding of the pathomechanisms lying underneath.

https://ift.tt/2NHzGZm

Conjunctival provocation tests: prediction of seasonal allergy

Purpose of review The conjunctival provocation test (CPT) is often used to clearly identify the specific allergen causing the symptoms of allergic rhinoconjunctivitis but also to assess the clinical efficacy of an allergen immunotherapy (AIT). As there is no consensus about its predictive value, the aim of this publication is to evaluate under which conditions the CPT can predict the symptom severity during the allergy season after previous AIT. Recent findings Three out of four randomized controlled trials (RCTs) showed a correlation between CPT reactivity and symptoms occurring under natural allergen exposure after previous AIT. Furthermore, one RCT found that performing the CPT 4 weeks after initiating AIT can identify early responders who also show a benefit during the season. Another RCT suggested that conducting the CPT prior to starting AIT can be used to identify patients who may benefit more from treatment than others. Summary The assessment of the reviewed literature led us to the conclusion that the CPT has a predictive value and can consequently be used to assess the efficacy of an administered AIT if performed according to a standardized challenge protocol with high-quality allergen extracts.

https://ift.tt/2N9qMqc

Precision medicine in food allergy

Purpose of review To familiarize the reader with the concept of precision medicine in food allergy through the most recent insights in the diagnosis, prognosis, and management of the disease. Recent findings With the advent of omics sciences, a new era is commencing. Food protein allergens characterization and quantification together with the immunoglobulin E epitope mapping will contribute to the diagnosis/prognosis of food allergy and will lead to a better safety assessment of foods. The characterization of biomarkers able to identify specific phenotypes and endotypes will improve the diagnostic accuracy. This together with a better understanding of mechanisms of action of the different therapeutic options will allow the accurate selection of the appropriate patient. Summary In the near future, advances in technologies and data interpretation will allow a better understanding of the pathogenesis of food allergy and the development of a personalized treatment tailored on the specific patient' profile.

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Discovery of pre-therapy 2-deoxy-2- 18 F-fluoro-D-glucose positron emission tomography-based radiomics classifiers of survival outcome in non-small-cell lung cancer patients

Abstract

Purpose

The aim of this multi-center study was to discover and validate radiomics classifiers as image-derived biomarkers for risk stratification of non-small-cell lung cancer (NSCLC).

Patients and methods

Pre-therapy PET scans from a total of 358 Stage I–III NSCLC patients scheduled for radiotherapy/chemo-radiotherapy acquired between October 2008 and December 2013 were included in this seven-institution study. A semi-automatic threshold method was used to segment the primary tumors. Radiomics predictive classifiers were derived from a training set of 133 scans using TexLAB v2. Least absolute shrinkage and selection operator (LASSO) regression analysis was used for data dimension reduction and radiomics feature vector (FV) discovery. Multivariable analysis was performed to establish the relationship between FV, stage and overall survival (OS). Performance of the optimal FV was tested in an independent validation set of 204 patients, and a further independent set of 21 (TESTI) patients.

Results

Of 358 patients, 249 died within the follow-up period [median 22 (range 0–85) months]. From each primary tumor, 665 three-dimensional radiomics features from each of seven gray levels were extracted. The most predictive feature vector discovered (FVX) was independent of known prognostic factors, such as stage and tumor volume, and of interest to multi-center studies, invariant to the type of PET/CT manufacturer. Using the median cut-off, FVX predicted a 14-month survival difference in the validation cohort (N = 204, p = 0.00465; HR = 1.61, 95% CI 1.16–2.24). In the TESTI cohort, a smaller cohort that presented with unusually poor survival of stage I cancers, FVX correctly indicated a lack of survival difference (N = 21, p = 0.501). In contrast to the radiomics classifier, clinically routine PET variables including SUV_max, SUV_mean and SUV_peak lacked any prognostic information.

Conclusion

PET-based radiomics classifiers derived from routine pre-treatment imaging possess intrinsic prognostic information for risk stratification of NSCLC patients to radiotherapy/chemo-radiotherapy.

https://ift.tt/2NIYuzO

Novel ethosomal gel of clove oil for the treatment of cutaneous candidiasis

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2NCUe56

Novel ethosomal gel of clove oil for the treatment of cutaneous candidiasis

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2NCUe56

Dengue fever in a kidney transplant recipient with complicated clinical course: a case report

Dengue fever is the commonest mosquito-borne illness in the tropics and subtropics. Renal transplantation is one of the ever expanding modes of treatment of end-stage renal disease. Hepatitis B is a common inf...

https://ift.tt/2C72XLw

Successful treatment of out-of-hospital cardiopulmonary arrest due to streptococcal toxic shock syndrome – effectiveness of extracorporeal membrane oxygenation and the rapid antigen group A streptococcus test: a case report

Streptococcal toxic shock syndrome caused by Streptococcus pyogenes, a group A streptococcus, infection is a rare condition that rapidly progresses to multiple organ failure, shock, and death. It is thus importan...

https://ift.tt/2NdK8Lb

Oral Ondansetron Offers Effective Antidiarrheal Activity for Carcinoid Syndrome Refractory to Somatostatin Analogs

AbstractObjectives.Somatostatin analogs (SSAs) are standard for symptomatic patients with neuroendocrine tumors (NETs). However, most patients experience tachyphylaxis, and limited options exist for this so‐called "refractory carcinoid syndrome." Recently, 5‐HT3 antagonist ondansetron has been associated with reduction of bowel movement in a small series. The aim of this analysis was to assess effectiveness of ondansetron for symptomatic treatment of carcinoid syndrome.Design and Patients.We have analyzed patients given ondansetron as bridging therapy for refractory carcinoid syndrome. The dose was 2 × 8 mg for 5 days, followed by reduction to 1 × 8 mg in case of benefit.Results.A total of 14 patients with small bowel NETs metastatic to the liver were identified. All patients had been treated with SSAs for a median time of 18 months before aggravation of diarrhea. One patient had to be excluded because of an underlying infectious cause of diarrhea. The median number of daily bowel movements was 7 (range, 5–13) before initiation of therapy. At this time, seven patients had stable disease, whereas six patients showed radiological progression with symptomatic breakthrough. All 13 patients were scheduled for salvage therapy. Remarkably, in 85% (11/13) ondansetron resulted in a clinically relevant decrease of bowel movements to a median of 3 (1–4). The median time of ondansetron intake was 29 days (7 days to 29 months). In four patients, diarrhea recurred after initial improvement at an interval of 22–43 days, whereas the remaining seven had an ongoing benefit, including two long‐term responders who refused further therapy because of pronounced decrease of symptoms (ondansetron for 14+ and 29+ months).Conclusion.Ondansetron offers symptomatic relief in the majority of patients. Although there was no influence on 5‐HIAA levels, evidence from two patients suggests prolonged benefit.Implications for Practice.Somatostatin analogs are standard treatment in patients with carcinoid syndrome and have an overall response rate of up to 50%. This symptomatic benefit, however, is lost in many patients because of the development of tachyphylaxis or tumor progression. Patients with this "refractory carcinoid syndrome" pose a therapeutic challenge and are sometimes faced with a detrimental effect on quality of life. In this article, the authors suggest the 5‐HT3 receptor antagonist ondansetron as potential symptomatic therapy for patients with refractory diarrhea due to carcinoid syndrome. Although the number of patients in this retrospective series is limited, treatment was easily applicable, feasible, and safe and resulted in an ongoing symptomatic benefit in 85% of patients, including two long‐term responders.

https://ift.tt/2LKzQwU

Prognostic Value of the Progesterone Receptor by Subtype in Patients with Estrogen Receptor‐Positive, HER‐2 Negative Breast Cancer

AbstractBackground.In estrogen receptor‐positive (ER+), human epidermal growth factor receptor 2 (HER‐2) negative breast cancers, the progesterone receptor (PR) is an independent prognostic marker. Little is known about the prognostic value of PR by tumor grade. We assessed this in two independent datasets.Patients and Methods.Women with primary operable, invasive ER+ HER‐2 negative breast cancer diagnosed between 2000 and 2012, treated at University Hospitals Leuven, were included. We assessed the association of PR status and subtype (grade 1–2 vs. grade 3) with distant recurrence‐free interval (DRFI) and breast cancer‐specific survival. The interaction between PR status and subtype was investigated, and associations of PR status by subtype were calculated. The BIG 1‐98 data set was used for validation.Results.In total, 4,228 patients from Leuven and 5,419 from BIG 1‐98 were analyzed. In the Leuven cohort, the adjusted hazard ratio (HR) of PR‐positive versus PR‐negative tumors for DRFI was 0.66 (95% confidence interval [CI], 0.50–0.89). For the interaction with subtype (p = .34), the HR of PR status was 0.79 (95% CI, 0.61–1.01) in luminal A‐like and 0.59 (95% CI, 0.46–0.76) in luminal B‐like tumors. In luminal A‐like tumors, observed 5‐year cumulative incidences of distant recurrence were 4.1% for PR‐negative and 2.8% for PR‐positive tumors, and in luminal B‐like 18.7% and 9.2%, respectively. In the BIG 1‐98 cohort, similar results were observed; for the interaction with subtype (p = .12), the adjusted HR of PR status for DRFI was 0.88 (95% CI, 0.57–1.35) in luminal A‐like and 0.58 (95% CI, 0.43–0.77) in luminal B‐like tumors. Observed 5‐year cumulative incidences were similar.Conclusion.PR positivity may be more protective against metastatic relapse in luminal B‐like versus luminal A‐like breast cancer, but no strong conclusions can be made. In absolute risk, results suggest an absent PR is clinically more important in high compared with low proliferative ER+ HER‐2 negative tumors.Implications for Practice.An absent progesterone receptor (PR) predicts a worse outcome in women treated for an estrogen receptor‐positive, human epidermal growth factor receptor 2 negative breast cancer. As low proliferative tumors lacking PR are now also classified high risk, the prognostic value of PR across risk groups was studied. Despite a negative test for interaction of the prognostic value of PR by tumor grade, the magnitude of an absent PR on breast cancer relapse is much larger in high than in low proliferative breast cancers.

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The Role Of Primary Care Physicians in Childhood Cancer Survivorship Care: Multiperspective Interviews

AbstractBackground.Primary care physicians (PCPs) are well placed to provide holistic care to survivors of childhood cancer and may relieve growing pressures on specialist‐led follow‐up. We evaluated PCPs' role and confidence in providing follow‐up care to survivors of childhood cancer.Subjects, Materials, and Methods.In Stage 1, survivors and parents (of young survivors) from 11 Australian and New Zealand hospitals completed interviews about their PCPs' role in their follow‐up. Participants nominated their PCP for an interview for Stage 2. In Stage 2, PCPs completed interviews about their confidence and preparedness in delivering childhood cancer survivorship care.Results.Stage 1: One hundred twenty survivors (36% male, mean age: 25.6 years) and parents of young survivors (58% male survivors, survivors' mean age: 12.7 years) completed interviews. Few survivors (23%) and parents (10%) visited their PCP for cancer‐related care and reported similar reasons for not seeking PCP‐led follow‐up including low confidence in PCPs (48%), low perceived PCP cancer knowledge (38%), and difficulty finding good/regular PCPs (31%). Participants indicated feeling "disconnected" from their PCP during their cancer treatment phase. Stage 2: Fifty‐one PCPs (57% male, mean years practicing: 28.3) completed interviews. Fifty percent of PCPs reported feeling confident providing care to childhood cancer survivors. PCPs had high unmet information needs relating to survivors' late effects risks (94%) and preferred a highly prescriptive approach to improve their confidence delivering survivorship care.Conclusion.Improved communication and greater PCP involvement during treatment/early survivorship may help overcome survivors' and parents' low confidence in PCPs. PCPs are willing but require clear guidance from tertiary providers.Implications for Practice.Childhood cancer survivors and their parents have low confidence in primary care physicians' ability to manage their survivorship care. Encouraging engagement in primary care is important to promote holistic follow‐up care, continuity of care, and long‐term surveillance. Survivors'/parents' confidence in physicians may be improved by better involving primary care physicians throughout treatment and early survivorship, and by introducing the concept of eventual transition to adult and primary services. Although physicians are willing to deliver childhood cancer survivorship care, their confidence in doing so may be improved through better communication with tertiary services and more appropriate training.

https://ift.tt/2LNlfkJ

Cognitive behavioural therapy for eating disorders: how do clinician characteristics impact on treatment fidelity?

Abstract

Background

Clinicians routinely report not practising evidence-based treatments with eating disorders. There has been limited research investigating the impact of adaptable clinician characteristics such as self-efficacy and therapeutic optimism in this area. This study evaluated if there is a relationship between clinician therapeutic optimism, self-efficacy and the provision of evidence-based practice in the treatment of bulimia nervosa and binge eating disorder.

Method

A survey developed for this study was administered to 100 psychologists who were recruited online via a range of organisations affiliated with psychology and/or eating disorders. The survey measured demographic factors, eating disorder treatment knowledge, treatment fidelity, the use of individual treatment components and a range of clinician characteristics including self-efficacy and therapeutic optimism.

Results

Results demonstrated that clinician self-efficacy was positively associated with and predicted treatment fidelity. Therapeutic optimism had significant low correlations with treatment fidelity but did not predict treatment fidelity.

Conclusion

These findings would suggest that strengthening clinician self-efficacy is useful in improving evidence-based practice in the treatment of binge eating disorder and bulimia nervosa and may also have implications in the training of clinicians. The study also demonstrated that the use of a range of knowledge translation strategies are valuable in enhancing clinician adherence to evidence-based practice. Further research with direct measures of treatment fidelity is needed to clarify these findings.

https://ift.tt/2Pn1JxC

A retrospective intercenter comparison of two surgical protocols through the dental arch relationship of 5- to 6-year-old unilateral cleft patients

Abstract

Objectives

The objectives of this retrospective equivalence trial were to assess the dental arch relationship of 5- to 6-year-old patients with unilateral cleft lip and palate (UCLP) treated in two specialized cleft centers with a different surgical protocol using the 5-Year-Olds' Index and the modified Huddart/Bodenham scoring system, and to determine the correlation between these two scoring indices.

Materials and methods

The dental arch relationship of seventy-three 5- to 6-year-old patients with complete UCLP was evaluated on plaster casts using the 5-Year-Olds' Index and the modified Huddart/Bodenham scoring system. The sagittal occlusion, overbite, and overjet were also recorded. Inter- and intra-examiner agreement was determined using Intraclass Correlation Coefficients.

Results

A good to very good inter- and intra-examiner agreement was found. No significant mean difference in outcome based on the 5-Year-Olds' Index, the modified Huddart/Bodenham scoring system, overjet, or overbite was detected. For mean difference in sagittal occlusion, the hypothesis that both centers are clinically equivalent was confirmed. A strong negative correlation (r_s = − 0.832) between the 5-Year-Olds' Index and the modified Huddart/Bodenham scoring system was found.

Conclusions

The dental arch relationship of 5- to 6-year-old unilateral cleft patients treated in two Belgian cleft centers is clinically equivalent based on sagittal occlusion, despite substantial differences in their treatment protocol. Clinical equivalence for other parameters was not confirmed. There is a strong correlation between the 5-Year-Olds' Index and the modified Huddart/Bodenham scoring system.

Clinical relevance

A well-implemented treatment protocol for cleft patients is of the utmost importance, but case load and skill of the surgeon are also important factors for the quality of the results.

https://ift.tt/2NBMpN7

Correction: Environmental Risk Factors for Type 1 Diabetes Mellitus Development

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0723-6799

[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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The Untold Story of the First Hand Transplant: Dedicated to the Memory of one of the Great Minds of the Ecuadorian Medical Community and the World

J reconstr Microsurg
DOI: 10.1055/s-0038-1668535

Background In 1964, faced with the challenge of traumatic amputation, a team of surgeons at Clinica Guayaquil was convinced that the transplantation of a hand could significantly improve function and quality of life for the recipient. With a current but basic understanding of immunosuppression, the surgeons identified a recipient and waited for the correct donor. A human hand transplant had never been performed to date. Methods The surgeons' criteria for the recipient included a young healthy individual who had sustained a traumatic amputation at the distal forearm level with full motion of the proximal joints. Communication with receiving hospitals and military facilities identified what they perceived to be a feasible donor for an allograft transplantation. Consent was obtained from the family in conjunction with the local military medical authorities and the clergy. Iced saline solution and Heparin irrigation were to be used to prepare the donor extremity. The immunosuppression regimen, limited at the time, consisted only of intravenous cortisone, Imuran, and a single dose of radiation. Results A member of the Ecuadorian marine sustained a limited blast injury that amputated his dominant hand but spared the forearm. He was transferred to the emergency department of Clinica Guayaquil. A donor who had recently died in a nearby hospital was identified not long after. A successful technical surgical transplantation was achieved. Consultants from major hospitals around the world (including Peter Bent Brigham Hospital) convened at the patient's bedside to observe the results. Despite all efforts, the patient suffered an irreversible rejection at 21 days post-transplant. Conclusions This was the first allograft transplantation of a hand. The surgeons embarked on an intervention never tried before, firmly believing that better function and quality of life would result. The bravery of this surgical team was commendable. This early surgical endeavor opened the way for future successes in transplant surgery today.
[...]

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Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Response to Letter to Editor “Optical coherence tomography (OCT) findings in obstructive sleep apnea“ by Piotr Kanclerz

We thank the reader for his comments concerning our review on obstructive sleep apnea syndrome (OSAS) and the eye (especially the retina and the optic nerve). Piotr Kanclerz reviewed the studies reporting the OCT findings of the optic nerve in OSAS subjects. Most particularly, the authors cited the following reference1 "Grzybowski A, Ascaso FJ, Mateo J, Cabezón L, Casas P. Other Neurological Disorders: Migraine, Neurosarcoidosis, Schizophrenia, Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS).

https://ift.tt/2LJxZIR

Age-related hearing loss and cognitive decline — The potential mechanisms linking the two

The amount of attention to age-related hearing loss (ARHL) has been growing, not only from the perspective of being one of the most common health conditions affecting older adults, but also from the perspective of its relation to cognition. Results from a number of epidemiological and laboratory studies have demonstrated a significant link between ARHL and cognitive decline. The Lancet International Commission on Dementia, Prevention, Intervention, and Care has estimated that mid-life hearing loss, if eliminated, might decrease the risk of dementia by nine percent, since hearing loss is a modifiable age-associated condition linked to dementia.

https://ift.tt/2NBmMfh

Issue Information

International Forum of Allergy &Rhinology, Volume 8, Issue 9, Page 971-973, September 2018.


https://ift.tt/2PkPotI

“Medical Emergencies in the dental practice – Management Requirements and International Practitioner Proficiency. A Scoping Review”

Australian Dental Journal, Volume 0, Issue ja, -Not available-.


https://ift.tt/2MJg6z8

Assessment of endothelial function during the loading phase of infliximab in psoriasis: a potential predictor of its drug survival

International Journal of Dermatology, EarlyView.


https://ift.tt/2N8wXe4

Basal cell carcinoma treated with Mohs micrographic surgery in young Ibero‐American patients

International Journal of Dermatology, EarlyView.


https://ift.tt/2wz5sjz

Autoimmune skin disease among dermatology outpatients in Botswana: a retrospective review

International Journal of Dermatology, EarlyView.


https://ift.tt/2N4c83M

Controversies in off‐label prescriptions in dermatology: the perspective of the patient, the physician, and the pharmaceutical companies

International Journal of Dermatology, EarlyView.


https://ift.tt/2wAAMyJ

Percutan nasal septal retraction technique for dorsal cartilagenous deviations

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2C4B9Y3

The Effect of Ventilation Tube Insertion to the Health‐Related Quality of Life in a Group of Children in Southeast Anatolia

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PVsN7U

Fluoroscopic Balloon Diameter Measurement at Different Pressures during Eustachian Balloon Dilation

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2LLgQhY

Atopic Dermatitis and Cancer in Solid Organs: a Systematic Review and Meta‐Analysis

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2C4er2r

Creation and pilot test results of the dermatology‐specific proxy instrument the Infants and Toddlers Dermatology Quality of Life

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PTN0ek

Evaluation of a non‐ablative, fractional 1565 nm laser for the improvement of striae distensae albae

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2NEkThJ

Investigation of the Predisposing Factor of Pemphigus and its clinical subtype through a Genome‐wide association and next generation sequence analysis

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PU9jR5

Chromoblastomycosis: an autochthonous case of a tropical disease

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2NyhZLn

Bier's spots

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2wqMzjN

The impact of atopic dermatitis on sexual health

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2NGrZmc

Manipulating mindsets to improve patient outcomes: Is it ethical? Can it be avoided?

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PWrtlB

Does the Dermatology Life Quality Index (DLQI) underestimate the disease‐specific burden of psoriasis patients?

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2NGrOaw

Vancomycin‐induced red man syndrome presentation in a preterm infant

Pediatric Dermatology, EarlyView.


https://ift.tt/2orpn0g

Sinecatechins ointment for the treatment of warts in children

Pediatric Dermatology, EarlyView.


https://ift.tt/2wDlAk8

The value of full‐body skin examination: Poland syndrome diagnosed as an incidental finding

Pediatric Dermatology, EarlyView.


https://ift.tt/2wwZGQn

An atypical presentation of herpes simplex virus infection in Harlequin ichthyosis

Pediatric Dermatology, EarlyView.


https://ift.tt/2NB8hbk

Remission of seizures with immunosuppressive therapy in Parry‐Romberg syndrome and en coup de sabre linear scleroderma: Case report and brief review of the literature

Pediatric Dermatology, EarlyView.


https://ift.tt/2wuZiSj

Localized infantile hemangiomas of the face and scalp: Predilection for the midline and periorbital and perioral skin

Pediatric Dermatology, EarlyView.


https://ift.tt/2wwmXBe

Terminal osseous dysplasia presenting with intracytoplasmic inclusion bodies in digital fibromas

Pediatric Dermatology, EarlyView.


https://ift.tt/2oqzr9R

Ulcerated congenital plexiform fibrohistiocytic tumor: Case report and literature review

Pediatric Dermatology, EarlyView.


https://ift.tt/2NB7Z4e

Chronic urticaria in infants as the first manifestation of autoinflammatory disease

Pediatric Dermatology, EarlyView.


https://ift.tt/2wwMETb

Segmental Hailey‐Hailey disease of the vulva

Pediatric Dermatology, EarlyView.


https://ift.tt/2NBXOMC

Pediatric ocular lichen planus and lichen planopilaris: One new case and a review of the literature

Pediatric Dermatology, EarlyView.


https://ift.tt/2wwMsmV

Intracochlear Sound Pressure Measurements in Normal Human Temporal Bones During Bone Conduction Stimulation

Abstract

Bone conduction (BC) is heavily relied upon in the diagnosis and treatment of hearing loss, but is poorly understood. For example, the relative importance and frequency dependence of various identified BC sound transmission mechanisms that contribute to activate the cochlear partition remain unknown. Recently, we have developed techniques in fresh human cadaveric specimens to directly measure scalae pressures with micro-fiberoptic sensors, enabling us to monitor the input pressure drive across the cochlear partition that triggers the cochlear traveling wave during air conduction (AC) and round-window stimulation. However, BC stimulation poses challenges that can result in inaccurate intracochlear pressure measurements. Therefore, we have developed a new technique described here that allows for precise measurements during BC. Using this new technique, we found that BC stimulation resulted in pressure in scala vestibuli that was significantly higher in magnitude than in scala tympani for most frequencies, such that the differential pressure across the partition—the input pressure drive—was similar to scala vestibuli pressure. BC (stimulated by a Bone Anchored Hearing Aid [Baha]) showed that the mechanisms of sound transmission in BC differ from AC, and also showed the limitations of the Baha bandwidth. Certain kinematic measurements were generally proportional to the cochlear pressure input drive: for AC, velocity of the stapes, and for BC, low-frequency acceleration and high-frequency velocity of the cochlear promontory. Therefore, our data show that to estimate cochlear input drive in normal ears during AC, stapes velocity is a good measure. During BC, cochlear input drive can be estimated for low frequencies by promontory acceleration (though variable across ears), and for high frequencies by promontory velocity.

https://ift.tt/2PlFl7O

Effects of 3,3′-Iminodipropionitrile on Hair Cell Numbers in Cristae of CBA/CaJ and C57BL/6J Mice

Abstract

This study examines absolute hair cell numbers in the cristae of C57BL/6J mice and CBA/CaJ mice from weaning to adulthood as well as the dose required for 3,3′-iminodiproprionitrile (IDPN)-injury of the cristae in C57BL/6J mice and CBA/CaJ mice, the two mouse strains most commonly used by inner ear researchers. In cristae of CBA/CaJ and C57BL/6J mice, no loss of hair cells was observed up to 24 weeks. In both strains, dose-dependent loss of hair cells was observed 7 days after IDPN treatment of 2-month-old mice (IC₅₀ = 16.1 mmol/kg in C57BL/6J mice vs. 25.21 mmol/kg in CBA/CaJ mice). Four-month-old C57BL/6J mice exposed to IDPN developed dose-dependent vestibular dysfunction as indicated by increased activity and circling behavior in open field tests and by failure to swim 7 days after treatment. IDPN-hair cell injury in C57BL/6J mice and CBA/CaJ mice represents a fast and predictable experimental model for the study of vestibular degeneration and a platform for the testing of vestibular therapies.

https://ift.tt/2wwpw7j

Table of contents

The Laryngoscope, Volume 128, Issue 8, Page iii-vi, August 2018.


https://ift.tt/2LLEL0N

Masthead

The Laryngoscope, Volume 128, Issue 8, Page i-ii, August 2018.


https://ift.tt/2wvAuKd

Micromammal taphonomy and site formation process of Nutria Mansa 1 archaeological site (Buenos Aires, Argentina)

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2N7Z39A

The role of hypoxic signalling in metastasis: towards translating knowledge of basic biology into novel anti-tumour strategies

Abstract

Hypoxia is a characteristic feature of many cancer types, which ensues when the growth of a tumour outpaces its oxygen supply. The cellular response to reduced oxygen tension is centred around the hypoxia-inducible transcription factors (HIFs), which become stabilized under hypoxic conditions. In addition, a number of oxygen-independent mechanisms of HIF regulation have been described, which also play a role at distinct stages of tumour progression. Hypoxia and HIF activity have been linked to the control of all hallmarks of cancer, and increased levels of hypoxia or HIFs in human tumours are typically associated with poor prognosis. In this review, we describe the current knowledge about the role of hypoxic signalling in tumour metastasis, which is the main cause of cancer-related mortality. The members of the HIF family, HIF1α, HIF2α and HIF3α, play important functions at all key stages of metastatic dissemination. This includes local migration within the tumour and invasion of the surrounding stromal tissue through induction of an epithelial-mesenchymal transition (EMT)-like process, remodelling of the extracellular matrix, intravasation and extravasation, survival and dissemination through the circulation, generation of premetastatic niches to support secondary tumour growth, colonisation of distant sites, and tumour cell dormancy. The central role of hypoxic signalling in tumour growth and metastasis, as well as its involvement in therapy resistance, have motivated efforts to monitor tumour hypoxia through various invasive and non-invasive techniques, and to identify inhibitors of HIFs, their regulators or their targets. Recent progress in these areas has provided indications that such approaches may represent a viable strategy for translating basic knowledge about tumour hypoxia and HIF biology into novel therapeutic strategies for metastatic cancer.

https://ift.tt/2C674HC

Intracochlear Sound Pressure Measurements in Normal Human Temporal Bones During Bone Conduction Stimulation

Abstract

Bone conduction (BC) is heavily relied upon in the diagnosis and treatment of hearing loss, but is poorly understood. For example, the relative importance and frequency dependence of various identified BC sound transmission mechanisms that contribute to activate the cochlear partition remain unknown. Recently, we have developed techniques in fresh human cadaveric specimens to directly measure scalae pressures with micro-fiberoptic sensors, enabling us to monitor the input pressure drive across the cochlear partition that triggers the cochlear traveling wave during air conduction (AC) and round-window stimulation. However, BC stimulation poses challenges that can result in inaccurate intracochlear pressure measurements. Therefore, we have developed a new technique described here that allows for precise measurements during BC. Using this new technique, we found that BC stimulation resulted in pressure in scala vestibuli that was significantly higher in magnitude than in scala tympani for most frequencies, such that the differential pressure across the partition—the input pressure drive—was similar to scala vestibuli pressure. BC (stimulated by a Bone Anchored Hearing Aid [Baha]) showed that the mechanisms of sound transmission in BC differ from AC, and also showed the limitations of the Baha bandwidth. Certain kinematic measurements were generally proportional to the cochlear pressure input drive: for AC, velocity of the stapes, and for BC, low-frequency acceleration and high-frequency velocity of the cochlear promontory. Therefore, our data show that to estimate cochlear input drive in normal ears during AC, stapes velocity is a good measure. During BC, cochlear input drive can be estimated for low frequencies by promontory acceleration (though variable across ears), and for high frequencies by promontory velocity.

https://ift.tt/2PlFl7O

Effects of 3,3′-Iminodipropionitrile on Hair Cell Numbers in Cristae of CBA/CaJ and C57BL/6J Mice

Abstract

This study examines absolute hair cell numbers in the cristae of C57BL/6J mice and CBA/CaJ mice from weaning to adulthood as well as the dose required for 3,3′-iminodiproprionitrile (IDPN)-injury of the cristae in C57BL/6J mice and CBA/CaJ mice, the two mouse strains most commonly used by inner ear researchers. In cristae of CBA/CaJ and C57BL/6J mice, no loss of hair cells was observed up to 24 weeks. In both strains, dose-dependent loss of hair cells was observed 7 days after IDPN treatment of 2-month-old mice (IC₅₀ = 16.1 mmol/kg in C57BL/6J mice vs. 25.21 mmol/kg in CBA/CaJ mice). Four-month-old C57BL/6J mice exposed to IDPN developed dose-dependent vestibular dysfunction as indicated by increased activity and circling behavior in open field tests and by failure to swim 7 days after treatment. IDPN-hair cell injury in C57BL/6J mice and CBA/CaJ mice represents a fast and predictable experimental model for the study of vestibular degeneration and a platform for the testing of vestibular therapies.

https://ift.tt/2wwpw7j

A Milroy case with FLT4/VEGFR3 mutation and an unusual skin biopsy

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2N8d3Qo

A Milroy case with FLT4/VEGFR3 mutation and an unusual skin biopsy

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2N8d3Qo

Rehabilitating the brain through meditation and electrical stimulation

Publication date: Available online 31 August 2018

Source: Cortex

Author(s): Michael I. Posner

Abstract

This paper is a review of our recent studies and ideas related to the neuropsychological issues that Robert Rafal and I worked together to understand attention and hopefully improve it in a variety of patients. Rehabilitation is also a goal of my current research to determine if non invasive stimuli can improve white matter in humans. We have found that fractional anisotropy (FA) is improved in pathways surrounding the anterior cingulate cortex (ACC) following two week to four weeks of meditation training. We hypothesized that the frontal theta increased following meditation training might be a cause of the improved connectivity. This was confirmed by a mouse study using optogenetics to impose theta rhythms in the ACC. We have evidence that electrical stimulation while performing a task that activates the ACC can also increase theta. We plan studies to determine whether two to four weeks of stimulation can improve FA in pathways surrounding the anterior cingulate.

https://ift.tt/2wwVDU5

Induction of protective cellular immune responses against experimental visceral leishmaniasis mediated by dendritic cells pulsed with the N-terminal domain of Leishmania infantum elongation factor-2 and CpG oligodeoxynucleotides

Publication date: November 2018

Source: Molecular Immunology, Volume 103

Author(s): Maria Agallou, Eleni Pantazi, Elisavet Tsiftsaki, Dimitra K. Toubanaki, Catherine Gaitanaki, Despina Smirlis, Evdokia Karagouni

Abstract

Leishmania elongation factor 2 (EF-2) has been previously identified as a T_H1-stimulatory protein. In this study, we assayed the protective potential of the N-terminal domain of EF-2 (N-LiEF-2, 1–357 aa) that has been predicted to contain several overlapping MHC class I and II-restricted epitopes injected in the form of dendritic cell (DC)-based vaccine. Ex vivo pulsing of DCs with the recombinant N-LiEF-2 domain along with CpG oligodeoxynucleotides (ODNs) resulted in their functional differentiation. BALB/c vaccinated with CpG-triggered DCs pulsed with N-LiEF-2 were found to be the most immune-reactive in terms of induction of DTH responses, increased T cell proliferation and IL-2 production. Moreover, vaccination induced antigen-specific T_H1 type immune response as evidenced by increased IFN-γ and TNFα levels followed by a significant increase of nitrite (NO) and reactive oxygen species (ROS) in splenocyte cultures. Vaccinated mice showed a pronounced decrease in parasite load in spleen and liver when challenged with L. infantum, increased expression of Stat1 and Tbx21 mRNA transcripts versus reduced expression of Foxp3 transcripts and were able to produce significantly elevated levels of IL-2, IFN-γ and TNFα but not IL-10 compared to non-vaccinated mice. Both antigen and parasite-specific CD4⁺ T and CD8⁺ T cells contributed to the IFN-γ production indicating that both subtypes contribute to the resistance to infection and correlated with robust nitrite generation, critical in controlling Leishmania infection. Together, these findings demonstrated the immunogenic as well as protective potential of the N-terminal domain of Leishmania EF-2 when given with CpG-triggered DCs representing a basis for the development of rationalized vaccine against leishmaniasis.

https://ift.tt/2onQWrc

Interleukin-33 deficiency exacerbated experimental autoimmune encephalomyelitis with an influence on immune cells and glia cells

Publication date: September 2018

Source: Molecular Immunology, Volume 101

Author(s): Yifan Xiao, Lin Lai, Huoying Chen, Junyu Shi, FanFan Zeng, Jun Li, Huiting Feng, Jie Mao, Feng Zhang, Naming Wu, Yong Xu, Zheng Tan, Feili Gong, Fang Zheng

Abstract

Interleukin (IL)-33, a member of the IL-1 cytokine family, is highly expressed in central nervous system (CNS), suggesting its potential role in CNS. Although some studies have focused on the role of IL-33 in multiple sclerosis (MS) / experimental autoimmune encephalomyelitis (EAE), an autoimmune disease characterized by demyelination and axonal damage in CNS, the exact role of IL-33 in MS/EAE remains unclear and controversial. Here, we used IL-33 knockout mice to clarify the role of endogenous IL-33 in EAE by simultaneously eliminating its role as a nuclear transcription factor and an extracellular cytokine. We found that the clinical score in IL-33 knockout EAE mice was higher accompanied by more severe demyelination compared with the wild-type (WT) EAE mice. As for the main immune cells participating in EAE in IL-33 knockout mice, pathogenic effector T cells increased both in peripheral immune organs and CNS, while CD4⁺FOXP3⁺ regulatory T cells decreased in spleen and lymph nodes, Th2 cells and natural killer (NK) cells decreased in CNS. Additionally, the populations of microglia/macrophages and CD11C⁺CD11B⁺ dendritic cells (DCs) increased in CNS of IL-33 knockout mice with EAE, among which iNOS-producing microglia/macrophages increased. Moreover, resident astrocytes/microglia were more activated in IL-33 knockout mice with EAE. In vitro, after blocking the IL-33, the proliferation of primary astrocytes, the production of MCP-1/CCL2 and TNF-α by astrocytes, and the production of TNF-α by primary microglia stimulated by the homogenate of the peak stage of EAE were increased. Our results indicate that IL-33 plays a protective role in EAE and exerts extensive influences on multiple immune cells and neural cells involved in EAE.

https://ift.tt/2NBPLj7

rhPLD2 inhibits airway inflammation in an asthmatic murine model through induction of stable CD25+ Foxp3+ Tregs

Publication date: September 2018

Source: Molecular Immunology, Volume 101

Author(s): Chuan-Xing Yu, Ling-Yu Bai, Jun-Jin Lin, Song-Bo Li, Jun-Ying Chen, Wen-Juan He, Xiu-Ming Yu, Xi-Ping Cui, Hui-Li Wang, Yi-Zhong Chen, Ling Zhu

Abstract

Our previous studies have shown that recombinant human phospholipase D2 (rhPLD2) plays a modulator role on NF-κB and PKC signaling pathways. It also inhibits IL-5-induced inflammatory response in chronic asthmatic guinea pigs. Additionally, increasing evidence also has revealed that the adoptive transfer of induced regulatory T cells (Tregs) may be a therapeutic solution to airway allergic diseases. To investigate the epigenetic, transcriptomic and phenotypic variability of Treg population in an ovalbumin (OVA)-induced airway inflammation model derived from the induction of rhPLD2, OVA-induced asthmatic murine model is used in this study. The lung inflammation, eosinophil infiltration, the differentiation and proliferation of T helper cells and the amplification of Tregs were examined in this mouse model with and without rhPLD2 induction. Our data showed that rhPLD2 administration in asthmatic mice significantly increases CD4⁺CD25⁺ Foxp3⁺ Treg cell numbers and alleviates lung inflammation. The addition of rhPLD2 in vitro enhanced the demethylation of Treg-specificdemethylated region (TSDR) in iTregs, suggesting that rhPLD2 protein may be involved in improving the quality and quantity of Treg cells that eventually significantly reduces lung inflammation in asthmatic murine model. These results suggest that rhPLD2 could have a clinical impact treating patients with allergic airway inflammation via promoting and stabilizing iTreg differentiation and function.

https://ift.tt/2oscUJS

TET mediated epigenetic regulation of iNKT cell lineage fate choice and function

Publication date: September 2018

Source: Molecular Immunology, Volume 101

Author(s): Ageliki Tsagaratou

Abstract

During the last years, intensive research has shed light in the transcriptional networks that shape the invariant NKT (iNKT) cell lineage and guide the choices towards functionally distinct iNKT cell subsets (Constantinides and Bendelac, 2013; Engel and Kronenberg, 2014; Gapin, 2016; Kim et al., 2015). However, the epigenetic players that regulate gene expression and orchestrate the iNKT cell lineage choices remain poorly understood. Here, we summarize recent advances in our understanding of epigenetic regulation of iNKT cell development and lineage choice. Particular emphasis is placed on DNA modifications and the Ten Eleven Translocation (TET) family of DNA demethylases.

https://ift.tt/2NyNVPX

Topical 3-bromopyruvate is a novel targeted therapy for melanoma in a preclinical model

Publication date: Available online 30 August 2018

Source: Journal of Dermatological Science

Author(s): Masayuki Yamada, Masami Kagaya, Natsuko Noguchi, Shigeharu Ueki, Naoko Hasunuma, Shin-Ichi Osada, Motomu Manabe

Abstract

Background

Targeting cancer metabolism is a promising strategy in improving cancer treatment.

Objective

To introduce a targeted therapy with topical 3-bromopyruvate (3BP), aglycolytic inhibitor, into the clinic in the near future.

Method

We investigated the anti-tumor efficacy of 3BP on melanoma cells in vitro and in a preclinical model.

Results

Our cell-based study demonstrated that 3BP showed cytotoxicity for melanoma cells under anchorage-dependent or independent cell growth via a reactive oxygen species-mediated and caspase-independent cell death pathway. Moreover, 3BP inhibited both self-renewal potential and growth of slow-cycling phenotype in melanoma cells. Remarkably, the preclinical mouse xenograft model shed light on topical application of 3BP, showing significant anti-tumor effects with no apparent toxicity in surrounding normal tissues.Conclusion: We have now proposed that a targeted therapy with topical 3BP is an innovative strategy for adjuvant chemotherapy of technically or medically unresectable melanoma and possibly other skin cancers.

https://ift.tt/2MF7Jod

Blind source separation with mixture models – A hybrid approach to MR brain classification

Publication date: Available online 31 August 2018

Source: Magnetic Resonance Imaging

Author(s): Megha Maria Cheriyan, Prawin Angel Michael, Anil Kumar

Abstract

The development of automated segmentation approaches, which do not suffer from excessive computational burden and intra- and inter-observer variability, is the holy grail of multispectral MR image classification. A new segmentation approach to the data set of MR brain images using a combination of Independent Component Analysis (ICA) with a generalized version of the popular Gaussian Mixture Model (GMM) for unsupervised classification is proposed to be superior to conventional methods in this paper. We propose to optimize the parameters of the mixture model using a meta-heuristic approach like the Particle Swarm Optimization (PSO) to escape the problem of local traps (maxima or minima). Experiments were carried out initially on a synthetic MR Brainweb image set as proof of concept and subsequently on 152 sets of clinical MR images with T1w, T2w and FLAIR sequences. The major advantage of the proposed algorithm is the increased accuracy of lesion classification – average of 94.79% (±1.7) against 85.85% (±3.1) without ICA. As a result of the incorporation of ICA, the inherent computational overhead was also lowered as evidenced by faster convergence. Comparative studies using quantitative and qualitative analysis against conventional algorithms establish the superiority of the proposed approach.

https://ift.tt/2LMvGES

High spatial resolution BOLD fMRI using simultaneous multislice excitation with echo-shifting gradient echo at 7 Tesla

Publication date: Available online 31 August 2018

Source: Magnetic Resonance Imaging

Author(s): Shi Su, Na Lu, Lin Jia, Xiaojing Long, Chunxiang Jiang, Hang Zhang, Ye Li, Kaibao Sun, Rong Xue, Lijuan Zhang, Xin Liu, Guoxi Xie

Abstract

We introduce an accelerated gradient echo (GRE) sequence combining simultaneous multislice excitation (SMS) with echo-shifting technique for high spatial resolution blood oxygen level dependent (BOLD) functional MRI (fMRI). The simulation was conducted to optimize scan parameters. To validate the feasibility of the proposed technique, the visual and motor task experiments were performed at 7.0 Tesla (T). The single-shot EPI sequence was also applied in comparison with the proposed technique. The simulation results showed that an optimized flip angle of 9° provided maximal BOLD contrast for our scanning scheme, allowing low power deposition and SMS acceleration factor of 5. Additionally, parallel acquisition imaging with acceleration factor of 2 was utilized, which allowed a total acceleration factor of 10 in volunteer study. The experiment results showed that geometric distortion-free BOLD images with voxel size of 1.0 × 1.0 × 2.5 mm³ were obtained. Significant brain activation was identified in both visual and motor task experiments, which were in accordance with previous investigations. The proposed technique has potential for high spatial resolution fMRI at ultra-high field because of its fast acquisition speed and sufficient BOLD sensitivity.

https://ift.tt/2MD8VZk

Mitral annular velocity measurement with cardiac magnetic resonance imaging using a novel annular tracking algorithm: Validation against echocardiography

Publication date: Available online 31 August 2018

Source: Magnetic Resonance Imaging

Author(s): Paaladinesh Thavendiranathan, Christoph Guetter, Juliana Serafim da Silveira, Xiaoguang Lu, Debbie Scandling, Hui Xue, Marie-Pierre Jolly, Subha V. Raman, Orlando P. Simonetti

Abstract

Background

Doppler based mitral annular velocities are an integral part of echocardiographic left ventricular diastolic function assessment. Although these measurements can be obtained by phase contrast cardiac magnetic resonance imaging (PC-CMR), this approach has limitations. The aims of this study were to assess the accuracy and reproducibility of a high temporal resolution steady-state free precession (SSFP) cine acquisition coupled with semi-automated mitral annular tracking to measure tissue velocity, and compare to echocardiography as the reference method.

Methods

High temporal resolution (17 ms) 4-chamber cines were acquired in 25 volunteers using retrospective and prospective gating on a 3.0 T magnet. Mitral annular early (e′) and late (a′) tissue velocities were derived using a novel algorithm to semi-automatically detect the mitral valve insertion points and track its motion. Additionally, PC-CMR was used to measure mitral inflow early diastolic (E) velocity. Those measurements were also obtained using echocardiography based pulsed and tissue Doppler techniques, on the same day.

Results

Subjects were on average 34 ± 14 years-old (48% male). The lateral annulus e′ measurements had the best agreement with echocardiography with a concordance correlation coefficient (CCC) of 0.76 and 0.75 for prospectively and retrospectively gated cine CMR respectively. There was no significant difference in the lateral annular tissue velocities between echocardiography (13.8 ± 3.7 cm/s) and prospective (13.4 ± 3.7 cm/s) or retrospective (14.0 ± 3.7) acquisitions. Similarly, CMR measurement of E/e′ (a surrogate marker for LV filling pressures) using the lateral e′ velocity showed moderate agreement with echocardiography (CCC of 0.56 and 0.51 for prospective and retrospective acquisitions respectively) without a significant difference in ratios (5.3 ± 1.6 and 5.0 ± 1.3) compared to echocardiography (5.2 ± 1.4). Intra- and inter-observer reproducibility of the CMR-based annular velocity measurements was good.

Conclusion

Measurements of mitral annular tissue velocities can be obtained from SSFP 4-chamber cine images using a semi-automated annular tracking algorithm, and demonstrates moderate agreement with echocardiography. The semi-automated method can provide quantitative mitral annular velocity measurements directly from conventional cine images, thereby providing additional clinically relevant information. The accuracy of this method in patients with diastolic dysfunction remains to be determined.

https://ift.tt/2LMvANw

Association among T2 signal intensity, necrosis, ADC and Ki-67 in estrogen receptor-positive and HER2-negative invasive ductal carcinoma

Publication date: Available online 30 August 2018

Source: Magnetic Resonance Imaging

Author(s): Soo-Yeon Kim, Eun-Kyung Kim, Hee Jung Moon, Jung Hyun Yoon, Ja Seung Koo, Sungheon Gene Kim, Min Jung Kim

Abstract

Purpose

To determine whether T2 signal intensity, necrosis, and ADC values are associated with Ki-67 in patients with Estrogen Receptor (ER)-positive and Human epidermal growth factor receptor type 2 (HER2)-negative invasive ductal carcinoma (IDC).

Materials and methods

Between March 2012 and February 2013, one hundred eighty seven women with ER-positive and HER2-negative IDC who underwent breast MRI and subsequent surgery were included. Intratumoral signal intensity was evaluated based on a combination of T2-weighted (low or equal, high, or very high) and contrast-enhanced MR images (enhancement or not). Necrosis was defined as very high T2 and no enhancement. Using the analysis of variance and pairwise t-test, a model based on intratumoral signal intensity was developed to assess Ki-67 of the surgical specimen. Inter-observer agreement for the developed model was analyzed. Conventional mean and minimum apparent diffusion coefficient (ADC) measurements were performed and correlated with Ki-67.

Results

As the grade of the developed model increased (Grade I: low or equal T2, Grade II: high T2, or necrosis < 50%, Grade III: necrosis ≥ 50%), mean Ki-67 significantly increased (Grade I to III: 12.5%, 17.6%, 45.0%, respectively; P < 0.001). Good inter-observer agreement was found for the model (κ = 0.846, P < 0.001). ADC did not show significant correlations with Ki-67 (Pearson's correlation coefficient, 0.140 [P = 0.057] for mean ADC; −0.079 [P = 0.284] for minimum ADC).

Conclusion

Intratumoral signal intensity but not ADC was associated with Ki-67 in patients with ER-positive and HER2-negative IDC.

https://ift.tt/2MG56Tr

‘Chronic traumatic ulcer of lateral tongue’- An underestimated ‘oral potentially malignant disorder’?

Publication date: Available online 30 August 2018

Source: Oral Oncology

Author(s): Prashanth Panta, Sachin C. Sarode, Gargi S. Sarode, Shankargouda Patil

https://ift.tt/2LIVWAd

A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity

Publication date: Available online 31 August 2018

Source: Journal of Autoimmunity

Author(s): Prabhakaran Kumar, Palash Bhattacharya, Bellur S. Prabhakar

Abstract

The immune system ensures optimum T-effector (Teff) immune responses against invading microbes and tumor antigens while preventing inappropriate autoimmune responses against self-antigens with the help of T-regulatory (Treg) cells. Thus, Treg and Teff cells help maintain immune homeostasis through mutual regulation. While Tregs can contribute to tumor immune evasion by suppressing anti-tumor Teff response, loss of Treg function can result in Teff responses against self-antigens leading to autoimmune disease. Thus, loss of homeostatic balance between Teff/Treg cells is often associated with both cancer and autoimmunity. Co-stimulatory and co-inhibitory receptors, collectively known as co-signaling receptors, play an indispensable role in the regulation of Teff and Treg cell expansion and function and thus play critical roles in modulating autoimmune and anti-tumor immune responses. Over the past three decades, considerable efforts have been made to understand the biology of co-signaling receptors and their role in immune homeostasis. Mutations in co-inhibitory receptors such as CTLA4 and PD1 are associated with Treg dysfunction, and autoimmune diseases in mice and humans. On the other hand, growing tumors evade immune surveillance by exploiting co-inhibitory signaling through expression of CTLA4, PD1 and PDL-1. Immune checkpoint blockade (ICB) using anti-CTLA4 and anti-PD1 has drawn considerable attention towards co-signaling receptors in tumor immunology and created renewed interest in studying other co-signaling receptors, which until recently have not been as well studied. In addition to co-inhibitory receptors, co-stimulatory receptors like OX40, GITR and 4-1BB have also been widely implicated in immune homeostasis and T-cell stimulation, and use of agonistic antibodies against OX40, GITR and 4-1BB has been effective in causing tumor regression. Although ICB has seen unprecedented success in cancer treatment, autoimmune adverse events arising from ICB due to loss of Treg homeostasis poses a major obstacle. Herein, we comprehensively review the role of various co-stimulatory and co-inhibitory receptors in Treg biology and immune homeostasis, autoimmunity, and anti-tumor immunity. Furthermore, we discuss the autoimmune adverse events arising upon targeting these co-signaling receptors to augment anti-tumor immune responses.

https://ift.tt/2wtjzYI

Lipocalin-2 is a pathogenic determinant and biomarker of neuropsychiatric lupus

Publication date: Available online 30 August 2018

Source: Journal of Autoimmunity

Author(s): Elise V. Mike, Hadijat M. Makinde, Maria Gulinello, Kamala Vanarsa, Leal Herlitz, Gaurav Gadhvi, Deborah R. Winter, Chandra Mohan, John G. Hanly, C.C. Mok, Carla M. Cuda, Chaim Putterman

Abstract

Neuropsychiatric manifestations in lupus (NPSLE) affect ∼20–40% of patients. In the central nervous system, lipocalin-2 (LCN2) can promote injury through mechanisms directly linked to NPSLE, including brain barrier disruption, neurotoxicity, and glial activation. Since LCN2 is elevated in lupus and has been implicated in neuroinflammation, we investigated whether LCN2 is required for the pathogenesis of NPSLE. Here, we investigated the effects of LCN2 deficiency on the development of neurobehavioral deficits in the B6.Sle1.Sle3 (Sle1,3) mouse lupus model. Sle1,3 mice exhibited depression-like behavior and impaired spatial and recognition memory, and these deficits were attenuated in Sle1,3-LCN2KO mice. Whole-brain flow cytometry showed a significant increase in brain infiltrating leukocytes in Sle1,3 mice that was not reduced by LCN2 deficiency. RNA sequencing on sorted microglia revealed that several genes differentially expressed between B6 and Sle1,3 mice were regulated by LCN2, and that these genes are key mediators of the neuroinflammatory cascade. Importantly, LCN2 is upregulated in the cerebrospinal fluid of NPSLE patients across 2 different ethnicities. Our findings establish the Sle1,3 strain as an NPSLE model, demonstrate that LCN2 is a major regulator of the detrimental neuroimmune response in NPSLE, and identify CSF LCN2 as a novel biomarker for NPSLE.

https://ift.tt/2wwaD4O

Inflammatory markers in palatine tonsils of children with obstructive sleep apnea syndrome

Publication date: Available online 31 August 2018

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Vitor Guo Chen, Viviane Maria Guerreiro da Fonseca, Jônatas Bussador Amaral, Cíntia Meirelles Camargo-Kosugi, Gustavo Moreira, Eduardo Macoto Kosugi, Reginaldo Raimundo Fujita

Abstract

Introduction

Obstrutive sleep apnea syndrome is characterized by repeated episodes of upper airway obstruction, associated with intermittent hypoxia and hypercapnia, and the main risk factor in childhood is adenotonsillar hypertrophy. The lymphocytes in these structures are responsible for local and systemic immune responses.

Objective

Verify the levels of the inflammatory markers, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, CRP and α1-GP, in the tonsils of children with and without obstructive sleep apnea syndrome.

Methods

This cross-sectional prospective study included 34 children with complains of snoring, difficulty breathing during sleep or recurrent tonsillitis. Patients underwent to a complete otorhinolaryngological examination, nasal endoscopy and polysomnography and were divided into two groups with 17 children each: obstructive sleep apnea syndrome group and control group. All underwent an adenotonsillectomy. Cytokines were measured in the collected tonsils (ELISA and Multiplex methods).

Results

Statistically significant increasing were observed between IL-8 and IL-10 cytokines of patients with obstructive sleep apnea when compared to the control group; also between c-reactive protein and α1-GP of the tonsils cortical region in children with obstructive sleep apnea syndrome when compared with the medullary region. There were no statistically significant differences for the remaining inflammatory mediators.

Conclusion

After the analysis of the levels of pro and anti-inflammatory markers (IL-1β, IL-4, IL-6, IL-8, IL-10, Il-15, TNF-α, CRP, α1-GP) in the tonsils, we observed higher levels of markers IL-8 and IL-10 in pediatric patients with obstructive sleep apnea syndrome.

Resumo

Introdução

A síndrome da apneia obstrutiva do sono é caracterizada por episódios repetidos de obstrução das vias aéreas superiores, associados a hipóxia intermitente e hipercapnia, e o principal fator de risco na infância é a hipertrofia adenotonsilar. Os linfócitos nessas estruturas são responsáveis por respostas imunes locais e sistêmicas.

Objetivo

Dosar os marcadores inflamatórios, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, PCR e α1-GP, nas tonsilas de crianças com e sem síndrome da apneia obstrutiva do sono.

Método

Estudamos prospectivamente 34 crianças que se queixavam de ronco, dificuldade para respirar durante o sono ou tonsilites recorrentes. Os pacientes foram submetidos a exame otorrinolaringológico completo, endoscopia nasal e polissonografia e foram divididos em dois grupos com 17 crianças cada: síndrome de apneia obstrutiva do sono e controle. Todos foram submetidos à adenotonsilectomia. As citocinas foram medidas nas tonsilas coletadas (métodos ELISA e Multiplex).

Resultados

Com diferenças estatisticamente significantes, observou-se aumento das citocinas IL-8 e IL-10 em pacientes com apneia obstrutiva do sono em comparação ao grupo controle, assim como aumento dos níveis de proteína C reativa. e de α1-GP na região cortical das tonsilas de crianças portadoras de síndrome da apneia obstrutiva do sono em comparação com a região medular. Não houve diferenças estatisticamente significantes para o restante dos mediadores inflamatórios.

Conclusão

Após a análise dos níveis de marcadores pró e anti-inflamatórios (IL-1β, IL-4, IL-6, IL-8, IL-10, Il-15, TNF-α, PCR, α1-GP) nas tonsilas, observamos níveis mais altos de marcadores IL-8 e IL-10 em pacientes pediátricos com síndrome da apneia obstrutiva do sono.

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Cross-cultural adaptation of the Amsterdam inventory for auditory disability and handicap to Brazilian Portuguese

Publication date: Available online 30 August 2018

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Sthella Zanchetta, Humberto Oliveira Simões, Pamela Papile Lunardelo da Silva Lunardelo, Marina de Oliveira Canavezi, Ana Cláudia Mirândola Barbosa Reis, Eduardo Tanaka

Abstract

Introduction

Patient-reported outcome measures, inventory and or questionnaire, allow patients to present their perspective of the impact of their individual condition on a day-to-day basis, independent of the analysis of test results by the expert clinician. Outcome measures are recommended when there is evidence showing their reliability, validity and sensitivity. There are standardized patient-reported outcome measures for hearing in English language; however, other languages lack these instruments.

Objective

Adapt the Amsterdam inventory for auditory disability and handicap to Brazilian Portuguese and analyze its validation measures.

Methods

We conducted two studies. In Study 1, we translated and adapted the Amsterdam inventory for auditory disability and handicap to Brazilian Portuguese according to good practice guidelines; this included the pre-test stage. In Study 2, we administered the Portuguese version to adults with and without hearing loss (n = 31 and 18, respectively) and analyzed the measures of instrument validation, reliability, and reproducibility. Moreover, we calculated the correlation between pure tone thresholds and scores on the questionnaire.

Results

The results obtained in Study 1 demonstrated the feasibility of the translation process and the instrument's cultural adaptation, as well as its applicability, resulting in the Portuguese version of the Amsterdam inventory for auditory disability and handicap. In Study 2, the results revealed construct values for the questions and domains, as well as for the total reliable score. The intra-interviewer test–retest condition showed excellent reproducibility (ICC = 0.97). Finally, there was a strong positive correlation (r = 0.83) between the mean pure tone threshold and the hearing difficulties values, as measured by the instrument's scores.

Conclusion

The English version of the Amsterdam inventory for auditory disability and handicap could be translated and adapted to Brazilian Portuguese. An analyses of the validation process yielded reliable, consistent, and stable results.

Resumo

Introdução

Medidas de resultados relatados pelo paciente, inventários e/ou questionários, permitem que os pacientes apresentem suas perspectivas do impacto de sua condição no dia-a-dia, independente da análise dos resultados dos testes realizados pelo especialista. Esses instrumentos são recomendados quando há evidências mostrando sua confiabilidade, validade e sensibilidade. Existem medidas de resultados relatados pelo paciente padronizadas para a audição em língua inglesa; no entanto, esses instrumentos não existem em outras línguas.

Objetivo

Adaptar o Amsterdam Inventory for Auditory Disability and Handicap para o português brasileiro e avaliar suas medidas de validação.

Método

Realizamos dois estudos. No estudo 1, traduzimos e adaptamos o Amsterdam Inventory for Auditory Disability and Handicap para o português brasileiro de acordo com as diretrizes de boas práticas; incluindo a fase de pré-teste. No estudo 2, aplicamos a versão em português em adultos com e sem perda auditiva (n = 31 e 18, respectivamente) e analisamos as medidas de validação, confiabilidade e reprodutibilidade do instrumento. Além disso, calculamos a correlação entre os limiares de tons puros e os escores do questionário.

Resultados

Os resultados obtidos no estudo 1 demonstraram a viabilidade do processo de tradução e adaptação cultural do instrumento, assim como sua aplicabilidade, resultando na versão em português da Amsterdam Inventory for Auditory Disability and Handicap. No estudo 2, os resultados revelaram valores de constructo para as questões e domínios, bem como para o escore total confiável. A condição de teste-reteste intra-entrevistador mostrou excelente reprodutibilidade (CCI = 0,97). Por fim, houve forte correlação positiva (r = 0,83) entre o limiar médio de tom puro e os valores das dificuldades auditivas, medidos pelos escores do instrumento.

Conclusão

A versão em inglês do Amsterdam Inventory for Auditory Disability and Handicap foi traduzida e adaptada para o português brasileiro. Uma análise do processo de validação produziu resultados confiáveis, consistentes e estáveis.

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Does a strong IgG response precede allergic sensitization?

Allergy, Volume 73, Issue 9, Page 1924-1925, September 2018.


https://ift.tt/2onyU8u

Very rarely chronic urticaria can be caused by cancer and if so, resolves with its cure

Allergy, Volume 73, Issue 9, Page 1925-1926, September 2018.


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In this Issue: Graphical Abstracts

Allergy, Volume 73, Issue 9, Page 1759-1761, September 2018.


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Issue Information ‐ TOC

Allergy, Volume 73, Issue 9, Page 1757-1758, September 2018.


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Issue Information ‐ Cover and Editorial Board

Allergy, Volume 73, Issue 9, Page 1755-1755, September 2018.


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Corrigendum

Allergy, Volume 73, Issue 9, Page 1929-1929, September 2018.


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Removal of hexavalent chromium from water by modified sponge iron particles and insights into mechanism

Abstract

Sponge iron particles modified with expanded graphite and Cu were used to purify solutions contaminated with aqueous Cr(VI). A removal mechanism that involved physical adsorption and a redox reaction is proposed. The reaction, which consisted of rapid adsorption, a desorption stage, and an adsorption–desorption equilibrium stage, corresponded to a first-order kinetic model. The properties of the adsorption materials before and after use were investigated by X-ray diffraction, scanning electron microscopy–energy-dispersive spectroscopy, Fourier-transform infrared spectroscopy, energy-dispersive X-ray fluorescence spectroscopy, and surface area measurements. Changes in the surface properties, e.g., attachment of material to the surface and filling of pores with Cr, were clearly observed. The Langmuir model best described Cr(VI) adsorption on the sponge iron and its modified particles. Removal efficiencies of 98.7, 98.8, and 100% were achieved in 7 h at a Cr(VI) dosage of 10 mg/L. Sponge iron particles are therefore potential adsorbents and after modification give good removal of Cr(VI) ions from contaminated water.

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Comparison Between a Standard Tube and the Ultra-thin Tritube for Intubation of the Trachea and for Maintaining Access to the Trachea After Anaesthesia, in Patients With an Expected Difficult Direct Laryngoscopy

Conditions:   Oral Neoplasm;   Pharynx Cancer;   Larynx Cancer
Interventions:   Device: Tritube;   Device: Standard enditracheal tube
Sponsor:   Michael Seltz Kristensen
Not yet recruiting

https://ift.tt/2LDrhEl

Abemaciclib + Nivolumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed or Recurred Within Six Months After Platinum-based Chemotherapy

Condition:   Head and Neck Squamous Cell Carcinoma
Interventions:   Drug: Abemaciclib;   Drug: Nivolumab;   Procedure: Tumor biopsy;   Procedure: Peripheral blood;   Other: EORTC QLQ-30
Sponsors:   Washington University School of Medicine;   Eli Lilly and Company
Not yet recruiting

https://ift.tt/2NaJPAM

Apatinib Combined With S-1 for the Treatment of Recurrent/Metastatic Head and Neck Malignancies

Condition:   Head and Neck Cancer
Intervention:   Drug: Apatinib
Sponsors:   China International Medical Foundation;   Chinese Society of Clinical Oncology
Not yet recruiting

https://ift.tt/2LKrFke

Do Changes in ctDNA Predict Response for Patients With Oesophageal Cancer Receiving Duvalumab

Condition:   Oesophageal Cancer
Intervention:   Drug: Durvalumab
Sponsors:   Simon C Pacey, MD;   AstraZeneca
Not yet recruiting

https://ift.tt/2N30Kox

Comparison Between a Standard Tube and the Ultra-thin Tritube for Intubation of the Trachea and for Maintaining Access to the Trachea After Anaesthesia, in Patients With an Expected Difficult Direct Laryngoscopy

Conditions:   Oral Neoplasm;   Pharynx Cancer;   Larynx Cancer
Interventions:   Device: Tritube;   Device: Standard enditracheal tube
Sponsor:   Michael Seltz Kristensen
Not yet recruiting

https://ift.tt/2LDrhEl

Abemaciclib + Nivolumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed or Recurred Within Six Months After Platinum-based Chemotherapy

Condition:   Head and Neck Squamous Cell Carcinoma
Interventions:   Drug: Abemaciclib;   Drug: Nivolumab;   Procedure: Tumor biopsy;   Procedure: Peripheral blood;   Other: EORTC QLQ-30
Sponsors:   Washington University School of Medicine;   Eli Lilly and Company
Not yet recruiting

https://ift.tt/2NaJPAM

Apatinib Combined With S-1 for the Treatment of Recurrent/Metastatic Head and Neck Malignancies

Condition:   Head and Neck Cancer
Intervention:   Drug: Apatinib
Sponsors:   China International Medical Foundation;   Chinese Society of Clinical Oncology
Not yet recruiting

https://ift.tt/2LKrFke

Do Changes in ctDNA Predict Response for Patients With Oesophageal Cancer Receiving Duvalumab

Condition:   Oesophageal Cancer
Intervention:   Drug: Durvalumab
Sponsors:   Simon C Pacey, MD;   AstraZeneca
Not yet recruiting

https://ift.tt/2N30Kox

Nodal metastases distribution in laryngeal cancer requiring total laryngectomy: Therapeutic implications for the N0 Neck

Publication date: Available online 31 August 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): D. Riviere, J. Mancini, L. Santini, A. Loth bouketala, A. Giovanni, P. Dessi, N. Fakhry

Abstract

Objectives

Neck dissection is a controversial surgical procedure in patients with squamous cell carcinoma of the Larynx free of any node metastasis detected in preoperative staging. The aim of this study was to investigate the distributions of lymph node metastases in laryngeal squamous cell carcinoma and improve the rationale for elective treatment of N0 neck.

Material and methods

Retrospective single-center series of Seventy-eight successive patients with laryngeal squamous cell carcinoma who underwent neck dissection between 2008 and 2015.

Results

Surgery was first-line treatment in 37 patients (47%) and for recurrent disease in 41 (53%). The rate of occult nodal metastasis was 14% (n = 11): levels IIa and/or III were affected in 9 cases (11.5%) compared with single cases of IIb and IV involvement (1.3% each). The rate of occult nodal metastasis was significantly lower among patients operated on for recurrent disease after radiotherapy than in patients who never had any radiotherapy of the cervical lymph nodes (0% vs. 16.7%, P = 0.03).

Conclusions

Selective cervical lymph node dissection in levels IIa and III sparing levels IIb and IV seems to be ideal in total laryngectomy in patients with cN0 laryngeal squamous cell carcinoma. Omitting lymph node dissection altogether may be considered in total laryngectomy on a cN0 patient showing recurrence after radiotherapy.

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Familial acanthosis nigricans with the FGFR3 mutation: Differences of pigmentation between male and female patients

The Journal of Dermatology, EarlyView.


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Magnetic resonance spectroscopy may serve as a presurgical predictor of somatostatin analog therapy response in patients with growth hormone-secreting pituitary macroadenomas

Abstract

Purpose

Somatostatin analogs (SSAs) are considered one of the most effective medical treatments for patients with growth hormone-secreting pituitary adenomas (GH-PAs). The postoperative electron microscopy (EM) pathological subtype and SSTR2 expression in the tumor are the most established predictors of patient response to SSA therapy. The aim of this study was to evaluate how will magnetic resonance spectroscopy (MRS) measurements before surgery predict the EM pathological subtypes and SSTR2 expression of tumors, and thereby serve as an indicator for the therapeutic sensitivity to SSAs of patients with GH-PAs.

Methods

Eighteen patients with GH pituitary macroadenomas who underwent transsphenoidal surgery were included in this retrospective study. The preoperative MRS data and T2 signal intensity were obtained from patients by 1.5 T MR spectroscopy of the sellar mass. The EM pathological subtypes of tumors were determined after surgery through examination of cell granulations. The expressions of somatostatin receptor 2 (SSTR2), SSTR5, P21, P27, and Ki-67 were evaluated by immunohistochemistry.

Results

The MRS parameters that were found to significantly predict the EM pathological subtypes of tumors, as calculated by the receiver operating characteristic curve, were the choline (Ch) value at 3140.5 MR units (sensitivity 69.2%, specificity 100%) and the choline/creatine (Ch/Cr) ratio at 1.27 (sensitivity 92.3%, specificity 100%). Further, the Ch/Cr ratio, but not other MRS data, was shown to negatively correlate with the expression of SSTR2 (P = 0.02). The Ch/Cr ratio was also found to positively correlate with the Ki-67 value (P < 0.05) and T2 signal (P < 0.05), but not with other factors that were examined in this study. Moreover, the Ch/Cr ratio could predict the EM pathological subtypes of tumors with an accuracy of 83.3% (5/6) for patients with an isointense T2 signal.

Conclusion

The Ch/Cr ratio by MRS could effectively predict the tumor subtype and was significantly correlated with the expression of SSTR2, which was consistent with other predictors. It was also able to distinguish the patients with isointense T2 signals. Our results provide a potentially new and non-invasive method to predict the response to SSAs in patients with GH pituitary macroadenomas.

https://ift.tt/2wu3r9c

Hinführung zum Thema – Schmerzen bei an Krebs erkrankten Menschen

https://ift.tt/2PQHnxE

The Glutamine‐Glutamate Cycle Regulates Synaptic Glutamate Release in the Ventrolateral Ventromedial Nucleus of the Hypothalamus of Perinatal Female Rats

Journal of Neuroendocrinology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2wylB93

Aktuelle pathophysiologische Entwicklungen bei fibrosierenden Erkrankungen: Ansatzpunkte für neue Konzepte in der Therapie

Zusammenfassung

Die Fibrose ist ein häufiges Symptom zahlreicher Hauterkrankungen unterschiedlicher Genese. Die Pathogenese fibrosierender Veränderungen der Haut und anderer Organsysteme ist bisher nicht ausreichend verstanden, und die derzeitigen Therapiemöglichkeiten sind unzureichend. Fibrosierende Erkrankungen der Haut führen zu einer Gewebeverhärtung und zu einem Funktionsverlust, die in der Folge mit schwerwiegenden Einschränkungen der Lebensqualität, gesteigerter Morbidität und letztlich einer erhöhten Mortalität einhergehen können. Epidemiologische Studien weisen darauf hin, dass in den westlichen Industrienationen bis zu 45 % aller Todesursachen auf Erkrankungen zurückzuführen sind, die mit einer Gewebefibrose in unterschiedlichen Organen einhergehen. Aktuell stehen nur wenige spezifisch für fibrosierende Erkrankungen zugelassene Medikamente zur Verfügung. Die Entwicklung neuer, ursachenbasierter und damit effizienter Therapieansätze ist dringend erforderlich. Dies stellt einerseits eine große Herausforderung dar, eröffnet zugleich aber auch die Möglichkeit, einen besonderen Beitrag zur Aufklärung dieses medizinisch ungelösten Problems zu leisten. Im Folgenden sind ausgewählte Erkenntnisse der letzten Jahre mit Fokus auf der Rolle der Immunantwort in der Fibrogenese dargestellt.

https://ift.tt/2NAfUyK

Update: Asthma Yardstick: Practical recommendations for a sustained step-up in asthma therapy for poorly controlled asthma

Publication date: Available online 30 August 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): John J. Oppenheimer, Larry Borish

https://ift.tt/2LJlWeH

Biologics and Small Molecule Agents in Allergic and Immunologic Skin Diseases

Abstract

Purpose of Review

Biologics and small molecules are key therapeutic options in the treatment of chronic immunologic and allergic skin conditions. By directly targeting innate and inflammatory responses within the skin, including pro-inflammatory cytokines and cellular signaling pathways, these new agents have the potential to counteract the inflammatory cascade responsible for various conditions, including psoriasis and atopic dermatitis. Over the past decade, groundbreaking research identifying key cytokines and receptors involved in the pathogenesis of these diseases has allowed for the development of highly efficacious biologics and small molecules that are associated with unprecedented rates of skin clearance and favorable adverse event profiles.

Recent Findings

This narrative review evaluates new and upcoming biologic and small molecule agents for the treatment of two allergic/immunologic skin diseases—atopic dermatitis and psoriasis. Numerous small molecules and biologics targeting TNF-α, IL-12/23, IL-17 and IL-17R, and IL-23 are commercially available for the treatment of psoriasis, and newer agents are in various stages of development. Currently, dupilumab, a monoclonal antibody that blocks IL-4R∝, is the only approved biologic for atopic dermatitis. Antibodies targeting IL-13 and IL-31 and small molecules that inhibit Janus kinase and pruritus-mediating receptors are currently being studied in clinical trials. Further investigations into the pathophysiology of atopic dermatitis will likely yield additional therapeutic options in the future.

Summary

This article reviews recent literature on small molecules and biologics for the treatment of atopic dermatitis and psoriasis.

https://ift.tt/2C5m5tq

Dapagliflozin-Associated Euglycemic Diabetic Ketoacidosis in a Patient Presenting with Acute Pancreatitis.

Related Articles

Dapagliflozin-Associated Euglycemic Diabetic Ketoacidosis in a Patient Presenting with Acute Pancreatitis.

Case Rep Endocrinol. 2018;2018:6450563

Authors: Badwal K, Tariq T, Peirce D

Abstract
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a class of medications used for glycemic control in type II diabetes mellitus. Their mechanism of action involves preventing resorption of glucose at the proximal kidney, thereby promoting glucosuria and weight loss. However, they have also been found to be associated with euglycemic diabetic ketoacidosis (euDKA). This case describes a 25-year-old male with a history of type II diabetes on metformin, sitagliptin, and dapagliflozin who was admitted with his third episode of pancreatitis secondary to hypertriglyceridemia. His home oral glycemic agents were continued as inpatient. Despite tight euglycemic control, the patient developed profound metabolic acidosis and was found to have an elevated beta-hydroxybutyrate level and normal lactic acid level. He was admitted into the intensive care unit and started on an insulin drip, and after resolution of his acidosis he was transitioned to basal insulin successfully. He was discharged with an insulin regimen while his oral glycemic agents were discontinued indefinitely. SGLT-2 inhibitors are associated with euDKA, most likely as a result of their non-insulin-dependent glucose clearance, hyperglucagonemia, and decreased ketone clearance. The aim of this case report is to inform the physician about the possibility of euDKA in a patient with type II diabetes on a SGLT-2 inhibitor presenting with an acute illness.

PMID: 30159178 [PubMed]

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