Updated evidence-based (S2e) European Dermatology Forum guideline on topical corticosteroids in pregnancy

Abstract

Background

Topical corticosteroids may be needed for treating skin conditions in pregnancy. Nevertheless, only limited data on the fetal effects of topical corticosteroids are available.

Objective

To update an evidence-based guideline on the safe use of topical corticosteroids in pregnancy.

Methods

A guideline subcommittee of the European Dermatology Forum updated the guideline by adding and appraising new evidence.

Results

The current best evidence from 14 observational studies with 1 601 515 study subjects found no significant associations between maternal use of topical corticosteroids of any potency and some adverse pregnancy outcomes including mode of delivery, birth defect, preterm delivery and fetal death. However, maternal use of potent/very potent topical corticosteroids, especially in large amounts, is associated with an increase in the risk of low birthweight.

Conclusion

Mild/moderate topical corticosteroids should be preferred to potent/very potent ones in pregnancy. The well-known topical side-effects of corticosteroids on the mother's side need to be considered as well.

http://ift.tt/2lg5OVo

Omega-3 fatty acids as adjunctive treatment for bexarotene-induced hypertriglyceridaemia in patients with cutaneous T-cell lymphoma

Summary

Background

Bexarotene is an oral retinoid approved for treating cutaneous T-cell lymphoma (CTCL) in patients resistant to first-line systemic treatment. Hypertriglyceridaemia is an unavoidable adverse effect of bexarotene therapy, and requires monitoring because of the risk of developing pancreatitis. Therefore, prophylactic hypolipidaemic therapy, usually with a fibrate alone, is required for preventing bexarotene-induced hypertriglyceridaemia. Despite these measures, a large number of patients develop very severe hypertriglyceridaemia.

Aim

To assess the lipid metabolism changes before and after the use of a combination of omega-3 fatty acids (n-3 FA) plus fenofibrate compared with fenofibrate alone as a more effective lipid-lowering therapy in patients with CTCL treated with bexarotene.

Methods

From January 2005 to January 2013, we analysed all 25 patients with CTCL treated with bexarotene. The first 18 consecutively enrolled patients received fenofibrate alone as a lipid-lowering therapy, and the next 7 consecutively enrolled patients received a combination of fenofibrate and n-3 FA.

Results

Data for all 25 consecutive patients with CTCL treated with bexarotene were evaluated. Of these, 24 patients (96%) developed hypertriglyceridaemia despite the hypolipidaemic therapy, with this being very severe (> 11.2 mmol/L) in 20% of the cases. Of the 18 patients receiving fenofibrate alone, 5 (28%) developed very severe hypertriglyceridaemia, compared with none of the 7 patients treated with the n-3 FA combination.

Conclusions

Our results suggest that the n-3 FA combination may be more effective than fibrate alone for preventing bexarotene-induced hypertriglyceridaemia.

http://ift.tt/2kT0jjC

Concept of the Ambulatory Pain Physician

Abstract

Purpose of Review

Given the growing number of ambulatory surgeries being performed and the variability in postoperative pain requirements, early discharge, and inconsistent follow-up, ambulatory surgery presents a unique challenge for this patient population and warrants the presence of an ambulatory pain specialist to evaluate a patient preoperatively and postoperatively to optimize patient safety and satisfaction. This article explores the crucial role that a dedicated pain physician would have in the ambulatory surgery setting.

Recent Findings

The prevalence of chronic pain, opioid use, and substance abuse is growing in this country, while ambulatory and same-day surgery have also experienced considerable growth. Inevitably, more patients with challenging chronic pain or substance abuse are having ambulatory surgery. Increased BMI, advanced age, more comorbidities warranting a higher ASA physical status classification, and longer surgeries are now all components of ambulatory surgery that contribute to increased risk too. Certain surgeries including breast surgery, inguinal hernia repair, and thoracotomy are at higher risk for the conversion of acute to chronic pain, and an ambulatory pain specialist would be beneficial for added focus on these patients.

Summary

Multimodal pain control with non-opioids and regional anesthesia adjuvants are beneficial, while emphasis on a patient's functional capacity may be more useful than quantifying the severity of pain. Despite the best efforts of patients' primary care providers or surgeons, patients often are discharged with more chronic opioid therapy than they presented with, and an ambulatory pain specialist can help manage the complications and prevent further escalation of this opioid epidemic. An onsite anesthesiologist with interest in pain management in each ambulatory surgery center administering anesthesia and available onsite to deal with immediate preoperative, intraoperative, and recovery room would be ideal to curb and manage complication from uncontrolled pain and related pain issues.

http://ift.tt/2lygbXf

Primary and secondary prevention of cardiovascular disease in patients with hyperlipoproteinemia (a)

Abstract

General lipoprotein (Lp) (a) screening can help to identify patients at high risk for cardiovascular disease. Non-invasive methods allow early detection of clinically asymptomatic incipient atherosclerotic disease. Medical treatment options are still unsatisfactory. Lp(a) apheresis is an established treatment in Germany for secondary prevention of progressive cardiovascular disease. Statin-based lowering of LDL cholesterol and thrombocyte aggregation inhibitors still represent the basis of medical treatment. Target levels for LDL-cholesterol should be modified in patients with hyperlipoproteinemia (a).

http://ift.tt/2mjehIA

The German Lipoprotein Apheresis Registry (GLAR) – almost 5 years on

Abstract

Background

Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology and of Lipidologists and completed the data set for the registry according to the current guidelines and the German indication guideline for apheresis in 2009. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data are available over nearly 5 years now.

Methods and results

During the time period 2012–2016, 71 German apheresis centers collected retrospective and prospective observational data of 1435 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-C levels and/or high Lp (a) levels suffering from cardiovascular disease (CVD) or progressive CVD. A total of 15,527 completely documented LA treatments were entered into the database. All patients treated by LA showed a median LDL-C reduction rate of 67.5%, and a median Lp (a) reduction rate of 71.1%. Analog to the Pro(a)LiFe pattern, patient data were analyzed to the incidence rate of coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y‑1) and prospectively two years on LA treatment (y + 1 and y + 2). During two years of LA treatment a MACE reduction of 78% was observed. In the years considered, side effects of LA treatment were low (5.9%) and mainly comprised puncture problems.

Conclusions

The data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp (a) levels, progressive CVD, and maximally tolerated lipid lowering medication. In addition, LA treatments were found to be safe with a low rate of side effects.

http://ift.tt/2ly9btw

Lipoprotein (a) and coronary heart disease – is there an efficient secondary prevention?

Abstract

Lipoprotein (a) (Lp (a)) is one risk factor for the development of cardiovascular diseases. Several studies have shown that Lp (a) hyperlipoproteinaemia has a particular influence on the development of coronary heart disease (CHD). A retrospective single-centre observation study was performed to evaluate the effectiveness of lipid apheresis on the basis of consecutively performed percutaneous coronary interventions (PCI) in patients with high Lp (a) values and angiographically documented CHD.

In 23 pts (male 18, age 60.04 ± 0.58 years) with angiographically documented CHD (first manifestation 48.00 ± 9.41 years), elevated LDL cholesterol (144.39 ± 92.01 mg/dl) and Lp (a) (133.04 ± 39.68 mg/dl), 49 PCI and 3 coronary artery bypass grafting (CABG) procedures had been performed prior to the initiation of lipid apheresis. Following the initiation of weekly lipid apheresis, LDL cholesterol was 99.43 ± 36.53 mg/dl and Lp (a) 91.13 ± 33.02 mg/dl. In a time interval of 59.87 ± 49.49 months (median 51.00, range 1–153 months) 15 pts did not require an additional PCI. In 8 pts (7 pts 3‑vessel disease, 1 pt 2‑vessel disease) 14 PCI – no CABG – were performed after 69.38 ± 71.67 months (median: 32.50, range 17–232 months). The incidence of PCI could thus be reduced by 71.43%.

http://ift.tt/2mje0p0

Effects of Dietary Macronutrient Composition on FNDC5 and Irisin in Mice Skeletal Muscle

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


http://ift.tt/2mrmv0f

Escalating dosimetry of UVA-1 in the treatment of alopecia areata

Abstract

Background

Phototherapy can be an option in unresponsive alopecia areata (AA); however, variable results have been reported with its use. We could not find literature of treatment with UVA-1 in AA. A study was designed to evaluate progressive dosimetry to determine the initial dose and its increments.

Methods

Patients with unresponsive AA were recruited. Twenty-five sessions of 30 J/cm² were administered. If hair regrowth was <75%, the dose was escalated to 60 J/cm². If hair improvement remained <75%, an additional 25 sessions at 120 J/cm² were indicated. If total hair regrowth occurred before 75 sessions, a final visit was performed for biopsies and severity of alopecia tool (SALT) evaluation. Clinical and histopathological assessments were performed blindly. Adverse effects were recorded.

Results

Nine men and 13 women were included; 16 were initially S₁, one S₃, and five S₄. Median age was 32 years and median evolution 10 months. Nine patients achieved an S₀, eight S₁, and five S₄ (P = 0.005). The most notable improvement was with 60 J/cm² (P = 0.02). Biopsies exhibited an absence of inflammation in five patients and mild persistence in 17. An increase of 43.75% in anagen hairs (P ≤ 0.001) was achieved, telogen hairs decreased 16.3% (P = 0.06), and catagen hairs were reduced 22.7% (P = 0.005). Pearson's correlation was −0.82 and P ≤ 0.001, when correlating anagen hairs with final SALT. Improvement has continued for 6 months post treatment. Mild xerosis was observed in all patients, and six (28.6%) developed transient mild hyperpigmentation.

Conclusions

This study provides a basis for UVA-1 dosimetry evaluating its therapeutic value in AA.

http://ift.tt/2lLUlAj

Pseudochromhidrosis: report and review of literature

Abstract

Chromhidrosis is a rare condition where colored sweat comes from the apocrine or eccrine glands. Pseudochromhidrosis is an uncommon condition where colored sweat is related to specific dye-producing bacteria, drugs, dyes, or chemical agents. This article provides a literature review of the various etiology, investigation, treatment, and prognosis. We propose an investigative algorithm to assist dermatologists, pediatric dermatologists, and general practitioners to diagnose this uncommon condition. The treatment options rely on the primary etiology such as removing dyes and chemical agents first and then treating the chromogenic bacteria. Topical and oral erythromycin seems to be the most effective treatment both in unidentified and identified chromogenic bacteria cases. Results and prognosis were excellent and without recurrence.

http://ift.tt/2lfE9UL

Mycetoma-like chromoblastomycosis: a diagnostic dilemma

Abstract

Objectives

Mycetoma and chromoblastomycosis are subcutaneous fungal infections caused by pigmented fungi, common in the tropics and subtropics. Here we report a pregnant woman who presented with a swelling around the ankle joint which was clinically diagnosed as a case of mycetoma; however, further investigations revealed it to be a case of chromoblastomycosis.

Methods

24 year old primigravida presented with an indurated swelling around the ankle joint with multiple nodules and sinuses draining serosanguinous discharge. There was no improvement with antibiotic therapy or surgical debridement. Patient was investigated in detail including radiographs, KOH smear, pus culture and biopsy for histopathology and fungal culture.

Results

o grains were identified from the discharge and KOH smear was negative for fungal elements. Pus culture revealed no bacterial growth. On the other hand, histopathology and fungal culture confirmed it to be a case of chromoblastomycosis caused by Fonsecaea pedrosoi. Treatment was initiated with terbinafine 250 mg daily, and patient showed excellent response within 6 months of therapy.

Conclusion

This unusual mycetoma-like presentation of chromoblastomycosis has not been previously reported in literature and may be attributed to the altered immune status in pregnancy. This should alert the clinician about the need to be vigilant of the atypical presentations of well-known dermatological conditions, especially in special situations like pregnancy.

http://ift.tt/2lLNwyw

Hyperbaric oxygen therapy for chronic ulcers in systemic sclerosis – case series

Abstract

Background

Digital and leg ulcers are extremely painful, hard to heal manifestations of systemic sclerosis (SSc). Many treatments have been tried for these challenging complications, but use of hyperbaric oxygen therapy (HBOT) is very limited. HBOT has been used as an adjunctive therapy for treating chronic wounds, and nonhealing SSc wounds, which have a hypoxic nature, may also benefit from it.

Methods

This is a retrospective analysis of six SSc patients who underwent HBOT for their ulcers. Patient demographics, ulcer properties, and details of treatments were evaluated.

Results

Three patients had digital ulcers, and the other three had leg ulcers. Three patients (two leg ulcers and one digital ulcer) had bilateral lesions. All patients had been treated for at least one and a half months with various modalities. After HBOT was applied, four patients' ulcers healed completely and two patients had near-complete healing. Amputation was not required for any.

Conclusion

This case series, which has the largest patient population up to present, shows adjunctive HBOT may be helpful in the treatment of SSc ulcers.

http://ift.tt/2lfzdPQ

Accelerated nail growth rate in HIV patients

Abstract

Background

Many factors have been noted to alter the growth rate of both finger and toe nails, some with harder evidence than others. Infectious diseases are among the ones reported as slowing the growth rate. However, on previous studies we noticed that patients living with HIV and onychomycosis could be cured without the use of antifungal therapy, only with the immunological improvement provided by the combined antiretroviral therapy, and we wanted to prove that the growth rate is also increased in this group and thus probably contributes to the cure of onychomycosis.

Methods

This was an observational, descriptive, and prospective study. We marked with a scalpel the nail plate of the first finger of the non-dominant hand and the same foot, and measured the nail growth in the subsequent medical appointments with a magnifying glass and a millimetric scale.

Results

Thirteen patients completed the study, and were paired with healthy controls by age and gender. After performing Mann-Whitney U test, our results showed statistical significance among both groups, showing that patients with HIV have faster nail growth rates than those in the HIV negative group.

Conclusions

There is little data on HIV nail growth rate to compare our results, but what we see in the clinical practice is that this group of patients shows a faster nail growth rate, as has also been reported for longer eyelashes, and this could be an important factor in the cure rates of onychomycosis.

http://ift.tt/2lLNuGU

Amoxicillin-induced generalized eruption associated with Epstein-Barr virus reactivation in pregnancy

http://ift.tt/2lfJziq

Pediatric pyoderma gangrenosum: a systematic review and update

Abstract

Pyoderma gangrenosum (PG) is a sterile neutrophilic disorder that rarely affects children. Clinical, epidemiological, and therapeutic data on pediatric PG is poor as there are many newly reported associated diseases and drugs. This paper aims to review all recent available data on pediatric PG. A systematic review of the literature was conducted using Embase, Medline, and Cochrane databases. A total of 132 articles were included in the review. The most commonly reported underlying diseases in pediatric PG are inflammatory bowel diseases followed by hematologic disorders, vasculitis, immune deficiencies and Pyogenic Arthritis, Pyoderma gangrenosum and Acne (PAPA) syndrome. More than half of the cases occur with no underlying disease. The most frequently reported clinical presentation is multiple disseminated ulcers. Treatment should be tailored according to the underlying etiology. It includes systemic steroids, corticosteroid sparing agents such as dapsone and cyclosporine, and TNF-alpha inhibitors such as adalimumab and infliximab. Response to treatment is high with cure rates reaching 90%. A high index of suspicion and a thorough workup are mandatory in the management of pediatric PG.

http://ift.tt/2lLQrqQ

Leprosy in Puerto Rico: insight into the new millennia

Abstract

Background

Leprosy, or Hansen's disease, is a chronic infectious disease caused by the bacillus Mycobacterium leprae. In 2000, the World Health Organization (WHO) defined the elimination of the disease as a global prevalence of less than one case per 10,000 population. However, disease transmission is an ongoing worldwide public health concern, as evidenced by the more than 220,000 new cases diagnosed each year.

Methods

This study is an update of the incidence and prevalence of leprosy in Puerto Rico for the period of 2000–2014. A retrospective analysis of data was obtained from the Tropical Disease Clinic (TDC) of the University of Puerto Rico School of Medicine.

Results

Sixty-three new cases of leprosy are detailed in this study. Disease incidence and prevalence were 1.65 and 5.26 per 100,000 inhabitants (of the island of Puerto Rico), respectively, and an average of 4.2 new cases per year. Most of the male patients in the study suffered from lepromatous leprosy (P = 0.026). In all, 47 (74.6%) patients had been born in Puerto Rico, and 29 (46%) had an affected family member or were in close contact with someone with leprosy.

Conclusions

Compared to those of previous studies, these results demonstrate a decrease in both the incidence and prevalence of leprosy in Puerto Rico over the past 15 years. The relatively high prevalence of leprosy in Puerto Rico means that it remains endemic on the island. Concerted efforts must be undertaken to achieve the goal of the elimination of this old and stigmatized disease.

http://ift.tt/2lfM8Rw

Der physiologische und der pathologische Schluckvorgang

Zusammenfassung

In Deutschland leiden derzeit schätzungsweise 5 Mio. Menschen an einer Schluckstörung. Diese Zahl wird voraussichtlich aufgrund der längeren Lebenserwartung, aber auch durch das vermehrte Überleben von extrem Frühgeborenen noch zunehmen. Diagnostisch wird ausgehend von den 4 Schluckphasen zunächst analysiert, ob ein anatomisch-organisches oder ein funktionelles Hindernis vorliegt. Dazu gehört die Erhebung einer ausführlichen Anamnese und die Untersuchung der Hirnnervenfunktionen, des orofazialen Bereichs, der Schluckreflexe, des pharyngealen und des ösophagealen Transportwegs. Es wird auf altersabhängige Variationen des Schluckvorgangs, nasale Regurgitation, Retentionen im Zungengrund und Hypopharynx oder Anzeichnen für eine Aspiration geachtet.

http://ift.tt/2mrkHo9

Likelihood of Immediate Food Challenge Reactions Varies by Age, History, Allergens, and Levels of Sensitization

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2mdN0KL

Alveolar Macrophages in Allergic Asthma: the Forgotten Cell Awakes

Abstract

Purpose of Review

The role of alveolar macrophages in innate immune responses has long been appreciated. Here, we review recent studies evaluating the participation of these cells in allergic inflammation.

Recent Findings

Immediately after allergen exposure, monocytes are rapidly recruited from the bloodstream and serve to promote acute inflammation. By contrast, resident alveolar macrophages play a predominantly suppressive role in an effort to restore homeostasis. As inflammation becomes established after repeated exposures, alveolar macrophages can polarize across a continuum of activation phenotypes, losing their suppressive functions and gaining pathogenic functions.

Summary

Future research should focus on the diverse roles of monocytes/macrophages during various types and phases of allergic inflammation. These properties could lead us to new therapeutic opportunities.

http://ift.tt/2lwWLly

Phenotype-Driven Therapeutics in Severe Asthma

Abstract

Inhaled corticosteroids are the mainstay of asthma treatment using a step-up approach with incremental dosing and additional controller medications in order to achieve symptom control and prevent exacerbations. While most patients respond well to this treatment approach, some patients remain refractory despite high doses of inhaled corticosteroids and a long-acting β-agonist. The problem lies in the heterogeneity of severe asthma, which is further supported by the emergence of severe asthma phenotypes. This heterogeneity contributes to the variability in treatment response. Randomized controlled trials involving add-on therapies in poorly controlled asthma have challenged the idea of a "one size fits all" approach targeting specific phenotypes in their subject selection. This review discusses severe asthma phenotypes from unbiased clustering approaches and the most recent scientific evidence on novel treatments to provide a guide in personalizing severe asthma treatment.

http://ift.tt/2mikS5N

Contemporary Use of Corticosteroids in Rhinology

Abstract

Purpose of Review

Exogenously administered corticosteroids are widely used today in the field of rhinology. Allergic rhinitis (AR), non-allergic rhinitis (NAR), acute rhinosinusitis (ARS), chronic rhinosinusitis with (CRSwNP) and without (CRSsNP) nasal polyps, and autoimmune disorders with nasal manifestations are common diseases treated effectively with intranasal and oral glucocorticoids. We focus on physiological pathways, therapeutic benefits, indications, contra-indications, and side effects of glucocorticoid utilization in the treatment of rhinologic disorders such as AR, NAR, ARS, CRSsNP, and CRSwNP.

Recent Findings

Second-generation intranasal steroid (INS) agents have pharmacokinetic characteristics that minimize their systemic bioavailability, resulting in minimum risk for systemic adverse events. Several studies have demonstrated the symptomatic efficacy of both intranasal and oral corticosteroids in ARS. Moreover, intranasal and systemic steroid administration has been repeatedly proven beneficial in the conservative and perioperative management of CRSwNP. For patients with AR, there is no need for oral steroids, with the exception of severe cases, as there is lack of superiority to INS. SCUAD patients challenge currently available treatment schemes, underlining the importance of research in the field.

Summary

Corticosteroids' effectiveness in the treatment of various rhinologic disorders is indisputable. However, their characteristics, and potential side effects, make a clear consensus for utilization difficult.

http://ift.tt/2lwZhZc

Effects of Allergic Sensitization on Antiviral Immunity: Allergen, Virus, and Host Cell Mechanisms

Abstract

Purpose of Review

Multiple clinical and epidemiological studies demonstrate links between allergic sensitization and virus-induced atopic disease exacerbations. This review summarizes the recent findings regarding allergen, viral, and host cellular mechanisms relevant to these observations.

Recent Findings

Recent studies have focused on the molecular pathways and genetic influences involved in allergen-mediated inhibition of innate antiviral immune responses. Multiple tissue and cell types from atopic individuals across the atopy spectrum exhibit deficient interferon responses to a variety of virus infections. Impairment in barrier function, viral RNA and DNA recognition by intracellular sensing molecules, and dysregulation of signaling components are broadly affected by allergic sensitization. Finally, genetic predisposition by numerous nucleotide polymorphisms also impacts immune pathways and potentially contributes to virus-associated atopic disease pathogenesis.

Summary

Allergen-virus interactions in the setting of atopy involve complex tissue and cellular mechanisms. Future studies defining the pathways underlying these interactions could uncover potential therapeutic targets. Available data suggest that therapies tailored to restore specific components of antiviral responses will likely lead to improved clinical outcomes in allergic disease.

http://ift.tt/2mioVPS

Immunoprofiling as a predictor of patient’s response to cancer therapy—promises and challenges

Daniel Bethmann | Zipei Feng | Bernard A Fox

http://ift.tt/2lQqfvF

Likelihood of Immediate Food Challenge Reactions Varies by Age, History, Allergens, and Levels of Sensitization

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2lfnsZH

Identification of potential therapeutic target genes, key miRNAs and mechanisms in oral lichen planus by bioinformatics analysis

Publication date: June 2017
Source:Archives of Oral Biology, Volume 78
Author(s): Cuihua Gong, Shangtong Sun, Bing Liu, Jing Wang, Xiaodong Chen
The study aimed to identify the potential target genes and key miRNAs as well as to explore the underlying mechanisms in the pathogenesis of oral lichen planus (OLP) by bioinformatics analysis. The microarray data of GSE38617 were downloaded from Gene Expression Omnibus (GEO) database. A total of 7 OLP and 7 normal samples were used to identify the differentially expressed genes (DEGs) and miRNAs. The DEGs were then performed functional enrichment analyses. Furthermore, DEG-miRNA network and miRNA-function network were constructed by Cytoscape software. Total 1758 DEGs (598 up- and 1160 down-regulated genes) and 40 miRNAs (17 up- and 23 down-regulated miRNAs) were selected. The up-regulated genes were related to nuclear factor-Kappa B (NF-κB) signaling pathway, while down-regulated genes were mainly enriched in the function of ribosome. Tumor necrosis factor (TNF), caspase recruitment domain family, member 11 (CARD11) and mitochondrial ribosomal protein (MRP) genes were identified in these functions. In addition, miR-302 was a hub node in DEG-miRNA network and regulated cyclin D1 (CCND1). MiR-548a-2 was the key miRNA in miRNA-function network by regulating multiple functions including ribosomal function. The NF-κB signaling pathway and ribosome function may be the pathogenic mechanisms of OLP. The genes such as TNF, CARD11, MRP genes and CCND1 may be potential therapeutic target genes in OLP. MiR-548a-2 and miR-302 may play important roles in OLP development.



http://ift.tt/2lftnO5

Is there a role for regenerative medicine in chronic rhinosinusitis with nasal polyps?

Fabiana C.P. Valera, Leandra M. Endam, Badr Ibrahim, Emmanuelle Brochiero, Martin Y. Desrosiers
Braz J Otorhinolaryngol 2017;83:1-2

Resumo - Texto Completo - PDF

http://ift.tt/2l5Fk8j

Immediate effects of an anchor system on the stability limit of individuals with chronic dizziness of peripheral vestibular origin

Almir Resende Coelho, Ana Paula do Rego Andre, Júlia Licursi Lambertti Perobelli, Lilian Shizuka Sonobe, Daniela Cristina Carvalho de Abreu
Braz J Otorhinolaryngol 2017;83:3-9

Resumo - Texto Completo - PDF

http://ift.tt/2kSuKWS

Mode of recording and modulation frequency effects of auditory steady state response thresholds

Bahram Jalaei, Moslem Shaabani, Mohd Normani Zakaria
Braz J Otorhinolaryngol 2017;83:10-5

Resumo - Texto Completo - PDF

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Hearing performance as a predictor of postural recovery in cochlear implant users

Mario Edvin Greters, Roseli Saraiva Moreira Bittar, Signe Schuster Grasel, Jeanne Oiticica, Ricardo Ferreira Bento
Braz J Otorhinolaryngol 2017;83:16-22

Resumo - Texto Completo - PDF

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Clinical outcome and patient satisfaction using biodegradable (NasoPore) and non‐biodegradable packing, a double‐blind, prospective, randomized study

Pawel Krzysztof Burduk, Malgorzata Wierzchowska, Blazej Grześkowiak, Wojciech Kaźmierczak, Katarzyna Wawrzyniak
Braz J Otorhinolaryngol 2017;83:23-8

Resumo - Texto Completo - PDF

http://ift.tt/2l5GQao

Prevalence of dizziness in the population of Minas Gerais, Brazil, and its association with demographic and socioeconomic characteristics and health status

Tiago Ferreira Martins, Patrícia Cotta Mancini, Luiza de Marilac de Souza, Juliana Nunes Santos
Braz J Otorhinolaryngol 2017;83:29-37

Resumo - Texto Completo - PDF

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Human papillomavirus in oral cavity and oropharynx carcinomas in the central region of Brazil

Guilherme Petito, Megmar Aparecida dos Santos Carneiro, Sílvia Helena de Rabello Santos, Antonio Marcio Teodoro Cordeiro Silva, Rita de Cassia Alencar, Antonio Paulo Gontijo, Vera Aparecida Saddi
Braz J Otorhinolaryngol 2017;83:38-44

Resumo - Texto Completo - PDF

http://ift.tt/2l5ECbc

A possible cause of epistaxis: increased masked hypertension prevalence in patients with epistaxis

Baran Acar, Bunyamin Yavuz, Erdem Yıldız, Selcuk Ozkan, Mehmet Ayturk, Omer Sen, Onur Sinan Deveci
Braz J Otorhinolaryngol 2017;83:45-9

Resumo - Texto Completo - PDF

http://ift.tt/2kSylEw

Assessment of Eustachian tube function in patients with tympanic membrane retraction and in normal subjects

Inesângela Canali, Letícia Petersen Schmidt Rosito, Bruno Siliprandi, Cláudia Giugno, Sady Selaimen da Costa
Braz J Otorhinolaryngol 2017;83:50-8

Resumo - Texto Completo - PDF

http://ift.tt/2l5EfNM

Effectiveness of caudal septal extension graft application in endonasal septoplasty

Yunus Karadavut, Ilker Akyıldız, Hatice Karadaş, Aykut Erdem Dinç, Gökçe Tulacı, Eren Tastan
Braz J Otorhinolaryngol 2017;83:59-65

Resumo - Texto Completo - PDF

http://ift.tt/2kSBioJ

Distinct characteristics of nasal polyps with and without eosinophilia

Changzhi Sun, Hong Ouyang, Renzhong Luo
Braz J Otorhinolaryngol 2017;83:66-72

Resumo - Texto Completo - PDF

http://ift.tt/2l5Lndc

Sonographic scoring of solid thyroid nodules: effects of nodule size and suspicious cervical lymph node

Ozlem Unsal, Meltem Akpinar, Bilge Turk, Irmak Ucak, Alper Ozel, Semra Kayaoglu, Berna Uslu Coskun
Braz J Otorhinolaryngol 2017;83:73-9

Resumo - Texto Completo - PDF

http://ift.tt/2kSBbcF

Association of the C47T polymorphism in superoxide dismutase gene 2 with noise‐induced hearing loss: a meta‐analysis

Jing Wang, Jun Li, Kang Peng, Zi-Ying Fu, Jia Tang, Ming-Jian Yang, Qi-Cai Chen
Braz J Otorhinolaryngol 2017;83:80-7

Resumo - Texto Completo - PDF

http://ift.tt/2l5Hvc0

The role of Onodi cells in sphenoiditis: results of multiplanar reconstruction of computed tomography scanning

Mehmet Senturk, Ibrahim Guler, Isa Azgin, Engin Umut Sakarya, Gultekin Ovet, Necat Alatas, Ismet Tolu, Omer Erdur
Braz J Otorhinolaryngol 2017;83:88-93

Resumo - Texto Completo - PDF

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Which features of advanced head and neck basal cell carcinoma are associated with perineural invasion?

André Bandiera de Oliveira Santos, Natalia Martins Magacho de Andrade, Lenine Garcia Brandão, Claudio Roberto Cernea
Braz J Otorhinolaryngol 2017;83:94-7

Resumo - Texto Completo - PDF

http://ift.tt/2l5FyMM

Obstructive sleep apnea and oral language disorders

Camila de Castro Corrêa, Maria Gabriela Cavalheiro, Luciana Paula Maximino, Silke Anna Theresa Weber
Braz J Otorhinolaryngol 2017;83:98-104

Resumo - Texto Completo - PDF

http://ift.tt/2kSqxTc

Sinusitis in patients undergoing allogeneic bone marrow transplantation – a review

Joanna Ewa Drozd‐Sokolowska, Jacek Sokolowski, Wieslaw Wiktor‐Jedrzejczak, Kazimierz Niemczyk
Braz J Otorhinolaryngol 2017;83:105-11

Resumo - Texto Completo - PDF

http://ift.tt/2l5Lqp8

Speech auditory brainstem response (speech ABR) in the differential diagnosis of scholastic difficulties

Milaine Dominici Sanfins, Letícia Reis Borges, Thalita Ubiali, Maria Francisca Colella-Santos
Braz J Otorhinolaryngol 2017;83:112-6

Resumo - Texto Completo - PDF

http://ift.tt/2kSqwyC

Bilateral oropharyngeal hairy polyps: a rare cause of dyspnea in newborns

Rasim Yilmazer, Burak Kersin, Erkan Soylu, Gokhan Altin, Asli Cakir, Fahrettin Yilmaz
Braz J Otorhinolaryngol 2017;83:117-8

Resumo - Texto Completo - PDF

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Betel nut chewing, oral premalignant lesions, and the oral microbiome

by Brenda Y. Hernandez, Xuemei Zhu, Marc T. Goodman, Robert Gatewood, Paul Mendiola, Katrina Quinata, Yvette C. Paulino

Oral cancers are attributed to a number of causal agents including tobacco, alcohol, human papillomavirus (HPV), and areca (betel) nut. Although betel nut chewing has been established as an independent cause of oral cancer, the mechanisms of carcinogenesis are poorly understood. An investigation was undertaken to evaluate the influence of betel nut chewing on the oral microbiome and oral premalignant lesions. Study participants were recruited from a dental clinic in Guam. Structured interviews and oral examinations were performed. Oral swabbing and saliva samples were evaluated by 454 pyrosequencing of the V3- V5 region of the 16S rRNA bacterial gene and genotyped for HPV. One hundred twenty-two adults were enrolled including 64 current betel nut chewers, 37 former chewers, and 21 with no history of betel nut use. Oral premalignant lesions, including leukoplakia and submucous fibrosis, were observed in 10 chewers. Within-sample bacterial diversity was significantly lower in long-term (≥10 years) chewers vs. never chewers and in current chewers with oral lesions vs. individuals without lesions. Between-sample bacterial diversity based on Unifrac distances significantly differed by chewing status and oral lesion status. Current chewers had significantly elevated levels of Streptococcus infantis and higher and lower levels of distinct taxa of the Actinomyces and Streptococcus genera. Long-term chewers had reduced levels of Parascardovia and Streptococcus. Chewers with oral lesions had significantly elevated levels of Oribacterium, Actinomyces, and Streptococcus, including Streptococcus anginosus. In multivariate analyses, controlling for smoking, oral HPV, S.anginosus, and S. infantis levels, current betel nut chewing remained the only predictor of oral premalignant lesions. Our study provides evidence that betel nut chewing alters the oral bacterial microbiome including that of chewers who develop oral premalignant lesions. Nonetheless, whether microbial changes are involved in betel nut-induced oral carcinogenesis is only speculative. Further research is needed to discern the clinical significance of an altered oral microbiome and the mechanisms of oral cancer development in betel nut chewers.

http://ift.tt/2lGyMku

An avoidable cause of thymoglobulin anaphylaxis

Thymoglobulin® (anti-thymocyte globulin [rabbit]) is a purified pasteurised, gamma immune globulin obtained by immunisation of rabbits with human thymocytes. Anaphylactic allergic reactions to a first injectio...

http://ift.tt/2lfl6Kn

Low prevalence of human papillomavirus in head and neck squamous cell carcinoma in the northwest region of the Philippines

by Pia Marie Albano, Dana Holzinger, Christianne Salvador, Jose Orosa III, Sheryl Racelis, Modesty Leaño, Danilo Sanchez Jr, Lara Mae Angeles, Gordana Halec, Markus Schmitt, John Donnie Ramos, Michael Pawlita

Background

Geographic heterogeneity of human papillomavirus (HPV) involvement in head and neck squamous cell carcinoma (HNSCC) has been observed over the last few years. This trend has not been evaluated in the Philippines. Hence, this study aims to provide for the first time a data on the prevalence of HPV in HNSCC in the northwestern region of the Philippines.

Methods

Two hundred one (201) biopsy samples (179 formalin fixed paraffin embedded and 22 fresh frozen) from 163 Filipino HNSCC cases (oral cavity = 88; larynx = 60; oropharynx = 15) diagnosed between 2003 to 2013 were initially included in this study. HPV DNA was detected by two methods: (1) BSGP5+/6+-PCR/ multiplex human papillomavirus genotyping and (2) TaqMan probes-based real-time qPCR. Presence of HPV type-specific transcripts were also analyzed by reverse transcription-PCR with subsequent hybridization to oligonucleotide probes coupled to Luminex beads. Co-amplification of the β-globin and ubiquitin C genes served as internal positive controls for DNA and RNA analyses, respectively.

Results and conclusions

Of the 163, 82 (50.3%) cases had at least one tissue sample that was valid for molecular analysis. Only two of the DNA valid cases (2.4%) were HPV DNA-positive (HPV11 and HPV33). All HPV mRNA assays rendered negative results except for HPV11 transcripts. Results of this study may indicate that there is probably very low prevalence of HPV-associated HNSCC among Filipino adults living in a rural region of the Philippines. This study could serve as a benchmark for designing follow-up studies that would assess possible changes in trends of HNSCC among Filipinos in different ethnic regions of the country, especially urban areas in which the population is expected to adapt Western style sexual behavior. A prospective sampling of fresh frozen tissue is also highly recommended to ensure better molecular analyses.

http://ift.tt/2lQ9zS8

Tropomyosin-1 acts as a potential tumor suppressor in human oral squamous cell carcinoma

by Hao Pan, Liqun Gu, Binjie Liu, Yiping Li, Yuehong Wang, Xinna Bai, Long Li, Baisheng Wang, Qian Peng, Zhigang Yao, Zhangui Tang

It is widely accepted that oral squamous cell carcinoma (OSCC) is a major contributor to the incidence and mortality of neck and head cancer. Tropomyosin-1 (TPM1), which is expressed at a low level, has been considered a prominent tumor-suppressing gene in a variety of solid tumors, although the precise mechanism of the TPM1 gene in OSCC progression remains unknown. We found that TPM1 expression levels decreased in OSCC patients and OSCC cell lines. The overall and cancer-specific survival of patients who exhibited low TPM1 levels were inferior to those of patients who had high TPM1 levels. It was also found that OSCC patients who suffered from disease stageⅠ-Ⅱ were more likely to have an up-regulated TPM1 expression level, and OSCC patients with lymph node metastasis had a higher probability of exhibiting reduced TPM1 expression. We show that overexpression of TPM1 can promote cell apoptosis and inhibit migration. Our results suggest that TPM1 can suppress tumors in OSCC, and the TPM1 expression level is related to OSCC patient prognosis.

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Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma

by Xiao-lei Gao, Jia-shun Wu, Min-xin Cao, Shi-yu Gao, Xiao Cen, Ya-ping Jiang, Sha-sha Wang, Ya-jie Tang, Qian-ming Chen, Xin-hua Liang, Yaling Tang

Collective invasion of cells plays a fundamental role in tissue growth, wound healing, immune response and cancer metastasis. This paper aimed to investigate cytokeratin-14 (CK14) expression and analyze its association with collective invasion in the invasive front of salivary adenoid cystic carcinoma (SACC) to uncover the role of collective invasion in SACC. Here, in the clinical data of 121 patients with SACC, the positive expression of CK14 was observed in 35/121(28.93%) of the invasive front of SACC. CK14 expression in the invasive front, local regional recurrence and distant metastasis were independent and significant prognostic factors in SACC patients. Then, we found that in an ex vivo 3D culture assay, CK14 siRNA receded the collective invasion, and in 2D monolayer culture, CK14 overexpression induced a collective SACC cell migration. These data indicated that the presence of characterized CK14+ cells in the invasive front of SACC promoted collective cell invasion of SACC and may be a biomarker of SACC with a worse prognosis.

http://ift.tt/2kZ03fh

Parenclitic Network Analysis of Methylation Data for Cancer Identification

by Alexander Karsakov, Thomas Bartlett, Artem Ryblov, Iosif Meyerov, Mikhail Ivanchenko, Alexey Zaikin

We make use of ideas from the theory of complex networks to implement a machine learning classification of human DNA methylation data, that carry signatures of cancer development. The data were obtained from patients with various kinds of cancers and represented as parenclictic networks, wherein nodes correspond to genes, and edges are weighted according to pairwise variation from control group subjects. We demonstrate that for the 10 types of cancer under study, it is possible to obtain a high performance of binary classification between cancer-positive and negative samples based on network measures. Remarkably, an accuracy as high as 93−99% is achieved with only 12 network topology indices, in a dramatic reduction of complexity from the original 15295 gene methylation levels. Moreover, it was found that the parenclictic networks are scale-free in cancer-negative subjects, and deviate from the power-law node degree distribution in cancer. The node centrality ranking and arising modular structure could provide insights into the systems biology of cancer.

http://ift.tt/2iLewhu

Macrolide Antibiotics Exhibit Cytotoxic Effect under Amino Acid-Depleted Culture Condition by Blocking Autophagy Flux in Head and Neck Squamous Cell Carcinoma Cell Lines

by Kazuhiro Hirasawa, Shota Moriya, Kana Miyahara, Hiromi Kazama, Ayako Hirota, Jun Takemura, Akihisa Abe, Masato Inazu, Masaki Hiramoto, Kiyoaki Tsukahara, Keisuke Miyazawa

Autophagy, a self-digestive system for cytoplasmic components, is required to maintain the amino acid pool for cellular homeostasis. We previously reported that the macrolide antibiotics azithromycin (AZM) and clarithromycin (CAM) have an inhibitory effect on autophagy flux, and they potently enhance the cytocidal effect of various anticancer reagents in vitro. This suggests that macrolide antibiotics can be used as an adjuvant for cancer chemotherapy. Since cancer cells require a larger metabolic demand than normal cells because of their exuberant growth, upregulated autophagy in tumor cells has now become the target for cancer therapy. In the present study, we examined whether macrolides exhibit cytotoxic effect under an amino acid-starving condition in head and neck squamous cancer cell lines such as CAL 27 and Detroit 562 as models of solid tumors with an upregulated autophagy in the central region owing to hypovascularity. AZM and CAM induced cell death under the amino acid-depleted (AAD) culture condition in these cell lines along with CHOP upregulation, although they showed no cytotoxicity under the complete culture medium. CHOP knockdown by siRNA in the CAL 27 cells significantly suppressed macrolide-induced cell death under the AAD culture condition. CHOP^-/- murine embryonic fibroblast (MEF) cell lines also attenuated AZM-induced cell death compared with CHOP^+/+ MEF cell lines. Using a tet-off atg5 MEF cell line, knockout of atg5, an essential gene for autophagy, also induced cell death and CHOP in the AAD culture medium but not in the complete culture medium. This suggest that macrolide-induced cell death via CHOP induction is dependent on autophagy inhibition. The cytotoxicity of macrolide with CHOP induction was completely cancelled by the addition of amino acids in the culture medium, indicating that the cytotoxicity is due to the insufficient amino acid pool. These data suggest the possibility of using macrolides for "tumor-starving therapy".

http://ift.tt/2gH8GYj

Diagnostic Value and Interreader Agreement of the Pancreaticolienal Gap in Pancreatic Cancer on MDCT

by Khoschy Schawkat, Wolfgang Kühn, Daniel Inderbitzin, Beat Gloor, Johannes T. Heverhagen, Val Murray Runge, Andreas Christe

Objective

The aim of this retrospective study was to evaluate the diagnostic value and measure interreader agreement of the pancreaticolienal gap (PLG) in the assessment of imaging features of pancreatic carcinoma (PC) on contrast-enhanced multi-detector computed tomography (CE-MDCT).

Materials and Methods

CE-MDCT studies in the portal venous phase were retrospectively reviewed for 66 patients with PC. The age- and gender-matched control group comprised 103 healthy individuals. Three radiologists with different levels of experience independently measured the PLG (the minimum distance of the pancreatic tail to the nearest border of the spleen) in the axial plane. The interreader agreement of the PLG and the receiver operating characteristic (ROC) curve was used to calculate the accuracy of the technique.

Results

While the control group (n = 103) showed a median PLG of 3 mm (Range: 0 – 39mm) the PC patients had a significantly larger PLG of 15mm (Range: 0 – 53mm)(p 12 mm for PC, with a sensitivity of 58.2% (95% CI = 45.5–70.1), specificity of 84.0% (95% CI = 75.6–90.4) and an area under the ROC curve of 0.714 (95% CI = 0.641 to 0.780). The mean interreader agreement showed correlation coefficient r of 0.9159. The extent of the PLG did not correlate with tumor stage but did correlate with pancreatic density (fatty involution) and age, the density decreased by 4.1 HU and the PLG increased by 0.8 mm within every 10 y.

Conclusion

The significant interreader agreement supports the use of the PLG as a characterizing feature of pancreatic cancer independent of the tumor stage on an axial plane. The increase in the PLG with age may represent physiological atrophy of the pancreatic tail.

http://ift.tt/2gbAEyN

Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer

by Noah D. Peyser, Kelsey Pendleton, William E. Gooding, Vivian W. Y. Lui, Daniel E. Johnson, Jennifer R. Grandis

Background

Hyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA).

Methods and Findings

Mutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression. mRNA expression levels of 1279 genes were found to be associated with pSTAT3(705) expression. Association of pSTAT3(Y705) expression with caspase-8 mRNA expression was validated by immunoblot analysis in HNSCC cells. Mutation, promoter hypermethylation, and copy number alteration of any gene were not significantly associated with increased pSTAT3(Y705) protein expression.

Conclusions

These cumulative results suggest that unbiased approaches may be useful in identifying the molecular underpinnings of oncogenic signaling, including STAT3 activation, in HNSCC. Larger datasets will likely be necessary to elucidate signaling consequences of infrequent alterations.

http://ift.tt/2fZVQ7L

Tumor-Specific D-Dimer Concentration Ranges and Influencing Factors: A Cross-Sectional Study

by Jing Yu, Dongqing Li, Dansheng Lei, Feng Yuan, Feng Pei, Huifeng Zhang, Anming Yu, Kun Wang, Hu Chen, Liang Chen, Xianglei Wu, Xianli Tong, Yefu Wang

D-dimer level in cancer patients is associated with risk of venous thromboembolism and deep venous thrombosis. Most cancer patients have "abnormal" D-dimer levels based on the current normal reference range. To investigate tumor-specific D-dimer reference range, we compared D-dimer levels for nine different tumour types with healthy controls by using simultaneous quantile regression and constructing a median, 5th percentile, and 95th percentile model of normal tumour D-dimer concentration. Associations with tumour primary site, stage, pathological type, and treatment were also explored. Additionally, 190 patients were tracked to reveal the relevance of initial D-dimer levels to cancer prognosis. D-dimer ranges (median, 5th, 95th) in various cancers (mg/L) were: liver 1.12, 0.27, 5.25; pancreatic 0.96, 0.23, 4.81; breast 0.44, 0.2, 2.17; gastric 0.65, 0.22, 5.03; colorectal 0.73, 0.22, 4.45; lung 0.7, 0.25, 4.0; gynaecological 0.61, 0.22, 3.98; oesophageal 0.23, 0.7, 3.45; and head and neck 0.22, 0.44, 2.19. All were significantly higher than that of healthy controls (0.18, 0.07, 0.57). D-dimer peaked 1–2 days postoperatively but had decreased to the normal range by 1 week. Additionally, cancer patients with high initial D-dimer were shown a tendency of poor prognosis in survival rate. In conclusion, D-dimer levels in cancer depend on patient age, tumour primary site, and tumour stage. Thrombosis prevention is necessary if D-dimer has not decreased to the tumor-specific baseline a week after surgery.

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Glucose Metabolism and Its Complicated Relationship with Tumor Growth and Perfusion in Head and Neck Squamous Cell Carcinoma

by Noriyuki Fujima, Tomohiro Sakashita, Akihiro Homma, Kenji Hirata, Tohru Shiga, Kohsuke Kudo, Hiroki Shirato

Objective

To determine the relationship between tumor glucose metabolism and tumor blood flow (TBF) in head and neck squamous cell carcinoma (HNSCC).

Methods

We retrospectively analyzed 57 HNSCC patients. Tumor glucose metabolism was assessed by maximum and mean standardized uptake values (SUVmax and SUVmean) obtained by ¹⁸F-fluorodeoxyglucose positron-emission tomography. TBF values were obtained by arterial spin labeling with 3-tesla MRI. The correlations between both SUVs and TBF were assessed in the total series and among patients divided by T-stage (T1–T3 and T4 groups) and tumor location (pharynx/oral cavity and sinonasal cavity groups). Pearson's correlation coefficients were calculated for significant correlations.

Results

Significant correlations were detected: a negative correlation in the advanced T-stage group (TBF and SUV max: r, −0.61, SUVmean: r, −0.62), a positive correlation in the non-advanced T-stage pharynx/oral cavity group (TBF and SUVmax: r, 0.70, SUVmean: r, 0.73), a negative correlation in the advanced T-stage pharynx/oral cavity group (TBF and SUVmax: r, −0.62, SUVmean: r, −0.65), and a negative correlation in the advanced T-stage sinonasal cavity group (TBF and SUVmax: r, −0.61, SUVmean: r, −0.65).

Conclusion

Significant correlations between glucose uptake and TBF in HNSCC were revealed by the division of T-stage and tumor location.

http://ift.tt/2ej2ppu

mTOR Inhibition and Cardiovascular Diseases: Cardiac Hypertrophy.

Left ventricular hypertrophy (LVH) is highly prevalent in kidney transplant recipients, and is associated with poor clinical outcome. Immunosuppressive agents might affect LVH behavior after kidney transplantation. This review is an appraisal of available data regarding LVH in renal transplantation and especially of studies that evaluated LVH response to treatment. In particular, the role of mammalian target of rapamycin inhibitors adopted as immunosuppressive agents in kidney transplantation is reviewed in the light of recent studies that have shown LVH regression induced by this class of medications in kidney transplant recipients with posttransplant cardiomyopathy. Larger randomized controlled trials are warranted in order to confirm these findings and to ascertain the impact of such LVH regression on hard endpoints in kidney transplant recipients with posttransplant cardiomyopathy. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2mihdoC

mTOR Inhibition & Cardiovascular Diseases: Dyslipidemia and Atherosclerosis.

Inhibitors of the mechanistic target of rapamycin (mTOR) have unique anti-atherosclerotic effects such as depletion of plaque macrophages, induction of autophagy and activation of cholesterol efflux. However, a common side effect of their use is dyslipidemia, a well-known risk factor for atherosclerosis. Indeed, mTOR inhibitors prevent lipid storage, increase LDL cholesterol levels and activate lipolysis. Although the net effect of mTOR inhibition seems favorable, the use of cholesterol lowering drugs to manage dyslipidemia remains the most recommended strategy. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2lxcnpp

Mammalian Target of Rapamycin Inhibition & Clinical Transplantation: Liver.

The evidence base concerning use of mammalian target of rapamycin (mTOR) inhibitor therapy after liver transplantation is evolving rapidly, clarifying their benefits and disadvantages in different clinical scenarios. The H2304 trial showed that starting everolimus at 1 month posttransplant, with reduced tacrolimus, achieves a sustained improvement in renal function versus standard tacrolimus-based therapy, with at least equivalent immunosuppressive efficacy. Randomized studies evaluating early discontinuation of CNI therapy after introduction of an mTOR inhibitor consistently demonstrated a substantial improvement in renal function versus standard CNI therapy. However, concomitant mycophenolic acid is advisable to avoid an increase in mild biopsy-proven acute rejection, and induction with an interleukin-2 receptor antagonist may also be helpful. High-quality robust data regarding prevention of posttransplant malignancies under mTOR inhibitors is lacking in liver transplantation, although there are some indications of benefit. In maintenance patients, robust data are limited regarding mTOR inhibitor initiation in response to deteriorating renal function or other indications but late conversion (>1 year) appears ineffective. Rates of mTOR inhibitor discontinuation due to adverse events are high, affecting at least a quarter of patients. In conclusion, the evidence base for use of mTOR inhibitors early posttransplant to support CNI reduction now convincingly demonstrates a renal advantage, but adequate adjunctive immunosuppression is essential to preserve efficacy. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2miDQJJ

Disparities in waitlist and posttransplantation outcomes in liver transplant registrants and recipients 18-24 years old: analysis of the UNOS database.

Background: We evaluated liver transplantation waitlist and posttransplantation outcomes in 18-24 year olds compared to both younger (0-17 year old) and older (25-34 year old) registrants and recipients. Methods: Utilizing national data from the United Network for Organ Sharing, competing risk, Cox regression and Kaplan-Meier analyses were performed on first-time liver transplant registrants (n=13,979) and recipients (n=8,718) ages 0-34 years old between 2002 to 2015. Results: Among nonStatus 1A registrants, both 0-17 and 25-34 year olds were less likely to experience drop-out from the waiting list compared to 18-24 year olds (adjusted hazard ratio [AHR] 0-5 year olds=0.36, 6-11=0.29, 12-17=0.48, 18-24=1.00, 25-34=0.82). Although there was no difference in risk of graft failure across all age groups, both younger and older age groups had significantly lower risk of posttransplant mortality compared to 18-24 year olds (AHR for 0-5 year olds=0.53, 6-11=0.48, 12-17=0.70, 18-24=1.00, 25-34=0.77). This may be related to lower likelihood of re-transplantation after graft failure in 18-24 year olds. Conclusions: This national registry study demonstrates for the first time poorer waitlist and postliver transplant outcomes in young adults ages 18-24 years at the time of listing and transplantation compared to older and younger age groups. Given the potential survival benefit in transplanting young adults and the shortage of solid organs for transplant, future studies are critical to identify and target modifiable risk factors to improve waitlist and long-term posttransplant outcomes in 18-24 year old registrants and recipients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Peritransplant energy changes and their correlation to outcome after human liver transplantation.

Background: The ongoing shortage of donor livers for transplantation and the increased use of marginal livers necessitate the development of accurate pretransplant tests of viability. Considering the importance energy status during transplantation, we aimed to correlate peritransplant energy cofactors to posttransplant outcome and subsequently model this in an ex vivo setting. Methods: Sequential biopsies were taken from 19 donor livers postpreservation, as well as 30 min after portal venous (PVR) and hepatic arterial reperfusion (HAR) and analyzed by LC-MS for energetic cofactors (ATP/ADP/AMP, NADH/NAD+, NADPH/NADP+, FAD+, GSSG/GSH). Energy status was correlated to posttransplant outcome. In addition, 4 discarded human DCD livers were subjected to ex vivo reperfusion, modeling reperfusion injury and were similarly analyzed for energetic cofactors. Results: A rapid shift towards higher energy adenine nucleotides was observed following clinical reperfusion, with a 2.45-, 3.17- and 2.12-fold increase in ATP:ADP, ATP:AMP and energy charge (EC) after PVR, respectively. Seven of the 19 grafts developed early allograft dysfunction (EAD). Correlation with peritransplant cofactors revealed a significant difference in EC between EAD and normal functioning grafts (0.09 vs. 0.31, P

http://ift.tt/2milg4m

Strategies to Obtain Diverse and Specific Human Monoclonal Antibodies from Transgenic Animals.

Techniques to obtain large quantities of antigen-specific monoclonal antibodies, mAbs, were first established in the 1970s when Georges Kohler and Cesar Milstein immortalized antibody-producing mouse B-lymphocytes by fusion with myeloma cells ( http://ift.tt/1P0TTD6). Combined with the expression of human antibodies in transgenic animals, this technique allowed upon immunization the generation of highly specific fully human mAbs for therapeutic applications. Apart from being extremely beneficial, mAbs are a huge success commercially. However, despite cell fusion generating many useful mAbs questions have been asked about which types of cells are prone to fuse and whether other methods may identify a wider range of binders. The discovery that expression libraries, using E.coli or yeast, produced different specificities was intriguing and more recently Next Generation Sequencing has identified wide-ranging usage with highly diverse and unique repertoires. Another strategy is the combination of flow cytometry sorting of antigen-binding B-lymphocytes and single cell RT-PCR followed by re-expression, which has identified many high affinity mAbs. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2miOQXp

mTOR Inhibition & Clinical Transplantation: Pancreas & Islet.

This brief overview discusses the beneficial and deleterious effects of mTOR inhibitors on beta-cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from >80% to

http://ift.tt/2lxbKfr

Expanding the Donor Pool Through Intensive Care to Facilitate Organ Donation: Results of A Spanish Multicenter Study.

Background: Intensive Care to facilitate Organ Donation (ICOD) may help to increase the donor pool. We describe the Spanish experience with ICOD. Methods: ACCORD-Spain consisted of an audit of the donation pathway from patients dead as a result of a devastating brain injury (possible donors) in 68 hospitals during 11/1/2014-4/30/2015. We focused on possible donors whose family was interviewed to discuss organ donation once intensive care with a therapeutic purpose was deemed futile and brain death (BD) was a likely outcome. Results: Of the 1970 possible donors in ACCORD-Spain, in 257 the family was interviewed once the decision had been made not to intubate/ventilate (n=105), with the patient under intubation/ventilation outside of the ICU (n=59), or with the patient intubated/ventilated within the ICU (n=93). Consent to ICOD was obtained in 174 cases. Consent was higher when the donor coordinator participated in the interview [OR 2.32; 95%CI 1.33-4.11; p=0.003]. 131 patients developed BD, of whom 117 transitioned to actual donation after BD. Of the 35 patients who did not develop BD, 2 transitioned to actual donation after circulatory death. 16 patients subject to ICOD were finally medically unsuitable organ donors. ICOD contributed to 24% of the 491 actual donors registered in ACCORD-Spain. Conclusions: Despite the complexity of the interview, the majority of families consent to ICOD. Estimating the probability of BD and assessing medical suitability are additional challenges of the practice. ICOD represents a clear opportunity to increase the donor pool and ensures organ donation is posed at every end-of-life care pathway. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Clinical-scale Rapid Autologous BK-virus Specific T Cell Line generation from Kidney Transplant Recipients with Active Viremia for Adoptive Immunotherapy.

Background: Polyomavirus-associated nephropathy (PVAN) following BK virus reactivation in kidney transplant recipients (KTR) can compromise graft survival. Lowering immunosuppression is the only established approach to prevent or treat PVAN but nonspecifically increasing host immune competence also augments rejection risk. Ex vivo T cell stimulation/expansion offers the possibility to generate BK-specific T cell lines for adoptive immunotherapy. The objective of this study was to develop and characterize a clinical scale protocol to generate BK-specific T cell lines from viremic KTR. Methods: Peripheral blood mononuclear cells from healthy controls (HC) and viremic KTR were stimulated using BK-virus peptide libraries loaded or not on monocytes-derived dendritic cells. Cell counts, flow cytometry and next-generation sequencing were used to assess T cell expansion, differentiation and clonal diversity. Enzyme-linked immunospots, cytotoxicity assays as well as adoptive transfer in NOD/SCID/IL2R[gamma]null (NSG) mice were used to assess for pathogen-specificity and evidence of nonspecific alloreactivity. Results: T cell lines from KTR and HC showed similar characteristics, implying that ongoing immunosuppression and chronic virus exposure do not compromise the differentiation, specificity or clonal diversity of T cell lines following ex vivo production. Using antigen-loaded dendritic cells improved T cell expansion, favored central memory T cell differentiation. The T cell lines were antigen-specific and showed no nonspecific alloreactivity in vitro and in vivo. Conclusions: Using a rapid, clinically-compliant culture system, we show that autologous BK virus-specific T cell lines can be reliably generated from viremic KTR. Our results pave the way for the treatment or prevention of PVAN with adoptive immunotherapy. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Effect of Calcineurin Inhibitor-Free Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate after Heart Transplantation.

Background: Albuminuria in maintenance heart transplantation (HTx) is associated with poor renal response when switching to a calcineurin inhibitor (CNI)-lowered or free immunosuppressive regimen using everolimus (EVR), but the significance of albuminuria associated with EVR treatment after early CNI withdrawal in de novo HTx is unknown. Methods: We tested if glomerular filtration rate (mGFR, measured by CrEDTA clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the SCHEDULE trial, where de novo HTx patients (n=115) were randomized to EVR with complete CNI elimination 7-11 weeks post-HTx or standard CNI immunosuppression. Results: In 66 patients UACR measures were available at 1 year. In 7 patients in the EVR group a CNI was reintroduced within 12 months. Median mGFR was significantly higher in the EVR group both 1 and 3 years post-HTx (p=0.0004, p=0.03). Median UACR at 1 year was significantly higher in the EVR group (p=0.002). There was no correlation between log(UACR) at 1 year and mGFR at 1 or 3 years (r=-0.01, p=0.9; r=0.15, p=0.26), and in the EVR group nor between log(UACR) at 1 year and change in mGFR ([DELTA]1-3 years) (r=0.27, p=0.14). Excluding patients in the EVR group in whom a CNI was reintroduced did not significantly change the results. Conclusions: The effects of EVR with early CNI withdrawal after HTx on albuminuria and renal function appear dissociated; hence the clinical significance of albuminuria in this setting is uncertain and should not necessarily rule out EVR-based immunosuppression. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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mTOR Inhibition & Clinical Transplantation: Kidney.

No abstract available

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Alveolar Macrophages in Allergic Asthma: the Forgotten Cell Awakes

Abstract

Purpose of Review

The role of alveolar macrophages in innate immune responses has long been appreciated. Here, we review recent studies evaluating the participation of these cells in allergic inflammation.

Recent Findings

Immediately after allergen exposure, monocytes are rapidly recruited from the bloodstream and serve to promote acute inflammation. By contrast, resident alveolar macrophages play a predominantly suppressive role in an effort to restore homeostasis. As inflammation becomes established after repeated exposures, alveolar macrophages can polarize across a continuum of activation phenotypes, losing their suppressive functions and gaining pathogenic functions.

Summary

Future research should focus on the diverse roles of monocytes/macrophages during various types and phases of allergic inflammation. These properties could lead us to new therapeutic opportunities.

http://ift.tt/2lwWLly

Phenotype-Driven Therapeutics in Severe Asthma

Abstract

Inhaled corticosteroids are the mainstay of asthma treatment using a step-up approach with incremental dosing and additional controller medications in order to achieve symptom control and prevent exacerbations. While most patients respond well to this treatment approach, some patients remain refractory despite high doses of inhaled corticosteroids and a long-acting β-agonist. The problem lies in the heterogeneity of severe asthma, which is further supported by the emergence of severe asthma phenotypes. This heterogeneity contributes to the variability in treatment response. Randomized controlled trials involving add-on therapies in poorly controlled asthma have challenged the idea of a "one size fits all" approach targeting specific phenotypes in their subject selection. This review discusses severe asthma phenotypes from unbiased clustering approaches and the most recent scientific evidence on novel treatments to provide a guide in personalizing severe asthma treatment.

http://ift.tt/2mikS5N

Contemporary Use of Corticosteroids in Rhinology

Abstract

Purpose of Review

Exogenously administered corticosteroids are widely used today in the field of rhinology. Allergic rhinitis (AR), non-allergic rhinitis (NAR), acute rhinosinusitis (ARS), chronic rhinosinusitis with (CRSwNP) and without (CRSsNP) nasal polyps, and autoimmune disorders with nasal manifestations are common diseases treated effectively with intranasal and oral glucocorticoids. We focus on physiological pathways, therapeutic benefits, indications, contra-indications, and side effects of glucocorticoid utilization in the treatment of rhinologic disorders such as AR, NAR, ARS, CRSsNP, and CRSwNP.

Recent Findings

Second-generation intranasal steroid (INS) agents have pharmacokinetic characteristics that minimize their systemic bioavailability, resulting in minimum risk for systemic adverse events. Several studies have demonstrated the symptomatic efficacy of both intranasal and oral corticosteroids in ARS. Moreover, intranasal and systemic steroid administration has been repeatedly proven beneficial in the conservative and perioperative management of CRSwNP. For patients with AR, there is no need for oral steroids, with the exception of severe cases, as there is lack of superiority to INS. SCUAD patients challenge currently available treatment schemes, underlining the importance of research in the field.

Summary

Corticosteroids' effectiveness in the treatment of various rhinologic disorders is indisputable. However, their characteristics, and potential side effects, make a clear consensus for utilization difficult.

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Effects of Allergic Sensitization on Antiviral Immunity: Allergen, Virus, and Host Cell Mechanisms

Abstract

Purpose of Review

Multiple clinical and epidemiological studies demonstrate links between allergic sensitization and virus-induced atopic disease exacerbations. This review summarizes the recent findings regarding allergen, viral, and host cellular mechanisms relevant to these observations.

Recent Findings

Recent studies have focused on the molecular pathways and genetic influences involved in allergen-mediated inhibition of innate antiviral immune responses. Multiple tissue and cell types from atopic individuals across the atopy spectrum exhibit deficient interferon responses to a variety of virus infections. Impairment in barrier function, viral RNA and DNA recognition by intracellular sensing molecules, and dysregulation of signaling components are broadly affected by allergic sensitization. Finally, genetic predisposition by numerous nucleotide polymorphisms also impacts immune pathways and potentially contributes to virus-associated atopic disease pathogenesis.

Summary

Allergen-virus interactions in the setting of atopy involve complex tissue and cellular mechanisms. Future studies defining the pathways underlying these interactions could uncover potential therapeutic targets. Available data suggest that therapies tailored to restore specific components of antiviral responses will likely lead to improved clinical outcomes in allergic disease.

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Management of Vascular Injuries During Endoscopic Skull Base Surgery: Current Strategies and Simulation-Based Educational Paradigms

Abstract

Purpose of Review

With fully endoscopic surgery rapidly emerging as a preferred modality of care in the minimally invasive approach to the ventral skull base, surgeons may increasingly encounter critical vascular structures reached via narrow corridors. Internal carotid artery (ICA) injury is a rare but much dreaded complication during endoscopic endonasal approaches (EEA). We reviewed management strategies and outcomes following ICA injury during skull base surgery as well as currently available simulation teaching models.

Recent Findings

Multiple simulation models of ICA injury during EEA have been developed in recent years to prepare surgical trainees for this uncommon intraoperative scenario. These high-flow simulators aim to be reproducible and realistic. Current educational models include a live sheep ICA model, a perfusion-based human cadaveric model, and synthetic skull base models created using selective laser sintering. The live sheep model has allowed further investigation of optimal hemostatic agents and techniques in variable injury patterns, including the crushed muscle patch and endoscopic ligation devices. The perfusion-based human cadaveric model provides the most realistic anatomical scenario for simulation. Emphasized concepts and maneuvers in each of these models include appropriate use of suction, initial packing and hemostasis without causing vessel occlusion, and placement of a muscle patch. Preliminary validation of these simulation models suggests their efficacy in improving psychomotor surgical skills and trainee self-confidence as well as potentially translating to patient outcomes in the post-training incidences of carotid injury.

Summary

It is important for skull base surgeons to be optimally prepared for and adept in the management of ICA injury. Several simulation platforms are highlighted and worthy of incorporation into organized resident and fellow training programs. Further research into hemostatic strategies and biomaterials, and objective validation pertaining to the efficacy of these simulation models are necessary to guide future curriculum development in skull base surgical training.

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Diagnostic values for egg white specific IgE levels with the skin prick test in Turkish children with egg white allergy

Publication date: Available online 23 February 2017
Source:Allergologia et Immunopathologia
Author(s): H.T. Nacaroglu, S.B. Erdem, S. Karaman, D. Dogan, C.S. U.Karkiner, E. T. Kanık, D. Can
BackgroundThe diagnostic values for the skin prick test (SPT) diameters and egg white-specific IgE (EW-sIgE) levels that will allow us to predict the result of the oral food challenge test (OFC) in the diagnosis of egg white allergy vary by the community where the study is carried out.ObjectiveThis study aimed to determine the diagnostic values of SPT and EW-sIgE levels in the diagnosis of egg white allergy.Methods59 patients followed with the diagnosis of egg allergy September 2013 to September 2015 were included in our retrospective cross-sectional study. The patients were investigated in terms of egg and anaphylaxis history or the requirement of the OFC positivity. The demographic, clinical and laboratory findings of the cases were recorded, and they were compared with the patients with the suspected egg allergy but negative OFC (n=47).ResultsIn the study, for all age groups, the value of 5mm in SPT was found to be significant at 96.4% positive predictive value (PPV) and 97.8% specificity and the value of 5.27kU/L for EW-sIgE was found to be significant at 76% PPV and 86.6% specificity for egg white. The diagnostic power of the SPT for egg white (AUC: 72.2%) was determined to be significantly higher compared to the diagnostic power of the EW-sIgE (AUC: 52.3%) (p<0.05).ConclusionAlong with the determination of the diagnostic values of communities, the rapid and accurate diagnosis of the children with a food allergy will be ensured, and the patient follow-up will be made easier.



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Strategies to alter the natural history of childhood asthma

Purpose of review: Asthma exhibits significant heterogeneity in occurrence and severity over the lifespan. Our goal is to discuss recent evidence regarding determinants of the natural history of asthma during childhood, and review the rationale behind and status of major efforts to alter its course. Recent findings: Variations in microbial exposures are associated with risk of allergic disease, and the use of bacterial lysates may be a promising preventive strategy. Exposure to air pollution appears to be particularly damaging in prenatal and early life, and interventions to reduce pollution are feasible and result in clinical benefit. E-cigarette use may have a role in harm reduction for conventional cigarette smokers with asthma, but has undefined short-term and long-term effects that must be clarified. Vitamin D insufficiency over the first several years of life is associated with risk of asthma, and vitamin D supplementation reduces the risk of severe exacerbations. Summary: The identification of risk factors for asthma occurrence, persistence and severity will continue to guide efforts to alter the natural history of the disease. We have reviewed several promising strategies that are currently under investigation. Vitamin D supplementation and air pollution reduction have been shown to be effective strategies and warrant increased investigation and implementation.

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Prenatal exposures and the development of childhood wheezing illnesses

Purpose of review: To critically evaluate and summarize studies published between July 2015 and June 2016 linking prenatal exposures and the onset of childhood wheezing illnesses and to discuss future research directions in this field. Recent findings: The aggregated evidence indicates a consistent detrimental effect of prenatal exposure to parental smoking, outdoor air pollution, and maternal stress on childhood wheezing illnesses. Less consistent evidence suggests an adverse impact of maternal obesity during pregnancy and prenatal exposure to antibiotics on these outcomes. There is insufficient evidence to support an association between in-utero exposure to acetaminophen or prenatal levels of specific nutrients (such as vitamin D, folic acid, or polyunsaturated fatty acids) and childhood wheezing illnesses. Summary: Several common potentially modifiable prenatal exposures appear to be consistently associated with childhood wheezing illnesses (e.g. parental smoking, outdoor air pollution, and maternal stress). However, the effect of many other prenatal exposures on the onset of childhood wheezing illnesses remains unclear. The existing scientific evidence from the past year does not allow us to make any new recommendations on primary prevention measures. Intervention studies will best demonstrate whether changing the prenatal environment can prevent childhood wheezing illnesses and asthma.

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A wide scope of new developments in occupational allergy and clinical immunology

No abstract available

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Editorial introductions

No abstract available

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Progress with Structure–Activity Relationship modelling of occupational chemical respiratory sensitizers

Purpose of review: This appraises currently available computer-based ('in silico') models relating the molecular structure of low molecular weight compounds to their respiratory sensitization hazard. The present review places focus on the two main applications of such structure--activity relationship (SAR) models: hypotheses on disease mechanisms and toxicological prediction. Recent findings: Analyses of the chemical structures of low molecular weight organic compounds known to have caused occupational asthma has led to the development of mechanistic alerts usually based on electrophilic reaction chemistry and protein cross-linking potential. Protein cross-linking potential has also been found to be a consistent feature of chemicals that have caused human cases of hypersensitivity pneumonitis. Stepwise iteration of quantitative SAR (QSAR) modelling has shown appreciable improvements in predictivity for occupational asthma hazard and useful prospects for practical application. A good case has also been made for the potential use of structural alert-based mechanistic SARs in predictive toxicology. Summary: Further understanding of the molecular interactions between chemical respiratory sensitizers and components of human proteins have been obtained from in-vitro and in-silico techniques. There have been developments in both qualitative (mechanistic) SARs and QSARs, which offer potential for use in a predictive algorithm for the toxicological screening of industrial chemicals for respiratory sensitization potential.

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The effect of obesity, weight gain, and weight loss on asthma inception and control

Purpose of review: There is ample and growing evidence that obesity increases the risk of asthma and morbidity from asthma. Here, we review recent clinical evidence supporting a causal link between obesity and asthma, and the mechanisms that may lead to 'obese asthma'. Recent findings: Although in some children obesity and asthma simply co-occur, those with 'obese asthma' have increased asthma severity, lower quality of life, and reduced medication response. Underlying mechanistic pathways may include anatomical changes of the airways such as obstruction and dysanapsis, systemic inflammation, production of adipokines, impaired glucose–insulin metabolism, altered nutrient levels, genetic and epigenetic changes, and alterations in the airway and/or gut microbiome. A few small studies have shown that weight loss interventions may lead to improvements in asthma outcomes, but thus far research on therapeutic interventions for these children has been limited. Summary: Obesity increases the risk of asthma – and worsens asthma severity or control – via multiple mechanisms. 'Obese asthma' is a complex, multifactorial phenotype in children. Obesity and its complications must be managed as part of the treatment of asthma in obese children.

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Social media use for occupational lung disease

Purpose of review: Social media have great impact on all aspects of life throughout the world. The utilization of social media for occupational lung disease, however, has been much more limited. This article summarizes recent literature concerning social media for occupational lung disease and identifies areas for additional use. Recent findings: Social media are used in six relevant areas: information dissemination, peer-to-peer communication, survey research data collection, participatory research and exposome data acquisition, assessing public concerns, and knowledge generation. There are very clear advantages for information dissemination from experts to workers and on a peer-to-peer basis, although variable credibility and accuracy concerns persist. For research, social media have been used for acquiring data posted for nonresearch purposes and for efficiently collecting information specifically for research. The benefits of efficiency, democracy, and very large data sources may counterbalance concerns about inadequate specification of recruitment strategies and limited control over data quality. Summary: The potential benefits of using social media for lung health–workplace interactions are much greater than the very limited current utilization.

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Incorporating technology to advance asthma controller adherence

Purpose of review: Technological innovations, including text messaging, smart phone applications, and electronic monitoring devices, aimed at improving asthma controller adherence are being rapidly introduced both into clinical care and directly marketed to patients. This review analyzes recent clinical trials implementing these interventions, with a focus on their benefits and shortcomings. Recent findings: Poor medication adherence continues to exert significant morbidity on patients with asthma. Objective, real-time measures to monitor adherence can overcome the limitations of prior methods, including self-report and prescription refills. Technological advances, especially those incorporating reminder systems, have demonstrated improved controller adherence. The increased adherence in these trials has not translated into consistent clinical improvement, including reducing hospitalizations, emergency department visits, and asthma exacerbations, possibly secondary to study design and poor inhalation technique. Summary: Novel monitoring and reminder technology can augment patient medication adherence and provide clues to management before escalating therapy. Further studies are needed to investigate the overarching clinical impact of this technology, especially as it grows into routine clinical practice.

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Silicosis and autoimmunity

Purpose of review: Of the various environmental, occupational, and medical substances that cause dysregulation of autoimmunity, the effects and causative mechanisms of silica particles and asbestos fibers are discussed in this review. Recent findings: With respect to silica, many epidemiological studies have shown a significant association between silica exposure and the occurrence of autoimmune diseases. Although the importance of the NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome as the initial immune reaction against silica particles has been identified, the mechanisms involved that lead to various autoimmune diseases in patients exposed to silica remain largely unknown. Silica can activate various immune cells and investigation of the associated imbalance of regulatory T cells, responder T cells as well as Th17 cells might be key in furthering our understanding of silica-induced autoimmune alterations. On the other hand, asbestos exposure shows less association with autoimmune diseases. However, interesting findings pertaining to the detection of antiendothelial and mesothelial cell antibodies in asbestos-exposed patients have been reported. Summary: Taken together, further investigations may contribute in delineating the mechanisms involved in environmental factor-induced modification of autoimmunity.

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Childhood asthma is a risk factor for the development of chronic obstructive pulmonary disease

Purpose of review: This review will catalog the many recent longitudinal studies that have investigated the relationship between asthma and lung function, or the persistence and trajectories of lung function deficits. Recent findings: Recent work has reported on 50-year follow-ups of some prominent population cohorts. A history of asthma confers a 10–30-fold risk of chronic obstructive pulmonary disease. Individuals reaching a reduced maximum growth of forced expiratory volume in 1 s in early adulthood are at risk for early or more severe chronic obstructive pulmonary disease (COPD). Summary: Taken together, there is a wealth of overlapping cohort studies of lung function, asthma and COPD. These show that asthma is associated with reduced lung function, which may start in infancy or prenatally, persists through childhood and adulthood and predisposes for early or more severe COPD.

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Traffic-related air pollution and allergic disease: an update in the context of global urbanization

Purpose of review: The review aims to give an update on the literature around traffic-related air pollution (TRAP) and allergic disease in the context of global urbanization, as the most populous countries in the world face severe TRAP exposure challenges. Recent findings: As research continues to show that gene–environment interactions and epigenetics contribute to the TRAP–allergy link, evidence around the links to climate change grows. Greenspace may provide a buffer to adverse effects of traffic on health, overall, but pose risks in terms of allergic disease. Summary: The link between traffic-related pollution and allergy continues to strengthen, in terms of supportive observational findings and mechanistic studies. Levels of TRAP across the world, particularly in Asia, continue to dramatically exceed acceptable levels, suggesting that the related adverse health consequences will accelerate. This could be counterbalanced by primary emission control and urban planning. Attention to combined effects of TRAP and allergen exposure is critical to avoiding misleading inferences drawn though examination only of isolated factors.

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Microbes, allergic sensitization, and the natural history of asthma

Purpose of review: Understanding factors that lead to asthma development in early life is essential to developing strategies aimed at primary or secondary prevention. Recent findings: This article will review current evidence addressing the development of early life allergic sensitization in relation to microbes and the gut and airway microbiome. Wheezing illnesses, particularly viral, remain a significant risk factor for asthma inception; however, bacterial pathogens have recently emerged as an additional important contributor to asthma risk, either alone or as cofactors with viral infections. The combined influence and interaction of early life viral wheezing and aeroallergen sensitization is important, with allergic sensitization preceding the onset of viral wheeze. Lastly, we review recent data from longitudinal studies regarding the development of irreversible airway obstruction and its impact on the natural history of asthma. Summary: The development of asthma remains complex and incompletely understood. There is interplay between genetic predisposition and environmental exposures, including allergens and microbes. Interventions aimed at these risk factors during the preschool years may prevent the longitudinal course of asthma progression to irreversible airway obstruction.

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Update on asthma and cleaning agents

Purpose of review: Asthma due to cleaning products has been known for 20 years, and the interest in this topic is still large because of the number of cleaning workers with respiratory problems. In this review, we sought to highlight the most recent findings on the relationship between exposure to cleaning products and asthma and to summarize the specific literature published between 2013 and 2016. Recent findings: Women are confirmed as most of workers exposed to cleaning products and have a higher frequency than men of work-related respiratory symptoms and diseases. Many cases of asthma due to cleaning products occur in healthcare occupations. The increased risk of asthma has been shown to be related to the number of years in the job and to early life disadvantage. Recent evidence suggests that predisposition to adult-onset asthma may be related to interaction between genes and occupational exposure to low-molecular weight agents/irritants. There is some evidence that an irritant mechanism is more common, although several case reports showed animmunologic mechanism (e.g. disinfectants, amine compounds, aldehydes and fragrances). Summary: The review updated recent findings on epidemiology, cleaning agents and their mechanism, and prevention of asthma due to cleaning agents. This article provides new information on the level of exposure, which is still high in professional cleaners and even more in domestic cleaners, and on the frequency of asthma in professional and domestic cleaners. An irritant mechanism is more common, although an immunological mechanism is possible, especially in healthcare workers exposed to disinfectants.

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Management of preschool recurrent wheezing and asthma: a phenotype-based approach

Purpose of review: The purpose of this review is to summarize the recent evidence on the management of preschool children with wheezing and asthma, and to propose a phenotype-based approach to the management of these children. Recent findings: Recent studies have begun to identify populations of preschool children that are likely to benefit from inhaled corticosteroids (ICS) therapy and defined ICS regimens: daily ICS in preschool children with persistent asthma, and pre-emptive high-dose intermittent ICS among preschool children with intermittent disease reduce the risk of exacerbation. In addition, among preschool children with mild persistent asthma, the presence of aeroallergen sensitivity and/or blood eosinophil counts of 300/μL or greater are predictors of good response to daily ICS therapy. Other studies identified intermittent azithromycin as a therapy to prevent, and potentially to treat, acute exacerbations. The uncertainty of the role of oral corticosteroids (OCS) as a therapy for acute exacerbations continues, as a recent meta-analysis showed that OCS did not prevent hospitalizations or urgent visits, and did not reduce the need for additional courses of OCS. Whereas previous epidemiologic studies suggested acetaminophen may increase risk of exacerbations, a clinical trial clearly demonstrated acetaminophen use, compared to ibuprofen use,does not increase exacerbation risk among preschool children with mild-persistent asthma. Summary: Recent studies have shown potential for phenotypic-driven therapies for the management of preschool children with asthma. Targeting airway bacteria has emerged as a promising therapeutic approach, but its effect on antibiotic resistance still needs to be investigated. Finally, more studies are required to evaluate if oral corticosteroids provide any benefits for acute episodic wheeze.

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Pediatric asthma – moving ahead faster than ever

No abstract available

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Current and future management of the young child with early onset wheezing

Purpose of review: In this review, we discuss current thinking in relation to available guidelines for the care of preschool-aged children with recurrent wheezing, while highlighting the gaps in our knowledge and discussing changes that could occur over the next 5 years. Recent findings: The Asthma Predictive Index as well as allergen-specific IgE, peripheral eosinophil count and exhaled nitric oxide are perhaps underutilized sources of information that can assist in predicting progression to asthma and response to therapies. Inhaled corticosteroids and leukotriene receptor antagonists decrease impairment and exacerbation frequency in wheezing children but are not disease modifying. Macrolides may be useful during acute wheezing episodes for preventing progression to more severe symptoms. Monoclonal antibodies targeting IgE and TH2 cytokines have been successful in trials of adults and older children with asthma, but trials in younger children are needed. Summary: Establishing the phenotype and endotype of young wheezing children can be useful for prognostication of future asthma risk as well as for selection of the most appropriate treatment. Primary asthma prevention strategies are needed during the critical developmental window in early life prior to the onset of irrecoverable loss of lung function.

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Asthma guidelines: the Global Initiative for Asthma in relation to national guidelines

Purpose of review: To compare and contrast national asthma guidelines with the Global Initiative for Asthma (GINA) strategy for asthma management and prevention. Recent findings: The common goal of GINA and national asthma guidelines is to improve asthma care using the best evidence available from published data. This evidence-based approach has evolved from an initial perspective of expert opinion but with that evolution has not always considered the breadth of asthma phenotypes. GINA and national guidelines differ in a number of ways. GINA reviews available data and updates the core document and recommendations based on the latest data on a yearly basis to offer local, regional and national guidelines materials needed for knowledge mobilization. It remains the purview of those organizations to structure and implement those locally appropriate guidelines. Summary: Both GINA and national guidelines have furthered asthma care to narrow the care gap from what is known to how asthma care is delivered, hopefully in a more directed, personalized manner. As well, both GINA and national guidelines have helped to shape the direction of research for the future benefit of children and their families.

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Building school health partnerships to improve pediatric asthma care: the School-based Asthma Management Program

Purpose of review: Children with asthma require care that is seamlessly coordinated so that asthma symptoms are recognized and managed at home and at school. The purpose of this review is to discuss recent consensus recommendations in school-based asthma care. Recent findings: The School-based Asthma Management Program (SAMPRO) provides a widely endorsed framework to coordinate care with schools and consists of four components: establishing a circle of support around the child with asthma; facilitating bidirectional communication between clinicians and schools; comprehensive asthma education for schools; and assessment and remediation of environmental asthma triggers at school. SAMPRO standardizes recommendations for school-based asthma care coordination and provides a toolkit with websites and resources useful for the care of children with asthma in the school setting. Summary: The review will discuss the need for coordinated school asthma partnerships, the inception and development of SAMPRO, and its vision to improve pediatric asthma care coordination within the circle of support, comprising clinicians, school nurses, families, and communities.

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Psoriasis et phénomène de Koebner inversé après tatouage

Publication date: Available online 22 February 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): N. Kluger, M.-H. Jegou




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Living with ‘melanoma’…for a day: a phenomenological analysis of medical students’ simulated experiences

Abstract

Background

Despite the rising incidence of melanoma, medical students have progressively fewer opportunities to encounter patients with this important condition. Curricula tend to attach the greatest value to intellectual forms of learning. Compared to intellectual learning, however, experiential learning affords students deep insights about a condition. Doctors who experience ill health are more empathic towards patients. However opportunities to learn about cancer experientially are limited. Temporary transfer tattoos can simulate the ill health associated with melanoma. We reasoned that, if doctors who have been sick are more empathic, temporarily 'having' melanoma might have a similar effect.

Objectives

Explore the impact of wearing a melanoma tattoo on medical students' understanding of patienthood and attitudes towards patients with melanoma.

Methods

Ten fourth year medical students were recruited to a simulation. They wore a melanoma tattoo for 24 hours and listened to a patient's account of receiving their diagnosis. Data were captured using audio-diaries and face-to-face interviews, transcribed, and analysed phenomenologically using the template analysis method.

Results

There were four themes: 1) Melanoma simulation: opening up new experiences.

2) Drawing upon past experiences.3) A transformative introduction to patienthood.

4) Doctors in the making: seeing cancer patients in a new light.

Conclusions

By means of a novel simulation, medical students were introduced to lived experiences of having a melanoma. Such an inexpensive simulation can prompt students to reflect critically on the empathetic care of such patients in the future

This article is protected by copyright. All rights reserved.

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