Αρχειοθήκη ιστολογίου

Τετάρτη 31 Ιανουαρίου 2018

Intestinal-type adenocarcinoma of the sinonasal tract: an update

Purpose of review Intestinal-type adenocarcinoma (ITAC) is one of the most frequent sinonasal tumors, especially in European countries. The purpose of this article is to review the most recent literature, with special emphasis on biological and genetic profile and treatment guidelines. Recent findings Results on large series support transnasal endoscopic surgery as the technique of choice in the large majority of patients with ITAC. Adjuvant radiotherapy is recommended in advanced-stage and high-grade lesions. More robust data are required to confirm that early-stage, low-grade lesions can be treated with exclusive surgery. The efficacy of new chemotherapy and biotherapy regimens and the added value of heavy particle radiotherapy are currently under evaluation. With a 5-year overall survival ranging between 53 and 83%, which is mainly impacted by local recurrences, ITAC requires a more detailed understanding of its biology. Genetic and biological studies have identified alterations in the molecular pathways of EGFR, MET, and H-RAS which might be considered as potential targets for biotherapy. Summary Surgery still plays a key role in the treatment of ITAC, but multidisciplinary management is mandatory. Although further validation is needed, the role of nonsurgical treatment strategies is rising, in agreement with the progresses made in the biological profiling of the disease. Correspondence to Piero Nicolai, MD, Unit of Otorhinolaryngology, Spedali Civili of Brescia, University of Brescia, Piazza Spedali Civili, 1, 25123 Brescia, Italy. Tel: +39 0303995319; fax: +39 030395212; e-mail: pieronicolai@virgilio.it Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Real world data on the efficacy and safety of apremilast in patients with moderate to severe plaque psoriasis

Abstract

Background

Psoriasis is a chronic inflammatory skin disease, which requires long term, safe and effective treatment. Apremilast, a small-molecule PDE4 inhibitor, has been introduced as psoriasis (and psoriatic arthritis) treatment in Europe in 2015.

Objective

We analysed and report the efficacy and safety of apremilast in the first 51 patients with psoriasis that have undergone treatment with this novel small molecule in our outpatient clinic.

Method

Our primary endpoint was the evaluation of clinical response to apremilast according to the percentage of PASI reduction (ΔPASI) at 16 weeks after treatment initiation. Secondary endpoints were the evaluation at week 16 of: (i) Psoriasis Area Severity Index (PASI); (ii) Dermatology Life Quality Index (DLQI); (iii) Physician Global Assessment (PGA); (iv) Psoriasis Scalp Severity Index (PSSI); and (v) the percentage of patients who achieved ΔPASI50, ΔPASI75, ΔPASI90 and ΔPASI100; (vi) adverse events (AE); (vii) reasons for drug discontinuation; and (viii) drug survival.

Results

59.3% of the patients who remained on apremilast achieved at least ΔPASI75 at week 16, while 11.1% achieved combined 50%≤PASI<75% and DLQI≤5 (satisfactory response) adequate enough to maintain treatment. Five patients (18.5%) also achieved ΔPASI100. Patients discontinued apremilast (28%), mostly during the first four weeks due to adverse events (12%) with gastrointestinal symptoms being the most common, and later due to lack of efficacy (16%). A statistically significant improvement of PASI, DLQI, PGA and PSSI scores was observed after 4 and 16 weeks of treatment relative to pre-treatment measurements.

Conclusion

Apremilast is a safe and efficacious treatment for psoriasis patients as it produces ΔPASI75 and ΔPASI50 responses combined with DLQI≤5 in 16 weeks in 70.4% of the patients. These results, from a real-world setting, confirm the efficacy and safety of apremilast which has been demonstrated in large phase III clinical trials.

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Outcomes of Donation After Cardiac Death Liver Grafts from Donors ≥ 50 years of Age: A Multi-center Analysis

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ABSTRACTIntroductionAs the population in the United States continues to age, an increase in the number of potential DCD donors with advanced chronological age can be expected. The aim of this study was to analyze a multi-institutional experience in liver transplantation using DCD donor age ≥50 years.MethodsAll DCD LT performed at Mayo Clinic Florida, Mayo Clinic Rochester and Mayo Clinic Arizona from 2002-2016 were included. Recipients of DCD LT were divided into 2 groups: those with donor age ≥50 years(N=155) and those with donor age

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Inequalities in zoster disease burden: a population-based cohort study to identify social determinants using linked data from the UK Clinical Practice Research Datalink

Abstract

Background

Zoster vaccination was introduced in England in 2013, where tackling health inequalities is a statutory requirement. However, specific population groups with higher zoster burden remain largely unidentified.

Objective

To evaluate health inequalities in zoster disease burden prior to zoster vaccine introduction in England.

Methods

This population-based cohort study utilised anonymised UK primary care data linked to hospitalisation and deprivation data. Individuals aged ≥65 years without prior zoster history (N=862,470) were followed from 01/09/2003-31/08/2013. Poisson regression was used to obtain adjusted rate ratios (ARR) for the association of socio-demographic factors (ethnicity, immigration status, individuals' area-level deprivation, care home residence, living arrangements) with first zoster episode. Possible mediation by co-morbidities and immunosuppressive medications was also assessed.

Results

There were 37,014 first zoster episodes, with incidence of 8.79 (95% confidence interval (CI):8.70-8.88) per 1,000 person-years at risk. In multivariable analyses, factors associated with higher zoster rates included care home residence (10% higher versus those not in care homes), being female (16% higher versus males), non-immigrants (~30% higher than immigrants) and White ethnicity (for example, twice the rate compared to those of Black ethnicity). Zoster incidence decreased slightly with increasing deprivation (ARR most versus least deprived=0.96 (95%CI:0.92-0.99) and among those living alone (ARR 0.96 (95%CI:0.94-0.98). Mediating variables made little difference to the ARR of social factors but were themselves associated with increased zoster burden (ARR varied from 1.11-3.84).

Conclusions

The burden of zoster was higher in specific socio-demographic groups. Further study is needed to ascertain whether these individuals are attending for zoster vaccination.

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The PARACELSUS score: A novel diagnostic tool for pyoderma gangrenosum

Abstract

Background

The lack of objective diagnostic criteria renders pyoderma gangrenosum (PG) a diagnosis of exclusion. The diagnostic approaches proposed to date have not been systematically evaluated. Thus, PG remains a challenging and frequently misdiagnosed disorder.

Objectives

To develop and assess a comprehensive yet clinically practicable as well as sensitive diagnostic scoring system for PG.

Methods

Clinical history and images of a total of 60 subjects with previously confirmed PG located on the lower extremity as well as a control cohort of 50 patients with venous leg ulcers were retrospectively evaluated by expert teams at two tertiary dermatological centres specializing in wound care using a newly developed diagnostic scoring system composed of ten criteria.

Results

The three major diagnostic criteria are rapidly progressing disease, assessment (absence) of relevant differential diagnoses and reddish-violaceous wound border (prevalent in 98.3% of PG patients, respectively). Minor criteria (evident in 61-95% of PG cases) include amelioration (alleviation) by immunosuppressant drugs, characteristically irregular shape of ulceration, extreme pain >4/10 on visual analogue scale, and localization of lesion at site of trauma. Three additional criteria (observed in up to 60% of PG subjects) encompass suppurative inflammation in histopathology, undermined wound margins as well as concomitant systemic disease. A total score value of ten points or higher indicates a high likelihood of PG and differentiates PG from venous leg ulcers. The initial letters of the above-listed criteria form the acronym PARACELSUS.

Conclusion

The PARACELSUS score represents a novel, easily implementable, effective and sensitive diagnostic tool for PG.

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Sirolimus for treatment of Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon: A retrospective cohort study

Abstract

Kaposiform hemangioendothelima (KHE) is a locally aggressive vascular tumor that mainly occurs during childhood and invades adjacent tissue and organ. It is commonly complicated by Kasabach-Merritt phenomenon (KMP) in about 50%-70% of the cases. KMP is most often associated with a rapidly growing, large solitary tumor that may result in severe hemorrhage and directly responsible for high mortality and morbidity.

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Utility of Radionuclide Bone Scintigraphy in Complex Regional Pain Syndrome

Abstract

Purpose of Review

To describe the current understanding of the role of three-phase bone scintigraphy (TPBS) in the diagnosis and management of complex regional pain syndrome (CRPS), discuss its advantages and limitations, and present three examples of TPBS patterns typically seen in CRPS patients.

Recent Findings

CRPS is a debilitating disorder frequently presenting with pain to ordinarily non-painful stimuli, redness, swelling, following fractures, stroke, myocardial infarction, surgery, or even minor trauma, and its diagnosis, based on clinical criteria and supportive imaging findings, is difficult. Of the available adjunctive diagnostic imaging modalities, radionuclide bone scintigraphy using a TPBS protocol is the most sensitive and specific for detecting abnormalities commonly seen with this condition—classically, increased periarticular uptake on delayed phase of TPBS, with variable increased uptake on perfusion phases, depending on chronicity. Recent studies have (1) demonstrated a more heterogeneous correlation of TPBS findings with CRPS diagnosis using the current Budapest criteria than in studies using older criteria, (2) pointed to the utility of novel quantitative scintigraphic techniques, and (3) highlighted the value of the early perfusion phases of TPBS in predicting treatment response.

Summary

TPBS remains a valuable imaging adjunct to clinical diagnosis of CRPS. In combination with a multi-modal analgesic approach, TPBS can be used to follow disease course and potentially treatment response, although prospective trials are needed to further delineate its role.



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Medical Cannabis for Neuropathic Pain

Abstract

Purpose of Review

Many cultures throughout history have used cannabis to treat a variety of painful ailments. Neuropathic pain is a complicated condition that is challenging to treat with our current medications. Recent scientific discovery has elucidated the intricate role of the endocannabinoid system in the pathophysiology of neuropathic pain. As societal perceptions change, and legislation on medical cannabis relaxes, there is growing interest in the use of medical cannabis for neuropathic pain.

Recent Findings

We examined current basic scientific research and data from recent randomized controlled trials (RCTs) evaluating medical cannabis for the treatment of neuropathic pain. These studies involved patients with diverse etiologies of neuropathic pain and included medical cannabis with different THC concentrations and routes of administration. Multiple RCTs demonstrated efficacy of medical cannabis for treating neuropathic pain, with number needed to treat (NNT) values similar to current pharmacotherapies.

Summary

Although limited by small sample sizes and short duration of study, the evidence appears to support the safety and efficacy of short-term, low-dose cannabis vaporization and oral mucosal delivery for the treatment of neuropathic pain. The results suggest medical cannabis may be as tolerable and effective as current neuropathic agents; however, more studies are needed to determine the long-term effects of medical cannabis use. Furthermore, continued research to optimize dosing, cannabinoid ratios, and alternate routes of administration may help to refine the therapeutic role of medical cannabis for neuropathic pain.



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Liponeurofibroma: Clinicopathological features and histogenesis

Abstract

A neurofibroma is a common cutaneous benign tumor of neural origin. Various histological variants have been reported. Recently, sporadic reports of fatty variants have been reported but their clinicopathological features have not been well studied. The purpose of this study was to examine liponeurofibroma, and to report the distinctive clinicopathological features and histogenesis in comparison with the classic form. A retrospective study was performed on 130 cases. Immunohistochemical staining was performed for S100, factor VIIIa, perilipin and vascular endothelial growth factor. Masson's trichrome stain was also used. Intratumoral adipocytes were examined with transmission electron microscopy. Thirty-two (24.6%) cases were classified as liponeurofibroma on microscopic examination. This variant was more common in patients with neurofibromatosis type 1, older age and female sex. The most prevalent location was the head and neck. Intratumoral fat deposits showed differences in morphology and size compared with subcutaneous fat on light microscopy. Neurofibromatosis type 1 had the highest odds of fatty change in liponeurofibroma. In sporadic cases, fatty change can be caused by senescence, chronic injury, or tissue hypoxia secondary to internal or external stimuli. Further investigation is needed to identify the pathomechanism of fatty change in various cutaneous neoplasms, including neurofibroma.



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Posterior reversible encephalopathy syndrome secondary to asymptomatic poststreptococcal glomerulonephritis in a child with sickle cell anemia: a case report

Posterior reversible encephalopathy syndrome is a neurotoxic condition that occurs as a result of the failure of posterior circulatory autoregulation in response to acute changes in blood pressure. Overperfusi...

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Correction to: An exotic abscess within the United Kingdom from The Gambia: a case report

In the publication of this article [1], there is an error in an authors name.

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Carcinoid heart disease revealed by cyanosis with both right and left valvular involvement: a case report

Carcinoid heart disease is a frequent complication of carcinoid syndrome. It is related to the release by the carcinoid tumor and/or its metastases of bioactive substances such as serotonin. It is characterize...

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Burden of atopic dermatitis in Japanese adults: Analysis of data from the 2013 National Health and Wellness Survey

Abstract

Atopic dermatitis is a chronic inflammatory skin disease. The objective of this study was to characterize the burden of atopic dermatitis in Japanese adult patients relative to the general population. Japanese adults (≥18 years) with a self-reported diagnosis of atopic dermatitis and adult controls without atopic dermatitis/eczema/dermatitis were identified from the 2013 Japan National Health and Wellness Survey. Atopic dermatitis patients were propensity-score matched with non-atopic dermatitis controls (1:2 ratio) on demographic variables. Patient-reported outcome data on comorbidities, mood and sleep disorders, health-related quality of life, work productivity and activity impairment, and health-care resource utilization were analyzed in atopic dermatitis patients and matched controls. A total of 638 Japanese adult patients with atopic dermatitis were identified, of whom 290 (45.5%) rated their disease as "moderate/severe" and 348 (54.5%) as "mild". The analysis cohort comprised 634 atopic dermatitis patients and 1268 matched controls. Atopic dermatitis patients reported a significantly higher prevalence of arthritis, asthma, nasal allergies/hay fever, anxiety, depression and sleep disorders compared with controls (all P < 0.001). Atopic dermatitis patients also reported a significantly poorer health-related quality of life, higher overall work and activity impairment, and higher health-care resource utilization (all P < 0.001). Self-rated disease severity was not associated with disease burden, except for a significantly higher overall work and activity impairment. In conclusion, Japanese adult patients with atopic dermatitis reported a substantial disease burden relative to adults without atopic dermatitis, suggesting an unmet need for effective strategies targeting disease management.



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Case of psoriatic patient who maintains long-term remission after anti-hepatitis C virus agents and ustekinumab treatment



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Use of balloon catheter dilation vs. traditional endoscopic sinus surgery in management of light and severe chronic rhinosinusitis of the frontal sinus: a multicenter prospective randomized study

OBJECTIVE: Chronic rhinosinusitis (CRS) of the frontal sinus is a complex pathological condition and many surgical techniques were described to treat this area endoscopically, like traditional endoscopic sinus surgery (ESS) and balloon catheter dilation (BCD).

PATIENTS AND METHODS: We designed a multicenter prospective randomized study to assess the validity and safety of BCD vs. ESS in symptomatological chronic rhinosinusitis of the frontal sinus enrolling a population of 102 adult patients (64 men and 38 women; overall 148 frontal sinuses studied) with non-polypoid CRS. For a better evaluation of the disease, in our study we decided to analyze both radiological (Lund-McKay CT scoring modified by Zinreich) and symptomatological results (SNOT-20 questionnaire). We divided the population affected in two groups, one with light/mild frontal CRS and the other with moderate/severe frontal CRS, basing on radiological findings at Lund-MacKay modified by Zinreich score. Every group was divided in two subgroups, in one we used BCD and in the other we used traditional ESS.

RESULTS: The current literature does not support the suggestion that indications for BCD and ESS are identical, and additional research is needed to determine the role for BCD in specific patient populations. The results showed a not statistically significative difference between BCD and conventional ESS of the frontal sinus in patients with light/mild CRS and in patients with moderate/severe CRS at Lund-Mackay modified by Zinreich score. The same not statistically significative difference was observed comparing the results of SNOT-20 questionnaire in the group of light/mild frontal chronic rhinosinusitis. However, we noticed a statistically significant better outcome of SNOT-20 score in patients with moderate/severe chronic rhinosinusitis that underwent BCD of frontal sinus compared to ESS.

CONCLUSIONS: BCD and ESS are two alternative weapons in the baggage of every endoscopic surgeon, even because they present similar outcomes, safeness and effectiveness both in light/mild and moderate/severe chronic rhinosinusitis of the frontal sinus. An interesting result of our study was the statistically significant better outcome of SNOT-20 score in patients that underwent BCD of frontal sinus for a moderate/severe CRS, compared to those that underwent a traditional ESS.

L'articolo Use of balloon catheter dilation vs. traditional endoscopic sinus surgery in management of light and severe chronic rhinosinusitis of the frontal sinus: a multicenter prospective randomized study sembra essere il primo su European Review.



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Role of Otoacoustic Emissions in Hearing Assessment of Neonates: A Prospective Observational Study

Abstract

Hearing plays an important role for children in learning speech and language, socialization and cognitive development. The child learns to speak based on what is heard (Rundjan et al. in Sari Pediatr 6(4):149–154, 2005). The aim of the study was to find out the percentage of hearing loss by OAE among low risk and high risk neonates. All the neonates (Low and High risk) born in a tertiary care center were screened by OAE before their discharge from the hospital and after stabilizing high risk neonates. The referred neonates were followed after two weeks. Total 722 neonates were screened of which 130 were high risk and 592 were low risk. Neonates with Serum bilirubin > 20 mg/dl or requiring exchange transfusion were excluded as OAE will be unreliable in them and they should be subjected to BERA directly. Percentage of bilateral hearing loss came to be 4.2%, 4 participants were lost to follow up and percentage of hearing loss on subsequent OAE came to be 11.6%. Low birth weight was an important risk factor for hearing loss (p value significant on initial and follow-up). Percentage of hearing loss with low birth weight, hyperbilirubenemia, low apgar score and prematurity to be 16%. Mechanical ventilation contributed 13% of total hearing loss followed by ototoxicity. Neonates with family history of childhood SNHL, in utero infection, craniofacial anomaly and bacterial meningitis contributed 3% of total hearing loss. On subsequent follow-up, one neonate was low-risk and the other 25 were high risk, of which 3 high risks showed sustained OAE refer. However the low risk neonate had normal outer hair cell function i.e. OAE pass. This study clearly demonstrates importance of Universal Neonatal Hearing Screening Programme so that hearing loss can be detected as early as possible and possible intervention can be taken at the earliest.



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Narrow band imaging for head and neck malignancies: Lessons learned from mistakes

Abstract

Background

The accuracy of white light endoscopy in combination with narrow band imaging (WLE + NBI) for diagnosis of squamous cell carcinoma (SCC) does not reach 100%. We evaluated the characteristics of the false-negative and false-positive cases.

Methods

Five hundred thirty lesions of the upper airways were evaluated. The WLE was followed by NBI examination before performing a biopsy.

Results

The false-negative lesions (7.36%) were represented by submucosal and non-SCC tumors. Among the 25 non-SCC tumors, 72% did not show any suspicious vascular pattern under NBI. The false-positive lesions (6.04%) were mainly represented by postradiotherapy mucosal changes, ulcers, and infections. Regarding papillomas, NBI accuracy reached 95.32%, although cases with dysplasia were difficult to distinguish from SCC.

Conclusion

The WLE + NBI improved diagnostic accuracy, but not all lesions were ideally evaluated with current defined patterns. An accurate anamnesis is mandatory, because, in some cases, it may be more relevant than the NBI pattern.



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Head and neck lymphedema management: Evaluation of a therapy program

Abstract

Background

The purpose of this pilot study was to examine a therapeutic intervention for head and neck lymphedema. The 22-week intervention involved therapist-led care and participant self-management. Effectiveness was evaluated using a previously described lymphedema assessment tool, the Assessment of Lymphedema of the Head and Neck (ALOHA) to detect change over the course of the 22 weeks of treatment, and before and after a single treatment session.

Methods

A prospective observational pilot study was conducted with a cohort of 10 participants assessed. Measurements of size (tape measurements) and water content (tissue dielectric constant [TDC]) were used, per the ALOHA protocol. Participants received 13 lymphedema therapy treatments at reducing frequencies over 22 weeks and daily self-management.

Results

There was an overall significant reduction in lower neck circumference (F [2.15,19.35] = 7.11; P = .004), upper neck circumference (F [5,45] = 7.27; P < .001) and TDC (F (5,45) = 8.92; P < .001) over time. There were no significant differences over the course of treatment for mean ear-to-ear measurements or before and after a single session of treatment.

Conclusion

This pilot study found a reduction in head and neck lymphedema over the 22-week lymphedema treatment course. This intervention may be successful in reducing head and neck lymphedema; however, further studies are needed to investigate these findings in a larger sample with the use of a control group to negate improvements from healing over time.



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Extended endonasal approach versus maxillary swing approach to the parapharyngeal space

Abstract

Background

The nasopharyngeal and parapharyngeal spaces are difficult for surgeons to access. Of the various external routes described, the maxillary swing has emerged as the gold standard because of its simplicity. However, its morbidity has led to the development of less invasive techniques. The purpose of our study was to compare the surgical anatomy of the maxillary swing with that of the endoscopic endonasal approach.

Methods

Each procedure was performed on 10 anatomic specimens. The exposure and the limits obtained were evaluated. A CT scan analysis was performed.

Results

The endoscopic endonasal approach extended the limits, offering wider exposure. The endoscopic endonasal approach made possible better visualization of deep structures and precise dissection of the parapharyngeal spaces. However, the maxillary swing provided better access to the oropharynx and could be completed 3 times faster.

Conclusion

The endoscopic endonasal approach provides excellent exposure, a wide dissection range, and precise definition of anatomic structures, making it an alternative of choice rather than the maxillary swing approach.



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Modified combination of platelet count and neutrophil “to” lymphocyte ratio as a prognostic factor in patients with advanced head and neck cancer

Abstract

Background

We evaluated the prognostic potential of the combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) in patients with advanced head and neck cancer.

Methods

We proposed a modified COP-NLR scoring system defined as follows: score 0 (platelet count level <300 × 109/L and NLR <3); score 1 (platelet count level ≥300 × 109/L and NLR <3); and score 2 (NLR ≥3). We assessed whether the modified scoring system had better performance as an indicator of prognosis than the existing COP-NLR scoring system (original and 4-group scores).

Results

A total of 248 patients were enrolled. The Akaike Information Criterion value with the modified COP-NLR score was the smallest among the 3 models. The 3-year survival rates according to the modified COP-NLR scores of 0, 1, and 2 were 80.6%, 59.9%, and 23.8%, respectively.

Conclusion

The modified COP-NLR score is a useful prognostic marker in patients with advanced head and neck cancer.



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Intraoperative cardiac arrest etiologies in head and neck surgery: A comprehensive review

Abstract

Background

The etiologies of intraoperative cardiac arrest within otolaryngology are not well understood as they are rare events.

Methods

A comprehensive review of the etiologies and corresponding pathophysiologic neural mechanisms of intraoperative cardiac arrest in otolaryngologic surgery are examined.

Results

The occurrence of this rare complication has been described in a range of head and neck procedures, including but not limited to suspension laryngoscopy and oncologic resections in the neck, maxilla and thyroid. Three anatomically distinct pathways leading to intraoperative cardiac arrest are described: direct vagal stimulation, the trigeminocardiac reflex and the baroreceptor reflex. All three share the final common pathway of parasympathetic signaling to the sinoatrial node via the cardiac fibers of the vagus nerve.

Conclusion

With a firm understanding of the mechanistic underpinning of this rare phenomenon, otolaryngologic surgeons can be better prepared for its occurrence.



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Effects of excessive fibrin deposit and polylactide adhesion barrier on wound healing in thyroidectomy murine wound model

Abstract

Background

We hypothesize that excessive fibrin formation and inflammation induced by antiadhesive material, SurgiWrap (SW), would have an adverse effect on wound healing. It was evaluated by a thyroidectomy murine wound model.

Methods

Excessive fibrin formation was induced by isthmectomy without hemostasis. Rats were allocated into isthmectomy with SurgiWrap (I+SW+), I+SW-, I-SW+, I-SW-, and isthmectomy after electrocautery for hemostasis (I+C+SW-). The SWs were placed on the superficial and visceral layers for gross and microscopic evaluation.

Results

Microscopic examination showed collagen deposition occurred in the I-SW- sham group and at a higher level in I+C+SW-. The collagen deposition decreased in groups without SW with time but increased in groups with SW. Use of SW produced more inflammation and more collagen deposition. The I+SW + group developed the largest area of collagen deposition at 4 weeks and more collagen deposition than the I-SW + group.

Conclusion

The SW induced more collagen deposition increasing with time. The collagen deposition produced by SW was worsened by excessive fibrin formation and inflammation.



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Application of Sal classification to parotid gland fine-needle aspiration cytology: 10-year retrospective analysis of 312 patients

Abstract

Background

The accuracy of fine-needle aspiration biopsy (FNAB) is controversial in parotid tumors. We aimed to compare FNAB results with the final histopathological diagnosis and to apply the "Sal classification" to our data and discuss its results and its place in parotid gland cytology.

Methods

The FNAB cytological findings and final histological diagnosis were assessed retrospectively in 2 different scenarios based on the distribution of nondefinitive cytology, and we applied the Sal classification and determined malignancy rate, sensitivity, and specificity for each category.

Results

In 2 different scenarios FNAB sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were found to be 81%, 87%, 54.7%, and 96.1%; and 65.3%, 100%, 100%, and 96.1%, respectively. The malignancy rates and sensitivity and specificity were also calculated and discussed for each Sal category.

Conclusion

We believe that the Sal classification has a great potential to be a useful tool in classification of parotid gland cytology.



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Outcomes utilizing intensity-modulated radiotherapy in oropharyngeal cancers: Tonsils versus base of tongue

Abstract

Background

The purpose of this study was to present the outcomes of oropharyngeal cancers treated with intensity-modulated radiotherapy (IMRT) especially the differences between tonsillar and base of tongue (BOT) primaries.

Methods

Retrospective analysis of 124 patients with biopsy proven squamous cell carcinomas of the oropharynx, treated with IMRT.

Results

Human papillomavirus (HPV) association correlated with improvement in survivals in both tonsillar and BOT primaries. At the 2-year median follow-up, the cumulative incidences of locoregional recurrences were 8% in both the tonsil and BOT groups (P = .76) but the distant metastases were 8% in the tonsil group versus 26% in the BOT group (P = .009). Thirty percent of tonsil primaries has ≥N2c neck disease as compared to 54% of BOT. Incidence of distant metastases increases with advanced nodal classification, especially >N2c.

Conclusion

Even though the locoregional controls are excellent with IMRT and chemotherapy, these patients continue to fail distantly, particularly significant for the BOT group and for nodal stage >N2c.



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Blaschkoid Acute Graft-vs-Host Disease

This case report describes a patient who developed acute graft-vs-host disease along the lines of Blaschko.

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Trends in Melanoma Incidence Among Non-Hispanic Whites

This analysis examines data from 2 major databases on melanoma incidence trends among the non-Hispanic white population in the United States by 10-year age groups.

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Rapid Repigmentation of Vitiligo-Affected Skin After Tofacitinib Plus UV-B

This case report describes 2 patients who experienced rapid repigmentation of vitiligo-affected skin after tofacitinib plus low-dose, narrowband UV-B therapy.

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Follicular and Epidermal Cell Suspension for Vitiligo Treatment

This randomized clinical trial compares the effects of combined epidermal cell suspension and follicular cell suspension with those of epidermal cell suspension alone in treatment of vitiligo.

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Prevalence and Types of Genital Lesions in Organ Transplant Recipients

This medical record review assesses the prevalence and types of genital lesions observed in organ transplant recipients.

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Role of Otoacoustic Emissions in Hearing Assessment of Neonates: A Prospective Observational Study

Abstract

Hearing plays an important role for children in learning speech and language, socialization and cognitive development. The child learns to speak based on what is heard (Rundjan et al. in Sari Pediatr 6(4):149–154, 2005). The aim of the study was to find out the percentage of hearing loss by OAE among low risk and high risk neonates. All the neonates (Low and High risk) born in a tertiary care center were screened by OAE before their discharge from the hospital and after stabilizing high risk neonates. The referred neonates were followed after two weeks. Total 722 neonates were screened of which 130 were high risk and 592 were low risk. Neonates with Serum bilirubin > 20 mg/dl or requiring exchange transfusion were excluded as OAE will be unreliable in them and they should be subjected to BERA directly. Percentage of bilateral hearing loss came to be 4.2%, 4 participants were lost to follow up and percentage of hearing loss on subsequent OAE came to be 11.6%. Low birth weight was an important risk factor for hearing loss (p value significant on initial and follow-up). Percentage of hearing loss with low birth weight, hyperbilirubenemia, low apgar score and prematurity to be 16%. Mechanical ventilation contributed 13% of total hearing loss followed by ototoxicity. Neonates with family history of childhood SNHL, in utero infection, craniofacial anomaly and bacterial meningitis contributed 3% of total hearing loss. On subsequent follow-up, one neonate was low-risk and the other 25 were high risk, of which 3 high risks showed sustained OAE refer. However the low risk neonate had normal outer hair cell function i.e. OAE pass. This study clearly demonstrates importance of Universal Neonatal Hearing Screening Programme so that hearing loss can be detected as early as possible and possible intervention can be taken at the earliest.



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Acute Progressive Visual Loss in a Case of Acute Myeloid Leukemia: Challenges in the Utility of Molecular Tests in Early Diagnose of Cytomegalovirus Retinitis

Cytomegalovirus (CMV) retinitis is one of the rare but debilitating presentations of the CMV infection in children with leukemia. Herein, we report a 12-year-old boy with acute myeloid leukemia complicated by rapid progressive visual loss during relapse of leukemia. The definite diagnosis of CMV retinitis was made after vitreous aspiration. Despite prompt treatment and ophthalmologic intervention, he died because of AML relapse. Viral infections, especially cytomegalovirus infection, may present with vague clinical pictures during any time of chemotherapy, which may not be easily distinguishable from bacterial or fungal retinitis and also chemotherapy-induced retinopathies. Clinician should consider CMV retinitis in seropositive patients especially those without detectable viremia.

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Steady Increase in Eyelid Cancer Found in England

Since 2000, the incidence of squamous cell carcinoma of the eyelid in England has increased by around 2% per year, with men affected nearly twice as often as women.
Medscape Medical News

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ANKRD1 regulates innate immune responses against herpes simplex virus 1: A potential role in eczema herpeticum

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Lianghua Bin, Xiaozhao Li, Brittany Richers, Joanne E. Streib, Jack W. Hu, Patricia Taylor, Donald Y.M. Leung
BackgroundAtopic dermatitis (AD) is a common inflammatory skin disease. A subset of AD is susceptible to disseminated herpes simplex virus (HSV) infection, a complication termed as eczema herpeticum(ADEH+). The immune mechanisms causing ADEH+ remain elusive. Using RNA-sequencing, we recently found that ankyrin repeat domain 1 (ANKRD1) was significantly induced in human peripheral blood mononuclear cells (PBMCs) upon HSV-1 stimulation; and its induction in ADEH+ was significantly reduced as compared to AD patients without a history of EH (ADEH-).ObjectiveTo validate ANKRD1 gene expression in non-atopic (NA), ADEH- and ADEH+ subjects; to delineate the biological function of ANKRD1 and the signaling pathway(s) involved.MethodsPurification of human PBMCs, monocytes, B cells, dendritic cells, T cells and NK cells; RNA extraction and qRT-PCR; small interfering RNA technique; co-immunoprecipitation; and western-blot assays were used.ResultsANKRD1 was significantly reduced in PBMCs from ADEH+ patients after HSV-1 stimulation as compared to PBMCs from ADEH-. We found that the induction of ANKRD1 by HSV-1 and multiple pathogen pattern recognition receptor (PRR) agonists are mediated by inflammatory cytokines. Silencing ANKRD1 gene expression in APCs led to increased viral load and reduced IFNb1 and IL-29 production. Using co-immunoprecipitation methods, we demonstrated that ANKRD1 formed protein complexes with IRF3 and IRF7, which are important transcription factors regulating PRRs' signaling transduction. Over-expression of ANKRD1 enhanced the IRF3-mediated signaling pathways.ConclusionANKRD1 is involved in IRF3 mediated anti-viral innate immune signaling pathways. Its reduced expression in ADEH+ subjects may contribute to the pathogenesis of ADEH+.



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A comparative analysis of human bone marrow-resident and peripheral memory B cells

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Sonya C. Becker, Martin Szyska, Angela Mensen, Katharina Hellwig, Raik Otto, Lisa Olfe, Hans-Dieter Volk, Thomas Dörner, Bernd Dörken, Carmen Scheibenbogen, Jörg Schröder, Andreas C. Hocke, Il-Kang Na




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Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Steven F. Weinstein, Rohit Katial, Shyamalie Jayawardena, Gianluca Pirozzi, Heribert Staudinger, Laurent Eckert, Vijay N. Joish, Nikhil Amin, Jaman Maroni, Paul Rowe, Neil M.H. Graham, Ariel Teper
BackgroundDupilumab, an anti-IL-4Rα monoclonal antibody, inhibits IL-4/IL-13 signaling, key drivers of type 2/Th2 immune diseases (e.g. atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting β2-agonists.ObjectiveTo examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR).MethodsPost-hoc analysis reporting data from the phase 2b study for the 200 and 300 mg q2w doses under investigation in phase 3 (NCT02414854). PAR was defined at study entry as a specific response to typical perennial antigens (immunoglobulin E [IgE]≥0.35 Ku/L).ResultsOverall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w vs placebo significantly improved SNOT-22 total score (LS mean difference −5.98 [95% CI, −10.45, −1.51], P = 0.009) and all 4 AR-associated symptoms evaluated (nasal blockage: −0.60 [−0.96, −0.25]; runny nose: −0.67 [−1.04, −0.31]; sneezing: −0.55 [−0.89, −0.21]; post-nasal discharge: −0.49 [−0.83, −0.16]; all P < 0.01]. Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant decreases in SNOT-22 total score (−1.82 [−6.46, 2.83], P = 0.443 vs placebo] and in each AR-associated symptom. In non-PAR patients, no differences were observed for these measures vs placebo.ConclusionDupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.



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Intravenous immunoglobulin treatment abrogates transplacental autoantibody transfer in a murine pemphigus model

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Sachiko Ono, Gyohei Egawa, Tetsuya Honda, Kenji Kabashima




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Intestinal IFN-γ-producing Tr1-cells co-express CCR5 and PD-1, and down-regulate IL-10 in the inflamed gut of IBD patients

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Johanna Sophie Alfen, Paola Larghi, Federica Facciotti, Nicola Gagliani, Roberto Bosotti, Moira Paroni, Stefano Maglie, Paola Gruarin, Chiara Maria Vasco, Valeria Ranzani, Cristina Frusteri, Andrea Iseppon, Monica Moro, Maria Cristina Crosti, Stefano Gatti, Massimiliano Pagani, Flavio Caprioli, Sergio Abrignani, Richard A. Flavell, Jens Geginat
BackgroundIL-10 is an anti-inflammatory cytokine that is required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type-1 regulatory (Tr1-) cells, but is also produced by CD25+ Tregs.ObjectiveWe aimed to identify and characterize human intestinal Tr1-cells, and to investigate if they are a relevant cellular source of IL-10 in inflammatory bowel diseases (IBDs).MethodsCD4+T-cells isolated from the intestinal lamina propria of humans and mice were analyzed for phenotype, cytokine production and suppressive capacities. Intracellular IL-10 expression by CD4+T-cell subsets in the inflamed gut of IBD patients with Crohn's Disease or Ulcerative Colitis was compared to non-inflamed controls. Finally, the effects of pro-inflammatory cytokines on T-cell IL-10 expression were analyzed, and IL-1P εξπρεσσiον ανδ IL-23 responsiveness were assessed.ResultsIntestinal Tr1-cells could be identified by the co-expression of CCR5 and PD-1 in humans and mice. CCR5+PD-1+Tr1-cells expressed IFN-γ ανδ ΙL-10 and efficiently suppressed T-cell proliferation and transfer colitis. Intestinal IFN-γ+Tr1-cells, but neither IL-7R+ helper T-cells nor CD25+Tregs, showed lower IL-10 expression in patients with IBDs. Tr1-cells were responsive to IL-23, and IFN-γ+Tr1-cells down-regulated IL-10 with IL-1β and IL-23. Conversely, CD25+Tregs expressed higher levels of IL-1R, but showed nevertheless stable IL-10 expression.ConclusionsWe provide the first ex vivo characterization of human intestinal Tr1-cells. The selective down-regulation of IL-10 by IFN-γ+Tr1-cells in response to pro-inflammatory cytokines is likely to drive excessive intestinal inflammation in IBDs.

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Short term ibrutinib therapy suppresses skin test responses and eliminates IgE-mediated basophil activation in adults with peanut or tree nut allergy

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Melanie C. Dispenza, Jacqueline A. Pongracic, Anne Marie Singh, Bruce S. Bochner

Teaser

Two doses of ibrutinib significantly reduced skin prick test area and anti-IgE-induced basophil activation responses in peanut and tree nut allergic adults. Ibrutinib or other BTK inhibitors could potentially be used to prevent anaphylaxis.


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The Obese-Asthma Phenotype in Children: An Exacerbating Situation?

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Cristina Longo, Gillian Bartlett, Tibor Schuster, Francine M. Ducharme, Brenda MacGibbon, Tracie A. Barnett
BackgroundCurrent evidence regarding the relationship between childhood obesity, decreased response to inhaled corticosteroids (ICS), and poor asthma control is conflicting.ObjectivesWe assessed if obesity: i) is associated with time-to-first exacerbation among children with asthma initiating Step-3 maintenance therapies; ii) modifies the effectiveness of Step-3 therapies.MethodsA retrospective cohort study was conducted from clinical data linked to health and drug administrative databases. The cohort consisted of children aged 2-18 years with specialist-confirmed asthma, who initiated medium/high-dose ICS monotherapy or low/medium-dose ICS with LTRA/LABA (combination therapy) at the Montreal Children's Hospital Asthma Center from 2000 to 2007. Children were classified as exposed to Step-3 therapies when they were dispensed a corresponding drug claim during follow-up, while those without claims were classified as non-adherers. Marginal structural Cox models were used to estimate the effect of obesity (BMI>97th percentile) and treatment on time-to-exacerbation, defined as any emergency department visit, hospitalization, or use of oral corticosteroids for asthma.ResultsOf the 4621 cohort patients, 231 initiated ICS monotherapy and 97 initiated combination therapy. The HR for obesity was 1.67 (95%CI 1.41-1.98). Compared to non-obese non-adherers, the HR for obese non-adherers was 1.54 (95%CI 0.97-2.45); the HR for ICS monotherapy in obese and non-obese children was 0.85 (95%CI 0.47-1.52) and 0.58 (95%CI 0.37-0.91), respectively; and the HR for combination therapy in obese and non-obese children was 0.50 (95%CI 0.13-1.89) and 0.46 (95%CI 0.23-0.92), respectively.ConclusionObesity may be a determinant of shorter exacerbation-free time in children with asthma; however, we could not rule out a differential response to Step-3 therapies by obesity status potentially due to a lack of precision.

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The role of local CpG DNA methylation in mediating the 17q21 asthma-susceptibility GSDMB/ORMDL3 expression quantitative trait locus

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Parul H. Kothari, Weiliang Qiu, Damien C. Croteau-Chonka, Fernando D. Martinez, Andrew H. Liu, Robert F. Lemanske, Carole Ober, Jerry A. Krishnan, Dan L. Nicolae, Kathleen C. Barnes, Stephanie J. London, Albino Barraza-Villarreal, Steven R. White, Edward T. Naureckas, Joshua Millstein, W. James Gauderman, Frank D. Gilliland, Vincent J. Carey, Scott T. Weiss, Benjamin A. Raby




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Protein corona-mediated targeting of nano-carriers to B cells allows redirection of allergic immune responses

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Limei Shen, Stefan Tenzer, Wiebke Storck, Dominika Hobernik, Verena Katharina Raker, Karl Fischer, Sandra Decker, Andrzej Dzionek, Susanne Krauthäuser, Mustafa Diken, Alexej Nikolaev, Joachim Maxeiner, Petra Schuster, Cinja Kappel, Admar Verschoor, Hansjörg Schild, Stephan Grabbe, Matthias Bros
BackgroundNanoparticle (NP) based vaccines are attractive immunotherapy tools due to their capability to co-deliver antigen and adjuvant to antigen presenting cells. Their cellular distribution and serum protein interaction ("protein corona") after systemic administration and its impact on functional properties of NP is poorly understood.ObjectivesWe analyzed the relevance of the protein corona on cell type-selective uptake of dextran (DEX)-coated NP and determined the outcome of vaccination with NP that codeliver antigen and adjuvant in disease models of allergy.MethodsThe role of protein corona constituents for cellular binding/uptake of DEX-NP was analyzed in vitro and in vivo. DEX-NP conjugated with the model antigen ovalbumin (OVA), and immunostimulatory CpG-rich oligonucleotides (ODN) were administered to monitor the induction of cellular and humoral immune responses. Therapeutic effects of this DEX-NP vaccine in mouse models of OVA-induced anaphylaxis and allergic asthma were assessed.ResultsDEX-NP triggered lectin-induced complement activation yielding deposition of activated complement C3 on the DEX-NP surface. In spleen, DEX-NP predominantly targeted B cells via their complement receptor CR1/2. The DEX-NP vaccine elicited much stronger OVA-specific IgG2a production than co-administered soluble OVA plus CpG ODN. B cell binding of the DEX-NP vaccine was critical for IgG2a production. Treatment of OVA-sensitized mice with the DEX-NP vaccine prevented the induction of anaphylactic shock and allergic asthma, accompanied by IgE inhibition.ConclusionsOpsonization of lectin-coated NP by activated complement components results in selective B cell targeting. The intrinsic B cell targeting property of lectin-coated NP can be exploited for the treatment of allergic immune responses.



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Benralizumab attenuates airway eosinophilia in prednisone-dependent asthma

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Roma Sehmi, Hui Fang Lim, Manali Mukherjee, Chynna Huang, Katherine Radford, Paul Newbold, Louis-Philippe Boulet, Delbert Dorscheid, James G. Martin, Parameswaran Nair




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T cell gene therapy for perforin deficiency corrects cytotoxicity defects and prevents Haemophagocytic Lymphohistiocytosis manifestations

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Sujal Ghosh, Marlene Carmo, Miguel Calero-Garcia, Ida Ricciardelli, Juan Carlos Bustamante Ogando, Michael P. Blundell, Axel Schambach, Philip G. Ashton-Rickardt, Claire Booth, Stephan Ehl, Kai Lehmberg, Adrian J. Thrasher, H Bobby Gaspar
BackgroundMutations in the PRF1 gene account for up to 58% of familial haemophagocytic lymphohistiocytosis (FHL) syndromes. The resulting defects in effector cell cytotoxicity lead to hypercytokinaemia and hyperactivation with inflammation in various organs.ObjectiveTo determine whether autologous gene corrected T cells can restore cytotoxic function, reduce disease activity and prevent haemophagocytic lymphohistiocytosis (HLH) symptoms in in vivo models.MethodsWe developed a gammaretroviral vector to transduce murine CD8-T cells in the prf-/- mouse model. To verify functional correction of prf-/- CD8-T cells in vivo, we used a lymphocytic choriomeningitis virus (LCMV) epitope transfected murine lung carcinoma cell tumour model. Further, we challenged gene corrected and uncorrected mice with LCMV. One patient sample was transduced with a PRF1 encoding lentiviral vector to study restoration of cytotoxicity in human cells.ResultsWe demonstrated efficient engraftment and functional reconstitution of cytotoxicity after intravenous administration of gene corrected prf-/- CD8-T cells into prf-/- mice. In the tumour model, infusion of prf-/- gene corrected CD8-T cells eliminated the tumour as efficiently as the transplant of wild type CD8-T cells. Similarly, mice reconstituted with gene corrected prf-/- CD8-T cells, displayed complete protection from the HLH phenotype after infection with LCMV. Patient cells showed correction of cytotoxicity in human CD8-T cells after transduction.ConclusionThese data demonstrate the potential application of T cell gene therapy in reconstituting cytotoxic function and protection against HLH in perforin deficiency.



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Umbilical cord blood transplantation without in vivo T-cell depletion for children with MHC class II deficiency

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Reem A. Elfeky, Juliana M. Furtado-Silva, Robert Chiesa, Kanchan Rao, Giovanna Lucchini, Persis Amrolia, Austen Worth, Bobby Gaspar, Waseem Qasim, Paul Veys




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ADA2 deficiency: clonal lymphoproliferation in a subset of patients

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Luca Trotta, Timi Martelius, Timo Siitonen, Timo Hautala, Sari Hämäläinen, Hanna Juntti, Mervi Taskinen, Mette Ilander, Emma Irene Andersson, Andrey Zavialov, Meri Kaustio, Riikka Keski-Filppula, Michael Hershfield, Satu Mustjoki, Terhi Tapiainen, Mikko Seppänen, Janna Saarela




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Increased GATA-3 and T-bet expression in eosinophilic esophagitis vs gastroesophageal reflux disease

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Benjamin L. Wright, Nathalie Nguyen, Kelly P. Shim, Joanne C. Masterson, Elizabeth A. Jacobsen, Sergei I. Ochkur, James J. Lee, Glenn T. Furuta




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Asthma, COPD and overlap in a national cohort: ACO on a gradient

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Arnaud Bourdin, Carey M. Suehs, Gregory Marin, Isabelle Vachier, Eric Matzner-Lober, Pascal Chanez, Nicolas Molinari




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Abnormal differentiation of B cells and megakaryocytes in Roifman syndrome

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Jessica Heremans, Josselyn E. Garcia-Perez, Ernest Turro, Susan M. Schlenner, Ingele Casteels, Roxanne Collin, Francis de Zegher, Daniel Greene, Stephanie Humblet-Baron, Sylvie Lesage, Patrick Matthys, Christopher J. Penkett, Karen Put, Kathleen Stirrups, Chantal Thys, Chris Van Geet, Erika Van Nieuwenhove, Carine Wouters, Isabelle Meyts, Kathleen Freson, Adrian Liston
BackgroundRoifman syndrome is a rare inherited disorder characterized by spondyloepiphyseal dysplasia, growth retardation, cognitive delay, hypogammaglobulinemia and, in some patients, thrombocytopenia. Compound heterozygous variants in small nuclear RNA gene RNU4ATAC, necessary for U12-type intron splicing, were recently identified to drive Roifman syndrome.ObjectiveWe studied three patients from two unrelated kindreds harboring compound heterozygous or homozygous stem II variants in RNU4ATAC to gain insights in the mechanisms behind this disorder.MethodsWe systematically profiled the immunological and hematological compartments of the three Roifman patients and performed RNA sequencing to unravel important splicing defects in both cell lineages.ResultsThe patients exhibited a dramatic reduction in B cells, with differentiation halted at the transitional B cell stage. Despite abundant BAFF availability, development past this BAFF-dependent stage was crippled, with disturbed minor splicing of the critical MAPK1 signaling component. In the hematological compartment, Roifman patients demonstrated defects in megakaryocyte differentiation, with inadequate generation of proplatelets. Roifman platelets were rounder, with elevated tubulin and actin levels, and contained increased alpha and dense granule markers. Significant minor intron retention in 354 megakaryocyte genes was observed, including DIAPH1 and HPS1, genes known to regulate platelet and dense granule formation, respectively.ConclusionTogether, our results provide novel molecular and cellular data towards understanding the immunological and hematological features of Roifman syndrome.

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Single cell profiling of peanut-responsive T cells in peanut allergic subjects reveals heterogeneous effector Th2 subsets

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): David Chiang, Xintong Chen, Stacie M. Jones, Robert A. Wood, Scott H. Sicherer, A. Wesley Burks, Donald Y.M. Leung, Charuta Agashe, Alexander Grishin, Peter Dawson, Wendy F. Davidson, Leah Newman, Robert Sebra, Miriam Merad, Hugh A. Sampson, Bojan Losic, M. Cecilia Berin
BackgroundThe contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood.ObjectivesOur objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of individuals with and without peanut allergy (PA).MethodsWe obtained samples from PA individuals, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (CoFAR6). Subjects were confirmed as PA, or if they passed a 1 g peanut challenge they were termed high-threshold (HT). Healthy controls (HC) were also recruited. Peanut-responsive T cells were identified by CD154 expression after 6-18h of stimulation with peanut extract. Cells were analyzed by flow cytometry and single cell RNA sequencing.ResultsPA individuals had tissue and follicle-homing peanut-responsive CD4+ T cells with a heterogeneous pattern of Th2 differentiation, while controls had undetectable T cell responses to peanut. The PA group had a delayed and IL-2-dependent upregulation of CD154 on cells expressing Treg markers, which was absent in HC or HT individuals. Depletion of Tregs in vitro enhanced cytokine production in HC and PA subjects, but cytokines associated with highly differentiated Th2 cells were more resistant to Treg suppression in PA subjects. Analysis of gene expression by single cell RNAseq identified T cells with highly correlated expression of IL4, IL5, IL9, IL13 and the IL-25 receptor IL17RB.ConclusionsThese results demonstrate the presence of highly differentiated Th2 cells producing Th2-associated cytokines with functions beyond IgE-class switch in peanut allergy. A multi-functional Th2 response was more evident than a Treg deficit among peanut-responsive T cells.

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Toll-like Receptor 2 Ligation of Mesenchymal Stem Cells Alleviates Asthmatic Airway Inflammation

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Hui-Chieh Yu, Bor-Luen Chiang




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Basophils from allergic patients are neither hyper-responsive to activation signals nor hypo-responsive to inhibition signals

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Lydie Cassard, Katia Sperber, Tan-Phuc Buivan, Aurélie Cotillard, Raphaëlle Bourdet-Sicard, Matthew L. Albert, Estelle Mottez, Jérôme Laurent, Marie-Thérèse Guinnepain, Marc Daëron
BackgroundBasophil activation contributes to inflammatory reactions, especially in allergy. It is controlled, positively and negatively, by several mechanisms. High-affinity IgE receptors (FcεRI) generate a mixture of activation and inhibition signals upon aggregation, whose ratio depends on the concentration of allergen recognized by receptor-bound IgE. Low-affinity IgG receptors (FcγRIIA/B) generate inhibition signals when co-engaged with FcεRI by allergen-antibody immune complexes. Commensal and probiotic bacteria such as L. paracasei generate inhibition signals by still unclear mechanisms.ObjectiveInvestigate whether mechanisms that control, positively and negatively, basophil activation, which were unraveled and studied in basophils from normal donors, are functional in allergic patients.MethodsFcεRI and FcγRIIA/B expression, FcεRI-dependent activation, FcεRI-dependent inhibition, and FcγRIIB-dependent inhibition were examined in blood basophils incubated overnight with L. paracasei or without, and challenged under 10 experimental conditions. Basophils from normal donors were compared with basophils from patients who consulted an allergology outpatient clinic over a period of 3 months with respiratory allergy, anaphylaxis antecedents, chronic urticaria, and/or atopic dermatitis.ResultsPatient basophils expressed neither more FcεRI nor less FcγRIIB than basophils from normal donors. They were neither hyper-reactive to positive regulation nor hypo-reactive to negative regulation, whatever the receptors or the mechanisms involved and whatever the allergic manifestations patients suffered from.ConclusionRegulatory mechanisms that control basophil activation are fully functional in allergic patients. Intrinsic defects in these mechanisms do not explain allergic manifestation. Based on these mechanisms, "immune checkpoint modifiers" can be developed as novel therapeutic tools for allergy.

Teaser

Basophils from allergic patients are neither hyper-responsive to IgE-induced activation nor hypo-responsive to IgG- and/or lactobacilli-induced inhibition. Mechanisms that control basophil activation can therefore be used as therapeutic tools in allergic diseases.


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Engineering and stable production of recombinant IgE for cancer immunotherapy and AllergoOncology

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Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Silvia Crescioli, Giulia Chiaruttini, Silvia Mele, Kristina M. Ilieva, Giulia Pellizzari, Daniel I.R. Spencer, Richard A. Gardner, Katie E. Lacy, James F. Spicer, Andrew N.J. Tutt, Gerd K. Wagner, Sophia N. Karagiannis

Teaser

We developed a versatile, novel, time- and resource-effective tool for production of functional IgE at high yields that has wide application potential in basic research and clinical evaluations in allergy, cancer immunotherapy and AllergoOncology.


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How to prevent and improve crepey skin

A look at crepey skin, a common complaint where the skin looks thin and wrinkled. Included is detail on prevention and the role of nutrition.

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Engaging Universities as Partners and Proponents of the New Urban Agenda: Coordination, Spatial Strategies, Access

Addie, JD; (2016) Engaging Universities as Partners and Proponents of the New Urban Agenda: Coordination, Spatial Strategies, Access. UCL City Leadership Lab: London, UK. Green open access

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Italo Calvino prima e dopo la guerra: il fascismo, Ariosto e l’uomo a cavallo

Sica, B; (2017) Italo Calvino prima e dopo la guerra: il fascismo, Ariosto e l'uomo a cavallo. In: Turi, N, (ed.) Raccontare la guerra. I conflitti bellici e la modernità. (pp. 127-152). Firenze University Press: Florence, Italy. Green open access

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Submission to the UN Day of General Discussion on the Right to Education for Persons with Disabilities, 15th April 2015

Scior, K; Hamid, A; Kett, M; (2015) Submission to the UN Day of General Discussion on the Right to Education for Persons with Disabilities, 15th April 2015. UN Committee on the Convention on the Rights of Persons with Disabilities: Geneva, Switzerland.

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Protein losses and urea nitrogen underestimate total nitrogen losses in peritoneal dialysis and haemodialysis patients

Salame, C; Eaton, SJ; Grimble, G; Davenport, A; (2018) Protein losses and urea nitrogen underestimate total nitrogen losses in peritoneal dialysis and haemodialysis patients. Journal of Renal Nutrition (In press).

http://ift.tt/2nsxedh

We Will Always Have International Law: Editorial Note

Paparinskis, M; (2018) We Will Always Have International Law: Editorial Note. Baltic Yearbook of International Law (In press).

http://ift.tt/2DQVssJ

Nomination to a Public Service

Gonis, N; (2015) Nomination to a Public Service. In: Bastianini, G and Gonis, N and Russo, S, (eds.) Charisterion per Revel A. Coles: trenta testi letterari e documentari dall'Egitto (P. Coles). (pp. 147-149). Firenze University Press: Florence, Italy.

http://ift.tt/2nvWRtt

Profiles in paint: contrasting responses to a common artistic exercise by people with different dementias

Harrison, CR; Carton, AM; Brotherhood, EV; Hardy, CJD; Cohen, MH; Warren, JD; Crutch, SJ; (2017) Profiles in paint: contrasting responses to a common artistic exercise by people with different dementias. Arts and Health 10.1080/17533015.2017.1402795 . (In press).

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The role of secondary outcomes in multivariate meta-analysis

White, IR; Copas, JB; Jackson, D; Riley, RD; (2018) The role of secondary outcomes in multivariate meta-analysis. Journal of the Royal Statistical Society. Series C (Applied Statistics) (In press).

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A comparison of 7 random-effects models for meta-analyses that estimate the summary odds ratio

Jackson, D; Law, M; Stijnen, T; Viechtbauer, W; White, IR; (2018) A comparison of 7 random-effects models for meta-analyses that estimate the summary odds ratio. Statistics in Medicine 10.1002/sim.7588 . (In press). Green open access

http://ift.tt/2DPJIX9

rpsftm: An R package for rank preserving structural failure time models

Allison, A; White, IR; Bond, S; (2017) rpsftm: An R package for rank preserving structural failure time models. The R Journal , 9 (2) pp. 342-353. Green open access

http://ift.tt/2nsG3Uk

Motor Neuron Gene Therapy: Lessons from Spinal Muscular Atrophy for Amyotrophic Lateral Sclerosis

Tosolini, AP; Sleigh, JN; (2017) Motor Neuron Gene Therapy: Lessons from Spinal Muscular Atrophy for Amyotrophic Lateral Sclerosis. Frontiers in Molecular Neuroscience , 10 , Article 405. 10.3389/fnmol.2017.00405 . Green open access

http://ift.tt/2DRzvJS

Customs House Receipt

Gonis, Nikolaos; (2015) Customs House Receipt. In: Charisterion per Revel A. Coles : trenta testi letterari e documentari dall'Egitto (P. Coles). (pp. 118-119). Firenze University Press: Florence, Italy.

http://ift.tt/2nuIbef

Imaging the human placental microcirculation with micro-focus computed tomography: Optimisation of tissue preparation and image acquisition

Pratt, R; Hutchinson, JC; Melbourne, A; Zuluaga, MA; Virasami, A; Vercauteren, T; Ourselin, S; ... David, AL; + view all Pratt, R; Hutchinson, JC; Melbourne, A; Zuluaga, MA; Virasami, A; Vercauteren, T; Ourselin, S; Sebire, NJ; Arthurs, OJ; David, AL; - view fewer (2017) Imaging the human placental microcirculation with micro-focus computed tomography: Optimisation of tissue preparation and image acquisition. Placenta , 60 pp. 36-39. 10.1016/j.placenta.2017.09.013 . Green open access

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Sustained striatal dopamine levels following intestinal levodopa infusions in Parkinson's disease patients

Politis, M; Sauerbier, A; Loane, C; Pavese, N; Martin, A; Corcoran, B; Brooks, DJ; ... Piccini, P; + view all Politis, M; Sauerbier, A; Loane, C; Pavese, N; Martin, A; Corcoran, B; Brooks, DJ; Ray-Chaudhuri, K; Piccini, P; - view fewer (2017) Sustained striatal dopamine levels following intestinal levodopa infusions in Parkinson's disease patients. Movement Disorders , 32 (2) pp. 235-240. 10.1002/mds.26848 .

http://ift.tt/2num87k

Radiocarbon test for demographic events in written and oral history

Edinborough, K; Porcic, M; Martindale, A; Brown, TJ; Supernant, K; Ames, KM; (2017) Radiocarbon test for demographic events in written and oral history. Proceedings of the National Academy of Sciences of the United States of America , 114 (47) pp. 12436-12441. 10.1073/pnas.1713012114 .

http://ift.tt/2DQNBv5

A Coptic account of wine on an amphora

Tait, William J; Bailey, DM; (2015) A Coptic account of wine on an amphora. In: Bastianini, G and Gonis, N and Russo, S, (eds.) Charisterion per Revel A. Coles: trenta testi letterari e documentari dall'Egitto (P.Coles). (pp. 154-164). Firenze University Press: Florence, Italy.

http://ift.tt/2nsFGco

Key components of the delirium syndromeand mortality: greater impact of acutechange and disorganised thinking in aprospective cohort study

Diwell, RA; Davis, DH; Vickerstaff, V; Sampson, EL; (2018) Key components of the delirium syndromeand mortality: greater impact of acutechange and disorganised thinking in aprospective cohort study. BMC Geriatrics , 18 , Article 24. 10.1186/s12877-018-0719-1 . Green open access

http://ift.tt/2DPqvoO

Demographic History of the Genus Pan Inferred from Whole Mitochondrial Genome Reconstructions

Lobon, I; Tucci, S; De Manuel, M; Ghirotto, S; Benazzo, A; Prado-Martinez, J; Lorente-Galdos, B; ... Marques-Bonet, T; + view all Lobon, I; Tucci, S; De Manuel, M; Ghirotto, S; Benazzo, A; Prado-Martinez, J; Lorente-Galdos, B; Nam, K; Dabad, M; Hernandez-Rodriguez, J; Comas, D; Navarro, A; Schierup, MH; Andres, AM; Barbujani, G; Hvilsom, C; Marques-Bonet, T; - view fewer (2016) Demographic History of the Genus Pan Inferred from Whole Mitochondrial Genome Reconstructions. Genome Biology and Evolution , 8 (6) pp. 2020-2030. 10.1093/gbe/evw124 . Green open access

http://ift.tt/2nuhqqn

Evaluating Bayesian spatial methods for modelling species distributions with clumped and restricted occurrence data

Redding, DW; Lucas, TCD; Blackburn, TM; Jones, KE; (2017) Evaluating Bayesian spatial methods for modelling species distributions with clumped and restricted occurrence data. PLOS ONE , 12 (11) , Article e0187602. 10.1371/journal.pone.0187602 . Green open access

http://ift.tt/2DQKnYz

The Tractatus on unity

Zalabardo, JL; (2018) The Tractatus on unity. Australasian Philosophical Review (In press).

http://ift.tt/2E404Li

A Multicenter Open-label Phase II Trial to Evaluate Nivolumab and Ipilimumab for 2nd Line Therapy in Elderly Patients With Advanced Esophageal Squamous Cell Cancer

Conditions:   Esophageal Cancer;   Oesophageal Cancer;   Oesophageal Cancer Metastatic;   Esophageal Cancer Metastatic;   Esophageal Cancers NOS;   Oesophageal Cancer Nos;   GastroEsophageal Cancer;   Gastrooesophageal Cancer
Interventions:   Drug: Nivolumab;   Drug: Ipilimumab
Sponsors:   AIO-Studien-gGmbH;   Bristol-Myers Squibb
Not yet recruiting

http://ift.tt/2BGvORh

Radiofrequency in Differentiated Thyroid Cancer Metastatic Lymph Node: Prospective Study of Safety and Efficacy

Condition:   Differentiated Thyroid Cancer
Intervention:   Device: Radiofrequency (RF star electrode electrode_Fixed)
Sponsor:   Assistance Publique - Hôpitaux de Paris
Not yet recruiting

http://ift.tt/2norWjK

Interest of a Tongue Strength Measurement in the Screening for Sarcopenia in Hospitalized Elderly Patients

Condition:   Sarcopenia
Interventions:   Device: Tongue strength measurement;   Procedure: Blood sampling;   Diagnostic Test: Mini Mental State Examination (MMSE);   Diagnostic Test: Minimal nutritional assessment (MNA-SF);   Diagnostic Test: Dual-energy x-ray absorptiometry (DEXA);   Device: Dynamometer (Hand grip );   Diagnostic Test: Walking speed
Sponsor:   Murielle Surquin
Not yet recruiting

http://ift.tt/2BHuPQK

Tension pneumoperitoneum

A 35-year-old man stopped breathing after injecting a large dose of heroin. He subsequently received cardiopulmonary resuscitation from friends. He arrived to accident and emergency department with Glasgow Coma Scale of 13. On examination, he had distended and tense abdomen. CT Thorax, Abdomen, and Pelvis confirmed massive tension pneumoperitoneum. A 14 Fr intravenous cannula was inserted through the umbilicus to relieve the intra-abdominal pressure. An emergency laparotomy showed petechia along the anterior gastric wall, haematoma of lesser omentum but showed no evidence of gastrointestinal perforation or organ injury. Air leak test performed by insufflating air into the stomach via nasogastric tube and abdomen filled with normal saline showed no leak. On-table oesophagogastroduodenoscopy showed mild oesophagitis and petechia of cardiac gastric mucosa. He was treated with intravenous antibiotics and discharged on the fifth postoperative day with adequate analgesia.



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Neurofibromatosis type 1: a case highlighting pulmonary and other rare clinical manifestations

Neurofibromatosis type 1 (NF1)-related lung disease is a rare but increasingly recognised, high morbidity associated feature of the condition. We present a 48-year-old male patient with NF1, who was initially admitted for a subarachnoid haemorrhage requiring aneurysmal coil embolisation. During his recovery, he developed a left-sided pneumothorax requiring chest tube placement followed by concerns for re-expansion pulmonary oedema requiring intubation. Subsequently, the patient also developed a right-sided pneumothorax requiring additional chest tube placement but did not develop right-sided pulmonary oedema. During his hospitalisation, the patient also exemplified other important NF1-related pathophysiology including pheochromocytoma, cerebrovascular abnormalities and cardiovascular manifestations. Due to his multiple comorbidities and poor prognosis, we held a goals of care discussion with the patient's mother, and with her agreement, the patient underwent compassionate withdrawal of artificial life support.



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Effective uric acid reduction with probenecid and febuxostat in a patient with chronic kidney disease

A 33-year-old male with poorly controlled chronic tophaceous gout and chronic kidney disease (CKD) with estimated glomerular filtration rate (GFR) of 37 cc/min. His uric acid was 11 mg/dL despite maximal dosing of febuxostat. He had previously failed pegloticase infusions as well. This patient had a reduction in his uric acid level to less than 6 mg/dL following addition of probenecid to his febuxostat regimen. Most guidelines recommend against utilisation of probenecid therapy in patients with GFR <50, but there is no obvious contraindication to its use, provided renal calculi do not develop. Our case illustrates the synergistic effect probenecid can add to maximal xanthine oxidase inhibitor therapy for patients with refractory hyperuricaemia in a patient with CKD stage IIIb. With the approval of a new uricosuric medication, lesinurad, probenecid may remain a suitable alternative for patients with financial limitations to achieve target uric acid levels.



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High-dose steroids as a therapeutic option in the management of spur cell haemolytic anaemia

Spur cell haemolytic anaemia (SCA) is a form of anaemia that can be seen in patients with severely impaired liver function or advanced cirrhosis. It is associated with high mortality. The treatment options for SCA secondary to cirrhosis are limited. Our patient is a middle-aged man who developed SCA and was not a candidate for liver transplantation or splenectomy. High-dose steroids helped ameliorate haemolysis and improve anaemia and general condition of our patient.



http://ift.tt/2ErPwmY

Antenatal chemotherapy in a case of diffuse large B-cell lymphoma

A 28-year-old pregnant woman in the sixth month of gestation presented with complaints of altered bowel habit for a month, on examination found to have generalised lymphadenopathy, pedal oedema and locally infiltrating ano-rectal growth. Rectal growth biopsy was reported as high-grade B-cell lymphoma. After a discussion in a multidisciplinary panel consisting of haemato-oncologists, obstetricians and physicians, she was planned to receive antenatal chemotherapy. She delivered a live baby of 1.86 kg at 36 weeks of gestational age by normal vaginal delivery. After 6 cycles of chemotherapy she had complete regression of the disease.



http://ift.tt/2DNaL1f

Cisplatin-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) with life-threatening hyponatraemia

We present a case of cisplatin-induced syndrome of inappropriate antidiuretic hormone (SIADH) in a patient with metastatic recurrent urothelial carcinoma. Cisplatin-induced SIADH is an uncommon but potentially life-threatening toxicity. Pharmacogenetic characteristics may result in different toxicity profiles in different populations. With such widespread use of cisplatin in a diverse range of cancers, prompt recognition is crucial to detect and prevent severe neurological sequelae.



http://ift.tt/2EqeoeM

When a wound is the harbinger of a serious underlying systemic illness

A 55-year-old woman presented with progressive enlarging and painful non-healing ulcers on her bilateral lower extremities; biopsy was consistent with pyoderma gangrenosum. Workup for an underlying illness revealed a cavitary lung nodule and an ulcerating mass in the anal canal. Patient did not have any respiratory or gastrointestinal symptoms. Differential diagnosis included inflammatory bowel disease, rectal carcinoma or infection such as tuberculosis, fungal process. Histopathology did not reveal any malignancy, inflammatory bowel disease or infection. Serological studies were positive for perinuclear antineutrophil antibodies specific to proteinase-3 antigen, and the patient was ultimately diagnosed with granulomatosis with polyangiitis. Intravenous pulse dose steroids were initiated followed by monthly pulse cyclophosphamide for 6 months, resulting in rapid and significant improvement of the wounds.



http://ift.tt/2DQxyJA

Two patients with localised hyperhidrosis of the hand based on functional and structural abnormalities of sweat glands

A 14-year-old girl and a 30-year-old woman presented with localised hyperhidrosis on the dorsal hand and wrist, respectively, provoked by different stimuli such as physical activity and minor trauma to the skin. The skin was seemingly normal in both patients where an iodine–starch test revealed a well-demarcated area of hyperhidrosis. Following histopathological examination, the diagnosis was unilateral localised hyperhidrosis in both cases; one with normal histology and one with a nevus sudoriferous. Both patients were successfully treated with botulinum toxin type A. The 30-year-old woman additionally used low-dose propantheline bromide periodically and experienced long-term remission on this therapy. Hyperhidrosis may embarrass and interfere with patients' school and careers, and it is therefore important to tailor an effective individual treatment.



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Is eosinophilic esophagitis a member of the atopic march?

The Atopic March refers to the natural history of allergic diseases as they develop over the course of infancy and childhood. As we detail in our accompanying review (see page XXX in this issue), "the March" classically begins with atopic dermatitis (AD), and progresses to immunoglobulin E (IgE)–mediated food allergy (FA), asthma, and allergic rhinitis (AR). In addition to its characteristic progression, members of the March have been shown to predispose to the development of subsequent allergic conditions.

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Instructions for Authors



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What can we learn about predictors of atopy from birth cohorts and cord blood biomarkers?

Atopic disorders such as allergy and asthma are affecting children at an increasing rate.1 The reason for this increase and the precise mechanisms behind the development of allergic disorders in children are unclear. Factors such as family history, prenatal exposures, and early childhood exposures are each known to be involved in atopy development in children. The use of large-scale birth cohorts has presented a useful opportunity to study the relations among risk factors, potential biomarkers in cord blood, early life exposures, and their associations with atopy.

http://ift.tt/2GuxBMV

Information for Readers



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Suspected asthma status and time spent in physical activity across multiple childhood age groups

Asthma is the most common chronic condition in children worldwide; however, rates of overdiagnosis are high, particularly when the case definition is not confirmed by spirometric assessment.1 However, it is important to encourage physical activity (PA) in children and adolescents across age groups regardless of asthma status because a physically active lifestyle is associated with many beneficial health outcomes.2

http://ift.tt/2Gx2QqL

Current insights in allergen immunotherapy

Allergen-specific immunotherapy (AIT) in its subcutaneous and sublingual forms is currently a well-established and experimentally supported treatment for respiratory allergy and hymenoptera venom allergy. There have been advances in its use linked strictly to the advancement in the knowledge of the molecular mechanisms of allergy, the production of well-characterized extracts, and diagnostic techniques. The use of AIT in asthma and the application of new approaches are expanding. We briefly review the advances and concerns in the use of AIT.

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Can the atopic march be predicted?

The "atopic march" refers to the progression from inflammatory skin manifestations in early life, usually diagnosed as "atopic dermatitis," to subsequent food allergy, asthma, and allergic rhinitis. Hill and Spergel1 note that the skin inflammation likely results from a primary skin barrier defect interacting with genetic or environmental susceptibility, which could lead to the development of inflammation mediated by T-helper cell type 2. However, up to two-thirds of children with atopic dermatitis do not have atopy as judged by skin prick test reactions or serum immunoglobulin E levels.

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Clinical and economic burden of hospitalizations with registration of penicillin allergy

Penicillin allergy is commonly reported, but only a minority of claimants has a confirmed diagnosis. Nevertheless, patients labeled as having penicillin allergy are treated with second-line antibiotics, which are more expensive and less effective, possibly increasing the risk of drug-resistant infections.

http://ift.tt/2GxZEuY

Allergic sensitization and sleep in children with asthma

Esteban et al1 investigated the association between increased allergic sensitization and sleep outcomes in 196 urban schoolchildren, aged 7 to 9 years, with persistent asthma. By hierarchical regression analysis, the number of positive allergy test results significantly predicted variability in sleep efficiency. In addition, variability in forced expiratory volume in 1 second was a significant moderator in the association between number of positive allergy test results and variability in sleep efficiency.

http://ift.tt/2rSJQj4

The atopic march: Fact or folklore?

Atopic dermatitis, allergic rhinitis, and asthma are common, frequently appear together, and usually begin in early life, thus posing lifelong burdens for many affected patients. Based on clinical observations and studies of disease prevalence, it has been proposed that the sequential development of atopic dermatitis, asthma, and allergic rhinitis is a causal relationship now known as the "atopic march"1 (Fig 1). The concept of an atopic march has captured our interest because it earmarked an allergic harbinger of "bad things" to follow.

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The atopic march

The atopic march refers to the natural history of allergic diseases as they develop during infancy and childhood. Introduced by the American allergists A. F. Coca and R. A. Cooke in 1923, the term atopy became closely associated with the IgE molecule after its identification as the carrier of hypersensitivity.1 However, in the context of the atopic march, IgE is a pathophysiologic mediator of some, but not all, atopic diseases. As such, it is better to consider the atopic march as a progression of allergic conditions that have common genetic and environmental predisposing factors, share the immunologic feature of one or more allergen-specific TH2 responses, and are characterized by a type 2 effector phase that can include generation of specific IgE, activation of granulocytes, and other innate features such as mucous production and edema.

http://ift.tt/2rSlQN7

Recent advances in asthma

Low intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) during pregnancy may be associated with an increased risk of childhood wheezing and asthma. Most previous trials of this issue have been underpowered, with inconclusive results. This randomized controlled trial with long-term follow-up evaluated the effects of n-3 LCPUFA supplementation during pregnancy on the risk of wheeze and asthma in offspring. At 24 weeks' gestation, 736 pregnant women were assigned to supplementation with fish oil, containing 2.4 g of n-3 LCPUFA, or olive oil.

http://ift.tt/2GzfPsa

Authors' response

We appreciate the comments on our manuscript. Our study1 investigated the association between allergic sensitization and sleep outcomes in a sample of urban children with persistent asthma. In response to the submitted comments, we would like to clarify our rationale for the specific data analyses mentioned.

http://ift.tt/2GzfIge

Home-based subcutaneous immunoglobulin therapy vs hospital-based intravenous immunoglobulin therapy: A prospective economic analysis

Home-based subcutaneous immunoglobulin (SCIg) administration used for immunoglobulin replacement therapy for patients with primary immunodeficiency has been demonstrated to have benefits compared with hospital-based intravenous immunoglobulin (IVIg) therapy.

http://ift.tt/2rSJM2O

Is the better part of valor truly discretion?

Peanut allergy affects 1.4% to 4.5% of children, depending on the study and methodology. Self-reported estimates have shown an alarming 3-fold increase in US populations over 10 years, whereas UK data from a longitudinal birth cohort with challenge-based evidence have not reflected such an alarming increase.1–4 Unfortunately, for years, the common peanut allergy management paradigm was to strictly avoid any potential exposure (including trace amounts) and carry self-injectable epinephrine. Now, we find the field on the cusp of what could be 2 therapies approved by the US Food and Drug Administration (FDA) for the treatment of peanut allergy in children in late 2018 or early 2019 (a commercial low-dose oral immunotherapy [OIT] capsule and an epicutaneous patch).

http://ift.tt/2rV9Eet

Patterns of electronic cigarette use in youth with asthma: Results from a nationally representative sample

The prevalence of electronic cigarette (EC) use among youth in the United States is rising, with an estimated 4.3% of middle and 11.3% of high school students reporting EC use in 2016.1 Harm perception and family tobacco use could be contributing factors.2 Approximately 1 in 3 middle and high school students in the United States believe EC use is less harmful than cigarettes, regardless of smoking status.2 Adolescents who currently use ECs or have a family member who uses tobacco products are more likely to endorse ECs as less harmful than cigarettes.

http://ift.tt/2GzM6iq

Contribution of an impaired epithelial barrier to the atopic march

Allergic childhood diseases exhibit a high degree of comorbidity. The concept of the atopic march is based on observations that eczema tends to precede later development of asthma and allergic rhinitis (AR). The causal nature of this progression, however, remains a topic of debate. It has been suggested that the atopic march is initiated through eczema in early childhood and that eczema promotes the development of food and airway allergies by driving systemic sensitization through a compromised epithelial barrier.

http://ift.tt/2rURUjq

Editorial Board



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Component-resolved diagnosis in selecting patients for yellowjacket venom immunotherapy

Venom immunotherapy is effective in preventing systemic allergic reactions (SARs), but the diagnosis of venom allergy is problematic.

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Table of Contents



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Editorial Board



http://ift.tt/2rUOEoi

Synchrotron analysis of human organ tissue exposed to implant material

Swiatkowska, I; Mosselmans, FW; Geraki, T; Wyles, CC; Maleszewski, JJ; HENCKEL, J; Sampson, B; ... Hart, A; + view all Swiatkowska, I; Mosselmans, FW; Geraki, T; Wyles, CC; Maleszewski, JJ; HENCKEL, J; Sampson, B; Potter, D; Osman, I; Trousdale, RT; Hart, A; - view fewer (2018) Synchrotron analysis of human organ tissue exposed to implant material. Journal of Trace Elements in Medicine and Biology , 46 pp. 128-137. 10.1016/j.jtemb.2017.12.007 .

http://ift.tt/2ErDc6c

Societal costs of permanent childhood hearing loss at teen age: a cross-sectional cohort follow-up study of universal newborn hearing screening

Chorozoglou, M; Mahon, HM; Pimperton, H; Worsfold, S; Kennedy, C; (2018) Societal costs of permanent childhood hearing loss at teen age: a cross-sectional cohort follow-up study of universal newborn hearing screening. BMJ Paediatrics Open (In press).

http://ift.tt/2DQG1MP

Photoinduced Formation Mechanism of the Thymine-Thymine (6-4) Adduct in DNA; a QM(CASPT2//CASSCF):MM(AMBER) study

Giussani, A; Conti, I; Nenov, A; Garavelli, M; (2017) Photoinduced Formation Mechanism of the Thymine-Thymine (6-4) Adduct in DNA; a QM(CASPT2//CASSCF):MM(AMBER) study. Faraday Discussions 10.1039/C7FD00202E .

http://ift.tt/2EsHlqC

Key acceptability attributes of orodispersible films

Scarpa, M; Paudel, A; Kloprogge, F; Kai Hsiao, W; Bresciani, M; Gaisford, S; Orlu, M; (2018) Key acceptability attributes of orodispersible films. European Journal of Pharmaceutics and Biopharmaceutics 10.1016/j.ejpb.2018.01.003 . (In press).

http://ift.tt/2DQFNFt

Serum Albumin as a Prognostic Marker for Serious Non-AIDS Endpoints in the Strategic Timing of Antiretroviral Treatment (START) Study

Ronit, A; Sharma, S; Baker, JV; Mngqibisa, R; Delory, T; Caldeira, L; Ndembi, N; ... International Network for Strategic Initiatives in Global HIV Tr, ; + view all Ronit, A; Sharma, S; Baker, JV; Mngqibisa, R; Delory, T; Caldeira, L; Ndembi, N; Lundgren, JD; Phillips, AN; International Network for Strategic Initiatives in Global HIV Tr, ; - view fewer (2018) Serum Albumin as a Prognostic Marker for Serious Non-AIDS Endpoints in the Strategic Timing of Antiretroviral Treatment (START) Study. Journal of Infectious Diseases 10.1093/infdis/jix350 . (In press).

http://ift.tt/2Esk7Rt

Multilingual London and its Literatures

Salverda, R; (2006) Multilingual London and its Literatures. Opticon 10.5334/opt.010603 . Green open access

http://ift.tt/2DNHS5i

Electronic Devices For Cognitive Impairment Screening: A Systematic Literature Review

Antonio Garcia-Casal, J; Franco-Martin, M; Victoria Perea-Bartolome, M; Miguel Toribio-Guzman, J; Garcia-Moja, C; Goni-Imizcoz, M; Csipke, E; (2017) Electronic Devices For Cognitive Impairment Screening: A Systematic Literature Review. International Journal of Technology Assessment in Health Care , 33 (6) pp. 654-673. 10.1017/S0266462317000800 .

http://ift.tt/2EpGZAM

Africa's urban adaptation transition under a 1.5° climate

Pelling, M; Leck, H; Pasquini, L; Ajibade, I; Osuteye, E; Parnell, S; Lwasa, S; ... Boubacar, S; + view all Pelling, M; Leck, H; Pasquini, L; Ajibade, I; Osuteye, E; Parnell, S; Lwasa, S; Johnson, C; Fraser, A; Barcena, A; Boubacar, S; - view fewer (2018) Africa's urban adaptation transition under a 1.5° climate. Current Opinion in Environmental Sustainability , 31 pp. 10-15. 10.1016/j.cosust.2017.11.005 . (In press). Green open access

http://ift.tt/2DR73DZ

TARGETING THE T-CELL RECEPTOR Β-CONSTANT DOMAIN FOR IMMUNOTHERAPY OF T-CELL MALIGNANCIES

Maciocia, P; Wawrzyniecka, P; Philip, B; Ricciardelli, I; Akarca, AU; Onohua, S; Cole, D; ... Pule, M; + view all Maciocia, P; Wawrzyniecka, P; Philip, B; Ricciardelli, I; Akarca, AU; Onohua, S; Cole, D; Sewell, A; Peggs, K; Linch, D; marafioti, T; Pule, M; - view fewer (2017) TARGETING THE T-CELL RECEPTOR Β-CONSTANT DOMAIN FOR IMMUNOTHERAPY OF T-CELL MALIGNANCIES. Presented at: 14th International Conference on Malignant Lymphoma Palazzo dei Congressi,, Lugano.

http://ift.tt/2EnK1FH

The virtual maze: A behavioural tool for measuring trust

Hale, J; Payne, MEM; Taylor, KM; Paoletti, D; Hamilton, AFDC; (2018) The virtual maze: A behavioural tool for measuring trust. Quarterly Journal of Experimental Psychology 10.1080/17470218.2017.1307865 . (In press). Green open access

http://ift.tt/2DS2vxb

Targeting T-Cell Receptor β-Constant Domain for Immunotherapy of T-Cell Malignancies

Maciocia, P; Wawrzyniecka, P; Philip, B; Ricciardelli, I; Akarca, AU; Onuoha, S; Cole, D; ... Pule, MA; + view all Maciocia, P; Wawrzyniecka, P; Philip, B; Ricciardelli, I; Akarca, AU; Onuoha, S; Cole, D; Sewell, A; Peggs, KS; Linch, DC; marafioti, T; Pule, MA; - view fewer (2016) Targeting T-Cell Receptor β-Constant Domain for Immunotherapy of T-Cell Malignancies. Presented at: UNSPECIFIED.

http://ift.tt/2Er7RAl

Sciencey Girls: Discourses Supporting Working-Class Girls to Identify with Science

Godec, S; (2018) Sciencey Girls: Discourses Supporting Working-Class Girls to Identify with Science. Education Sciences , 8 (1) , Article 19. 10.3390/educsci8010019 . Green open access

http://ift.tt/2DO5bMm

A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers

Vehof, J; Hysi, PG; Hammond, CJ; (2017) A Metabolome-Wide Study of Dry Eye Disease Reveals Serum Androgens as Biomarkers. Ophthalmology , 124 (4) pp. 505-511. 10.1016/j.ophtha.2016.12.011 . Green open access

http://ift.tt/2Eskco9

Adaptive designs in clinical trials: why use them, and how to run and report them

Pallmann, P; Sydes, MR; Other authors, M; (2018) Adaptive designs in clinical trials: why use them, and how to run and report them. BMC Medicine 10.1186/s12916-018-1017-7 . (In press).

http://ift.tt/2DOCoXY

Investigation of Resistance Switching in SiOx RRAM Cells Using a 3D Multi-Scale Kinetic Monte Carlo Simulator

Sadi, T; Mehonic, A; Montesi, L; Buckwell, M; Kenyon, A; Asenov, A; (2018) Investigation of Resistance Switching in SiOx RRAM Cells Using a 3D Multi-Scale Kinetic Monte Carlo Simulator. Journal of Physics: Condensed Matter 10.1088/1361-648X/aaa7c1 . (In press).

http://ift.tt/2EpZuFd

Deeper Understanding of Interstitial Boron-Doped Anatase Thin Films as A Multifunctional Layer Through Theory and Experiment

Quesada-Gonzalez, M; Williamson, BAD; Sotelo-Vazquez, C; Kafizas, A; Boscher, ND; Quesada-Cabrera, R; Scanlon, DO; ... Parkin, IP; + view all Quesada-Gonzalez, M; Williamson, BAD; Sotelo-Vazquez, C; Kafizas, A; Boscher, ND; Quesada-Cabrera, R; Scanlon, DO; Carmalt, CJ; Parkin, IP; - view fewer (2018) Deeper Understanding of Interstitial Boron-Doped Anatase Thin Films as A Multifunctional Layer Through Theory and Experiment. The Journal of Physical Chemistry C , 122 (1) pp. 714-726. 10.1021/acs.jpcc.7b11142 .

http://ift.tt/2DNM8S8

Tourism livelihoods in Smøla, Norway

Kelman, I; Linnell, J; Thomassen, J; Follestad, A; Risan, T; (2017) Tourism livelihoods in Smøla, Norway. Journal of Marine and Island Cultures , 6 (2) , Article v6n2. 10.21463/jmic.2017.06.2.01 . Green open access

http://ift.tt/2Esut3E

Histoid leprosy: clinical and histopathological analysis of patients in follow-up in University Clinical Hospital of endemic country

Abstract

Background

Histoid leprosy (HL) is a rare form of lepromatous leprosy, characterized by hyperchromic indurated nodules above normal skin. Its main histopathological aspect is spindle cells. Because it may simulate other aspects, such as dermatofibroma and neurofibroma, histoid leprosy poses itself as a diagnostic challenge.

Methods

This is a retrospective study with all patients having been selected from the leprosy clinic of the Hospital das Clínicas da Universidade de São Paulo from 2006 to 2016.

Results

There were 12 patients in this study, eight in the histoid group and four in the lepromatous leprosy group. The prevalence of HL was 1.12% in all leprosy subjects. All individuals from HL group were "de novo" cases, and the histopathological analysis of skin lesions presented spindle cells generating a storiform pattern. Immunohistochemistry for CD68, vimentin, and anti-BCG were positive in all 12 cases. Factor XIIIa was visualized only in the papillary dermis, and S100 protein was negative in all biopsies. Smooth-muscle actin was present in 62.5% of the HL samples.

Conclusion

The prevalence of HL was similar to previous reports. However, all histoid patients were "de novo" cases, differing from published studies. Fusocellular macrophage transformation could be explained by the differences in cytoskeleton proteins expressed in histoid lesions in comparison to other leprosy variants, with emphasis on vimentin and smooth muscle actin.



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Miescher nevus as devil's mark, but also as beauty mark



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Retrospective review of 18 British South Asian women with frontal fibrosing alopecia



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Safety of intranasal corticosteroid sprays during pregnancy: an updated review

Abstract

Introduction

Rhinitis and rhinosinusitis are commonly encountered in pregnant women. Intranasal corticosteroid (INCS) sprays are generally safe and effective in the treatment of these conditions in the general population. However, the use of some of these INCS sprays during pregnancy is still controversial.

Objective

To review the current literature about the safety of intranasal corticosteroid sprays during pregnancy.

Methodology

Using different search engines, each type of INCS was reviewed separately (triamcinolone, beclomethasone, budesonide, fluticasone propionate, fluticasone furoate, mometasone, and ciclesonide). A total of 51 full-length articles were examined for eligibility. After applying inclusion and exclusion criteria, a total of three articles were reviewed.

Results

No significant association with congenital organ malformations has been linked to intranasal use of beclomethasone, budesonide, fluticasone propionate, fluticasone furoate, or mometasone. Intranasal triamcinolone, however, has been found to have a significant association with respiratory tract defects. Data about the safety of intranasal ciclesonide during pregnancy are not available.

Conclusion

Lacking sufficient clinical trials on the use of intranasal corticosteroid sprays in pregnancy, we suggest that the intranasal use of fluticasone furoate, mometasone, and budesonide is safe if they are used at the recommended therapeutic dose after a proper medical evaluation. Intranasal fluticasone propionate might be a safe option in the absence of other INCS options due to its questionable efficacy during pregnancy. Risk-benefit ratio should always be considered before prescribing any intranasal corticosteroid sprays during pregnancy.



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Comment on “The effect of septoplasty surgery on serum oxidative stress levels”



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Virtual 3D planning of tracheostomy placement and clinical applicability of 3D cannula design: a three-step study

Abstract

Aim

We aimed to investigate the potential of 3D virtual planning of tracheostomy tube placement and 3D cannula design to prevent tracheostomy complications due to inadequate cannula position.

Materials and methods

3D models of commercially available cannula were positioned in 3D models of the airway. In study (1), a cohort that underwent tracheostomy between 2013 and 2015 was selected (n = 26). The cannula was virtually placed in the airway in the pre-operative CT scan and its position was compared to the cannula position on post-operative CT scans. In study (2), a cohort with neuromuscular disease (n = 14) was analyzed. Virtual cannula placing was performed in CT scans and tested if problems could be anticipated. Finally (3), for a patient with Duchenne muscular dystrophy and complications of conventional tracheostomy cannula, a patient-specific cannula was 3D designed, fabricated, and placed.

Results

(1) The 3D planned and post-operative tracheostomy position differed significantly. (2) Three groups of patients were identified: (A) normal anatomy; (B) abnormal anatomy, commercially available cannula fits; and (C) abnormal anatomy, custom-made cannula, may be necessary. (3) The position of the custom-designed cannula was optimal and the trachea healed.

Conclusions

Virtual planning of the tracheostomy did not correlate with actual cannula position. Identifying patients with abnormal airway anatomy in whom commercially available cannula cannot be optimally positioned is advantageous. Patient-specific cannula design based on 3D virtualization of the airway was beneficial in a patient with abnormal airway anatomy.



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Commentary on “Clinical and audiologic characteristics of patients with sensorineural tinnitus and its association with psychological aspects: an analytic retrospective study”



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European status on temporal bone training: a questionnaire study

Abstract

Purpose

In otorhinolaryngology training, introduction to temporal bone surgery through hands-on practice on cadaveric human temporal bones is the gold-standard training method before commencing supervised surgery. During the recent decades, the availability of such specimens and the necessary laboratory facilities for training seems to be decreasing. Alternatives to traditional training can consist of drilling artificial models made of plaster or plastic but also virtual reality (VR) simulation. Nevertheless, the integration and availability of these alternatives into specialist training programs remain unknown.

Methods

We conducted a questionnaire study mapping current status on temporal bone training and included responses from 113 departments from 23 countries throughout Europe.

Results

In general, temporal bone training during residency in ORL is organized as in-house training, or as participation in national or international temporal bone courses or some combination hereof. There are considerable differences in the availability of training facilities for temporal bone surgery and the number of drillings each ORL trainee can perform. Cadaveric dissection is still the most commonly used training modality.

Conclusions

VR simulation and artificial models are reported to be used at many leading training departments already. Decreasing availability of cadavers, lower costs of VR simulation and artificial models, in addition to established evidence for a positive effect on the trainees' competency, were reported as the main reasons. Most remaining departments expect to implement VR simulation and artificial models for temporal bone training into their residency programs in the near future.



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