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

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.

This article is protected by copyright. All rights reserved.

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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.

This article is protected by copyright. All rights reserved.

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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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Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro

Abstract

Objective

To analyze the influence of an oral bisphosphonate and compare the potency to intravenous bisphosphonates on various cell types as regards the rarity of bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) caused by oral bisphosphonate.

Materials and methods

A viability assay (MTT), a migration assay (Boyden chamber), and an apoptosis assay (Caspase-Glo® 3/7) were performed to analyze the effect of bisphosphonates on human fibroblasts, umbilical vein endothelial cells (HUVEC), and osteoblasts.

Results

Alendronate and intravenous bisphosphonates suppressed cell viability and migration, and induced apoptosis in all tested cell types. Alendronate had a greater impact than ibandronate on the characteristics in fibroblasts and osteoblasts but not as strong as zoledronate.

Conclusions

The incidence of BP-ONJ in oral bisphosphonate treatment is reported to be much lower than that in intravenous bisphosphonates. However, the influences of alendronate on human cells were at least as strong as ibandronate, although it was lower than zoledronate.

Clinical relevance

Alendronate showed strong enough effects to suppress human somatic cells and was comparable to certain intravenous bisphosphonates in potency. This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies.

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Assessment of condylar morphology and position using MSCT in an Asian population

Abstract

Objectives

The purpose of the present study was to investigate the volume, surface, morphometric index (MI), and position of the condyle in a normal population by applying Mimics 17.0 software. Then, the difference between left and right sides, sex, and age can be explored, which will contribute to establish the reference value of condylar morphology and position in normal individuals, and help us to study characteristics of condylar morphology and position in abnormal individuals.

Materials and methods

Three-hundred subjects were enrolled in our study from the radiology department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital. They were divided into three groups according to the age: group 1 (18–24 years old), group 2 (25–34 years old), and group 3 (35–44 years old). Each group included 100 subjects (with 50 males and 50 females). They were examined using multislice computed tomography (MSCT) after that. All images of condyle were reconstructed by Mimics 17.0 software, so as to measure the volume, surface, and MI of condyle, and to analyze the position of condyle in the articular fossa by means of joint spaces.

Results

The differences of condylar volume, surface, and MI between left and right sides were not obvious (P > 0.05). The condylar volume and surface were greater in males than females (P < 0.05), while their condylar MI existed no difference (P > 0.05). No statistical differences were found in volume and surface among three age groups. However, the MI of group 1 was statistically lower than that of group 3 (P < 0.05). On the other hand, no significant differences were found between left and right condylar position (P > 0.05). Nevertheless, there were significant differences of condylar position regarding the gender and age (P < 0.05).

Conclusions

This study showed no significant differences in condylar morphology and position between left and right sides, but factors of gender and age were proven to have a certain influence on the morphology and position of the condyle. This information can be clinically useful in establishing the diagnostic criteria for condylar morphology and position in the normal Asian population.

Clinical relevance

Examination of condylar morphology and position is important for evaluating the abnormalities and bony changes that affect the temporomandibular joint (TMJ). So, this will be conducive to the diagnosis and the evaluation of therapeutic effect of temporomandibular joint diseases. Also, it is important to evaluate these indexes prior to commencing orthodontic treatment, because TMJ abnormalities play a critical role in orthodontic treatment planning.

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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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The effects of rhBMP-2/7 heterodimer and RADA16 hydrogel scaffold on bone formation during rabbit mandibular distraction

Publication date: Available online 31 January 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Ling-fei Ren, Geng-sheng Shi, Yong-qing Tong, Song-yao Jiang, Feng Zhang
PurposeThe effects of a rhBMP-2/7 heterodimer and a RADA16 (Ac-RADARADARADARADA-CONH2) hydrogel scaffold on bone formation during distraction osteogenesis were evaluated.MethodsForty New Zealand white rabbits, which underwent mandibular lengthening, were randomly divided into five groups. One group served as a control group. The others received 2 μg rhBMP-2 homodimer, 2 μg rhBMP-2/7 heterodimer, 100 μL RADA16 or 100 μl RADA16+2 μg rhBMP-2/7 heterodimer in the mandibular distraction gap at the beginning of distraction. [¹⁸F^-] fluoride positron emission tomography (PET) was used to assess osteogenesis both after distraction and at the end of consolidation. Dual-energy X-ray absorptiometer (DEXA) examination and bone histology were also evaluated.ResultsAt the end of distraction, the radioactivity concentration in the distracted area was significantly higher in the RADA16+ rhBMP-2/7 heterodimer group than the other groups (p<0.01); differences between the other four groups were also statistically significant in the following order: rhBMP-2/7 heterodimer group > rhBMP-2 homodimer group > RADA16 group (or control group) (p<0.05). However, the radioactivity concentration of the RADA16 group was slightly higher than that of the control group with a non-significant difference (p>0.05). By the end of consolidation, activity in the control group, RADA16 group, rhBMP-2 homodimer group and rhBMP-2/7 heterodimer group had significantly diminished (p<0.05); however, the activity in the RADA16+ rhBMP-2/7 heterodimer group remained at the same level (p>0.05). DEXA results and bone histology findings indicated that more callus regeneration was noted in the RADA16+ rhBMP-2/7 heterodimer group than any other group.ConclusionRhBMP-2/7 heterodimer and RADA16 hydrogel scaffold significantly promote mandibular distraction osteogenesis.



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Custom-made titanium miniplates associated with a ultra-high molecular weight polyethylene graft in orthognathic surgery: an adjunct to maxillary advancement.

Publication date: Available online 31 January 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): José Thiers Carneiro Júnior, Paulo Hemerson de Moraes, Douglas Voss de Oliveira, Nayara Cristina Monteiro Carneiro
Patients with considerable maxillomandibular anteroposterior discrepancies and maxillary hypoplasia, require corrective treatment through orthognathic surgery. However, in the treatment of severe maxillary retrognathism, it is necessary to reconstruct the areas of bone deficiency through grafting techniques in addition to maxillary advancement using only the Le Fort I osteotomy. Treatment in these patients is more challenging and requires high surgical predictability. Alloplastic materials have often been used for the reconstruction of poor bone contours. Ultrahigh molecular weight polyethylene (UHMWPE) is currently an excellent alternative as a filler material for poor bone regions and is a good substitute for autografts and other alloplastic materials for their unique properties, including high biocompatibility. The insertion of this material in the fixation system customized in orthognathic surgeries planned virtually is an innovative technique. This paper describes an association of UHMWPE inserted into the custom-made titanium miniplates manufactured by CAD-CAM (computer-aided desing/computer-aided manufacturing) technology in a surgery orthognathic of maxillary advancement and mandibular retrusion to treat a patient with Crouzon's syndrome with class III malocclusion and severe maxillary retrognathism.



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Long-Term Effects of Distraction Osteogenesis of the Mandible

Publication date: Available online 31 January 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Zachary S. Peacock, Alfonso Salcines, Maria J. Troulis, Leonard B. Kaban
PurposeTo assess the fate of the permanent teeth in and adjacent to the regenerate in pediatric patients who underwent mandibular distraction osteogenesis (DO). Second, to compare the post-operative growth of the distracted mandible to age and gender matched controls.MethodsThis was a retrospective cohort study of children who underwent mandibular DO, during the primary or mixed dentition period and prior to completion of somatic growth (males ≤ 14 years old; females ≤12 years old), at Massachusetts General Hospital from 1996-2014. From the DO Registry, subjects were selected who had complete clinical and radiographic records and ≥1 year follow-up. Patients with disorders of dental development (e.g. ectodermal dysplasia) were excluded. Panoramic radiographs were used to assess changes in morphology, eruption and orientation of the the dentition. Standardized digital lateral cephalograms were used to assess the mandible (SNB, mandibular unit length, ramus height, body length) preoperatively(T0), at end-distraction(T1), 1 year post-device removal(T2) and longest follow-up(T3).ResultsA total of 118 patients in the registry had DO during the study period. For assessment of the effects on the dentition, 26 patients, who had 36 osteotomies and distraction wounds, met inclusion criteria. In this sample, 22/26 subjects (85%) experienced 52 adverse effects in 38/90 permanent teeth (42.2%) assessed. Cephalometric measurements at T3 indicated that there was net mandibular growth at longest follow-up, after a period of skeletal relapse during T1-T2; however, only 2/25 (8%) subjects regained a growth rate in the vector of DO that matched or exceeded normal age and gender matched controls.ConclusionDO commonly results in adverse effects on the dentition within and adjacent to the DO gap with only a minority resolving over time. Net growth of the mandible occurs after DO but at a slower rate and lesser magnitude than that of age and sex matched controls.



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Management of facial pyoderma gangrenosum using platelet-rich fibrin: a technical report

Publication date: Available online 31 January 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Leonzio Fortunato, Selene Barone, Francesco Bennardo, Amerigo Giudice
This report describes a case of local pyoderma gangrenosum that was treated with short-term immunosuppressive therapy and the topical application of platelet-rich fibrin (PRF).Medical treatment included an oral corticosteroid therapy and a topical treatment with PRF in solid and liquid form. The previously mentioned therapy initially led to the reduction of the ulcer's size and an improvement of the symptoms, until the ulcer was completely healed after a few weeks. A relapse was treated only with the application of PRF to the affected tissue with an excellent recovery. The efficacy of PRF as a guide for wound healing is due to the continuous release of growth factors involved in tissue repair mechanisms. PRF has proved to be suitable for the management of facial pyoderma gangrenosum while allowing a reduction of systemic corticosteroids therapy. The ease of preparation, low cost, and outpatient use make PRF an optimal scaffold for tissue healing processes. 



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The influential bony factors and vectors for predicting soft tissue responses after orthognathic surgery in mandibular prognathism

Publication date: Available online 31 January 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Yoon-Sic Han, Ho Lee
PurposeTo identify hard tissue points and vectors that have the greatest effect on soft tissue movements after orthognathic surgery in patients with mandibular prognathism.Patient and MethodsThis retrospective study involved patients who underwent mandibular setback surgery with or without maxillary advancement. Multiple linear regression models were adapted to evaluate the association between the eight hard tissue landmark (predictor variables) changes and 11 soft tissue responses (outcome variables) based on the x and y coordinates assessed from superimposed pre- and postoperative three-dimensional computed tomography images.ResultsA total of 50 patients (42 patients underwent two-jaw surgery; eight patients underwent one-jaw surgery; mean age, 23 ± 4 years) were included in the present study. Our statistical models demonstrated that horizontal hard tissue changes had a greater influence on the soft tissue responses than the vertical changes did, and these changes were more notable in the lower facial area (lower lip contour and chin profile) than the midfacial area (nasal profile, upper lip contour, upper lip length, and nasolabial angle). In the horizontal soft tissue response model, the ratio of soft tissue A point to A point was 0.86 (95% CI, 0.674-1.049):1; the ratio of soft tissue B point to B point was almost 1 (95% CI, 0.919-1.071):1; and the ratio of the soft tissue pogonion to the pogonion was 0.88 (95% CI, 0.805-0.963):1.ConclusionsHorizontal or vertical bone tissue changes affected both the horizontal and vertical soft tissue changes in most areas. Our study demonstrated that the soft tissue response is not a linear change, but a more complicated and dynamic reaction.



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Clinical and radiographic performance of the rough surfaced implants placed in the atrophic posterior maxilla with sinus membrane elevation without bone graft: A prospective and preliminary study

Publication date: Available online 31 January 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Suhyun Park, Hyun-Joong Yoon
PurposeThe aim of this prospective and preliminary study was to compare the clinical and radiographic outcomes of two types of rough surfaced implants after implant placement in the atrophic posterior maxilla with sinus membrane elevation without bone grafting using the crestal approach.Materials and MethodsAll clinical and radiographic records for 28 patients who received 40 implants were included in this study. The patients were recalled for radiographic and clinical examinations at 1, 3, and 6 months and every 6 months thereafter following implantation.CBCT images were taken to evaluate the amount of bone gain in the maxillary sinus. Standardized periapical digital radiographs were taken to evaluate changes in the crestal peri-implant bone level and peri-implant fixture radiolucency.ResultsThe Kaplan-Meier survival estimates demonstrated a 100% probability of survival to 24 months. There were no significant differences in cervical bone loss (CBL) and residual bone height (RBH) between the TS III CA group and the TS III SA group during the 2 years of follow up after implant placement. The CBL values according to gender, implant placement region, prosthesis type, and the time of implantation were not significantly different between the two groups.ConclusionThis preliminary study demonstrates that two types of rough surfaced implants placed in the atrophic posterior maxilla with sinus membrane elevation without a bone graft have good clinical and radiographic outcomes.



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Does the medical comorbidity profile of OSA patients treated with maxillomandibular advancement differ from that of OSA patients managed nonsurgically?

Publication date: Available online 31 January 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Richard Ngo, Elaina Pullano, Zachary S. Peacock, Edward T. Lahey, Meredith August
PurposeObstructive sleep apnea (OSA) patients with retrognathia and measurable anatomic airway determinants may represent a subset of OSA patients and have distinct comorbidity profiles. Our aim is to compare the medical comorbidities of OSA patients managed surgically with maxillomandibular advancement (MMA) to those of non-surgical patients.Patients and MethodsThis is a cross-sectional retrospective study. Subjects for both cohorts were identified through the Massachusetts General Hospital Oral and Maxillofacial Surgery(OMS) data registry and the MGH Research Patient Data Registry(RPDR). Inclusion criteria consisted of clinical records documenting BMI, apnea-hypopnea index(AHI), respiratory disturbance index(RDI), and/or O2 nadir. The primary predictor variable was the treatment modality chosen: surgical(MMA) or nonsurgical. Demographic information and OSA parameters were evaluated. The primary outcome variable was the number of documented comorbidities in each group. Two-sample t-tests were used for continuous variables. Chi-square or Fisher's exact tests were used for categorical variables.ResultsThe non-surgical cohort consisted of 71 subjects(67.6% male) and the surgical cohort of 51 subjects(84.3% male). Comparison of descriptive characteristics showed that the nonsurgical cohort had a higher average age(49±9.4) than the surgical cohort(41±10.7; P< .001). A higher average BMI was also present among the nonsurgical group(42.3±11.9 nonsurgical vs. 29.7±5.5 surgical; P<.001). Polysomnogram parameters were comparable with exception of a higher Epworth Sleepiness Scale (ESS) in the surgical cohort(15.5±5.30 surgical vs. 9.90±6.80 nonsurgical; P=.005). The non-surgical cohort had a higher total number of comorbidities(7± 4 nonsurgical vs. 4± 3 surgical; P<0.001). Hypertension, cardiovascular disease, hyperlipidemia, pulmonary hypertension, obstructive pulmonary disease, and type 2 diabetes mellitus (DM) had higher prevalence within the non-surgical group.ConclusionThe results of this study suggest that non-surgically managed OSA patients tend to have more complex medical comorbidity profiles than those managed surgically. Obesity (BMI>30) was more prevalent in the nonsurgical cohort, which may be contributory. The additive contribution of OSA needs to be further elucidated.



http://ift.tt/2DRa2w8

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.

http://ift.tt/2Fxfmp3

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.

http://ift.tt/2E0SDo2

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.

http://ift.tt/2Fx9Xhx

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.

http://ift.tt/2E0H1l3

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.

http://ift.tt/2Fy2oqW

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.

http://ift.tt/2E4WHDN

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.

http://ift.tt/2Fy3L8W

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.

http://ift.tt/2E4WBvV

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.

http://ift.tt/2FwPCJe

Blaschkoid Acute Graft-vs-Host Disease

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

http://ift.tt/2E5LH9r

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.

http://ift.tt/2FzFIqp

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.

http://ift.tt/2E3HC5e

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.

http://ift.tt/2FzFG1L

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.

http://ift.tt/2E1JR9d

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.

http://ift.tt/2Fxfmp3

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.

http://ift.tt/2BJCFcY

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

http://ift.tt/2rFLc0u

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+.



http://ift.tt/2DQgzXM

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

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




http://ift.tt/2Eudxtm

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.



http://ift.tt/2DLr2np

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

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




http://ift.tt/2Etie6T

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.

Graphical abstract

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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

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.


http://ift.tt/2ErcNp5

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>97^th 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.

Graphical abstract

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

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




http://ift.tt/2EsalPf

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.



http://ift.tt/2DRtRDp

Benralizumab attenuates airway eosinophilia in prednisone-dependent asthma

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




http://ift.tt/2EtfxT1

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.



http://ift.tt/2DRtfh5

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

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




http://ift.tt/2Esa8eV

ADA2 deficiency: clonal lymphoproliferation in a subset of patients

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




http://ift.tt/2DRtDMz

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

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




http://ift.tt/2Esa1Qx

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

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




http://ift.tt/2DRtyZh

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.

Graphical abstract

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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.

Graphical abstract

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

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




http://ift.tt/2EqSLek

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

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.


http://ift.tt/2EtibYL

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.

http://ift.tt/2DPrfGn

Relationship of aspiration pneumonia to cognitive impairment and oral condition: a cross-sectional study

Abstract

Objectives

The objective of this study was to investigate the relationship of the incidence of aspiration pneumonia to cognitive impairment and the oral condition.

Materials and methods

A total of 1174 elderly patients were analyzed in a cross-sectional study. Cognitive function was evaluated by the Clinical Dementia Rating scale and the oral condition was evaluated by inspection and palpation. Swallowing was examined in 196 patients by video-endoscopic evaluation. The Mann-Whitney U test or chi-square test was used for statistical analysis. Conditional logistic regression analysis was performed to compute the odds ratio (OR) and 95% confidence interval (CI).

Results

Loss of posterior occlusion, impaired tongue movements, and impaired cognition were factors significantly related to aspiration pneumonia. The incidence of aspiration pneumonia was higher in patients with both cognitive impairment and loss of posterior occlusion compared with those having either factor alone (OR: 5.16). There was no statistical association between impaired swallowing and the incidence of aspiration pneumonia in elderly patients with normal cognitive function (cognitive impairment, OR: 3.45; normal function, OR: 0.94).

Conclusion

Co-existence of cognitive impairment and oral frailty significantly enhances the risk of aspiration pneumonia.

Clinical relevance

Early and simple evaluation of the oral condition and cognitive function can predict the risk of aspiration pneumonia.

http://ift.tt/2GAf6GO

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

The demographic features of concomitant facial fractures with closed head injuries in maricopa arizona

Publication date: Available online 31 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Malcolm Harris, Tara Brantley, Douglas Hammond, Sabah Kalamchi
Objectives:1. To investigate the demographic profile of American Native patients with concomitant facial fractures and closed head injuries (CHI).2. To explore the validation of the craniofacial crumble zone.Patients and MethodsThis is a retrospective observational case controlled study of 2131 maxillofacial fractures from 2010 to 2014 of which 173 (8%) had concomitant CHI.Results133 (77%) were males, mean age 40.6 years. Only 2.1% of the local population were Native Americans but represented 24% of the CHI patients and sustained assault injuries 4.6 times more than other groups (p-value <0.001) and 2.6 times more concussion (p-value <0.001). Other trauma comparisons were not significant. 86 (50%) of the 173 patient's blood alcohol levels exceeded 80mg/100mL, compared to 93% of the Native Americans.ConclusionsThe Native American patients had a highly significant predisposition to violence and road traffic accidents with maxillofacial and CHI. Their high blood alcohol levels also reflected longstanding serious sociological problems. This study is an invaluable model to investigate the relative ethnic/racial role of comminuted paranasal structures for the protection of the brain, that is the crumble zone.



http://ift.tt/2EpQpMG

Differentiation between benign and malignant palatal tumors using conventional MRI: a retrospective analysis of 130 cases

Publication date: Available online 31 January 2018
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Yingyan Zheng, Zebin Xiao, Hua Zhang, Dejun She, Xuehua Lin, Yu Lin, Dairong Cao
ObjectivesTo evaluate the discriminative value of conventional maganetic resonance imaging (MRI) between benign and malignant palatal tumors.Study DesignConventional MR imaging features of 130 patients with palatal tumors confirmed by histopathology were retrospectively reviewed. Clinical data and imaging findings were assessed between benign and malignant tumors and between benign and low-grade malignant salivary gland tumors. The variables that were significant in differentiating benign from malignant lesions were further identified using logistic regression analysis. Moreover, imaging features of each common palatal histologic entity were statistically analyzed with the rest of the tumors to define their typical imaging features.ResultsOlder age, partially-defined and ill-defined margins, and absence of a capsule were highly suggestive of malignant palatal tumors, especially ill-defined margins (β = 6.400). The precision in determining malignant palatal tumors achieved a sensitivity of 92.8% and a specificity of 85.6%. In addition, irregular shape, ill-defined margins, lack of a capsule, perineural spread, and invasion of surrounding structures were more frequently associated with low-grade malignant salivary gland tumors.ConclusionConventional MRI is useful for differentiating benign from malignant palatal tumors as well as benign salivary gland tumors from low-grade salivary gland malignancies.



http://ift.tt/2DOPVyK

Assessing the influence of chin prominence on profile esthetics: A survey study

Publication date: Available online 31 January 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Akın Buğra Pişiren, Ayça Arman-Özçırpıcı, Nilüfer İrem Tunçer
PurposeThe aim of this survey study was to assess the influence of chin prominence on the perception of profile esthetics between genders by orthodontists, oral and maxillofacial surgeons (OMF), plastic surgeons, orthognathic patients and laypersons.Materials and MethodsA total of 731 observers participated in this study. Profile photographs of one female and one male showing ideal soft tissue values, skeletal class 1 relationship, and normodivergent facial type were modified with photo editing program (Adobe Photoshop CC software), so that the chin was moved posteriorly up to 10 mm and anteriorly up to 8 mm at 2-mm intervals. Participants were asked to rate 11 female and 11 male profile images and to assess whether surgery was needed.ResultsWithin the limits of this study, ideal, slightly concave and slightly convex profiles for females, and ideal and slightly concave profiles for males were found more acceptable. Surgery was desired for 50.9% of retrusive profiles and 57.3% of protrusive profiles. Female participants had a higher rate of desire for surgery than male participants, and clinicians desired surgery significantly less than others. Desire for surgery started from 4 mm in males and females for all groups, from −6 mm in orthodontists and OMFs, from −4 mm in other groups in females, and from −6mm in males for all groups.ConclusionClinicians tend to operate more pronounced cases when compared to laypeople. A significantly higher rate of surgery was desired for protrusive chin profiles, and female participants had a higher desire for surgery.



http://ift.tt/2DQzLVo

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.

http://ift.tt/2DPVYTN

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

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

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.

http://ift.tt/2EsAnBN

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.

http://ift.tt/2DKWbr5

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.

http://ift.tt/2EucPN2

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

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.

http://ift.tt/2rSAAvj

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.

http://ift.tt/2rS2ibR

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.

http://ift.tt/2rUiGbN