Risk of malignancy with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment Registry

The effect of systemic therapy on malignancy risk among patients with psoriasis is not fully understood.

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Pancreatic injury in children: a case report and review of the literature

Trauma is the main cause of morbidity and mortality in the pediatric population. Blunt trauma to the abdomen accounts for the majority of abdominal injuries in children. Pancreatic injury, although uncommon (2...

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Plasma-rich plasma, the ultimate secret for youthful skin elixir and hair growth triggering

Summary

The clinical application of platelet-rich plasma (PRP) is based on the increase in the concentration of growth factors that are released from alpha-granule of the concentrated platelets and in the secretion of proteins which are able to capitalize on the healing process at the cellular level. It has been invented to restore the natural beauty by starting the natural rejuvenation process of the skin and aiming to make it function as a younger one and to keep the skin youthful and maintain it. Besides that, it is also emerged to include hairs as a new injectable procedure to enable stimulating hair growth locally and topically; preventing its fall; improving hair shaft, hair stem, and its caliber; increasing its shine, vitality, and pliability; and declining hair splitting and breakage. Thus, youth is in your blood as it has a magical power imposed in the platelet factors. There is, however, no standardization of the techniques besides insufficient description of the adopted procedures. Not long, autologous platelet-rich plasma (PRP) has surfaced strongly in diverse medical specialties including plastic, wound healing and diabetic ulcers, orthopedic, trauma, ocular surgery, dry eye for eyelid injection, urology for urinary incontinence, sexual wellness, cutaneous surgery, sport medicine, dentistry and dermatology, and aesthetic applications. PRP proved to promote wound healing and aid in facelift, volumetric skin, skin rejuvenation, regeneration, and reconstruction; improve wrinkling; stimulate hair growth; increase hair follicle viability and its survival rate; prevent apoptosis; increase and prolong the anagen hair growth stage; and delay the progression to catagen hair cycle stage with increased density in hair loss and hair transplantation. The aims of this extensive review were to cover all PRP application aspects that are carried out in aesthetic dermatology and to assess the literature on platelet-rich plasma outcomes on main aesthetic practices of general dermatology. A literature review was conducted by searching through PubMed, Biomedical Library database, Google Scholar, and Research Gate for the terms PRP, platelet-rich plasma, platelet-rich fibrin matrix, platelet preparations, platelet application therapy, platelet growth factors, platelet facial, platelet facial rejuvenation, platelet hairs, and platelet wound healing, from inception till 2017, and they were combined using Boolean operators. All those retrieved articles in English language were looked at and explored thoroughly.

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Paracrine crosstalk between endothelial cells and melanocytes through clusterin to inhibit pigmentation

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Variation of the epidermal expression of glucocorticoid receptor-beta as potential predictive marker of bullous pemphigoid outcome

Abstract

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease in Western countries. Although topical and/or systemic glucocorticoids treatment efficacy is widely recognized, up to 30% of patients with BP may undergo a relapse during the first year of treatment. We investigated the protein expression of the total glucocorticoid receptor and GRβ isoform in the skin biopsy specimens from patients with BP, and wondered whether such investigation at baseline provided a tool to predict disease outcome. Total GR and GRβ protein expressions were detected by immunohistochemistry at baseline on 12 patients who later relapse and 11 patients who remained on remission in comparison with 14 control patients. The expression of GRβ in the epidermis of patients with BP who later relapse was significantly higher than that in the epidermis of patients with BP controlled upon corticosteroid treatment, which was also higher than control patients. Thus, our results suggest that increased protein expression of GRβ in skin epithelial cells is predictive of reduced steroid treatment efficacy, and therefore of increased risk of disease relapse in patients with BP.

This article is protected by copyright. All rights reserved.

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Monitoring UV-induced signaling pathways in an ex vivo skin organ culture model using phospho-antibody array

Abstract

We investigated UV-induced signaling in an ex vivo skin organ culture model using phospho-antibody array. Phosphorylation modulations were analyzed in time-course experiments following exposure to solar-simulated UV and validated by western blot analyses. We found that UV induced P-p38 and its substrates, P-ERK1/2 and P-AKT which were previously shown to be upregulated by UV in cultured keratinocytes and in vivo human skin. This indicates that phospho-antibody array applied to ex vivo skin organ culture is a relevant experimental system to investigate signaling events following perturbations. Since the identified proteins are components of pathways implicated in skin tumorigenesis, UV-exposed skin organ culture model could be used to investigate the effect on these pathways of NMSC cancer drug candidates. In addition, we found that phospho-HCK is induced upon UV exposure, producing a new candidate for future studies investigating its role in the skin response to UV and UV-induced carcinogenesis.

This article is protected by copyright. All rights reserved.

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Activation of NLRP3 signaling accelerates skin wound healing

Abstract

The process of skin wound healing involves the following three steps: inflammation, tissue formation, and tissue remodeling. These optimal steps are required for the development of normal wound healing. Recent reports demonstrated that inflammasomes are involved in the innate immune response. In the present study, we examined whether the activation of inflammasomes affects the process of skin wound repair. The skin wound repair model was established using wild-type (WT), NACHT, LRR and PYD domains-containing protein 3 (NALP3) knockout (KO) and ASC-KO mice. The wounds were observed every other day and changes in wound size over time were calculated using photography. Wound repair in NALP3-KO and ASC-KO mice was significantly impaired compared with WT mice. Isoliquiritigenin, an inhibitor of NALP3, decreased the rate of wound repair in WT mice. mRNA expression of pro-inflammatory cytokines in the wound sites of NALP3-KO mice was markedly decreased compared with WT mice. Treatment with adenosine triphosphate (ATP), a ligand of NALP3, up-regulated the mRNA expression of pro-inflammatory cytokines at the wound site and accelerated wound healing in the WT mice. Scratch assay revealed that ATP accelerated wound closure in mouse embryonic fibroblasts from WT mice but not from NALP3-KO mice. In conclusion, the present study demonstrated that NALP3 pathway activation is involved in wound repair, and the topical use of ATP may be useful as an effective treatment for accelerating wound healing.

This article is protected by copyright. All rights reserved.

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Human Tissue Inhibitor of Metalloproteinases-1 Improved Wound Healing in Diabetes through Its Anti-apoptotic Effect

Abstract

Impaired wound healing accompanies severe cell apoptosis in diabetic patients. Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) was known to have effects on promoting growth and anti-apoptosis for cells. we aimed to determine the actual levels of TIMP-1 and cell apoptosis in: 1) the biopsies of diabetic and non-diabetic foot tissue; 2) the human fibroblasts with or without treatments of Advanced Glycation End Products (AGEs). Next, in both human fibroblasts and the animal model of diabetic rats, to determine the improved levels of cell apoptosis and wound healing after the treatments of either active protein of TIMP-1 or in vivo expression of gene therapy vector-mediated TIMP-1. The levels of TIMP-1 were significantly reduced in diabetic skin tissues and in AGEs-treated fibroblasts. Both AGEs-treated cells were effectively protected from apoptosis by active protein of TIMP-1 at appropriate dose level. So did the induced in vivo TIMP-1 expression after gene delivery. Similar effects were also found on the significant improvement of impaired wound healing in diabetic rats. We concluded that TIMP-1 improved wound healing through its anti-apoptotic effect. Treatments with either active protein TIMP-1 or TIMP-1 gene therapy delivered in local wound sites may be used as a strategy for accelerating diabetic wound healing.

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House Dust Mite allergens Der f and Der p induce IL-31 production by blood derived T cells from Atopic Dermatitis patients

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Evidence for a contributory role of a xenogeneic immune response in experimental epidermolysis bullosa acquisita

Abstract

Autoimmune diseases affect a large fraction of the population in Western countries. To elucidate the underlying causes, autoantibody transfer-induced mouse models have been established that greatly contributed to the understanding of the pathophysiology of these diseases. However, the role of a potentially co-occurring murine xenogeneic immune response to commonly utilized rabbit anti-mouse IgG remains poorly understood. Using the established rabbit anti-mouse type VII collagen (COL7) IgG-induced mouse model of the mucocutaneous blistering disorder epidermolysis bullosa acquisita (EBA), we found in this study a profound T and B cell response along with an altered cytokine expression profile in draining lymph nodes of mice injected with the xenogeneic IgG. This was associated with the formation of circulating and skin-bound mouse anti-rabbit IgG in wild-type but not CD154-deficient or B-cell deficient JHT mice challenged with pathogenic rabbit IgG. Development of EBA skin lesions was attenuated in the two mouse strains lacking a B cell response at later observation time points, but was not affected in mice treated with the T cell trafficking blocker FTY720. Collectively, our results implicate a host's xenoreactive immune response to rabbit anti-mouse COL7 IgG, a confounding effect that may contribute to immune complex-driven inflammation and tissue damage in this antibody transfer-induced EBA mouse model, especially at later time points. In this regard, it may be recommended to finish the evaluation of results obtained by experiments employing antibody-transferred mouse models within the first 2 weeks after the pathogenic antibody injection.

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A comprehensive approach to evaluating and classifying sun-protective clothing

Abstract

Background

National standards for clothing designed to protect the wearer from the harmful effects of solar ultraviolet radiation (UVR) have been implemented in Australia/New Zealand, Europe, and the USA. Industry standards reflect the need to protect the skin by covering a considerable proportion of the potentially exposed body surface area (BSA) and by reducing UVR-transmission through fabric (the Ultraviolet Protection Factor; UPF).

Objectives

This research aimed to develop a new index for rating sun-protective clothing that incorporates the BSA coverage of the garment in addition to the UPF of the fabric.

Methods

A mannequin model was fixed to an optical bench and marked with horizontal lines at 1 cm intervals. An algorithm (the Garment Protector Factor; GPF) was developed based on the number of lines visible on the clothed versus unclothed mannequin and the UPF of the garment textile. This data was collected in 2015-16 and analysed in 2016.

Results

The GPF weights fabric UPF by BSA coverage above the minimum required by international sun-protective clothing standards for upper-body, lower-body and full-body garments. GPF increases with BSA coverage of the garment and fabric UPF. Three nominal categories are proposed for the GPF: 0 ≤ GPF < 3 for garments that 'meet' minimum standards; 3 ≤ GPF < 6 for garments providing 'good' sun-protection; and GPF ≥ 6 indicating 'excellent' protection.

Conclusions

Adoption of the proposed rating scheme should encourage manufacturers to design sun-protective garments that exceed the minimum standard for BSA coverage, with positive implications for skin cancer prevention, consumer education and sun-protection awareness.

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Anti-inflammatory effect of Astaxanthin in phthalic anhydride-induced atopic dermatitis animal model

Abstract

In this study, we investigated anti-dermatitic effects of Astaxanthin (AST) in phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. AD-like lesion was induced by the topical application of 5% PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100 μl of 1 mg/ml and 2 mg/ml of AST (10 μg or 20 μg/cm²) was spread on the dorsum of ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor-κB (NF-κB) activity. We also measured tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and immunoglobulinE (IgE) concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). AST treatment attenuated the development of PA-induced AD. Histological analysis showed that AST inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. AST treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as release of TNF-α, IL-1β, IL-6, and IgE. In addition, AST (5, 10, and 20μM) potently inhibited lipopolysaccharide (LPS) (1 μg/ml)-induced nitric oxide (NO) production, expression of iNOS and COX-2, and NF-κB DNA binding activities in RAW 264.7 macrophage cells. Our data demonstrated that AST could be a promising agent for AD by inhibition of NF-κB signaling.

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CD8+ lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury

Abstract

The molecular links between sterile inflammation and induction of adaptive immunity have not been fully identified. Here, we examine how damage associated molecular patterns (DAMPs), as opposed to pathogen associated molecules (PAMPs), regulates the immune response to non-self-antigens presented at the site of the physical injury. Heat applied briefly to the skin invokes sterile inflammation, characterised by local cell death and caspase-1 activation without demonstrably disrupting skin integrity. Co-delivery of ovalbumin (OVA) with heat injury induces OVA-specific CD8⁺ T cell responses and this is dependent on caspase-1 activation and MyD88 signalling. Using Id2flox/flox-CD11cCre+ mice, we demonstrate that CD8⁺ lineage DCs are required to induce OVA-specific CD8⁺ T cell responses following heat injury. Consistent with this observation, intradermal administration of CD8⁺ lineage DCs but not CD11b⁺ lineage DCs restores priming of CD8⁺ T cell responses in Casp-1^-/- mice. Thus, we conclude that a sterile injury induces CD8⁺ T cell immune responses to local antigen through caspase-1 activation and requires CD8⁺ lineage DCs, a finding of significance for immunotherapy and for the pathogenesis of autoimmunity.

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Structural proteins of the dermal-epidermal junction targeted by autoantibodies in pemphigoid diseases

Abstract

The dermal-epidermal junction consists of a network of several interacting structural proteins which strengthen adhesion and mediate signaling events. This structural network consists of hemidesmosomal-anchoring filament complexes connecting the basal keratinocytes to the basement membrane. The anchoring filaments in turn interact with the anchoring fibrils to attach the basement membrane to the underlying dermis. Several of these structural proteins are recognized by autoantibodies in pemphigoid diseases, a heterogeneous group of clinically and immunopathologically diverse entities. Targeted proteins include the two intracellular plakins plectin isoform 1a and BP230 (also called bullous pemphigoid antigen (BPAG) 1 isoform e (BPAG1e)), which are connected to the intermediate filaments and to the cell surface receptor α6β4 integrin, which in turn is connected to laminin 332, a component of the anchoring filaments. Further essential adhesion proteins are BP180, a transmembrane protein, laminin γ1, and type VII collagen. Latter protein is the major constituent of the anchoring fibrils. Additionally, a 105 kDa protein of the lower lamina lucida has been described as autoantigen. Mutations in the corresponding genes of these adhesion molecules lead to inherited epidermolysis bullosa emphasizing the importance of these proteins for the integrity of the dermal-epidermal junction. This review will provide an overview on the structure and function of the proteins situated in the dermal-epidermal junction targeted by autoantibodies.

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Natural course of tonsillectomy pain: A prospective patient cohort study

Publication date: Available online 8 September 2017
Source:Auris Nasus Larynx
Author(s): Min-Su Kim, Hyo Geun Choi, Eun-Kyu Park, So Young Kim, Jin-Hwan Kim, Bumjung Park
ObjectiveThe aim of this study was to determine the natural course of pain after tonsillectomy.MethodsThis study included 119 patients that underwent tonsillectomy between November 2013 and November 2015. After undergoing tonsillectomy, patients scored their pain using the visual analogue scale three times daily (morning, midday, and evening) for 2 weeks. A linear mixed model was used for statistical analyses.ResultsIncreasing postoperative days was negatively associated with pain following tonsillectomy surgery (estimated value [EV] of visual analogue score [VAS]/day=−0.42, 95% confidence interval [CI]=−0.43 to −0.41, P<0.001); the post-tonsillectomy pain curve illustrated this negative correlation. Postoperative pain was less in children and adolescents (≤18years old) than in adults (>18 years old) (EV=−0.81, 95% CI=−1.56 to −0.08, P=0.031). Mean tonsillectomy-associated pain on postoperative day 1 was 6.4 VAS. It decreased slightly to 5.3 VAS until postoperative day 7, after which it reduced sharply to 3.7 VAS within 3 days; on postoperative day 14 it had decreased to 1.6 VAS. Pain assessments were higher in the morning (EV=0.59, 95% CI=0.50 to 0.69, P<0.001) compared with assessments conducted in the evening.ConclusionThe natural course of postoperative tonsillectomy pain follows a gradual decline for 1 week after surgery, but decreases more rapidly after this period.



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Relationship between swallowing function and breathing/phonation

Publication date: Available online 8 September 2017
Source:Auris Nasus Larynx
Author(s): Satoshi Yamaguchi, Mariko Ishida, Kanako Hidaka, Shinya Gomi, Sachiyo Takayama, Kazuki Sato, Yuma Yoshioka, Nozomu Wakayama, Kuwon Sekine, Shoji Matsune, Toshiaki Otsuka, Kimihiro Okubo
ObjectiveClarification of the association between the swallowing function and respiratory and phonatory functions.MethodsThe subjects were 30 patients with a chief complaint of swallowing disorder with clear consciousness capable of retaining a sitting position. Patients with organic and functional diseases of the larynx were excluded. Twenty-two and eight patients were male and female, respectively, and the mean age was 77.0±14.6years old. The chest expansion score was measured as an index of the respiratory function, and the maximum phonation time (MPT) was measured as an index of the phonatory function. The presence or absence of aspiration was judged using videoendoscopic swallowing study (VESS) and videofluoroscopic swallow studies (VFSS). The patients were divided into those with and without aspiration, and the chest expansion score and MPT were compared. In addition, the distance of laryngeal elevation was measured in the lateral view of VFSS, and its correlations with the chest expansion score and MPT were closely analyzed. To evaluate reliability of the test, the distance of laryngeal elevation and videoendoscopic score were compared between the presence and absence of aspiration.ResultsThe distance of laryngeal elevation was significantly shortened and the videoendoscopic score was significantly higher in the group with aspiration, as previously reported. On comparison of the chest expansion score between the groups with and without aspiration, no significant difference was noted at the axillary or xiphoid process level, and shortening was significant only at the 10th rib level in the group with aspiration. On comparison of MPT, it was significantly shortened in the group with aspiration. In addition, a significant positive correlation with the distance of laryngeal elevation was noted in both chest expansion score and MPT.ConclusionIt was suggested that declines of the respiratory and phonatory functions are risk factors of aspiration through limiting laryngeal elevation, and the chest expansion score at the 10th rib level and MPT are useful for screening of aspiration.



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Atopowe zapalenie skóry. Czy zawsze choroba alergiczna?

Publication date: Available online 8 September 2017
Source:Alergologia Polska - Polish Journal of Allergology
Author(s): Barbara Rogala




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Grzybica skóry gładkiej leczona jako alergia kontaktowa

Publication date: Available online 8 September 2017
Source:Alergologia Polska - Polish Journal of Allergology
Author(s): Monika Sikorska, Roman Nowicki
Fungal skin infections are caused mainly by dermatophytes of the genus Trichophyton, Microsporum and Epidermophyton. Proper diagnosis based on clinical picture and mycological examination makes it possible to implement effective treatment – local, general or combination.Mycobacterial mycosis mostly develops on the skin of the scalp in the form of single or multiple lesions without inflammation. Zoophilic dermatophyte Microsporum canis is the most common causative pathogen, anthropophilic species such as Microsporum audouinii and Microsporum ferrugineum are observed occasionally. In case of zoonitic mycosis, a characteristic inflammation is formed on the periphery. Outside the scalp, skin of the face, neck, shoulders and the trunk can also be affected.Mycosis of smooth skin manifests in the form of oval or round erythematous patches or plaques with sharply defined borders, which spread circumferentially. The periphery of the lesion is inflamed with scaling and pustules, and centrally located resolution is observed. Pruritus in majority of the cases is a chief complaint. In most of the cases, a single lesion is observed, but over time, lesions tend to multiply and fuse together. Differential diagnosis of mycosis of the smooth skin includes seborrheic dermatitis, Gilbert's pink dandruff, mycosis fungoides, psoriasis and nummular dermatitis.The basis of treatment for microsporiasis is the use of topical preparations with antifungal agents. Local treatment is sufficient in most of the cases. General treatment (terbinafine, itraconazole, fluconazole or chleeprazole) is recommended if there is no improvement after topical treatment or in advanced disease stages.This article presents the case of a woman whose single facial fungal skin lesion was misdiagnosed as allergic contact dermatitis. Topical treatment with moderate-potent corticosteroids was used to achieve initial clinical improvement but discontinuation of therapy led to evolution of the lesion, which partially lost its original ring-shaped nature. The final diagnosis was based on mycological examination, and local and general antifungal treatment led to permanent cure.Not typical mycotic skin disease altered by immunosuppressive treatment is termed tinea incognito. Carelessly prescribing and using corticosteroids for infectious skin lesions results in complications as well as postponement of proper diagnosis and initiation of the treatment.



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Wpływ środowiska wiejskiego na rozwój astmy i alergii u dzieci

Publication date: Available online 8 September 2017
Source:Alergologia Polska - Polish Journal of Allergology
Author(s): Piotr Fuss, Katarzyna Bal-Gierańczyk, Joanna Jerzyńska, Iwona Stelmach
Children who grow up on dairy farms rarely develop asthma or allergies. Researchers suspect a key reason is that the kids breathe in air full of lipopolysaccharides, molecules from the cell wall of bacteria G-, known as endotoxins. Endotoxin-reduced epithelial cell cytokines activate dendritic cells (DCs), thus suppressing type 2 immunity to house dust mites and reducing the overall reactivity of the immune system and later protecting children from asthma. Schuijs et al showed that an enzyme involved in this defense, called A20, is made by the epithelial cells. Loss of the ubiquitin-modifying enzyme A20 abolished the protective effect. Thus, the farming environment protects from allergy by modifying the communication between barrier epithelial cells and DCs through A20 induction. Their study offers new support for the hygiene hypothesis, which posits that zeal for cleanliness and widespread use of antibiotics have purged the environment of microorganisms that once taught a child's developing immune system not to overreact to foreign substances. This paper is a summary of up-to-date information on hygiene hypothesis. The purpose is to review the important recent advances made in how innate immune cells, microbes, and the environment contribute to the expression of allergic disease, emphasizing the allergen-related signals that drive allergic responses.



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Metastatic cancer in the Middle Age: the possible case of a female skeleton from Bormio (Italy)

Abstract

Secondary signs of cancer are difficult to assess in the archaeological context, as other lesions may mimic metastases on dry bones. Furthermore the low life expectancy, lower level of environmental cancer risk factors and pollution than the present times can contribute in limiting the frequency of signs of cancer in archaeological populations.

This study focuses on a female adult skeleton from the necropolis of Bormio (North-Italy), dating back to Middle Ages, which shows multiple lytic lesions on cranium, upper limbs, ribs and pelvis; lesions are oval in shape, with a diameter ranging from 1-2 mm to 80 mm. The lesions appearance and distribution at macroscopic and radiographic level, together with sex and age indications suggest the diagnosis of metastatic cancer. Possible diagnostic hypotheses of the possible sites of original cancer were performed as well, based on modern epidemiological data.

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Validation of the MASK-rhinitis visual analogue scale on smartphone screens to assess allergic rhinitis control

Abstract

Background

Visual Analogue Scale (VAS) is a validated tool to assess control in allergic rhinitis patients.

Objective

The aim of the present study was to validate the use of VAS in the MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) App (Allergy Diary) on smartphones screens to evaluate allergic rhinitis symptoms and disease control.

Methods

Each user filled 4 different VAS measuring overall, nasal, ocular and asthma symptoms at least once. Following COSMIN guidelines, we evaluated internal consistency, (Cronbach's alpha-coefficient and test-retest), reliability (intraclass correlation coefficients), sensitivity and acceptability, of the MASK-Rhinitis VAS.

Results

Between August 1^st, 2015 and July 31^st, 2016, the app was used 14,612 times in 15 countries. 1,225 users used it more than once, during the evaluated period. The tool resulted to be statistically satisfactory, showing excellent internal consistency (Cronbach's test >0.84, test-retest >0.7), reliability (>0.9) and acceptability. In addition, the tool had a good sensitivity when users (n=521) answered the VAS twice in less than three hours.

Conclusions & Clinical Relevance

The MASK-rhinitis VAS is a reliable and valid tool to assess allergic control on smartphone screens, at the population level.

This article is protected by copyright. All rights reserved.

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Clinical, histological, and immunohistochemical markers of resistance to Methyl-aminolevulinate Photodynamic therapy in Bowen's disease

Abstract

Bowen's disease (BD) is an intraepidermic squamous cell carcinoma (SCC), which principally appears on photoexposed areas.¹ Methyl-aminolevulinate (MAL) photodynamic therapy (PDT) is an excellent option for the treatment of BD (strength of recommendation, A; quality of evidence, 1). However, despite good response rates, some tumors prove non-responsive due to primary or acquired resistance.² The present study sought to identify clinical, histological, and molecular variables implicated in the response to MAL-PDT in BD.

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Polyclonal hyperglobulinemia and elevated acute phase reactants in hidradenitis suppurativa

Abstract

Hidradenitis suppurativa (HS) is a chronic, painful inflammatory skin disease characterized by recurrent nodules and abscesses affecting intertriginous areas including the axilla, inframammary, and anogenital regions. Hurley staging (I-III) is commonly used to classify patients, with mild disease limited to inflammatory cystic nodules (stage I), that may be connected by isolated tunnels/sinuses (stage II), or form a network of bridging tunnels/sinuses (stage III) associated with odiferous, purulent drainage. The cause of HS is unknown but it is generally considered to be multifactorial. It appears that an aberrant innate immune response initiates cutaneous inflammation in early lesions and recruitment of the adaptive immune system may be involved in maintaining HS chronicity.¹ Only a few published studies have focused on the humoral immune system in HS. The sera of patients with advanced HS revealed elevations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IgE.^2-4 Significantly increased levels of C-reactive protein (CRP) have been found across all three Hurley stages.⁵

This article is protected by copyright. All rights reserved.

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Variation in dermoscopic features of basal cell carcinoma as a function of anatomic location and pigmentation status

Abstract

Detecting basal cell carcinomas (BCCs) early and at relatively small sizes may expand therapeutic choices and enable less invasive treatment options. To this end, dermoscopy is a useful tool to diagnose BCC at early stages with high sensitivity and specificity.¹ Superficial BCCs have been shown to be independently associated with location on the trunk and extremities and nodular BCCs have been independently associated with a head/neck location.^2,3 Few studies have evaluated dermoscopic variation in BCC morphology as a function of anatomic location and pigmentation status.^4,5 Herein, we evaluate BCC dermoscopic morphology based on pigmentation status and anatomic location.

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Treatment of superficial basal cell carcinoma by topical photodynamic therapy with fractionated 5-aminolevulinic acid 20% versus two stage topical methylaminolevulinic acid: results of a randomized controlled trial

Summary

Background

Basal cell carcinoma (BCC) is the most common type of skin cancer with growing incidence rates. Photodynamic therapy (PDT) is a frequently used treatment, especially for superficial BCC (sBCC). Two topical photosensitizing agents are currently used to treat sBCC: 5-aminolevulinic acid (ALA) and its methyl-ester (MAL). Previous research showed a high efficacy of ALA-PDT using a 2-fold fractionated illumination scheme in which two light fractions of 20 and 80 J/cm2 are delivered, four and six hours after ALA application.

Objectives

To evaluate whether this 2-fold ALA-PDT is superior to conventional MAL-PDT for sBCC.

Methods

We performed a single blind, randomized multi-centre trial in the Netherlands.

Results

162 patients were randomized to either conventional MAL-PDT or 2-fold ALA-PDT. After 12 months a total of 6 treatment failures occurred after ALA-PDT and 13 after MAL-PDT. The 12 months cumulative probability of remaining free from treatment failure was 92.3% (95% CI [83.7-96.5]) and 83.4 (95% CI [73.1-90.0]), respectively (p=0.091).

Conclusions

The 2-fold ALA-PDT scheme resulted in fewer recurrences, although the difference between both treatment groups was not statistically significant. On the contrary, it resulted in higher pain scores and more post-treatment side-effects compared to MAL-PDT.

This article is protected by copyright. All rights reserved.

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Can the extent of heart rate reduction predict the clinical response of infantile hemangiomas to propranolol?

Abstract

Propranolol is the first-line medical treatment of complicated infantile hemangiomas (IH)¹. It was suggested that a heart rate (HR) reduction of more than 20% compared to baseline HR might be an early marker of response to propranolol². We aim to explore the relationship between the extent of HR reduction and clinical response of IH to propranolol.

This article is protected by copyright. All rights reserved.

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Information for Readers

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3





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Table of Contents

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3





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Instructions for Authors

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3





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Editorial Board

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3





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Evaluating proteins for potential allergenicity using bioinformatic approaches

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Deendayal Dinakarpandian, Chitra Dinakar




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Genetically modified products and food allergy

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): John Compton, Joseph B. Fanning, Andrew S. Nickels




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Predictors of granulomatous lymphocytic interstitial lung disease in common variable immunodeficiency: Methodological issues

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Erfan Ayubi, Saeid Safiri




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Penicillin skin testing

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Roland Solensky




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Single recombinant and purified major allergens and peptides

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Mirela Curin, Viktoriya Garib, Rudolf Valenta
ObjectiveTo review the current knowledge regarding recombinant and purified allergens and allergen-derived peptides.Data SourcesPubMed, homepages relevant to the topic, and the National Institutes of Health clinical trial database were searched.Study SelectionsThe literature was screened for studies describing purified and recombinant allergens and allergen-derived peptides. Studies relevant to the topic were included in this review.ResultsAdvantages and drawbacks of pure and defined recombinant allergens and peptides over allergen extracts in the context of allergy research, diagnosis, and allergen immunotherapy are discussed. We describe how these molecules are manufactured, which products are currently available on the market, and what the regulative issues are. We furthermore provide an overview of clinical studies with vaccines based on recombinant allergens and synthetic peptides. The possibility of prophylactic vaccination based on recombinant fusion proteins consisting of viral carrier proteins and allergen-derived peptides without allergenic activity are also discussed.ConclusionDuring the last 25 years more than several hundred allergen sequences were determined, which led to a production of recombinant allergens that mimic biochemically and immunologically their natural counterparts. Especially in Europe, recombinant allergens are increasingly replacing allergen extracts in diagnosis of allergy. Despite many challenges, such as high cost of clinical trials and regulative issues, allergy vaccines based on recombinant allergens and peptides are being developed and will likely soon be available on the market.



http://ift.tt/2eSJqDZ

An unusual cause of fever in a patient with common variable immunodeficiency

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Andrew T. Dang, Gene Schwartz, LaQuita Jones, Michael J. Absalon, Richard L. McMasters, Amal Assa'ad




http://ift.tt/2jbl3SZ

The allergenicity of genetically modified foods from genetically engineered crops

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): S. Eliza Dunn, John L. Vicini, Kevin C. Glenn, David M. Fleischer, Matthew J. Greenhawt




http://ift.tt/2eTibZO

Knowledge of food protein–induced enterocolitis syndrome among general pediatricians

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Elizabeth Feuille, Nikhil R. Menon, Faith Huang, Matthew Greenhawt, Anna Nowak-Wegrzyn




http://ift.tt/2vTdiHz

Unusual presentation of combined immunodeficiency in a child with homozygous DOCK8 mutation

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Barbara A. Brunet, Ray Rodriguez




http://ift.tt/2jc1NVp

Allergic sensitization and objective measures of sleep in urban school-aged children with asthma

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Cynthia A. Esteban, Robin S. Everhart, Sheryl J. Kopel, Robert B. Klein, Daphne Koinis-Mitchell
BackgroundAllergic sensitization is associated with increased child asthma morbidity and decreased pulmonary function. Nocturnal symptoms and/or awakenings typically are measured by self-report from diary data, whereas objective assessments of sleep in child asthma studies are lacking.ObjectiveTo investigate the association between increased allergic sensitization (number of positive allergy test results measured by skin prick test or specific immunoglobulin E) and sleep outcomes (sleep efficiency, sleep duration, and mean number of awakenings measured by actigraphy) in urban schoolchildren with persistent asthma.MethodsOne hundred ninety-six children with persistent asthma (7–9 years old) attending public school in 1 of 4 large urban school districts completed allergy testing during a study clinic visit. Forced expiratory volume in 1 second was monitored at home using a handheld spirometer. Sleep outcomes were measured with a wrist Actiwatch during a 1-month period in the fall and winter seasons.ResultsNumber of positive allergy test results significantly predicted mean sleep efficiency (P = .02), such that children with more positive test results experienced less efficient sleep. Number of positive allergy test results significantly predicted mean number of night awakenings (P = .05), such that children with more positive allergy test results experienced more night awakenings. 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 (P = .04). Racial and ethnic differences in allergic sensitization and sleep outcomes were found between African Americans and Latinos.ConclusionMore positive allergy test results were associated with poorer sleep outcomes measured objectively in this sample of urban children. Implications for environmental control interventions and asthma treatments in different racial and ethnic groups are discussed.



http://ift.tt/2jbJEY4

Author's response

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Stella Hartono, Megan S. Motosue, Shakila Khan, Vilmarie Rodriguez, Vivek N. Iyer, Rohit Divekar, Avni Y. Joshi




http://ift.tt/2vTDul9

The national cost of asthma among school-aged children in the United States

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Patrick W. Sullivan, Vahram Ghushchyan, Prakash Navaratnam, Howard S. Friedman, Abhishek Kavati, Benjamin Ortiz, Bob Lanier
BackgroundRecent research has quantified the national health care resource use (HCRU) and health care expenditure (HCE) burden associated with adult asthma; however, estimates specific to school-aged children are more than 2 decades old.ObjectiveTo estimate the national HCRU and HCEs attributable to asthma among school-aged children in the United States.MethodsThis was a cross-sectional retrospective analysis of school-aged children (aged 6–17 years) in the nationally representative 2007–2013 Medical Expenditure Panel Survey. All-cause HCRU and HCEs of school-aged children with asthma were compared with school-aged children without asthma, controlling for sociodemographics and comorbidities. HCRU encounters included emergency department (ED) and outpatient visits, hospitalizations, and prescriptions. Expenditures included total, medical, ED, inpatient, outpatient, and pharmacy. Negative binomial regression analyses were used for HCRU and Heckman selection with logarithmic transformation, and smearing retransformation was used for HCEs.ResultsThere were 44,320 school-aged children of whom 5,890 had asthma. Children with asthma incurred a higher rate of all-cause annual ED visits (incidence rate ratio [IRR], 1.5; P < .001), hospitalizations (IRR, 1.4; P < .05), outpatient visits (IRR, 1.4; P < .001), and prescription drugs (IRR, 3.3; P < .001) compared with school-aged children without asthma. They incurred US$847 (2015 dollars) more annually in all-cause expenditures (P < .001). Private insurance and Medicaid paid the largest share of expenditures. Pharmacy and outpatient costs represented the largest proportion of total expenditures. On the basis of the nationally representative Medical Expenditure Panel Survey sample weights from 2013, the total annual HCEs attributable to asthma for school-aged children in the United States was US$5.92 billion (2015 dollars).ConclusionChildhood asthma continues to represent a prevalent and significant clinical and economic burden in the United States. More aggressive treatment and asthma management programs are needed to address this national financial and resource burden.



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Sensitization profiles to peanut allergens across the United States

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Andre Valcour, Joseph E. Jones, Jonas Lidholm, Magnus P. Borres, Robert G. Hamilton
BackgroundMeasurement of IgE antibody to peanut components can aid in the prediction of allergic responses the food.ObjectiveTo investigate the association between patient demographics (age, location) and allergic sensitization to peanut components across the United States.MethodsSerum samples from 12,155 individuals with peanut extract specific IgE levels of 0.35 kUA/L or higher were analyzed for IgE antibodies to Ara h 1, 2, 3, 8, and 9 by ImmunoCAP.ResultsAmong this population of peanut sensitized individuals, 79.1% of children (<3 years old) were sensitized to one or more peanut storage proteins (Ara h 1, 2, and/or 3), in contrast to 64.2% of adolescents (12–15 years old) and 22.1% of adults (>20 years old). Although sensitization was more prevalent to Ara h 2 than to the other storage proteins, a sizable fraction of patients were sensitized to Ara h 1 and/or 3 but not to Ara h 2 (eg, 13% of children <3 years old). Moreover, 9.6% of children, 10.2% of adolescents, and 10.5% of adults were sensitized to Ara h 9, whereas 2.4% of children, 49.4% of adolescents, and 42.9% of adults produced IgE to Ara h 8 (pathogenesis-related protein 10). Sensitization to Ara h 8 alone was markedly higher in the Northeastern United States relative to other regions of the country.ConclusionWe conclude that sensitization to individual peanut components is highly dependent on age and geographic location. Given that a severe allergic reaction to peanut is unlikely in individuals with isolated sensitization to Ara h 8, a sizable fraction of patients, in particular adolescents and adults, may be at lower risk than anticipated based only on demonstration of sensitization to whole peanut extract.



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Lymphoproliferative responses to dendritic cell presentation of sensitizing allergens in atopic children with multiple allergies

Publication date: September 2017
Source:Annals of Allergy, Asthma & Immunology, Volume 119, Issue 3
Author(s): Tim H. Scott-Taylor, Stefan-Claudiu Axinia, Stephan Strobel
BackgroundPeripheral blood mononuclear cells (PBMCs) proliferate inconsistently, rendering current lymphoproliferation assays unreliable in diagnosis.ObjectiveTo investigate the utility and nature of proliferation responses in allergy by comparison of the standard lymphoproliferation with a new dendritic cell (DC) stimulated assay.MethodsMonocyte-derived DCs were pulsed with allergens and incubated with autologous T cells for 7 days. DC-stimulated and standard PBMC proliferation responses to 3 common dietary allergens in children with allergy and without atopy were measured by incorporation of tritiated thymidine and reduction of carboxyl fluorescein succinimidyl ester staining.ResultsThe DC presentation of sensitizing allergens induced significantly higher proliferative responses than PBMC stimulation (P = .04) and greater distinction between normal and allergic responses. DC-induced stimulation indices of children without sensitivity and those with allergy were significantly different with all 3 foods (P < .001). All children with allergy presented with peanut allergy and 12 of 14 (86%) β-lactoglobulin–pulsed DC preparations proliferated more than 3.3-fold above un-pulsed cells, but 8 of 18 children (44%) with ovalbumin egg allergy showed proliferation below this level. The stimulation index of DC tritiated thymidine incorporation correlated closely with carboxyl fluorescein succinimidyl ester reduction (P < .001). Sensitivity of detection of peanut, milk, or egg allergy was 100%, 85.7%, or 55.6% and specificity was 60%, 88.9%, or 86.7%, respectively. DC-stimulated T cells expressed increased levels of CD45 RO and CD25 and most produced interferon-γ. DC-stimulated proliferation correlated with total immunoglobulin E and peanut antigen-stimulated proliferation correlated with peanut specific immunoglobulin E (P = .03).ConclusionThe DC-induced lymphoproliferation had higher sensitivity, specificity, and reproducibility than the standard assay and caused increased memory and activated T-cell proliferation in children with food allergy.



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Difference in glycogen metabolism (glycogen synthesis and glycolysis) between normal and dysplastic/malignant oral epithelium

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Hitoshi Aizawa, Shin-ichi Yamada, Tiepeng Xiao, Tetsu Shimane, Kiyonori Hayashi, Fangfang Qi, Hirokazu Tanaka, Hiroshi Kurita
BackgroundThe purpose of this study was to investigate a difference in glycogen metabolism (glycogen synthesis and glycolysis) between the iodine stained (normal non-keartinized) and the unstained (dysplasctic/malignant) oral epithelium.MethodsTwenty-one frozen tissue samples of iodine-stained and unstained mucosal tissue were obtained from 21 OSCC patients. Serial frozen sections were cut and examined with the hematoxylin-eosin and periodic acid-Schiff methods and immunohistochemical (IHC) staining for Ki67, P53, molecules associated with glycogenesis (i.e., glycogen synthase (GS) and phospho-glycogen synthase (PGS)), and molecules associated with glycogenolysis (i.e., glycogen phosphorylase isoenzyme BB (GPBB) examine the glycogen metabolism in OSCC. Additionally, in vitro study, the expression levels of GS and GPBB in the cultured cells were analyzed by immunofluorescent staining, Western blot analysis, and the real-time quantitative polymerase chain reaction (PCR).ResultsThere was no significant difference in GS and PGS immunoactivity between iodine stained and unstained area. On the other hand, significantly greater GPBB immunoreactivity was observed in the basal and parabasal layers of iodine-unstained epithelium, where higher positivity for p53 and Ki67 was also showed. Additionally, western blot analysis, immunofluorescent staining, and real-time quantitative PCR revealed that the oral squamous cancer cells exhibited greater expression of GPBB than normal epithelial cells.ConclusionsThe results of this study showed that GPBB expression, which resulted in up-regulation of glycogenolysis, is enhanced in oral dysplastic/malignant epithelium compared with non-keartinized normal epithelium, in spite of the fact that glycogenesis continues in both of them. Premalignant and malignant epithelial cells consume greater quantities of energy due to their increased proliferation, and hence, exhaust their glycogen stores, which resulting in negative stain reaction with iodine solution.

Graphical abstract

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Computed tomography evaluation of the morphometry and variations of the infraorbital canal concerning endoscopic surgery

Publication date: Available online 8 September 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Gülay Açar, Kemal Emre Özen, İbrahim Güler, Mustafa Büyükmumcu
IntroductionThe course of the infraorbital canal may leave the infraorbital nerve susceptible to injury during reconstructive and endoscopic surgery manipulating the roof of the maxillary sinus.ObjectiveWe investigated both the morphometry and variations of the infraorbital canal and aimed to show the relationship between them concerning endoscopic approaches.MethodsThis retrospective study was performed on paranasal multidetector computed tomography images of 200 patients.ResultsThe infraorbital canal corpus types were categorized as Type 1; within the maxillary bony roof (55.3%), Type 2; partially protruding into maxillary sinus (26.7%), Type 3; within the maxillary sinus (9.5%), Type 4; located anatomically at the outer limit of the zygomatic recess of the maxillary bone (8.5%). The internal angulation and the length of the infraorbital canal, the infraorbital foramen entry angles and the distances related to the infraorbital foramen localization were measured and their relationships with the infraorbital canal variations were analyzed. We reported that the internal angulations in both of sagittal and axial sections mostly found in infraorbital canal Type 1 and 4 (69.2%, 64.7%) but, there was commonly no angulation in Type 3 (68.4%) (p<0.001). The length of the infraorbital canal and the distances from the infraorbital foramen to the infraorbital rim and piriform aperture was measured as the longest in Type 3 and the smallest in Type 1 (p<0.001). The sagittal infraorbital foramen entry angles were detected significantly smaller in Type 3 and larger in Type 1 than that in other types (p=0.003). The maxillary sinus septa and the Haller cell were observed in 28% and 16% of the images, respectively.ConclusionPrecise knowledge of the infraorbital canal corpus types and relationship with the morphometry allow surgeon to choose an appropriate surgical approach to avoid iatrogenic infraorbital nerve injury.



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A Clinical and Biological Umbrella Protocol for Smoker or Non-smoker Patients With OPML or HNSCC

Conditions:   Premalignant Lesion;   Head and Neck Squamous Cell Carcinoma (HNSCC)
Interventions:   Procedure: Samples collection;   Behavioral: Psychological and Sociological evaluation;   Behavioral: Intensive and sustained smoking cessation program;   Behavioral: Tobacco and alcohol status follow-up
Sponsor:   Centre Leon Berard
Not yet recruiting - verified September 2017

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A Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma (Toca 6)

Conditions:   Colorectal Cancer;   Triple Negative Breast Cancer;   Pancreatic Cancer;   Non-Small Cell Lung Cancer;   Head and Neck Cancer;   Ovarian Cancer;   Lymphoma;   Sarcoma;   Bladder Cancer;   Melanoma;   IDH1 Mutated Solid Tumors;   IDH1 Mutated or MGMT Methylated Recurrent High Grade Glioma
Interventions:   Biological: Toca 511;   Drug: Toca FC
Sponsor:   Tocagen Inc.
Recruiting - verified September 2017

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Adenoid hypertrophy in children and allergic rhinitis

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Reply to Dijemeni et al.’s comments concerning: “The comparability of drug-induced sedation classification systems”

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In this issue

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Sialadenoma Papilliferum: Analysis of Seven New Cases and Review of the Literature

Abstract

Sialadenoma papilliferum (SP) is a rare benign salivary gland neoplasm that comprises from 0.4 to 1.2% of all salivary gland tumors. The tumor is so named because of its microscopic resemblance to the syringocystadenoma papilliferum, an uncommon benign tumor of sweat gland origin. The purpose of this paper is to report the clinical and microscopic features of seven new cases of SP and combine them with cases previously reported in the English language literature to further define this unusual lesion. Combining our cases with acceptable cases from the literature, the palate (especially the hard palate) was the most common site, with 80% of the cases occurring in this location. Other locations in decreasing order were buccal mucosa, upper lip, retromolar pad, and parotid gland. Age at diagnosis ranged from 18 to 87 years with a peak in the 6th decade and an average age of 56.4 years. Microscopically, the lesions demonstrated a papillary surface morphology, and the papillary projections varied from long and pointed to short and blunted. The supporting connective tissue contained a variable number of convoluted ductal structures, which often fused with the overlying surface epithelium. The ductal structures exhibited papillary infoldings and were lined by a double layer of epithelium consisting of basal cell layer and a luminal layer of cuboidal-to-columnar ductal cells. Immunohistochemical reactivity with p63 and p40 indicated that the basal cell layer was comprised predominantly of neoplastic myoepithelial cells. The luminal cells were immunoreactive with epithelial membrane antigen characteristic of ductal cell differentiation. Conservative surgical treatment was accomplished in most cases and appears to be adequate treatment as only two recurrences were documented. Several case reports of purported malignant transformation in SP have been reported in the literature, but in our opinion, there is insufficient evidence in the publications to unequivocally determine whether any of the malignancies truly originated within a pre-existing SP.

http://ift.tt/2f83HCa

Profiling dendritic cell subsets in the patients with active pulmonary tuberculosis

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Yuan-Bin Lu, De-Qian Xiao, Kui-Di Liang, Jun-Ai Zhang, Wan-Dang Wang, Shi-Yan Yu, Bi-Ying Zheng, Yu-Chi Gao, You-Chao Dai, Yan Jia, Chen Chen, Ze-Gang Zhuang, Xin Wang, Xiao-Xia Fu, Yong Zhou, Jixin Zhong, Zheng W. Chen, Jun-Fa Xu
Dendritic cell (DC) plays an important role in the immune response against pulmonary tuberculosis. However, the phenotypic profile of DC subsets in peripheral blood in individuals with active pulmonary tuberculosis (APT) is still inconclusive. Here, we demonstrated that the absolute numbers of total DC (tDC), myeloid DC (mDC) and plasmacytoid DC (pDC) in individuals with APT were decreased compared to healthy controls (HCs). The decreased number of DCs, especially of pDC, seems to be a useful diagnostic marker of APT. Meanwhile, the number of DCs was associated with the prolonged/complicated TB, ATD treatment effect and lymphocyte immune reactions, as manifested that relapsed APT patients with a higher number of tDC and lower number of pDC compared to newly diagnosed patients. Interestingly, mDC from APT patients displayed high expressions of CD83 and CCR7, but pDC displayed low expressions of CD83 and CCR7. Moreover, DCs from APT patients expressed lower levels of HLA-DR and CD80, but expressed a higher level of CD86 than those from HCs. However, the antigen uptake capacity of DC subsets was not different between APT and HCs, despite the antigen uptake capacity of pDC was much lower than that of mDC in both APT patients and HCs. Our data represent a systematic profile of DC subsets in the blood of APT patients, and would represent a useful biomarker for APT.



http://ift.tt/2vSwg10

Effect of lentivirus-mediated gene silencing, targeting toll-like receptor 2, on corneal allograft transplantation in rats

Publication date: November 2017
Source:Molecular Immunology, Volume 91
Author(s): Lang Bai, Weiyi Liang, Minting Chen, Yacouba Cissé, Jing Liu, Yaru Su, Jian Yu, Qiong Liu
AimThe present work aims to assess the effectiveness of lentiviral vector (LV) mediated Toll-like receptor 2 (TLR2) gene silencing in the survival of transplanted corneal allografts, against immune rejection, in rats.MethodsLV mediated TLR2 small interference RNA (SiRNA) with enhanced green fluorescent protein (eGFP) [LV-TLR2-siRNA-eGFP] was realised and transfected to both rat corneal epithelial (EC) and stromal cells (SC). Multiplicity of infection (MOI) was optimized for transfection efficiency using flow cytometric (FCM) analysis. Viability of transfected cells and the success rate of TLR2 gene silencing were respectively determined by CCK-8 assay and western blot assay. The in-vivo experiments were subjected to a penetrating keratoplasty (PK) performed between host Sprague Dawley (SD) and donor Wistar/SD rats, randomly dividing them into 4 groups including the allograft, isograft, allograft treated with LV-eGFP (LV blank control) and allograft treated with LV-TLR2-siRNA-eGFP (LV treated group). The rejection index (RI) was then recorded under a slit lamp, every day following surgery. Expression of the TLR2 and Myeloid differentiation primary response gene 88 (MyD88) were detected by using immunohistochemistry on day 9 post-surgery, whereas grafts's TLR2 and MyD88 mRNA were determined on day 5, 9, and 14 post-surgery performing RT-PCR and, normal rat corneas were included as additional controls.ResultsTransfected cells showed the strongest eGFP expression when MOI was 200 with an efficiency of 77.5% for EC and 76.3% for SC. CCK-8 assay, as measured at 72 and 96h post transfection, showed no significant changes in the cell viability (both EC and SC) between the transfected and the control group (p>0.05, p>0.05). Western blot results demonstrated a successful down regulation of TLR2 expression by LV-TLR2-SiRNA-eGFP, in both EC and SC. In vivo, compared to allograft group, LV treated group demonstrated less edema, opacity and neovascularization. Immunohistochemical analysis revealed a lower expression of TLR2 and MyD88 in isograft and LV treated group as compared to allograft group. TLR2 and MyD88 mRNA were detected in all grafts, and increased over time. With its highest expression in allograft group (peak on day 9), the mRNA expression for TLR2 and MyD88 showed a significant difference amongst the groups, on both day 9 and 14 (p<0.001).ConclusionsLV mediated TLR2 siRNA could effectively down regulate the TLR2 expression via RNA interference and prolong the survival of corneal grafts, although not necessarily able to prevent the rejection.



http://ift.tt/2wORtpw

Sialadenoma Papilliferum: Analysis of Seven New Cases and Review of the Literature

Abstract

Sialadenoma papilliferum (SP) is a rare benign salivary gland neoplasm that comprises from 0.4 to 1.2% of all salivary gland tumors. The tumor is so named because of its microscopic resemblance to the syringocystadenoma papilliferum, an uncommon benign tumor of sweat gland origin. The purpose of this paper is to report the clinical and microscopic features of seven new cases of SP and combine them with cases previously reported in the English language literature to further define this unusual lesion. Combining our cases with acceptable cases from the literature, the palate (especially the hard palate) was the most common site, with 80% of the cases occurring in this location. Other locations in decreasing order were buccal mucosa, upper lip, retromolar pad, and parotid gland. Age at diagnosis ranged from 18 to 87 years with a peak in the 6th decade and an average age of 56.4 years. Microscopically, the lesions demonstrated a papillary surface morphology, and the papillary projections varied from long and pointed to short and blunted. The supporting connective tissue contained a variable number of convoluted ductal structures, which often fused with the overlying surface epithelium. The ductal structures exhibited papillary infoldings and were lined by a double layer of epithelium consisting of basal cell layer and a luminal layer of cuboidal-to-columnar ductal cells. Immunohistochemical reactivity with p63 and p40 indicated that the basal cell layer was comprised predominantly of neoplastic myoepithelial cells. The luminal cells were immunoreactive with epithelial membrane antigen characteristic of ductal cell differentiation. Conservative surgical treatment was accomplished in most cases and appears to be adequate treatment as only two recurrences were documented. Several case reports of purported malignant transformation in SP have been reported in the literature, but in our opinion, there is insufficient evidence in the publications to unequivocally determine whether any of the malignancies truly originated within a pre-existing SP.

http://ift.tt/2f83HCa

A Comparison of Alkaline Water and Mediterranean Diet vs Proton Pump Inhibition for Treatment of Laryngopharyngeal Reflux.

A Comparison of Alkaline Water and Mediterranean Diet vs Proton Pump Inhibition for Treatment of Laryngopharyngeal Reflux.

JAMA Otolaryngol Head Neck Surg. 2017 Sep 07;:

Authors: Zalvan CH, Hu S, Greenberg B, Geliebter J

Abstract
Importance: Laryngopharyngeal reflux (LPR) is a common disorder with protean manifestations in the head and neck. In this retrospective study, we report the efficacy of a wholly dietary approach using alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions compared with that of the traditional treatment approach of proton pump inhibition (PPI) and standard reflux precautions.
Objective: To determine whether treatment with a diet-based approach with standard reflux precautions alone can improve symptoms of LPR compared with treatment with PPI and standard reflux precautions.
Design, Setting, and Participants: This was a retrospective medical chart review of 2 treatment cohorts. From 2010 to 2012, 85 patients with LPR that were treated with PPI and standard reflux precautions (PS) were identified. From 2013 to 2015, 99 patients treated with alkaline water (pH >8.0), 90% plant-based, Mediterranean-style diet, and standard reflux precautions (AMS) were identified. The outcome was based on change in Reflux Symptom Index (RSI).
Main Outcomes and Measures: Recorded change in the RSI after 6 weeks of treatment.
Results: Of the 184 patients identified in the PS and AMS cohorts, the median age of participants in each cohort was 60 years (95% CI, 18-82) and 57 years (95% CI, 18-93), respectively (47 [56.3%] and 61 [61.7%] were women, respectively). The percentage of patients achieving a clinically meaningful (≥6 points) reduction in RSI was 54.1% in PS-treated patients and 62.6% in AMS-treated patients (difference between the groups, 8.05; 95% CI, -5.74 to 22.76). The mean reduction in RSI was 27.2% for the PS group and 39.8% in the AMS group (difference, 12.10; 95% CI, 1.53 to 22.68).
Conclusions and Relevance: Our data suggest that the effect of PPI on the RSI based on proportion reaching a 6-point reduction in RSI is not significantly better than that of alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions, although the difference in the 2 treatments could be clinically meaningful in favor of the dietary approach. The percent reduction in RSI was significantly greater with the dietary approach. Because the relationship between percent change and response to treatment has not been studied, the clinical significance of this difference requires further study. Nevertheless, this study suggests that a plant-based diet and alkaline water should be considered in the treatment of LPR. This approach may effectively improve symptoms and could avoid the costs and adverse effects of pharmacological intervention as well as afford the additional health benefits associated with a healthy, plant-based diet.

PMID: 28880991 [PubMed - as supplied by publisher]

http://ift.tt/2wO8Gj8

Dietary Modifications in the Treatment of Laryngopharyngeal Reflux-Will "an Apple a Day" Keep the Laryngopharyngeal Reflux Away?

Dietary Modifications in the Treatment of Laryngopharyngeal Reflux-Will "an Apple a Day" Keep the Laryngopharyngeal Reflux Away?

JAMA Otolaryngol Head Neck Surg. 2017 Sep 07;:

Authors: Kavitt RT

PMID: 28880985 [PubMed - as supplied by publisher]

http://ift.tt/2jbaHT5

Association of a Perioperative Education Program With Unplanned Readmission Following Total Laryngectomy.

Association of a Perioperative Education Program With Unplanned Readmission Following Total Laryngectomy.

JAMA Otolaryngol Head Neck Surg. 2017 Sep 07;:

Authors: Graboyes EM, Kallogjeri D, Zerega J, Kukuljan S, Neal L, Rosenquist KM, Nussenbaum B

Abstract
Importance: Patients undergoing total laryngectomy (TL) are at high risk for 30-day hospital readmission. Strategies to decrease the readmission rate remain unknown.
Objectives: To assess the association of a comprehensive perioperative TL education program with unplanned readmissions; to determine the program's association with the rate of readmissions for stomal or tracheoesophageal puncture (TEP) complications and patient and caregiver knowledge of and preparedness for TL.
Design, Setting, and Participants: This single-institution prospective pilot study was conducted between December 1, 2014, and November 30, 2016, among 50 patients undergoing a perioperative TL education program at a tertiary care academic medical center.
Intervention: The perioperative TL education program consisted of speech-language pathology counseling, a hands-on class with an otolaryngology nurse educator, a TL "Journal Guide" booklet, and a prehospital discharge competency assessment. A family member or friend acting as a laryngectomy coach accompanied patients throughout.
Main Outcomes and Measures: The primary outcome was the rate of 30-day unplanned readmission. Secondary measures included the rate of readmission for stomal or TEP complications and change in knowledge of and preparedness for TL.
Results: Of the 50 patients (12 women and 38 men; median age, 61 years [range, 47-86 years]) who underwent the TL education program, the 30-day unplanned readmission rate was 20% (n=10). Only 1 patient (2%) had a readmission for a stomal or TEP complication. Patients increased their TL knowledge (median improvement in TL knowledge test score, 3.5 [95% CI, 2.8-4.2] of 12) and preparedness (median improvement in TL preparedness score, 3.1 [95% CI, 2.4-3.8] of 10) after undergoing the intervention.
Conclusions and Relevance: This prospective pilot study evaluated an intervention to decrease unplanned readmission in head and neck oncology patients. It provides data indicating that a comprehensive perioperative TL education program is feasible. This program has the potential to decrease 30-day readmission for stomal or TEP complications and merits further study in a larger, multicenter clinical trial.

PMID: 28880984 [PubMed - as supplied by publisher]

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Treatment withdrawal and end-of-life care in the intensive care unit

1F052C063A07

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Table of Contents

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Cover

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Subscriptions

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Introduction: Antibody-Mediated Therapy Special Issue

In 1896, The Lancet hailed the application of serum antitoxins (antibodies) that neutralize diphtheria or its toxins as 'the most important advance of the century in the medical treatment of infective disease' (1). In 2013, the use of monoclonal antibodies (mAbs) for cancer immunotherapy was hailed as the 'breakthrough of the year' (2). The ready availability of serum and the relatively high concentrations of antibodies there have meant that, as new technologies have emerged over the intervening decades, novel and refined antibody-based therapies have paralleled breakthroughs in basic research investigating the structure of antibodies, the genetic and molecular mechanisms involved in their production and their many effector functions. As our knowledge of the complexity of the immune system and its role in health and disease has grown, the central role of antibodies has remained unchallenged; and the extraordinary properties resulting from the combination of constant and variable features, allowing both predictability and manipulation, have allowed us to exploit antibody molecules to serve as reagents and as drugs.

http://ift.tt/2wdWPsK

Antibody therapy for the management of severe asthma with eosinophilic inflammation

Abstract

One of the characteristic features of asthma is chronic airway inflammation typically with eosinophil infiltration. Most asthmatics can be treated successfully with conventional treatment appropriate for their severity, but in some severe cases, asthma cannot be well controlled even with thorough treatment and this condition is known as 'refractory asthma'. To overcome severe refractory asthma, a new therapeutic strategy with biologics has been developed based on the knowledge of molecular mechanisms of airway inflammation in asthma, induced by the condition of high T_h2-type responses and activation of eosinophils as well as allergic reactions. Humanized anti-human IgE antibody (anti-IgE; omalizumab) was the first biological preparation approved for treating asthma. Based on clinical evidence, treatment with anti-IgE (anti-IgE therapy) has been accepted as a new therapeutic approach for severe allergic asthma in adults since 2009 and in children since 2012 and has been shown to have ~60% efficacy. More recently, a humanized anti-IL-5 antibody (anti-IL-5; mepolizumab) was launched in June 2016 and has attracted great interest due to its potential effects. Several clinical studies are also ongoing to evaluate the biological preparations targeting IL-5 receptor α (IL-5Rα), IL-4 receptor α (IL-4Rα), which is shared by IL-4 and IL-13, thymic stromal lymphopoietin (TSLP) and IL-33. The new strategy with biologics targeting eosinophilic airway inflammation might open a new array for us to overcome severe refractory asthma in the future.

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Polymorphisms of immunoglobulin receptors and the effects on clinical outcome in cancer immunotherapy and other immune diseases: a general review

Abstract

Receptors for the Fc domain of immunoglobulins [Fc receptors (FcRs)] are essential for the maintenance of antibody-mediated immune responses. FcRs consist of activating- and inhibitory-type receptors that regulate adequate thresholds for various immune cells. In particular, polymorphisms and/or gene copy-number variations of FcRs for IgG (FcγRs) are closely associated with the development of inflammatory disorders, including autoimmune diseases. Recent evidence has implicated polymorphisms of FcRs in the efficacy of monoclonal antibody (mAb)-mediated therapy. This review provides an overview of genetic variations in human FcγRs and the clinical contribution of FcγR polymorphisms in mAb treatments for cancer, autoimmune diseases and allergies.

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Efficiency of antibody therapy in demyelinating diseases

Abstract

Monoclonal antibody therapy is a new treatment strategy for many types of diseases including cancers and autoimmune diseases, realizing a high efficacy and tolerability. In multiple sclerosis (MS) and neuromyelitis optica (NMO) spectrum disorders, several monoclonal antibodies have been suggested to decrease the incidence of clinical relapse and the disease activity. In MS, anti-α4 integrin (natalizumab), anti-CD52 (alemtuzumab), anti-CD25 (daclizumab) and anti-CD20 (ocrelizumab) have been shown to effectively reduce the relapses in randomized controlled trials and have been approved by the Food and Drug Administration. Specifically, ocrelizumab is the first drug that has shown significant suppression of brain volume loss and suppression of chronic disability progression. In NMO, though there have yet to be any approved monoclonal antibodies, rituximab, anti-complement C5 (eculizumab), anti-IL-6 receptor (tocilizumab), anti-CD19 (inebilizumab) and non-pathogenic anti-aquaporin 4 (aquaporumab) have been suggested to be effective, and some of these are now under clinical trials. Aquaporumab is a non-pathogenic recombinant human monoclonal antibody that competitively inhibits the binding of the pathogenic auto-antibody against aquaporin 4 in NMO patients; thus, it is expected to be highly disease specific with less non-specific adverse events. Some of these monoclonal antibodies in MS and NMO are known to cause several notable adverse events. Natalizumab and rituximab increase the risk of progressive multifocal leukoencephalopathy. Eculizumab increases the risk of meningococcal infection. Tocilizumab is known to cause intestinal diverticulitis that can cause intestinal perforation. In this review, we summarize the characteristics of, evidence for and notable adverse events of each monoclonal antibody in MS and NMO.

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Glycosylation of IgG-Fc: a molecular perspective

Abstract

Antibodies of the IgG class carry a pair of oligosaccharides (N-glycans) in the Fc region. The importance of the N-glycan is clearly demonstrated by its profound effect in the physicochemical and biological properties of antibodies. The term 'glycoengineering' has been coined to describe contemporary strategies to improve the performance of therapeutic monoclonal antibodies on the basis of modifications in the structure and composition of the N-glycan. These methodologies have resulted in the approval and commercialization of a new generation of antibodies with improved therapeutic efficacy. So far, these advances have been driven by herculean efforts in a process of trial-and-error. The collective work of researchers in this field is progressively revealing the molecular basis of N-glycans for the function of antibodies. This knowledge will ultimately be conducive to the application of rational approaches for the successful manipulation of antibodies using glycoengineering strategies. Herein, we review advances in our understanding of the role of the N-glycan in the structural and dynamic integrity, and biological activity, of antibodies. Since the N-glycan has a multifaceted effect in antibodies, in this review we have emphasized the importance of integrating various techniques that address this problem from multiple points of view. In particular, the combination of X-ray crystallography with nuclear magnetic resonance, molecular dynamics simulations and biophysical approaches based on thermodynamic principles, has emerged as a powerful combination that is deepened our understanding of this unique system with critical implications for human well-being.

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Diversification of IgG effector functions

Abstract

IgG is the major immunoglobulin class produced during an immune response against foreign antigens and efficiently provides protection through its bifunctional nature. While the Fab domains confer highly specific recognition of the antigen, the Fc domain mediates a wide range of effector functions that modulate several aspects of innate and adaptive immunity. Engagement of the various types of Fcγ receptors (FcγRs) by an IgG Fc domain can activate distinct immunomodulatory pathways with pleiotropic functional consequences for several leukocyte types. Fc effector functions are not limited to phagocytosis and cytotoxicity of IgG-opsonized targets but exhibit remarkable diversity and include modulation of leukocyte activity and survival, cytokine and chemokine expression, maturation of antigen-presenting cells, antigen processing and presentation, B-cell selection and IgG affinity maturation, as well as regulation of IgG production. These functions are initiated upon specific interactions of the Fc domain with the various types of FcγRs—a process that is largely determined by the structural heterogeneity of the IgG Fc domain. Modulation of the Fc-associated glycan structure and composition along with differences in the primary amino acid sequence among the IgG subclasses represent the two main diversification mechanisms of the Fc domain that generate a spectrum of Fc domain phenotypes with distinct affinity for the various FcγR types and differential capacity to activate immunomodulatory pathways.

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Ormdl3 Upregulates Airway Smooth Muscle Proliferation, Contraction, and Ca2+ Oscillations in Asthma

Publication date: Available online 7 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Jun Chen, Marina Miller, Hirotoshi Unno, Peter Rosenthal, Michael Sanderson, David H. Broide
BackgroundAirway hyperresponsiveness (AHR) is a major feature of asthma attributed predominantly to an extrinsic immune/inflammatory response increasing airway smooth muscle (ASM) contractility.ObjectiveWe investigated whether increased ASM expression of ORMDL3, a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro, as well as influenced airway contractility and calcium flux in ASM in precision cut lung slices from WT and hORMDL3^Zp3-Cre mice (which express increased levels of human ORMDL3).MethodsLevels of ASM proliferation and contraction were assessed in ASM cells transfected with ORMDL3 in vitro. In addition, airway contractility and calcium oscillations were quantitated in ASM cells in precision cut lung slices derived from naïve WT and naïve hORMDL3^Zp3-Cre mice which do not have a blood supply.ResultsIncreased ASM expression of ORMDL3 in vitro resulted in increased ASM proliferation and contractility. Precision cut lung slices derived from naïve hORMDL3^Zp3-Cre mice which do not have airway inflammation exhibit increased airway contractility with increased calcium oscillations in ASM cells. Increased ASM ORMDL3 increases ASM sarcoplasmic reticulum Ca²⁺ ATPase 2b (SERCA2b) which increases ASM proliferation and contractility.ConclusionOverall, these studies provide evidence that an intrinsic increase in ORMDL3 in ASM can induce increased ASM proliferation and contractility which may contribute to increased AHR in the absence of airway inflammation in asthma.

Teaser

This study demonstrates that an intrinsic increase in ORMDL3 in ASM can induce increased ASM proliferation and contractility which might contribute to increased AHR in the absence of airway inflammation in asthma.


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miRNA-155 mediates down-regulation of the high-affinity receptor for IgE via Toll-like receptor signaling

Publication date: Available online 7 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Nicole Leib, Nadine Herrmann, Susanne Koch, Tim J. Stroisch, Sylvia Schnautz, Helene Wilms, Thomas Bieber

Teaser

miRNA-155 contributes to the inflammatory process in AD by regulating the expression of the high-affinity receptor for IgE (FcεRI) via its transcription factor PU.1. miRNA-155 may represent an interesting new target in AD therapy.


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Role of B cells in T helper cell responses in a mouse model of asthma

Publication date: Available online 7 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Tomasz Piotr Wypych, Roberta Marzi, Gregory F. Wu, Antonio Lanzavecchia, Federica Sallusto
BackgroundThe importance of B lymphocytes to present antigens for antibody production is well documented. In contrast, very little is known about their capacity to influence CD4⁺ T cell activation during primary or secondary response to allergens.ObjectiveUsing mouse models of asthma, we investigated the role of B cells as antigen presenting cells in propagation and initiation of T helper cell responses.MethodsMice were immunized via intranasal route with house dust mite extract (HDM) derived from Dermatophagoides pteronyssinus. To investigate the importance of B cells in maintenance of allergic response, B cells were depleted in HDM-sensitized animals. To investigate the role of B cells in T cell priming, B cells were depleted before HDM sensitization; furthermore, HDM sensitization was performed in mice with MHC-II expression restricted to the B cell lineage.ResultsWe found that B cells serve as potent antigen presenting cells ex-vivo and restimulate in vivo-primed HDM-specific T helper cells. HDM antigens were taken up by B cells independently of the B cell receptor specificity, indicating that HDM uptake and antigen presentation to CD4⁺ T cells is not restricted to rare B cells carrying HDM-specific B cell receptors. B cell depletion before HDM challenge in HDM-sensitized mice resulted in a dramatic reduction of allergic response, indicating the role of B cells in amplification of Th2 responses. In contrast, HDM sensitization of mice in which MHC-II expression was restricted to B cells revealed the inability of these cells to initiate Th2 responses, but highlighted their unexpected role in priming Th1 and Th17 responses.ConclusionCollectively, these data reveal new mechanisms leading to initiation and exacerbation of allergic response that may have implications for designing new therapeutic strategies to combat house dust mite allergy.

Graphical abstract

Teaser

B cells efficiently take up HDM antigens independently of their B cell receptor specificity and serve as potent antigen presenting cells, influencing both propagation and initiation of T helper cell response in vivo.


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Impaired Humoral and Cellular Immune Responses to Influenza Vaccination in COPD Patient

Publication date: Available online 7 September 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Aurélien Parpaleix, Laurent Boyer, Aurelie Wiedemann, Christine Lacabaratz, Laurent Margarit, Vincent Enouf, Philippe Le Corvoisier, Anne Lino, Ala Covali-Noroc, Bruno Housset, Christos Chouaid, Bernard Maitre, Yves Lévy, Jean-Daniel Lelièvre, Serge Adnot




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Sialadenoma Papilliferum: Analysis of Seven New Cases and Review of the Literature

Abstract

Sialadenoma papilliferum (SP) is a rare benign salivary gland neoplasm that comprises from 0.4 to 1.2% of all salivary gland tumors. The tumor is so named because of its microscopic resemblance to the syringocystadenoma papilliferum, an uncommon benign tumor of sweat gland origin. The purpose of this paper is to report the clinical and microscopic features of seven new cases of SP and combine them with cases previously reported in the English language literature to further define this unusual lesion. Combining our cases with acceptable cases from the literature, the palate (especially the hard palate) was the most common site, with 80% of the cases occurring in this location. Other locations in decreasing order were buccal mucosa, upper lip, retromolar pad, and parotid gland. Age at diagnosis ranged from 18 to 87 years with a peak in the 6th decade and an average age of 56.4 years. Microscopically, the lesions demonstrated a papillary surface morphology, and the papillary projections varied from long and pointed to short and blunted. The supporting connective tissue contained a variable number of convoluted ductal structures, which often fused with the overlying surface epithelium. The ductal structures exhibited papillary infoldings and were lined by a double layer of epithelium consisting of basal cell layer and a luminal layer of cuboidal-to-columnar ductal cells. Immunohistochemical reactivity with p63 and p40 indicated that the basal cell layer was comprised predominantly of neoplastic myoepithelial cells. The luminal cells were immunoreactive with epithelial membrane antigen characteristic of ductal cell differentiation. Conservative surgical treatment was accomplished in most cases and appears to be adequate treatment as only two recurrences were documented. Several case reports of purported malignant transformation in SP have been reported in the literature, but in our opinion, there is insufficient evidence in the publications to unequivocally determine whether any of the malignancies truly originated within a pre-existing SP.

http://ift.tt/2f83HCa

Early signs and symptoms of intracranial complications of otitis media in pediatric and adult patients: A different presentation?

Publication date: November 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 102
Author(s): N.A. Van der Poel, E. van Spronsen, D.A. Dietz de Loos, F.A. Ebbens
ObjectivesThe aim of this study was to review the clinical presentation and early signs and symptoms of otogenic intracranial complications (OIC) in children and adults.Methods: retrospective chart review. The medical records of all children and adults admitted in our center with OIC during the period 2008–2017 were reviewed. Data concerning clinical presentation, treatment and outcomes were reviewed and analyzed.ResultsWe included 47 patients with OIC: 21 children (range 1–13 years) and 26 adults (range 22–71 years). We included more patients with acute otitis media than with chronic otitis media (children 5% adults 19%, all with cholesteatoma).In children; the most common OIC was central cerebral venous thrombosis. In both children and adults; otogenic symptoms such as otalgia and otorrhea were present. Children presented more frequently with headache and nausea. Adults presented more frequently with decreased consciousness. Hearing loss was the most common long-term sequel. Three adults died.ConclusionsIn our series, we found that OIC in children present as 'mimicking meningitis' (e.g. nausea and vomiting). Adults on the other hand have a clinical presentation 'mimicking stroke' (e.g. neurological deficits and decreased level of consciousness). In children, sinus thrombosis was observed more frequently than in adults.Despite the low mortality rate, death still occurs. Long -term sequelae most frequently include hearing loss in children as well as in adults.



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A Japanese population-based meta-analysis of vonoprazan versus PPI for Helicobacter pylori eradication therapy: Is superiority an illusion?

Abstract

Background

Vonoprazan (VPZ) is a novel acid suppressant that has been used in Helicobacter pylori (H. pylori) eradication therapies in recent years. However, the efficacy and safety of VPZ vs proton-pump inhibitor (PPI) in H. pylori eradication therapies remain controversial.

Objective

To perform a meta-analysis in order to assess the efficacy and safety of VPZ vs PPI for H. pylori eradication.

Materials and Methods

The PubMed, EMBASE, and Cochrane Library databases were searched up to July 10, 2017, for relevant randomized controlled trials (RCTs) and nonrandomized clinical studies (NRCTs). The pooled eradication rate (ER) and pooled occurrence rates of adverse events were used to compare the efficacy and safety of VPZ - and PPI-containing regimens.

Result

A total of 14 studies with 14 636 patients were included in this meta-analysis. The results showed that the pooled ER of VPZ -containing regimens was much higher than that of PPI-containing regimens when used as first-line therapies. This difference was significant for both intention-to-treat (85.1% vs 68.0%, P < .00001) and per-protocol analyses (89.0% vs 74.2%, P < .00001). Moreover, subgroup analysis indicated significant superiority of VPZ in both patients with clarithromycin-resistant strains (81.5% vs 40.9%, P < .00001) and those with clarithromycin-susceptible strains (94.9% vs 89.6%, P = .006). However, VPZ did not show superiority to PPI as part of a second-line triple therapy based on both intention-to-treat (83.4% vs 82.0%, P = .79) and per-protocol analyses (89.3% vs 90.1%, P = .06). Finally, RCT subgroup analysis showed the safety of VPZ -containing regimens to be better than PPI-containing regimens (26.4% vs 33.3%, P = .008), whereas there was no significant difference in this regard for the NRCT subgroup analysis (5.7% vs 4.7%, P = .08).

Conclusions

The efficacy of VPZ is superior to PPI in first-line H. pylori triple eradication therapies but not in second-line therapies. The safety of VPZ -containing regimens appears to be equal or even superior to that of PPI. However, most reports included in this study had low levels of evidence. Hence, adequate and high-quality RCTs will be needed to support our results.

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Antiseptische Wirkstoffe in Topika

Zusammenfassung

Die topische Therapie ist auch im 21. Jahrhundert eine wichtige Domäne bei der Behandlung dermatologischer Krankheitsbilder. Da bei chronischen Erkrankungen multiresistente Keime ein immer größeres Problem in der medizinischen Versorgung sind, ist es wichtig, geeignete therapeutische Managementoptionen bei akuten und chronischen Dermatosen zu finden. Auch die Diskussion um das Mikrobiom der Haut zeigt, dass es bei Hautinfektionen wichtig ist, die residente Hautflora möglichst wenig zu verändern. Hier wird die Frage nach Alternativen zu topischen Antibiotika, wie z. B. topische Antiseptika, immer lauter. Sie sollten sicher, gut und schnell wirksam, wenig allergisierend und toxisch sein sowie trotz längerer oder häufiger Anwendung wenig Resistenzen entwickeln. In diesem Beitrag liegt der Schwerpunkt auf dem Einsatz der Antiseptika bei medizinischen Indikationen. Wirkmechanismen, Verträglichkeit, Maximalkonzentrationen und mögliche Kontraindikationen werden aufgezeigt und praktische Beispiele mit Rezepturoptionen wiedergegeben.

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Evaluation of the natural history of patients who aspirate

Objectives/Hypothesis

The natural clinical progression of aspiration to eventual pulmonary compromise is not well understood. We hypothesized that dietary modification recommendations, Penetration-Aspiration Scale (PAS) score, and dysphagia etiology would be associated with changes in time to first pulmonary event and overall survival for patients with documented aspiration on radiologic testing. This study identified a cohort of patients with detectable unsensed penetration or aspiration on videofluoroscopic swallowing study (VFSS), and followed this cohort over time for development of pulmonary events and death. We then evaluated the association of aspiration severity and dietary modification recommendations on incidence of these endpoints.

Study Design

Retrospective chart review.

Methods

A total of 2,616 VFSS exam reports were reviewed from our institution performed between January 1, 2009 and December 31, 2010. Aspiration or unsensed penetration (PAS of 5 or greater) was detected in 564 (21.5%) of these patients, who were then included in the study cohort. Medical records were reviewed retrospectively for development of pulmonary events (pneumonia, pneumonitis, or other life-threatening pulmonary illness) and all-cause mortality for up to 54 months after initial VFSS. Univariate Kaplan-Meier analysis and multivariate Cox regression were performed for time to first pulmonary event and survival predicted by recommended diet, PAS score, and dysphagia etiology.

Results

Dysphagia etiology was highly associated with increased development of pulmonary events for some patients, especially those with generalized nonspecific dysphagia due to deconditioning or frailty (hazard ratio [HZ] vs. stroke 2.95, 95% confidence interval [CI]: 1.53-5.69, P = .001) and esophageal dysphagia (HZ: 2.66, 95% CI: 1.17-6.02, P = .019). Dysphagia etiology was also associated with increased mortality for patients with generalized nonspecific dysphagia due to deconditioning or frailty (HZ: 3.32, 95% CI: 2.0-5.52, P < .001), postsurgical patients (HZ: 1.73, 95% CI: 1.05-2.86, P = .032), and chronic neurologic disease (HZ: 1.87, 95% CI: 1.12-3.13, P = .017). Dietary modification recommendations at the time of VFSS (prohibition of oral intake or modification of food consistency) had no significant impact on time to first pulmonary event (P = .37) or survival (P = .17), whereas PAS score was associated with decreased time to first pulmonary event on univariate but not multivariate analysis (HZ for 1-point increase: 1.6, 95% CI: 0.99-1.36, P = .067). Kaplan-Meier estimate of overall 3-year mortality for this patient cohort was 39%.

Conclusions

Etiology of dysphagia is associated with a higher mortality rate and development of pulmonary events in patients with unsensed penetration or aspiration on VFSS, especially for those patients with generalized deconditioning and frailty or esophageal dysphagia. Severity of aspiration as defined by PAS was not associated with altered overall survival. Recommendations for dietary modification to a nothing by mouth status or modified food consistency had no statistically significant association with development of pulmonary events or survival in patients with detectable unsensed penetration or aspiration on VFSS compared to full-diet recommendation.

Level of Evidence

4. Laryngoscope, 2017

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