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Τρίτη 7 Αυγούστου 2018

Mechanistic and pharmacological assessment of murine IL-23 mediated psoriasiform dermatitis; implications for drug discovery

Animal models of Psoriasis (PsO) are important for our understanding of the pathophysiology of human disease but rarely manifest all features of the disease. In order to facilitate greater understanding of the underlying biology of PsO it is key that we understand the strengths and limitations of models used.

Potential adverse effects of antimicrobial chemotherapy based on ultraviolet-A irradiation of polyphenols against the oral mucosa in hamsters and wounded skin in rats

Publication date: Available online 7 August 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): Keisuke Nakamura, Taichi Tenkumo, Takayuki Mokudai, Midori Shirato, Kirika Ishiyama, Taro Kanno, Keiichi Sasaki, Yoshimi Niwano

Abstract

Antimicrobial chemotherapy based on ultraviolet-A (UVA) irradiation of polyphenol solution has been proposed as an adjunctive treatment for dental caries. However, the safety of this treatment has not been thoroughly evaluated. Therefore, the aim of the present study was to assess the influence of this treatment on the oral mucosa in hamsters and wounded skin in rats. An oral mucosal irritation test was performed in hamsters. The cheek pouch was everted and treated with UVA irradiation (wavelength: 365 nm) of pure water, 1 mg/mL of caffeic acid, or 1 mg/mL of grape seed extract using a light-emitting diode at an irradiance of 275 mW/cm2. Each treatment was performed for 2 or 5 min and repeated three times. Macroscopic and histological evaluations were performed 24 h after the last treatment. We also examined the effects of the treatment on the healing process of skin wounds in rats. Full-thickness skin wounds created on the back of the rats were treated for 2 min as described above, but only once. The wound area was then assessed daily for 9 days. The results demonstrated that the treatment induced oral mucosal irritation depending on the irradiation time; however, it did not influence the wound healing process. The oral mucosal irritation potential of three treatment sessions performed for 2 and 5 min was minimal and mild to moderate, respectively, according to histological analysis. These findings suggest that the duration of treatment based on UVA irradiation of polyphenols in the oral cavity should be as short as possible, considering the clinical efficacy of the antimicrobial effects and the irritation potential.

Graphical Abstract

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The association between ambient air pollution exposure and mental health status in Chinese female college students: a cross-sectional study

Abstract

The association between exposure to air pollution and mental health has not been adequately studied. Accordingly, this study aimed to explore the association between exposure to ambient air pollution and mental health status among female college students. We performed a cross-sectional study involving female students attending college located in Anshan, a heavy industry city in Northeast China. The investigation was performed using electronic questionnaires including the Symptom Checklist-90 (SCL-90), Pittsburgh Sleep Quality Index (PSQI), Cornell Medical Index (CMI), and general well-being (GWB) scale between March and April 2017. The individual daily average of time spent outdoors in each season was used as an indicator of exposure to ambient air pollution. The association between mental health status and exposure to ambient air pollution was analyzed using general linear regression. Of the 412 female participants, 346 (83.98%) submitted valid questionnaires. Multivariate linear regression indicated that GWB was negatively associated with the SCL-90 score, and annual average daily outdoor time and sleep quality were positively associated with the SCL-90 score. This study demonstrated that exposure to ambient air pollution may be a risk factor for mental health problems among female college students.



Global Guidelines and Initiatives from the European Confederation of Medical Mycology to improve Patient Care and Research Worldwide: New Leadership is about Working Together

Mycoses, Volume 0, Issue ja, -Not available-.


The importance of early implementation of laser treatment in facial scars: A single-institution retrospective study

Background: Interest in minimizing scars especially on face has been rising recently.

Mycosis fungoides in Puerto Rico

Mycosis fungoides (MF) and Sezary syndrome compromise about 53% of cutaneous lymphomas. Disease stage depends on involved body surface area, clinical presentation and the presence or absence systemic involvement, which will determine treatment. MF is generally diagnosed at early stages and carries a chronic and indolent disease course. In 2007, 30 MF cases in Puerto Rico were described from 1983 to 2002. We performed a retrospective chart review of MF cases (1999-2016) to compare these populations and identify any changes in disease prognosis and treatment response given different and new treatment modalities are now available.

Real-world use of secukinumab for the treatment of plaque psoriasis and psoriatic arthritis: Experience of four dermatology units in Spain

Introduction: Worldwide, there is an increasing trend to use real-world data to inform decision making in health care. The data regarding appropriate drug use, effectiveness, and cost-effectiveness in real-world clinical practice is intended to complement the findings from clinical trials, and to evaluate a drug's real-world value. Secukinumab is a fully humanized anti–interleukin (IL) 17A antibody that specifically binds to IL-17A receptors. In recent years, IL-17A has been recognized to play an important role in the disease pathology.

Comorbid conditions in lichen planopilaris: A retrospective data analysis of 334 patients

Background: Lichen planopilaris (LPP) is a rare cicatricial, lymphocyte mediated alopecia. It is thought to have an autoimmune pathogenesis, and possibly related to other autoimmune diseases; however, data are limited. In addition, studies examining comorbid conditions are lacking.

Small molecule inhibitor of the Wnt pathway (SM04755) as a potential topical treatment for psoriasis

Background: Psoriasis (PSO) is an autoimmune disease causing patches of thick, inflamed, scaly skin due to excessive proliferation of skin cells. Wnt signaling plays an important role in PSO, regulating inflammation and keratinocyte proliferation. SM04755, a novel, topical small-molecule Wnt pathway inhibitor was previously shown to inhibit inflammation and keratinocyte proliferation in vitro and in an IMQ-induced mouse PSO model. In this study, the effects of SM04755 on inflammation and skin health were evaluated in a model using reconstitution of ICR scid mice with minor histocompatibility mismatched naive CD4+ T lymphocytes, which more closely resembles human PSO pathophysiology.

Time to tumor response and planned subgroup analyses from the BOLT trial for sonidegib in advanced basal cell carcinoma

Background: Sonidegib 200 mg once daily (qd) was approved in the United States for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy based on results of the phase 2 BOLT study (NCT01327053). Here we report time to tumor response and planned subgroup analyses from the 30-month efficacy data from BOLT.

Editorial Board



Teledermatology in rural and remote British Columbia: A survey of primary care providers

Teledermatology, defined as the delivery of dermatology care at a distance through telecommunication technologies, has been proposed as a strategy to improve dermatology access to underserved populations. One such population is in rural and remote British Columbia, an area where there are currently no regularly practicing dermatologists. To gain an understanding of teledermatology utilization, attitudes and experiences in this area, we distributed a 14-question survey containing 10 questions related to the study objective.

Retrospective comparison of the clinical effects of programmed death protein 1 inhibitors to treat melanoma versus nonmelanoma skin cancer

Background: Programmed death protein (PD) 1 inhibitors have revolutionized treatment for cancers such as melanoma. However, clinical benefits and risks of PD-1 inhibitors among nonmelanoma skin cancers (NMSCs) are less well known, although off-label usage has been reported in the medical literature.

Two cases of cutaneous endometriosis

Cutaneous endometriosis (CEM) is a rare cutaneous manifestation of a common gynecological disease. More than 70% of CEM lesions are seen at sites of previous surgical scars, however primary lesions can arise de-novo in previously normal epithelium. The clinical presentation can vary and mimic other common dermatologic conditions. We present 1 primary and 1 secondary case of young healthy African American women with umbilical CEM. A 30-year-old woman presented with 2 umbilical lesions present for 1 year, associated with intermittent pain, swelling, and bleeding with menstrual cycles.

Subject satisfaction demonstrated for two on-label injection volumes of abobotulinumtoxinA when used to treat moderate to severe glabellar lines

Introduction: In the U.S., glabellar lines (GLs) are most often treated with botulinum toxin type A (BoNT-A) and satisfaction with treatment is typically measured using patient-reported outcomes. Dysport (abobotulinumtoxinA [ABO]) is approved in the U.S. for the treatment of GLs and can be injected at 2 different injection volumes, 0.05 mL and 0.08 mL. In this study, we evaluated both on-label injection volumes in subjects with moderate to severe GLs at maximum frown and asked them to complete questionnaires before and after treatment to assess treatment satisfaction and health-related quality of life subject-reported outcomes, which is the focus of this report.

Secondary localized cutaneous amyloidosis in mycosis fungoides

Secondary localized cutaneous amyloidosis is often not clinically apparent, but may be seen histologically. It is associated with several skin tumors, and has been reported with PUVA use. To date, there are three reported cases of secondary localized cutaneous amyloidosis associated with mycosis fungoides before any treatment. We present a case of a 39-year-old woman who presented to the dermatology clinic for evaluation of facial acne. During the exam, several 5-10 mm hypopigmented patches were noted on the bilateral ventral forearms.

Ustekinumab an alternative therapeutic option for refractory erytroderma pytiriasis rubra pilaris disease

Introduction: Pityriasis rubra pilaris (PRP) is a rare, chronic erythematous squamous disorder. PRP is divided into six subtypes, type 1 being the most common and classic form in adults. PRP erytroderma may be a therapeutic challenge because standard therapies are lacking due to its unclear pathogenesis. Ustekinumab is a monoclonal antibody that is approved for the treatment of psoriasis, but has been shown to be effective as an off-label use treatment for PRP. We report a case of refractory erythroderma type 1 PRP with complete resolution with ustekinumab therapy.

Treating to target: Exploration of Investigator Global Assessment and body surface area (IGA×BSA) as a practical minimal disease activity goal

Objective: Psoriasis Area Severity Index (PASI) is typically used in clinical trials, but may not be pragmatic for use in clinical practice. The Investigator Global Assessment (IGA) and percentage of affected body surface area (BSA) are measures of psoriasis disease activity that are easily performed in routine clinical practice. This retrospective pooled analysis explored cutoff values of the product of IGA and BSA (IGA×BSA) that correlate with minimal disease activity (MDA) and would allow for a treat-to-target approach that may be feasible in clinical practice.

The sun and your health: Targeting teenagers and adolescents in British Columbia

Introduction: Skin cancer is one of the most preventable forms of cancer. Approximately 85% of skin cancer cases could be avoided by reducing ultraviolet (UV) exposure, especially during childhood and adolescence. We conducted a pilot study to evaluate UV exposure and sun safety behaviors in this age group. In addition, the effectiveness in changing sun protection knowledge, attitudes, and behaviors using an innovative intervention was compared with the strategy of using education alone.

The effect of topical sunscreen plus antioxidant against the visible light biologic effects

Background: Visible light (VL) has been shown to induce erythema, pigmentation, and photodamage. Sunscreens effective against VL contain inorganic filters, but are often cosmetically unacceptable in darker skin tones. Antioxidants possess photoprotective properties and may serve as an alternative.

Sparing the use of steroids in the treatment of Sweet syndrome: A case report

Sweet syndrome is an acute febrile neutrophilic dermatosis first decribed in 1964. It is an uncommon disease, with no racial predisposition, that affects mostly women 30-60 years of age. Its physiopathology is unknown and 20% of the cases are linked to malignant tumors. It can also be associated with autoimmune diseases, drug intake, pregnancy and 60% are idiopathic. It can present with papules, nodules, and erythematous plaques, most of the times painful. Edema is associated, and can lead to vesicules, bullae, and/or pustules.

Spontaneous regression of Merkel cell carcinoma is associated with clonal T-cell expansion

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin tumor. MCC is immunogenic and highly responsive to immune checkpoint inhibitors. There are at least 45 reported cases of spontaneous regression of both local and metastatic MCC following biopsies, excisions, fine needle aspirations, and in 1 case after allergic contact dermatitis. Spontaneous tumor regression has also been observed in other tumor types, however the mechanism is poorly understood. There has been speculation that trauma-induced antigen shedding and subsequent recruitment of a host immune response drives tumor regression.

Serratia pyoderma mimicking acne vulgaris

A 17-year-old woman with no significant medical history presented complaining of acne. She reported that three days before her "acne" started she applied tea tree oil (TTO) for a few pimples. Photos on the patient's phone before TTO application revealed completely clear facial skin. Within a few days of TTO use she developed a facial eruption. She was evaluated by her pediatrician who prescribed minocycline for 10 days along with adapalene and benzoyl peroxide. She did not improve and was referred to dermatology.

Safety and efficacy of microfocused ultrasound with visualization for the correction of moderate-to-severe atrophic acne scars

Background and objective: Microfocused ultrasound with visualization (MFU-V; Ulthera) has been shown to induce collagen production and remodeling of tissue layers in the skin. The purpose of this study was to assess the efficacy and safety of MFU-V for improving the appearance of atrophic acne scars.

Mitigation of NOx emission using aromatic and phenolic antioxidant-treated biodiesel blends in a multi-cylinder diesel engine

Abstract

The present work analyzes the effect of antioxidants on engine combustion performance of a multi-cylinder diesel engine fueled with PB30 and PB50 (30 and 50 vol.% palm biodiesel (PB)). Four antioxidants namely N,N′-diphenyl-1,4-phenylenediamine (DPPD), N-phenyl-1,4-phenylenediamine (NPPD), 2(3)-tert-Butyl-4-methoxyphenol (BHA), and 2-tert-butylbenzene-1,4-diol (TBHQ) were added at concentrations of 1000 and 2000 ppm to PB30 and PB50. TBHQ showed the highest activity in increasing oxidation stability in both PB30 and PB50 followed by BHA, DPPD, and NPPD respectively, without any negative effect on physical properties. Compared to diesel fuel, PB blends showed 4.61–6.45% lower brake power (BP), 5.90–8.69% higher brake specific fuel consumption (BSFC), 9.64–11.43% higher maximum in cylinder pressure, and 7.76–12.51% higher NO emissions. Carbon monoxide (CO), hydrocarbon (HC), and smoke opacity were reduced by 36.78–43.56%, 44.12–58.21%, and 42.59–63.94%, respectively, than diesel fuel. The start of combustion angles (SOC) of PB blends was − 13.2 to − 15.6 °CA BTDC, but the combustion delays were 5.4–7.8 °CA short compared to diesel fuel which were − 10 °CA BTDC and 11°CA respectively. Antioxidant fuels of PB showed higher BP (1.81–5.32%), CO (8.41–24.60%), and HC (13.51–37.35%) with lower BSFC (1.67–7.68%), NO (4.32–11.53%), maximum in cylinder pressure (2.33–4.91%) and peak heat release rates (HRR) (3.25–11.41%) than baseline fuel of PB. Similar SOC of − 13 to − 14 °CA BTDC was observed for PB blended fuels and antioxidants. It can be concluded that antioxidants' addition is effective in increasing the oxidation stability and in controlling the NOx emissions of palm biodiesel fuelled diesel engine.



Aesthetic Auricular Reconstruction in Adult Patients with Rib Cartilage Calcification Using a Modified Two-Step Technique

Abstract

Background

It is very important for congenital microtia patients to achieve better aesthetic appearance, craniofacial balance and mental health through auricular reconstruction. But there are great challenges for plastic surgeons on how to perform this technique in adult patients with tough and rigid rib cartilage because of the different extent of calcification. To lower the harvest of the cartilage and reduce the suffering during the operation, in this study, we report a modified two-step method for adult patients who suffered rib cartilage calcification in auricular reconstruction.

Methods

From January 2012 to January 2018, 89 adult patients (aged from 24 to 50) with cartilage calcification were enrolled and received auricular reconstruction using the modified two-step technique. The whole procedure was performed in two surgical stages. In the first stage, rib cartilages were harvested and modified cartilage frameworks were designed, fabricated and grafted, which included an ear-shaped framework and a C-shaped base part. The ear-shaped framework was inserted into the mastoid region through a W-shaped incision, but the C-shaped base part was embedded subcutaneously in the donor site. In the second stage, the C-shaped base part was transplanted into the mastoid region to elevate the reconstructed ear. A retro-auricular fascia flap and a free skin graft were used to cover the posterior side of the reconstructed ear.

Results

The patients were followed for 6 to 24 months. During the follow-up visiting, 80 cases (89%) were satisfied with the outcomes in size, shape, location and details of reconstructed ears.

Conclusion

Our modified technique is safe and effective for auricular reconstruction, reduces the harvest of cartilage and decreases the suffering as well in adult patients with congenital microtia and rib cartilage calcification.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.



Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) reduction by granular zero-valent iron in continuous flow reactor

Abstract

Wastewater streams containing hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) are subject to regulatory discharge regulations that require processing through industrial waste treatment. Thus, the development of easy-to-apply technologies for the treatment of RDX-laden wastewater streams is imperative. In the present study, the reduction of RDX by granular zero valent iron (GZVI) in batch and column experiments was investigated. Preliminary batch tests conducted under both oxic and anoxic conditions showed that after 3.0 h of reaction with GZVI, RDX was mainly converted to formaldehyde (CH2O), nitrate (NO3), and ammonium (NH4+). Column filtration tests showed that pretreatment of the GZVI media with acid wash and low influent pH (4.0 ± 0.1) achieved 99% removal of RDX up to 5000 bed volume. BOD tests carried out on the post-treatment streams showed increased biodegradability of the treated wastewater, leading to a lower environmental impact for the final waste.



Decentralization, national context and environmental policy performance: a fuzzy set qualitative comparative analysis

Abstract

This study examines the complex relationship between decentralization, national context and environment policy performance with the cross-sectional data from 118 countries. Decentralization is decomposed into three dimensions: political, fiscal and administrative. Both multiple regression analysis and fuzzy set qualitative comparative analysis are adopted. Results show that: (1) political, fiscal and administrative decentralization differ in their impacts on environmental policy performance. (2) There are multiple pathways, constituted by specific configurations of decentralization and context conditions, to high (or low) environmental policy performance. (3) High environmental policy performance occurs most often when a country is fiscally and administratively decentralized and its context is favorable, i.e. advanced economy, good governance and stringent environmental regulations. In this situation, political decentralization seems to be irrelevant to the outcome. (4) Low environmental policy performance occurs most often when a country, without the favorable context mentioned above, become fiscally centralized, regardless of whether political and administrative decentralization is present or not. This study suggests policy makers should keep in mind the contextual fit of decentralization and adopt a configurational thinking in environmental governance.



Facilitated expansion of Th17 cells in lupus nephritis patients

Clinical &Experimental Immunology, Volume 0, Issue ja, -Not available-.


Precipitating anti‐dsDNA peptide repertoires in lupus

Clinical &Experimental Immunology, Volume 0, Issue ja, -Not available-.


Dual-Energy CT Pulmonary Angiography: Quantification of Disease Burden and Impact on Management

Abstract

Purpose of Review

Computed tomography pulmonary angiography (CTPA) has become the imaging modality of choice for patients with suspected pulmonary embolism (PE). Post-processing techniques currently available for dual-energy CT pulmonary angiography (DE-CTPA) enhance image quality and provide additional value in the diagnosis of PE. The objective of this article is to summarize these recent developments and discuss the appropriate use of DE-CTPA post-processing applications.

Recent Findings

DE-CTPA post-processing applications enable reconstruction of virtual monoenergetic images (VMI) and color-coded iodine-perfusion maps to increase contrast conditions and visualize lung perfusion defects in case of embolic occlusion of pulmonary arteries. Both techniques revealed a superior diagnostic performance for the detection of pulmonary emboli and assessment of the pulmonary perfusion compared to the standard image reconstructions.

Summary

DE-CTPA is a well-established method for excluding or diagnosing PE. Continued developments in DE-CTPA post-processing techniques improve patient management and allow for a quantification of disease burden.



Optimizing Cardiac CTA Acquisition in Congenital Heart Disease

Abstract

Purpose of Review

The purpose of this review of performance of cardiac computed tomographic angiography (CCTA) in patients with congenital heart disease (CHD) is to describe a strategy for optimizing CCTA protocols for various forms of CHD at diagnosis and throughout the lifetime of a patient.

Recent Findings

Recent expert consensus statements provide key recommendations for patient selection and technical performance of CCTA with tips to optimize contrast injection, scan acquisition, and understanding anatomy and postoperative changes in patients with CHD. Spectral CT will become invaluable in acquiring image data which has potential for enabling improved image quality and perhaps physiologic information.

Summary

CCTA is an important non-invasive imaging modality for making initial diagnosis and providing follow-up imaging in patients of all ages with CHD. Optimization of imaging protocols requires combined expertise in all forms of CHD, surgical palliation procedures, and knowledge of surgical options for CHD surgery.



What do Vitiligo Impact Scale (VIS)‐22 scores mean? Studying the clinical interpretation of scores using an anchor‐based approach

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


PACAP38 and PAC1 receptor blockade: a new target for headache?

Pituitary adenylate cyclase activating polypeptide-38 (PACAP38) is a widely distributed neuropeptide involved in neuroprotection, neurodevelopment, nociception and inflammation. Moreover, PACAP38 is a potent i...

Advective pore-water transport of hydrocarbons in North East Scotland coastal sands

Abstract

Oil spills in the marine environment can cause ecosystem-level impacts. Dispersant application as an oil spill response measure leads to the widespread distribution of hydrocarbons in the water column and marine sediments. The North Sea is an area of intense hydrocarbon production and is at risk of oil spills, which are of concern to its benthic ecosystem due to its sediments' high permeability. Here, entrainment of hydrocarbons via pore-water advection into permeable North Sea sands and the associated effect of Superdispersant-25, a commercial oil dispersant, were evaluated in a laboratory. Centrally stirred chambers that induce advective pore-water fluxes in sediments were filled with sediment, seawater and mixtures of oil and Superdispersant-25. Dispersant application had contrasting effects on hydrocarbon interactions with sediment: (1) it reduced accumulation of hydrocarbons in surface sediments and (2) facilitated the entrainment of hydrocarbons up to 8 cm deep into sediments by increasing hydrocarbon solubility in seawater and its subsequent washout or pumping into sediment by pore-water movement. Results here show that dispersant application can have counter-intuitive effects on hydrocarbon interactions with marine sediments and highlight the need for further research in this area to make better informed decision in an oil spill response scenario.



Relationship between phytoplankton community and environmental factors in landscape water with high salinity in a coastal city of China

Abstract

Relationship between phytoplankton community and environmental variables was explored in three landscape water bodies (namely Jiyun River Oxbow (JRO), Qingjing Lake (QL), and Jiyun River (JR)) with high salinity, located in Sino-Singapore Tianjin Eco-city of China, using redundancy analysis (RDA). A total of 48 species of phytoplankton were identified during the study period, in which Chlorophyta and Bacillariophyta accounted for 35.42 and 31.25%, respectively. The most dominant species of the studied water bodies were Cyclotella meneghiniana (Bacillariophyta) and Aphanocapsa elachista (Cyanophyta). The diversity index ranged from 0.56 to 1.42, with an average of 1.11, reflecting low biodiversity in the phytoplankton community. Moreover, the average density of phytoplankton was 42.39 × 106 cells/L, indicating that those landscape water bodies belonged to moderate eutrophication. The results of RDA revealed that the most significant environmental factors influencing phytoplankton community were water temperature (WT), dissolved total phosphorus (DTP), salinity, and total nitrogen (TN) (p < 0.05, Monte Carlo permutation test). Meanwhile, Aphanocapsa elachista was positively correlated with WT, TN, and salinity, while Cyclotella meneghiniana was positively related to salinity and negatively related to TP. The results suggested that salinity was a non-negligible key factor affecting the phytoplankton community of the water body with high salinity.



Overall Survival and Risk of Second Malignancies with Cancer Chemotherapy and G-CSF Support

Abstract
Background
The use of supportive granulocyte colony-stimulating factor (G-CSF) to reduce the risk of neutropenic complications in high-risk cancer patients is consistently recommended by several clinical practice guidelines. However, in a previous meta-analysis, G-CSF prophylaxis was associated with an increased risk of secondary malignancies while reducing long-term mortality. We present here an updated systematic review and meta-analysis.
Materials and methods
A systematic literature search was performed to identify randomized controlled trials of cancer patients receiving conventional-dose chemotherapy, assigned to primary G-CSF support or a control group without initial G-CSF, with at least 2 years of follow-up. Studies were categorized into 1 of 4 groups, based on the chemotherapy regimen and study design. An updated meta-analysis was performed; relative risk (RR) and 95% confidence intervals (CI) for all-cause mortality and secondary malignancies were calculated.
Results
Of 2604 articles screened, 14 eligible studies were identified and combined with studies identified in the previous systematic literature searches. The updated meta-analysis included a total of 68 studies presenting 71 separate comparisons. Survival was significantly improved in patients receiving primary G-CSF support, compared with patients without primary G-CSF support (mortality RR = 0.92; 95% CI: 0.90–0.95; P <0.0001). The largest improvement in survival was observed with dose-dense chemotherapy regimens with G-CSF support, compared with controls receiving no G-CSF support (mortality RR = 0.86; 95% CI: 0.80–0.92; P <0.0001). Patients who received primary G-CSF support experienced a significantly higher risk of secondary malignancies, compared with controls (RR = 1.85; 95% CI: 1.19–2.88; P <0.01).
Conclusions
Our findings demonstrate that overall survival is improved in patients receiving intensified chemotherapy with primary G-CSF support, compared to those receiving standard chemotherapy. Primary G-CSF support was also associated with a higher risk of developing secondary malignancies, including secondary acute myeloid leukemia and myelodysplastic syndrome.

Heterogeneity of EGFR-mutant clones and PD-L1 highly-expressing clones affects treatment efficacy of EGFR-TKI and PD-1 inhibitor



Photocrosslinking of G‐Quadruplex Forming Sequences found in Human Promoters

Photochemistry and Photobiology, Volume 0, Issue ja, -Not available-.


Provocation Tests in Nonimmediate Hypersensitivity Reactions to β-Lactam Antibiotics in Children: Are Extended Challenges Needed?

Publication date: Available online 7 August 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Rosa García Rodríguez, Lucia Moreno Lozano, Alba Extremera Ortega, Jesús Borja Segade, Pedro Galindo Bonilla, Elisa Gómez Torrijos

Background

β-Lactam antibiotics are the most common trigger of reactions in children with most of them being nonimmediate (85.5%), but proven allergy after the allergological workup is between 7% and 10%. There is no agreement on how to perform the provocation tests in these types of hypersensitivity reactions.

Objective

To determine whether or not repeated doses of the β-lactams are required to reproduce a nonimmediate reaction in children.

Methods

This is a retrospective observational study. We included children under 14 years who were referred for a nonimmediate reaction to β-lactams. All patients underwent a 1-day hospital provocation and were kept under observation at home during the following days for at least the time elapsed between the first dose and the symptoms of the index reaction. If no reaction was triggered, the patient resumed the provocation at home with 2 daily therapeutic doses for an equal of interval time.

Results

Ninety-seven patients were included in the study. A positive reaction was recorded in 14 of them (14.4%). The short hospital provocation triggered 3 immediate reactions and 8 delayed reactions. The home rechallenge developed 1 immediate reaction and 2 delayed reactions.

Conclusions

Nonimmediate reactions to β-lactams in children may be triggered with a 1-day provocation test. We suggest to perform a 1-day provocation test followed by an observational period of at least the time interval of the index reaction. If this challenge is negative, an extended home provocation could subsequently be carried out.



Landscape Plant Selection Criteria for the Allergic Patient

Publication date: Available online 7 August 2018

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Brett J. Green, Estelle Levetin, W. Elliott Horner, Rosa Codina, Charles S. Barnes, Warren V. Filley

Patients with pollen-related allergies are concerned about the species within their landscape that provoke their symptoms. Allergists are often asked for guidance but few information sources are available to aid patients in the recognition of allergenic plants and strategies to avoid personal exposure to them. Landscaping and horticultural workers also have few reliable guidance references, and what is available usually extols the virtues of the plants rather than their negative features. The aim of this article was to provide the results of the Landscape Allergen Working Group that was formed by the AAAAI Aerobiology Committee, which aimed to fill these existing knowledge gaps and develop guidance on producing a low-allergenic landscape. Within the context that complete pollen avoidance is unrealistic, the workgroup introduces selection criteria, avoidance strategies, and guidance on low-allergenic plants that could be selected by patients to reduce the overall pollen burden in their landscape environment. Specific focus is placed on entomophilous plants, which require insects as dispersal vectors and generally produce lower quantities of pollen, compared with anemophilous (wind-pollinated) species. Other biological hazards that can be encountered while performing landscaping activities are additionally reviewed and avoidance methods presented with the aim of protecting gardeners, and workers in the landscape and horticulture industries. The guidance presented in this article will ultimately be a helpful resource for the allergist and assist in engaging patients who are seeking to reduce the burden of allergen in their landscape environment.



Linking HIV and Viral Hepatitis Surveillance Data: Evaluating a Standard, Deterministic Matching Algorithm — 6 US Health Jurisdictions

Abstract
Accurate interpretations and comparisons of linkage results across jurisdictions require valid and reliable matching methods. We compared existing matching methods used by 6 US state and local health departments (Houston, Texas; Louisiana; Michigan; New York City, New York; North Dakota; and Wisconsin) to link human immunodeficiency virus and viral hepatitis surveillance data with a 14-key automated, hierarchical deterministic matching method. Applicable years varied by disease and jurisdiction, ranging from 1979 to 2016. We calculated percentage agreement and Cohen's kappa coefficient to compare the matching methods used within each jurisdiction. We calculated sensitivity, specificity, and positive predictive value of each matching method, compared with a new standard that included manual review of discrepant cases. Agreement between the existing matching method and the deterministic matching method was 99.6% or higher in all jurisdictions; Cohen's kappa values ranged from 0.87 to 0.98. Sensitivity of the deterministic matching method ranged from 97.4% to 100% in the 6 jurisdictions; specificity ranged from 99.7% to 100%; and positive predictive value ranged from 97.4% to 100%. Although no gold standard exists, prior assessments of existing methods and review of discrepant classifications suggest good accuracy and reliability of our deterministic matching method, with the advantage that our method reduces the need for manual review and allows for standard comparisons across jurisdictions when linking human immunodeficiency virus and viral hepatitis data.

Education and Cognitive Aging: Accounting for Selection and Confounding in the Danish Registry-SHARE Data Linkage

Abstract
Earlier studies report inconsistent associations between education and cognitive aging. We assess the association accounting for selective dropout due to death or dementia, and, in a sub-sample, accounting for confounding by early life intelligence. Data from the Danish component of the Survey of Health, Ageing and Retirement in Europe (N = 3400) were linked to registry data (education records, dementia diagnoses and mortality), and The Danish Conscription Database (youth intelligence measures for 854 men). Word recall and verbal fluency were assessed up to 4 times over 10 years (2004-2013) and combined by averaging the Z-scores. We estimated a joint model linking a time-to-event model for dementia or death to a linear mixed-effects model for cognitive change. Rate of cognitive decline was slower among people with high education compared to low education (β = 0.112, 95% confidence interval (CI): 0.056, 0.170). Adjusting for youth intelligence did not attenuate the association between education and cognitive decline (β unadjusted = 0.136, 95% CI: 0.028, 0.244 vs β adjusted = 0.145, 95% CI: 0.022, 0.269). The results suggest that higher education may slow cognitive decline in later life. In this sample, results changed little when accounting for selective attrition and confounding by intelligence.

Measurement of Vaccine Direct Effects under the Test-Negative Design

Abstract
Test-negative designs are commonplace in assessments of influenza vaccination effectiveness, estimating this value from the exposure odds ratio (OR) of vaccination among individuals treated for acute respiratory illness who test positive for influenza virus infection. This approach is widely believed to recover the vaccine direct effect by correcting for differential healthcare-seeking behavior among vaccinated and unvaccinated persons. However, the relation of the measured OR to true vaccine effectiveness is poorly understood. We derive the OR under circumstances of real-world test-negative studies. The OR recovers the vaccine direct effect when two conditions are met: (1) individuals' vaccination decisions are uncorrelated with exposure or susceptibility to the test-positive or test-negative conditions, and (2) vaccination confers "all-or-nothing" protection (whereby certain individuals have no protection while others are perfectly protected). Biased effect size estimates arise if either condition is unmet. Such bias may suggest misleading associations of vaccine effectiveness with time since vaccination or the force of infection of influenza. The test-negative design may also fail to correct for differential healthcare-seeking behavior among vaccinated and unvaccinated persons without stringent criteria for enrollment and testing. Our findings demonstrate a need to reassess how data from test-negative studies can inform policy decisions.

Cross‐elicitation responses to 2‐methoxymethyl‐p‐phenylenediamine in p‐phenylenediamine‐allergic individuals: Results from open use testing and diagnostic patch testing

Contact Dermatitis, EarlyView.


Inter-operator variability in the sensitivity of sentinel lymph node biopsy for melanoma

Publication date: Available online 7 August 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Conrad Harrison, Jeremy N. Rodrigues, Oliver Cassell

Abstract
Introduction and aims

Plastic surgery trainees, in some circumstances, can progress to consultant level having performed only 15 generic lymph node surgeries, with no mention specifically of sentinel lymph node biopsy (SLNB) on the training log. The majority of SLNBs carried out for melanoma at our centre since 1999 have been performed by eight surgeons, six of whom had been formally trained and mentored in our unit or previously completed skin cancer fellowships. Two surgeons started performing the procedure without formal training or specialist fellowships. We analysed the first 40 cases performed by each consultant hypothesising that those with more extensive training would achieve higher sensitivities.

Methods

Using our centre's prospectively collected data set we studied 320 procedures. Sensitivities were calculated and compared between surgeons with less extensive and more extensive training.

Results

The two surgeons without formal training had a combined sensitivity of 85% (80 cases, 17 positive results, 3 false negative results). The six surgeons who had been practising after extensive training had a combined sensitivity of 94% (240 cases, 44 positive results, 3 false negative results). SLNBs in the head and neck region accounted for 17% of total cases, but 50% of false positive results.

Conclusions

There is likely to be a learning curve for this operation, and in the era of adjuvant therapy a false negative result may affect survival. Training requirements may not be enough to ensure consistency amongst newly qualified plastic surgeons. We advocate a similar level of experience to that required of breast surgeons before performing the procedure independently.



Aspect of brow position changes after bilateral ptosis correction surgery

Publication date: Available online 7 August 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Ji Sun Baek, Jung Hye Lee, Hye Sun Choi, Sung Joo Kim, Jae Woo Jang



Evaluación de indicadores de estructura en la atención al paciente con cáncer de piel en los servicios de dermatología

Publication date: Available online 6 August 2018

Source: Actas Dermo-Sifiliográficas

Author(s): T. Kueder-Pajares, M.A. Descalzo, I. García-Doval, L. Ríos-Buceta, D. Moreno-Ramírez

Resumen
Introducción y objetivos

Recientemente se han consensuado unos indicadores de calidad de la atención del cáncer de piel no melanoma y melanoma promovidos por la Fundación Piel Sana AEDV. El objetivo de este estudio es conocer la adherencia a estos criterios de calidad asistencial.

Material y métodos

En noviembre de 2016 se realizó una encuesta anónima que constaba de 32 preguntas, dirigida a los responsables de los servicios de dermatología y venereología españoles incluidos en la base de datos de la AEDV. Las preguntas de la encuesta hacían referencia a los diferentes indicadores consensuados previamente.

Resultados

Fueron respondidas 104 de las 150 encuestas enviadas (69,3% de porcentaje de respuesta). El menor porcentaje conseguido de respuesta a una pregunta fue del 56% (n = 84). Más del 85% de los encuestados contestaron a 29 (91%) o más preguntas. Los indicadores con mayor implantación fueron la disponibilidad de TAC o RMN para el estudio de carcinoma espinocelular (98%), seguidos de la existencia de un modelo estandarizado para la realización del informe anatomopatológico de melanoma (90%). Los indicadores con menor implantación se relacionaron con el acceso a electroquimioterapia (25%) y el acceso a otras terapias invasivas para el melanoma locorregionalmente avanzado (20%).

Conclusiones

Se ha encontrado variabilidad en la adherencia de estos criterios en los diferentes centros. Con los datos obtenidos se pueden identificar posibilidades de mejora en los centros. Futuras investigaciones deberían centrarse en la medición de indicadores de proceso y resultado.

Abstract
Introduction and objectives

A series of quality indicators for melanoma and nonmelanoma skin cancer were recently approved within a project promoted by the Healthy Skin Foundation of the Spanish AEDV. The aim of this study was to evaluate adherence to these indicators.

Material and methods

In November 2016, an anonymous questionnaire consisting of 32 items was sent to the heads of Spanish dermatology and venereology departments listed in the AEDV's database. The questions referred to the above-mentioned quality of care indicators.

Results

The questionnaire was completed by 104 of the 150 people contacted (response rate, 69.3%). The lowest response rate for any given question was 56% (84 respondents). Over 85% of respondents answered 29 questions or more (91%). The most widely used indicators were those related to the use of computed tomography or magnetic resonance imaging for squamous cell carcinoma (98%), followed by the availability of a standardized melanoma pathology report (90%). The least widely used indicators were related to availability of electrochemotherapy (25%) and other invasive therapies for locoregionally advanced melanoma (20%).

Conclusions

Adherence to quality of cancer care criteria at the different hospitals evaluated varied. Our findings could be useful for identifying areas for improvement at different hospitals. Future studies should focus on measuring both process and outcome indicators.



Regret-sensitive treatment decisions

The threshold approach to medical decision-making, in which treatment decisions are made based on whether the probability of sickness exceeds a predetermined threshold, was introduced by (Pauker and Kassirer, ...