Systematic review of atopic dermatitis disease definition in studies using routinely-collected health data

Abstract

Background

Routinely collected electronic health data (RCD) obtained for administrative and clinical purposes are increasingly used to study atopic dermatitis (AD). Methods for identifying AD patients in RCD differ, and it is unknown how this might affect study results.

Objectives

We sought to evaluate how AD patients have been identified in studies using RCD, to determine whether these methods were validated, and to estimate how the method for identifying AD patients affected variability in prevalence estimates.

Methods

We systematically searched PubMed, EMBASE, and Web of Science for studies utilizing RCD that reported on AD as a primary outcome. Studies of localized AD and other types of dermatitis were excluded. The protocol for this review was registered in PROSPERO (CRD42016037968).

Results

59 studies met eligibility criteria. Medical diagnosis codes for inclusion and exclusion, number of occasions of a code, type of provider associated with a code, and prescription data were used to identify AD patients. Only two studies described validation of their methods and no study reported on disease severity. Prevalence estimates ranged from 0.18%-38.33% (median 4.91%) and up to 3-fold variation in prevalence was introduced by differences in the method for identifying AD patients.

Conclusions

This systematic review highlights the need for clear reporting of methods for identifying AD patients in routinely collected electronic health data to allow for meaningful interpretation and comparison of results.

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Dermatology Training Across the Globe

Abstract

Dermatology residency program rankings often stem from assessments by practicing physicians or evaluations of scholarly achievements such as grants and publicatons.^1-3 Such rankings, however, are continuously changing, and fail to account for the specific missions of dermatology training programs.² Additionally, a global comparison of dermatology training requirements and a worldwide understanding of the ideal dermatology curriculum remains missing from the literature. Therefore, this study aims to compare and contrast accreditation requirements for dermatology training programs across the world. As a secondary objective, it attempts to identify the different missions of dermatology training programs around the world to create a global vision of what constitutes an ideal dermatology training program.

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Computerized planimetry to assess clinical responsiveness in a phase II randomized trial of topical R333 for discoid lupus erythematosus

Abstract

Background

R333 is a topical janus kinase and spleen tyrosine kinase inhibitor being evaluated for discoid lupus erythematosus (DLE) treatment. There is no validated measure to assess area of active DLE lesions.

Objectives

To evaluate R333 efficacy and assess a technique to measure responsiveness.

Methods

54 DLE patients were randomized in a double blind design to R333 or placebo. The primary endpoint was the proportion of patients achieving ≥50% decrease in erythema and scale based on lesional CLASI for all treated lesions at week 4. Two-dimensional area measurements for each lesion were recorded at baseline and week 1-6. 88 photographs (44 pre- and 44 post-treatment) were obtained from the trial and change in size of active areas was analyzed by computerized planimetry and physician assessed area change.

Results

36 patients were randomized to R333 and 18 patients were randomized to placebo. The primary endpoint was not achieved. There was a strong association between lesion activity and physician global assessment, a measure of activity of all treated lesions (p<10^-6). Photos of 42 patients assessed by computerized planimetry demonstrated excellent inter-rater and intra-rater reliability. Area change by computerized planimetry showed a strong correlation with physician assessed area change (Spearman r=0.72). Area change by two-dimensional measurements showed a weak correlation with physician assessed area change (Spearman r=0.29)

Conclusion

Four weeks of R333 treatment did not result in significant improvement in lesion activity. Lesion activity and area change using computerized planimetry are better determinants of responsiveness as compared to area change using two-dimensional measurements.

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Vulvo-vaginal rejuvenation: Fact or fiction? Fractional carbon dioxide laser for genitourinary syndrome of menopause

Efficacy and safety of fezakinumab (an anti-IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments - A randomized, double-blind, phase 2a trial

IL-22 promotes epidermal hyperplasia and inhibits skin barrier function.

Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE)

Interleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis.

Acrodermatitis acidaemica

Summary

Methylmalonic acidaemia (MMA) is an inborn error of amino acid metabolism that may be associated with cutaneous manifestations mimicking other diagnoses, including staphylococcal scalded skin syndrome (SSSS), psoriasis and acrodermatitis enteropathica. Whether this is due to the underlying metabolic disorder itself or occurs as a consequence of dietary restriction has yet to be elucidated. Skin biopsies typically show histological features shared by a number of other metabolic disorders and nutritional deficiency-associated diseases. Some presentations, especially SSSS-like eruptions, may be associated with acute metabolic decompensation. An underlying metabolic disorder, such as MMA, should be considered in a diagnosed adult or undiagnosed child presenting with skin eruptions that resemble those listed above, so that specialist management may be initiated early.

Seasonal variation and source apportionment of PM 2.5 -bound trace elements at a coastal area in southwestern Taiwan

Abstract

The aim of this study is to investigate the seasonal variations and source apportionment on atmospheric fine particulate matter (PM_2.5) mass and associated trace element concentrations at a coastal area, in Chiayi County of southwestern Taiwan. Particle measurements were conducted in 2015. Twenty-three trace elements in PM_2.5 were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Multiple approaches of the enrichment factor (EF) analysis and positive matrix fraction (PMF) model were used to identify potential sources of PM_2.5-bound trace elements. Daily mean concentration of PM_2.5 in cold season (25.41 μg m⁻³) was higher than that in hot season (13.10 μg m⁻³). The trace elements contributed 11.02 and 10.74% in total PM_2.5 mass concentrations in cold season and hot season, respectively. The results of EF analysis confirmed that Sb, Mo, and Cd were the top three anthropogenic trace elements in the PM_2.5; furthermore, carcinogenic elements (Cr, Ni, and As) and other trace elements (Na, K, V, Cu, Zn, Sr, Sn, Ba, and Pb) were attributable to anthropogenic emissions in both cold and hot seasons; however, highly enriched Li and Mn were observed only in cold season. The PMF model identified four main sources: iron and steel industry, soil and road dust, coal combustion, and traffic-related emission. Each of these sources has an annual mean contribution of 8.2, 27.5, 11.2, and 53.1%, respectively, to PM_2.5. The relative dominance of each identified source varies with changing seasons. The highest contributions occurred in cold season for iron and steel industry (66.2%), in hot season for traffic-related emission (58.4%), soil and road dust (22.0%), and coal combustion (2.8%). These findings revealed that the PM_2.5 mass concentration, PM_2.5-bound trace element concentrations, and their contributions were various by seasons.

Is there an association of ABO blood groups and Rhesus factor with alopecia areata?

Summary

Background/Objectives

Alopecia areata (AA) is an autoimmune disease characterized by noncicatricial hair loss localized on hair, beard, mustache, eyebrow, eyelash, and sometimes on the body. Although etiopathogenesis is not fully understood, many studies show remarkable associations between various diseases and ABO blood groups. However, there is no study with AA and blood groups.

Methods

Healthy people and patients with AA were included in this study. A total of 155 patients with AA and 299 healthy controls were included in the study.

Results

ABO blood group distribution in patients with AA and distribution of healthy donors were similar. However, Rhesus factor positivity in the AA group was significantly higher than in healthy donors. The relationship between stress and AA was high as known. But, ABO blood group and Rhesus factor were not in a significant connection with stress.

Conclusion

We conclude that there was no association between ABO blood group and AA, but the observed distribution of Rhesus blood group differed slightly but significantly from that of the healthy population. The result of the study shows a small but statistically significant difference in the Rh blood group between patients with AA and the healthy population blood groups. This result is important because it suggests that genetic factors may influence the development of AA. The role of blood groups in the development of AA remains to be determined. We believe that the studies which will be carried out in other centers with wider series will be more valuable to support this hypothesis.

The Impact of Reported Beta-Lactam Allergy in Hospitalized Patients with Hematologic Malignancies Requiring Antibiotics

Abstract

Background

Patients hospitalized with hematologic malignancy are particularly vulnerable to infection. The impact of reported beta-lactam (BL) allergy in this population remains unknown.

Objective

To define the impact of reported BL-only allergy (BLOA) label on clinical outcomes compared to those with no BL allergy (NBLA) in hematologic malignancy inpatients requiring systemic antibiotics.

Methods

Retrospective cohort study of adult inpatients with hematologic malignancy admitted at two tertiary care hospitals 2010-2015. The primary outcome was hospital length of stay (LOS) after first antibiotic. Secondary outcomes included re-admission, mortality, complications, total hospital charges, and antibiotic usage.

Results

In our cohort (n=4671), 38.3% had leukemia, 4.9% had Hodgkin's lymphoma, 36.1% had non-Hodgkin's lymphoma and 20.7% had multiple myeloma. Among subjects, 35.1% reported antibiotic allergy, 14.1% (n=660) had BLOA (including 9.3% with penicillin-only allergy and 3.3% cephalosporin-only allergy). Subjects with BLOA had longer median LOS compared to NBLA (11.3 vs. 7.6 days, p<0.001), which remained significant after multivariable adjustment. Patients with BLOA also had significantly worse outcomes compared to NBLA in terms of mortality rate at 30-days (7.6% vs. 15.8%, p=0.017) and 180-days (15.8% compared to 12.2%, p=0.013), 30-day re-admission rate (19.2% vs. 15.1%, p=0.008), Clostridium difficile rate (17.7% vs. 11.6%, p<0.001), total hospital charges ($223046 vs. $173256, p<0.001), antibiotic classes used (median 3 vs. 2 classes/patient, p<0.001), and antibiotic duration (median 9.0 vs. 6.0 days, p<0.001).

Conclusion

In hospitalized patients with hematologic malignancy requiring antibiotics, patients with reported BL allergy have worse clinical outcomes and higher healthcare cost than those without BL allergy label.

A nosocomial foodborne outbreak of a VIM carbapenemase-expressing Citrobacter freundii

Abstract

Background

A foodborne outbreak of VIM carbapenemase-expressing Citrobacter freundii (CPC) occurred between February and June 2016 at a major university hospital in Germany.

Methods

An explosive increase of CPC isolated from rectal swabs of patients during weekly routine screening led to the declaration of an outbreak. A hospital-wide prevalence screening was initiated as well as screening of all patients on admission and before transfer to another ward, and canteen staff, patient rooms, medical and kitchen inventory and food. Swabs were streaked out on selective plates. All CPC isolates were analysed by mass spectrometry and selected isolates by whole-genome sequencing.

Results

In total, 76 mostly unrelated cases in different wards were identified. The CPC was isolated from retained samples of prepared vegetable salads and puddings and from a mixing machine used to prepare them only after an overnight culture. The immediate ban on serving potential source food resulted in a sharp decline and finally disappearance of novel cases. Repeated testing of pre-sliced vegetables showed a high degree of contamination with C. freundii without a carbapenemase, indicating a possible source.

Conclusions

This report demonstrates that an explosive increase in carbapenemase-expressing Enterobacteriaceae contamination may be caused by a food-borne source, and suggests that pre-sliced vegetables have to be taken into account as a putative pathogen repository. It also underlines the importance of appropriate cooling, transport, re-heating and distribution of meals and indicates that probing of non-organic surfaces is limited by low sensitivity, which may be increased by additional overnight cultivation in appropriate media.

Combating Global Antibiotic Resistance: Emerging One Health Concerns in Lower- and Middle-Income Countries

Abstract

Antibiotic misuse in lower- and middle-income countries (LMICs) contributes to the development of antibiotic resistance that can disseminate globally. Strategies specific to LMICs that seek to reduce antibiotic misuse by humans, but simultaneously improve antibiotic access, have been proposed. However, most approaches to date have not considered the growing impact of animal and environmental reservoirs of antibiotic resistance, which threaten to exacerbate the antibiotic resistance crisis in LMICs. In particular, current strategies do not prioritize the impacts of increased antibiotic use for terrestrial food-animal and aquaculture production, inadequate food safety, and widespread environmental pollution. Here, we propose new approaches that address emerging, One Health challenges.

Could conjunctivitis in dupilumab treated atopic dermatitis patients be caused by colonization with Demodex and increased IL-17 levels? Reply from authors

Abstract

In studies in atopic dermatitis (AD), dupilumab has been associated with higher rates of conjunctivitis compared with placebo. Consistent with previous studies, in LIBERTY AD CAFÉ (NCT02755649), all cases but one were mild or moderate, most (62–89%) were recovered/resolved or recovering/resolving by end of treatment, and no patients permanently discontinued study treatment because of conjunctivitis.¹ No patients reported atopic keratoconjunctivitis in this study.

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Mass balance of arsenic fluxes in rivers impacted by gold mining activities in Paracatu (Minas Gerais State, Brazil)

Abstract

Arsenic (As) is a dangerous and carcinogenic element and drinking water is its main pathway of human exposure. Gold mines are widely recognized as important sources of As pollution. This work proposes the assessment of As distribution along watersheds surrounding "Morro do Ouro" gold mine (Paracatu, southeastern Brazil). A balance approach between filtered As fluxes (As < 0.45 μm) and suspended particulate material (AsSPM) in different river segments was applied. Ultrafiltration procedure was used to categorize As into the following classes: particulate > 0.1 μm, colloidal < 0.1 μm to > 10 kDa, dissolved < 10 kDa to > 1 kDa, and truly dissolved < 1 kDa. By applying this approach, arsenic contributions from mining facilities were quantified in order to identify critical fluvial segments and support decision makers in actions of remediation. The mass balance indicated the occurrence of a decreasing gradient from upstream to downstream: (i) of the As concentrations higher than the limit established by Brazilian law (10 μg L⁻¹); (ii) of the ratio between specific fluxes (g As km⁻² day⁻¹) and those determined using an uncontaminated watershed (a proxy for estimating the anthropic contribution), from 103 to 101; (iii) of the specific fluxes As < 0.45 μm and AsSPM from 102 to 100; and (iv) of the negative balance output minus input for each river segment that suggests As accumulation in sediments along the rivers in both urban and rural areas, mainly due to SPM sedimentation and sorption by Fe oxyhydroxides. Ultrafiltration shattering showed concentrations of decreasing As with particle size; the SPM load (> 0.1 μm) was almost one order higher to dissolved load (< 1 kDa).

Silicone Migration after Buttock Augmentation

Summary: We present the case of a 30-year-old woman who presented with enlarged inguinal lymph nodes and sacral hyperpigmentation 4 months after gluteal augmentation with silicone implants. Inguinal lymph node biopsy revealed granulomatous lymphadenitis due to foreign material. Upon right buttock implant revision, a 1.5-cm-thick capsule was noted with the absence of peri-implant inflammatory fluid and no macroscopic implant defects. Analysis of the implant by the manufacturer revealed a microscopic silicone leak. The patient's recovery was uneventful, and her symptoms resolved shortly after her reoperation.

Predictors of Success Following Muller’s Muscle-Conjunctival Resection

Purpose: This study aims to describe Muller's muscle-conjunctival resection surgery in terms of outcomes and potential factors that may predict final positions. Methods: This cross-sectional cohort study included patients undergoing Muller's muscle-conjunctival resection surgery for involutional ptosis over a 15-year period. Success was defined in 2 ways: 1) final marginal reflex distance 1 (MRD1) ≥2.5 mm (MRD1 success) and 2) final difference in MRD1 ≤1 mm between eyelids (symmetry success). Percentages of patients achieving both outcomes were calculated. Predictors of outcome were assessed using bivariate analysis and multivariate models. Results: The final sample included 315 eyes in 192 patients. The mean age (standard deviation) was 67.9 (11.9) years, and 60.0% were female. MRD1 ≥2.5 mm was achieved in 65.7% of the sample. Symmetry within 1 mm was achieved in 82.9% of the sample. Significant (p

A Novel Technique for Measuring Eyelid Force

Purpose: We present a novel technique to directly measure the eyelid upward force generation. This technique can be used during routine clinical examination using an inexpensive, portable force gauge. Methods: This prospective case series was conducted January to June 2015 in an ophthalmology clinic affiliated with a tertiary care medical center. A convenience sample of 42 patients (40–90 years of age) without known eyelid pathology participated. The eyelid upward net force generated was measured directly using a handheld dynamometer noninvasively attached to the upper eyelid. Comparison of the eyelid-brow upward force generated with eyelid upward net force generated allowed us to assess the contribution of levator and frontalis muscles to the force generated during upgaze. Data were evaluated with relation to gender and age. Results: Upper eyelid force generated was 53.3 g OD and 53.9 g OS; the generated force during frontalis muscle fixation was 38.4 g OD and 41.1 g OS. The levator and frontalis muscles showed a 3:1 ratio respectively in their contribution to the force generated during upgaze. Although no statistically significant differences were seen between eyes, gender, or within age groups, younger patients showed increased generating force which is attributed to the levator muscle. Interclass correlation coefficient showed virtually no correlation between clinical eyelid assessments and direct muscle force measurement. Reliability for repeated direct force measurements by the same physician was strong, with interclass correlation coefficient 0.951 to 0.969. No adverse events occurred. Conclusions: We describe a simple, reliable, inexpensive, new method for assessing upper eyelid upward force generation. Because the levator muscle serves as the primary contributor to eyelid elevation, this directly measurable eyelid assessment may help to increase understanding of its functional contribution and assessment when assessing eyelid pathologies. Accepted for publication July 11, 2017. Presented at Annual Conference of Ocular Microsurgery, January 8-10, 2015 in Eilat, Israel. The authors have no financial or conflicts of interest to disclose. Shay Ofir, Avner Belkin, and Arie Y. Nemet contributed to conception, design, analysis, writing, and literature search; Shay Ofir contributed to data collection, materials and patient recruitment; Arie Y. Nemet contributed to critical revision and final approval; and Shay Ofir had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Address correspondence and reprint requests to Shay Ofir, MD, Department of Ophthalmology, Meir Medical Center, 59 Tshernichovsky St., Kfar Saba 44281, Israel. E-mail: shayofirl@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Medial Buttressing in Orbital Blowout Fractures

Purpose: To study whether ethmoidectomy predisposes the orbit to medial wall fracture with lesser trauma. Methods: An interventional cadaver study of 5 heads (10 orbits); the left or right orbit was randomized to undergo endoscopic complete ethmoidectomy with the fellow orbit as control. Fractures were induced with direct globe trauma, and heads underwent CT scanning. Energy to induce fracture, peak orbital pressure at time of fracture, fracture pattern, and volume of herniated tissue were measured and analyzed. Results: Fractures were induced in both orbits of all cadavers. Experimental orbits after ethmoidectomy sustained orbital fracture at less energy required (2.14 ± 0.66 vs. 3.10 ± 0.19 J, mean difference: −0.96 ± 0.33 J, p

Seminoma Metastatic to the Orbit

Purpose: Seminomas are solid tumors in young men, but which rarely metastasize to the orbit. The authors review the known literature on seminoma metastatic to the orbit, and describe an additional case in a 33-year-old man. Methods: A literature search was performed on the MEDLINE database using keywords "seminoma," "testicular germ-cell tumors," "testicular cancer," "testicular neoplasm," "orbital metastasis," and "germ-cell neoplasms." Results: Malignant neoplasms of the testis account for only 1% of cancers in men. None-the-less, testicular germ cell seminoma is the most common solid tumor found in young men between the ages of 15 and 39. Only seven previous cases have been mentioned in the literature. The pathogenesis remains unclear although genetic, environmental, and maternal factors may play a role. The number of cases is too few to determine the best treatment options, but surgical excision and adjunctive orbital radiotherapy appear to be most appropriate. Conclusions: Although metastases to the orbit are rare, seminoma should be considered in the differential diagnosis of all young men with proptosis. Accepted for publication October 9, 2017. The authors have no financial or conflicts of interest to disclose. Dr. Carol Shields served as guest editor for this submission. Address correspondence and reprint requests to Jonathan J. Dutton, M.D., Ph.D., Department of Ophthalmology, University of North Carolina, Chapel Hill, NC 27599. E-mail: jonathan_dutton@med.unc.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Gelatin-Based Hemostatic Agents: Histopathologic Differences

Purpose: To delineate the histopathologic appearance of gelatin-based hemostatic agents, Surgiflo, Gelfoam, and Floseal, which are used by ophthalmic plastic surgeons, and which may incidentally be found as foreign materials in histopathologic tissue samples. Methods: Histopathologic analysis was performed with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, and elastin staining on tissue samples in which gelatin-based agents were found. To better characterize these materials, similar analyses were performed on in vitro samples of commonly used gelatin-based hemostatic agents. Results: Surgiflo and Gelfoam are composed of small stellate pieces of gelatin with a smooth, homogeneous quality. In tissues, they are faintly positive with periodic acid-Schiff staining, amphophilic with Masson trichrome staining, and ink-black with elastin staining. Floseal has a distinctly different morphology of large rectangular sheets, yet almost identical in vitro staining properties. Discussion: While the morphology of the gelatin-based hemostatic agents is consistent under various conditions, the staining properties of these materials differ based on whether they have been in contact with human tissue. Conclusions: Gelatin-derived hemostatic agents are best identified based on their morphologic characteristics. Elastin staining highlights these materials prominently within tissue samples and may be helpful in distinguishing them from other foreign materials. Accepted for publication November 16, 2017. Natalie Wolkow received a Heed Ophthalmic Fellowship. The remaining authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Frederick A. Jakobiec, M.D., D.Sc., Department of Ophthalmology, David G. Cogan Laboratory of Ophthalmic Pathology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Suite 328, Boston, MA 02114. E-mail: Fred_Jakobiec@meei.harvard.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Improved Long-term Volume Retention of SVF-gel Grafting with Enhanced Angiogenesis and Adipogenesis

Background The apoptosis of mature adipocytes after fat grafting can result in chronic inflammation, absorption, and fibrosis, leading to unpredictable outcomes. Selective elimination of mature adipocytes may result in better outcomes and a different underlying retention mode. We previously developed a mature-adipocyte-free product, SVF-gel, derived from lipoaspirate, which eliminates adipocytes while preserving the stromal vascular fraction. This study investigated the retention and regeneration mode of SVF-gel grafting. Methods Nude mice were grafted with human-derived SVF-gel or Coleman fat. Detailed cellular events over 3 months were investigated histologically and immunohistochemically. Results The retention rate 90 days after grafting was significantly higher for SVF-gel grafts than for standard Coleman fat (82% ± 15% vs. 42% ± 9%, P

Measurement of warping angle in human rib graft; Experimental study

To determine the warping angle of the costal cartilage in vivo. A nasal framework reconstruction with a rib graft was performed in a total of 130 patients. After the cartilage specimens were prepared, the remaining grafts were used for the experimental study. The angle of warping in all grafts was measured at 0, 30, and 60 minutes, after 24 hours and after one week. In this study, 8 subgroups of graft thicknesses from central and peripheral groups, which were determined according to the perichondral distance of the grafts, were evaluated, and the warping angles of a total of 48 osteochondral and chondral grafts were individually measured. Three-way analysis of variance was used to compare the change in warping over time to detect differences in the grafts. Significant differences were not observed in the 1-3 mm thick grafts of peripheral and central origin before 30 minutes(P>0.05), although significant differences were observed in these groups for all time periods after 30 minutes(P0.05). In the central origin grafts thinner than 1 mm, significant differences were not observed in the warping angle for all time periods(P>0.05), although significant differences were observed in the same grafts of peripheral origin(P

Cheek Volumization and Nasolabial folds

The impression that cheek filling results in longitudinal shortening ("lift") of the skin and elevation of the nasolabial crease(NLC) or nasolabial fold (NLF) has become common within the facial injection community, but remains unsubstantiated. In this study, seventy-seven patients were evaluated pre and post-injection injection of the cheeks with an Hyaluronic Acid filler using a 3-dimensional camera system. A constant pattern of skin expansion away from the center of the injection and perpendicular to the surface of the skin was observed. A subgroup of 37 patients without differences in their pre and post-injection facial expression were analyzed by direct comparison and failed to demonstrate lateral traction (or "pull") on the intervening skin from the cheek injection site to the nasolabial crease. Further, there was no photographic difference in the nasolabial fold or nasolabial crease. The only patients who demonstrated photographic improvement of the medial face were those who had filler placed directly in the transition between the lateral nasolabial fold and cheek (nasojugal crease). It is likely that expanding the nasojugal crease is the direct visual cue that leads to perceived improvement in the nasolabial fold. No disclosures Corresponding author Val Lambros, MD , Clinical professor of Plastic Surgery, University of California Irvine, 2121 E Coast Highway #200, Corona Del Mar Ca 92925, Lambrosone@aol.com ©2018American Society of Plastic Surgeons

Consequences of the F.D.A. Directed Moratorium on Silicone Gel Breast Implants – 1992-2006

The FDA silicone gel breast implant moratorium occurred 25 years ago. The immediate and long-term consequences of the moratorium are reviewed and assessed. Financial Disclosure Statement: Nothing to disclose. Corresponding Author: Norman M. Cole, M.D., 2208 Lake Ridge Drive, Belmont, NC 28012 USA ©2018American Society of Plastic Surgeons

Commentary on Norm Cole’s “Moratorium Consequences.”

No abstract available

“A fresh cadaver study on indocyanine green fluorescence lymphography: A new whole body imaging technique for investigating the superficial lymphatics.”

Background: Identification of the lymphatic system in cadavers is painstaking because lymphatic vessels have very thin walls and are transparent. Selection of appropriate contrast agents is a key factor for successfully visualizing the lymphatics. In this study, we introduce a new imaging technique of lymphatic mapping in whole body of fresh cadavers. Methods: Ten fresh human cadavers were used for this study. We injected 0.1 mL of indocyanine green fluorescence (ICG) solution subcutaneously at multiple spots along the watershed lines between lymphatic territories and hand and foot regions. After the body was scanned by the near infrared camera system, fluorescent tissues were harvested and histological examination was performed under the microscope equipped with the infrared camera system to confirm they were the lymphatics. Results: Subcutaneously injected ICG was immediately transported into the lymphatic vessels after gentle massage on the injection points. Sweeping massage along the lymphatic vessels facilitated ICG transport inside the lymphatic vessel to move towards the lymph nodes. The lymphatic system was visualized well in the whole body. Histological examinations confirmed that ICG was detected in the lymphatic lumens specifically, even when located far from the injected points. Conclusions: The lymphatic system could be visualized in whole body fresh cadavers, as in living bodies, using ICG fluorescence lymphography. Compatibility of ICG lymphography would be open to use cadaveric specimens for macro and microscopical analysis. Financial Disclosure Statement: The authors have no financial interest to declare in relation to the content of this article. Acknowledgments: This work was supported by the Japan Society for the Promotion of Science via Grants-in-Aid for Scientific Research (KAKENHI Award Number: 16K20358) and Research Foundation for the Electrotechnology of Chubu. Corresponding author: Akira Shinaoka, Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, 700-8558, Japan. Email: a-shinaoka@okayama-u.ac.jp ©2018American Society of Plastic Surgeons

Beyond JAAD April 2018

Vitamin K5 is an efficient photosensitizer for ultraviolet A light inactivation of bacteria

Abstract

Photodynamic treatment combining light and a photosensitizer molecule can be an effective method to inactivate pathogenic bacteria. This study identified vitamin K5 as an efficient photosensitizer for ultraviolet light A (UVA)-induced bacterial inactivation. Six bacterial species, Bacillus cereus (vegetative form), Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, and two species of antibiotic-resistant bacteria, Pseudomonas aeruginosa* and Staphylococcus aureus*, were suspended in aqueous solutions with or without vitamin K5 and exposed to UVA irradiation. UVA irradiation (5.8 J cm⁻²) with vitamin K5 (1600 μmol l⁻¹) reduced the colony forming units (CFU) of these bacteria by three to seven logs. Antibiotic resistant bacteria were also susceptible to the bactericidal effects of UVA and vitamin K5 combination treatment. Inactivation of bacteria in human plasma required higher doses of UVA light and vitamin K5. UVA irradiation (30 J cm⁻²) with vitamin K5 (2000 μ mol l⁻¹) reduced Escherichia coli and Staphylococcus aureus spiked into human plasma by seven logs CFU/ml. Reactive oxygen species, such as superoxide anion radicals and hydroxyl radicals, were found to be generated in vitamin K5 aqueous solution after UVA irradiation, suggesting these oxygen species may mediate the inactivation of the bacteria.

EsrB negatively regulates expression of the glutamine sythetase GlnA in the fish pathogen Edwardsiella piscicida

Abstract

Edwardsiella piscicida is a gram-negative bacterial pathogen invading a wide range of fish species. Response regulator EsrB is essential for activation of type III and type VI secretion systems (T3/T6SS). In this study, proteomes of the wild type E. piscicida EIB202 and a ΔesrB mutant strains were compared to identify the regulon components of EsrB cultured in DMEM allowing T3/T6SS expression. As a result, 19 proteins showed different expression, which were identified to be associated with T3/T6SS, related to amino acid transport and metabolism, and energy production. Particularly, GlnA, a glutamine synthetase essential for ammonia assimilation and glutamine biosynthesis from glutamate, was found to be regulated negatively by EsrB. Moreover, GlnA affected bacterial growth in vitro and bacterial colonization in vivo. Collectively, our results indicated that EsrB plays important roles in regulating the expression of metabolic pathways and virulence genes, including glutamine biosynthesis in E. piscicida during infection.

Prevalence of metabolic syndrome in children with moderate to severe psoriasis treated with TNF inhibitors in comparison to conventional agents

Abstract

Association of childhood psoriasis with metabolic syndrome has not been studied well. TNF-alfa contributes to the inflammation seen in metabolic syndrome, and recently etanercept has shown to reduce the levels of inflammatory markers. Assessment of prevalence of metabolic syndrome in juvenile psoriasis patients in Kuwait. We included 236 patients with moderate to severe psoriasis below 18 years treated for at least 24 weeks with TNF inhibitors (Group A), and equal number of age and sex matched cases treated with conventional medications (Group B). The metabolic syndrome (MBS) was defined according to the International Diabetes Foundation (IDF 2007 criteria for children). Increased waist circumference was seen in 56.77% of cases in Group A. Triglyceridemia was less frequent in Group A. MBS was higher in Group B [41·52% vs. 50·42%, odds ratio (OR) 1·76, 95% CI 1.19–2.41; p = .005]. Psoriasis is associated with higher prevalence of metabolic syndrome in children. Six months of anti TNF treatment showed lesser association with metabolic syndrome. With fasting blood glucose, and serum TG seen in significantly lesser number of patients in this group.

Clinical evaluation of a novel fractional radiofrequency device for hair growth: Fractional radiofrequency for hair growth stimulation

Abstract

AGA is a common disorder. Different treatments are available to prevent hair loss and achieve hair growth with variable results. The purpose of the present study was to evaluate the efficacy and safety of a novel fractional radiofrequency (RF) device (HairLux, Innogen Technologies Ltd., Yokneam, Israel), to prevent hair loss and induce hair growth. Twenty-five patients received 10 fractional RF treatments every 2 weeks, and were followed up 2 months after the last treatment. All patients were evaluated by global photography. In 10 patients, blinded manual hair counts were performed. Patients demonstrated less hair shedding, fuller hair, and faster hair growth. There was an average increase of 31.6% in hair density (based on hair counts) and 18% increase in hair shaft thickness. All subjects tolerated the treatments well. The HairLux device is effective and safe for hair growth stimulation in AGA. Ten treatment sessions are recommended to maximize results.

PD-1 blockade in HIV-infected patients with lung cancer: a new challenge or already a strategy?

HIVanti-PD-1CD4viral loadlung cancer

The US Food and Drug Administration’s Use of Regular Approval for Cancer Drugs Based on Single Arm Studies: Implications for Subsequent Evidence Generation

Unique Genetic Profiles from Cerebrospinal Fluid Cell-free DNA in Leptomeningeal Metastases of EGFR-mutant Non-Small Cell Lung Cancer: A New Medium of Liquid Biopsy

Abstract

Background

Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.

Patients and methods

Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.

Results

28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26) and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared to those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; p < 0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% vs. 33.3%; p =0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.

Conclusion

CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR–mutant NSCLC.

Uncovering the links between systemic hormones and oncogenic signaling in the pathogenesis of meningioma

Final Results of a Multi-institutional Phase II Trial of Re-Irradiation with Concurrent Weekly Cisplatin and Cetuximab for Recurrent or Second Primary Squamous Cell Carcinoma of the Head and Neck

Abstract

Background

The optimal regimen of chemotherapy and re-irradiation (re-XRT) for recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We report the final outcomes of a multi-center Phase II trial evaluating cetuximab and cisplatin-based chemotherapy concurrent with re-XRT for patients with recurrent HNSCC.

Methods and Materials

Patients with unresectable recurrent disease or positive margins after salvage surgery arising within a previously irradiated field with KPS≥70 were eligible for this trial. Cetuximab 400mg/m² was delivered as a loading dose in Week 1 followed by weekly cetuximab 250mg/m² and cisplatin 30mg/m² concurrent with 6 weeks of IMRT to a dose of 60-66 Gy in 30 daily fractions. Patients who previously received both concurrent cetuximab and cisplatin with radiation or who received radiotherapy less than 6 months prior were ineligible.

Results

From 2009 to 2013, 48 patients enrolled on this trial. 2 did not receive any protocol treatment. Of the remaining 46 patients, 34 were male and 12 female, with a median age of 62 years (range 36-85). Treatment was feasible and only 1 patient did not complete the treatment course. Common Grade 3 or higher acute toxicities were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%), mucositis (11%) and anorexia (11%). There were no Grade 5 acute toxicities. Eight Grade 3 late toxicities were observed, 4 of which were swallowing-related. With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4% and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was significantly improved with young age (p=0.01). OS was not associated with radiation dose, surgery prior to re-XRT or interval from prior XRT.

Conclusions

Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good treatment outcomes for patients with high-risk features. Younger patients had significantly improved OS.

ClinicalTrials.Gov Identifier

NCT00833261

Activity and safety of afatinib in a window pre-operative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN)

Abstract

Background

To investigate the activity and safety of afatinib in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN).Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5:1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were performed at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other endpoints included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic enhanced contrast (DCE)-MRI, diffusion weighted (DW)-MRI, safety and translational research (TR).

Results

Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47-87%) had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI, 8-44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST.One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3 –hypoxia score expression and with TP53 wild type.

Conclusion

Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity.

Clinical trial registration

ClinicalTrials.gov: NCT01538381

Trichloroacetic acid (80%) as a chemical debridement method for chronic venous leg ulcers—A pilot study

Debridement is essential for the optimal care of venous leg ulcers. Several debridement methods with different limitations may be deployed. Trichloroacetic acid (TCA) is used for several dermatological purposes. Its application as a chemical debridement method for leg ulcers has never been explored. We designed a prospective study to determine the role of 80% TCA solution as a chemical debridement method for leg ulcers, regarding efficacy and procedure-associated pain. Chronic venous leg ulcers were treated with 3 cycles of 80% TCA solution or curettage over 1 week. Pain and the mean percentage of fibrin and devitalized tissue covering wound bed were evaluated. At the end of the study, a trend towards larger fibrin mean reduction among the TCA treated ulcers was observed, although this difference was not statistically significant (P = .35). The mean pain score after TCA application was significantly reduced compared to pain after curettage alone (P < 0.001). TCA presented several advantages over mechanical debridement: it is a more selective debridement method, has haemostatic properties, and a simpler and faster application. The 80% TCA solution may be a cheap, simple, and considerably less-painful chemical debridement method for venous leg ulcers compared to classical mechanical debridement.

The effect of 22.5 kHz low-frequency contact ultrasound debridement (LFCUD) on lower extremity wound healing for a vascular surgery population: A randomised controlled trial

The aim of this study was to compare changes in wound size and appearance and health complication rates in patients with vasculopathy and lower-extremity wounds treated with or without low-frequency contact ultrasound debridement (LFCUD) This study was a randomised controlled trial. The study was conducted in a vascular surgery service, including outpatient wound clinic and inpatient ward, in a tertiary care academic centre. In total, 70 patients with vasculopathy and lower-extremity wounds of mixed aetiology were enrolled in the trial; 68 completed the study. Patients were randomised to receive LFCUD plus usual care (n = 33) or usual care (n = 37) at 4 weekly visits, and were followed thereafter for up to 12 wk. The main outcome measures included closed wounds, change in wound surface area (WSA), and wound appearance by the revised Photographic Wound Assessment Tool (revPWAT). After 4 weekly LFCUD treatments, patients in the LFCUD group had significantly better wound appearance (total revPWAT score) compared with the control group treated only with usual care (P = <0.05). LFCUD-treated wounds also had a significant reduction in WSA over 4 wk that was not found in the UC group. LFCUD treatment was also associated with a greater number of healed wounds, odds ratio 5.00 (95% CI 1.24-20.25), and fewer instances of wound deterioration. Weekly LFCUD applications to patients with significant vasculopathy resulted in superior healing outcomes when compared with current usual wound care practice.

Direct repression of IGF2 is implicated in the anti-angiogenic function of microRNA-210 in human retinal endothelial cells

Abstract

Pathological angiogenesis leads to the development of retinal vasculopathies and causes severe vision impairment. Increased understanding of the mechanisms underlying the angiogenic behavior of retinal endothelial cells helps provide new insights for developing treatment of retinal vasculopathies. Pro-angiogenic function of miR-210 has previously been identified. However, the functional implication of miR-210 in retinal endothelial cells remains unknown. Human retinal microvascular endothelial cells (HRECs) were employed to investigate the impact of miR-210 on the angiogenic capacity of retinal endothelial cells. It was observed that without affecting the viability of HRECs, miR-210 significantly suppressed the migration and capillary-like tube formation in HRECs. Moreover, pro-angiogenic insulin growth factor 2 (IGF2) was newly identified as a direct target of miR-210 in HRECs. MiR-210 decreased the expression of IGF2 at both mRNA and protein levels in HRECs. IGF2-simulated activation of p38 MAPK was attenuated by miR-210 in HRECs. Recombinant IGF2 protein rescued miR-210-induced impairment of tube formation in HRECs. Therefore, in contrast to the previously reported pro-angiogenic function of miR-210, the current work reveals novel anti-angiogenic activity of miR-210 in HRECs. Furthermore, IGF2 is identified for the first time as a direct target of miR-210 in HRECs, adding new mechanistic insights into the expression regulation of pro-angiogenic IGF2 in human retinal endothelial cells. The current work helps increase the understanding of regulatory mechanisms underlying retinal endothelial cell physiology, justifying further evaluation for the therapeutic implications of miR-210/IGF2 interaction in the treatment of related retinal vasculopathies.

The Infinity from Nothing paradox and the Immovable Object meets the Irresistible Force

Abstract

In this paper I present a novel supertask in a Newtonian universe that destroys and creates infinite masses and energies, showing thereby that we can have infinite indeterminism. Previous supertasks have managed only to destroy or create finite masses and energies, thereby giving cases of only finite indeterminism. In the Nothing from Infinity paradox we will see an infinitude of finite masses and an infinitude of energy disappear entirely, and do so despite the conservation of energy in all collisions. I then show how this leads to the Infinity from Nothing paradox, in which we have the spontaneous eruption of infinite mass and energy out of nothing. I conclude by showing how our supertask models at least something of an old conundrum, the question of what happens when the immovable object meets the irresistible force.

Childhood alopecia areata—Data from the National Alopecia Areata Registry

Abstract

Background/Objectives

Alopecia areata may occur at any age and is the third-most-common dermatosis in children. The objective of this study was to investigate the clinical and epidemiologic features of children and adolescents with alopecia areata based on the data of the National Alopecia Areata registry on children and adolescents.

Methods

Two thousand two hundred eighteen children and adolescents with alopecia areata self-enrolled in the National Alopecia Areata Registry and completed a web-based, self-administered, short-intake screening questionnaire (first tier). In the second tier, 643 patients participated in a clinical examination and completed a long-form questionnaire.

Results

Mean age of onset was 5.9 ± 4.1 years. With a female to male ratio of 1.5:1, alopecia areata was more prevalent in girls, but boys were significantly more likely to have a severe type (P = .009). One-fourth of all children had a positive family history, with 8% having more than three affected relatives. The disease most commonly associated with alopecia areata was atopic dermatitis (32.7%).

Conclusion

Childhood alopecia areata is more prevalent in girls than in boys, but boys have more extensive alopecia areata. Despite the low prevalence, congenital alopecia areata is an important differential diagnosis for neonatal hair loss. Alopecia areata runs in families, suggesting an underlying genetic background. One-quarter of the children reported at least one affected first-degree relative; 8% had more than three affected relatives.

Use of antiviral medications in drug reaction with eosinophilia and systemic symptoms (DRESS): A case of infantile DRESS

Abstract

A 3-month-old girl with Sturge-Weber syndrome presented with a morbilliform rash, eosinophilia, and fulminant liver failure to our tertiary pediatric hospital. She was diagnosed with drug reaction with eosinophilia and systemic symptoms complicated by viremia and evidence of viral hepatitis on liver biopsy. We discuss the role of viral reactivation in drug reaction with eosinophilia and systemic symptoms and the relevance of antiviral therapy in management.

A comprehensive next-generation sequencing assay for the diagnosis of epidermolysis bullosa

Abstract

Background

Historically, diagnosis of epidermolysis bullosa has required skin biopsies for electron microscopy, direct immunofluorescence to determine which gene(s) to choose for genetic testing, or both.

Methods

To avoid these invasive tests, we developed a high-throughput next-generation sequencing (NGS)-based diagnostic assay called EBSEQ that allows simultaneous detection of mutations in 21 genes with known roles in epidermolysis bullosa pathogenicity. Mutations are confirmed with traditional Sanger sequencing.

Results

We present our EBSEQ assay and preliminary studies on the first 43 subjects tested. We identified 11 cases of epidermolysis bullosa simplex, five cases of junctional epidermolysis bullosa, 11 cases of dominant dystrophic epidermolysis bullosa, 15 cases of recessive dystrophic epidermolysis bullosa, and one case that remains without diagnosis. We also found an additional 52 variants of uncertain clinical significance in 17 of the 21 epidermolysis bullosa-associated genes tested. Three of the variants of uncertain clinical significance were also found in three other patients, for a total of 49 unique variants of uncertain clinical significance. We found the clinical sensitivity of the assay to be 75% to 98% and the analytical sensitivity to be 99% in identifying base substitutions and small deletions and duplications. Turnaround time was 3 to 6 weeks.

Conclusions

EBSEQ is a sensitive, relatively rapid, minimally invasive, comprehensive genetic assay for the diagnosis of epidermolysis bullosa.

Oxybutynin 3% gel for the treatment of primary focal hyperhidrosis in adolescents and young adults

Abstract

Background/Objectives

There are no reliably effective, well-tolerated topical agents for the treatment of hyperhidrosis. We sought to evaluate the efficacy and tolerability of oxybutynin 3% gel in adolescents and young adults with primary focal hyperhidrosis.

Methods

Patients with severe axillary hyperhidrosis were treated with topical oxybutynin 3% gel for 4 weeks. Response to treatment was assessed by calculating change in Hyperhidrosis Disease Severity Score from baseline to weeks 1 and 4. Change in health-related quality of life was assessed using the Children's Dermatology Life Quality Index or the Dermatology Life Quality Index. Adverse effects were evaluated using patient diaries, investigator global review, and physical examination.

Results

Of 10 patients aged 13-24 enrolled, seven completed the study. Of those who completed the study, four (57.1%) reported reduction in axillary Hyperhidrosis Disease Severity Score at week 1 and all seven (100%) at week 4. Six patients (85.7%) reported reduction in Children's Dermatology Life Quality Index or Dermatology Life Quality Index score. Anticholinergic adverse effects were infrequent. The majority of treatment-related adverse events were mild to moderate in severity. One patient experienced a severe adverse event.

Conclusion

Oxybutynin 3% gel reduced hyperhidrosis severity and improved health-related quality of life in this small pilot study. Safety and efficacy should be further evaluated in a large, prospective, placebo-controlled study.

Severe ectropion in lamellar ichthyosis managed medically with oral acitretin

Abstract

Congenital ectropion is commonly associated with lamellar ichthyosis. Severe eyelid ectropion may cause corneal exposure, keratopathy, and permanent corneal scarring. We report a neonate with severe, bilateral, congenital ectropion and eclabium managed using oral retinoids. Both corneas were protected with topical antibiotics and lubricating eyedrops and eye ointments. At 12-month follow-up, the child was doing well, with no ectropion or corneal opacity.

Issue Information

Patient-Reported-Outcome-Messung (PROM) psychosozialer Belastung und Symptome für ambulante Patienten unter kurativer oder palliativer Tumortherapie

Zusammenfassung

Hintergrund

Palliative Unterstützung sollte früh in die Tumortherapie eingebunden werden, doch der Bedarf der Patienten bleibt oft unerkannt und unbehandelt. Die Autoren analysierten die Rücklaufquote einer quartalsweisen Patientenbefragung mit validierten Fragebögen und erfassten die Bedarfe der Tumorpatienten, die sich in kurativer oder palliativer Behandlung befanden.

Methoden

Bei der Entwicklung des Fragebogens wurden die 3 validierten Instrumente Hornheider Fragebogen (HSI), PHQ4 Fragebogen (Patient Health Questionnaire) und der MIDOS Fragebogen (MInimal DOcumentation System) kombiniert. 96 (13,6 %) kurativ und 609 (81,4 %) palliativ behandelte Patienten füllten einen Fragebogen aus.

Ergebnisse

Zwischen Oktober 2013 und März 2016 wurden 75 % der ausgeteilten Fragebögen ausgefüllt. Unter den kurativ und palliativ behandelten Patienten hatten 34 (35,8 %) und 272 (45,0 %) Patienten einen pathologischen HSI-Score (p = 0,094), bei 7 (11,3 %) und 51 (13,7 %) Patienten ergab der PHQ4 einen mittleren oder schlechten Score (p = 0,845) und 6 (6,5 %) und 70 (12,1 %) Patienten gaben ein schlechtes oder sehr schlechtes Allgemeinbefinden an (p = 0,388). 340 von 669 (50,8 %) Patienten wiesen auf die zusätzliche Belastung ihrer Angehörigen hin.

Schlussfolgerung

Die Analyse zeigt die Durchführbarkeit einer quartalsweise durchgeführten Patientenbefragung zur Erfassung des palliativen Bedarfs im Routinebetrieb einer onkologischen Ambulanz. Hauptsymptome beider Patientengruppen waren Müdigkeit und Schwäche. Weiterhin gab ein Großteil der Patienten eine Belastung der Angehörigen an.

Neue diagnostische und therapeutische Aspekte zu Chordomen

Zusammenfassung

Hintergrund

Chordome zählen zu den primären, malignen Knochentumoren und treten mit Schwerpunkt im Sakrum und Clivus entlang der Wirbelsäule auf (ICD-O: 9370/3). Man geht davon aus, dass sie aus Resten der Chorda dorsalis entstehen. Aufgrund des seltenen Auftretens zählen sie zu den sog. „orphan diseases".

Methoden

Es wurden eine Recherche und Auswertung aktueller Literatur und klinischer Studien durchgeführt.

Ergebnisse

Die primäre Therapie stellt heutzutage die Chirurgie dar; allerdings kann dies v. a. im Clivus problematisch sein. Zudem treten häufig Rezidive und nicht selten Metastasen auf. In der rezidivierten Situation wird die Hochdosisbestrahlung mit Protonen empfohlen. Aufgrund des generell langsamen Wachstums der Chordome ist eine konventionelle Chemotherapie problematisch. In den letzten Jahren konnten für Chordome molekularpathologische Signalwege mit entsprechenden Zielstrukturen identifiziert werden, die erste Ansätze für eine zielgerichtete Therapie bieten.

A photonumeric scale for the assessment of atrophic facial photodamage

Summary

Background

Photonumeric scales have consistently shown superiority over descriptive equivalents. They have the advantage of providing a consistent visual frame of reference by minimising variability in perception and subjectivity. A photonumeric scale to assess hypertrophic facial photodamage already exists. However, there is currently no objective measure for atrophic facial photodamage. To address this, we have devised a nine-point photonumeric standardised scale.

Objectives

To design, test and validate a photonumeric scale for the assessment of atrophic facial photodamage against a descriptive scale for the same indication.

Methods

A pool of 393 facial photographs (en face and 45º oblique) from 131 individuals with atrophic facial photodamage was created. Five photographic standards were selected and assigned grades 0 through 8, where 0 is no photodamage and 8 is severe atrophic photodamage, thus making a nine-point scale. Twenty photographs spanning the entire range of values were selected to test the scale. Testing was performed alongside a descriptive equivalent. A panel of 10 dermatologists, 10 non-dermatology clinicians and 14 dermatology scientists marked the two scales; marking was repeated one week later.

Results

There was a significantly greater agreement between the graders using the photonumeric scale than the descriptive scale (kappa values 0.71 and 0.37 with standardised errors of 0.57 and 0.17 respectively) with no significant difference in repeatability between the two methods (p < 0.05).

Conclusions

The study describes a new photonumeric scale for atrophic photodamage. This would be a useful adjunct in both the clinical and research settings.

This article is protected by copyright. All rights reserved.

Could conjunctivitis in dupilumab treated atopic dermatitis patients be caused by colonization with demodex and increased IL-17 levels?

Abstract

de Bruin-Weller et al., reported alarmingly high rates of unspecified and allergic conjunctivitis in trial patients with moderate-to-severe atopic dermatitis (AD) who underwent treatment with dupilumab; an antibody that inhibits signaling of IL-4 and IL-13.¹ Importantly, the exact pathogenic mechanism behind incident conjunctivitis in dupilumab-treated patients is unclear. While all, but one case, were considered to be of mild or moderate severity, and most resolved after treatment discontinuation, ocular complications may ultimately deprive AD patients from effective treatment with dupilumab. For these reasons, the medical community needs to rapidly identify the pathogenic mechanism.

This article is protected by copyright. All rights reserved.

High-salt- and cholesterol diet-associated cognitive impairment attenuated by tannins-enriched fraction of Emblica officinalis via inhibiting NF-kB pathway

Abstract

Metabolic disorders are closely associated with dietary habits and seem to be related to neuroinflammation and neurodegenerative disease in humans. Emblica officinalis (EOT) fruits not only have good nutritional value but also have excellent therapeutic potential. We used a tannins-enriched fraction of EOT fruit with the expectation of controlling diet-induced neuroinflammation and cognitive impairment in rats. A high-salt and cholesterol diet (HSCD) was used to induce neuroinflammation and cognitive impairment in rats. The diet of the rats was then supplemented with EOT (100 and 200 mg/kg b.w.) for 7 weeks. In order to evaluate the neuroprotective effects of EOT; in silico study, neurobehavioral tests, biochemical analyses, and immunohistochemical studies were performed. In silico study of p50 (NF-κB1) receptors with emblicanin (the main constituent of EOT) suggests that EOT has binds to NF-κB. EOT treatment reversed the HSCD-induced behavioral and memory disturbances in a step-down-type passive avoidance test. EOT treatment also inhibited HSCD-induced NF-κB upstream signaling, including the release of Th1, such as TNF-α, and downstream signaling Th2, such as IL-10, by flow cytometer. In addition, EOT treatment attentuated the HSCD-induced increase in the level of cognitive impairment markers, such as amyloid β. Furthermore, immunohistochemical results demonstrated that EOT modulated neuronal cell death by inhibiting the overexpression of NF-kB in brain. This study confirms that EOT may be a promising therapy in ameliorating the neurotoxicity of HSCD; however further studies are warranted to elucidate the exact mechanism of action of EOT.