The Laryngoscope, EarlyView.
https://ift.tt/2PpiITF
Δευτέρα 29 Οκτωβρίου 2018
Hairy polyps: A new case presentation and a pathogenetic hypothesis
Endoscopic Transcanal Autologous Cartilage Ossiculoplasty
Abstract
This was a randomized clinical trial, of thirty-two patients undergoing endoscopic ossiculoplasty, as a second look surgery, at 6 months after primary endoscopic cholesteatoma surgery, in a duration of 9 years. All patients underwent trans-canal endoscopic ossiculoplasty under local anesthesia. Prosthesis used were (1) Titanium partial ossicular replacement prosthesis (PORP) in fourteen, (2) Titanium total ossicular replacement prosthesis (TORP) in six and (3) Autologous cartilage in twelve cases. Puretone audiometry (PTA) were done preoperatively and postoperatively at 2 months and 3 years. Out of twenty-four cases, which presented only with stapes superstructure; fourteen underwent PORP ossiculoplasty and twelve had cartilage short columella ossiculoplasty (SCC). Out of eight cases, which had only mobile stapes footplate, six underwent TORP ossiculoplasty and only two underwent long columella cartilage ossiculoplasty (LCC). Pre-operative average air conduction threshold (AC) of pure tone audiometry were 45.47 dB (PORP), 66.10 dB (TORP), 49.15 dB (SCC) and 59.15 dB (LCC) groups. The post-operative AC at 2 months were respectively 27.37 dB (PORP), 45.83 dB (TORP), 29.99 dB (SCC) and 39.15 dB (LCC) groups. The gap of air and bone conduction (ABG) at 2 months post-operative stage were 19.05 dB (PORP), 20 dB (TORP), 20.32 dB (SCC) and 39.15 dB (LCC) groups and not much changed after 3 years. Extrusion occurred in three PORPs and four TORPs at 4–8 years after surgery. Four cases were lost to follow up. No extrusion occurred in cartilage ossiculoplasty. Trans-canal endoscopic autologous cartilage ossiculoplasty shows encouraging results comparable to titanium prosthesis in repairing ossicles in cholesteatoma disease.
https://ift.tt/2SuJM2j
Submental Ectopic Thyroid Cyst: An Atypical Presentation
Abstract
It is very unusual of an ectopic thyroid to be presented as a submental swelling, clinically mimicking a submental cyst. Suspicious of the disease with complete clinical, biochemical and radiological correlation is the mainstay of diagnosis as the first FNAC is not confirmatory of the ectopic thyroid especially in cases of dysgenesis of thyroid tissue in an unusual location. Here we have presented a rare case of an ectopic thyroid gland presented with a submental swelling successfully managed with the conservative treatment.
https://ift.tt/2zfZ3Ls
Endoscopic Transcanal Autologous Cartilage Ossiculoplasty
Abstract
This was a randomized clinical trial, of thirty-two patients undergoing endoscopic ossiculoplasty, as a second look surgery, at 6 months after primary endoscopic cholesteatoma surgery, in a duration of 9 years. All patients underwent trans-canal endoscopic ossiculoplasty under local anesthesia. Prosthesis used were (1) Titanium partial ossicular replacement prosthesis (PORP) in fourteen, (2) Titanium total ossicular replacement prosthesis (TORP) in six and (3) Autologous cartilage in twelve cases. Puretone audiometry (PTA) were done preoperatively and postoperatively at 2 months and 3 years. Out of twenty-four cases, which presented only with stapes superstructure; fourteen underwent PORP ossiculoplasty and twelve had cartilage short columella ossiculoplasty (SCC). Out of eight cases, which had only mobile stapes footplate, six underwent TORP ossiculoplasty and only two underwent long columella cartilage ossiculoplasty (LCC). Pre-operative average air conduction threshold (AC) of pure tone audiometry were 45.47 dB (PORP), 66.10 dB (TORP), 49.15 dB (SCC) and 59.15 dB (LCC) groups. The post-operative AC at 2 months were respectively 27.37 dB (PORP), 45.83 dB (TORP), 29.99 dB (SCC) and 39.15 dB (LCC) groups. The gap of air and bone conduction (ABG) at 2 months post-operative stage were 19.05 dB (PORP), 20 dB (TORP), 20.32 dB (SCC) and 39.15 dB (LCC) groups and not much changed after 3 years. Extrusion occurred in three PORPs and four TORPs at 4–8 years after surgery. Four cases were lost to follow up. No extrusion occurred in cartilage ossiculoplasty. Trans-canal endoscopic autologous cartilage ossiculoplasty shows encouraging results comparable to titanium prosthesis in repairing ossicles in cholesteatoma disease.
https://ift.tt/2SuJM2j
Submental Ectopic Thyroid Cyst: An Atypical Presentation
Abstract
It is very unusual of an ectopic thyroid to be presented as a submental swelling, clinically mimicking a submental cyst. Suspicious of the disease with complete clinical, biochemical and radiological correlation is the mainstay of diagnosis as the first FNAC is not confirmatory of the ectopic thyroid especially in cases of dysgenesis of thyroid tissue in an unusual location. Here we have presented a rare case of an ectopic thyroid gland presented with a submental swelling successfully managed with the conservative treatment.
https://ift.tt/2zfZ3Ls
The role of long‐wavelength ultraviolet A1 (UVA1) in acral vitiligo
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2PuefPv
Combinatorial application of dissolving microneedle patch and cream for improvement of skin wrinkles, dermal density, elasticity, and hydration
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2RmsHGw
Differin® and depilation, a word of warning
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2PsEc1W
The role of long‐wavelength ultraviolet A1 (UVA1) in acral vitiligo
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2PuefPv
Combinatorial application of dissolving microneedle patch and cream for improvement of skin wrinkles, dermal density, elasticity, and hydration
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2RmsHGw
Differin® and depilation, a word of warning
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2PsEc1W
The Association Between Metabolic Syndrome and Serum Concentrations of Micronutrients, Inflammation, and Oxidative Stress Outside of the Clinical Reference Ranges: A Cross-Sectional Study
Metabolic Syndrome and Related Disorders, Ahead of Print.
https://ift.tt/2SuIiFm
Cosmetics, Vol. 5, Pages 63: Nanoemulsions as a Form of Perfumery Products
Cosmetics, Vol. 5, Pages 63: Nanoemulsions as a Form of Perfumery Products
Cosmetics doi: 10.3390/cosmetics5040063
Authors: Elzbieta Sikora Miastkowska Małgorzata Katarzyna Wolinska Kennard Elwira Lason
Alcohol-based perfumes, e.g., eau de parfum, eau de toilette, eau de cologne or au fraiche, are the most common type of fragrance products available on the market. There are also alcohol-free fragrance products, mainly in the form of solid or oil perfume. From the consumers’ point of view, such perfumery products are of interest; therefore, looking for new solutions is still interesting. Nanoemulsions are liquid, kinetically stable colloidal dispersions, consisting of an aqueous phase, an oil phase and a surfactant, with or without a co-surfactant. They are transparent, not greasy, easy to spray and spread. Additionally, they show capacity to protect fragrances from oxidation. The development of a water-based perfumes in the form of stable nanoemulsions containing fragrance compositions (in the range of 5–15%), stabilized by nonionic surfactants, allows to create safe products for a wider group of consumers, including children, adolescents and people with sensitive skin. In this article, an application of nanoemulsions as a potential form of perfumery products were described.
https://ift.tt/2SuRARO
MicroRNA-146b-3p Promotes Cell Metastasis by Directly Targeting NF2 in Human Papillary Thyroid Cancer
Thyroid, Ahead of Print.
https://ift.tt/2AAtiiq
Homeostasis in Topical Photoprotection: Getting the Spectral Balance Right
Abstract
The solar radiation range has harmful and beneficial effects. Sunscreens, which selectively block specific spectral regions, may potentially interfere with skin homeostasis. For instance, the ultraviolet (UV) B waveband produces erythema and DNA damage; simultaneously, it induces pre-vitamin D3 synthesis. UVA1 and visible light can both induce pigmentation in skin phototypes IV–VI, and act in synergy to induce erythema and persistent pigment darkening. In contrast, UVA may contribute to blood pressure control and cardioprotection by inducing release of nitric oxide from intracutaneous photolabile nitric oxide derivatives. Finally, infrared A radiation alters the collagen equilibrium of the dermal extracellular matrix but is involved in the regulation of body temperature and in nitric oxide release, with a potential beneficial impact on blood pressure regulation. Ideally, photoprotection should thus be performed with a neutral density filter, mitigating all radiation ranges homogeneously, to maintain solar spectrum homeostasis. Natural compounds such as mycosporine-like amino acids are promising natural UV radiation-filtering compounds for an improved homeostasis with our environment. Lastly, we should not forget individual characteristics and behavior, as homeostasis differs according to individual phototypes and skin exposure behaviors.
https://ift.tt/2yG1NlX
Unusual Clinical Presentations of Malignant Melanoma: A Review of Clinical and Histologic Features with Special Emphasis on Dermatoscopic Findings
Abstract
This review presents the main challenges encountered when diagnosing unusual variants of malignant melanoma with the aim of raising awareness to allow application of the most appropriate treatment strategies. Although these melanomas are often rare, their misdiagnosis potentially jeopardizes patients' health and survival, and has medicolegal implications. The clinical and histologic presentations of melanoma vary greatly, and assessment of uncommon melanomas can be difficult for practitioners because of their scarcity and resemblance to other dermatologic entities. The most problematic melanoma types are desmoplastic melanoma, polypoid melanoma, primary dermal melanoma, verrucous malignant melanoma, pigmented epithelioid melanocytoma, mucosal melanoma, follicular melanoma and melanoma with non-melanocytic differentiation. The two most difficult-to-diagnose subtypes of melanoma are the nevoid and the amelanotic melanomas. Some specific attributes of these variants can be more easily recognized with digital dermatoscopy, facilitating early detection and possibly avoiding invasive procedures. Key cases with the most notable clinical, dermatoscopic, and histopathologic features are presented, highlighting the practical issues of making an accurate diagnosis and choosing the best therapy.
https://ift.tt/2yFSiDr
Sentinel Lymph Node Biopsy: Past and Present Implications for the Management of Cutaneous Melanoma with Nodal Metastasis
Abstract
Although significant progress has been made in the understanding of melanoma pathophysiology and therapy, patients with metastatic melanoma still have a poor prognosis. The management of regional nodes remains a matter of debate. By replacing elective lymph node dissection, sentinel lymph node biopsy has revolutionized the treatment of malignant melanoma. In this paper, the history of the procedure is traced, and the indication for completion lymphadenectomy after positive sentinel node biopsy is discussed in light of the recent studies that addressed this issue. The role of adjuvant therapies in the management of patients with stage III melanoma is also discussed.
https://ift.tt/2OegFNy
Noninvasive Imaging Tools in the Diagnosis and Treatment of Skin Cancers
Abstract
In the 1980s, the increasing incidence of skin cancers prompted the development of noninvasive medical devices to improve skin cancer diagnosis in daily dermatology practice. As a result of the development of these noninvasive techniques, diagnosis is now established earlier and with better accuracy. These advances are of great benefit to high-risk patients, who previously would have had to undergo several excisions. In this review, we focus on the classic technique of dermoscopy and the more recent digital version, as well as on advanced noninvasive imaging techniques, such as reflectance confocal microscopy and optical coherence tomography. On the basis of their specific features, these noninvasive medical devices can be used not only to diagnose and monitor melanoma and nonmelanoma skin cancers but also to choose the best therapy and follow the patient's response to treatment in vivo.
https://ift.tt/2yGSO4d
Toxic Side Effects of Targeted Therapies and Immunotherapies Affecting the Skin, Oral Mucosa, Hair, and Nails
Abstract
Targeted therapies and immunotherapies are associated with a wide range of dermatologic adverse events (dAEs) resulting from common signaling pathways involved in malignant behavior and normal homeostatic functions of the epidermis and dermis. Dermatologic toxicities include damage to the skin, oral mucosa, hair, and nails. Acneiform rash is the most common dAE, observed in 25–85% of patients treated by epidermal growth factor receptor and mitogen-activated protein kinase kinase inhibitors. BRAF inhibitors mostly induce secondary skin tumors, squamous cell carcinoma and keratoacanthomas, changes in pre-existing pigmented lesions, as well as hand-foot skin reactions and maculopapular hypersensitivity-like rash. Immune checkpoint inhibitors (ICIs) most frequently induce nonspecific maculopapular rash, but also eczema-like or psoriatic lesions, lichenoid dermatitis, xerosis, and pruritus. Of the oral mucosal toxicities observed with targeted therapies, oral mucositis is the most frequent with mammalian target of rapamycin (mTOR) inhibitors, followed by stomatitis associated to multikinase angiogenesis and HER inhibitors, geographic tongue, oral hyperkeratotic lesions, lichenoid reactions, and hyperpigmentation. ICIs typically induce oral lichenoid reactions and xerostomia. Targeted therapies and endocrine therapy also commonly induce alopecia, although this is still underreported with the latter. Finally, targeted therapies may damage nail folds, with paronychia and periungual pyogenic granuloma distinct from chemotherapy-induced lesions. Mild onycholysis, brittle nails, and a slower nail growth rate may also be observed. Targeted therapies and immunotherapies often profoundly diminish patients' quality of life, which impacts treatment outcomes. Close collaboration between dermatologists and oncologists is therefore essential.
https://ift.tt/2OemeLK
Genomic Profiling of Parathyroid Carcinoma Reveals Genomic Alterations Suggesting Benefit from Therapy
AbstractBackground.Parathyroid carcinoma (PC) is a rare endocrine malignancy that can cause life‐threatening hypercalcemia. We queried whether comprehensive genomic profiling (CGP) of PC might identify genomic alterations (GAs), which would suggest benefit from rationally matched therapeutics.Methods.We performed hybrid‐capture‐based CGP to identify GAs and tumor mutational burden (TMB) in tumors from patients with this malignancy.Results.There were 85 total GAs in 16 cases (5.3 GAs per case), and the median TMB was 1.7 mutations per megabase (m/Mb), with three cases having >20 m/Mb (18.7%). The genes most frequently harboring GA were CDC73 (38%), TP53 (38%), and MEN1 (31%). All MEN1‐mutated cases also had loss of heterozygosity at that locus, but in contrast all CDC73‐mutated cases retained heterozygosity. GAs suggesting potential benefit from matched targeted therapy were identified in 11 patients (69%) and most frequently found in PTEN (25%), NF1 (12.5%), KDR (12.5%), PIK3CA (12.5%), and TSC2 (12.5%). A patient whose tumor harbored KDR T668 K and who was treated with cabozantinib experienced a > 50% drop in parathyroid hormone level and radiographic partial response of 5.4 months with duration limited by toxicity.Conclusion.CGP identified GAs in PC that suggest benefit from targeted therapy, as supported by an index case of response to a matched tyrosine kinase inhibitor. Moreover, the unexpectedly high frequency of high TMB (>20 m/Mb) suggests a subset of PC may benefit from immune checkpoint inhibitors.Implications for Practice.Parathyroid carcinoma (PC) is a rare endocrine malignancy that can cause life‐threatening hypercalcemia. However, its molecular characteristics remain unclear, with few systemic therapeutic options available for this tumor. Hybrid‐capture‐based comprehensive genomic profiling of 16 primary cancers demonstrated presence of potentially actionable genomic alterations, including PTEN, NF1, KDR, PIK3CA, and TSC2, and a subset of hypermutated cancers with more than 20 mutations per megabase, the latter of which could benefit from immune checkpoint inhibitor therapy. A case benefiting from rationally matched targeted therapy for activating KDR mutation is also presented. These findings should be further investigated for their therapeutic potential.
https://ift.tt/2Jouxnv
Enrichment of HER2 Amplification in Brain Metastases from Primary Gastrointestinal Malignancies
AbstractBackground.In nongastric gastrointestinal (GI) cancers, HER2‐positive (HER2+) disease is not common. In breast cancer, HER2 status is associated with increased risk of brain metastases and response to HER2‐targeted therapy. The purpose of this project was to compare HER2 status in GI cancer brain metastases versus matched prior sites of disease in order to determine if HER2+ disease is more common intracranially.Materials and Methods.We identified 28 patients with GI cancer who had craniotomy for brain metastases between 1999 and 2017 with intracranial metastatic tissue available at Massachusetts General Hospital. Twenty‐four patients also had tissue from a prior site of disease. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) for HER2 were performed on all samples. A tumor was defined as HER2+ if it had 3+ staining by IHC or amplification by FISH.Results.A prior site of disease (including intracranial metastases) was HER2+ for 13% of evaluable patients: 3 of 11 patients with colorectal cancer and no patients with esophageal or pancreatic cancer. The most recent brain metastases were HER2+ for 32% of patients: 2 of 3 esophageal squamous cell carcinomas, 3 of 10 esophageal adenocarcinomas (ACs), 3 of 14 colorectal ACs, and 1 of 1 pancreatic AC. Only 37.5% of patients with HER2+ brain metastasis had concordant HER2+ prior tissue (κ = 0.38, p = .017).Conclusion.In this cohort of patients with GI cancer with brain metastases, HER2+ status was more common intracranially compared with prior sites of disease. These findings suggest that testing HER2 in patients with GI cancer with brain metastases may lead to additional therapeutic options, regardless of HER2 status in previously examined tissue.Implications for Practice.HER2 amplification is a well‐known driver of oncogenesis in breast cancer, with associated increased risk of brain metastases and response to HER2‐directed therapy. In nongastric gastrointestinal (GI) cancers, HER2 amplification is not common and consequently is infrequently tested. The current study shows that brain metastases in patients with GI primary malignancies have a relatively high likelihood of being HER2 positive despite HER2 amplification or overexpression being less commonly found in matched tissue from prior sites of disease. This suggests that regardless of prior molecular testing, patients with GI cancer with brain metastases who have tissue available are likely to benefit from HER2 assessment to identify potential novel therapeutic options.
https://ift.tt/2DdKkp9
Influence of ambient air pressure changes on vestibular symptoms after stapes surgery
To examine if vestibular irritation after stapes surgery may be provoked by pressure changes across the tympanic membrane, which consecutively results in displacements of the ossicular chain and the piston prosthesis suspended to it.
https://ift.tt/2COVoYs
Adrenal Incidentaloma: Picking out the High-Risk Patients
Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0713-0598
Patients with adrenal incidentalomas and autonomous cortisol secretion (ACS) have been recognized as a category at risk of developing cardiovascular and metabolic co-morbidities. Considering the increasing number of patients affected by this condition, it is important to perform an accurate subtyping of the patients, in the light of a tailored treatment. This review aims to identify the phenotypic characteristics of patients with adrenal incidentalomas and ACS who are at risk of developing severe cortisol-related co-morbidities. ACS has been associated with severe alteration of the cardiovascular profile, including hypertension, diabetes, and atherosclerosis. Moreover, ACS has been identified as a contributing factor to the development of cardiovascular events and related mortality. Patients with ACS are also at risk of incident bone fractures, which occur in half of the patients independently of the bone mass density, and infectious diseases. Severity and persistence of hypercortisolism are among the main contributing factors for cardiovascular diseases and bone fractures. Moreover, progression of hypercortisolism over time and altered circadian cortisol rhythm seem to be important additional factors. The role of potential novel biomarkers is also discussed in this review.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2qhlegr
Polycystic Ovary Syndrome is Associated with Elevated Periostin Levels
Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0752-0061
Purpose Periostin is a secreted extracellular matrix protein that is strongly associated with triglyceride metabolism, chronic inflammation, and insulin resistance. Growing evidence suggests that there is a link between periostin and ovarian function. Our aim was to ascertain whether circulating periostin levels are altered in women with polycystic ovary syndrome (PCOS) and to further explore the relationship between periostin and glucose metabolism disorder in PCOS patients. Methods In total, 50 women with PCOS and 30 age-matched controls without PCOS were recruited for this cross-sectional study. Periostin levels were measured using ELISA as well. Results Circulating periostin levels were significantly elevated in PCOS women compared with controls [4206.75(222.00, 4815.25) vs. 430.75(142. 13, 730.86) ng/ml, P=0. 005]. Spearman's correlation analysis showed that serum periostin levels had a positive correlation with body mass index (BMI), uric acid, homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitive C reactive protein (hs-CRP), and a negative correlation with insulin sensitivity index (ISI). Logistic regression models revealed that PCOS was correlated with waist to hip ratio (WHR), fasting blood glucose (FBG), and periostin levels. In addition, multivariate linear regression analyses showed that FBG, HOMA-IR, and the lipid accumulation index (LAP) were independent factors influencing serum periostin levels. Conclusion PCOS is associated with elevated levels of periostin.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2CNc9U6
Impact of community respiratory viral infections in urban children with asthma
Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on asthmatic children in the community, particularly in the high-risk urban environment, is less well-defined.
https://ift.tt/2Q8TJ49
Gray matter differences associated with age and sex hormone levels between premenopausal and perimenopausal women, a voxel‐based morphometry study
Journal of Neuroendocrinology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yEgWUW
Introduction: Special Issue—The Origins of Macrophages and Their Roles Beyond Immunology
In the context of ontogeny and phylogeny, macrophages emerge much earlier than other hematopoietic cells, including monocytes, implying that their roles extend beyond immunology. Phagocytosis, a representative function of macrophages, has been examined since the late 19th century and such studies were the basis of characterizing innate immunity. Macrophages also make a range of cytokines important in both innate and adaptive immunity. Recently, their non-immunological homeostatic roles in organ development, angiogenesis, tissue repair/regeneration and metabolism have also become clear. This involvement in so many responses in virtually all tissues requires them to be enormously flexible but their phenotypic and functional heterogeneity have made it difficult to delineate the origins of macrophages in specific sites under different circumstances.
https://ift.tt/2yHFSe8
https://ift.tt/2yHFSe8
Myositis ossificans traumatica of the masticatory muscles: etiology, diagnosis and treatment
Abstract
Background
Myositis ossificans describes a heterotopic bone formation within a muscle. Thereby myositis ossificans is classified in two different groups: myositis ossificans progressiva (MOP) which describes a genetic autosomal dominant rare disease and myositis ossificans traumatica (MOT). The exact pathogenesis of MOT is unclear. The aim of this article was to analyse and interpret the existing literature reporting MOT of masticatory muscles and compare the results with our own clinical experience with MOT. Risk-factors, etiology, clinical features, diagnostic imaging, as well as different treatment options were evaluated and recommendations for the prevention, diagnosis, and therapy of MOT of the masticatory muscles were given.
Methods
Following the PRISMA-Guidelines, a systematic search within the PubMed/Medline database with a view to record literature of MOT of the masticatory muscles was performed. Furthermore, the database of our own clinic was screened for cases of MOT.
Results
In total, 63 cases of MOT of the masticatory muscles which were reported in English-based literature were included in this study. Overall, 25 female and 37 male patients could be analysed whereas one patient's gender was unknown. Complication of wisdom-tooth infection (n = 3) as well as the results of dental procedures like dental extraction (n = 7), mandibular nerve block (n = 4), periodontitis therapy (n = 1) were reported as MOT cases. From the 15 reported cases that appeared after dental treatment like extraction or local anesthesia the medial pterygoid (n = 10) was the most affected muscle. Hereof, females were more affected (n = 9) than males (n = 6). The most reported clinical symptom of MOT was trismus (n = 54), followed by swelling (n = 17) and pain (n = 13). One clinical case provided by the authors was detected.
Conclusions
Dental procedures, such as local anesthesia or extractions, may cause MOT of the masticatory musculature. Demographical analyses demonstrate that females have a higher risk of developing MOT with respect to dental treatment. The most important treatment option is surgical excision. Subsequent physical therapy can have beneficial effects. Nevertheless, a benefit of interpositional materials and drugs as therapy of MOT of the masticatory muscles has not yet been proven. Myositis ossificans progressiva has to be excluded.
https://ift.tt/2JpMyla
Tape stripping alters the microbe‐host correlations in mouse skin
Allergy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2ETviGv
Fractionated stereotactic radiation therapy for adrenal metastases: contributing to local tumor control with low toxicity
Abstract
Purpose
To report on the Erlangen (UK-Er) experience with linear accelerator stereotactic body radiation therapy (LINAC SBRT) for adrenal metastasis from various primary tumors.
Materials and methods
33 patients were treated. Primary sites included lung (n = 19), melanoma (n = 8), colorectal (n = 2), hepatocellular (n = 1), esophageal (n = 2), and breast cancer (n = 1). 14 patients were treated palliatively, 19 patients were treated with local curative intent.
Radiation treatment
Treatment planning was done based on an exhale, mid-ventilation, and inspiration CT series. Further planning CTs were done to check for the correctness of the breathing pattern. Irradiation was performed using a NOVALIS (Varian, Palo Alto, CA, USA; Brainlab AG, München, Germany) linear accelerator. The isocenter was verified before each treatment session using the BrainLab ExacTrac® (Brainlab AG, München, Germany) system to minimize setup errors. Dose was prescribed to the planning target volume (PTV) surrounding 90% isodose.
Follow-up
Depending on their overall performance status and prognosis, patients received clinical check-ups and radiological imaging. Median follow-up was 11 months.
Statistical analysis
IBM SPSS v. 24 was used for univariate analysis using Kaplan–Meier curves, nonparametric Kruskal–Wallis test, and the chi-square test for frequency distributions. Toxicity was graded according to NCI CTCAE v4.0. Depending on radiologic imaging, patients were classified as stable, regression, and progression.
Results
Median survival was 11 months, median PFS was 5 months. Median local failure-free survival was 21 months. Patients who were treated with curative intent showed a better survival curve (p < 0.0001) and PFS (p = 0.004). BED ranged from 42 to 108.8 Gy, median BED was 67.2 Gy. Three BED groups were formed. Overall survival curves differed significantly (p = 0.046), favoring the high-dose group. 21 patients were free from any adverse events or discomfort. In 7 cases, a grade I toxicity was noted.
https://ift.tt/2Jn75XR
Developing combination strategies using PD-1 checkpoint inhibitors to treat cancer
Abstract
More than 3000 clinical trials are evaluating the clinical activity of the PD-1 checkpoint inhibitors as monotherapies and in combinations with other cancer therapies [1]. The PD-1 checkpoint inhibitors are remarkable for their clinical activities in shrinking tumors across a wide range of tumor types, in causing durable responses, and in their tolerability. These attributes position them as favorable agents in clinical combinations. Historically, approaches to cancer therapy combinations focused on agents with orthogonal activities to avoid shared resistance mechanisms and shared toxicities. Although CTLA-4/PD-1 combinations have progressed based on possible immune interactions, additional approaches have used more orthogonal treatments such as standard of care chemotherapies and anti-angiogenesis inhibitors. Using the concept of independent activity pioneered by Bliss [2], examples of these approaches were compared. Both standard of care chemotherapy and anti-angiogenesis combinations show promising clinical activity above that predicted by the independent contributions of the agents tested on their own. In contrast, the combinations of CTLA4/PD-1 checkpoint inhibitors in renal cancer and melanoma show no more activity than that predicted by the independent contributions of the monotherapies. This update on approaches to the development of clinical combination therapies highlights the potential importance of combining PD-1 checkpoint inhibitors with a broad range of clinically active partners.
https://ift.tt/2PZ3gu9
Rising to the challenges of precision medicine: nasal inflammation research in China
International Forum of Allergy &Rhinology, EarlyView.
https://ift.tt/2Oec0v4
Seventeen New Cases of Chronic Ulcerative Stomatitis with Literature Review
Abstract
Chronic ulcerative stomatitis (CUS) is a poorly understood disease with clinical and histologic overlap with lichen planus (LP). Unlike classic LP, direct immunofluorescence (DIF) studies in cases of CUS exhibit a granular pattern of IgG in nuclei of basal and parabasal cells. This study assesses the demographic, clinical, histologic, and DIF features of CUS. It is important to differentiate CUS from LP and other vesiculobullous diseases (VBD) because lesions of CUS are resistant to steroid therapy, which is typically used to control LP and VBD. A literature review and IRB-approved retrospective search of CUS was performed within the archives of the University of Florida (UF) Oral Pathology Biopsy Service from 2007 to 2017. Fifty-two cases were identified from the literature and seventeen new cases were identified in our series. All UF patients were female and the median age was 64-years. The majority of patients were Caucasian and the most common location was buccal mucosa. Frequent clinical presentations were pain, erythema, leukoplakia, and ulcerations. Histologic features included epithelial separation, atrophic epithelium, and a chronic inflammatory infiltrate. All cases were confirmed with DIF testing that showed a speckled pattern of IgG staining in basal and parabasal cell nuclei. Fibrinogen was present in eleven cases and two cases were positive for C3. The results of our series are in accordance with the literature. Since CUS has overlapping features with LP and VBD, clinicians and pathologists should consider this entity and confirm diagnosis with DIF testing when recalcitrant oral ulcerative diseases are encountered.
https://ift.tt/2qgN5gR
Seventeen New Cases of Chronic Ulcerative Stomatitis with Literature Review
Abstract
Chronic ulcerative stomatitis (CUS) is a poorly understood disease with clinical and histologic overlap with lichen planus (LP). Unlike classic LP, direct immunofluorescence (DIF) studies in cases of CUS exhibit a granular pattern of IgG in nuclei of basal and parabasal cells. This study assesses the demographic, clinical, histologic, and DIF features of CUS. It is important to differentiate CUS from LP and other vesiculobullous diseases (VBD) because lesions of CUS are resistant to steroid therapy, which is typically used to control LP and VBD. A literature review and IRB-approved retrospective search of CUS was performed within the archives of the University of Florida (UF) Oral Pathology Biopsy Service from 2007 to 2017. Fifty-two cases were identified from the literature and seventeen new cases were identified in our series. All UF patients were female and the median age was 64-years. The majority of patients were Caucasian and the most common location was buccal mucosa. Frequent clinical presentations were pain, erythema, leukoplakia, and ulcerations. Histologic features included epithelial separation, atrophic epithelium, and a chronic inflammatory infiltrate. All cases were confirmed with DIF testing that showed a speckled pattern of IgG staining in basal and parabasal cell nuclei. Fibrinogen was present in eleven cases and two cases were positive for C3. The results of our series are in accordance with the literature. Since CUS has overlapping features with LP and VBD, clinicians and pathologists should consider this entity and confirm diagnosis with DIF testing when recalcitrant oral ulcerative diseases are encountered.
https://ift.tt/2qgN5gR
TERT promoter mutational screening as a tool to predict malignant behaviour in follicular thyroid tumours—three examples from the clinical routine
Abstract
Follicular thyroid adenomas (FTAs) and carcinomas (FTCs), collectively the most common thyroid neoplasms, constitute a significant clinical challenge since histological evidence of invasive behaviour is required for a malignant diagnosis. Small subsets of FTAs relapse as manifest malignant FTCs, indicating that histology is not always adequate to predict malignant potential. Lately, recurrent mutations in the promoter of the Telomerase reverse transcriptase (TERT) gene have been coupled to FTCs, whereas FTAs usually lack this aberrancy. We describe three patients with follicular thyroid tumours in which TERT promoter mutational screening was employed as part of the clinical work-up to pinpoint malignant potential. In two retrospective analyses of seemingly benign lesions, the detected mutations predicted future skeletal metastases, and in one prospective case, the mutational screening led to a different clinical management of the afflicted patient. We therefore consider TERT promoter mutational screening an adjunct tool of value in equivocal cases.
https://ift.tt/2qfBdvh
Carbonic anhydrases II, IX, and XII in Barrett’s esophagus and adenocarcinoma
Abstract
The aim of our retrospective study was to investigate the expression and clinical significance of the cancer-associated carbonic anhydrases (CAs) II, IX, and XII in Barrett's esophagus and esophageal adenocarcinoma (EAC). We evaluated 101 archival specimens from patients with EAC as well as seven and 26 samples from patients with high-and low-grade dysplasia, respectively. In addition, normal esophageal squamous epithelium, gastric, and intestinal metaplasia were analyzed when present. The expression patterns of isozymes were detected by immunohistochemistry. CAII and CIX expression levels were lower in the squamous epithelium than in the columnar cells while CAXII showed an opposite pattern and was present mainly in squamous epithelium. Expression patterns in benign, dysplastic, or malignant esophageal columnar lesions were not significantly different. The assessment of clinicopathological associations showed that CAII was significantly downregulated in metastatic disease (p = 0.026). CAIX showed no association with prognosis, although there appeared to be an association (p = 0.056) between high expression and nodal spread. In conclusion, CAII, CAIX, and CAXII do not serve as biomarkers for different phases in the development of EAC.
https://ift.tt/2Q3WJyD
A study of neurite orientation dispersion and density imaging in ischemic stroke
Publication date: Available online 29 October 2018
Source: Magnetic Resonance Imaging
Author(s): Zhenxiong Wang, Shun Zhang, Chengxia Liu, Yihao Yao, Jingjing Shi, Ju Zhang, Yuanyuan Qin, Wenzhen Zhu
Abstract
Objectives
To demonstrate the feasibility of the neurite orientation dispersion and density imaging (NODDI) technique in characterizing the microstructural changes in brain tissues during ischemic stroke and to compare its sensitivity with diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI).
Methods
Seventy-one patients with hyperacute/acute/subacute ischemic stroke were enrolled in the study. A multishell diffusion magnetic resonance imaging (dMRI) protocol was performed for each subject. Diffusion data were analyzed using the NODDI and diffusional kurtosis estimator toolboxes. Then, NODDI metrics between the lesions and the contralateral tissues were compared to evaluate their values in ischemic stroke. NODDI metrics among different stroke periods and the correlations between NODDI and the duration since stroke onset were analyzed as well. To compare the NODDI's sensitivity with established diffusion techniques, paired t-tests were performed to determine the absolute percentage changes of diffusion metrics between NODDI and DTI/DKI.
Results
Compared with the contralateral tissues, lesions showed significantly increased values of intracellular volume fraction (Vic) and orientation dispersion index (ODI) and decreased values of isotropic volume fraction (Viso). ODI value was significantly different among three periods and showed fair to good positive correlation with the duration since stroke onset (R = 0.450). NODDI metrics showed significantly larger absolute percentage changes than that of DTI and DKI (P < 0.05, respectively).
Conclusion
NODDI allowed efficient evaluation of microstructural changes in brain tissues during ischemic stroke and showed increased sensitivity compared with DTI and DKI. The possible biophysical mechanisms underlying ischemia could be further elucidated using this advanced diffusion technique.
https://ift.tt/2SpZKeh
Gellan gum-based gels with tunable relaxation properties for MRI phantoms
Publication date: Available online 28 October 2018
Source: Magnetic Resonance Imaging
Author(s): Pawel Brzozowski, Kalin I. Penev, Francisco M. Martinez, Timothy J. Scholl, Kibret Mequanint
Abstract
Object
The research follows the analysis of gellan gum-based gels as novel MRI phantom material with the implementation of a design of experiments model to obtain tunable relaxation properties.
Materials and methods
Gellan gum gels doped with newly synthesized superparamagnetic iron oxide nanoparticles (SPIONs) and either MnCl2 or GdCl3 were prepared and scanned from 230 μT to 3 T. Nineteen gel samples were formulated with varying concentrations of contrast agents to determine the linear, quadratic, and interactive effects of the contrast agents by a central composite design of experiment. To inhibit microbial growth in the gels and to enable long-term use, methyl 4‑hydroxybenzoate (methylparaben) was utilized.
Results
The model containing SPIONs and metal salts relaxivity was analyzed with ANOVA, and the resulting significant coefficients were tabulated. The mathematical model was able to accurately predict the intended relaxation property from the concentration of the contrast agent with adjusted R2 values > 0.97 for longitudinal (R1) relaxation rates and 0.87 for transverse (R2) relaxation rates.
Conclusion
The gel material maintained physical, chemical, and biological stability for at least four months and contained controllable relaxation properties while maintaining optical clarity.
https://ift.tt/2zb5YWh
Targeting cytokines to treat autoinflammatory diseases
Publication date: Available online 28 October 2018
Source: Clinical Immunology
Author(s): Jonathan S. Hausmann
Abstract
Autoinflammatory diseases are rare group conditions manifested by recurrent fevers, systemic inflammation, and dysfunctions of the innate immune system. These conditions are characterized by overproduction or lack of inhibition of various cytokines, and the advent of biologic drugs that block specific cytokines involved in these conditions have revolutionized their treatment. In this review, I will discuss the most common autoinflammatory conditions of adulthood including Familial Mediterranean Fever, cryopyrin-associated periodic syndrome, mevalonate kinase deficiency/hyperimmunoglobulinemia D Syndrome, TNF receptor-associated autoinflammatory syndrome, and systemic juvenile idiopathic arthritis/adult-onset Still's disease. I will discuss how IL-1, IL-6, IL-18, and TNF play pathogenic roles in these conditions and will review the evidence behind cytokine blockade for these diseases. Throughout the paper, I will reflect on gaps in knowledge of autoinflammatory diseases and will highlight the latest advances and newest drugs in development.
https://ift.tt/2CMTt6S
Gastric outlet obstruction secondary to orbera intragastric balloon
Abstract
Intragastric balloons are used as a temporary restrictive method in obesity to induce weight loss. They are typically recommended when patients have mild obesity and have failed traditional first line treatments of diet, exercise and behaviour modification. We report a case of a 45-year-old female who presented with nausea, vomiting and abdominal pain two weeks following an uncomplicated insertion of an intragastric balloon. Following investigation, she was found to have a gastric outlet obstruction which required endoscopic removal of the balloon. While a rare occurrence, gastric outlet obstruction as seen in this case, highlights the importance of early recognition in order to proceed with swift diagnosis and intervention in order to prevent significant morbidity such as ischaemia and perforation.https://ift.tt/2zbLpt0
Oesophageal adenocarcinoma following gastric band surgery in two patients
Abstract
Oesophageal adenocarcinoma following gastric band surgery has only been reported three times previously. The incidence is higher in morbidly obese patients, and its pathogenesis is correlated to reflux-induced microenvironmental changes. Bariatric surgery is transformative and its potential benefit for a substantial population is huge. Although no causal relationship with bariatric procedures has been evidenced to date, symptoms of adenocarcinoma—particularly anorexia, weight loss and dysphagia—can easily be overshadowed by alterations in eating patterns associated with weight-loss procedures. We report two cases of oesophageal adenocarcinoma in patients who had undergone a gastric banding procedure, and invite readers to consider the role that pre- and post-operative acid reflux dynamics may have precipitating neoplastic disease, and how endoscopic surveillance may play a role in prevention.https://ift.tt/2StlJkc
Surgical management of a giant right atrial myxoma
Abstract
Cardiac tumours represent around 0.2% of tumours overall, and primary cardiac tumours are even more uncommon. We report the case of a 72-year-old female with a 7 cm × 4 cm right atrial mass which was prolapsing through the tricuspid valve. The mass was resected and histological analysis confirmed a myxoma. This report describes a rare finding of a giant right atrial mxyoma and subsequent surgical management.https://ift.tt/2zaE5xG
Tulip piercing the aorta: a rare case of IVC filter aortic perforation and obstruction
ABSTRACT
Prolonged implantation of inferior vena cava (IVC) filters can lead to significant morbidity. We present a 25-year-old man with antiphospholipid syndrome, lower extremity deep vein thrombosis, and subsequent Gunther-Tulip IVC filter placement. More than 10 years following IVC filter placement he developed progressive abdominal and back pains. Cross-sectional angiography revealed that he had a chronic IVC occlusion, and IVC filter limb extensions into the infrarenal aorta, lumbar spine, and right psoas muscle. The IVC filter limb protruding into the aorta had also pierced through the backwall to lead to partial lumen thrombosis and obstruction. The patient underwent a transabdominal exposure of the infrarenal IVC and aorta, filter explantation and aortic patch angioplasty repair. This case highlights the severity of aortic injury from a protruding IVC filter limb that necessitated open aortic repair. Improved selection, monitoring and retrieval stewardship of IVC filters can help reduce the risk of unintended aortic complications.https://ift.tt/2SsXRxd
Hemothorax after emphysematous bullectomy using a linear staple device with bioabsorbable polyglycolic acid felt
Abstract
A linear stapler with bioabsorbable polyglycolic acid felt is widely used during the resection of emphysematous lung. Currently, an improved staple device with polyglycolic acid felt is being used owing to a history of complications, such as bleeding, that was associated with the previous model. Here, we report a case of a 69-year-old man who presented to our department for treatment of left lower lobe lung cancer using the new staple device. A left lower lobectomy and emphysematous bullectomy were performed. Reoperation was performed following the diagnosis of a postoperative hemothorax. During that operation, a staple with reinforcing material was found to be in contact with the proliferating vessels on the lung surface, resulting in an active bleed. The vessel was cauterized, and the bleeding stopped. This is the first case study to report bleeding associated with the improved staple device.https://ift.tt/2zdbwzT
A left ventricular assist device for a patient with peripartum cardiomyopathy
Abstract
Since its introduction in Japan in 1980, the extracorporeal left ventricular assist device has been used as a bridge to the recovery of cardiac function or to heart transplantation by many institutions. In this case report, we describe a 23-year-old female with peripartum cardiomyopathy. She had a persistently low cardiac index despite intensive care with intravenous inotropes, intra-aortic balloon pumping and extracorporeal membrane oxygenation; thus, we implanted an extracorporeal left ventricular assist device. Thereafter, her cardiac function gradually improved; the device was removed 2 months after the implantation. She currently has good heart function.https://ift.tt/2Svxab4
Endo GIA stapler malfunction in a small bowel loop resection
Abstract
Endovascular gastrointestinal anastomosis (Endo-GIA) staplers are widely used in various surgical procedures despite difficulties in operating them and associated mechanical failures. We present a case of a patient whose post-operative recovery was complicated by intraoperative Endo-GIA stapler failure, which is rarely reported in literature. Our report describes the behavior and consequences of surgical stapler failure so surgeons can anticipate challenges of newer surgical devices while maintaining optimal patient outcomes.https://ift.tt/2zbLbCa
Primitive synovial sarcoma of suboccipital region in child
Abstract
Synovial sarcoma (SS) most commonly affects the lower limbs of males in the third to fifth decades of life, with masses of the head and neck accounting for 3–10% of all cases, mainly as a metastatic lesion. The lack of specific symptoms and radiological features in addition to the diversity of their microscopic aspects may cause confusion in the diagnosis; hence, knowledge of the unusual locations of SSs is very important. The immunohistochemistry, and more recently the cytogenetic studies, contribute to the differential diagnosis. We report the case of a 12-year-old girl with a rare primary SS in the suboccipital region, which underwent complete surgical resection.https://ift.tt/2SqGnBD
Segmental intestinal dilatation associated with ileal gastric heterotopia in a young woman
Abstract
Segmental intestinal dilatation (SID) is a rare gastrointestinal disorder characterized by marked bowel dilatation and can result in signs of intestinal obstruction, abdominal pain and gastrointestinal bleeding. SID is seen most commonly in pediatric patients, with most cases being reported in neonates and infants. Definitive treatment is resection of the dilated segment of bowel with primary anastomosis. This article describes a rare case of SID in an adult patient—a 26-year-old female who presented with chronic abdominal pain. The patient experienced complete resolution of symptoms following surgical resection.https://ift.tt/2z9AUWX
The impact factor in peril?
Publication date: Available online 28 October 2018
Source: European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): O. Laccourreye, H. Maisonneuve
https://ift.tt/2Pvwx2A
Ethmoid labyrinth: A true sinus? Phylogenetic data
Publication date: Available online 28 October 2018
Source: European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): J.M. Prades, N. Laroche, M. Gavid
https://ift.tt/2RjhAy3
High-dose intraoperative remifentanil infusion increases early postoperative analgesic consumption: a prospective, randomized, double-blind controlled study
Abstract
Purpose
The purpose of this study was to determine whether intraoperative infusion of remifentanil induces acute tolerance to opioids, and compare the postoperative pain and opioid consumption by the effect site concentrations of remifentanil.
Methods
One hundred and ninety-eight patients undergoing gastrectomy were randomly assigned to maintain target effect site concentrations of remifentanil at 0 (Group 1, n = 39), 2 (Group 2, n = 40), 4 (Group 3, n = 39), 8 (Group 4, n = 40), or 12 ng/ml (Group 5, n = 40) during operation. Postoperative pain intensities and fentanyl requirement were recorded at postoperative 2, 6, 24, and 48 h.
Results
Fentanyl requirement for postoperative 2 h was significantly greater in Group 5 compared to Group 1 (376 ± 116 vs. 283 ± 129 µg, P = 0.03). However, there were no differences in fentanyl requirements among the groups after postoperative 2 h. Also, total fentanyl consumption for 48 h was similar in all groups (Group 1; 3106 ± 629, Group 2; 2970 ± 705, Group 3; 3017 ± 555, Group 4; 3151 ± 606, and Group 5; 2984 ± 443 µg, P = 0.717). Pain scores at rest and during deep breathing were comparable in all groups at the time of each examination.
Conclusion
Intraoperative infusion of remifentanil with 12 ng/ml of effect site concentration in patients undergoing gastrectomy increases early postoperative fentanyl requirement. Acute opioid tolerance would be developed by higher concentration of remifentanil than dosage of common anesthetic practice.
https://ift.tt/2Q3Vr6w
An Analysis of Perioperative Outcomes Following Cervical Abscess Drainage in Children Under 2 Years
Publication date: Available online 28 October 2018
Source: International Journal of Pediatric Otorhinolaryngology
Author(s): Jonathan A. Harounian, Vijay A. Patel, Michele M. Carr
Abstract
Objective
To identify risk factors and determine perioperative morbidity of children under 2 years of age undergoing cervical abscess drainage.
Methods
Patients who underwent cervical abscess drainage 1-18 years of age were queried via the ACS- National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database (2012-2015). Analyzed outcomes include length of stay, operative time, readmission/reoperation rate, and postoperative complications.
Results
A total of 2181 children were identified, 858 were <2 (51.5% male) and 1323 were > 2 years (57.1% male) (p=0.011). The younger cohort was found to undergo more lateral approaches for cervical abscess drainage whereas the older cohort was found to undergo more intraoral approaches for pharyngeal abscess drainage (p<0.001), suggesting a difference in abscess location related to age at clinical presentation. The younger cohort was also found to have a higher preoperative white blood cell count (20.7 vs. 17.5, p<0.001) but no significant difference in preoperative fulminant sepsis was observed. Younger children were found to have both a longer wait-time until surgery (1.4 vs. 1.1 days, p=0.003) and a prolonged length of stay (LOS) (4.3 vs. 3.4 days, p<0.001). Operative time was found to be lower in the younger cohort (18.4 vs. 21.5 minutes, p=0.003), Finally, the younger cohort was found to have an increased incidence and duration of postoperative mechanical ventilation (63 vs. 41, and 0.4 vs. 0.1 days, p<0.001.).There were no differences in post-op complications (wound infection, dehiscence, pneumonia, reintubation, and reoperation/readmission). Linear regression for LOS showed that major contributors were operative time, days of postop ventilation, and days from admission to surgery with R=0.700.
Conclusion
Children under 2 years of age have longer LOS that may in part be due to a greater likelihood of postoperative ventilation and a delay in operative intervention, despite having surgical approaches associated with a shorter LOS. They are no more prone to complications than are older children. Recognition of these critical factors plays a role in optimizing perioperative risk assessment and procedural planning within this patient population.
https://ift.tt/2Q302pP
PentoxIfylline and Tocopherol for the Treatment of Post-radiotherapy Fibrosis in Head and Neck Cancer Patients
Condition: Head and Neck Fibrosis
Interventions: Combination Product: Arm B: A combination of pentoxifylline and tocopherol acetate in addition to best standard care [a structured programme of rehabilitation exercises] for 6 months; Procedure: • Arm A: Best standard of care only [a structured programme of rehabilitation exercises] for 6 months
Sponsors: University College, London; National Institute for Health Research, United Kingdom
Not yet recruiting
https://ift.tt/2OSuMx0
Interventions: Combination Product: Arm B: A combination of pentoxifylline and tocopherol acetate in addition to best standard care [a structured programme of rehabilitation exercises] for 6 months; Procedure: • Arm A: Best standard of care only [a structured programme of rehabilitation exercises] for 6 months
Sponsors: University College, London; National Institute for Health Research, United Kingdom
Not yet recruiting
https://ift.tt/2OSuMx0
GP-induced Chemotherapy Combined With IMRT and TPF-induced Chemotherapy Combined With IMRT in the Treatment of Distant Metastatic Nasopharyngeal Carcinoma
Condition: Advanced Nasopharyngeal Carcinoma
Interventions: Drug: GP+IMRT; Drug: TPF+IMRT
Sponsor: Guiyang Medical University
Not yet recruiting
https://ift.tt/2COSAuH
Interventions: Drug: GP+IMRT; Drug: TPF+IMRT
Sponsor: Guiyang Medical University
Not yet recruiting
https://ift.tt/2COSAuH
PentoxIfylline and Tocopherol for the Treatment of Post-radiotherapy Fibrosis in Head and Neck Cancer Patients
Condition: Head and Neck Fibrosis
Interventions: Combination Product: Arm B: A combination of pentoxifylline and tocopherol acetate in addition to best standard care [a structured programme of rehabilitation exercises] for 6 months; Procedure: • Arm A: Best standard of care only [a structured programme of rehabilitation exercises] for 6 months
Sponsors: University College, London; National Institute for Health Research, United Kingdom
Not yet recruiting
https://ift.tt/2OSuMx0
Interventions: Combination Product: Arm B: A combination of pentoxifylline and tocopherol acetate in addition to best standard care [a structured programme of rehabilitation exercises] for 6 months; Procedure: • Arm A: Best standard of care only [a structured programme of rehabilitation exercises] for 6 months
Sponsors: University College, London; National Institute for Health Research, United Kingdom
Not yet recruiting
https://ift.tt/2OSuMx0
GP-induced Chemotherapy Combined With IMRT and TPF-induced Chemotherapy Combined With IMRT in the Treatment of Distant Metastatic Nasopharyngeal Carcinoma
Condition: Advanced Nasopharyngeal Carcinoma
Interventions: Drug: GP+IMRT; Drug: TPF+IMRT
Sponsor: Guiyang Medical University
Not yet recruiting
https://ift.tt/2COSAuH
Interventions: Drug: GP+IMRT; Drug: TPF+IMRT
Sponsor: Guiyang Medical University
Not yet recruiting
https://ift.tt/2COSAuH
An Algorithmic Approach to the Treatment of Frontal Fibrosing Alopecia-A Systematic Review
Publication date: Available online 28 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Yemisi Dina, Crystal Aguh
https://ift.tt/2JnugRU
Present and future perspective of photodynamic therapy for cutaneous squamous cell carcinoma
Publication date: Available online 28 October 2018
Source: Journal of the American Academy of Dermatology
Author(s): Uma Keyal, Anil Kumar Bhatta, Guolong Zhang, Xiuli Wang
Abstract
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Surgery remains the main stay of treatment but, some patients are not eligible for surgery and more importantly, lesions at critical site need nonsurgical approach for tissue preservation. In this context, photodynamic therapy (PDT) has been extensively studied as noninvasive or minimally invasive treatment and studies have shown promising results in terms of safety, efficacy and cosmetic outcome. Also, studies have proposed different mechanism for its efficacy. However, human studies demonstrating its efficacy are limited in terms of sample size and tumor depth of invasion. Exciting results are mainly seen in case report in microinvasive SCC, which is defined as SCC limited to papillary dermis. This inadequacy is due to inadequate penetration of topically applied photosensitizers through keratinized tumor surface. To overcome these hurdles, pretreatment with lasers or microneedles and encapsulation of photosensitizers into nanoparticles have been tried. Hence, present paper will discuss studies that have demonstrated the efficacy and safety of PDT for cSCC, studies that have postulated the mechanism of action of PDT, agents that have been used as PDT enhancers and finally, the recent use of adjuvant therapy in combination with PDT.
https://ift.tt/2DblyG2
Seventeen New Cases of Chronic Ulcerative Stomatitis with Literature Review
Abstract
Chronic ulcerative stomatitis (CUS) is a poorly understood disease with clinical and histologic overlap with lichen planus (LP). Unlike classic LP, direct immunofluorescence (DIF) studies in cases of CUS exhibit a granular pattern of IgG in nuclei of basal and parabasal cells. This study assesses the demographic, clinical, histologic, and DIF features of CUS. It is important to differentiate CUS from LP and other vesiculobullous diseases (VBD) because lesions of CUS are resistant to steroid therapy, which is typically used to control LP and VBD. A literature review and IRB-approved retrospective search of CUS was performed within the archives of the University of Florida (UF) Oral Pathology Biopsy Service from 2007 to 2017. Fifty-two cases were identified from the literature and seventeen new cases were identified in our series. All UF patients were female and the median age was 64-years. The majority of patients were Caucasian and the most common location was buccal mucosa. Frequent clinical presentations were pain, erythema, leukoplakia, and ulcerations. Histologic features included epithelial separation, atrophic epithelium, and a chronic inflammatory infiltrate. All cases were confirmed with DIF testing that showed a speckled pattern of IgG staining in basal and parabasal cell nuclei. Fibrinogen was present in eleven cases and two cases were positive for C3. The results of our series are in accordance with the literature. Since CUS has overlapping features with LP and VBD, clinicians and pathologists should consider this entity and confirm diagnosis with DIF testing when recalcitrant oral ulcerative diseases are encountered.
https://ift.tt/2qgN5gR
Commentary on letter to editor titled “surgical management of patients with Eagle syndrome”
Publication date: Available online 28 October 2018
Source: American Journal of Otolaryngology
Author(s): Frances Mei Hardin, Roy Xiao, Brian B. Burkey
https://ift.tt/2EQu3Yz
Defining Pollen Seasons: Background and Recommendations
Abstract
Purpose of Review
The definition of a pollen season determines the start and the end of the time period with a certain amount of pollen in the ambient air. Different pollen season definitions were used for a long time including the use of different terms for data and methods used to define a pollen season. Recently suggested pollen season definitions for clinical trials were tested and applied for the first time to more aeroallergens.
Recent Findings
This is a review on pollen season definitions and the latest recommendations. Recently, proposed terminology in aerobiology is promoted here in order to support reproducibility and repeatability in research. Two pollen season definitions, one based on percentages and one based on pollen concentrations, were tested.
Summary
Percentage definitions can be recommended for standard aerobiological routines and for retrospective applications, whereas pollen concentrations definitions can be recommended for prospective applications such as clinical trials.
https://ift.tt/2z6FtBi
Impact of community respiratory viral infections in urban children with asthma
Publication date: Available online 29 October 2018
Source: Annals of Allergy, Asthma & Immunology
Author(s): Toby C. Lewis, Ediri E. Metitiri, Graciela B. Mentz, Xiaodan Ren, Adam M. Goldsmith, Breanna N. Eder, Kyra E. Wicklund, Megan P. Walsh, Adam T. Comstock, Jeannette M. Ricci, Sean R. Brennan, Ginger L. Washington, Kendall B. Owens, Bhramar Mukherjee, Thomas G. Robins, Stuart A. Batterman, Marc B. Hershenson, the Community Action Against Asthma Steering Committee
Abstract
Background
Upper respiratory tract viral infections cause asthma exacerbations in children. However, the impact of natural colds on asthmatic children in the community, particularly in the high-risk urban environment, is less well-defined.
Objective
We hypothesized that children with high-symptom upper respiratory viral infections have reduced airway function and greater respiratory tract inflammation than children with virus-positive low-symptom illnesses or virus-negative upper respiratory tract symptoms.
Methods
We studied 53 asthmatic children from Detroit, Michigan during scheduled surveillance periods and self-reported respiratory illnesses for one year. Symptom score, spirometry, fraction of exhaled nitric oxide (FeNO) and nasal aspirate biomarkers, viral nucleic acid and rhinovirus (RV) copy number were assessed.
Results
Of 658 aspirates collected, 22.9% of surveillance samples and 33.7% of respiratory illnesses were virus-positive. Compared to the virus-negative asymptomatic condition, children with severe colds (symptom score ≥5) showed reduced forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75), higher nasal mRNA expression of C-X-C motif chemokine ligand (CXCL)-10 and melanoma differentiation-associated protein 5, and higher protein abundance of CXCL8, CXCL10 and C-C motif chemokine ligands (CCL)-2, CCL4, CCL20 and CCL24. Children with mild (symptom score 1-4) and asymptomatic infections showed normal airway function and fewer biomarker elevations. Virus-negative cold-like illnesses demonstrated increased FeNO, minimal biomarker elevation and normal airflow. RV copy number was associated with nasal chemokine levels but not symptom score.
Conclusion
Urban asthmatic children with high-symptom respiratory viral infections have reduced FEF25-75 and more elevations of nasal biomarkers than children with mild or asymptomatic infections, or virus-negative illnesses.
https://ift.tt/2OcPD9i
Expression of human and Porphyromonas gingivalis glutaminyl cyclases in periodontitis and rheumatoid arthritis–a pilot study
Publication date: Available online 28 October 2018
Source: Archives of Oral Biology
Author(s): Philip Bender, Andreas Egger, Martin Westermann, Nadine Taudte, Anton Sculean, Jan Potempa, Burkhard Möller, Mirko Buchholz, Sigrun Eick
Abstract
Objectives
Human glutaminyl cyclases (QC and isoQC) play an important role in maintaining inflammatory conditions. Meanwhile a glutaminyl cyclase synthesized by Porphyromonas gingivalis (PgQC), a key pathogen in developing periodontitis and a potential link of periodontitis with rheumatoid arthritis (RA), was discovered. This study was aimed to determine the expression of QC, isoQC and PgQC in patients with chronic periodontitis (CP) and RA.
Design
Thirty volunteers were enrolled in a pilot study and divided into 3 groups (healthy, CP and RA individuals). Blood samples, biofilm and gingival crevicular fluid (GCF) were analysed for mRNA expression of QC, isoQC and P. gingivalis QC. Major bacteria being associated with periodontal disease were quantified in subgingival biofilm and protein levels for monocyte chemoattractant protein (MCP)-1, MCP-3 and interleukin (IL)-1β) were determined in the GCF. Expression of PgQC on the mRNA and protein levels was assessed in two P. gingivalis strains.
Results
PgQC is expressed in P. gingivalis strains and the protein seems to be located mainly in peri-plasmatic space. mRNA expression of QC was significantly increased in the peripheral blood from RA patients vs. healthy subjects and CP patients (p = 0.013 and p = 0.003, respectively). In GCF of RA patients, QC mRNA was detected more frequently than in healthy controls (p = 0.043). In these samples IL-1β levels were also elevated compared to GCF from periodontally healthy individuals (p = 0.003). PgQC was detected in eight out of the 13 P. gingivalis positive biofilm samples.
Conclusion
Activity of QC may play a supportive role in maintaining chronic periodontal inflammation and destruction in RA. PgQC is expressed in vivo but further research is needed to evaluate biological importance of this enzyme and if it constitutes a potential target in periodontal antimicrobial therapy.
https://ift.tt/2ET0CVR
Comparative analysis of blood parameters of the erythrocyte lineage between patients with chronic periodontitis and healthy patients: Results obtained from a meta-analysis
Publication date: Available online 28 October 2018
Source: Archives of Oral Biology
Author(s): Luiz Felipe de Carvalho França, Felipe Rodolfo Pereira da Silva, David di Lenardo, Even Herlany Pereira Alves, Hélio Mateus Silva Nascimento, Isabela Aparecida Tito da Silva, Any Carolina Cardoso Guimarães Vasconcelos, Daniel Fernando Pereira Vasconcelos
Abstract
Objective
Quantitatively evaluate blood parameters of the erythrocyte lineage in patients with chronic periodontitis and healthy controls by means of a meta-analysis.
Material and methods
A review of literature was performed in the scientific databases for studies published before September, 2016. The abstracts were evaluated and the extraction of data performed by two examiners. The parameters assessed were: hemoglobin levels, number of circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in patients with chronic periodontitis and healthy controls. The calculations were obtained through the statistical software Review Manager version 5.3, with calculation of Mean Difference, heterogeneity (I²) and funnel plot with P < 0.05.
Results
Nine case/control studies composed the results with 342 patients with chronic periodontitis and 359 healthy controls. There was a significant decrease in hemoglobin levels (MD = -1.60, 95% CI: -2.72, -0.48, P = 0.005) and number of circulating red blood cells (MD = -0.51, 95% CI: -0.78, -0.24, P = 0.0002), hematocrit (MD = -4.41, IC 95%: -7.13, -1.68, P = 0.002), mean corpuscular hemoglobin (MD = -0.80; IC 95%: -1.38, -0,22, P = 0.007) and mean corpuscular hemoglobin concentration (MD = -0.93, IC 95%: -1.63, -0.23, P = 0.009) in patients with chronic periodontitis when compared to healthy controls. No publication bias was found through the funnel plot asymmetry.
Conclusion
There is an associated of the reduction of hematological parameters (such as levels of hemoglobin and circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) to patients with chronic periodontitis.
https://ift.tt/2AyB6B7
Defining Pollen Seasons: Background and Recommendations
Abstract
Purpose of Review
The definition of a pollen season determines the start and the end of the time period with a certain amount of pollen in the ambient air. Different pollen season definitions were used for a long time including the use of different terms for data and methods used to define a pollen season. Recently suggested pollen season definitions for clinical trials were tested and applied for the first time to more aeroallergens.
Recent Findings
This is a review on pollen season definitions and the latest recommendations. Recently, proposed terminology in aerobiology is promoted here in order to support reproducibility and repeatability in research. Two pollen season definitions, one based on percentages and one based on pollen concentrations, were tested.
Summary
Percentage definitions can be recommended for standard aerobiological routines and for retrospective applications, whereas pollen concentrations definitions can be recommended for prospective applications such as clinical trials.
https://ift.tt/2z6FtBi
Hip Mobilization at Preterm Age May Accelerate Developmental Dysplasia Recovery
Purpose. Few studies have described mobilization approaches in developmental dysplasia of the hip (DDH). The present study describes the hip mobilization of a preterm infant (born at 33 6/7 weeks of gestational age) diagnosed with DDH. Design and Methods. During the 43-day hospital stay, the infant was seen twice a week (ten sessions, 20 minutes each). All sessions included hip approximation maneuvers, with the hip positioned in abduction, lateral rotation and flexion, and lower limbs passive mobilization, which were taught to the mother. Early intervention with auditory, tactile, visual, and vestibular stimulations was also performed. The infant was assessed with hip ultrasound before and after treatment. Results. At 34 2/7 weeks of gestational age, she was classified as Graf IIa (left: alpha: 55°, beta: 68°; right: alpha: 59°, beta: 64°). At 40 5/7 weeks, she was classified as Graf I for left (alpha: 67°; beta: 42°) and right (alpha: 66°; beta: 42°) hips. Practical Implications. The intervention seemed to accelerate the acquisition of stability of dysplasic hips in a preterm infant. The outcome supports further investigation of hip approximation maneuvers as part of early stimulation in preterm infants with DDH during hospital stay.
https://ift.tt/2yBHq9C
Dissociation of Appetitive Overexpectation and Extinction in the Infralimic Cortex
Abstract
Behavioral change is paramount to adaptive behavior. Two ways to achieve alterations in previously established behavior are extinction and overexpectation. The infralimbic (IL) portion of the medial prefrontal cortex controls the inhibition of previously established aversive behavioral responses in extinction. The role of the IL cortex in behavioral modification in appetitive Pavlovian associations remains poorly understood. Here, we seek to determine if the IL cortex modulates overexpectation and extinction of reward learning. Using overexpectation or extinction to achieve a reduction in behavior, the present findings uncover a dissociable role for the IL cortex in these paradigms. Pharmacologically inactivating the IL cortex left overexpectation intact. In contrast, pre-training manipulations in the IL cortex prior to extinction facilitated the reduction in conditioned responding but led to a disrupted extinction retrieval on test drug-free. Additional studies confirmed that this effect is restricted to the IL and not dependent on the dorsally-located prelimbic cortex. Together, these results show that the IL cortex underlies extinction but not overexpectation-driven reduction in behavior, which may be due to regulating the expression of conditioned responses influenced by stimulus–response associations rather than stimulus–stimulus associations.https://ift.tt/2yG6yvV
Regorafenib or rechallenge chemotherapy: which is more effective in the third-line treatment of metastatic colorectal cancer?
Abstract
Purpose
To assess the efficacy and safety of regorafenib versus rechallenge chemotherapy in previously treated mCRC patients in third-line setting.
Materials and methods
The data of 104 patients diagnosed with mCRC enrolled from 2010 to 2017 in six oncology centers were analyzed. Tumor treatment options were obtained from follow-up and treatment files. Rechallenge chemotherapy was identified as the re-use of the regimen which was previously administered to patients in one of the therapy lines and obtained disease control, these were the patients whose disease did not progress within 3 months.
Results
A total of 104 patients had received previously two lines of chemotherapy regimens for mCRC. Of these, 73 patients with mCRC who received regorafenib and 31 those who received rechallenge chemotherapy in third-line therapy were analyzed. Overall survival was better with rechallenge than it was with regorafenib (HR 0.29 95% CI 0.16–0.54, p < 0.001). Median OS was 12.0 months (95% CI 8.1–15.9) in rechallenge versus 6.6 months (95% CI 6.0–7.3) in regorafenib group (p < 0.001). Progression-free survival in the rechallenge group showed a higher median value of 9.16 months (95% CI 7.15–11.18) versus with that recorded in the regorafenib group of 3.41 months (95% CI 3.01–3.82), in favor of rechallenge chemotherapy. The most common adverse events of regorafenib was liver function test abnormality and hand–foot syndrome. Although grade 3 or 4 adverse events were similar, non-hematologic toxicities were more common than those of rechallenge.
Conclusions
Rechallenge is still a valuable option against regorafenib in patients who achieved disease control in one of the first two lines of therapy. Even though mCRC patients treated with regorafenib benefited clinically from this treatment, we revealed that chemotherapy rechallenge compared to regorafenib was more effective in the third-line treatment for mCRC patients.
https://ift.tt/2Odz1hw
An Update on Drug-Induced Pigmentation
Abstract
Drug-induced pigmentation accounts for up to 20% of all cases of acquired pigmentation. A thorough review of medical history and previous and ongoing medications as well as a complete skin examination can guide diagnosis. Implicated agents include alkylating/cytotoxic agents, analgesics, antiarrhythmics, anticoagulants, antiepileptics, antimalarials, antimicrobials, antiretrovirals, metals, prostaglandin analogs, and psychotropic agents, among others. Confirming true drug associations can be challenging, especially in the setting of delayed onset of pigmentation and coexisting polypharmacy.
https://ift.tt/2qgFBdN
Immunosuppressive circuits in tumor microenvironment and their influence on cancer treatment efficacy
Abstract
It has been for long conceived that hallmarks of cancer were intrinsic genetic features driving tumor development, proliferation, and progression, and that targeting such cell-autonomous pathways could be sufficient to achieve therapeutic cancer control. Clinical ex vivo data demonstrated that treatment efficacy often relied on the contribution of host immune responses, hence introducing the concept of tumor microenvironment (TME), namely the existence, along with tumor cells, of non-tumor components that could significantly influence tumor growth and survival. Among the complex network of TME-driving forces, immunity plays a key role and the balance between antitumor and protumor immune responses is a major driver in contrasting or promoting cancer spreading. TME is usually a very immunosuppressed milieu because of a vast array of local alterations contrasting antitumor adaptive immunity, where metabolic changes contribute to cancer dissemination by impairing T cell infiltration and favoring the accrual and activation of regulatory cells. Subcellular structures known as extracellular vesicles then help spreading immunosuppression at systemic levels by distributing genetic and protein tumor repertoire in distant tissues. A major improvement in the knowledge of TME is now pointing the attention back to tumor cells; indeed, recent findings are showing how oncogenic pathways and specific mutations in tumor cells can actually dictate the nature and the function of immune infiltrate. As our information on the reciprocal interactions regulating TME increases, finding a strategy to interfere with TME crosstalk becomes more complex and challenging. Nevertheless, TME interactions represent a promising field for the discovery of novel biomarkers and therapeutic targets for improving treatment efficacy in cancer.
https://ift.tt/2zbcAUR
Dexmedetomidine preserves the endothelial glycocalyx and improves survival in a rat heatstroke model
Abstract
Purpose
Heatstroke causes systemic inflammation, followed by vascular endothelial damage. The normal vascular endothelium is coated by endothelial glycocalyx (EGCX). Dexmedetomidine (DEX) has an anti-inflammatory effect, but there has been little investigation on the influence of heatstroke on EGCX and the effect of DEX on this condition. Therefore, we examined whether EGCX was disrupted in heatstroke and if DEX improved survival and preserves EGCX.
Methods
Anesthetized Wistar rats were randomly assigned to three groups: a DEX group treated with DEX (5 µg/kg/h) and 0.9% saline infused continuously at 10 ml/kg/h during heat exposure; a NSS group given 0.9% saline during heat exposure; and a SHAM group given 0.9% saline alone without heat exposure. Heatstroke was induced by exposure to an ambient temperature of 40 °C with relative humidity of 60%. The survival rate was assessed up to 2 h after the start of heat exposure. Plasma levels of syndecan-1 and the thickness of EGCX using electron microscopy were measured when the systolic blood pressure fell to less than 80 mmHg.
Results
The survival rate after 2 h of heat exposure was significantly higher in the DEX group compared to the NSS group (89% vs. 22%, P = 0.004). Plasma levels of syndecan-1 were 0.6 ± 1.3, 9.7 ± 5.9, and 2.1 ± 3.4 ng/ml in the SHAM, NSS and DEX groups, respectively (P = 0.013). The thickness of EGCX was significantly higher in the DEX group compared with the NSS group (P = 0.001).
Conclusions
EGCX was disrupted in heatstroke, and DEX improved survival and preserved EGCX.
https://ift.tt/2Pxdcy2
Post-mortem diagnosis of Pompe disease by exome sequencing in a Moroccan family: a case report
Pompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy. Its prevalence ranges...
https://ift.tt/2EPBhwb
A randomized controlled trial protocol assessing the effectiveness, safety and cost‐effectiveness of methotrexate vs. ciclosporin in the treatment of severe atopic eczema in children: the TREatment of severe Atopic eczema Trial (TREAT)
British Journal of Dermatology, EarlyView.
https://ift.tt/2JmVUyq
A randomized controlled trial protocol assessing the effectiveness, safety and cost‐effectiveness of methotrexate vs. ciclosporin in the treatment of severe atopic eczema in children: the TREatment of severe Atopic eczema Trial (TREAT)
British Journal of Dermatology, EarlyView.
https://ift.tt/2JmVUyq
Suprapubic catheterization is expedient for the surgical excision of female genital tumors
Dermatologic Therapy, EarlyView.
https://ift.tt/2Ocxl7P
Improvement of exertional dyspnea and breathing pattern of inspiration to expiration after bronchial thermoplasty
Bronchial thermoplasty (BT) is a bronchoscopic treatment that can ameliorate the symptoms of severe asthma. However, little is known about the mechanism by which BT improves exertional dyspnea without signific...
https://ift.tt/2Rr7eMP
First reported case in Canada of anaphylaxis to lupine in a child with peanut allergy
Lupine is a member of the legume family and is often used in many food products in Europe (e.g. pasta, pizza, sauces, etc.) as a wheat or soy substitute. Lupine cross-reacts with peanut, and cases of allergic ...
https://ift.tt/2PqtTvb
Suprapubic catheterization is expedient for the surgical excision of female genital tumors
Dermatologic Therapy, EarlyView.
https://ift.tt/2Ocxl7P
Cutaneous localization of angioimmunoblastic T‐cell lymphoma may masquerade as B cell lymphoma or classical Hodgkin lymphoma: a histologic diagnostic pitfall
Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2PoOtfz
Mechanisms of injury in APOL1-associated kidney disease
Background An improved understanding of the pathogenesis in apolipoprotein L1 gene (APOL1)-gene associated chronic kidney disease (CKD) arose from observations in kidney transplantation. APOL1 genotyping could soon improve the safety of living kidney donation in individuals with recent African ancestry and alter the allocation of deceased donor kidneys. Methods This manuscript reviews the potential mechanisms that underlie development of APOL1-associated nephropathy. Roles for circulating APOL1 protein versus intrinsic renal expression of APOL1 are discussed, as well as the requirement for modifying genetic and/or environmental factors. Results Abundant evidence supports local kidney production of APOL1 renal-risk variant protein in the development of nephropathy; this is true in both native kidney disease and after renal transplantation. Only a minority of kidneys from individuals with APOL1 high-risk genotypes will develop CKD or manifest shorter renal allograft survival after transplantation. Therefore, modifying factors that explain why only a subset of kidneys develops nephropathy remain critical to identify. It appears likely that environmental exposures, as opposed to major APOL1-second gene interactions, will prove to be stronger modifiers of the risk for nephropathy. Conclusions The evolving understanding of the pathogenesis in APOL1-associated nephropathy will identify biomarkers predicting nephropathy in individuals at high genetic risk and lead to novel therapies to prevent or slow native CKD progression and prolong survival of transplanted kidneys. In the interim, the National Institutes of Health-sponsored "APOL1 Long-term Kidney Transplantation Outcomes" (APOLLO) Network will determine whether APOL1 genotyping in individuals with recent African ancestry improves outcomes and safety in kidney transplantation. Support: NIH R01 DK084149 (BIF), R01 DK070941 (BIF), R01 MD009055 (JD & BIF), U01 DK116041 (BIF) Disclosures: Wake Forest University Health Sciences and Barry Freedman have rights to an issued United States patent related to APOL1 genetic testing (www.apol1genetest.com). Dr. Freedman is a consultant for Ionis and AstraZeneca Pharmaceuticals. Author contributions: LM, JD and BIF all contributed to the research design, preparation of the manuscript and performance of the research contained in the manuscript. Correspondence: Barry I. Freedman, MD, Internal Medicine – Nephrology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157 USA. Email: bfreedma@wakehealth.edu. Phone: 336-716-6461. Fax: 336-716-4318 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2DazQ9I
https://ift.tt/2DazQ9I
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