Oncocytic metaplasia represents a histopathologic feature that can be observed in normal tissue such as salivary and lacrimal glands but may also constitute a degenerative metaplastic process as a result of repeated oxidative damage during cellular aging. Although cutaneous oncocytic metaplasia has been considered rare, the finding was seen in over one-third of melanocytic nevi prospectively evaluated, in one study. This case series reports on a small series of oncocytic melanocytic tumors, with the aim of describing this phenomenon in varied contexts and also describing the use of a mitochondrial antigen immunostain, which has not been previously reported. Correspondence: Timothy McCalmont, MD, UCSF Dermatopathology Service, University of California, San Francisco, 1701 Divisadero Street, Suite 280, San Francisco, CA 94115 (e-mail: tim.mccalmont@ucsf.edu). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2J9bIDl
Πέμπτη 19 Απριλίου 2018
Verrucous Plaque With Unusually Large Candida Blastoconidia: A Unique Clinicopathological Presentation of Systemic Mucocutaneous Candidiasis
Abstract: Mucocutaneous candidiasis is a common infection affecting both immunocompetent and immunosuppressed individuals. Diversity in the clinical and histopathological presentation of mucocutaneous candidiasis is well known. However, the occurrence of cutaneous verrucous lesions and giant yeast-like structures has been rarely reported. In this article, we describe a case of disseminated mucocutaneous candidiasis in an immunosuppressed patient who presented as a verrucous plaque on the scrotum with giant Candida blastoconidia. This peculiar presentation expands the clinicopathological spectrum of mucocutaneous candidiasis and highlights the wide range of clinical manifestations and great morphologic variability of this common fungal infection. Correspondence: Eduardo Rozas-Muñoz, MD, Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain (e-mail: docrozas@yahoo.com). E. Rozas-Muñoz, A. Mozos, J. F. Mir-Bonafé, X. Cubiró, F. Sánchez-Reus, C. Monteagudo, and L. Puig had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: E. Rozas-Muñoz, A. Mozos, J. F. Mir-Bonafé, X. Cubiró, and L. Puig. Acquisition of data: E. Rozas-Muñoz, A. Mozos, J. F. Mir-Bonafé, X. Cubiró, Sanchez-Reus, and C. Monteagudo. Analysis and interpretation of data: E. Rozas-Muñoz, A. Mozos, J. F. Mir-Bonafé, F. Sánchez-Reus, C. Monteagudo, and L. Puig. Drafting of the manuscript: E. Rozas-Muñoz, A. Mozos, and L. Puig. Critical revision of the manuscript for important intellectual content: E. Rozas-Muñoz, A. Mozos, F. Sánchez-Reus, C. Monteagudo, and L. Puig. Statistical analysis: Non applicable. Obtained funding: None. Administrative, technical, or material support: None. Study supervision: Non applicable. The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2JYmWMa
https://ift.tt/2JYmWMa
Role of Direct Immunofluorescence in Cutaneous Small-Vessel Vasculitis: Experience From a Tertiary Center
Abstract: Skin is commonly affected by vasculitic process and often subjected to biopsy. Cutaneous vasculitis can be either primary or part of a systemic vasculitic process. This study was conducted to evaluate the diagnostic utility of direct immunofluorescence (DIF) in determination of etiology of cutaneous vasculitis. All histologically proven cases of cutaneous vasculitis over the past two and half years were retrospectively analyzed along with their clinical and DIF findings (IgG, IgA, IgM, and C3). Within this study period, a total of 198 cases of small-vessel vasculitis were diagnosed based on skin biopsy and DIF findings. The mean age of patients was 31.2 years (range 1–84 years) with slight male dominance (M:F ratio 1.06:1). Henoch–Schonlein purpura/IgA vasculitis was the commonest clinical diagnosis (31%), followed by urticarial vasculitis (11%) and others. Idiopathic vasculitis was suspected in 33% cases. Overall, DIF was positive in 60% (119/198) cases, with vascular deposition of IgA being commonest, followed by C3. The clinical diagnosis of Henoch–Schonlein purpura could be confirmed in 61.5% (40/65) cases by DIF, whereas another 20 unsuspected cases were picked up as IgA vasculitis based on DIF findings. DIF findings confirmed lupus vasculitis in 50% cases. Other cases showed variable nonspecific deposition of C3 and IgM in 42% cases. DIF can be highly useful to classify cutaneous vasculitis, with maximum efficacy for diagnosis of IgA vasculitis and lupus vasculitis. It can aid in the accurate diagnosis even when the histological changes are minimal. All cases of suspected cutaneous vasculitis should be subjected to DIF. Correspondence: Bishan Radotra, MD, PhD, Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India (e-mail: bishanradotra@gmail.com). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2K1qjCf
https://ift.tt/2K1qjCf
Cutaneous Metastasis of Adenocarcinoma of the Ampulla of Vater
Abstract: Cutaneous metastases from an adenocarcinoma of the Ampulla of Vater are very rare, with only a few cases previously reported. We present here an additional case in a 57-year-old woman who complained of a painful growth on her frontal scalp that she had noticed 4 months earlier. Her medical history included an ampullary adenocarcinoma, which was diagnosed 4 years ago, excised through a Whipple procedure, and treated using chemotherapy and radiotherapy. The scalp biopsy showed a dermal and epidermotropic well-differentiated glandular neoplasm with abundant neutrophils within the luminae of the tumoral glands. The tumor failed to express p63 and cytokeratin 5/6, whereas it was intensively positive for CK7 and E-cadherin. CDX2 expression was weak and focal. The immunohistochemical expression of DNA mismatch-repair proteins (MSH2, MSH6, MLH1, and PMS2) was preserved. Despite oncological treatment, the patient developed multiple cutaneous metastases during the ensuing several months, and eventually died 6 years after her initial diagnosis with widespread metastases. Correspondence: Angel Fernandez-Flores, MD, PhD, Servicio de Anatomía Patologica, Hospital El Bierzo, Medicos sin Fronteras 7, 24411 Ponferrada, Spain (e-mail: dermatopathonline@gmail.com). The authors declare no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2J8FgRI
https://ift.tt/2J8FgRI
Recapitulating spatiotemporal tumor heterogeneity in vitro through engineered breast cancer microtissues
Publication date: Available online 19 April 2018
Source:Acta Biomaterialia
Author(s): Claudia Mazio, Costantino Casale, Giorgia Imparato, Francesco Urciuolo, Paolo Antonio Netti
Tumor and microenvironmental heterogeneity hinders the study of breast cancer biology and the assessment of therapeutic strategies, being associated with high variability and drug resistance. In this context, it is mandatory to develop three-dimensional breast tumor models able to reproduce this heterogeneity and the dynamic interaction occurring between tumor cells and microenvironment. Here we show a new breast cancer microtissue model (T-µTP) uniquely able to present intra-tumor morphological heterogeneity in a dynamic and responsive endogenous matrix. T-µTP consists of adenocarcinoma cells, endothelial cells and stromal fibroblasts. These three kinds of cells are totally embedded into an endogenous matrix which is rich in collagen and hyaluronic acid and it is directly produced by human fibroblasts. In this highly physiologically relevant environment, tumor cells evolve in different cluster morphologies recapitulating tumor spatiotemporal heterogeneity. Moreover they activate the desmoplastic and vascular reaction with affected collagen content, assembly and organization and the presence of aberrant capillary-like structures (CLS). Thus, T-µTP allows to outline main crucial events involved in breast cancer progression into a single model overcoming the limit of artificial extra cellular matrix surrogates. We strongly believe that T-µTP is a suitable model for the study of breast cancer and for drug screening assays following key parameters of clinical interest.Statement of SignificanceTumor and microenvironmental heterogeneity makes very hurdle to find a way to study and treat breast cancer. Here we develop an innovative 3D tumor microtissue model recapitulating in vitro tumor heterogeneity. Tumor microtissues are characterized by the activation of the stromal and vascular reaction too. We underline the importance to mimic different microenvironmental tumor features in the same time and in a single tissue in order to obtain a model of spatiotemporal tumor genesis and progression, suitable for the study of tumor treatment and resistance.
Graphical abstract
https://ift.tt/2qMBmXf
Biomimetic 3D in vitro model of biofilm triggered osteomyelitis for investigating hematopoiesis during bone marrow infections
Publication date: Available online 19 April 2018
Source:Acta Biomaterialia
Author(s): Annamarija Raic, Sophie Riedel, Elena Kemmling, Karen Bieback, Joerg Overhage, Cornelia Lee-Thedieck
In this work, we define the requirements for a human-based osteomyelitis model which overcomes the limitations of state of the art animal models. Osteomyelitis is a severe and difficult to treat infection of the bone that develops rapidly, making it difficult to study in humans. We have developed a 3D in vitro model of the bone marrow, comprising a macroporous material, human hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). Inclusion of biofilms grown on an implant into the model system allowed us to study the effects of postoperative osteomyelitis-inducing bacteria on the bone marrow. The bacteria influenced the myeloid differentiation of HSPCs as well as MSC cytokine expression and the MSC ability to support HSPC maintenance. In conclusion, we provide a new 3D in vitro model which meets all the requirements for investigating the impact of osteomyelitis.Statement of SignificanceImplant associated-osteomyelitis is a persistent bacterial infection of the bone which occurs in many implant patients and can result in functional impairments or even entire loss of the extremity. Nevertheless, surprisingly little is known on the triangle interaction between implant material, bacterial biofilm and affected bone tissue. Closing this gap of knowledge would be crucial for the fundamental understanding of the disease and the development of novel treatment strategies. For this purpose, we developed the first biomaterial-based system that is able to mimic implant-associated osteomyelitis outside of the body, thus, opening the avenue to study this fatal disease in the laboratory.
Graphical abstract
https://ift.tt/2HdR6NP
Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia
Publication date: Available online 19 April 2018
Source:Cancer Cell
Author(s): Michelle L. Churchman, Maoxiang Qian, Geertruy te Kronnie, Ranran Zhang, Wenjian Yang, Hui Zhang, Tobia Lana, Paige Tedrick, Rebekah Baskin, Katherine Verbist, Jennifer L. Peters, Meenakshi Devidas, Eric Larsen, Ian M. Moore, Zhaohui Gu, Chunxu Qu, Hiroki Yoshihara, Shaina N. Porter, Shondra M. Pruett-Miller, Gang Wu, Elizabeth Raetz, Paul L. Martin, W. Paul Bowman, Naomi Winick, Elaine Mardis, Robert Fulton, Martin Stanulla, William E. Evans, Mary V. Relling, Ching-Hon Pui, Stephen P. Hunger, Mignon L. Loh, Rupert Handgretinger, Kim E. Nichols, Jun J. Yang, Charles G. Mullighan
Somatic genetic alterations of IKZF1, which encodes the lymphoid transcription factor IKAROS, are common in high-risk B-progenitor acute lymphoblastic leukemia (ALL) and are associated with poor prognosis. Such alterations result in the acquisition of stem cell-like features, overexpression of adhesion molecules causing aberrant cell-cell and cell-stroma interaction, and decreased sensitivity to tyrosine kinase inhibitors. Here we report coding germline IKZF1 variation in familial childhood ALL and 0.9% of presumed sporadic B-ALL, identifying 28 unique variants in 45 children. The majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells. These results identify IKZF1 as a leukemia predisposition gene, and emphasize the importance of germline genetic variation in the development of both familial and sporadic ALL.
Graphical abstract
Teaser
Churchman et al. identify 28 unique germline IKZF1 coding variants in 45 children with acute lymphoblastic leukemia. Many of these variants are not predicted to be damaging using in silico prediction tools, but functional tests reveal that the majority of them have deleterious effects on IKAROS function.https://ift.tt/2qLxeHI
A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment
Publication date: Available online 19 April 2018
Source:Cancer Cell
Author(s): Amelie Griveau, Giorgio Seano, Samuel J. Shelton, Robert Kupp, Arman Jahangiri, Kirsten Obernier, Shanmugarajan Krishnan, Olle R. Lindberg, Tracy J. Yuen, An-Chi Tien, Jennifer K. Sabo, Nancy Wang, Ivy Chen, Jonas Kloepper, Louis Larrouquere, Mitrajit Ghosh, Itay Tirosh, Emmanuelle Huillard, Arturo Alvarez-Buylla, Michael C. Oldham, Anders I. Persson, William A. Weiss, Tracy T. Batchelor, Anat Stemmer-Rachamimov, Mario L. Suvà, Joanna J. Phillips, Manish K. Aghi, Shwetal Mehta, Rakesh K. Jain, David H. Rowitch
Gliomas comprise heterogeneous malignant glial and stromal cells. While blood vessel co-option is a potential mechanism to escape anti-angiogenic therapy, the relevance of glial phenotype in this process is unclear. We show that Olig2+ oligodendrocyte precursor-like glioma cells invade by single-cell vessel co-option and preserve the blood-brain barrier (BBB). Conversely, Olig2-negative glioma cells form dense perivascular collections and promote angiogenesis and BBB breakdown, leading to innate immune cell activation. Experimentally, Olig2 promotes Wnt7b expression, a finding that correlates in human glioma profiling. Targeted Wnt7a/7b deletion or pharmacologic Wnt inhibition blocks Olig2+ glioma single-cell vessel co-option and enhances responses to temozolomide. Finally, Olig2 and Wnt7 become upregulated after anti-VEGF treatment in preclinical models and patients. Thus, glial-encoded pathways regulate distinct glioma-vascular microenvironmental interactions.
Teaser
Griveau et al. show that Olig2+ glioma cells invade by single-cell vessel co-option, whereas Olig2− glioma cells promote angiogenesis and that anti-VEGF treatment selects for the Olig2+/Wnt7+ phenotype. Wnt7 is necessary for vessel co-option, and Wnt inhibition enhances the response to temozolomide treatment.https://ift.tt/2F226I8
Oral Health and Dietary Intake in Older Adults
Abstract
Purpose of Review
Previous studies have reported that dietary intake is related to systemic diseases and functions. The oral cavity is the first passage through which food passes for consumption, and decline of oral health is considered to be associated with a lower intake of some foods or nutrients. We focused on the relationship between oral health and dietary intake in older adults.
Recent Findings
Most studies have reported oral health, such as number of teeth, tooth loss, occlusal contacts, masticatory ability, denture use, occlusal force, dysphagia, and hyposalivation are associated with intake of some foods and nutrients adjusting for socioeconomic factors.
Summary
Healthy oral function can lead to enough intake of key nutrients. It is also necessary to clarify the association between oral health and malnutrition, such as weight loss or underweight, and the pathways from oral health to several systemic diseases.
https://ift.tt/2qNDv4V
Generation and characterization of hagfish variable lymphocyte receptor B against glycoprotein of viral hemorrhagic septicemia virus (VHSV)
Source:Molecular Immunology, Volume 99
Author(s): Jung Seok Lee, Jaesung Kim, Se Pyeong Im, Si Won Kim, Jassy Mary S. Lazarte, Jae Wook Jung, Tae Won Gong, Young Rim Kim, Jeong Ho Lee, Hyoung Jun Kim, Tae Sung Jung
Variable lymphocyte receptors B (VLRBs) are non-immunoglobulin components of the humoral immune system in jawless vertebrates including hagfish (Eptatretus burgeri) and lamprey (Petromyzon marinus). Hagfish VLRBs consist of leucine rich repeat (LRR) modules with a superhydrophobic C-terminal tail, the latter of which leads to extremely low expression levels in recombinant protein technology. Here, we present an artificially oligomerized VLRB (arVLRB) that conjugates via the C4bp oligomerization domain derived from human C4b-binding protein (hC4bp) rather than the superhydrophobic tail. The resulting arVLRB had a tightly multimerized form with seven monomeric VLRB arms and showed high expression and secretion levels in a mammalian expression system. To isolate antigen-specific arVLRB, we constructed large VLRB libraries from hagfish immunized with the fish pathogen, viral hemorrhagic septicemia virus (VHSV). The selected arVLRBs were found to recognize various types of antigens, including the recombinant target protein, purified viruses, and progeny viruses, with high antigen binding abilities and specificities. We also performed in vitro affinity maturation of the arVLRBs through LRRCT mutagenesis, and found that this enhanced their antigen-binding properties by at least 125-fold. Our epitope mapping analysis revealed that 37DWDTPL42, which is located in a region conserved among the glycoproteins of all VHSV isolates, is the recognition epitope of the arVLRBs. Thus, our newly developed arVLRB could prove useful in the development of universal diagnostic tools and/or therapeutic agents for the virus. Together, our novel findings provide valuable insights into hagfish VLRB and its potential use as a novel alternative to conventional antibodies for biotechnological applications.
https://ift.tt/2K1fUGH
Tree nut allergens
Source:Molecular Immunology
Author(s): Sabine Geiselhart, Karin Hoffmann-Sommergruber, Merima Bublin
Tree nuts are considered as part of a healthy diet due to their high nutritional quality. However, they are also a potent source of allergenic proteins inducing IgE mediated hypersensitivity often causing serious, life-threatening reactions. The reported prevalence of tree nut allergy is up to 4.9% worldwide. The general term "tree nuts" comprises a number of nuts, seeds, and drupes, derived from trees from different botanical families. For hazelnut and walnut several allergens have been identified which are already partly applied in component resolved diagnosis, while for other tree nuts such as macadamia, coconut, and Brazil nut only individual allergens were identified and data on additional allergenic proteins are missing. This review summarizes the current knowledge on tree nut allergens and describes their physicochemical and immunological characterization and clinical relevance.
https://ift.tt/2J9WAFL
Peanut allergens
Publication date: Available online 19 April 2018
Source:Molecular Immunology
Author(s): Chiara Palladino, Heimo Breiteneder
Peanut allergens have the potential to negatively impact on the health and quality of life of millions of consumers worldwide. The seeds of the peanut plant Arachis hypogaea contain an array of allergens that are able to induce the production of specific IgE antibodies in predisposed individuals. A lot of effort has been focused on obtaining the sequences and structures of these allergens due to the high health risk they represent. At present, 16 proteins present in peanuts are officially recognized as allergens. Research has also focused on their in-depth immunological characterization as well as on the design of modified hypoallergenic derivatives for potential use in clinical studies and the formulation of strategies for immunotherapy. Detailed research protocols are available for the purification of natural allergens as well as their recombinant production in bacterial, yeast, insect, and algal cells. Purified allergen molecules are now routinely used in diagnostic multiplex protein arrays for the detection of the presence of allergen-specific IgE. This review gives an overview on the wealth of knowledge that is available on individual peanut allergens.
https://ift.tt/2JYb3Wy
Review of surface particulate monitoring of dust events using geostationary satellite remote sensing
Source:Atmospheric Environment, Volume 183
Author(s): M. Sowden, U. Mueller, D. Blake
The accurate measurements of natural and anthropogenic aerosol particulate matter (PM) is important in managing both environmental and health risks; however, limited monitoring in regional areas hinders accurate quantification. This article provides an overview of the ability of recently launched geostationary earth orbit (GEO) satellites, such as GOES-R (North America) and HIMAWARI (Asia and Oceania), to provide near real-time ground-level PM concentrations (GLCs). The review examines the literature relating to the spatial and temporal resolution required by air quality studies, the removal of cloud and surface effects, the aerosol inversion problem, and the computation of ground-level concentrations rather than columnar aerosol optical depth (AOD).Determining surface PM concentrations using remote sensing is complicated by differentiating intrinsic aerosol properties (size, shape, composition, and quantity) from extrinsic signal intensities, particularly as the number of unknown intrinsic parameters exceeds the number of known extrinsic measurements. The review confirms that development of GEO satellite products has led to improvements in the use of coupled products such as GEOS-CHEM, aerosol types have consolidated on model species rather than prior descriptive classifications, and forward radiative transfer models have led to a better understanding of predictive spectra interdependencies across different aerosol types, despite fewer wavelength bands. However, it is apparent that the aerosol inversion problem remains challenging because there are limited wavelength bands for characterising localised mineralogy.The review finds that the frequency of GEO satellite data exceeds the temporal resolution required for air quality studies, but the spatial resolution is too coarse for localised air quality studies. Continual monitoring necessitates using the less sensitive thermal infra-red bands, which also reduce surface absorption effects. However, given the challenges of the aerosol inversion problem and difficulties in converting columnar AOD to surface concentrations, the review identifies coupled GEO-neural networks as potentially the most viable option for improving quantification.
https://ift.tt/2HBYxxz
Impacts of heterogeneous reactions to atmospheric peroxides: Observations and budget analysis study
Source:Atmospheric Environment, Volume 183
Author(s): Mengru Qin, Zhongming Chen, Hengqing Shen, Huan Li, Huihui Wu, Yin Wang
Atmospheric peroxides play important roles in atmospheric chemistry, acting as reactive oxidants and reservoirs of HOX and ROX radicals. Field measurements of atmospheric peroxides were conducted over urban Beijing from 2015 to 2016, including dust storm days, haze days and different seasons. We employed a box model based on RACM2 mechanism to conduct concentration simulation and budget analysis of hydrogen peroxide (H2O2) and peroxyacetic acid (PAA). In this study, heterogeneous reaction is found to be a significant sink for atmospheric H2O2 and PAA in urban Beijing. Here, we recommend a suitable uptake coefficient formula considering the water effect for model research of peroxides. It is found that H2O2 and PAA unexpectedly maintained considerable concentrations on haze days, even higher than that on non-haze days. This phenomenon is mainly ascribed to relatively high levels of volatile organic compounds and ozone on haze days. In addition, high levels of water vapor in pollution episode can promote not only the heterogeneous uptake to aerosol phase but also the production of H2O2. Atmospheric PAA formation is suggested to be sensitive to alkenes and NOX in urban Beijing. In particular, with the help of peroxides, sulfate formation rate from heterogeneous uptake could increase by ∼4 times on haze days, indicating the potential effect of peroxides on enhancement of aerosol oxidative property and secondary sulfate formation.
https://ift.tt/2vwUdet
Unique glandular ex-vivo Th1 and Th17 receptor motifs in Sjögren's syndrome patients using single-cell analysis
Source:Clinical Immunology
Author(s): Alexandria Voigt, Katherine Bohn, Sukesh Sukumaran, Carol M. Stewart, Indraneel Bhattacharya, Cuong Q. Nguyen
Primary Sjögren's syndrome (pSS) is an autoimmune disease in which the underlying cause has yet to be elucidated. The main objective of this study was to determine the T cell receptor (TCR) repertoires of individual infiltrating T helper (Th)-1 and 17 cells of pSS patients using single-cell analysis. Single-cell analysis of ex-vivo infiltrating T cells demonstrated that pSS patients had higher frequencies of activated Th17 cells. Single-cell TCR sequencing revealed that TCRβ variable (TRBV)3-1/joint (J)1-2 (CLFLSMSACVW) and TRBV20-1/J1-1 (SVGSTAIPP*T) were expressed by activated Th1 and Th17 cells in both cohorts. Uniquely, TCRα variable (TRAV)8–2/J5 (VVSDTVLETAGE) was expressed by Th1 cells present only in patients and complementarity-determining region (CDR)3α-specific motif (LSTD*E) present in both Th1/Th17 cells. The study demonstrates that both activated Th1 and Th17 cells of pSS patients showed restricted clonal diversities of which two CDR3 motifs were present in controls and patients, with another two motifs unique to pSS.
https://ift.tt/2K2ULvQ
Adjuvant Chemotherapy Seemed Not to Have Survival Benefit in Rectal Cancer Patients with ypTis‐2N0 After Preoperative Radiotherapy and Surgery from a Population‐Based Propensity Score Analysis
AbstractBackground.Adjuvant chemotherapy is currently offered routinely, as standard, after radical resection for patients with rectal cancer receiving neo‐adjuvant chemoradiation. However, the efficacy of adjuvant chemotherapy in patients with ypTis‐2N0M0 has not been documented to the same extent, and the survival benefit remained controversial. The purpose of this work was to determine the role of chemotherapy in patients with ypTis‐2N0M0 classification.Materials and Methods.Data were obtained from the Surveillance, Epidemiology, and End Results database (n = 4,217). A propensity score model was utilized to balance baseline covariates.Results.Of the 4,217 included patients, 335 with ypTis‐2N0M0 did not receive adjuvant chemotherapy. There were comparable cancer‐specific survivals (CSS) between those undergoing adjuvant chemotherapy or not (log‐rank test = 0.136, p = .712) in the overall sample. After propensity score matching, the cancer‐specific survival did not differ between the chemotherapy and observation groups (log‐rank test = 0.089, p = .765). Additionally, the Cox model did not demonstrate adjuvant chemotherapy as the prognostic factor, with hazard ratio = 0.95 (95% confidence interval 0.69–1.32) for CSS. Furthermore, the 10‐year cumulative CSS was 78.7% and 79.4% between the chemotherapy and observation groups, indicating no significance, and no impact of adjuvant chemotherapy on survival was observed in different subgroups stratified by T stage, histological grade, histology, lymph nodes, and tumor size.Conclusion.Patients with ypTis‐2N0 rectal cancer did not benefit from adjuvant chemotherapy after preoperative radiology and radical surgery in this cohort study. These results provided new insight into the routine use of adjuvant chemotherapy for patients with rectal cancer with completed neo‐adjuvant radiotherapy and curative surgery.Implications for Practice.Inconsistent recommendations for patients with rectal cancer receiving neo‐adjuvant chemoradiation are offered by clinical guidelines. Adjuvant chemotherapy had no cancer‐specific survival benefit, not only in the whole cohort, but also in the propensity score‐matched cohort. A Cox model also confirmed adjuvant chemotherapy was not a significant prognostic factor in ypTis‐2N0 rectal cancer. No survival benefit conferred by adjuvant chemotherapy was observed, regardless of whether T stage, histological type, grade, lymph nodes and tumor size varied.
https://ift.tt/2HdcSRQ
Lenalidomide in Pretreated Mantle Cell Lymphoma Patients: An Italian Observational Multicenter Retrospective Study in Daily Clinical Practice (the Lenamant Study)
AbstractBackground.Mantle cell lymphoma (MCL) has the worst prognosis of B‐cell subtypes owing to its aggressive clinical disease course and incurability with standard chemo‐immunotherapy. Options for relapsed MCL are limited, although several single agents have been studied. Lenalidomide is available in Italy for patients with MCL based on a local disposition of the Italian Drug Agency.Subjects, Materials, and Methods.An observational retrospective study was conducted in 24 Italian hematology centers with the aim to improve information on effectiveness and safety of lenalidomide use in real practice.Results.Seventy patients received lenalidomide for 21/28 days with a median of eight cycles. At the end of therapy, there were 22 complete responses (31.4%), 11 partial responses, 6 stable diseases, and 31 progressions, with an overall response rate of 47.1%. Eighteen patients (22.9%) received lenalidomide in combination with either dexamethasone (n = 13) or rituximab (n = 5). Median overall survival (OS) was reached at 33 months and median disease‐free survival (DFS) at 20 months: 14/22 patients are in continuous complete response with a median of 26 months. Patients who received lenalidomide alone were compared with patients who received lenalidomide in combination: OS and DFS did not differ. Progression‐free survivals are significantly different: at 56 months, 36% in the combination group versus 13% in patients who received lenalidomide alone. Toxicities were manageable, even if 17 of them led to an early drug discontinuation.Conclusion.Lenalidomide therapy for relapsed MCL patients is effective and tolerable even in a real‐life context.Implication for Practice.Several factors influence treatment choice in relapsed/refractory mantle cell lymphoma (rrMCL), and the therapeutic scenario is continuously evolving. In fact, rrMCL became the first lymphoma for which four novel agents have been approved: temsirolimus, lenalidomide, ibrutinib, and bortezomib. The rrMCL therapeutic algorithm is not so well established because data in the everyday clinical practice are still poor. Lenalidomide for rrMCL patients is effective and tolerable even in a real‐life context.
https://ift.tt/2qMApht
Recent Advances in the Treatment of Peripheral T‐Cell Lymphoma
AbstractPeripheral T‐cell lymphoma (PTCL) is a heterogeneous group of clinically aggressive diseases associated with poor outcome. Despite progress in the last several years, resulting in a deeper understanding of the natural history and biology of PTCL based on molecular profiling and next‐generation sequencing, there is a need for improvement in efficacy of chemotherapeutic regimens for newly diagnosed patients. Treatment in the front‐line setting is most often cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP‐like regimens, which are associated with a high failure rate and frequent relapses. Trials evaluating intensive chemotherapy have resulted in variable success in prolonging event‐free survival, but overall survival has remained unchanged. Furthermore, this strategy is limited to patients who are in complete remission after initial anthracycline‐based chemotherapy. Many patients are ineligible for hematopoietic stem cell transplantation because of age or failure to achieve remission. For relapsed disease, advances have been made in the therapeutic arsenal for PTCL. New drugs investigated in phase II studies have achieved response rates between 10% and 30%. However, to date the identification of new therapies has been largely empiric, and long‐term remissions are the exception to the rule. Current patient outcomes suggest the need for the identification and development of active and biologically rational therapies to improve disease management and to extend the duration of response with iterative biomarker evaluation. This review covers the management of PTCL and focuses on new agents and therapeutic combinations, based on a better understanding of biology and pathogenesis of the disease.Implications for Practice.Recent progress in understanding of the biology and pathogenesis of peripheral T‐cell lymphoma has led to the emergence of new drugs. Unfortunately, this has not been met with similar advances in outcome improvement. Anthracycline‐containing regimens, mostly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), are considered the standard of care, although the best first‐line approach remains to be defined. In the relapsed and refractory settings, several new agents achieved response rates between 10% and 30%, although these drugs do not significantly affect survival rates. Therapeutic options based on better molecular characterization of various histological types and combinations with the CHOP regimen or synergic combinations of new drugs may lead to better outcomes.
https://ift.tt/2HeeZET
Promoting Accrual of Older Patients with Cancer to Clinical Trials: An Alliance for Clinical Trials in Oncology Member Survey (A171602)
AbstractBackground.There are multiple known individual‐ and practice‐level barriers to enrollment of older patients with cancer to clinical trials, but little is known about how the clinical research workforce feels about potential higher‐level strategy changes aimed to promote increased enrollment of older patients.Subjects, Materials, and Methods.We invited all 11,351 Alliance for Clinical Trials in Oncology ("Alliance") members to participate in an anonymous, web‐based survey to examine awareness of current accrual patterns for older patients to clinical trials, to ascertain consensus on how to tackle enrollment challenges, and to provide the impetus for high‐level changes to improve clinical trial accrual of older patients with cancer.Results.During the period from February 28, 2017, to June 16, 2017, 1,146 Alliance members participated (response rate = 10%), including a national diverse sample of physicians, nurses, administrative/clinical research staff, and patient advocates with representation from community, academic, and rural sites. Overall, one third felt that >50% of clinical trial enrollees should be age ≥65, and 64.9% felt the Alliance could improve upon enrollment of older patients. The four most commonly ranked strategies to improve enrollment of older patients were creating more dedicated trials for this population (36.3%), minimizing exclusion criteria focused on comorbidity (35.5%), developing independent strategies for those aged ≥65 and for those aged ≥70 (33.2%), and requiring that most/all Alliance trials have a specific expansion cohort of older patients (30.0%).Conclusion.We anticipate that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials.Implications for Practice.This survey of the Alliance for Clinical Trials membership sought opinions on potential, large‐scale, national strategies to improve accrual of older adults with cancer. Consensus was found around multiple strategies, including creating more dedicated trials for older patients, developing less stringent eligibility criteria, and mandating expansion cohorts of older patients within broader Alliance trials. It is anticipated that the recommendations from >1,000 Alliance members will continue to propel important strategy changes aimed to improve accrual of older patients with cancer to clinical trials.
https://ift.tt/2qIpzJk
First Report of Dramatic Tumor Responses with Ramucirumab and Paclitaxel After Progression on Pembrolizumab in Two Cases of Metastatic Gastroesophageal Adenocarcinoma
AbstractCheckpoint inhibitors targeted at programmed cell death‐1 receptor (PD‐1) and its ligand (PD‐L1) can result in significant benefit to a small proportion of patients with cancer, including those with tumors of the stomach and gastroesophageal junction. These drugs are now approved for several solid tumors, including the recent accelerated approval of pembrolizumab for gastroesophageal adenocarcinomas in the third‐line setting and beyond based on the KEYNOTE‐059 phase II trial. Data are lacking on the efficacy of chemotherapy after progression on PD‐1 blockade in metastatic gastroesophageal adenocarcinoma. This report describes the exceptional response of two patients who received ramucirumab plus paclitaxel after progressive disease on pembrolizumab. This early clinical observation suggests that the sequence of administration of PD‐1 blockade and chemotherapy may be important in this disease.
https://ift.tt/2Hh3k8w
Outcome of Mismatch Repair‐Deficient Metastatic Colorectal Cancer: The Mayo Clinic Experience
AbstractBackground.Deficiencies in the DNA mismatch repair system cause errors during DNA replication, which in turn give rise to microsatellite instability (MSI). The impact of MSI on survival in metastatic colorectal cancer (mCRC) is unclear. This cohort study aims to investigate the prognostic and predictive value of MSI in mCRC prior to the immune therapy era.Materials and Methods.A total of 75 MSI‐high (MSI‐H) mCRC patients (pts) and 75 matched (age, gender, disease sidedness, metachronous/synchronous) microsatellite‐stable (MSS) mCRC pts were identified from 1,268 mCRC pts who had MSI/mismatch repair test results at Mayo Clinic Rochester between January 1992 and July 2016. A retrospective review was conducted by using data from electronic medical records. Statistical analyses utilized the Kaplan‐Meier method, log‐rank test, and Cox proportional hazards models.Results.The MSS group was well matched to the MSI‐H group based on age, gender, location, and chronicity of metastatic disease. MSI‐H mCRC pts had earlier disease recurrence (median time from initial diagnosis to metastatic disease diagnosis, MSI‐H group 12.9 vs. MSS group 20.9 months, p = .034). Median overall survival (OS) was 28.1 and 37.4 months for MSI‐H and MSS pts, respectively (p = .99). In total, 94.7% of MSI‐H pts and 98.7% of MSS pts had fluoropyrimidine‐based chemotherapy for metastatic disease, and there was no difference in OS between these two groups (32.3 vs. 37.4 months, p = .91). Forty‐three MSI‐H and thirty‐nine MSS pts had metastasectomy and/or ablation of metastases (p = .51) with longer median OS compared with pts without metastasectomy (MSI‐H: 82.0 vs. 13.9, p < .001; MSS: 69.9 vs. 19.7, p < .001). Age <65 years, BRAF wild type, and metastasectomy were associated with better OS in univariate analysis. Only metastasectomy remained statistically significant in multivariate analysis (p < .001).Conclusion.In mCRC, patients with MSI‐H tumors have similar, but numerically shorter, median overall survival compared with those with MSS tumors. In both groups, metastasectomy and ablation of metastatic disease should be considered to optimize OS.Implications for Practice.This study clearly demonstrated the survival benefits that aggressive metastasectomy provides in selected microsatellite instability‐high metastatic colorectal cancer patients. This could be meaningful practice‐changing information that has been long awaited.
https://ift.tt/2qMA9z1
Cardiovascular abnormalities in patients with oral cleft: a clinical-electrocardiographic-echocardiographic study
OBJECTIVES: The present study aims to describe the clinical, electrocardiographic, and echocardiographic cardiological findings in a group of patients with oral clefts. METHODS: This is a prospective cross-sectional study on 70 children (age range from 13 days to 19 years) with oral clefts who attended the multidisciplinary program of a university hospital from March 2013 to September 2014. The patients were evaluated by a pediatric cardiologist and underwent detailed anamnesis, physical examination, electrocardiogram, and echocardiogram. RESULTS: Sixty percent of the patients were male; 55.7% presented with cleft lip and palate, and 40.0% presented with health complaints. Comorbidities were found in 44.3%. Relevant pregnancy, neonatal, family and personal antecedents were present in 55.7%, 27.1%, 67.2%, and 24.3% of the patients, respectively. Regarding the antecedents, 15.2% of the patients presented with a cardiac murmur, 49.0% with a familial risk of developing plurimetabolic syndrome, and 6% with family antecedents of rheumatic fever. Electrocardiographic evaluation showed one case of atrioventricular block. Echocardiograms were abnormal in 35.7% of the exams, including 5 cases of mitral valve prolapse — one of which was diagnosed with rheumatic heart disease. CONCLUSION: The finding of a family risk of developing plurimetabolic syndrome and a diagnosis of rheumatic heart disease indicates that patients with oral clefts may be more prone to developing acquired heart disease. Thus, our findings highlight the importance of anamnesis and methodological triangulation (clinical-electrocardiographic-echocardiographic) in the investigation of patients with oral clefts and emphasize that cardiological follow-up to evaluate acquired and/or rhythm heart diseases is necessary. This strategy permits comorbidity prevention and individualized planned treatment.
https://ift.tt/2vr3CnL
Neuroprotective effects of erythropoietin on rat retinas subjected to oligemia
OBJECTIVES: Erythropoietin may have neuroprotective potential after ischemia of the central nervous system. Here, we conducted a study to characterize the protective effects of erythropoietin on retinal ganglion cells and gliotic reactions in an experimentally induced oligemia model. METHODS: Rats were subjected to global oligemia by bilateral common carotid artery occlusion and then received either vehicle or erythropoietin via intravitreal injection after 48 h; they were euthanized one week after the injection. The densities of retinal ganglion cells and contents of glial fibrillary acidic protein (astrocytes/Müller cells) and cluster of differentiation 68 clone ED1 (microglia/macrophages), assessed by fluorescence intensity, were evaluated in frozen retinal sections by immunofluorescence and epifluorescence microscopy. RESULTS: Retinal ganglion cells were nearly undetectable one week after oligemia compared with the sham controls; however, these cells were partially preserved in erythropoietin-treated retinas. The contents of glial fibrillary acidic protein and cluster of differentiation 68 clone ED1, markers for reactive gliosis, were significantly higher in retinas after bilateral common carotid artery occlusion than those in both sham and erythropoietin-treated retinas. CONCLUSIONS: The number of partially preserved retinal ganglion cells in the erythropoietin-treated group suggests that erythropoietin exerts a neuroprotective effect on oligemic/ischemic retinas. This effect could be related to the down-modulation of glial reactivity, usually observed in hypoxic conditions, clinically observed during glaucoma or retinal artery occlusion conditions. Therefore, glial reactivity may enhance neurodegeneration in hypoxic conditions, like normal-tension glaucoma and retinal ischemia, and erythropoietin is thus a candidate to be clinically applied after the detection of decreased retinal blood flow.
https://ift.tt/2HMD6HZ
Analysis of the Role of Physicians in the Cessation of Cigarette Smoking Based on Medical Specialization
OBJECTIVE: Physicians do not adequately use their unique professional privilege to prevent patients from smoking. The aim of this study was to investigate the type and extent of advice given to patients by physicians of different medical specialties regarding smoking cessation. METHODS: In total, 317 volunteer physicians were included in this study. The participants rated their attitudes toward the smoking habits of their patients by completing a questionnaire. The approaches used to address the smoking habits of patients significantly differed among physicians working at polyclinics, clinics and emergency service departments (p<0.001). Physicians working at clinics exhibited the highest frequency of inquiring about the smoking habits of their patients, while physicians working at emergency service departments exhibited the lowest frequency. RESULTS: Physicians from different medical specialties significantly differed in their responses. Physicians specializing in lung diseases, thoracic surgery, and cardiology were more committed to preventing their patients from cigarette smoking. CONCLUSIONS: The role of physicians, particularly pulmonologists and thoracic surgeons, is critical in the fight against cigarette smoking. Promoting physician awareness of this subject is highly important in all other branches of medicine.
https://ift.tt/2F1XPV8
Postoperative Monitoring of Free DIEP Flap in Breast Reconstruction with Near-Infrared Spectroscopy: Variables Affecting the Regional Oxygen Saturation
J reconstr Microsurg
DOI: 10.1055/s-0038-1636527
Background The timing of surgical reexploration in microanastomotic thrombosis is directly related to the salvage rate of free flap. Near-infrared spectroscopy (NIRS) is a noninvasive technique, which allows a continuous bedside monitoring of flap oxygenation. The current literature is lacking in the assessment of variables able to modify the NIRS monitoring. The aim of this study is to identify patient and flap-related variables that can affect regional oxygen saturation (rSO2). Methods We retrospectively analyzed the data obtained from 45 consecutive patients undergoing breast reconstruction with deep inferior epigastric perforator (DIEP) flap. The monitoring device used is the Somanetics INVOS 5100C Cerebral/Somatic Oximeter (Covidien). Baseline measures of demographic–anthropometric variables (age, weight, height, body mass index [BMI]) and flap factors (flap size in grams, skin flap area in square centimeters, perforator number, and perforator size in millimeters) were collected from preoperative and intraoperative assessment. We investigated the linear correlation between mean rSO2 and BMI, flap size, skin flap area, perforator number, and perforator size. Results A positive linear correlation between rSO2 values and skin flap area, perforator number, and perforator size was found. A negative linear correlation between rSO2 values and BMI and flap size was found. All correlations are statistically significant. Despite the overall negative linear correlation between rSO2 values and flap size, we observed a bimodal trend: a positive relation up to 800 g, which is inverted above 800 g. Conclusion The NIRS is a reliable additional tool in free flap monitoring. A careful evaluation should be given to patient and surgery factors that can change the oximetry data.
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Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | Full text
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DIEP Flap Breast Reconstruction Complication Rate in Previously Irradiated Internal Mammary Nodes
J reconstr Microsurg
DOI: 10.1055/s-0038-1625986
Background Postmastectomy radiation therapy (PMRT) is a widely accepted treatment for locally advanced breast cancer. Some patients require additional boost radiation to the internal mammary nodes as the part of regional nodal irradiation (RNI). Delayed breast reconstruction with an autologous free flap using the internal mammary vessels for microvascular flap anastomosis is a common practice for these patients. The aim of our study was to evaluate the effect of RNI on autologous microvascular breast reconstruction. Patients and Methods A retrospective study was performed on 57 patients (69 flaps) undergoing deep inferior epigastric perforator (DIEP) flap for delayed breast reconstruction after radiation therapy. The study group included 37 patients (65%) that received PMRT and RNI to the internal mammary nodes. The control group included 20 patients (35%) that received PMRT alone. Early and delayed surgical complications, including wound complications, fat necrosis, and flap loss, were compared between the groups. Results The patient demographics in both groups were similar. Complication rate showed a higher trend in the study group for flap loss (8.3% versus 0%) and vascular anastomosis failure (5.6% versus 0%), but with no statistical difference (p = 0.54, 0.53, respectively). The control group showed a higher trend in fat necrosis (25% versus 8.3%, p = 0.11). Conclusions DIEP flap breast reconstructions with internal mammary vessels anastomosis should be performed with cautious in patients who had received RNI to internal mammary nodes because of potential added risk for surgical complications.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2JaT66a
Free or Perforator-Pedicled Propeller Flaps in Lower Extremity Reconstruction: Defining the Coverage Failure
J reconstr Microsurg
DOI: 10.1055/s-0038-1641725
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Full text
https://ift.tt/2JZNywt
Moving toward uniform and evidence-based practice of radiotherapy for management of cervical cancer in Ontario, Canada
Source:Brachytherapy
Author(s): Negin Shahid, Timothy Craig, Mary Westerland, Allison Ashworth, Michelle Ang, David D'Souza, Raxa Sankreacha, Anthony Fyles, Michael Milosevic, Iwa Kong
PurposeTo recognize the practice of radiotherapy for management of cervical cancer in Ontario, Canada, and to use the results of the survey to harmonize and standardize practice across the province.Methods and MaterialsAn electronic survey (SurveyMonkey) was sent to all 14 provincial cancer centers by Cancer Care Ontario Gynecology Community of Practice (CoP) in 2013. The survey included 72 questions in four different categories: general/demographic, pretreatment assessment, external beam radiotherapy (EBRT), and brachytherapy (BT).ResultsTen of 14 centers treated cervical cancer patients and had a dedicated BT suite. All 10 centers had a peer review process for quality assurance. EBRT technique was a 4-field box in eight of 10 centers. The dose/fractionation for pelvic EBRT was 45–50 Gy in 1.8–2 Gy/fraction in all but one center. Nine of 10 centers used high-dose-rate BT. Only one center offered interstitial BT. For treatment planning, two centers used CT and MRI, five centers used CT, and three centers used orthogonal x-rays. Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology guidelines were used in four of seven of the centers for target volume delineation and in five of seven centers for organs at risk dose constraints. All but one center prescribed and reported dose to Point A.ConclusionsThe survey identified areas where practice varied across the province. Gynecology CoP used this information to identify priorities for practice change and implemented several strategies to harmonize the care of women with cervical cancer. This highlights the value of interdisciplinary, grass-roots initiatives such as CoPs to standardize practice in a practical manner that directly benefits patients.
https://ift.tt/2Hg4mxi
Serum 25-Hydroxyvitamin D and breast cancer risk by pathological subtype (MCC-Spain)
Publication date: Available online 19 April 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Virginia Lope, Adela Castelló, Antonio Mena-Bravo, Pilar Amiano, Nuria Aragonés, Tania Fernández-Villa, Marcela Guevara, Trinidad Dierssen-Sotos, Guillermo Fernandez-Tardón, Gemma Castaño-Vinyals, Rafael Marcos-Gragera, Víctor Moreno, Dolores Salas-Trejo, Marian Diaz-Santos, Madalen Oribe, Isabel Romieu, Manolis Kogevinas, Feliciano Priego-Capote, Beatriz Pérez-Gómez, Marina Pollán
Epidemiologic evidence on the association between vitamin D and breast cancer is still inconclusive. This study analyzes the association between serum 25-hydroxyvitamin D (25(OH)D) and breast cancer risk by pathologic subtype, stage at diagnosis and specific breast cancer risk factors. We conducted a population-based multicase-control study where 546 histologically-confirmed breast cancer cases and 558 population controls, frequently matched by geographic area, age and body mass index, were recruited in 12 Spanish provinces (MCC-Spain). Information was collected by a questionnaire and plasma 25(OH)D was measured by solid-phase extraction on-line coupled to liquid chromatography–tandem mass spectrometry (SPE–LC–MS/MS). Odds ratios and 95% confidence intervals were calculated using logistic and multinomial mixed regression models. We found a clear protective effect between 25(OH)D levels and breast cancer risk, with a significant dose-response trend (OR per 10 nmol/L = 0.88; 95%CI = 0.82-0.94). While no differences were observed between pre and postmenopausal women, stage at diagnosis, or across strata of the main breast cancer risk factors, the protection was more pronounced for triple negative tumors (OR per 10 nmol/L = 0.64; p-heterogeneity = 0.038). Similar results were observed when only cases sampled in the first month after diagnosis were considered. The protective effect of vitamin D on breast cancer risk may be subtype specific, being stronger for more aggressive tumors, which provides a new approach to prevent this disease.
https://ift.tt/2vv2saH
Is it worthy to treat hidradenitis suppurativa with adalimumab in patients with melanoma and other debilitating systemic diseases? A series of clinical dilemmas
Australasian Journal of Dermatology, EarlyView.
https://ift.tt/2HcuY6G
Clinicopathological, immunohistochemical and embryological aspects of cutaneous ciliated Müllerian cyst
Australasian Journal of Dermatology, EarlyView.
https://ift.tt/2qMANMP
Wedge‐shaped polydioxanone threads in a folded configuration (“Solid fillers”): A treatment option for deep static wrinkles on the upper face
Journal of Cosmetic Dermatology, EarlyView.
https://ift.tt/2JYmZry
Nabilone for Non-Chemotherapy Associated Nausea and Vomiting and Weight Loss Due to Medical Conditions: A Review of Clinical Effectiveness and Guidelines [Internet].
This report serves as an update to CADTH's 2014 Rapid Response report. This previous report reviewed four low quality studies and was unable to make any strong conclusions pertaining to the effectiveness of nabilone for non-chemotherapy nabilone for nausea or weight loss.
https://ift.tt/2HhYHXu
Scholar : These new articles for Canadian Journal of Latin American and Caribbean Studies / Revue canadienne des études latino-américaines et caraïbes are available online
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Scholar : These new articles for International Journal of Performance Arts and Digital Media are available online
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Scholar : These new articles for International Journal of Rail Transportation are available online
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Hormone Replacement Therapy After Oophorectomy and Breast Cancer Risk Among BRCA1 Mutation Carriers
This prospective cohort study examines the association between hormone replacement therapy use after oophorectomy and risk of breast cancer among women with a BRCA1 mutation.
https://ift.tt/2HMlVGn
https://ift.tt/2HMlVGn
Validity in Propensity Score–Matched Estimates of Adjuvant Chemotherapy Effects in Rectal Cancer
Current treatment guidelines in the United States for patients with stage T3 or greater or N+ rectal cancer recommend neoadjuvant chemoradiation therapy (nCRT) and 6 months of perioperative chemotherapy. However, there exists a paucity of direct evidence to support the administration of adjuvant chemotherapy following nCRT and radical surgery. The indication for adjuvant chemotherapy in these patients is therefore an important clinical concern and the topic of debate. In this issue of JAMA Oncology, 2 separate observational cohort studies have used the National Cancer Database (NCDB) to evaluate the association between adjuvant chemotherapy and overall survival among patients with ypT0N0 rectal cancer following nCRT and surgery. They conclude that adjuvant chemotherapy may improve survival. So do these 2 reports finally provide adequate support for current treatment guidelines?
https://ift.tt/2F0WuOn
https://ift.tt/2F0WuOn
Evaluating Treatment Effect Based on Duration of Response
This study evaluates the duration of response for crizotinib vs chemotherapy for patients with ALK-positive lung cancer using data from the PROFILE-1014 randomized clinical trial.
https://ift.tt/2HO8WnS
https://ift.tt/2HO8WnS
Addressing Financial Barriers to Enrollment in Clinical Trials
This Viewpoint discusses the need to refine existing guidance to clarify the broad acceptability of offering all types of payment to research participants to reduce financial burden for patients.
https://ift.tt/2F3PSyY
https://ift.tt/2F3PSyY
Patient’s Perception of Physicians’ Professionalism With vs Without Physician Computer Use
This randomized controlled crossover study compares patients' perception of physicians' compassion and patients' perception of physicians' communication skills and professionalism and patients' overall physician preference after watching two standardized scripted-video vignettes of physicians.
https://ift.tt/2HK5lqA
https://ift.tt/2HK5lqA
Association of Adjuvant Chemotherapy With Survival in Patients With Rectal Cancer
This propensity score–matched cohort study examines whether adjuvant chemotherapy is associated with improved overall survival in patients with rectal cancer and pathological complete response following neoadjuvant chemoradiation therapy and resection.
https://ift.tt/2EZRjyj
https://ift.tt/2EZRjyj
Misclassification of Upper Tract Urothelial Carcinoma in Patients With Lynch Syndrome
To the Editor As academic urologic oncologists with an interest in Lynch syndrome (LS)-related genitourinary cancers, we read with great interest the article by Samadder et al quantifying the prevalence of Utah families fulfilling Amsterdam criteria and the risk of colonic and extracolonic malignant neoplasms. The authors used the Utah Population Database and linked it to the Utah Cancer Registry. They described finding a high rate of kidney (standardized morbidity ratio [SMR], 3.22) and urinary bladder (SMR, 1.62) cancers in first-degree relatives of Amsterdam criteria pedigrees. The data are informative and we congratulate the authors on this effort, yet we have one concern.
https://ift.tt/2HL21vB
https://ift.tt/2HL21vB
Adjuvant Chemotherapy and Rectal Cancer Survival With Response Following Neoadjuvant Chemotherapy
This propensity score matching cohort analysis compares the overall survival between adjuvant chemotherapy and postoperative observation in patients with rectal cancer with pathologic complete response following neoadjuvant chemoradiotherapy and resection.
https://ift.tt/2vyObtw
https://ift.tt/2vyObtw
Misclassification of Upper Tract Urothelial Carcinoma in Patients With Lynch Syndrome—Reply
In Reply We thank Drs Matin and Coleman for their informative letter regarding our article. On review of the literature cited by the authors, we agree that there is confusion regarding the nomenclature describing genitourinary malignant neoplasms, especially as it applies to grouping of upper tract urothelial malignant neoplasms separately from renal cell carcinomas.
https://ift.tt/2HMlzj1
https://ift.tt/2HMlzj1
Visual Pathway Injuries in Pediatric Ocular Trauma – A Survey of the National Trauma Data Bank From 2008-2014
Source:Pediatric Neurology
Author(s): Ryan Gise, Timothy Truong, Afshin Parsikia, Joyce N. Mbekeani
IntroductionTraumatic visual pathway injuries (VPI) often are associated with severe head trauma and can have profound deleterious effects on developing children and can complicate rehabilitation. We sought to elucidate the epidemiology of pediatric VPI in the US.MethodsA retrospective evaluation of pediatric patients (<21years) with VPI, submitted to the NTDB (2008-2014), was conducted using ICD-9CM codes. Statistical analysis was performed with SPSS software. Variables were correlated using students' t and Chi-squared tests and logistic regression analyses. Statistical significance was set at p<0.05.Results970 (1.7%) of 58,765 pediatric patients admitted with ocular injuries had VPI. The majority were male (69.2%) and the mean (SD) age was 11.6(7.2) years. Traumatic optic neuropathy (TON) was the most common (86.1%) VPI and had the greatest odds of occurring with oculomotor nerve injury (OR=3.84, 95%CI=2.18-6.74; p<0.001). Associated ocular injuries were open adnexa wounds (87.4%) and orbital fractures (23%). Common mechanisms were motor vehicle occupant (MVTO) (21.5%) and firearms (15.6%). MVTO were most likely in Whites (OR=1.48, 95%CI=1.08-2.03; p<0.015) and firearms in Blacks (OR=4.86,95%CI=3.34–7.07; p<0.001). In the 0-3year age group, VPI were mostly due to falls (OR=2.88,95%CI=1.77–4.69) while the 19-21year group had the greatest association with firearms (OR=2.65,95%CI=1.79-3.93). Overall mortality was 17.6%.ConclusionsVPI occurred in both major and minor ocular injuries. The clear majority were TON that mostly were associated with oculomotor neuropathy. The common mechanisms, MVTO and firearms, revealed age and race disparity. Although infrequent, VPI may have devastating sequelae and should be considered in pediatric ocular injuries.
https://ift.tt/2JbXwtd
A Multidisciplinary Consensus for Clinical Care and Research Needs for Sturge-Weber Syndrome
Source:Pediatric Neurology
Author(s): Alejandro J. De la Torre, Aimee F. Luat, Csaba Juhász, Ho Mai Lan, Davis P. Argersinger, Kara M. Cavuoto, Mabel Enriquez-Algeciras, Stephanie Tikkanen, Paula North, Craig N. Burkhart, Harry T. Chugani, Karen L. Ball, Anna Lecticia Pinto, Jeffrey A. Loeb
Background and RationaleSturge-Weber syndrome (SWS) is a neurocutaneous disorder associated with port wine birthmark, leptomeningeal capillary malformations, and glaucoma. It is associated with an unpredictable clinical course. Due to its rarity and complexity, many physicians are unaware of the disease and its complications. A major focus moving ahead will be to turn knowledge gaps and unmet needs into new research directions.MethodsOn October 1 to 3, 2017, the Sturge-Weber Foundation assembled clinicians from the Clinical Care Network with patients from the Patient Engagement Network of the Sturge-Weber Foundation to identify our current state of knowledge, knowledge gaps and unmet needs.Results and ConclusionsOne clear unmet need is a need for consensus guidelines on care and surveillance. It was strongly recommended that patients be followed by multidisciplinary clinical teams with life-long follow up for children and adults to monitor disease progression in the skin, eye, and brain. Standardized neuroimaging modalities at specified time points are needed together with a stronger clinicopathological understanding. Uniform tissue banking and clinical data acquisition strategies are needed with cross-center, longitudinal studies that will set the stage for new clinical trials. A better understanding of the pathogenic roles of cerebral calcifications and stroke-like symptoms is a clear unmet need with potentially devastating consequences. Biomarkers capable of predicting disease progression will be needed to advance new therapeutic strategies. Importantly, how to deal with the emotional and psychological effects of SWS and its impact on quality of life is a clear unmet need.
https://ift.tt/2JX8a8J
A Neurological Disorder of the Thalamus Mimicking Low-Grade Glioma
Source:Pediatric Neurology
Author(s): Katherine Longardner, Denise Malicki, John Crawford
https://ift.tt/2Hf76eC
Scholar : Journal of Early Childhood Teacher Education, Volume 39, Issue 2, April-June 2018 is now available online on Taylor & Francis Online
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Development of a SERS strategy to overcome the nanoparticle stabilisation effect in serum-containing samples: Application to the quantification of dopamine in the culture medium of PC-12 cells
Publication date: 15 August 2018
Source:Talanta, Volume 186
Author(s): E. Dumont, C. De Bleye, J. Cailletaud, P.-Y. Sacré, P.-B. Van Lerberghe, B. Rogister, G.A. Rance, J.W. Aylott, Ph. Hubert, E. Ziemons
The analysis of serum samples by surface-enhanced Raman spectroscopy (SERS) has gained ground over the last few years. However, the stabilisation of colloids by the proteins contained in these samples has restricted their use in common practice, unless antibodies or aptamers are used. Therefore, this work was dedicated to the development of a SERS methodology allowing the analysis of serum samples in a simple and easy-to-implement way. This approach was based on the pre-aggregation of the colloid with a salt solution. Gold nanoparticles (AuNPs) were used as the SERS substrate and, owing to its physiopathological importance, dopamine was chosen as a model to implement the SERS approach. The presence of this neurotransmitter could be determined in the concentration range 0.5–50 ppm (2.64–264 µM) in the culture medium of PC-12 cells, with a R2 of 0.9874, and at even lower concentrations (0.25 ppm, 1.32 µM) in another matrix containing fewer proteins. Moreover, the effect of calcium and potassium on the dopamine exocytosis from PC-12 cells was studied. Calcium was shown to have a predominant and dose-dependant effect. Finally, PC-12 cells were exposed to dexamethasone in order to increase their biosynthesis and release of dopamine. This increase was monitored with the developed SERS approach.
Graphical abstract
https://ift.tt/2qKjih8
Speciation of organic/inorganic mercury and total mercury in blood samples using vortex assisted dispersive liquid-liquid microextraction based on the freezing of deep eutectic solvent followed by GFAAS
Publication date: 15 August 2018
Source:Talanta, Volume 186
Author(s): Reza Akramipour, Mohammad Reza Golpayegani, Simin Gheini, Nazir Fattahi
In this research, a new vortex assisted dispersive liquid−liquid microextraction based on the freezing of deep eutectic solvent (VADLLME−FDES) has been developed for the determination of organic mercury (R-Hg) and inorganic mercury (Hg2+) in blood samples prior to their analysis by graphite furnace atomic absorption spectrometry (GFAAS). In this method, a green solvent consisting of 1-octyl-3-methylimidazolium chloride and 1-undecanol was used as an extraction solvent, yielding the advantages of material stability, low density, and a suitable freezing point near room temperature. Under the optimum conditions, enrichment factor is 112. The calibration graph is linear in the range of 0.30–60 µg L−1 and limit of detection (LOD) is 0.10 µg L−1. Repeatability and reproducibility of the method based on seven replicate measurements of 5.0 µg L−1 of Hg2+ in analyzed samples were 3.7% and 6.2%, respectively. The relative recoveries of blood samples which have been spiked with different levels of Hg2+ are 90–109%. A new deep eutectic solvent consists of two parts: [DMIM]Cl and 1-undecanol in the molar ratio of 1–2. The accuracy of the proposed procedure was also assessed by determining the concentration of the mercury in a standard reference material. All organic mercury (R-Hg) species were converted to Hg2+ and finally, the concentration of R-Hg is simply calculated by mathematically subtracting the concentrations of Hg2+ from the concentration of total mercury (t-Hg). The extraction methodology is simple, rapid, cheap and green since small amounts of non-toxic solvents are necessary.
Graphical abstract
https://ift.tt/2vpKGWt
Digital analysis with droplet-based microfluidic for the ultrasensitive detection of β-gal and AFP
Publication date: 15 August 2018
Source:Talanta, Volume 186
Author(s): Songbai Tian, Zhen Zhang, Jinyang Chen, Mingyuan Du, Zheng Li, Hai Yang, Xinghu Ji, Zhike He
In this study, we presented a digital analysis with droplet-based microfluidic, which was applied for the detection of β-galactosidase (β-Gal) and AFP. The β-Gal was quantified according to the Poisson Distribution in digital analysis with droplets containing β-Gal and fluorogenic substrate fluorescein di-β-D-galactopyranoside (FDG). In our method, the lowest concentration of β-Gal we could accurately detect was 5 fM. We found that the digital detection could be applied in quantifying protein biomarkers, take AFP for model sample. The AFP was detected through indirect detection with excess streptavidin-conjugated β-galactosidase (SA-β-gal) as signal tag. To be specific, firstly SA-β-gal was conjugated to biotin-labeled AFP antibody, and then the unbounded signal tag in the reaction solution was taken out for digital detection with droplet-based microfluidic. As a result, the AFP could be also indirectly quantified at an fM level through subtraction. This experimental result demonstrated that the indirect detection with droplet-based digital analysis was able to detect biomarkers at a low level with a few samples on an ordinary flow-focusing microfluidic chip.
Graphical abstract
https://ift.tt/2HD4YRm
A colorimetric immunoassay based on glucose oxidase-induced AuNP aggregation for the detection of fumonisin B1
Publication date: 15 August 2018
Source:Talanta, Volume 186
Author(s): Xirui Chen, Yi Liang, Wenjing Zhang, Yuankui Leng, Yonghua Xiong
Naked-eye readout colorimetric signal-based assays are promising for high-throughput screening detection and point-of-care diagnostics in resource-constrained regions. Here, a novel direct competitive plasmonic enzyme-linked immunosorbent assay (dc-pELISA) based on gold nanoparticle (AuNP) aggregation with highly sensitive and robust naked-eye readout signal was developed and used to detect fumonisin B1 (FB1). AuNP aggregation was induced by a horseradish peroxidase (HRP)/hydrogen peroxide (H2O2)/tyramine (TYR) system, resulting in a dramatic color change from red to blue. In this system, H2O2 was produced via GOx-mediated glucose oxidation reaction, and FB1–GOx was used as a competitive antigen. The proposed pELISA demonstrated good linear detection of FB1 from 3.125 ng mL−1 to 25 ng mL−1 with a vivid color change from deep blue to red and a cutoff limit of 12.5 ng mL−1 observed by the naked eye. The average recoveries for FB1-spiked corn samples ranged from 76.5% to 96.8% with a relative standard derivation of 4.88~ 16.4%. Meanwhile, the proposed method exhibited excellent agreement (R2 = 0.927) with the conventional ELISA method in blindly detecting FB1 spiked corn samples. Additionally, the results of the proposed method for FB1 positive corn samples also showed a high consistency with those of the ultra performance liquid chromatography method. These results indicated acceptable accuracy and precision of the proposed colorimetric ELISA for quantitative detection of FB1 in actual corn samples.
Graphical abstract
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Alpha fetoprotein assessment by using a nano optical sensor thin film binuclear Pt-2-aminobenzimidazole-Bipyridine for early diagnosis of liver cancer
Publication date: 15 August 2018
Source:Talanta, Volume 186
Author(s): M.S. Attia, A.O. Youssef, Ziya A. Khan, M.N. Abou-Omar
A simple, precise and sensitive method in which, a nano optical sensor binuclear Pt-2-aminobenzimidazole-bipyridine, Pt(abi)(bpy) complex doped in sol gel is used for the early diagnosis of liver cancer. The idea depends on the assessment of the concentration of alpha fetoprotein (AFP) in the serum samples of different liver patients. The nano binuclear Pt(abi)(bpy) has strong emission spectrum upon excitation at 380 nm in distilled water. The assessment of alpha fetoprotein (AFP) depends on the quenching of the emission spectrum of the optical sensor at 610 nm in water by the alpha fetoprotein (AFP). The calibration plot was achieved over the concentration 5.0 – 350 U L−1 with a correlation coefficient of 0.997 and a detection limit of 3.0 U L−1. The method was used satisfactorily for the diagnosis of liver cancer in a number of serum samples collected from various patients and health state; healthy (≤ 30 U L−1), Virus B (42.2–69.5 U L−1), Virus C (75.7–98.4 U L−1), Cirrhosis (112–147 U L−1) and HCC (185.2–349.6 U L−1). Furthermore, the assessment of the alpha-fetoprotein by the proposed method increases its sensitivity (92.88%) and specificity (91.41%) for early diagnosis of HCC.
Graphical abstract
https://ift.tt/2HdvrFu
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