A network analysis of DSM-5 posttraumatic stress disorder and functional impairment in UK treatment-seeking veterans

Publication date: Available online 28 May 2018
Source:Journal of Anxiety Disorders
Author(s): Jana Ross, Dominic Murphy, Cherie Armour
Network analysis is a relatively new methodology for studying psychological disorders. It focuses on the associations between individual symptoms which are hypothesized to mutually interact with each other. The current study represents the first network analysis conducted with treatment-seeking military veterans in UK. The study aimed to examine the network structure of posttraumatic stress disorder (PTSD) symptoms and four domains of functional impairment by identifying the most central (i.e., important) symptoms of PTSD and by identifying those symptoms of PTSD that are related to functional impairment. Participants were 331 military veterans with probable PTSD. In the first step, a network of PTSD symptoms based on the PTSD Checklist for DSM-5 was estimated. In the second step, functional impairment items were added to the network. The most central symptoms of PTSD were recurrent thoughts, nightmares, negative emotional state, detachment and exaggerated startle response. Functional impairment was related to a number of different PTSD symptoms. Impairments in close relationships were associated primarily with the negative alterations in cognitions and mood symptoms and impairments in home management were associated primarily with the reexperiencing symptoms. The results are discussed in relation to previous PTSD network studies and include implications for clinical practice.



https://ift.tt/2smTasu

HeberFERON, a new formulation of IFNs with improved pharmacodynamics. Perspective for cancer treatment

Publication date: Available online 4 May 2018
Source:Seminars in Oncology
Author(s): Bello-Rivero Iraldo, Garcia-Vega Yanelda, Duncan-Roberts Yaquelin, Vazquez-Blonquist Dania, Hector Santana Milian, Besada-Perez Vladimir, Rios-Cabrera Margarita
The rational combination of recombinant IFN-α2b and IFN-γ resulted in a new formulation of IFNs (HeberFERON) with improved pharmacodynamics. In basal cell carcinomas HeberFERON produces a more rapid antitumor effect and results in a larger number of complete responses. In patients with glioblastoma multiforme, the administration of HeberFERON after surgery and radiotherapy results in an estimated overall survival of 19 months. Patients with state III or IV renal cell carcinoma  also ppear to benefit from the intravenous administration of HeberFERON, with prolongation of survival and a good quality of live. HeberFERON offers a promising alternative formulation of IFNs for the treatment of cancer with a very favorable safety profile.



https://ift.tt/2IQVGSU

CIGB-300: A peptide-based drug that impairs the Protein Kinase CK2-mediated phosphorylation

Publication date: Available online 3 May 2018
Source:Seminars in Oncology
Author(s): Silvio E. Perea, Idania Baladrón, Carmen Valenzuela, Yasser Perera
Protein kinase CK2 - formerly referred to as casein kinase II - is a serine/threonine kinase often found overexpressed in solid tumors and hematologic malignancies that phosphorylates many substrates integral to the hallmarks of cancer. CK2 has emerged as a viable oncology target having been experimentally validated with different kinase inhibitors including small molecule ATP-competitors, synthetic peptides and antisense oligonucleotides. To date only two CK2 inhibitors, CIGB-300 and CX-4945, have entered the clinic in Phase 1-2 trials. This review provides information on CIGB-300 a cell-permeable cyclic peptide that inhibits CK2-mediated phosphorylation by targeting the substrate phosphoacceptor domain. We review data that support the concept of CK2 as an anticancer target, address the mechanism of action and summarize preclinical studies showing antiangiogenic and antimetastatic effects as well as synergism with anticancer drugs in preclinical models. We also summarize early clinical research (Phase 1/2 trials) of CIGB-300 in cervical cancer including data in combination with chemoradiotherapy. The clinical data demonstrate the safety, tolerability and clinical effects of intratumoral injections of CIGB-300 and provide the foundation for future Phase 3 clinical trials in locally advanced cervical cancer in combination with standard chemoradiotherapy.



https://ift.tt/2xnXiyp

Nimotuzumab: beyond the EGFR signaling cascade inhibition

Publication date: Available online 2 May 2018
Source:Seminars in Oncology
Author(s): Zaima Mazorra, Lisset Chao, Anabel Lavastida, Belinda Sanchez, Mayra Ramos, Normando Iznaga, Tania Crombet
One of the most known oncogenes is the epidermal growth factor receptor (EGFR) family. It activates multiple signaling cascades which promote carcinogenesis and immune evasion. Therefore, these molecules have been extensively targeted in cancer immunotherapy. Beyond EGFR signaling cascade inhibition, some of these agents are able to induce T cell activation transforming a passive therapy into a vaccine-like effect.Nimotuzumab is an IgG1 humanized MAb directed against the extracellular domain of the EGFR blocking the binding to its ligands. It possesses unique pharmacodynamics properties, which allow treating patients for long–term period and with very low toxicity. Based on its clinical effect, nimotuzumab has been approved in Cuba and abroad for the treatment of different epithelial tumors. Recently, new potential mechanisms of action of nimotuzumab involving the activation of the innate and adaptive immune response have been reported.This review summarizes the main properties of nimotuzumab in comparison with others EGFR specific monoclonal antibodies highlighting its capacity to activate an effective immune response. In addition, differential clinical effect of this antibody and ongoing clinical trials to deeply characterize the biomarkers of clinical benefit are shown.



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CIMAvax-EGF: Toward long-term survival of advanced NSCLC

Publication date: Available online 1 May 2018
Source:Seminars in Oncology
Author(s): Danay Saavedra, Elia Neninger, Camilo Rodriguez, Carmen Viada, Zaima Mazorra, Agustin Lage, Tania Crombet
Lung cancer remains one of the leading causes of cancer related deaths. Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer. Medical and scientific progress has led to longer survival in an increasing number of patients suffering for cancer. Concerning patients with advanced NSCLC, there is a subgroup with long-term survival. The human Epidermal Growth Factor Receptor (EGFR) family plays a key role in tumor development. This cluster of genes is associated with augmented angiogenesis and enhanced proliferation, survival and migration of tumor cells. The CIMAvax-EGF vaccine consists of a chemical conjugate of the EGF with the P64 protein derived from the Meningitis B bacteria and the Montanide ISA 51, as adjuvant. The vaccine induces antibodies against EGF that results in EGF withdrawal. CIMAvax-EGF has been demonstrated to be safe and immunogenic in advanced NSCLC patients. Here, we summarize the current knowledge of the mechanism of action of CIMAvax-EGF, highlighting the impact of this anti-EGF based vaccine on the long-term survival of advanced NSCLC patients.



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Combining computational and experimental biology to develop therapeutically valuable IL2 muteins

Publication date: Available online 1 May 2018
Source:Seminars in Oncology
Author(s): Kalet León, Karina García-Martínez, Tania Carmenate, Gertrudis Rojas
High-dose IL2, first approved in 1992, has been used in the treatment of advanced renal cell carcinoma and melanoma. In these indications, IL2 induces long lasting objective responses in 5% to 20% of patients. However, toxicity and the unexpected expansion of regulatory T cells (Tregs) have limited its practical use and therapeutic impact, respectively. At the Center of Molecular Immunology in Havana, Cuba, a project was launched in 2005 to rationally design IL2 muteins that could be deployed in the therapy of cancer. The basic goal was to uncouple the pleiotropic effect of IL2 on different immune T cells, to obtain a mutein with a therapeutic index that was better than that achieved with wild type (wt) IL2. Using a combination of computational and experimental biology approaches, we predicted and developed two novel IL2 muteins with therapeutic potential. The first, designated no-alpha mutein, is an agonist of IL2R signaling with a reduced ability to expand Treg in vivo. In mice, the no-alpha mutein IL2 has higher antitumor activity and lower toxicity than wt IL2. It represents a potential best-in-class drug that has begun phase I/II clinical trials in solid tumors. The second, designated no-gamma mutein, is an antagonist of IL2R signaling, with some preferential affinity for Tregs. This mutein has antitumor activity in mice that likely derives from its ability to reduce Treg accumulation in vivo. It represents a first-in-class drug that offers a novel strategy to inhibit Treg activity in vivo.



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GM3(Neu5Gc) ganglioside: An evolution fixed neoantigen for cancer immunotherapy

Publication date: Available online 7 May 2018
Source:Seminars in Oncology
Author(s): Mayrel Labrada, Denise Dorvignit, Giselle Hevia, Nely Rodriguez, Ana M. Hernández, Ana M. Vázquez, Luis E. Fernández
Numerous molecules have been considered as target for cancer immunotherapy due to their levels of expression on tumor cells, their putative importance for tumor biology and relative immunogenicity. In this review we focused on the ganglioside GM3(Neu5Gc), a glycosphingolipid present on the outer side of plasma membranes of vertebrate cells. The reasons for selecting GM3(Neu5Gc) as a peculiar tumor specific antigen and its use as target for cancer immunotherapy are discussed, together with the development of antitumor therapies focused on this target by the Center of Molecular Immunology (CIM, Cuba).



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Differential effects of two therapeutic cancer vaccines on short- and long-term survival populations among patients with advanced lung cancer

Publication date: Available online 1 May 2018
Source:Seminars in Oncology
Author(s): Lizet Sanchez, Leacky Muchene, Patricia Lorenzo-Luaces, Carmen Viada, Pedro C. Rodriguez, Sailyn Alfonso, Tania Crombet, Elia Neninger, Ziv Shkedy, Agustin Lage
BackgroundProgress in immunotherapy has revolutionized the treatment landscape for advanced lung cancer, with emerging evidence of patients experiencing long-term survivals. The goal of this study was to explore the existence of short- and long-term survival populations and to assess the effect of immunotherapy on them.MethodsData from two randomized, multicenter, controlled clinical trials was used to evaluate the effect of two therapeutic vaccines (anti-idiotypic vaccine VAXIRA and anti-EGF vaccine CIMAVAX) on survival curves in advanced non–small cell lung cancer patients. Data were fitted to Kaplan-Meier, standard Weibull survival, and two-component Weibull mixture models. Bayesian Information Criterion was used for model selection.ResultsVAXIRA did not modify, neither the fraction of patients with long-term survivals (0.18 in the control group v 0.19 with VAXIRA, P = .88), nor the median overall survival of the patients in the short-term survival subpopulation (6.8 v 7.8 months, P = .24). However, this vaccine showed great benefit for the patients belonging to the subpopulation of patients with long-term survival (33.8 v 76.6 months, P <.0001). CIMAVAX showed impact in the overall survival of both short- and long-term populations (6.8 v 8.8 months, P = .005 and 33.8 v 61.8 months, P = .007). It also increased the proportion of patients with long-term survival (from 0.18 to 0.28, P = .02).ConclusionsThis study shows that therapeutic vaccines produce differential effects on short- and long-term survival populations and illustrates the application of advanced statistical methods to deal with the long-term evolution of patients with advanced lung cancer in the era of immunotherapy.



https://ift.tt/2LCwoG4

Clinical trial participation by adolescents and young adults with cancer: A continued cause for concern?

Publication date: Available online 30 April 2018
Source:Seminars in Oncology
Author(s): Victoria White, Gemma Skaczkowski, Antoinette Anazodo, Helen Bibby, Wayne Nicholls, Ross Pinkerton, Kate Thompson, Lisa M Orme, Rachel Conyers, Michael Osborn, Marianne B Phillips, Rosemary Harrup, Roderick Walker, Michael Coory
International data indicate that rates of clinical trial enrolment for Adolescents and Young Adults (AYAs) with cancer are markedly lower than for any other age group. This paper reviews the recent literature reporting international trends in clinical trial enrolment since 2010. Subsequently, we present the first population-based, national assessment of clinical trial enrolment for AYAs with cancer in Australia. Reported rates of trial enrolment from Australia, Canada, the United States and the United Kingdom were variable, though consistently low, ranging between 2% and 29%. Trial enrolment was higher for younger AYAs (typically 15-19 years) and those attending pediatric hospitals, and this was replicated in the recent Australian data. The findings highlight a lack of substantial improvement in AYA clinical trial enrolment and in particular, a need for improved opportunities to access trials for patients treated at adult centers.



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Back and forth between cancer treatment and cancer control programs: Insights from the Cuban experience

Publication date: Available online 30 April 2018
Source:Seminars in Oncology
Author(s): Agustin Lage, Teresa Romero
Cancer control is a wider concept than oncology, and includes comprehensive actions for prevention, early diagnosis, treatment, services organization, and education, aiming to modify hard indicators such as incidence, mortality rates, and survival at a population scale. Based on these concepts, organized national cancer programs appeared in several countries in the second half of the 20th century. But at the same time, scientific efforts began to modify the landscape of cancer control. Evidence of mortality reductions began to appear, cancer-driving mutations became measurable, many novel drugs were registered, the methodology of clinical trials spread through health systems, targeted drugs and immunotherapy entered into the mainstream of therapeutics, and treatment goals started to shift from cure to chronic control. The implementation and impact of organized interventions for cancer control show variations according to the context of diverse countries, and scientists and health decision makers can learn from studying these diverse experiences. Among the salient features of cancer control in Cuba are the simultaneous development of a primary care network with abundant human resources and a national biotechnology industry with capacity to provide both generic and innovating drugs and diagnostic systems. The program intentionally assumes the goal of accelerating the transformation of advanced cancer into a chronic disease susceptible of long-term control. The implications of this strategy for population interventions and for scientific research are discussed.



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An evidence-based review on the value of interim FDG-PET in assessing response to therapy in lymphoma

Publication date: Available online 22 April 2018
Source:Seminars in Oncology
Author(s): Hugo J.A. Adams, Thomas C. Kwee
Assessing response to therapy in lymphoma is important for determining patients' prognosis, guiding subsequent treatment, and may be used as an outcome measure of prognostic and therapeutic trials. Traditionally, computed tomography was the mainstay for response assessment and was predominantly performed at the end of treatment, whereas the most recent guidelines propose ¹⁸F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) for this purpose. However, the value of FDG-PET performed during treatment (interim FDG-PET) is still a topic of debate. The purpose of this scientific communication is to provide an evidence-based overview of the value of interim FDG-PET in patients with lymphoma. The article first describes the development of imaging-based response assessment in lymphoma, the rationale and limitations of using FDG-PET for this purpose, and continues with the evidence-based clinical utility of interim FDG-PET in three major lymphoma subtypes (Hodgkin lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma), and finishes with conclusions and recommendations for standard care and future research.



https://ift.tt/2xnufuD

AJCC-8ed nodal staging does not predict outcomes in surgically managed HPV-associated oropharyngeal cancer

Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Kealan C. Hobelmann, Michael C. Topf, Voichita Bar-Ad, Adam J. Luginbuhl, William M. Keane, Joseph M. Curry, David M. Cognetti
ObjectiveTo assess the pathological outcomes of surgically-managed human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (OPSCC) using the 8th Edition of the American Joint Committee on Cancer Staging Manual (AJCC-8ed).Materials and methodsA retrospective review was conducted of 156 patients with previously untreated OPSCC who underwent primary TORS between March 2010 and February 2015 to evaluate the impact of the new AJCC-8ed pathologic staging system. Only patients who had complete pathologic staging with neck dissection and at least 2 years of follow-up records or disease recurrence within 2 years were included for analysis.Results and conclusionsOf the 156 patients, 116 patients had neck dissections and adequate follow-up data. There were 10 total recurrences, including 2 regional recurrences and 1 local recurrence. Lymph node size, number of positive lymph nodes, and presence of any positive nodes were not associated with recurrence for HPV-positive patients. The presence of extranodal extension approached significance. Pathologic N-stage was not predictive of recurrence under the AJCC-7ed or the AJCC-8ed systems. Cancer staging under the AJCC-8ed, but not the AJCC-7ed system was significantly associated with recurrence. In conclusion, pathologic node status as defined in the AJCC-8ed pathologic staging system does not appear to drive prognosis for surgically managed patients. While the new AJCC-8ed staging is an improvement in prognostication, the use of T-stage alone is still a better predictor of recurrence. TORS with adjuvant therapy determined by pathologic findings provides excellent locoregional control for HPV-positive OPSCC.



https://ift.tt/2IVVP7y

Gene signatures and expression of miRNAs associated with efficacy of panitumumab in a head and neck cancer phase II trial

Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Marco Siano, Vittoria Espeli, Nicolas Mach, Paolo Bossi, Lisa Licitra, Michele Ghielmini, Milo Frattini, Silvana Canevari, Loris De Cecco
ObjectivePlatinum-based chemotherapy plus the anti-EGFR monoclonal antibody (mAb) cetuximab is used to treat recurrent/metastatic (RM) head-neck squamous cell carcinoma (HNSCC). Recently, we defined Cluster3 gene-expression signature as a potential predictor of favorable progression-free survival (PFS) in cetuximab-treated RM-HNSCC patients and predictor of partial metabolic FDG-PET response in an afatinib window-of-opportunity trial. Another anti-EGFR-mAb (panitumumab) was used as the treatment agent in RM-HNSCC patients in the phase II PANI01trial. PANI01 tumor samples were analyzed using functional genomics to explore response predictors to anti-EGFR therapy.Materials and methodsWhole-gene expression and real-time PCR analyses were applied to pre-treatment samples from 25 PANI01 patients. Three gene signatures (Cluster3 score, RAS onco-signature, microenvironment score) and seven selected miRNAs were separately analyzed for association with panitumumab efficacy.ResultsCluster3 expression levels had a profile with a significant bimodal separation of samples (P =  3.08 E−13). Higher RAS activation, microenvironment score, and miRNA expression were associated with low-Cluster3 patients. The same biomarkers were separately associated with PFS. Patients with high-Cluster3 had significantly longer PFS than patients with low-Cluster3 (median PFS: 174 versus 51 days; log-rank P = 0.0021). ROC analysis demonstrated accuracy in predicting PFS (AUC = 0.877).ConclusionsDespite differences in clinical settings and anti-EGFR inhibitors used for treatment, response prediction by the Cluster3 signature and selected miRNAs was essentially the same. Translation into a useful clinical assay requires validation in a broader setting.



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Can surgery be avoided in select breast cancer patients with complete radiological response to neoadjuvant chemotherapy?

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Anuradha Apte, Lesley Pennell, Sankaran Chandrasekahran




https://ift.tt/2J9BWJE

Treatment patterns for unilateral, non-invasive breast cancer in women diagnosed in England: Data from a population-based cohort

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Yasmin Jauhari, Melissa Gannon, Jibby Medina, Karen Clements, Kieran Horgan, David Dodwell, David Cromwell




https://ift.tt/2IYct2q

Optimizing treatment for children and adolescents with papillary thyroid carcinoma in post-Chernobyl exposed region: The roles of lymph node dissections in the central and lateral neck compartments

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Mikhail Fridman, Olga Krasko, Alfred King-yin Lam
There is lack of data to predict lymph node metastases in pediatric thyroid cancer. The aims are to study (1) the factors affecting the lymph node metastases in children and adolescence with papillary thyroid carcinoma in region exposed to radiation and (2) to evaluate the predictive significance of these factors for lateral compartment lymphadenectomy. Five hundred and nine patients with papillary thyroid carcinoma underwent total thyroidectomy and lymph nodes resection (central and lateral compartments of the neck) surgery during the period of 1991–2010 in Belarus were recruited. The factors related to lymph node metastases were studied in these patients. In the patients with papillary thyroid carcinoma, increase number of cancer-positive lymph nodes in the central neck compartment were associated with a risk to develop lateral nodal disease as well as bilateral nodal disease. Futhermore, positive lateral compartment nodal metastases are associated with age and gender of the patients, tumour size, minimal extra-thyroidal extension, solid architectonic, extensive desmoplasia in carcinoma, presence of psammoma bodies, extensive involvement of the thyroid and metastatic ratio index revealed after examination of the central cervical chain lymph nodes. The presence of nodal disease, degree of lymph node involvement and the distribution of lymph node metastases significantly increase the recurrence rates of patients with papillary thyroid carcinoma. To conclude, the lymph nodes metastases in young patients with papillary thyroid carcinoma in post-Chernobyl exposed region are common and the pattern could be predicted by many clinical and pathological factors.



https://ift.tt/2sh8isd

Enhanced pre-operative assessment of the axilla with grey-scale and contrast enhanced ultrasound (CEUS) may characterise a group of patients who can safely omit axillary surgery

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Karina Cox, Jenny Weeks, Pippa Mills, Ali Sever, Deborah Allen, Nick Wakeham, Neal Chhaya, Ruxandra Pietrosanu




https://ift.tt/2ITQIRu

Antidepressants appear safe in patients with carcinoid tumor: Results of a restrospective review

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Elie Isenberg-Grzeda, Meredith MacGregor, Afton Bergel, Stacy Eagle, Fernando Espi Forcen, Reema Mehta, Konstantina Matsoukas, Jonathan Wills, Diane Reidy-Lagunes, Yesne Alici
IntroductionPatients living with neuroendocrine tumors have high rates of depression, often necessitating antidepressants, including selective serotonin reuptake inhibitors (SSRI). Neuroendocrine tumors (NETs) secrete vasoactive substances, including serotonin, which contribute to the cluster of symptoms known as carcinoid syndrome (flushing and diarrhea). Controversy exists over whether or not antidepressants are safe in NET. We aimed to study the safety of antidepressant use in NET patients.MethodsWe conducted a retrospective chart review of patients with well differentiated NET who were also prescribed antidepressants from January 2008 through April 2015. The study took place at Memorial Sloan Kettering Cancer Center and was approved by the hospital's institutional review board.ResultsNinety-two patients were included. There were 16 (17.4%) patients with carcinoid syndrome (10 ileum, 1 duodenum, 1 jejunum and 4 unknown primary); and 76 (82.6%) patients without (41 lung, 9 pancreas, 8 ileal, 5 duodenum, 5 appendix, 2 unknown primary, 1 jejunum and 5 other). Median duration of antidepressant prescription was 11.6 months (range, 0–121) among those with carcinoid syndrome (N = 16) and 14.3 months (range, 0–172) among those without carcinoid syndrome (n = 76). Antidepressants were stopped in 31 cases (33.7%), though the reason was not specified in the majority of cases (n = 18; 58%). None of the patients developed carcinoid syndrome while being prescribed antidepressants. No patients developed carcinoid crisis.ConclusionOur findings do not support previous authors' recommendations that SSRIs must be avoided in NET patients. Several classes of antidepressants appeared safe in NET patients with and without carcinoid syndrome.



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A ‘best-practice’ pathway for the acute management of mastitis and breast abscess enables non-specialists to “get it right first time”

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Neill Patani, Findlay MacAskill, Sarah Eshelby, Asha Omar, Anika Kaura, Kayo Contractor, Paul Thiruchelvam, Sally Curtis, Janice Main, Deborah Cunningham, Katy Hogben, Ragheed Al-Mufti, Dimitri Hadjiminas, Daniel Leff




https://ift.tt/2xoNVhK

Morbidity of rectosigmoid resection in cytoreductive surgery for ovarian cancer. Risk factor analysis

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): M. Fournier, C. Huchon, C. Ngo, C. Bensaid, A.S. Bats, P. Combe, M.A. le FrèreBelda, L. Fournier, A. Berger, F. Lecuru
AimRectosigmoid resection is often performed during cytoreductive surgery for ovarian cancer, to achieve the goal of no residual tumour. Here, we evaluated the morbidity associated with rectosigmoid resection and the underlying risk factors.MethodsWe retrospectively assessed consecutive patients managed with rectosigmoid resection during cytoreductive surgery for ovarian cancer at our centre in Paris, France, between 2005 and 2013. All previously identified risk factors were analysed. Major complications were defined as grade III-IV in the Clavien-Dindo classification.ResultsOf 228 patients, 116 had primary and 112 interval surgery; 43/228 [18.9%]; experienced major complications, and these were more common after primary surgery [24.1% vs. 13.4%, p = .04]. The 69 patients who had rectosigmoid resection [33 primary vs. 36 interval surgery, p = .32] had a higher morbidity rate compared to the other patients [30.4% vs. 14.6%, p = .006]. The anastomotic leakage rate was 2.89%. By multivariate logistic regression, independent risk factors for morbidity were postmenopausal status [adjusted odds ratio (aOR), 13.7; 95% confidence interval (95%CI), 1.2;161.9], surgery after neoadjuvant chemotherapy [aOR, 4.4; 95%CI, 1.1;18.8], and peritoneal stripping of the left; paracolic gutter [aOR, 11.3; 95%CI, 2.3;54.3].ConclusionThe morbidity of rectosigmoid resection during cytoreductive surgery for ovarian cancer seems acceptable. Ileostomy does not seem associated with a lower risk of major complications or adjuvant bevacizumab with a higher complication rate.



https://ift.tt/2si27UM

Indocyanine green (ICG) fluorescence mapping for sentinel lymph node (SLN) localisation in early breast cancer

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Sujit Gnanakumar, Dorin Dumitru, Elena Provenzano, John Benson




https://ift.tt/2ITQKJ6

Robotic versus laparoscopic radical hysterectomy in early cervical cancer: A case matched control study

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Valerio Gallotta, Carmine Conte, Alex Federico, Giuseppe Vizzielli, Salvatore Gueli Alletti, Lucia Tortorella, Luigi Pedone Anchora, Francesco Cosentino, Vito Chiantera, Anna Fagotti, Marco D'Indinosante, Silvia Pelligra, Giovanni Scambia, Gabriella Ferrandina
BackgroundThis study aims at evaluating the feasibility, surgical outcome and oncological results observed after robotic radical hysterectomy (RH) compared to laparoscopy for patients with early stage cervical cancer (ECC) patients.MethodsBetween January 2010 and October 2016, 210 patients underwent RH for treatment of ECC: 70 underwent robotic approach (Cases), and 140 underwent laparoscopic approach (Controls).ResultsThere was no statistically significant difference between the two approaches with regard to clinical patient characteristics and in terms of extent of RH and rate of pelvic and aortic lymphadenectomy. Operative time was significantly longer in the robotic versus laparoscopic group (median = 243 min, range 90–612 versus median = 210 min, range 80–660; p value = 0.008). Conversion to laparotomy was necessary in 4 patients (1.9%) in the whole series.No difference was found in terms of intraoperative and postoperative complications between the two groups. Overall, during the observation period, 34 (16.2%) patients experienced any grade postoperative complications, and 21 (10.0%) had >G2 complications.The 3-yr DFS was 88.0% versus 84.0% in robotic and laparoscopic group, respectively (p value = 0.866). Central and/or lateral pelvic disease represented the most common site of relapse. The 3-yr OS was 90.8% in patients underwent robotic RH versus 94.0% in patients underwent laparoscopic RH (p value = 0.924).ConclusionsThe present study shows the equivalence of robotic and laparoscopic approaches to radical surgery of ECC patients, in terms of perioperative and postoperative outcomes with equivalent survival figures, and thus the choice of approach can be tailored to the choice of patient and surgeon.



https://ift.tt/2JaGNdv

Sentinel lymph node biopsy (SLNB) in clinically node negative early breast cancer: a publication-level meta-analysis

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Gurdeep Mannu, Carolyn Taylor, Paul McGale, David Dodwell




https://ift.tt/2IWmmhh

Complete cytoreduction after five or more cycles of neo-adjuvant chemotherapy confers a survival benefit in advanced ovarian cancer

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Andrew Phillips, Sudha Sundar, Kavita Singh, James Nevin, Ahmed Elattar, Sean Kehoe, Janos Balega
ObjectivesTo assess the impact of 5 or more cycles of neoadjuvant chemotherapy (NACT) and cytoreductive outcomes on overall survival (OS) in patients undergoing interval debulking surgery (IDS) for advanced ovarian cancer.MethodsA retrospective review of patients receiving NACT followed by IDS between 2007 and 2017. Patients were analysed according to number of NACT cycles received: group 1 consisted of patients receiving ≤4 cycles and group 2 consisted of those receiving ≥5 cycles. Outcomes were stratified by cytoreductive outcome, surgical complexity, stage and chemotherapy exposure.Results231 patients in group 1 and 167 in group 2 were identified. In group 1, the OS for those achieving Complete (R0), Optimal<1 cm (R1) and Suboptimal (R2) was 51.1, 36.1, and 34.3 months respectively. Statistically significant differences in survival were seen in patients achieving R0vR2 (p < 0.019) but not in R0vR1 (p = 0.125) or R1vR2 (p = 0.358). In group 2, the OS for those achieving R0, R1 and R2 was 53.0, 24.7, and 22.1 months respectively. Statistically significant differences were seen between R0vR1 and R0vR2 (p < 0.00001) but not between R1vR2 (p = 0.917). No difference in OS was seen between groups 1 and 2. In patients achieving R1, there was a trend towards decreasing OS with increasing exposure to NACT from 36.1 (95%CI 32.0–40.2)months with 3 cycles to 24.3 (95%CI 14.4–34.2)months with ≥6 cycles.ConclusionsSurgery with utilisation of cytoreductive procedures to achieve complete clearance should be offered to all patients even after ≥5 cycles if R0 can be achieved. R1 cytoreduction has questionable value in those receiving ≤4 cycles and no value in those receiving ≥5 cycles.



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Editorial Board

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6





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No difference in oncological outcomes after immediate or delayed reconstruction following mastectomy for breast cancer

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Elizabeth Morrow, Ross Dolan, Eva Weiler-Mithoff, Vivienne Blackhall, Laszlo Romics




https://ift.tt/2JaGFL3

Neo-adjuvant versus adjuvant chemotherapy in early breast cancer: EBCTCG patient-level meta-analysis of long-term outcomes among 4756 women in 10 randomised trials

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Paul McGale, Carolyn Taylor, Gurdeep Mannu, Jeremy Braybrooke, Rosie Bradley, Hongchao Pan, Yaochen Wang, Zhe Wang, David Dodwell




https://ift.tt/2xmSMQt

Chemotherapy utilisation in patients aged 50 years and over, diagnosed with invasive early breast cancer in England: Data from a population-based cohort

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Melissa Gannon, Yasmin Jauhari, Kieran Horgan, Jibby Medina, Karen Clements, David Cromwell, David Dodwell




https://ift.tt/2JaGoaZ

Hepatectomy increases metastatic graft and growth in an immunocompetent murine model of peritoneal metastases

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Rea Lo Dico, Annemilai Tijeras-Raballand, Philippe Bonnin, Jean Marie Launay, Rachid Kaci, Cynthia Pimpie, Brice Malgras, Anthony Dohan, Gianluigi Maria Lo Dico, Marc Pocard
BackgroundCurative surgery of synchronous peritoneal metastases (PM) and colorectal liver metastases (LM) has been recently investigated as feasible option. When synchronous peritoneal and liver resection is not achievable, the sequence of the surgery remains unknown. Our hypothesis was that liver resection (LR) promotes peritoneal growth resulting in a non-resectable PM. We sought to analyse the effects of major LR and liver regeneration after hepatectomy in a murine model of PM and the associated angiogenesis.MethodsMurine model of colorectal PM in Balb/C mice was developed by intraperitoneal injection of different CT-26 tumour cell concentrations. Five days after the injection, mice were randomized into three groups: 68% hepatectomy group, sham laparotomy and control group without surgery. On post-operative days 1, 5 and 20, PM was evaluated macroscopically, tumour growth and liver regeneration by immunohistochemistry, and angiogenesis by immunofluorescence. Circulating progenitor cells, plasmatic cytokines and digestive arterial blood flow velocity measurements were also analysed.ResultsReproducible murine model of limited colorectal PM was obtained. Surgery induced PM increases and promoted neo-angiogenesis. Major hepatectomy influence the tumour growth in the late phase after surgery, the extent of extra-peritoneal metastasis and the increase of Ki-67 expression in the remnant liver.ConclusionsThis animal model confirms the pro-tumoural and pro-angiogenic role of surgery, laparotomy and major LR, which promotes the increase of angiogenic factors and their participation in PM growth. These results suggest that peritoneal resection should be first step in the case of two-step liver and peritoneal surgery for patients with colorectal PM and LM.



https://ift.tt/2IYcrHQ

International validation of the European organisation for research and treatment of cancer QLQ-BRECON23 quality-of-life questionnaire for women undergoing breast reconstruction

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Zoe Winters, Maryam Afzal, Claudia Rutherford, Bernhard Holzner, Gerald Rumpold, Renee A. da Costa Vieira, Sue Hartup, Kathy Flitcroft, Vesna Bjelic-Radisic, Anne Oberguggenburger, Marie Panouilleres, Maria Mani, Guiseppe Catanuto, Michael Douek, Jalal Kokan, Madeleine Trudy King




https://ift.tt/2J9BM50

Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Federica Bruno, Dario Baratti, Antonia Martinetti, Daniele Morelli, Elisa Sottotetti, Chiara Bonini, Marcello Guaglio, Shigeki Kusamura, Marcello Deraco
BackgroundThe differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients.MethodsMarkers were dosed before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) by enzyme-linked immunosorbent assay (ELISA) in 30 DMPM patients and 14 controls with other PSMs. Receiver-operating characteristics (ROC) curve were plotted. The performance of each marker was assessed by the area under the ROC curve (AUC-ROC).ResultsMean mesothelin levels were 7.84 ng/dl (SD = 5.14) in DMPM group and 3.00 ng/dl (SD = 1.25) in controls (P = 0.001). Mean CEA levels were 5.3 ng/dl (SD = 4.7), and 61.96 ng/dl (SD = 112.5) in the two groups (P = 0.008). No statistical difference was seen for osteopontin (P = 0.738), CA19.9 (P = 0.081), CA125 (P = 0.600), and CA15.3 (P = 0.365). AUC-ROC was 0.836 for CA19.9, 0.812 for mesothelin, 0.793 for CEA, and lower for CA125 (0.652), osteopontin (0.531), and CA15.3 (0.481). Using diagnostic cut-offs selected by ROC methodology, sensitivity, specificity, positive and negative predictive values were 70.0%, 100.0%, 100.0%, and 60.9% for mesothelin >5.21 ng/dl, and 90.0%, 85.7%, 93.1%, and 80.0% for CA19.9 < 8.8 U/dl. At multivariate analysis, osteopontin correlated with survival (hazard rate 6.46; 95%CI 1.81–23.05; P = 0.004).ConclusionWhen assessing PSMs of unknown origin, elevated mesothelin with low CA19.9 may increase the suspicion index for DMPM. Ospeopontin warrants further investigations as a prognostic marker for DMPM.



https://ift.tt/2xoNPGU

The effect of clinical and tumour factors on prognosis after contralateral breast cancer (CBC) in Northern Ireland (NI)

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Colin McIlmunn, Finian Bannon, Deirdre Fitzpatrick, Kienan Savage, Stuart McIntosh




https://ift.tt/2sdzLv8

Targeted axillary lymph node dissection improves the accuracy of axillary assessment

Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Deyana Oweis, Rachel Howitt, Nidhi Sibal, Loraine Kalra, Adam Critchley, Henry Cain




https://ift.tt/2IV08Ms

Changes in Th17 cells function after nanocurcumin use to treat multiple sclerosis

Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Sanam Dolati, Majid Ahmadi, Reza Rikhtegar, Zohreh Babaloo, Hormoz Ayromlou, Leili Aghebati-Maleki, Mohammad Nouri, Mehdi Yousefi
BackgroundMS is a chronic inflammatory disease that causes to brain inflammation and Th17 cells are considered to be important in multiple sclerosis pathogenesis. In the current study, we aimed to identify nanocurcumin effects on Th17 cells frequency, cytokines secretion, and expression of transcription factor of patients with relapsing-remitting multiple sclerosis (RRMS).MethodsIn this study we investigated frequency of Th17 lymphocytes; the expression of transcription factor, associated cytokines and the concentration of them in 35 healthy controls, and from 25 patients at baseline and after 6 months of nanocurcumin treatment and also from 25 patients whose received placebo by flowcytometry, real-time PCR and ELISA, respectively.ResultsOur analysis revealed that the proportions of Th17 were increased dramatically, along with increases in the levels of IL-17A, IL-23, and RORγt expression in MS patients in compared with healthy control group. Post-treatment evaluation of the nanocurcumin group revealed a significant decrease in Th17 associated parameters such as Th17 frequency (p = 0.029), expression levels of RORγt (p < 0.0001) and IL-17 (p = 0.0044) and also secretion level of IL-17 (p = 0.0011), but IL-23 mRNA expression levels and IL-23 concentration were not influenced by nanocurcumin. However, in the placebo group there is no significant changes in these factors.ConclusionOur study suggests that the increase in proportion of Th17 cells might contribute to the pathogenesis of RRMS. The results of the current work indicated that nanocurcumin is able to restore the dysregulated of Th17 cells in MS patients.



https://ift.tt/2GXCgpS

Design, synthesis and investigation of potential anti-inflammatory activity of O-alkyl and O-benzyl hesperetin derivatives

Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Ai-Ling Huang, Yi-Long Zhang, Hai-Wen Ding, Bo Li, Cheng Huang, Xiao-Ming Meng, Jun Li
Hesperetin has been known to exert several activities such as anti-oxidant, antitumor and anti-inflammatory. To find hesperetin derivatives showing better activity, sixteen novel hesperetin derivatives were designed and synthesized. The new obtained compounds were investigated for their anti-inflammatory activity by inhibiting interleukin-1β (IL-1β), interleukin-6 (IL-6) and production of nitric oxide (NO) in mouse RAW264.7 macrophages, and the structure-activity relationship of them was discussed. Among them, the compound 1l, 2c demonstrated more effective inhibitory activity of IL-1β and IL-6, meanwhile, the compound 1l showed the best inhibition of NO production. The results of NO inhibition study were basically accord with the molecular docking results of inducible nitric oxide synthase (iNOS). Furthermore, the expression of LPS-induced iNOS and components of NF-κB signaling pathway were reduced by compound 1l. Our results suggest that the inhibitory effect of compound 1l on LPS-stimulated inflammatory mediator production in RAW 264.7 cells is associated with the suppression of NF-κB signaling pathway and inhibition of iNOS protein and iNOS activity. From in vivo study, it was also observed that compound 1l had hepato-protective and anti-inflammatory effects in CCl4-induced acute liver injury mouse models.

Graphical abstract

https://ift.tt/2kuZWZJ

Modular MLV-VLPs co-displaying ovalbumin peptides and GM-CSF effectively induce expansion of CD11b+ APC and antigen-specific T cell responses in vitro

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Patricia Gogesch, Stefan Schülke, Stephan Scheurer, Michael D. Mühlebach, Zoe Waibler
The development of novel vaccination strategies is a persistent challenge to provide effective prophylactic treatments to encounter viral infections. In general, the physical conjugation of selected vaccine components, e.g. antigen and adjuvant, has been shown to enhance the immunogenicity and hence, can increase effectiveness of the vaccine. In our proof-of-concept study, we generated non-infectious, replication deficient Murine Leukemia Virus (MLV)-derived virus-like particles (VLPs) that physically link antigen and adjuvant in a modular fashion by co-displaying them on their surface. For this purpose, we selected the immunodominant peptides of the model antigen ovalbumin (OVA) and the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) as non-classical adjuvant. Our results show that murine GM-CSF displayed on MLV-VLPs mediates expansion and proliferation of CD11b⁺ cells within murine bone marrow and total spleen cells. Moreover, we show increased immunogenicity of modular VLPs co-displaying OVA peptides and GM-CSF by their elevated capacity to induce OVA-specific T cell-activation and -proliferation within OT-I and OT-II splenocyte cultures. These enhanced effects were not achieved by using an equimolar mixture of VLPs displaying either OVA or GM-CSF. Taken together, OVA and GM-CSF co-displaying MLV-VLPs are able to target and expand antigen presenting cells which in turn results in enhanced antigen-specific T cell activation and proliferation in vitro. These data suggest MLV-VLPs to be an attractive platform to flexibly combine antigen and adjuvant for novel modular vaccination approaches.

Graphical abstract

https://ift.tt/2IT3Ev2

Dendritic cells with increased expression of suppressor of cytokine signaling 1(SOCS1) gene ameliorate lipopolysaccharide/d-galactosamine-induced acute liver failure

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Shan-Shan Li, Min Yang, Yong-Ping Chen, Xin-Yue Tang, Sheng-Guo Zhang, Shun-Lan Ni, Nai-Bin Yang, Ming-Qin Lu
Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure. Bone marrow derived dendritic cells were transfected with lentivirus encoding SOCS1 and negative control lentivirus, thereafter collected for costimulatory molecules analysis, allogeneic Mixed Lymphocyte Reaction and Western blot test of JAK/STAT pathway. C57BL/6 mice were randomly separated into normal control and treatment groups which respectively received tail vein injection of modified DCs, negative control DCs and normal saline 12 h earlier than acute liver failure induction. Our results indicated that DCs with overexpression of SOCS1 exhibited like regulatory DCs (DCregs) with low level of costimulatory molecules and poor allostimulatory ability in vitro, which was supposed to correlate with block of JAK2/STAT1 signaling. In vivo tests, we found that infusion of modified DCs increased survival rate of acute liver failure mice and alleviate liver injury via inhibition of TLR4/HMGB1 pathway. We concluded that DCs transduced with SOCS1 gene exhibit as DCregs through negative regulation of JAK2/STAT1 pathway and ameliorated lipopolysaccharide/d-galactosamine induced acute liver failure via inhibition of TLR4 pathway.



https://ift.tt/2GZFTvn

Modular MLV-VLPs co-displaying ovalbumin peptides and GM-CSF effectively induce expansion of CD11b+ APC and antigen-specific T cell responses in vitro

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Patricia Gogesch, Stefan Schülke, Stephan Scheurer, Michael D. Mühlebach, Zoe Waibler
The development of novel vaccination strategies is a persistent challenge to provide effective prophylactic treatments to encounter viral infections. In general, the physical conjugation of selected vaccine components, e.g. antigen and adjuvant, has been shown to enhance the immunogenicity and hence, can increase effectiveness of the vaccine. In our proof-of-concept study, we generated non-infectious, replication deficient Murine Leukemia Virus (MLV)-derived virus-like particles (VLPs) that physically link antigen and adjuvant in a modular fashion by co-displaying them on their surface. For this purpose, we selected the immunodominant peptides of the model antigen ovalbumin (OVA) and the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) as non-classical adjuvant. Our results show that murine GM-CSF displayed on MLV-VLPs mediates expansion and proliferation of CD11b⁺ cells within murine bone marrow and total spleen cells. Moreover, we show increased immunogenicity of modular VLPs co-displaying OVA peptides and GM-CSF by their elevated capacity to induce OVA-specific T cell-activation and -proliferation within OT-I and OT-II splenocyte cultures. These enhanced effects were not achieved by using an equimolar mixture of VLPs displaying either OVA or GM-CSF. Taken together, OVA and GM-CSF co-displaying MLV-VLPs are able to target and expand antigen presenting cells which in turn results in enhanced antigen-specific T cell activation and proliferation in vitro. These data suggest MLV-VLPs to be an attractive platform to flexibly combine antigen and adjuvant for novel modular vaccination approaches.

Graphical abstract

https://ift.tt/2IT3Ev2

Dendritic cells with increased expression of suppressor of cytokine signaling 1(SOCS1) gene ameliorate lipopolysaccharide/d-galactosamine-induced acute liver failure

Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Shan-Shan Li, Min Yang, Yong-Ping Chen, Xin-Yue Tang, Sheng-Guo Zhang, Shun-Lan Ni, Nai-Bin Yang, Ming-Qin Lu
Acute liver failure is a devastating clinical syndrome with extremely terrible inflammation reaction, which is still lack of effective treatment in clinic. Suppressor of Cytokine Signaling 1 protein is inducible intracellular negative regulator of Janus kinases (JAK)/signal transducers and activators of transcription (STAT) pathway that plays essential role in inhibiting excessive intracellular signaling cascade and preventing autoimmune reaction. In this paper, we want to explore whether dendritic cells (DCs) with overexpression of SOCS1 have a therapeutic effect on experimental acute liver failure. Bone marrow derived dendritic cells were transfected with lentivirus encoding SOCS1 and negative control lentivirus, thereafter collected for costimulatory molecules analysis, allogeneic Mixed Lymphocyte Reaction and Western blot test of JAK/STAT pathway. C57BL/6 mice were randomly separated into normal control and treatment groups which respectively received tail vein injection of modified DCs, negative control DCs and normal saline 12 h earlier than acute liver failure induction. Our results indicated that DCs with overexpression of SOCS1 exhibited like regulatory DCs (DCregs) with low level of costimulatory molecules and poor allostimulatory ability in vitro, which was supposed to correlate with block of JAK2/STAT1 signaling. In vivo tests, we found that infusion of modified DCs increased survival rate of acute liver failure mice and alleviate liver injury via inhibition of TLR4/HMGB1 pathway. We concluded that DCs transduced with SOCS1 gene exhibit as DCregs through negative regulation of JAK2/STAT1 pathway and ameliorated lipopolysaccharide/d-galactosamine induced acute liver failure via inhibition of TLR4 pathway.



https://ift.tt/2GZFTvn

Costunolide promotes the proliferation of human hair follicle dermal papilla cells and induces hair growth in C57BL/6 mice

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2xo7siq

Pigmented transverse nasal band: A distinct presentation

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2srsgQz

Costunolide promotes the proliferation of human hair follicle dermal papilla cells and induces hair growth in C57BL/6 mice

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2xo7siq

Pigmented transverse nasal band: A distinct presentation

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2srsgQz

A 9-year analysis of transoral laser microsurgery (TLM) of head and neck cancer on their potential suitability for transoral robotic surgery (TORS) for estimation of future TORS-specific caseload

OBJECTIVE: After that the establishment of transoral robotic surgery (TORS) for head and neck cancer has been adopted in North America, it has also recently been adopted in Europe. In these parts, transoral laser microsurgery (TLM) is widely applied. The aim of the study was to identify the absolute number of operations amenable to TORS at a TORS initiating institution on the basis of all former TLM cases.

PATIENTS AND METHODS: All laser surgery procedures from May 2004 to April 2013 (108 months) were initially retrospectively registered; after that, all stage pT1 and pT2 squamous cell carcinomas of the oropharynx, hypopharynx, and larynx were selected.

RESULTS: Over a period of nine years out of all TLM cases, there were 45 cases of pT1 and pT2 orohypopharyngeal and supraglottic squamous cell carcinomas, which could have been considered for TORS surgery. With the inclusion of a nowadays-typical TORS indication such as tonsil cancer, 142 cases would have been amendable to TORS.

CONCLUSIONS:  The indication for TORS would have been made in five of the TLM cases per year. Institutions initiating TORS, which own an intensive TLM experience, are encouraged to TORS indications in more than solely typical TLM indications. By indicating TORS instead of handheld surgery, a higher caseload of more than 15 cases per year can be achieved for TORS indications.

L'articolo A 9-year analysis of transoral laser microsurgery (TLM) of head and neck cancer on their potential suitability for transoral robotic surgery (TORS) for estimation of future TORS-specific caseload sembra essere il primo su European Review.

https://ift.tt/2xmzefk

Hepatic Abscess in a Returning Traveler with Crohn’s Disease: Differentiating Amebic from Pyogenic Liver Abscess

Liver abscess is a rare but serious complication of Crohn's disease. Patients with Crohn's disease are at risk for pyogenic liver abscesses due to immunosuppressive therapy, fistulous disease, and intraabdominal abscesses. Inflammatory bowel disease patients are also known to have a greater prevalence of amebiasis compared to the rest of the population; however, a higher incidence of amebic liver abscess has not been reported. We describe a case of a liver abscess in a patient with Crohn's disease that was initially presumed pyogenic but later determined to be amebic in origin. Epidemiology, clinical presentation, diagnosis, and treatment of amebic and pyogenic liver abscesses are discussed.

https://ift.tt/2kvWk9P

Sasa quelpaertensis leaves ameliorate alcohol-induced liver injury by attenuating oxidative stress in HepG2 cells and mice

Publication date: Available online 28 May 2018
Source:Acta Histochemica
Author(s): Kalahe Hewage Iresha Nadeeka Madushani Herath, So Jin Bing, Jinhee Cho, Areum Kim, Gyeonghun Kim, Ju-Sung Kim, Jae-Bum Kim, Yang Hoi Doh, Youngheun Jee
Oxidative stress plays a crucial role in the progression of alcoholic liver diseases and substances of antioxidant property are of special interest for therapeutic purposes. We investigated the hepatoprotective effect of leaf extracts of Sasa quelpaertensis, an edible bamboo mainly cultivated in Jeju Island, South Korea. We examined the cytotoxicity of different extracts (distilled water, 20–80% EtOH) of S. quelpaertensis on HepG2 cells and their hepatoprotective effect on HepG2 cells stimulated by ethanol (800 mM, 24 h). Furthermore, we measured reactive oxygen species (ROS) production, ethanol toxicity induced cell death, and the activity of antioxidant enzymes. In in vivo experiments, liver damage was induced by oral administration of 5 g/kg ethanol with or without potent ethanol extract of S. quelpaertensis (10 or 100 mg/kg) 12 h interval for a total of 3 doses. Only 80% ethanol extract of S. quelpaertensis (SQEE80) exhibited cytoprotective effect on HepG2 cells against alcohol-induced toxicity. SQEE80 treatment (250, 500 μg/mL) in ethanol exposed HepG2 cells showed significant attenuation of ROS production and ethanol toxicity induced cell death. Furthermore, SQEE80 markedly increased the activity of antioxidant enzyme glutathione peroxidase 1 in ethanol exposed HepG2 cells compared to ethanol stimulated cells. In in vivo experiments, SQEE80 treatment evidently suppressed the alcohol-induced histopathological changes in liver, serum ethanol content, and expression of cytochrome P450 2E1. Furthermore, SQEE80 significantly reversed the reduction of glutathione level in the ethanol challenged liver. Taken together, we suggest the possibility of developing SQEE80 as a natural hepatoprotective substance in attenuating alcohol-induced oxidative stress.



https://ift.tt/2L0S6Cu

A Review of the Associations Between Obstructive Sleep Apnea and Hypertensive Disorders of Pregnancy and Possible Mechanisms of Disease

Obesity is prevalent among pregnant women in the United States; 15-20% of obese pregnant women have obstructive sleep apnea. The prevalence of obstructive sleep apnea increases along with body mass index, age and in the presence of other co-morbidities. Untreated obstructive sleep apnea in women is associated with a range of cardiovascular, pulmonary and metabolic co-morbidities; recent studies suggest that women with obstructive sleep apnea in pregnancy may be at significantly greater risk of entering pregnancy with chronic hypertension and/or of developing hypertensive disorders of pregnancy: gestational hypertension; preeclampsia; or eclampsia.

https://ift.tt/2ITe21H

The recent progress of isoxazole in medicinal chemistry

Publication date: Available online 28 May 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Jie Zhu, Jun Mo, Hong-zhi Lin, Yao Chen, Hao-peng Sun
Isoxazole compounds exhibit a wide spectrum of targets and broad biological activities. Developing compounds with heterocycle rings has been one of the trends. The integration of isoxazole ring can offer improved physical-chemical properties. Because of the unique profiles, isoxazole ring becomes a popular moiety in compounds design. In this review article, the major focus has been paid to the applications of isoxazole compounds in treating multiple diseases, including anticancer, antimicrobial, anti-inflammatory, etc. Strategies for compounds design for preclinical, clinical, and FDA approved drugs were discussed. Also, the emphasis has been addressed to the future perspectives and trend for the application.

Graphical abstract

https://ift.tt/2xkTOg2

Genetic Testing and Autism: Tutorial for Communication Sciences and Disorders

Publication date: Available online 28 May 2018
Source:Journal of Communication Disorders
Author(s): Laura S. DeThorne, Stephanie Ceman
This tutorial provides professionals in communication sciences and disorders with an overview of the molecular basis and parental perceptions of genetic testing as associated with autism. The introduction notes the prominence of genetic testing within present-day medical practices and highlights related limitations and concerns through the lens of disability critique. The body of the tutorial provides an overview of four different forms of genetic variation, highlighting the potential associations with autism and available genetic testing. In sum, most autism cases cannot be associated directly with specified forms of genetic variation but are attributed instead to multiple genetic and environmental influences working in concert. Finally, the discussion focuses on parental perceptions of the genetic testing associated with autism, both the potential benefits and harms, and emphasizes the need to integrate first-person perspectives from autistic individuals.Learning Outcomes: Readers will a) gain an interdisciplinary introduction to the landscape of genetic testing and autism, b) become familiar with the different forms of genetic testing currently available, c) be able to highlight potential benefits and harms associated with genetic testing, and d) be able to offer three explicit recommendations for individuals and families considering genetic testing related to autism.



https://ift.tt/2IWcEeI

Frontotemporal dementia with Parkinsonism linked to chromosome-17 mutations enhance tau oligomer formation

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Sumihiro Maeda, Yuhei Sato, Akihiko Takashima
The P301 L mutation in tau, a microtubule-associated protein, causes frontotemporal dementia with Parkinsonism linked to chromosome-17 (FTDP-17) that is accompanied by formation of filamentous polymers of tau. The mutation reduces the binding capability of microtubules and enhances tau filament formation. However, it is unclear whether the P301 L mutation increases the formation of the intermediates of tau filaments that are suggested to be a toxic species of tau. To determine the amount and structure of the intermediates harboring with the P301L mutation, we purified recombinant versions of wild-type, P301L, and 4 other mutants (i.e., P301S, P301T, V337M, and R406W) tau proteins and analyzed the heparin-induced aggregation of those tau constructs. We found that all of the FTDP-17 mutants increased levels of the intermediate tau oligomers. The sizes were determined by atomic force microscopy and laser light scattering. The V337M and R406W oligomers were similar in size to the wild-type, but the P301L, P301T, and P301S mutants formed smaller oligomers. In a P301L transgenic mouse model, we found tau aggregates that were similar in size to the recombinant tau oligomer. These results indicate that FTDP-17 mutations contribute to the pathogenesis via the increased formation of tau oligomers.



https://ift.tt/2xhmsP0

Phosphorylation of SET mediates apoptosis via P53 hyperactivation and NM23-H1 nuclear import

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Mengjuan Wu, Guang Yu, Tonghai Yan, Dan Ke, Qun Wang, Rong Liu, Jian-Zhi Wang, Bin Zhang, Dan Chen, Xiaochuan Wang
Apoptosis plays an important role in neuron loss in Alzheimer's disease (AD). SET, an endogenous inhibitor of protein phosphatase-2A, is phosphorylated in AD brains and positively correlates with cell apoptosis. However, the mechanism underlying phosphorylated SET association with apoptosis remains unknown. Here, we show that mimetic phosphorylation of SET (S9E) induced apoptosis of primary cultured neurons. To investigate its mechanism, we overexpressed SET (S9E) in HEK293/tau cells and observed apoptosis accompanied with a marked increase of cleaved caspase-3 and cytoplasmic SET (S9E) retention with enhanced protein phosphatase-2A inhibition, which subsequently caused p53 hyperphosphorylation and activation. In addition, it caused the release of nucleoside diphosphate kinase A isoform a, a positive regulator of p53 with a DNase activity from SET/nucleoside diphosphate kinase A isoform a complex, and migration into the nucleus, resulting in DNA damage. Besides, it reduced nuclear tau accumulation leading to DNA protection deficiency. These findings suggest that SET phosphorylation is involved in the neuronal apoptotic pathway in AD and provide a new insight into the mechanism of this pathology.



https://ift.tt/2sfsc7b

Lifestyle-dependent brain change: a longitudinal cohort MRI study

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Regina EY. Kim, Chang-Ho Yun, Robert J. Thomas, Jang-Hoon Oh, Hans J. Johnson, Soriul Kim, Seungku Lee, Hyung Suk Seo, Chol Shin
We investigated both independent and interconnected effects of 3 lifestyle factors on brain volume, measuring yearly changes using large-scale longitudinal magnetic resonance imaging, in middle-aged to older adults. We measured brain volumes in a cohort (n = 984, 49–79 years) from the Korean Genome and Epidemiology Study group, using baseline and follow-up estimates after 4 years. In our analysis, the accelerated brain atrophy in normal aging was observed across regions (e.g., brain tissue: -0.098 ± 0.01 mL/y, p < 0.001). An independent lifestyle-specific trend of brain atrophy across time was also evident in men, where smoking (p = 0.012) and physical activity (p = 0.014) showed the strongest association with the atrophy rate. Linear regression analysis of the interconnected effect revealed that brain atrophy is mitigated by intense physical activity in smoking males. Lifestyle factors did not show any significant effect on brain volume in women. These results provide important information regarding lifestyle factors that affect brain aging in mid-to-late adulthood. Our findings may aid in the identification of preventive measures against dementia.



https://ift.tt/2xl56kn

The total number of myelinated nerve fibers is reduced in corpus callosum in brains from patients with Alzheimer's disease

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Rimvall Nicolai Køster, Riise Jesper, Pakkenberg Bente
The total number of myelinated fibers in corpus callosum (CC) in Alzheimer's disease is poorly described. Using a two-dimensional fractionator principle we estimated the total number of fibers in ten females patients with Alzheimer's disease (AD) (mean age 82.8 years) and 12 female control subjects (mean age 80.6 years) and found the mean number of myelinated fibers to be significantly 30% higher in the control group (90.0 × 10⁶; coefficient of variation = SD/mean = 27%) than in the AD group (69.3 × 10⁶; coefficient of variation = 20%) (p = 0.028). A significant loss of fibers (≥2.2 μm in diameter) was found in the anterior part of the CC in AD patients compared to control subjects (p = 0.045). For both groups, we found a positive correlation between the total number of myelinated fibers and CC cross-sectional area (AD, r = 0.81; control subjects, r = 0.73). There was a negative correlation in both groups between age and total number of myelinated fibers (AD, r = −0.81; controls subjects, r = −0.59). These results implicate a loss of intrahemispheric connections in the pathophysiology of AD.



https://ift.tt/2sly7aT

Stable olfactory sensory neuron in vivo physiology during normal aging

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Marley D. Kass, Lindsey A. Czarnecki, John P. McGann
Normal aging is associated with a number of smell impairments that are paralleled by age-dependent changes in the peripheral olfactory system, including decreases in olfactory sensory neurons (OSNs) and in the regenerative capacity of the epithelium. Thus, an age-dependent degradation of sensory input to the brain is one proposed mechanism for the loss of olfactory function in older populations. Here, we tested this hypothesis by performing in vivo optical neurophysiology in 6-, 12-, 18-, and 24-month-old mice. We visualized odor-evoked neurotransmitter release from populations of OSNs into olfactory bulb glomeruli, and found that these sensory inputs are actually quite stable during normal aging. Specifically, the magnitude and number of odor-evoked glomerular responses were comparable across all ages, and there was no effect of age on the sensitivity of OSN responses to odors or on the neural discriminability of different sensory maps. These results suggest that the brain's olfactory bulbs do not receive deteriorated input during aging and that local bulbar circuitry might adapt to maintain stable nerve input.



https://ift.tt/2xp7mao

Oxidative stress is bane in chronic liver diseases: Clinical and experimental perspective

Publication date: Available online 28 May 2018
Source:Arab Journal of Gastroenterology
Author(s): Devaraj Ezhilarasan
Oxidative stress plays an important role in the pathogenesis of various chronic liver diseases (CLD) and increasing evidence have confirmed the contributory role of oxidative stress in the pathogenesis of drugs and chemical-induced CLD. Chronic liver injury is manifested as necrosis, cholestasis, fibrosis, and cirrhosis. Chronic administration of anti-tubercular, anti-retroviral, immunosuppressive drugs is reported to induce free radical generation during their biotransformation in the liver. Further, these reactive intermediates are said to induce profibrogenic cytokines, several inflammatory markers, collagen synthesis during the progression of hepatic fibrosis. Oxidative stress and free radicals are reported to induce activation and proliferation of hepatic stellate cells in the injured liver leading to the progression of CLD. Hence, to counteract or to scavenge these reactive intermediates, several plant-derived antioxidant principles have been effectively employed against oxidative stress and came out with promising results in human and experimental models of CLD. This review summarizes the relationships between oxidative stress and different liver pathogenesis induced by drugs and xenobiotics, focusing upon different chronic liver injury induced by alcohol, antitubercular drugs and hyperactivity of antiretroviral drugs in HIV patients, viral hepatitis infection induced oxidative stress.



https://ift.tt/2ISgbuu

Magnifying endoscopy with narrow-band imaging to assist the linear stapler closure of the pharynx during total laryngectomy

This study aimed to present a novel technique for stapler-assisted laryngectomy under direct visualization using a videoendoscope with narrow-band imaging (NBI-endoscopy).

https://ift.tt/2kxJ7xu

Interactions médicamenteuses entre méthotrexate et antibiotiques

Publication date: Available online 28 May 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-L. Schmutz




https://ift.tt/2kAghw9

Interactions médicamenteuses entre méthotrexate et antibiotiques

Publication date: Available online 28 May 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): J.-L. Schmutz




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Editorial Board

Publication date: July–August 2018
Source:Microbiological Research, Volumes 212–213





https://ift.tt/2sdyoMC

Where Does Health Communication Technology Fit Into Allergy Practice?,

Over the past three decades, health and communication technologies (HCT) have evolved and joined forces to improve asthma management. Initially, technology was focused on the electronic measurement of patient adherence (Figure 1). As adherence-measurement devices improved, investigators began to use them as interventions to boost adherence, first by giving feedback directly to patients and later by adding communication technology. The more recent upsurge of available communication technology has introduced the role of smart phones, mobile apps, and interactive voice recognition (IVR) technology into healthcare.

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JACC Instructions for Authors

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SGLT-2 Inhibitors and Cardiovascular Risk: An Analysis of CVD-REAL

AbstractBackground

Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown.

Objectives

This study sought to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD.

Methods

The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes were identified. Patients prescribed an SGLT-2i or other glucose-lowering drugs (GLDs) were matched based on a propensity score for initiation of an SGLT-2i. Hazard ratios (HRs) for the risk of death, HF, and HF or death in patients with and without established CVD were estimated for each country and pooled.

Results

After propensity score matching, 153,078 patients were included in each group. At baseline, 13% had established CVD. Compared with therapy using other GLDs, initiation of an SGLT-2i was associated with lower risk of death in patients with and without CVD (HR: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.63, respectively). There were also associations between SGLT-2i and lower risk of HF (HR: 0.72; 95% CI: 0.63 to 0.82; and HR: 0.61; 95% CI: 0.48 to 0.78, respectively) and the composite of HF or death (HR: 0.63; 95% CI: 0.57 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.62, respectively) observed in patients with and without established CVD.

Conclusions

In this large, multinational, observational study, initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD. Ongoing clinical trials will provide further evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614)

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Supplemental Vitamins and Minerals for CVD Prevention and Treatment

Abstract

The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, β-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.

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Prevention of Heart Failure With SGLT-2 Inhibition: Insights From CVD-REAL

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Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women

AbstractBackground

Higher androgen and lower estrogen levels are associated with cardiovascular disease (CVD) risk factors in women. However, studies on sex hormones and incident CVD events in women have yielded conflicting results.

Objectives

The authors assessed the associations of sex hormone levels with incident CVD, coronary heart disease (CHD), and heart failure (HF) events among women without CVD at baseline.

Methods

The authors studied 2,834 post-menopausal women participating in the MESA (Multi-Ethnic Study of Atherosclerosis) with testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) levels measured at baseline (2000 to 2002). They used Cox hazard models to evaluate associations of sex hormones with each outcome, adjusting for demographics, CVD risk factors, and hormone therapy use.

Results

The mean age was 64.9 ± 8.9 years. During 12.1 years of follow-up, 283 CVD, 171 CHD, and 103 HF incident events occurred. In multivariable-adjusted models, the hazard ratio (95% confidence interval [CI]) associated with 1 SD greater log-transformed sex hormone level for the respective outcomes of CVD, CHD, and HF were as follows: total testosterone: 1.14 (95% CI: 1.01 to 1.29), 1.20 (95% CI: 1.03 to 1.40), 1.09 (95% CI: 0.90 to 1.34); estradiol: 0.94 (95% CI: 0.80 to 1.11), 0.77 (95% CI: 0.63 to 0.95), 0.78 (95% CI: 0.60 to 1.02); and testosterone/estradiol ratio: 1.19 (95% CI: 1.02 to 1.40), 1.45 (95% CI: 1.19 to 1.78), 1.31 (95% CI: 1.01 to 1.70). Dehydroepiandrosterone and SHBG levels were not associated with these outcomes.

Conclusions

Among post-menopausal women, a higher testosterone/estradiol ratio was associated with an elevated risk for incident CVD, CHD, and HF events, higher levels of testosterone associated with increased CVD and CHD, whereas higher estradiol levels were associated with a lower CHD risk. Sex hormone levels after menopause are associated with women's increased CVD risk later in life.

https://ift.tt/2sfLSre

Coronary Atherosclerotic Precursors of Acute Coronary Syndromes

AbstractBackground

The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden.

Objectives

The purpose of this study was to identify atherosclerotic features associated with precursors of ACS.

Methods

We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA–evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs).

Results

We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm³ fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm³ necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP.

Conclusions

Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden.

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Essentials of Advocacy: What Is Behind the Curtain?

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Coronary CT Angiography: Identification of Patients and Plaques "At Risk"

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Cannabis and Heart Disease: Forward Into the Great Unknown?

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Short-Term Global Cardiovascular Disease Risk Prediction in Older Adults

AbstractBackground

Current prevention guidelines recommend using the Pooled Cohort Equation (PCE) for 10-year atherosclerotic cardiovascular disease (CVD) risk assessment. However, the PCE has serious limitations in older adults: it excludes heart failure (HF) hospitalization, estimates 10-year risk, which may not be the most relevant time frame, and is not indicated for individuals age >79 years.

Objectives

This study sought to determine whether adding biomarkers to PCE variables improves global CVD (coronary heart disease, stroke, and HF) risk prediction in older adults over a shorter time period.

Methods

Atherosclerosis Risk in Communities study participants without prevalent CVD including HF (n = 4,760; age 75.4 ± 5.1 years) were followed for incident global CVD events. Adding N-terminal pro–B-type natriuretic peptide, high-sensitivity cardiac troponin T, and high-sensitivity C-reactive protein to the PCE and a "lab model" with the biomarkers, age, race, and gender were assessed for prediction improvement. Area under the receiver operating characteristic curve (AUC) and net reclassification index (NRI) were calculated.

Results

Over median follow-up of ~4 years, incident HF was the leading CVD event (n = 193 vs. 118 coronary heart disease and 81 stroke events). Compared to the PCE, each biomarker improved risk prediction. The largest improvement in risk prediction metrics was with the addition of all 3 biomarkers (AUC 0.103; continuous NRI 0.484). The lab model also performed better than the PCE model (AUC 0.091, continuous NRI 0.355).

Conclusions

Adding biomarkers to the PCE or a simpler "lab model" improves short-term global CVD risk prediction and may be useful to inform short-term preventive strategies in older adults.

https://ift.tt/2sfmlP8

Sex Steroids and Incident Cardiovascular Disease in Post-Menopausal Women: New Perspective on an Old Controversy

https://ift.tt/2IRUGtM

The Call for Precision Health Trials in Older Adults: One Size Does Not Fit All

https://ift.tt/2IUib5k

Cardiovascular Disease and Homelessness

Abstract

Cardiovascular disease (CVD) is a major cause of death among homeless adults, at rates that exceed those in nonhomeless individuals. A complex set of factors contributes to this disparity. In addition to a high prevalence of cigarette smoking and suboptimal control of traditional CVD risk factors such as hypertension and diabetes, a heavy burden of nontraditional psychosocial risk factors like chronic stress, depression, heavy alcohol use, and cocaine use may confer additional risk for adverse CVD outcomes beyond that predicted by conventional risk estimation methods. Poor health care access and logistical challenges to cardiac testing may lead to delays in presentation and diagnosis. The management of established CVD may be further challenged by barriers to medication adherence, communication, and timely follow-up. The authors present practical, patient-centered strategies for addressing these challenges, emphasizing the importance of multidisciplinary collaboration and partnership with homeless-tailored clinical programs to improve CVD outcomes in this population.

https://ift.tt/2IVzumK

Cocaine and Marijuana Use Among Young Adults With Myocardial Infarction

AbstractBackground

Substance abuse is increasingly prevalent among young adults, but data on cardiovascular outcomes remain limited.

Objectives

The objectives of this study were to assess the prevalence of cocaine and marijuana use in adults with their first myocardial infarction (MI) at ≤50 years and to determine its association with long-term outcomes.

Methods

The study retrospectively analyzed records of patients presenting with a type 1 MI at ≤50 years at 2 academic hospitals from 2000 to 2016. Substance abuse was determined by review of records for either patient-reported substance abuse during the week before MI or substance detection on toxicology screen. Vital status was identified by the Social Security Administration's Death Master File. Cause of death was adjudicated using electronic health records and death certificates. Cox modeling was performed for survival free from all-cause and cardiovascular death.

Results

A total of 2,097 patients had type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), with median follow-up of 11.2 years (interquartile range: 7.3 to 14.2 years). Use of cocaine and/or marijuana was present in 224 (10.7%) patients; cocaine in 99 (4.7%) patients, and marijuana in 125 (6.0%). Individuals with substance use had significantly lower rates of diabetes (14.7% vs. 20.4%; p = 0.05) and hyperlipidemia (45.7% vs. 60.8%; p < 0.001), but they were significantly more likely to use tobacco (70.3% vs. 49.1%; p < 0.001). The use of cocaine and/or marijuana was associated with significantly higher cardiovascular mortality (hazard ratio: 2.22; 95% confidence interval: 1.27 to 3.70; p = 0.005) and all-cause mortality (hazard ratio: 1.99; 95% confidence interval: 1.35 to 2.97; p = 0.001) after adjusting for baseline covariates.

Conclusions

Cocaine and/or marijuana use is present in 10% of patients with an MI at age ≤50 years and is associated with worse all-cause and cardiovascular mortality. These findings reinforce current recommendations for substance use screening among young adults with an MI, and they highlight the need for counseling to prevent future adverse events.

https://ift.tt/2J8HzI2

Predicting Cardiovascular Health in Coronary Artery Risk Development in Young Adults

https://ift.tt/2xjwZtd

BRCA1 Mutation Status and Follicular Fluid Exposure Alters NFκB Signaling and ISGylation in Human Fallopian Tube Epithelial Cells

Publication date: July 2018
Source:Neoplasia, Volume 20, Issue 7
Author(s): Julia Hollingsworth, Angela Lau, Alicia Tone, Alexandra Kollara, Lisa Allen, Terence J. Colgan, Valerie Dube, Barry Rosen, K. Joan Murphy, Ellen M. Greenblatt, Tomer Feigenberg, Carl Virtanen, Theodore J. Brown
Germline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed epithelial ovarian cancer histotype. Other identified risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation, during which the FTE cells become transiently exposed to follicular fluid (FF). To test whether mtBRCA1 or mtBRCA2 nonmalignant FTE cells respond differently to periovulatory FF exposure than control patient FTE cells, gene expression profiles from primary FTE cultures derived from BRCA1 or BRCA2 mutation carriers or control patients were compared at baseline, 24 hours after FF exposure, and 24 hours after FF replacement with culture medium. Hierarchical clustering revealed both FF exposure and BRCA mutation status affect gene expression, with BRCA1 mutation having the greatest impact. Gene set enrichment analysis revealed increased NFκB and EGFR signaling at baseline in mtBRCA1 samples, with increased interferon target gene expression, including members of the ISGylation pathway, observed after recovery from FF exposure. Gene set enrichment analysis did not identify altered pathway signaling in mtBRCA2 samples. An inverse relationship between EGFR signaling and ISGylation with BRCA1 protein levels was verified in an immortalized FTE cell line, OE-E6/E7, stably transfected with BRCA1 cDNA. Suppression of ISG15 and ISGylated protein levels by increased BRCA1 expression was found to be mediated by decreased NFκB signaling. These studies indicate that increased NFκB signaling associated with decreased BRCA1 expression results in increased ISG15 and protein ISGylation following FF exposure, which may be involved in predisposition to HGSOC.



https://ift.tt/2IOnJlY

Effects of wind–wave disturbances on adsorption and desorption of tetracycline and sulfadimidine in water–sediment systems

Abstract

Wind–wave disturbances frequently disperse sediment particles into overlying water, which facilitates the adsorption and desorption of contaminants in aquatic ecosystems. Tetracycline (TC) and sulfadimidine (SM2) are common antibiotics that are frequently found in aquatic environments. This study utilized microcosms, comprising sediment and water from Lake Taihu, China, to examine the adsorption and desorption of TC and SM2 under different wind–wave disturbances in a shallow lake environment. The adsorption experiments were conducted with three different concentrations (1, 5, 10 mg/L) of TC and SM2 in the overlying water, and two different (background and strong) wind–wave conditions for 72 h. Subsequently, four microcosms were employed in a 12-h desorption study. Analysis of adsorption progress showed that TC concentration in the overlying water decreased quickly, while SM2 remained almost constant. In the desorption experiments, SM2 released to the overlying water was an order of magnitude greater than TC. These results indicate that sediment particles strongly adsorb TC but weakly adsorb SM2. Compared to background conditions, the strong wind–wave conditions resulted in higher concentrations of TC and SM2 in sediment and facilitated their migration to deeper sediment during adsorption, correspondingly promoting greater release of TC and SM2 from sediment particles into the overlying water during desorption.

https://ift.tt/2IU6f3C

Halobenzoquinone-mediated assembly of amino acid modified Mn-doped ZnS quantum dots for halobenzoquinones detection in drinking water

Publication date: 5 October 2018
Source:Analytica Chimica Acta, Volume 1026
Author(s): Zhe Jiao, Pengfei Zhang, Hongwei Chen, Jingwen Li, Zhengquan Zhong, Hongbo Fan, Faliang Cheng
Halobenzoquinones (HBQs) were reported as disinfection byproducts (DBPs) which had potential risk of bladder cancer. In this paper, a highly selective analytical method for HBQs was developed by HBQs-mediated assembly of amino acid modified Mn-doped ZnS/Quantum Dots (Mn: ZnS QDs). In the presence HBQs, a charge-transfer complex (CTC) was formed between aromatic rings of HBQs and the primary amino groups on the surface of the QDs. The formation of CTC led to the aggregation of QDs, as a result fluorescence decreasing occurred. The decrease was correlated with the concentration of HBQs. Then a fluorescence sensor array for discrimination of three kinds of HBQs including 2,6-Dichloro-1,4-benzoquinone (DCBQ), 2,6-Dibromo-1,4-benzoquinone (DBBQ) and 2,3,6-trichloro-1,4-benzoquinone (TCBQ) was developed. Four kinds of amino acids including cysteine, threonine, tyrosine and tryptophan were embellished on the Mn: ZnS QDs. The different extents of aggregation led to different fluorescence decreasing effect, thus distinct fluorescence patterns were created. It showed that three kinds of HBQs could be discriminated successfully by fluorescence sensor array at a range of concentrations through principal component analysis (PCA). The unknown samples were predicted by with a stepwise linear discriminant analysis (SLDA) using Mahalanobis distance as a selection criterion with accuracy of 100%. Remarkably, the practicability of the proposed sensor array was further validated by identification of three kinds of HBQs at different concentrations in real drinking water samples. Compared to LC/MS/MS, this fluorescent sensor array-based method was proved to be more convenient since the nanoparticles can be prepared flexibly according to the property of the target.

Graphical abstract

https://ift.tt/2IS845h

Digital encoding based molecular imprinting suspension array for multiplexed label-free sensing of phenol derivatives

Publication date: 15 October 2018
Source:Sensors and Actuators B: Chemical, Volume 271
Author(s): Qinghua He, Tian Guan, Yonghong He, Bangrong Lu, Dongmei Li, Xuejing Chen, Guangxia Feng, Siyu Liu, Yanhong Ji, Meiguo Xin
A fluorescent suspension array combining digital encoding and molecular imprinting technologies was applied for multiplexed detection of phenols in aqueous medium. In this assay, nanomaterials such as silver (Ag), cuprous oxide (Cu2O), magnesium oxide (MgO), and zinc oxide (ZnO) were assembled on microbeads as digital encoding signal sources, then, (Digital encoding signal sources were produced by assembling silver (Ag), cuprous oxide Cu2O), magnesium oxide (MgO), and zinc oxide (ZnO) on microbeads. Molecular imprinted nanoparticles based on CdSe/ZnS quantum dots with various emission wavelengths (525, 565 and 585 nm) were grafted on the encoded beads through electrostatic adsorption and were used as the sensing units. The decoding spectra of the suspension array were stimulated and collected by a home-built laser induced breakdown spectroscopy system. The resulted spectra were transformed into digital sequences for encoding. As demonstrated in the gradient detections to various phenol solutions in concentration range of 0.98–62.5 μg/mL, the functionality of the suspension array was proven in the control experiments between the parent sensor beads and the molecular imprinting silica nanoparticles assembled sensor beads. Furthermore, the selectivity of suspension array was verified by the mixed adsorption experiments conducted in multicomponent analytes.



https://ift.tt/2L32b1A

Synthesis, structural characterization and photoluminescence property of two Zn2+/In3+-4,4′-oxydiphthalhydrazidate complexes

Publication date: 1 October 2018
Source:Inorganica Chimica Acta, Volume 482
Author(s): Juan Jin, Hou Chen, Xiao Zhang, Yu-Chang Wang, Zhen-Jiang Zhang, Qing-Feng Yang, Chen Lin, Ji-Rui Li, Qin-Jun Zhang
Under the hydrothermal conditions, two new 4,4′-oxydiphthalhydrazidate-containing compounds [Zn2(odpth)2(phen)2]·H2O 1 and [In(odpth)(ox)(phen)] 2 (odpth = 4,4′-oxydiphthalhydrazidate, phen = 1,10-phenanthroline, ox = oxalate), were obtained. Note that odpth ligand was derived from the hydrothermal in situ acylation reaction between 4,4′-oxydiphthalic acid (odpha) with N2H4⋅H2O. In compound 1, the odpth ligands exhibit a μ2-bridging mode, which link Zn(II) centers into a 1-D chained structure with ancillary phen molecules. Interestingly, in compound 2, the ox ligands exhibit a μ2-bridging mode, which link In(III) centers into a different 1-D chained structure with ancillary odpth and phen molecules. Although they are only 1-D chained coordination polymers, they all further self-assemble into the interesting supramolecular networks via π⋯π stacking or hydrogen-bonded interactions. The photoluminescence analyses indicate that the compounds in the different states (in the solid state or in aqueous solution) may exhibit different emission behaviors.

Graphical abstract

https://ift.tt/2Ja8nHY

Giant intrascrotal embryonal rhabdomyosarcoma in an adult: a case report and review of the literature

Intrascrotal embryonal rhabdomyosarcoma in adults is a rare tumor with high aggression and a poor prognosis. We report our patient's case and review the relevant literature to improve the understanding of this...

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Editorial Board

Publication date: June 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 135, Issue 3





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Contents

Publication date: June 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 135, Issue 3





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Laryngeal papillomatosis in Senegal: A ten-year experience

Publication date: June 2018
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 135, Issue 3
Author(s): S. Maïga, C. Ndiaye, M. Diouf, B.K. Diallo, M. Ndiaye, M.S. Diouf, I.C. Ndiaye, R. Diouf
ObjectivesThe objectives of this study were to describe the epidemiological, clinical and therapeutic characteristics of laryngeal papillomatosis in the Fann teaching hospital ENT department in Dakar, Senegal.Patients and methodsWe retrospectively reviewed all cases of laryngeal papillomatosis managed in the Fann teaching hospital ENT department between 1st January 2006 and 31st December 2015. Epidemiological, clinical and therapeutic characteristics of laryngeal papillomatosis were studied. Statistical analysis was performed with SPSS 18 software.ResultsThe median age at diagnosis was 11 years and the sex ratio was 1.88. The mean time to consultation was 4.5 years. The predominant symptom was dysphonia, present in all cases, followed by laryngeal dyspnoea in 64.6% of cases. The glottic area was involved in all patients. Tracheostomy was performed in 20.8% of cases. All patients in our study underwent endoscopic excision of the lesions.ConclusionLaryngeal papillomatosis is the most common benign tumor in children, but it can also occur in adults. Treatment has been revolutionized by progress in endoscopy and antiviral therapy. However, tracheostomy still occupies an important place in our practice.



https://ift.tt/2IQynsx

Memory responses of innate lymphocytes and parallels with T cells

Abstract

Natural killer (NK) cells are classified as innate immune cells, given their ability to rapidly respond and kill transformed or virally infected cells without prior sensitization. Recently, accumulating evidence suggests that NK cells also exhibit many characteristics similar to cells of the adaptive immune system. Analogous to T cells, NK cells acquire self-tolerance during development, express antigen-specific receptors, undergo clonal-like expansion, and can become long-lived, self-renewing memory cells with potent effector function providing potent protection against reappearing pathogens. In this review, we discuss the requirements for memory NK cell generation and highlight the similarities with the formation of memory T cells.

https://ift.tt/2GYBado

Investigation of the therapy targets of Yi-Qi-Yang-Yin-Hua-Tan-Qu-Yu recipe on type 2 diabetes by serum proteome labeled with iTRAQ

Publication date: 5 October 2018
Source:Journal of Ethnopharmacology, Volume 224
Author(s): Jing Zhao, Cheng-Ke Cai, Ming Xie, Jin-Na Liu, Bang-Zhong Wang
Ethnopharmacology relevanceBased on basic theories of Chinese medicine, Yi-Qi-Yang-Yin-Hua-Tan-Qu-Yu (YQYYHTQY) recipe was constituted by eleven kinds of Chinese herbs and effective in treatment of type 2 diabetes (T2DM). But the therapy target was unclear.ObjectiveIn this study, we used the serum proteome labeled by iTRAQ to find therapy target of YQYYHTQY recipe on T2DM.Materials and methodsThe rat model was induced by high-fat diet (HFD) and streptozotocin (STZ, 30 mg/kg). Drugs were administered to rats once daily for 14 days. Related laboratory parameters were observed. Serum proteome were compared between T2DM and YQYYHTQY group using the iTRAQ labeling quantitative proteomics technique. Functional differential proteins were analysis by STRING software. Target proteins were confirmed by ELISA kits.ResultsHyperglycemia, hyperinsulinemia, insulin resistance, decrease of glucose transporter, depilation, less activity, flock together, depression, ecchymosis of tongue and tail appearance, the typical diabetic patients "a little more than three" symptoms, as well as the decrease of grip strength, serum cyclic adenosine monophosphate (cAMP)/ cyclic guanosine monophosphate (cGMP) ratio, serum high density lipoprotein-cholesterol (HDL-C) and the increase of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), thromboxane B2 (TXB2)/ 6-keto prostaglandin F1α (6-keto PGF1α) ratio, endothelin-1 (ET-1) levels were found in T2DM group. After drugs treatment, all the above indexes almost were improved in different degrees and effect of YQYYHTQY recipe was superior to pioglitazone hydrochloride. In addition, there were 23 differential proteins, 5 up-regulated and 18 down-regulated proteins. Of them, there were 4 proteins related with diabetes, blood and behavior. Cell division control protein 42 homolog (CDC42) and Ras homolog gene family member A (RhoA) were the therapy targets of YQYYHTQY recipe on T2DM.ConclusionsYQYYHTQY recipe showed therapy effect on T2DM. CDC42 and RhoA proteins were the therapy targets of YQYYHTQY recipe.

Graphical abstract

https://ift.tt/2IUVZvW

Foaming of blood in endovenous laser treatment

Abstract

This work is dedicated to a challenging issue of modern phlebology—establishment of a physical mechanism of the endovenous laser treatment (EVLT) against great saphenous vein incompetence (protuberant varicosities). Using optical and acoustical methods, we have studied the laser-induced formation of microbubbles in an aqueous solution of surface-active substances, serum, and blood directly in patients while conducting EVLT of the great saphenous vein in a clinical setting. We have used lasers with wavelengths 0.97 and 1.47 μm. Their radiation was transmitted through a quartz-quartz polymer fiber 600 μm in diameter. It has been found that in all cases, the laser beam with moderate power (1–10 W) supplied through an optical fiber leads to the formation of micro-bubbled foam. It has been shown that laser exposure during EVLT induces blood boiling, which results in heating of the venous walls (thermal destruction of the intima) and provides effective foam occlusion of the blood vessels (hemostasis). Necessary and sufficient conditions for a successful EVLT are associated with the thermal destruction of intima and laser-induced foam hemostasis.

https://ift.tt/2ISAZlD

Effect of CO 2 concentration on strength development and carbonation of a MgO-based binder for treating fine sediment

Abstract

We previously described a MgO-based binder for treating fine sediment and simultaneously store CO₂. Here, we describe a study of the physical/mechanical characteristics and carbonation reactions of the MgO-based binder used to solidify/stabilize fine sediment in atmospheres containing different CO₂ concentrations. Carbonation of the sediment treated with the MgO-based binder at the atmospheric CO₂ concentration markedly improved the compressive strength of the product. The compressive strength was 4.78 MPa after 365 days of curing, 1.3 times higher than the compressive strength of sediment treated with portland cement. This improvement was caused by the formation of carbonation products, such as hydromagnesite, nesquehonite, and lansfordite, and the constant high pH (~ 12) of the specimen, which favored the growth of hydration products such as calcium silicate hydrates and portlandite. Very low compressive strengths were found when 50 and 100% CO₂ atmospheres were used because of excessive formation of carbonation products, which occupied 78% of the specimen depth. Abundant carbonation products increased the specimen volume and decreased the pH to 10.2, slowing the growth of hydration products. The absence of brucite in specimens produced in a 100% CO₂ atmosphere indicated that MgO carbonation is favored over hydration at high CO₂ concentrations.

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