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Δευτέρα 18 Φεβρουαρίου 2019

Endoscopic Sphenopalatine Artery Ligation

    Endoscopic sphenopalatine artery ligation (ESPAL) is the intervention of choice for refractory epistaxis in specialist ear, nose and throat (ENT)units and should be within the repertoire of competencies for all ENT trainees. Following its recent incorporation within the United Kingdom competency–based training syllabus as an explicit outcome standard, the ESPAL is not uncommonly being delivered by trainees under appropriate supervision. We assessed the efficacy and outcome of ESPAL in epistaxis management within our teaching hospitals.

    Retrospective, structured review of all ESPAL procedures performed for epistaxis between December 2005 and December 2013. The techniques of ligation, operator grade, and outcome were studied.

    Sixty-five patients (41 male:24 female; average age of 58.2 years) were identified in whom 67 artery ligations were performed (63 unilateral; 2 bilateral). Overall, success rate of ESPAL was 92.3% (60/65), with 5 rebleed cases recorded within 30 days of the primary procedure. Sixteen (24.6%) underwent "clipping," 26 (40.0%) had diathermy ligation, 18 (27.7%) had both clipping and diathermy, and in 5 (7.7%) patients, the ligation technique was not recorded. In 31 (47.7%) of 65 cases, a consultant was the principal surgeon. The remaining 34 (52.3%) of 65 cases were performed by trainees with (24, 70.6%) or without (10, 29.4%) supervision. There was no correlation between rebleed and operators' grade, level of supervision, or ligation technique.

    With appropriate training, ESPAL can achieve hemostasis in teams of varying grades of operators without significant reduction in outcome. To further enhance the technical learning curve, the utility of simulation-based training could offer continuous and longitudinal development of skills.

    Epistaxis is the commonest emergency in ear, nose and throat (ENT), with an estimated incidence of 108 in 100 000 population per year.1 In Scotland, this accounts for 1 in 3 of all ENT emergency admissions.2Effective initial management consists of localization of and direct therapy to the bleeding source (eg, silver nitrate cautery or bipolar diathermy) or application of localized pressure at the bleeding point with targeted, nasal packing. Despite being a common presentation, the management of epistaxis can be challenging due to its varying severity. The current lack of national guidelines results in management being dictated by the availability of local resources and personnel.3,4 While the majority of cases are conservatively managed, intractable epistaxis results in significant morbidity and even mortality, avoidance of which necessitates early surgical intervention in the form of artery ligation or embolization. With increasing refinements in endoscopic techniques and anatomical understanding of the locoregional nasal vasculature, endoscopic sphenopalatine artery ligation (ESPAL) has gradually emerged as the surgical intervention of choice for refractory epistaxis in specialist ENT units. Due to it being the most distal blood supply to the nasal cavity, ligation of sphenopalatine artery has gained popularity over the conventional approaches of external carotid and maxillary artery ligation, providing an inherently effective and localized control of epistaxis achievable endonasally with minimal access and minimal morbidity. Current evidence which comprises mainly of cohort studies has demonstrated that ESPAL benefits from both clinical and cost-effectiveness superiority, indicated by a high success rate of up to 100% in expert hands as well as shorter hospital stay.57

    Not only in the expert hands, being the intervention of choice for intractable epistaxis, ESPAL should also be within the repertoire of competencies for all ENT surgeons. Following its recent incorporation within the United Kingdom competency-based training syllabus as an explicit outcome standard upon the completion of training to becoming an independent practitioner, the trainee must be able to demonstrate ability to perform ESPAL with minimum supervision. Due to the engendered training appetite, it is therefore not uncommon for the ESPAL being increasingly delivered by trainees under appropriate supervision, especially in teaching units. The aim of this study was to assess the efficacy and outcome of ESPAL in epistaxis management as it is used by all grades of operator within our teaching hospitals.

    Study approval was obtained from NHS Greater Glasgow and Clyde clinical governance committee for surgery. A retrospective and structured review of records of ESPALs performed within all NHS North Glasgow hospitals over an 8-year period between December 2005 and December 2013 was conducted. All patients who underwent ESPAL were identified and indications for ESPAL were studied. Those patients in whom ESPAL was used for management of epistaxis were included in the study, while those who underwent ESPAL as an elective procedure in assisting the endoscopic excision of sinonasal tumors were excluded. Information on the techniques of ligation, operative details, and operator grade were extracted from operation notes. The efficacy of ESPAL and any related complications were specifically recorded.

    Success measure for an ESPAL procedure was defined as no further epistaxis or rebleed within 30 days of the index procedure, whereas any presentation of epistaxis out with this period of time was classified as a late rebleed and was recalled but not included in the primary failure rate. Where appropriate, statistical analysis was performed using Fisher exact or χ2 (GraphPad Prism, LaJolla, California).

    A total of 65 patients (41 male:24 female) underwent ESPAL for epistaxis management during the study period, in whom 67 artery ligations were performed (63 unilateral; 2 bilateral). The mean age of the study population was 58.2 years (range: 21-87 years). Overall, the follow-up period ranged from 1 to 8 years.

    Efficacy

    The overall success rate of ESPAL was 92.3% (60/65). Within 30 days of the primary procedure, a total of 5 (7.7%) rebleed cases were identified in which 2/5 had occurred within 24 hours and 3/5 were within 30 days. All 5 rebleed cases were recorded from the ipsilateral side of the initial presentation and among these, 4/5 had required readmission while 1/5 had occurred during the index admission. The outcome of the rebleed patients are summarized in Table 1.

    Table

    Table 1. Outcome of Patients With Rebleed Following the ESPAL Procedure.a

    Table 1. Outcome of Patients With Rebleed Following the ESPAL Procedure.a

    Of these 5 patients who had an unsuccessful primary procedure, there was only 1 case in which repeat ESPAL was performed. This was at 2-week interval from the index procedure requiring a readmission. Intraoperative findings confirmed division of the inferior turbinate branch of the sphenopalatine artery but intact posterior septal branches. Further diathermy and division was therefore carried out on the residual branches of the sphenopalatine artery and there was no subsequent epistaxis.

    Surgical Techniques

    The technique used for sphenopalatine artery ligation was analyzed. Of all 65 patients, 16 (24.6%) underwent "clipping" of the artery, 26 (40.0%) underwent diathermy, 18 (27.7%) had both clipping and diathermy, and in 5 (7.7%) patients, the ligation technique was not recorded. Within the remit of available data, there was no demonstrable superiority of clip application or diathermy in securing the sphenopalatine artery (P = .1893).

    Operator Grade

    In 31 (47.7%) of 65 cases, a consultant was the principal operating surgeon. The remaining 34 (52.3%) of 65 cases were performed by trainees with (24, 70.6%) or without (10, 29.4%) supervision by a consultant. There was no specific correlation observed between rebleed and operators' grade (P = 1.0000).

    Late Rebleed Patients

    In addition, a further 5 patients were identified during the follow-up study period where ipsilateral epistaxis had occurred beyond 30 days of the index procedure. These were recorded within a wide range of period from 6 weeks to 18 months. Of these 5 patients, 2 patients had spontaneous resolution following admission, 1 patient had nasal packing, 1 patient underwent examination under general anesthesia where generalized mucosal ooze was identified and managed with both diathermy and Floseal® (Baxter, Hayward, CA, US), while 1 patient had sphenopalatine foramen exploration which did not identify any remaining branches and an anterior ethmoidal ligation was subsequently performed.

    Follow-Up

    During the follow-up period, 4 patients died due to unrelated comorbidities at a period ranging between 6 and 38 months. In addition to rebleed cases, there were 2 postoperative complications recorded. One patient sustained an ipsilateral corneal abrasion due to the routine untaping of the eye and was reviewed postoperatively by ophthalmology. Topical antibiotics was commenced and there was no long-term sequelae. One patient developed dense postoperative adhesions requiring division both under local and general anesthesia; however, this was felt to be due to extensive and unsuccessful silver nitrate cautery prior to ESPAL.

    Endoscopic sphenopalatine artery ligation represents an effective and safe treatment of choice in refractory epistaxis, as evidenced by a 92.3% success rate from our series. Notably, this can be achieved by varying grades of operators without significant reduction in outcome. While the method of securing the sphenopalatine vessels remains a contentious issue, our series has shown no demonstrable superiority from either clips or diathermy application. With no current national consensus on epistaxis management or the optimal timing for surgical intervention, ESPAL is usually indicated in common practice after a watchful waiting period of up to 48 hours for persistent epistaxis.8,9 The minimally invasive nature and high efficacy of ESPAL continue to support its preeminence in the management for refractory epistaxis and it should be considered as early definitive management of epistaxis not amenable to conservative measures. In practical terms, we therefore advocate for epistaxis not controlled within 12 hours of admission, that a senior member of the team (registrar grade or above) should be contacted with a view to consider an ESPAL procedure.

    Our routine experience of ESPAL management of epistaxis has a success rate consistent with previously published cohort studies. This series of patients represents, to our knowledge, the largest group of epistaxis patients managed with ESPAL reported to date, also including multiple operators of varying grades.1012

    Being the current treatment of choice for refractory epistaxis, it is increasingly been recognized, particularly within the United Kingdom competency-based training syllabus, that ESPAL should be within the repertoire of competencies for all ENT trainees. Nevertheless, similar to most emergency operations, the acquisition of proficiency and training opportunities for ESPAL can be rendered ad hoc, for not uncommonly performed out of hours thus infrequently encountered by trainees. Furthermore, the on-going shaping and configuring of surgical training in the United Kingdom, in conjunction with the European Working Time Directive implementation, has shifted the paradigm toward competence-based training, which can inadvertently reduce the overall training time and operative experience in the emergency settings.

    In parallel to these, the engendered training appetite has resulted in ESPAL increasingly being delivered by trainees, under appropriate supervision and guidance. Although ESPAL remains a procedure performed for over 20 years with outcomes published in various cohort studies, our series is novel in studying and comparing the operative outcomes by varying grades of surgeons. Interestingly, our study did not show less efficacious outcome with ESPAL performed by trainees with appropriate supervision (70.6%) or in capable trainees when operating unsupervised (29.4%). The favorable outcome by trainees is likely to be underpinned by transferable competencies acquired from the robust training within the elective settings in a range of endoscopic skills, prior to its applications in the emergency procedure. To further enhance the technical learning curve for ESPAL, the utility of simulation training could offer continuous development of skills in a longitudinal manner.

    Our study has also highlighted the importance of appreciating variation in the sphenopalatine artery, which should prompt the surgeon to always actively search for all branches, including those posterior to the sphenopalatine foramen.13 Of note, a small group of late rebleed patients during the follow-up period were identified which occurred beyond 30 days of index procedure. This is unlikely to be attributed to the commonly perceived technical failure of clip dislodgement or incomplete division of vessels, but rather raises the possibility of subsequent neovascularization. As there is no known similar study with a prolonged follow-up post-ESPAL, the true incidence of this phenomenon can be difficult to ascertain. It, nevertheless, poses an interesting observation for studies in nasal vascular anatomy.

    Although embolization has been shown to have equal efficacy to ESPAL in cessation of refractory epistaxis, in our practice, this tends to be reserved in patients with anesthetic concern or rebleed cases. This is, in part, due to the limited availability of embolization which has its own significant risks. Furthermore, ESPAL has been shown to be superior to embolization in terms of cost-effectiveness.14 In the current climate of an aging population with increasing comorbidities, patients' suitability for general anesthesia can often become the main drawback for performing ESPAL. A recent study, however, has reported performing ESPAL under local anesthesia,15 thereby circumventing the anesthetic fitness barrier and thus potentially extend the applicability of the procedure.

    With an overall success rate of 92.3%, it would be appropriate to consider ESPAL as an early definitive management for intractable epistaxis. Endoscopic sphenopalatine artery ligation requires a sound understanding of the anatomical variation of sphenopalatine artery to ensure technical success. With appropriate training, there is no difference in outcome between ESPAL procedures performed by trainees compared to consultants. Thus, protocols should be developed that mandate the implementation of ESPAL in uncontrolled epistaxis.

    Authors' Note
    Oral presentation at 25th Congress of the European Rhinologic Society, on June 22-26, 2014; Scottish Otolaryngological Society (ENT Scotland) Summer Meeting, on May 13, 2016.

    Declaration of Conflicting Interests
    The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

    Funding
    The author(s) received no financial support for the research, authorship, and/or publication of this article.

    ORCID iD
    Shi Ying Hey, MRCS, DO-HNS https://orcid.org/0000-0003-3845-2566

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    The Full Moon on February 19th will be the biggest and brightest of 2019. .February’s full moon is commonly known as the Full Snow Moon. This year the Full Moon occurs on the Moon's closest point to Earth in it's orbit making it extra big and bright.


    Overstory-understory land cover mapping at the watershed scale: accuracy enhancement by multitemporal remote sensing analysis and LiDAR

    Abstract

    In forested watersheds, density, land cover, and its vertical structure are crucial factors for flood management, ecosystem monitoring, and biomass inventory. Nowadays, producing land cover maps with high accuracy has become a reality with the application of remote sensing techniques, but in some situations, it is not so easy to distinguish between the overstory and understory vegetation with only spectral information. The main goal of this study was to analyze the accuracy enhancement in overstory and understory land cover mapping at the watershed scale when using the data fusion of seasonal and annual time series of Sentinel-2 images complemented with low-density LiDAR and soil and vegetation indices. The study area was composed by two neighboring watersheds in Badajoz province (Spain). The accuracy of land cover classifications was trained in two ways: first, for each season and several soil-vegetation indices; and second, for the annual series and soil-vegetation indices. Next, LiDAR data were included in both analyses by means of a Boolean metric concerning the height. The obtained results showed that the overall accuracy was better with the annual evaluation when only spectral information was used for the classification. Additionally, if LiDAR data were included in the classification (data fusion), the overall accuracies were highly improved, especially in summer and autumn seasons. This improvement can be a significant issue in the analysis of vegetation structure and its spatial distribution as it is decisive for watershed ecosystem management.



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    Assessment of heavy metal pollution in water and surface sediment and evaluation of ecological risks associated with sediment contamination in the Ganga River: a basin-scale study

    Abstract

    We investigated eight heavy metals (Cr, Cd, Cu, Ni, Pb, Zn, Mn, and Fe) in water and bed sediment at 9 study sites along with 2320 km stretch of the Ganga River. Principal component analysis (PCA) and indices such as geo-accumulation index (Igeo), contamination factor (CF), enrichment factor (EF), pollution indices, and sediment quality guidelines were used to assess source apportionment and magnitude of contamination. Concentrations of Cr, Cd, Pb, Ni, Cu, and Fe in water have exceeded their respective standards in the middle and lower reaches of the river. Sediment Cr and Ni have reached probable effective concentration (PEC) at Kannauj, imposing likely threats to sediment dwellers. Highest Igeo values were recorded for Cr, Cd, and Pb at Kannauj, Rajghat, and Howrah. We further tested ecological risks (Er) and potential ecological risks (PERI) to assess individual and cumulative effects and found the Kannauj, Rajghat, and Howrah sites under the high-risk category. The modified pollution index (MPI) and the modified degree of contamination (mCd) also revealed the middle and lower river reaches under moderately to the heavily polluted category. Our study provides the first detailed watershed-scale database on heavy metal concentration in water and bed sediment, the magnitude of contamination, and likely ecological risks to aquatic organisms in the Ganga River. Given that the Ganga water is used for drinking and irrigation and the river harbors a diversity of habitats for fisheries, the study merits attention from a human health perspective as well.



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    Abstract

    Aims

    The badgers may affect soil chemical properties and plant species composition in two ways: by digging burrows (topsoil mixing) and by using latrines (fertilized soils). Here is reported which kind of badgers' activity plays a major role.

    Methods

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    Results

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    Conclusions

    Soil chemical properties and flora changes showed that badgers shape plant communities not by fertilization with excrements but, as a result of digging activity, by altering topsoil conditions.



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    Abstract

    Physical activity and sports play major roles in the overall health status of humans. It is well known that regular exercise helps to lower the risk for a broad variety of health problems, such as cardiovascular disease, type 2 diabetes, and cancer. Being physically active induces a wide variety of molecular adaptations, for example fiber type switches or other metabolic alterations, in skeletal muscle tissue. These adaptations are based on exercise-induced changes to the skeletal muscle transcriptome. Understanding their nature is crucial to improve the development of exercise-based therapeutic strategies. Recent research indicates that specifically epigenetic mechanisms, i.e., pathways that induce changes in gene expression patterns without altering the DNA base sequence, might play a major role in controlling skeletal muscle transcriptional patterns. Epigenetic mechanisms include DNA and histone modifications, as well as expression of specific microRNAs. They can be modulated by environmental factors or external stimuli, such as exercise, and eventually induce specific and fine-tuned changes to the transcriptional response. In this review, we highlight current knowledge on epigenetic changes induced in exercising skeletal muscle, their target genes, and resulting phenotypic changes. In addition, we raise the question of whether epigenetic modifications might serve as markers for the design and management of optimized and individualized training protocols, as prognostic tools to predict training adaptation, or even as targets for the design of "exercise mimics".



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    Selective delipidation of Mycobacterium bovis BCG enables direct pulmonary vaccination and enhances protection against Mycobacterium tuberculosis

    Selective delipidation of Mycobacterium bovis BCG enables direct pulmonary vaccination and enhances protection against Mycobacterium tuberculosis

    Selective delipidation of <i>Mycobacterium bovis</i> BCG enables direct pulmonary vaccination and enhances protection against <i>Mycobacterium tuberculosis</i>, Published online: 18 February 2019; doi:10.1038/s41385-019-0148-2

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    Abstract

    Electroencephalography (EEG)–based studies focus on depression recognition using data mining methods, while those on mild depression are yet in infancy, especially in effective monitoring and quantitative measure aspects. Aiming at mild depression recognition, this study proposed a computer-aided detection (CAD) system using convolutional neural network (ConvNet). However, the architecture of ConvNet derived by trial and error and the CAD system used in clinical practice should be built on the basis of the local database; we therefore applied transfer learning when constructing ConvNet architecture. We also focused on the role of different aspects of EEG, i.e., spectral, spatial, and temporal information, in the recognition of mild depression and found that the spectral information of EEG played a major role and the temporal information of EEG provided a statistically significant improvement to accuracy. The proposed system provided the accuracy of 85.62% for recognition of mild depression and normal controls with 24-fold cross-validation (the training and test sets are divided based on the subjects). Thus, the system can be clinically used for the objective, accurate, and rapid diagnosis of mild depression.

    Graphical abstract

    The EEG power of theta, alpha, and beta bands is calculated separately under trial-wise and frame-wise strategies and is organized into three input forms of deep neural networks: feature vector, images without electrode location (spatial information), and images with electrode location. The role of EEG's spectral and spatial information in mild depression recognition is investigated through ConvNet, and the role of EEG's temporal information is investigated using different architectures to aggregate temporal features from multiple frames. The ConvNet and models for aggregating temporal features are transferred from the state-of-the-art model in mental load classification.


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    Chronic Q Fever with Vascular Involvement: Progressive Abdominal Pain in a Patient with Aortic Aneurysm Repair in the United States

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    Bone marrow cryptococcosis has been rarely reported in the literature, and there are no established treatment guidelines specific to this AIDS-related complication. The recommended treatment for AIDS-related invasive fungal treatments include amphotericin B and flucytosine which are associated with an array of complications making optimal treatment recommendations difficult. This case presentation represents an example of a patient with newly diagnosed AIDS and bone marrow cryptococcosis, which was successfully managed with an antifungal regimen adjusted to her comorbidities.

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    NFAT1 Hypermethylation Promotes Epithelial-Mesenchymal Transition and Metastasis in Nasopharyngeal Carcinoma by Activating ITGA6 Transcription.

    NFAT1 Hypermethylation Promotes Epithelial-Mesenchymal Transition and Metastasis in Nasopharyngeal Carcinoma by Activating ITGA6 Transcription.

    Neoplasia. 2019 Feb 14;21(3):311-321

    Authors: Zhang J, Zheng ZQ, Yuan YW, Zhang PP, Li YQ, Wang YQ, Tang XR, Wen X, Hong XH, Lei Y, He QM, Yang XJ, Sun Y, Ma J, Liu N

    Abstract
    DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. We further established that the tumor suppressor effect of NFAT1 is mediated by its inactivation of ITGA6 transcription. Our findings suggest the significance of activating NFAT1/ITGA6 signaling in aggressive NPC, defining a novel critical signaling mechanism that drives NPC invasion and metastasis and providing a novel target for future personalized therapy.

    PMID: 30772768 [PubMed - as supplied by publisher]



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    Eur J Cancer. 2019 Feb 14;110:74-85

    Authors: Pearson ADJ, Scobie N, Norga K, Ligas F, Chiodin D, Burke A, Minard-Colin V, Adamson P, Marshall LV, Balakumaran A, Benettaib B, Bhargava P, Bollard CM, Bolotin E, Bomken S, Buechner J, Burkhardt B, Caron H, Copland C, Demolis P, Egorov A, Farhan M, Zugmaier G, Gross T, Horton-Taylor D, Klapper W, Lesa G, Marcus R, Miles RR, Nottage K, Pacaud L, Ricafort R, Schrappe M, Sterba J, Vezan R, Weiner S, Kim SY, Reaman G, Vassal G

    Abstract
    Paediatric Strategy Forums have been created by the multistakeholder organisation, ACCELERATE, and the European Medicines Agency to facilitate dialogue between all relevant stakeholders and suggest strategies in critical areas of paediatric oncology drug development. As there are many medicines being developed for B-cell malignancies in adults but comparatively few in children with these malignancies, a Paediatric Strategy Forum was held to discuss the best approach to develop these products for children. It was concluded that as current frontline therapy is highly successful, despite associated acute toxicity, de-escalation of this or substitution of presently used drugs with new medicines can only be undertaken when there is an effective salvage regimen, which is currently not available. Therefore priority should be given to developing treatment for patients with relapsed and refractory mature B-cell lymphomas. The consensus of the clinicians attending the meeting was that CAR T-cells, T-cell engagers and antibody drug conjugates (excluding those with a vinca alkaloid-like drug) presently have the greatest probability of providing benefit in relapse in view of their mechanism of action. However, as producing autologous CAR T-cells currently takes at least 4 weeks, they are not products which could be quickly employed initially at relapse in rapidly progressing mature B-cell malignancies but only for the consolidation phase of the treatment. Global, industry-supported, academic-sponsored studies testing compounds from different pharmaceutical companies simultaneously should be considered in rare populations, and it was proposed that an international working group be formed to develop an overarching clinical trials strategy for these disease groups. Future Forums are planned for other relevant paediatric oncologic diseases with a high unmet medical need and relevant molecular targets.

    PMID: 30772656 [PubMed - as supplied by publisher]



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    Hematopoietic stem cell transplantation for mucopolysaccharidoses; past, present, and future.

    Hematopoietic stem cell transplantation for mucopolysaccharidoses; past, present, and future.

    Biol Blood Marrow Transplant. 2019 Feb 14;:

    Authors: Taylor M, Khan S, Stapleton M, Wang J, Chen J, Wynn R, Yabe H, Chinen Y, Boelens JJ, Mason RW, Kubaski F, Horovitz DDG, Barth AL, Serafini M, Bernardo ME, Kobayashi H, Orii KE, Suzuki Y, Orii T, Tomatsu S

    Abstract
    Allogenic hematopoietic stem cell transplantation (HSCT) has been shown to be a treatment option for a selected group of patients with mucopolysaccharidoses (MPS) (MPS I, II, IVA, VI, and VII). Early diagnosis and timely referral to an expert in MPS are critical, followed by a complete examination and evaluation with a multidisciplinary team, including a transplant physician. Treatment recommendations for MPS are based on multiple factors such as biological, sociological, and financial effects. These include type of MPS, clinical severity, prognosis, present clinical signs and symptoms (disease stage), age at onset, the rate of progression, family significances and expectations, financial burdens, feasibility, availability, risks and benefits with available therapies such as HSCT, enzyme replacement therapy (ERT), surgical interventions, and other supportive care. To evaluate therapeutic efficacy and adverse effects of HSCT for MPS, international collaboration and data review are critical. Since the first attempt of HSCT in a patient with MPS in 1981, collaborative efforts to assess HSCT for MPS have been made continuously. Accumulation of data has made it possible to identify early outcomes (transplant outcomes) and long-term disease-specific outcomes resulting from HSCT. The recent identification of predictive factors and the development of innovative regimens have significantly improved the outcomes of both engraftment failure and transplant mortality. Assessment of long-term outcomes has also been described under consideration of a variety of factors: type of MPS, graft-type, age at transplantation, stage of disease progression, etc. Studies on the long-term outcomes are considered a key achievement for the use of HSCT in MPS communities. These studies have shown the effects and limitations of HSCT to improve disease manifestations and quality of life. In this review, we summarize the efficacy, side effects, risks, and the cost of HSCT for each type of MPS.

    PMID: 30772512 [PubMed - as supplied by publisher]



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    Ovarian carcinosarcoma: Current developments and future perspectives.

    Ovarian carcinosarcoma: Current developments and future perspectives.

    Crit Rev Oncol Hematol. 2019 Feb;134:46-55

    Authors: Boussios S, Karathanasi A, Zakynthinakis-Kyriakou N, Tsiouris AK, Chatziantoniou AA, Kanellos FS, Tatsi K

    Abstract
    Ovarian carcinosarcoma (OCS) constitute uncommon malignancies accounting for only 1-4% of ovarian cancers. Patients more often present with advanced stage disease and symptoms similar to those of epithelial ovarian cancers (EOC). Optimal tumor cytoreduction appears to be an important determinant of survival. Platinum-based chemotherapy remains the most commonly employed adjuvant treatment. The uncertain origin and poor prognosis of OCS motivate determination of the molecular basis of carcinosarcomas aggressive behavior in the hope of developing novel and effective treatment modalities. The present review summarizes the current knowledge on the epidemiology, pathology, prognostic factors, clinical presentation, and therapeutic interventions including future potential therapeutic targets.

    PMID: 30771873 [PubMed - in process]



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    The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper.

    The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper.

    Crit Rev Oncol Hematol. 2019 Feb;134:39-45

    Authors: Cristofanilli M, Pierga JY, Reuben J, Rademaker A, Davis AA, Peeters DJ, Fehm T, Nolé F, Gisbert-Criado R, Mavroudis D, Grisanti S, Giuliano M, Garcia-Saenz JA, Stebbing J, Caldas C, Gazzaniga P, Manso L, Zamarchi R, de Lascoiti AF, De Mattos-Arruda L, Ignatiadis M, Cabel L, van Laere SJ, Meier-Stiegen F, Sandri MT, Vidal-Martinez J, Politaki E, Consoli F, Generali D, Cappelletti MR, Diaz-Rubio E, Krell J, Dawson SJ, Raimondi C, Rutten A, Janni W, Munzone E, Carañana V, Agelaki S, Almici C, Dirix L, Solomayer EF, Zorzino L, Darrigues L, Reis-Filho JS, Gerratana L, Michiels S, Bidard FC, Pantel K

    Abstract
    BACKGROUND: The heterogeneity of metastatic breast cancer (MBC) necessitates novel biomarkers allowing stratification of patients for treatment selection and drug development. We propose to use the prognostic utility of circulating tumor cells (CTCs) for stratification of patients with stage IV disease.
    METHODS: In a retrospective, pooled analysis of individual patient data from 18 cohorts, including 2436 MBC patients, a CTC threshold of 5 cells per 7.5 ml was used for stratification based on molecular subtypes, disease location, and prior treatments. Patients with ≥ 5 CTCs were classified as Stage IVaggressive, those with < 5 CTCs as Stage IVindolent. Survival was analyzed using Kaplan-Meier curves and the log rank test.
    RESULTS: For all patients, Stage IVindolent patients had longer median overall survival than those with Stage IVaggressive (36.3 months vs. 16.0 months, P < 0.0001) and similarly for de novo MBC patients (41.4 months Stage IVindolent vs. 18.7 months Stage IVaggressive, p < 0.0001). Moreover, patients with Stage IVindolent disease had significantly longer overall survival across all disease subtypes compared to the aggressive cohort: hormone receptor-positive (44 months vs. 17.3 months, P < 0.0001), HER2-positive (36.7 months vs. 20.4 months, P < 0.0001), and triple negative (23.8 months vs. 9.0 months, P < 0.0001). Similar results were obtained regardless of prior treatment or disease location.
    CONCLUSIONS: We confirm the identification of two subgroups of MBC, Stage IVindolent and Stage IVaggressive, independent of clinical and molecular variables. Thus, CTC count should be considered an important tool for staging of advanced disease and for disease stratification in prospective clinical trials.

    PMID: 30771872 [PubMed - in process]



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    The interactive effect of the season and estuary position on the concentration of persistent organic pollutants in water and sediment from the Cua Dai estuary in Vietnam

    Abstract

    The current study was conducted in the Cua Dai estuary, Vietnam, (1) to assess the status of persistent organic pollutants (POPs) and (2) to examine the interactive effect of season and estuary position on the concentration of the pollutants in surface water and sediment. Fifty-two water and sediment samples were taken in the dry and rainy seasons from inner- and outer-estuary positions to analyze for six POPs, including hexachlorocyclohexane isomers (HCHs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), heptachlor, aldrin, dieldrin, and polychlorinated biphenyl (PCBs). The averaged concentrations of the respective POPs in water samples were 0.07, 0.1, 0.01, 0.03, 0.001, and 0.2 μg L−1 and in sediment samples were 2.6, 3.1, 0.9, 0.2, 0.2, and 121 μg kg−1. Of the six POPs examined, the concentration of DDTs in sediment samples and PCBs in water samples was significantly affected by the interactive effect of the two examined factors. The concentrations of HCHs, DDTs, heptachlor, and aldrin in water samples and of HCHs in sediment samples were significantly higher in the rainy season than in the dry season. Sediment samples collected from the inner position had a significantly higher concentration of HCHs and PCBs than in the outer position. Some mechanisms possibly influenced the varying POP concentration could include (1) greater riverine discharge in the rainy season and (2) the sea dilution effect in the outer position. Therefore, the concentration of the individual examined POPs in water and sediment in the Cua Dai estuary significantly depended on either the season, estuary position, or their combination.



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    Monitoring of pyrrolizidine alkaloids in beehive products and derivatives on the Belgian market

    Abstract

    Pyrrolizidine alkaloids (PAs) and related N-oxides (PANOs) are secondary plant metabolites thought to be found in approximately 3% of the flowering plants worldwide and exhibiting hepatotoxic properties to humans. As a consequence, beehive products are prone to be contaminated with those compounds by bees foraging PA-producing plants. Downstream contamination can also occur through food items containing honey. Analytical methods based on UHPLC separation and MS/MS detection were developed with a focus on very low LOQs and validated for the analysis of 16 PAs and 14 PANOs in honey, honey-based candies and snacks, as well as beehive product–based food supplements. A maximum level of 182 ng/g of PAs was detected in a Mediterranean honey, and high levels of heliotrine-type compounds were reported for the first time. An extensive sampling of honeys harvested in Belgium was performed (N = 374), the concentration levels were more limited with a maximum of 60 ng/g, and the contamination pattern was dominated by senecionine-type PAs. The PA levels in honey-based candies and snacks were very low, with respective maxima of 7.61 ng/g and 0.36 ng/g. Seventy-five percent among the pre-dosed food supplements based on beehive products were contaminated, with a maximum of 43 ng/g. The highest level was detected in a bee-collected pollen sample (1672 ng/g). The analytical results were consistent with the previously reported data for beehive products and confirmed that PA/PANO contamination in these food commodities is recurrent.



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    Health risk of metal exposure via inhalation of cigarette sidestream smoke particulate matter

    Abstract

    Cigarette sidestream smoke particulate matter (CSSP) is a major source of airborne metals in the indoor environment. However, the health impacts of inhalation of CSSP-bound metals are rarely studied. In this study, we quantify the amount of 37 metals discharged through CSSP from a leading Taiwan brand of cigarette, Long Life. We also estimate cancer and non-cancer risks due to inhalation of these metals and investigate possible modes of toxic action. Long Life CSSP exhibits a distinctive carcinogenic metal profile compared with Western brands. When released to a 60-m3 poorly ventilated room, Long Life CSSP metals increase the risk for cancer by a 9.26 or 20.90 in a million chance and the hazard quotient for non-cancer toxicity by 0.496 or 0.286 per cigarette depending on risk estimation system. Cd accounts for more than 90% and 80% of cancer and non-cancer risk, respectively. Long Life CSSP also contains considerable amounts of Al, Ba, and Fe. Metals are not responsible for CSSP-induced cytotoxicity, oxidative stress, and transactivation activity of AhR, Nrf2, and ERα. However, they diminish resveratrol-activated Nrf2 activity and downstream antioxidant gene expression in low-AhR-expressing lung cells. Our results suggest that chronic exposure to Long Life CSSP elevates Cd-associated cancer and non-cancer risks. Furthermore, exposure to Long Life CSSP metals may impair Nrf2-mediated antioxidant protection.



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    Reproduction of Eutropiichthys vacha (Schilbeidae) in the Ganges River (NW Bangladesh) with special reference to potential influence of climate variability

    Abstract

    The Batchwa vacha, Eutropiichthys vacha is commercially important, supporting a viable small- and large-scale fishery throughout the Ganges River, NW Bangladesh. This study provides detail information on reproduction of E. vacha including size at sexual maturity, spawning and peak spawning season, and fecundity based on 734 female specimens through regular monthly sampling using cast net, gill net, and square lift net in the Ganges River during January to December 2016. Also, our study estimated the effects of climate change including temperature and rainfall on reproduction of E. vacha in the Ganges River. For each individual, lengths (total length, TL; standard length, SL) and body weight (BW) were measured with slide caliper and digital balance, respectively. Gonads (ovaries) were collected carefully by ventral dissection of each female specimen and weighed to the nearest 0.01 g accuracy. The gonadosomatic index (GSI % = (GW/BW) ×100), modified gonadosomatic index (MGSI % = (GW/BW − GW) × 100), and Dobriyal index (DI = \( \sqrt[3]{\mathrm{GW}} \) ) were calculated to estimate the size at sexual maturity (L50) and spawning season. Based on GSI, MGSI, and DI, the L50 was calculated as 12.5 cm TL for female. The TL50, the TL at which 50% of individuals become mature, was calculated by logistic equation as 12.7 cm. Also, on the basis of higher values of GSI, MGSI, and DI, spawning season was ranged from April to August, with the peak in June–July, signifying the peak spawning season for E. vacha in the Ganges River. The total fecundity (FT) ranged from 4800 to 77,976 (mean ± SD, 31384 ± 23,747) and was highly correlated with TL and BW. Water temperature during the spawning period ranged from 28 to 34 °C, with an average of 31 °C and there was significant correlation between temperature and GSI. Also, the spawning season coincides with the peak rainfall and there was significant correlation between rainfall and GSI. Additionally, analysis of long data series indicated that annual average air temperature is increasing by 0.0258 °C/year, while the annual average rainfall is decreasing by 3.107 mm/year. Finally, the findings of this study would be very effective to impose specific management for E. vacha in the Ganges River and surrounding ecosystems.



    from Energy Ecology Environment Ambio via Terpsi Hori on Inoreader http://bit.ly/2TVdGND

    Small Cell Lung Cancer with Pituitary Metastasis Presenting as Secondary Adrenal Insufficiency: A Case Report and Literature Review.

    Small Cell Lung Cancer with Pituitary Metastasis Presenting as Secondary Adrenal Insufficiency: A Case Report and Literature Review.

    Am J Case Rep. 2019 Feb 17;20:207-211

    Authors: Atallah-Yunes SA, Clark J, Samanani S, Soe M

    Abstract
    BACKGROUND Pituitary gland metastasis is rarely the initial presentation of metastatic cancer. Most cases of pituitary gland metastasis are asymptomatic with diabetes insipidus being the most common symptomatic presentation. It can rarely present with symptoms of hormone underproduction such as secondary adrenal insufficiency. Although pituitary gland metastasis is rare, it is underestimated, as it is commonly misdiagnosed with pituitary gland adenoma due to the lack of clear radiological criteria differentiating between both. CASE REPORT We present a case of a 62-year-old male who presented with weakness, blurry vision, and persistent hypoglycemia despite intravenous dextrose infusion and having discontinued taking his diabetes medications. Chest x-ray showed a left hilar mass, while computed tomography scan demonstrated a left superior hilar mass and hilar lymphadenopathy with bilateral adrenal nodules and a T6 vertebral lesion suspicious for metastasis. Further workup showed secondary adrenal insufficiency with a low adrenocorticotropic hormone (ACTH) level. Vertebral biopsy was performed and confirmed the diagnosis of small cell carcinoma of the lung. This was followed by a brain magnetic resonance imaging (MRI), which showed multiple metastatic lesions with an enhancing mass involving the right clivus, sella, and suprasellar cistern with mass effect on the optic chiasm and involvement of the cavernous sinus supporting the diagnosis of pituitary gland metastasis of small cell lung cancer. The patient received brain radiation, and repeated MRI showed regression of the previous MRI findings. CONCLUSIONS Secondary adrenal insufficiency is an unusual presentation of pituitary gland metastasis. Physicians should take into consideration both radiological findings and presentation to differentiate between pituitary gland metastasis and pituitary adenoma.

    PMID: 30772889 [PubMed - in process]



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    Basilar occlusion and rupture secondary to rare fungal sinusitis: A case report.

    Basilar occlusion and rupture secondary to rare fungal sinusitis: A case report.

    World Neurosurg. 2019 Feb 14;:

    Authors: Monteiro A, Agnoletto GJ, Granja MF, Bit-Ivan EN, Sauvageau E

    Abstract
    BACKGROUND: Intracranial vascular infections of fungal etiology are extremely rare. The vast majority of cases occur in immunocompromised patients with invasive fungal disease, most commonly originating in the paranasal sinuses or the lungs. An extremely rare type in this part of the world, called Granulomatous Invasive Rhinosinusitis, has been reported to affect immunocompetent patients in most cases, and its causative strain has potential to invade the intracranial arteries.
    CASE DESCRIPTION: We present a rare case of basilar artery rupture and infarction secondary to granulomatous invasive rhinosinusitis in a 50 year old male who presented with ischemic symptoms and 6 month history of headache, dizziness and falls in Florida, USA. After biopsy, the patient developed subarachnoid hemorrhage and thrombosis. Several thrombectomy attempts were performed, resulting in persistent occlusion of the basilar artery and subsequent comatous state. After discussion with the patient's family, the decision of compassionate wean and autopsy authorization was made.
    CONCLUSIONS: Invasive fungal rhinosinusitis are more frequent nowadays due to increased use of immunosuppressive therapies. However, it is still a disease of immunocompromised. The development of new microbiology investigation techniques allowed for the discovery of fungal diseases that can also affect immunocompetent hosts, as in granulomatous invasive rhinosinusitis. This is an extremely rare condition is this part of the world, with very few cases in the last few decades.w.

    PMID: 30772526 [PubMed - as supplied by publisher]



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    Natural history of patients with psychogenic nonepileptic seizures.

    Natural history of patients with psychogenic nonepileptic seizures.

    Seizure. 2019 Feb 11;66:22-25

    Authors: Asadi-Pooya AA, Bahrami Z, Homayoun M

    Abstract
    PURPOSE: The purpose of this study was to investigate the long-term outcome of patients with psychogenic nonepileptic seizures (PNES), who never visited a psychologist and never received a proper therapy for their condition (due to lack of resources). We also aimed to investigate factors potentially associated with the outcome in these patients.
    METHODS: We studied all patients with PNES, who were admitted to the epilepsy monitoring unit at the Shiraz Comprehensive Epilepsy Center, from 2008 until 2013. In a phone call interview to the patients in November and December 2018, we obtained the following information: seizure outcome, history of receiving any psychotherapy after confirming their diagnosis at referral, and finally, their current marital status, education, and employment status.
    RESULTS: 69 patients had the inclusion criteria. Thirty-six patients (52%) were seizure-free during the past 12 months, but 33 (48%) still suffer from seizures. The only variable (at diagnosis), which was significantly associated with their outcome, was duration of their condition before they received a definite diagnosis.
    CONCLUSION: More than half of the patients with untreated PNES may become free of seizures after they receive a definite diagnosis and with the passage of time. Longer duration of PNES before the patients received a definite diagnosis may affect their long-term outcome.

    PMID: 30772644 [PubMed - as supplied by publisher]



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    Do recent research studies validate the medicinal plants used in British Columbia, Canada for immune-mediated and other problems in pets?

    Do recent research studies validate the medicinal plants used in British Columbia, Canada for immune-mediated and other problems in pets?

    J Ethnopharmacol. 2019 Feb 14;:

    Authors: Lans C

    Abstract
    ETHNOPHARMACOLOGICAL RELEVANCE: There are insufficient safe and effective treatments for chronic pain in pets. In cases such as osteoarthritis there is no commercially available cure and veterinarians use NSAIDs to manage pain. Pet owners may have to plan for a lifetime of plant-based treatment for the conditions that lead to chronic pain in pets. Phytopharmacotherapies have the advantage of being less toxic, cheap or free, readily available, are more likely to be safe for long-term use and have the potential to reset the immune system to normal functioning.
    AIM OF THE STUDY: To examine the recently published medicinal plant research that matches unpublished data on ethnoveterinary medicines (EVM) used for pets in Canada (British Columbia) to see if the EVM data can provide a lead to the development of necessary drugs.
    MATERIALS AND METHODS: In 2003 semi-structured interviews were conducted with 60 participants who were organic farmers or holisitic medicinal/veterinary practitioners obtained using a purposive sample. Medicinal plants are used to treat a range of conditions. A draft manual prepared from the data was then evaluated by participants at a participatory workshop that discussed the plant-based treatments. A copy of the final version of the manual was given to all research participants. In 2018, the recently published research matching the EVM data was reviewed to see if the EVM practices could serve as a lead for further research.
    RESULTS AND CONCLUSION: The injuries treated in pets in British Columbia included abscesses, sprains and abrasions. Dogs were also treated with medicinal plants for rheumatoid arthritis, joint pain and articular cartilage injuries. More than 40 plants were used. Anal gland problems were treated with Allium sativum L., Aloe vera L., Calendula officinalis L., Plantago major L., Ulmus fulva Michx., Urtica dioica L. and the lichen Usnea longissima Ach. Antioxidants in plants, such as diarctigenin from Arctium lappa, used in ethnoveterinary medicine for rheumatoid arthritis and joint pain in pets are said to be of use in treating pathological conditions such as inflammation and rheumatoid arthritis that are linked to excess production of reactive oxygen species. Understudied plants used for arthritis and joint pain include Hydrangea arborescens and Lactuca muralis. Asthma in pets was treated with: flaxseed oil (Linum usitatissimum L., Linaceae), borage (Borago officinalis L., Boraginaceae), mullein (Verbascum thapsus L., Scrophulariaceae), pumpkin (Cucurbita pepo L., Cucurbitaceae), lobelia (Lobelia inflata L., Lobeliaceae and ginger (Zingiber officinale Roscoe, Zingiberaceae). Pets with heart problems were treated with hawthorn (Crataegus oxyacantha L., Rosaceae), balm of Gilead (Cedronella canariensis (L.) Willd. ex Webb & Berth, Labiatae), horsetail (Equisetum palustre L., Equisetaceae), lady slipper (Cypripedium calceolus L., Orchidaceae), pine (Pinus ponderosa Douglas ex Lawson, Pinaceae), hops (Humulus lupulus L., Cannabinaceae), valerian (Valeriana officinalis L., Valerianaceae), lobelia (Lobelia inflata L., Campanulaceae), wood betony (Stachys officinalis (L.) Trev., Lamiaceae), and mistletoe (Viscum album L., Loranthaceae). Pets were treated with the following plants for epilepsy, motion sickness and anxiety- oatstraw (Avena sativa L., Poaceae), Valeriana officinalis, wild lettuce Lactuca muralis (L.) Fresen., Asteraceae), skullcap (Scutellaria lateriflora l., Lamiaceae), summer savoury (Satureja hortensis L., Lamiaceae) and passion flower (Passiflora incarnata L. (Passifloraceae). Plants used for cancer treatment included Phytolacca decandra, Ganoderma lucidum, Lentinula edodes, Rumex acetosella leaf, Arctium lappa root, Ulmus fulva bark and Rheum palmatum root, Frangula purshiana bark, Zingiber officinale root, Glycyrrhiza glabra root, Ulmus fulva bark, Althea officinalis root, Rheum palmatum stem, Rumex crispus root and Plantago psyllium seeds. Trifolium pratense was used for tumours in the prostate. The following plants were also used to treat cancer: Artemisia annua, Taraxacum officinale and Rumex crispus. These treatments were said to prolong the lives of the dogs treated. Stillingia sylvatica, Verbascum thapsus, Yucca schidigera and Iris versicolor are insufficiently studied, however the use of the other plants in the treatment of cancer is supported by the literature.

    PMID: 30772483 [PubMed - as supplied by publisher]



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    [Continuous spike-waves during slow-wave sleep: Experience during 20 years].

    [Continuous spike-waves during slow-wave sleep: Experience during 20 years].

    An Pediatr (Barc). 2019 Feb 13;:

    Authors: Escobar Fernández L, Coccolo Góngora A, Vázquez López M, Polo Arrondo AP, Miranda Herrero MC, Barredo Valderrama E, Castro de Castro P

    Abstract
    INTRODUCTION: Continuous spikes and waves during slow sleep (CSWS) is an EEG pattern that appears during childhood, and is often associated with cognitive impairment. It can appear in the course of epileptic syndromes, as well as in benign epilepsy. The aim of this study is to analyse epidemiological and clinical characteristic of patients with CSWS, in order to describe possible predictive factors in their outcome.
    METHODS: A retrospective study was conducted on paediatric patients with CSWS treated in a third-level hospital from November 1997 to November 2017.
    RESULTS: The study included 25 patients (68% male), of whom 76% had abnormalities in the neuroimaging or suffered from psychomotor development disorder (secondary CSWS). The rest were healthy, or diagnosed with idiopathic epilepsy. The mean age of onset of CSWS was 6.7 years, but earlier in the secondary CSWS cases. Symptoms were present during the CSWS episode in 72% of cases. All of them were treated with antiepileptic drugs, which were effective in 36%. CSWS stopped in 72%, and remission was longer if the CSWS onset occurred at an older age. One-third (33%) presented with sequelae, mostly cognitive and behavioural alterations. Outcome was poorer in those with secondary CSWS and, in those whose CSWS started at an earlier age and lasted longer.
    CONCLUSION: The CSWS pattern, although rare, is still a therapeutic challenge. A close follow-up of the patients with epilepsy is important, especially if associated with cognitive impairment, in order to establish an early diagnosis and treatment.

    PMID: 30772272 [PubMed - as supplied by publisher]



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    Are Requirements to Deposit Data in Research Repositories Compatible With the European Union's General Data Protection Regulation?

    New efforts and requirements to deposit data in research repositories are necessary to protect privacy interests and comply with the European Union's General Data Protection Regulation. The authors discuss some of the conflicts involved and why they must be reconciled to support ethical and lawful data sharing.

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    Proprotein Convertase Subtilisin/Kexin Type 9 Antibody and Statin-Associated Autoimmune Myopathy



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    Prevention of Shingles: Better Protection and Better Value With Recombinant Vaccine

    In their article, Prosser and colleagues evaluate the cost-effectiveness of recombinant zoster vaccine compared with zoster vaccine live and no zoster vaccination. The editorial discusses the findings in light of current immunization recommendations.

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    Cardiovascular Disease Risk Estimation in China

    Lu and colleagues estimated the prevalence of high cardiovascular disease (CVD) risk in a cohort of almost 1.7 million Chinese adults aged 35 to 75 years with no history of a CVD event. The editorialists see their findings as an important call to action for highly populated middle- and low-income countries in which worsening of the CVD risk factor profile is outpacing the current health sector response.

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    A Cost-Effectiveness Analysis of Vaccination for Prevention of Herpes Zoster and Related Complications: Input for National Recommendations

    Background:
    The U.S. Advisory Committee on Immunization Practices recently developed recommendations for use of a new recombinant zoster vaccine (RZV).
    Objective:
    To evaluate the cost-effectiveness of vaccination with RZV compared with zoster vaccine live (ZVL) and no vaccination, the cost-effectiveness of vaccination with RZV for persons who have previously received ZVL, and the cost-effectiveness of preferential vaccination with RZV over ZVL.
    Design:
    Simulation (state-transition) model using U.S. epidemiologic, clinical, and cost data.
    Data Sources:
    Published data.
    Target Population:
    Hypothetical cohort of immunocompetent U.S. adults aged 50 years or older.
    Time Horizon:
    Lifetime.
    Perspective:
    Societal and health care sector.
    Intervention:
    Vaccination with RZV (recommended 2-dose regimen), vaccination with ZVL, and no vaccination.
    Outcome Measures:
    The primary outcome measure was the incremental cost-effectiveness ratio (ICER).
    Results of Base-Case Analysis:
    For vaccination with RZV compared with no vaccination, ICERs ranged by age from $10 000 to $47 000 per quality-adjusted life-year (QALY), using a societal perspective and assuming 100% completion of the 2-dose RZV regimen. For persons aged 60 years or older, ICERs were less than $60 000 per QALY. Vaccination with ZVL was dominated by vaccination with RZV for all age groups 60 years or older.
    Results of Sensitivity Analysis:
    Results were most sensitive to changes in vaccine effectiveness, duration of protection, herpes zoster incidence, and probability of postherpetic neuralgia. Vaccination with RZV after previous administration of ZVL yielded an ICER of less than $60 000 per QALY for persons aged 60 years or older. In probabilistic sensitivity analyses, RZV remained the preferred strategy in at least 95% of simulations, including those with 50% completion of the second dose.
    Limitation:
    Few data were available on risk for serious adverse events, adherence to the recommended 2-dose regimen, and probability of recurrent zoster.
    Conclusion:
    Vaccination with RZV yields cost-effectiveness ratios lower than those for many recommended adult vaccines, including ZVL. Results are robust over a wide range of plausible values.
    Primary Funding Source:
    Centers for Disease Control and Prevention.

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    Characteristics of High Cardiovascular Risk in 1.7 Million Chinese Adults

    Background:
    As cardiovascular risk increases in China, interest in strategies to mitigate it is growing. However, national information about the prevalence and treatment of high cardiovascular disease (CVD) risk is limited.
    Objective:
    To assess the prevalence and treatment of high CVD risk as well as variations in risk across population subgroups.
    Design:
    National project of CVD screening and management.
    Setting:
    141 county-level regions in all 31 provinces of China.
    Participants:
    Local residents aged 35 to 75 years.
    Measurements:
    Rates of high CVD risk were assessed both in the overall study population and by age, sex, body mass index, geographic region, and socioeconomic status. Multivariable mixed models were fitted to assess the associations between individual characteristics and high CVD risk. Statin and aspirin use was evaluated among persons at high risk for CVD.
    Results:
    Among 1 680 126 participants, 9.5% (95% CI, 9.5% to 9.6%) had high risk for CVD. Mixed models identified persons who were of Han ethnicity, had medical insurance, were currently using alcohol, or were obese as more likely to be at high risk for CVD. Of those with high CVD risk, only 0.6% (CI, 0.5% to 0.6%) and 2.4% (CI, 2.3% to 2.5%) reported using statins and aspirin, respectively. Among persons with high CVD risk and hypertension, 31.8% were receiving antihypertensive medications.
    Limitation:
    Samples were not nationally representative.
    Conclusion:
    Of the 1.7 million participants, 1 in 10 had a high risk for CVD; among those at high risk, fewer than 3% were receiving statins or aspirin. An immense opportunity exists for risk mitigation in this substantial population.
    Primary Funding Source:
    Ministry of Finance and National Health Commission, China.

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    Balancing Protection and Free Movement of Personal Data: The New European Union General Data Protection Regulation

    The health care community is concerned that the General Data Protection Regulation, a recently adopted European Union data privacy law, may impede the flow of information needed to facilitate research and improve care. The authors address these concerns and contend that the regulation specifically aims to facilitate the free movement of data within the European Union rather than restrict or prohibit it.

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    Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway.

    Ursolic Acid Exhibits Potent Anticancer Effects in Human Metastatic Melanoma Cancer Cells (SK-MEL-24) via Apoptosis Induction, Inhibition of Cell Migration and Invasion, Cell Cycle Arrest, and Inhibition of Mitogen-Activated Protein Kinase (MAPK)/ERK Signaling Pathway.

    Med Sci Monit. 2019 Feb 17;25:1283-1290

    Authors: Liu P, Du R, Yu X

    Abstract
    BACKGROUND Ursolic acid is an important bioactive triterpenoid that has been reported to be of tremendous pharmacological importance. However, the anticancer potential of ursolic acid has not been examined against metastatic melanoma cells. Therefore, in this study we examined the anticancer potential of ursolic acid and its mode of action. MATERIAL AND METHODS WST-1 and colony formation assays were used for cell viability assessment. Cell cycle analysis was performed by flow cytometry. Apoptosis was detected by AO/EB staining using fluorescence microscopy. Cell migration and invasion were assessed by Boyden chamber assay. Protein expression was checked by Western blotting. RESULTS The results revealed that ursolic acid exerts significant (p<0.01) growth-inhibitory effects on SK-MEL-24 cells. The IC₅₀ of ursolic acid against SK-MEL-24 cells was 25 µM. Our investigation of the underlying mechanism revealed that ursolic acid prompts apoptotic cell death of the SK-MEL-24 cells, which was linked with increased expression of Bax and Caspase 3 and 9, and decreased expression of Bcl-2. Ursolic acid also halted the SK-MEL-24 cells at G0/G1 phase of the cell cycle and also downregulated the expression of Cyclin B1 and Cdc25. Ursolic acid significantly (p<0.01) inhibited the migration and invasion of SK-MEL-2 cells, indicative of its anti-metastatic potential. Finally, ursolic acid inhibited the MAPK/ERK pathway by suppressing the expression of p-P38 and p-ERK. CONCLUSIONS Ursolic acid appears to be a potent molecule for the treatment of melanoma.

    PMID: 30772887 [PubMed - in process]



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    Palbociclib triggers apoptosis in bladder cancer cells by Cdk2-induced Rad9-mediated reorganization of the Bak.Bcl-xl complex.

    Palbociclib triggers apoptosis in bladder cancer cells by Cdk2-induced Rad9-mediated reorganization of the Bak.Bcl-xl complex.

    Biochem Pharmacol. 2019 Feb 14;:

    Authors: Zhang G, Ma F, Li L, Li J, Li P, Zeng S, Sun H, Li E

    Abstract
    Palbociclib is a Cdk4/6 inhibitor approved for metastatic estrogen receptor-positive breast cancer. The drug is also under clinical evaluation for metastatic urothelial cancer and other solid tumors. Preclinical studies from multiple tumor types suggest that other factors also affect the sensitivity of individual tumors to Cdk4/6 inhibitor. We show here that Cdk2 has an essential role in palbociclib antitumor effect against bladder cancers. We found that palbociclib induced apoptosis instead of cell cycle arrest to exhibit its anticancer activity in T24 cells, as was evidenced by membrane blebbing, caspase-3 activation and AIF release from mitochondria. Cdk2 activation was important to palbociclib-induced apoptotic triggering activity, since depletion of Cdk2 significantly inhibited caspase-3 activation and cell apoptosis. Cdk2 activation caused p-Rad9 translocation to the mitochondria and subsequently interaction with Bcl-xl, leading to conformational activation of Bak and cell apoptosis. The anticancer activity and Cdk2 activation of palbociclib-treated mice were finally validated in a T24 xenograft model. Collectively, these results together demonstrate that palbociclib exerts its anticancer effect in T24 cells mainly through Cdk2 activation. Our findings provide new insights into the molecular interactions and anticancer mechanisms of Cdk4/6 inhibitors.

    PMID: 30772267 [PubMed - as supplied by publisher]



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    Annals Graphic Medicine: Introducing “Dr. Mom” and “Progress Notes”

    The ever-growing popularity of Annals Graphic Medicine has prompted us to expand it to include regular monthly features from 2 talented physician artists. Look for a new installment of "Dr. Mom" on the first Tuesday of the month and "Progress Notes" on the third Tuesday.

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    Annals for Hospitalists - 19 February 2019



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    Review: Prophylactic antibiotics reduce exacerbations but do not improve quality of life in patients with COPD



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    Annals On Call - Estimating Stroke Risk in Atrial Fibrillation



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    A Pound of Prevention? Assessing the Value of New Cholesterol-Lowering Drugs

    PCSK9 inhibitors substantially reduce cholesterol levels, but the U.S. Food and Drug Administration–approved PCSK9 inhibitors, alirocumab and evolocumab, came to market priced at $14 000 per year—more than 100 times the cost of a generic statin. Kazi and colleagues' cost-effectiveness analysis of alirocumab in secondary prevention is based on new trial results and updated pricing. The editorialist discusses the findings and what it takes for preventive therapies to be cost-effective.

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    Annals Graphic Medicine - Progress Notes: Cancer



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    Review: Adjuvant recombinant subunit vaccine prevents herpes zoster more than live attenuated vaccine in adults ≥ 50 years



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    Annals Consult Guys - Surgery With Aortic Stenosis?



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    Kidney Transplantation in Lupus Nephritis: Can We Do Even Better?

    Jorge and colleagues examined data from 1995 to 2014 to assess outcomes of patients with lupus nephritis who initiated dialysis and were placed on the waitlist for a kidney transplant. The editorialists discuss the findings in light of slow progress in the treatment of lupus nephritis. Given higher patient and allograft survival with both preemptive and early kidney transplant, it is essential that transplant be considered as promptly as possible for patients with lupus nephritis.

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    Annals for Hospitalists Inpatient Notes - Clinical Pearls—Acute Pancreatitis



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    Annals for Educators - 19 February 2019



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    Bun

    "Children don't fear death—they fear pain and abandonment. Even the wee ones can sense who can give them shelter."

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    In premenopausal women with recurrent cystitis, increasing water intake for 12 months reduced recurrence



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    Hotline: A Poem



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    Selective Use of Coronary Artery Calcium Testing for Shared Decision Making: Guideline Endorsed and Ready for Prime Time

    This commentary addresses the 2018 American Heart Association and American College of Cardiology risk assessment and cholesterol management recommendations about "risk enhancers" and coronary artery calcium testing.

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    Regarding a Letter to a Dying Friend



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    External Validation of the MEESSI Acute Heart Failure Risk Score A Cohort Study

    Background:
    The MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score was developed to predict 30-day mortality in patients presenting with acute heart failure (AHF) to emergency departments (EDs) in Spain. Whether it performs well in other countries is unknown.
    Objective:
    To externally validate the MEESSI-AHF score in another country.
    Design:
    Prospective cohort study. (ClinicalTrials.gov: NCT01831115).
    Setting:
    Multicenter recruitment of dyspneic patients presenting to the ED.
    Participants:
    The external validation cohort included 1572 patients with AHF.
    Measurements:
    Calculation of the MEESSI-AHF score using an established model containing 12 independent risk factors.
    Results:
    Among 1572 patients with adjudicated AHF, 1247 had complete data that allowed calculation of the MEESSI-AHF score. Of these, 102 (8.2%) died within 30 days. The score predicted 30-day mortality with excellent discrimination (c-statistic, 0.80). Assessment of cumulative mortality showed a steep gradient in 30-day mortality over 6 predefined risk groups (0 patients in the lowest-risk group vs. 35 [28.5%] in the highest-risk group). Risk was overestimated in the high-risk groups, resulting in a Hosmer–Lemeshow P value of 0.022. However, after adjustment of the intercept, the model showed good concordance between predicted risks and observed outcomes (P = 0.23). Findings were confirmed in sensitivity analyses that used multiple imputation for missing values in the overall cohort of 1572 patients.
    Limitations:
    External validation was done using a reduced model. Findings are specific to patients with AHF who present to the ED and are clinically stable enough to provide informed consent. Performance in patients with terminal kidney failure who are receiving long-term dialysis cannot be commented on.
    Conclusion:
    External validation of the MEESSI-AHF risk score showed excellent discrimination. Recalibration may be needed when the score is introduced to new populations.
    Primary Funding Source:
    The European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, and University Hospital Basel.

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    Being Relevant

    There was relief in knowing that my colleague could offer what this woman needed even when I couldn't—especially when I couldn't.

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    Αναζήτηση αυτού του ιστολογίου

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