Αρχειοθήκη ιστολογίου

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Τρίτη 3 Ιουλίου 2018

Minimally Invasive Versus Open Pancreaticoduodenectomy: A Propensity-matched Study From a National Cohort of Patients

imageObjective: To compare the perioperative outcomes of minimally invasive pancreaticoduodenectomy (MIPD) in comparison with open pancreaticoduodenectomy (OPD) in a national cohort of patients. Background: Limited well-controlled studies exist comparing perioperative outcomes between MIPD and OPD. Methods: Patients who underwent MIPD and OPD were abstracted from the 2014 to 2015 pancreas-targeted American College of Surgeons National Surgical Quality Improvement Program. OPD and MIPD patients were matched 3:1 using propensity score, and perioperative outcomes were compared. Results: A total of 4484 patients were identified with 334 (7.4%) undergoing MIPD. MIPD patients were younger, more likely to be White, and had a lower rate of weight loss. They were more likely to undergo classic Whipple and to have a drain placed. After 3:1 matching, 1002 OPD patients were compared with 334 MIPD patients. MIPD was associated with longer mean operative time (426.6 vs 359.6 minutes; P 14 days (16.5% vs 21.6%; P = 0.047). The 2 groups had a similar rate of 30-day mortality (MIPD 1.8% vs OPD 1.3%; P = 0.51), overall complications, postoperative pancreatic fistula, and delayed gastric emptying. A secondary analysis comparing MIPD without conversion or open assist with OPD showed that MIPD patients had lower rates of overall surgical site infection (13.4% vs 19.6%; P = 0.04) and transfusion (7.9% vs 14.4%; P = 0.02). Conclusions: MIPD had an equivalent morbidity and mortality rate to OPD, with the benefit of a decreased rate of prolonged length of stay, though this is partially offset by an increased readmission rate.

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The Southampton Consensus Guidelines for Laparoscopic Liver Surgery: From Indication to Implementation

imageObjective: The European Guidelines Meeting on Laparoscopic Liver Surgery was held in Southampton on February 10 and 11, 2017 with the aim of presenting and validating clinical practice guidelines for laparoscopic liver surgery. Background: The exponential growth of laparoscopic liver surgery in recent years mandates the development of clinical practice guidelines to direct the speciality's continued safe progression and dissemination. Methods: A unique approach to the development of clinical guidelines was adopted. Three well-validated methods were integrated: the Scottish Intercollegiate Guidelines Network methodology for the assessment of evidence and development of guideline statements; the Delphi method of establishing expert consensus, and the AGREE II-GRS Instrument for the assessment of the methodological quality and external validation of the final statements. Results: Along with the committee chairman, 22 European experts; 7 junior experts and an independent validation committee of 11 international surgeons produced 67 guideline statements for the safe progression and dissemination of laparoscopic liver surgery. Each of the statements reached at least a 95% consensus among the experts and were endorsed by the independent validation committee. Conclusion: The European Guidelines Meeting for Laparoscopic Liver Surgery has produced a set of clinical practice guidelines that have been independently validated for the safe development and progression of laparoscopic liver surgery. The Southampton Guidelines have amalgamated the available evidence and a wealth of experts' knowledge taking in consideration the relevant stakeholders' opinions and complying with the international methodology standards.

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Dynamic Angiogenic Switch as Predictor of Response to Chemotherapy-Bevacizumab in Patients With Metastatic Colorectal Cancer

Background: Previous studies have shown that metastatic colorectal carcinoma (mCRC) patients treated with bevacizumab, experience variation in the plasma levels of angiogenesis growth factors and related cytokines, called angiogenic switch (AS). The aim of the present study was to analyze the relationship between AS and the clinical response during standard chemotherapy-bevacizumab treatment. Patients and Methods: Patients with Eastern Cooperative Oncology Group 0-1 mCRC were eligible. Patients received treatment with standard dose capecitabine plus either oxaliplatin or irinotecan and bevacizumab for 6 cycles. Initial treatment was followed by maintenance therapy with bevacizumab plus capecitabine until progression. Plasma levels of angiogenic-related cytokines (hepatocyte growth factor, placental growth factor, macrophage chemoattractant protein-3, MM-9, eotaxin, basic fibroblast growth factor, and interleukin 18) were prospectively analyzed at baseline and every 8 weeks. Progression-free survival (PFS) was calculated using the Kaplan-Meier method. Results: A total of 71 patients were enrolled. AS was observed in 45 patients (63.4%), 28 of whom experienced AS at the first evaluation after treatment start. Disease control, which includes partial/complete response and stable disease, was seen in 96% of AS patients (43/45), but only in 15/26 (58%) for the remaining patients without evidence of AS (P

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Hereditary ataxias and paraparesias: clinical and genetic update

imagePurpose of review This review aims at updating the clinical and genetic aspects of hereditary spastic paraplegias (HSPs) and hereditary cerebellar ataxias (HCAs), focusing on the concept of spastic-ataxia phenotypic spectrum and on newly identified clinical overlaps with other neurological and nonneurological diseases. Recent findings Next-generation sequencing (NGS) has allowed the discovery of new genes involved in HSPs and HCAs. They include new HCAs genes such as GRM1 (SCA44), FAT2 (SCA45), PLD3 (SCA46), SCYL1 (SCAR21), UBA5 (SCAR24) and XRCC1 (SCAR26) as well as CAPN1 (SPG76) and CPT1C (SPG73) in HSPs. Furthermore, NGS allowed enriching known genes phenotype, reinforcing the overlap between HSPs and HCAs defining the spastic ataxia spectrum. Clear examples are the expanded phenotypes associated with mutations in SPG7, PNPLA6, GBA2, KIF1C, CYP7B1, FA2H, ATP13A2 and many others. Moreover, other genes not previously linked to HCAs and HSPs have been implicated in spastic or ataxic phenotypes. Summary The increase of HSPs and HCAs-related phenotypes and the continuous discovery of genes complicate clinical diagnostic in practice but, at the same time, it helps highlighting common pathological pathways, therefore opening new ways to the development of common therapeutic approaches.

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Cerebrovascular disorders

imagePurpose of review Not unexpected from the variety of cerebrovascular disorders and their morphologic and clinical consequences the contributions of neuroimaging are also quite diverse and go with different approaches in different directions. By reviewing the recent advances in these various areas, we will attempt to highlight those contributions, which may be most meaningful both for the clinician and the researcher dealing with cerebrovascular disorders. Recent findings After long expectations of the utility of mismatch concepts, such patient selection has proven successful in extending the benefit of recanalization of acute ischaemic stroke by mechanical thrombectomy beyond 6 h and the importance of infarct size and collaterals has been documented. Insights into the association of bleeding markers such as cerebral microbleeds and cortical superficial siderosis with spontaneous, treatment-related, first or recurrent intracerebral haemorrhage have been consolidated and explored further. New data have been added to better understand the clinical and prognostic impact of the various features of small vessel disease including cortical microinfarcts. Summary Neuroimaging findings increasingly serve to guide treatment decisions in acute ischaemic stroke, to identify morphologic markers associated with the risk for intracerebral haemorrhage and to detect and understand the consequences of chronically accumulating cerebrovascular damage.

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The changing landscape of motor neuron disease imaging: the transition from descriptive studies to precision clinical tools

imagePurpose of review Neuroimaging in motor neuron disease (MND) has traditionally been seen as an academic tool with limited direct relevance to individualized patient care. This has changed radically in recent years as computational imaging has emerged as a viable clinical tool with true biomarker potential. This transition is not only fuelled by technological advances but also by important conceptual developments. Recent findings The natural history of MND is now evaluated by presymptomatic, postmortem and multi-timepoint longitudinal imaging studies. The anatomical spectrum of MND imaging has also been expanded from an overwhelmingly cerebral focus to innovative spinal and muscle applications. In contrast to the group-comparisons of previous studies, machine-learning and deep-learning approaches are increasingly utilized to model real-life diagnostic dilemmas and aid prognostic classification. The focus from evaluating focal structural changes has shifted to the appraisal of network integrity by connectivity-based approaches. The armamentarium of MND imaging has also been complemented by novel PET-ligands, spinal toolboxes and the availability of magnetoencephalography and high-field magnetic resonance (MR) imaging platforms. Summary In addition to the technological and conceptual advances, collaborative multicentre research efforts have also gained considerable momentum. This opinion-piece reviews emerging trends in MND imaging and their implications to clinical care and drug development.

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Update on amino acid PET of brain tumours

imagePurpose of review The aim of this study was to give an update on the emerging role of PET using radiolabelled amino acids in the diagnostic workup and management of patients with cerebral gliomas and brain metastases. Recent findings Numerous studies have demonstrated the potential of PET using radiolabelled amino acids for differential diagnosis of brain tumours, delineation of tumour extent for treatment planning and biopsy guidance, differentiation between tumour progression and recurrence versus treatment-related changes, and for monitoring of therapy. The Response Assessment in Neuro-Oncology (RANO) working group – an international effort to develop new standardized response criteria for clinical trials in brain tumours – has recently recommended the use of amino acid PET imaging for brain tumour management in addition to MRI at every stage of disease. With the introduction of F-18 labelled amino acids, a broader clinical application has become possible, but is still hampered by the lack of regulatory approval and of reimbursement in many countries. Summary PET using radiolabelled amino acids is a rapidly evolving method that can significantly enhance the diagnostic value of MRI in brain tumours. Current developments suggest that this imaging technique will become an indispensable tool in neuro-oncological centres in the near future.

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Dystonia as a network disorder: a concept in evolution

imagePurpose of review This survey takes into consideration the most recent advances in both human degenerative ataxias, disorders with a well established cerebellar origin, and discoveries from dystonia rodent models aimed at discussing the pathogenesis of dystonia. Recent findings One common recurrent term that emerges when describing dystonia is heterogeneity. Indeed, dystonia encompasses a wide group of 'hyperkinetic' movement disorders, with heterogeneous causes, classification, anatomical and physiological substrates. In addition, the clinical heterogeneity of age at onset, symptom distribution and appearance of non-motor symptoms has supported the concept of dystonia as 'network' disorder. Pathophysiological alterations are thought to arise from dysfunction at cortico-thalamic-basal ganglia level, whereas, more recently, a role for cerebellar pathways emerged. Results from human and animal studies thus fuel the evolving concept of the network disorder. Summary Current evidence suggests the involvement of multiple brain regions and cellular mechanisms, as part of the neural dysfunction observed at system level in dystonia.

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Neuroimaging of brain trauma

imagePurpose of review The purpose of this review is to provide an update on advanced neuroimaging techniques in traumatic brain injury (TBI). We will focus this review on recent literature published within the last 18 months and the advanced neuroimaging techniques of perfusion imaging and diffusion tensor imaging (DTI). Recent findings In the setting of a moderate or severe acute closed head injury (Glasgow Coma Scale

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Progressive supranuclear palsy and multiple system atrophy: clinicopathological concepts and therapeutic challenges

imagePurpose of review This update discusses novel aspects on clinicopathological concepts and therapeutic challenges in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), arising from publications of the last 1.5 years. Recent findings The clinical criteria for diagnosis of PSP have been revised. Clinical variability of pathologically defined PSP and MSA makes the development of mature biomarkers for early diagnosis and biomarker-based trial design indispensable. Novel molecular techniques for biomarker supported diagnosis of PSP and MSA and for monitoring disease progression are being studied. Research in the pathophysiology of both diseases generates gradual progress in the understanding of the underlying processes. Several promising disease-modifying therapeutic approaches for PSP and MSA are now moving into clinical trials. Summary Recent research generates insights in the pathophysiological relevant processes and raises hope for earlier clinical diagnosis and disease-modifying therapies of patients with PSP and MSA.

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Neuroimaging in epilepsy

imagePurpose of review Epilepsy neuroimaging is important for detecting the seizure onset zone, predicting and preventing deficits from surgery and illuminating mechanisms of epileptogenesis. An aspiration is to integrate imaging and genetic biomarkers to enable personalized epilepsy treatments. Recent findings The ability to detect lesions, particularly focal cortical dysplasia and hippocampal sclerosis, is increased using ultra high-field imaging and postprocessing techniques such as automated volumetry, T2 relaxometry, voxel-based morphometry and surface-based techniques. Statistical analysis of PET and single photon emission computer tomography (STATISCOM) are superior to qualitative analysis alone in identifying focal abnormalities in MRI-negative patients. These methods have also been used to study mechanisms of epileptogenesis and pharmacoresistance. Recent language fMRI studies aim to localize, and also lateralize language functions. Memory fMRI has been recommended to lateralize mnemonic function and predict outcome after surgery in temporal lobe epilepsy. Summary Combinations of structural, functional and post-processing methods have been used in multimodal and machine learning models to improve the identification of the seizure onset zone and increase understanding of mechanisms underlying structural and functional aberrations in epilepsy.

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Myoclonus-dystonia: classification, phenomenology, pathogenesis, and treatment

imagePurpose of review The present study will highlight recent advances in the field of myoclonus-dystonia with a focus on clinical aspects, pathogenesis, and treatment. We will also discuss genetics, classification issues, and diagnostic criteria. Recent findings Myoclonus-dystonia is a clinical syndrome corresponding to the phenotype linked to SGCE, the main causative gene. Childhood-onset myoclonus that predominates over dystonia with prominent upper body involvement, an absence of truncal dystonia, associated anxiety or compulsivity, and a positive family history are helpful diagnostic clues. Recent studies demonstrated that zonisamide is an interesting therapeutic option in myoclonus-dystonia, and that bilateral pallidal stimulation has major and lasting therapeutic effects. Accumulating evidence suggests that an alteration in cerebello-thalamic pathway function may play a prominent role and that this is possibly related to a GABAergic deficit reflecting Purkinje cell dysfunction. Impaired striatal plasticity and disturbed serotonin homeostasis may also be implicated. Newly available cellular and rodent models may further assist in investigating the pathogenesis of this disorder. Summary Comprehensive analysis of the phenotype and precise classification are important in patients with myoclonus and dystonia to identify homogeneous groups of patients. This is critical to guide tailored therapeutic strategies and promote effective research.

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Recent advances in headache neuroimaging

imagePurpose of review Primary headaches, such as migraine and cluster headache, are one of the most common and disabling neurological diseases worldwide. Neuroimaging studies have changed the way we understand these diseases and have enriched our knowledge of the mechanisms of actions of currently available therapies. Recent findings The present review highlights the major findings reported in migraine and cluster headache neuroimaging over the last year. Widespread structural and functional abnormalities in cortical and subcortical areas involved in multisensory, including pain, processing have been shown in migraine and cluster headache patients during different phases of the disease. Beyond the involvement of single brain areas, dysfunctional brain networks contribute to their pathophysiology. New central mechanisms of action of headache preventive treatments have also been explored. Summary A better understanding of migraine and cluster headache biology has paved the way for the development of new improved treatments for both these conditions. Although significant advances have been made over the last year, there are still many unsolved questions to address.

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Editorial introductions

imageNo abstract available

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MRI in multiple sclerosis: what is changing?

imagePurpose of review To summarize recent findings from the application of MRI in the diagnostic work-up of patients with suspected multiple sclerosis (MS), and to review the insights into disease pathophysiology and the utility of MRI for monitoring treatment response. Recent findings New evidence from the application of MRI in patients with clinically isolated syndromes has guided the 2017 revision of the McDonald criteria for MS diagnosis, which has simplified their clinical use while preserving accuracy. Other MRI measures (e.g., cortical lesions and central vein signs) may improve diagnostic specificity, but their assessment still needs to be standardized, and their reliability confirmed. Novel MRI techniques are providing fundamental insights into the pathological substrates of the disease and are helping to give a better understanding of its clinical manifestations. Combined clinical-MRI measures of disease activity and progression, together with the use of clinically relevant MRI measures (e.g., brain atrophy) might improve treatment monitoring, but these are still not ready for the clinical setting. Summary Advances in MRI technology are improving the diagnostic work-up and monitoring of MS, even in the earliest phases of the disease, and are providing MRI measures that are more specific and sensitive to disease pathological substrates.

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Update in therapeutic strategies for Parkinson's disease

imagePurpose of review To review recent advances in therapeutics for motor and nonmotor symptoms of Parkinson's disease. Recent findings Neuroprotection remains a large area of investigation with preliminary safety data on alpha synuclein immunotherapy and glucagon-like peptide-1 agonists. Novel Monoamine Oxidase B and Caetchol-O-methyltransferase-inhibitors for motor fluctuations have shown benefit and are recently approved for clinical use. Long-acting amantadine has also been approved to reduce dyskinesia. Alternative delivery strategies (sublingual, inhaled) dopaminergics may prove useful for rapid reversal of Parkinson's disease motor symptoms. Advanced therapies (surgery and infusional therapies) continue to be useful in subgroups of patients for motor complications with improved safety and also benefit on some nonmotor symptoms, including neuropsychiatric issues. Specific therapeutics for cognition, swallowing, sleep, and mood disorders had moderate to limited benefits. Exercise-based therapy appears beneficial at all stages of Parkinson's disease. Summary The motor symptoms of Parkinson's disease can be reasonably treated and managed. However, therapies to slow or prevent disease progression remain a focus of research. Despite increased studies, treating nonmotor symptoms remains a challenge and an ongoing priority.

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Alzheimer's disease neuroimaging

imagePurpose of review The aim of this study was to discuss the contribution of neuroimaging studies to our understanding of Alzheimer's disease. We now have the capability of measuring both tau and beta-amyloid (Aβ) proteins in the brain, which together with more traditional neuroimaging modalities, has led the field to focus on using neuroimaging to better characterize disease mechanisms underlying Alzheimer's disease. Recent findings Studies have utilized tau and Aβ PET, as well as [18F]fluorodeoxyglucose PET, and structural and functional MRI, to investigate the following topics: phenotypic variability in Alzheimer's disease , including how neuroimaging findings are related to clinical phenotype and age; multimodality analyses to investigate the relationships between different neuroimaging modalities and what that teaches us about disease mechanisms; disease staging by assessing neuroimaging changes in the very earliest phases of the disease in cognitively normal individuals and individuals carrying an autosomal dominant Alzheimer's disease mutation; and influence of other comorbidities and proteins to the disease process. Summary The findings shed light on the role of tau and Aβ, as well as age and other comorbidities, in the neurodegenerative process in Alzheimer's disease. This knowledge will be crucial in the development of better disease biomarkers and targeted therapeutic approaches.

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The patchy tremor landscape: recent advances in pathophysiology

imagePurpose of review We focus on new insights in the pathophysiology of Parkinson's disease tremor, essential tremor, tremor in dystonia, and orthostatic tremor. Recent findings Neuroimaging findings suggest that Parkinson's disease resting tremor is associated with dopaminergic dysfunction, serotonergic dysfunction, or both. Not all tremors in Parkinson's disease have the same pathophysiology: postural tremor in Parkinson's disease can be subdivided into pure postural tremor, which involves nondopaminergic mechanisms, and re-emergent tremor, which has a dopaminergic basis. Unlike Parkinson's disease tremor, essential tremor has an electrophysiological signature suggestive of a single (or several tightly coupled) oscillators. Visual feedback increases essential tremor and enhances cerebral activity in the cerebello-thalamo-cortical circuit, supplementary motor area, and parietal cortex. Little is known about dystonic tremor but the available evidence suggests that both the basal ganglia and the cerebellum play a role. Finally, recent work in orthostatic tremor points towards the role of the pontine tegmentum and dysfunctional cerebellar-SMA circuitry. Summary Many pathological tremors involve the cerebello-thalamo-cortical circuitry, and the clinical and pathophysiological boundaries between tremor disorders are not always clear. Differences between tremor disorders – or even individual patients – may be explained by the specific balance of neurotransmitter degeneration, by distinct circuit dynamics, or by the role of regions interconnected to the cerebello-thalamo-cortical circuit.

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MRI of non-Alzheimer's dementia: current and emerging knowledge

imagePurpose of review The correct classification of non-Alzheimer's dementia is crucial to study disease mechanisms, predict disease progression and test disease-specific treatments. Brain atrophy assessment with morphometric MRI is currently the gold standard for in-vivo localization of neurodegeneration. Structural and functional connectivity biomarkers are becoming increasingly available. This review emphasizes the potential applications of MRI in the main non-Alzheimer's dementia such as dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). Recent findings MRI can predict co-occurrence of Alzheimer's disease pathology in DLB patients and pathological subtypes in patients with FTD. Innovative applications of brain connectivity are providing neural substrates explaining the network-dependent spread of pathology in non-Alzheimer's dementia. Advanced MRI can be relevant in characterizing the temporal sequence of the earliest functional and structural brain changes in individuals at risk for neurodegenerative non-Alzheimer's diseases. Summary Morphometric MRI is clinically applied at an individual level for the differentiation between Alzheimer's and non-Alzheimer's dementia and may help in predicting underlying pathology, which will be critical for the success of disease-modifying therapies. Longitudinal, multimodal MRI studies are required to demonstrate whether advanced magnetic resonance techniques can be reliable outcome measures to monitor disease progression in clinical trials, starting from the presymptomatic stage.

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Movement disorders in mitochondrial disease: a clinicopathological correlation

imagePurpose of review The scope of this review is to give an updated account of movement disorders associated with mitochondrial disease, with a particular focus on recently discovered clinicopathological correlations. Recent findings Movement disorders are common clinical manifestations of mitochondrial diseases, in part because of the high vulnerability of neurons controlling motor circuits to mitochondrial respiratory dysfunction and energy failure. Intriguingly, the clinicopathological correlations of movement disorders in mitochondrial disease do not always conform to established neurophysiological knowledge. In particular, nearly complete substantia nigra degeneration and nigrostriatal denervation can occur without being accompanied by any of the clinical signs traditionally associated with parkinsonism. This apparent paradox, may be because of compensation by concomitant impairment of other motor circuits involving the cerebellum and thalamus. Summary Movement disorders commonly accompany mitochondrial disease and may show paradoxical clinical−anatomical correlations. Further research is warranted in order to elucidate the mechanisms underlying the phenotypic expression of movement disorders in mitochondrial disease. This knowledge will advance our understanding of the pathogenesis of movement disorders in a broader clinical and pathophysiological context.

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Neuroimaging advances in Parkinson's disease

imagePurpose of review Neuroimaging in Parkinson's disease is an evolving field, providing in-vivo insights into the structural and biochemical changes of the condition, although its diagnosis remains clinical. Here, we aim to summarize the most relevant recent advances in neuroimaging in Parkinson's disease to assess the underlying disease process, identify a biomarker of disease progression and guide or monitor therapeutic interventions. Recent findings The clinical applications of imaging technology increasingly allow to quantify pigments (iron, neuromelanin) on MRI, proteins (tau), cell markers (phosphodiesterases, microglia) and neurotransmitter receptors (dopamine, serotonin, noradrenalin, cholin) via PET protocols, activity maps by resting-state and task-dependent functional MRI, as well as microstructural changes (free water) through diffusion-based assessments. Their application provides increasing insight on the temporal and spatial dynamics of dopaminergic and other neurotransmitter systems as well as anatomical structures and circuits in Parkinson's disease. An expanding list of PET tracers increases the yield of functional studies. Summary This review summarizes the most recent, relevant advances in neuroimaging technology in Parkinson's disease. In particular, the combination of different imaging techniques seems promising to maximize the scope of future work, which should, among others, aim at identifying the best imaging marker of disease progression.

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The expanding spectrum of paroxysmal movement disorders: update from clinical features to therapeutics

imagePurpose of review This review will discuss the expanding clinical spectrum of paroxysmal movement disorders and therapeutic options in light of emerging genotypic heterogeneity in these conditions. Recent findings Paroxysmal movement disorders comprise a heterogeneous group of rare neurological conditions characterized by intermittent episodes of abnormal movement associated with various triggers. As the clinical and genotypic spectrum of these disorders evolves, so also has the range of therapeutic options. Triheptanoin has recently been shown to be a very promising alternative to the ketogenic diet in paroxysmal exercise-induced dyskinesia. Four-aminopyridine is now considered first-line symptomatic therapy for episodic ataxia type-2, with pre-clinical findings indicating cerebellar neuroprotection. Summary In light of the newly emerging therapies, careful clinical phenotyping is needed to ensure diagnostic precision and timely initiation of appropriate therapies.

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Molecular mechanisms of acquired resistance to third-generation EGFR-TKIs in EGFR T790M-mutant lung cancer

Ann Oncol 2018; 29: i28–i37 (doi:10.1093/annonc/mdx705)

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Phase II study of nab-paclitaxel in refractory small bowel adenocarcinoma and CpG island methylator phenotype (CIMP)-high colorectal cancer

Ann Oncol 2018; 29: 139–144 (doi:10.1093/annonc/mdx688)

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Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

Ann Oncol 2017; 28: 2517–2525 (doi:10.1093/annonc/mdx352)

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Contender waveforms for Low-Power Wide-Area networks in a scheduled 4G OFDM framework

When designing new solutions for Low-Power Wide-Area (LPWA) networks, coexistence and integration into existing 4G frameworks should be considered to ease the deployment procedure and reduce costs. In a previo...

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Potentiation of PD-L1 blockade with a potency-matched dual cytokine–antibody fusion protein leads to cancer eradication in BALB/c-derived tumors but not in other mouse strains

Abstract

We have recently described a novel therapeutic antibody product (IL2–F8–TNFmut), featuring the simultaneous fusion of murine IL2 and of a TNF mutant with scFv(F8), an antibody specific to the alternatively-spliced extra domain A of fibronectin (EDA). Here, we report on the in vivo characterization of the anti-cancer activity of IL2–F8–TNFmut in four immunocompetent murine models of cancer, CT26, WEHI-164, F9 teratocarcinoma and Lewis lung carcinoma (LLC), using the product alone or in combination with a monoclonal antibody specific to murine PD-L1. All four models exhibited a strong expression of EDA-fibronectin, which was confined to vascular structures for F9 tumors, while the other three malignancies exhibited a more stromal pattern of staining. A complete and long-lasting tumor eradication of CT26 and WEHI-164 tumors was observed in BALB/c mice when IL2–F8–TNFmut was used in combination with PD-L1 blockade. The combination treatment led to improved tumor growth inhibition in 129/SvEv mice bearing murine teratocarcinoma or in C57BL/6 mice bearing murine LLC, but those cancer cures were difficult to achieve in those models. A microscopic analysis of tumor sections, obtained 24 h after pharmacological treatment, revealed that the PD-L1 antibody had homogenously reached tumor cells in vivo and that the combination of PD-L1 blockade with IL2–F8–TNFmut stimulated an influx of NK cells and of T cells into the neoplastic mass. These data indicate that potency-matched dual-cytokine fusion proteins may be ideally suited to potentiate the therapeutic activity of immune check-point inhibitors.



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Systemic-inflammation-based score can predict prognosis in metastatic gastric cancer patients before first-line chemotherapy

Future Oncology, Ahead of Print.


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Effects of physicochemical parameters on volatile sulphur compound formation from l-methionine catabolism by non-growing cells of Kluyveromyces lactis

The present study investigated for the first time the effects of various physicochemical parameters on the production of volatile sulphur compounds (VSCs) by non-growing cells of Kluyveromyces lactis supplemented...

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Poly-l-gamma-glutamic acid production by recombinant Bacillus subtilis without pgsA gene

Poly-gamma-glutamic acid (PGA) is a promising bio-based polymer that shares many functions with poly (acrylic acid) and its derivatives. Thus, technologies for efficient production and molecular size control o...

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Investigation into the potential for post-mortem formation of carboxyhemoglobin in bodies retrieved from fires

Abstract

The forensic investigation of a deceased person retrieved following a fire includes measuring carboxyhemoglobin. A carboxyhemoglobin saturation above 10% is considered indicative of respiration during a fire, implying the person had been alive. This relies on the assumption that carbon monoxide will not diffuse into blood used for toxicological analysis. This project investigated the potential for carbon monoxide to passively diffuse into a body and if carboxyhemoglobin levels could become elevated post-mortem. Stillborn piglets with intact skin were exposed to carbon monoxide. Carboxyhemoglobin formed in the hypostasis of the skin, but carboxyhemoglobin levels in blood from the heart and chest cavities were not significantly elevated. However, defects in the skin over body cavities (producing breaches to replicate cases with stab wounds or heat damage) resulted in cavity blood carboxyhemoglobin levels above 10%. A review of fire death cases in South Australia 2000–2015 was performed to determine the origin of the blood samples used for toxicological analysis and the incidence of cases with breaches of body cavities. This revealed a small number of cases in which blood from the cavities had been analyzed when cavity breaches were present. Thus, there is a potential for significant elevation of carboxyhemoglobin saturation post-mortem in forensic casework involving bodies retrieved from fires.



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Optimising Genomic Selection in Wheat: Effect of Marker Density, Population Size and Population Structure on Prediction Accuracy

Genomic selection applied to plant breeding enables earlier estimates of a line's performance and significant reductions in generation interval. Several factors affecting prediction accuracy should be well understood if breeders are to harness genomic selection to its full potential. We used a panel of 10,375 bread wheat (Triticum aestivum) lines genotyped with 18,101 SNP markers to investigate the effect and interaction of training set size, population structure and marker density on genomic prediction accuracy. Through assessing the effect of training set size we showed the rate at which prediction accuracy increases is slower beyond approximately 2,000 lines. The structure of the panel was assessed via principal component analysis and K-means clustering, and its effect on prediction accuracy was examined through a novel cross-validation analysis according to the K-means clusters and breeding cohorts. Here we showed that accuracy can be improved by increasing the diversity within the training set, particularly when relatedness between training and validation sets is low. The breeding cohort analysis revealed that traits with higher selection pressure (lower allelic diversity) can be more accurately predicted by including several previous cohorts in the training set. The effect of marker density and its interaction with population structure was assessed for marker subsets containing between 100 and 17,181 markers. This analysis showed that response to increased marker density is largest when using a diverse training set to predict between poorly related material. These findings represent a significant resource for plant breeders and contribute to the collective knowledge on the optimal structure of calibration panels for genomic prediction.



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AMA Urges Caution With Use of Wire-Bristle BBQ Grill Brushes

TUESDAY, July 3, 2018 -- The American Medical Association (AMA) states that caution should be exercised with use of wire-bristle grill brushes due to the potential health and safety risks associated with bristles that may break off and adhere to the...

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FDA Permits Marketing of Devices to Create Arteriovenous Fistula

TUESDAY, July 3, 2018 -- The U.S. Food and Drug Administration has permitted marketing of two catheter-based devices designed to create an arteriovenous (AV) fistula in patients with chronic kidney disease in need of hemodialysis. The devices are...

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HPV Cervical CA Screening Cuts Odds of Later CIN3+ Diagnosis

TUESDAY, July 3, 2018 -- The use of primary human papillomavirus (HPV) testing versus cytology results in reduced likelihood of cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) at 48 months, according to a study published in the...

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Vegetable Trays Tainted With Cyclospora Put Seven in Hospital

TUESDAY, July 3, 2018 -- Federal, state, and local health officials are investigating a Cyclospora outbreak linked to Del Monte 6 oz and 12 oz vegetable trays containing broccoli, cauliflower, carrots, and dill dip that were sold at Kwik Trip/Kwik...

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Oral Insulin Choline, Geranate Ionic Liquid Shows Promise

TUESDAY, July 3, 2018 -- An oral insulin formulation has been developed using choline and geranate (CAGE) ionic liquid, which significantly reduces blood glucose levels in vivo for a sustained period, according to a study published online June 25 in...

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Utility of Repeat Magnetic Resonance Imaging in Surgical Patients with Lumbar Stenosis without Disc Herniation

Publication date: Available online 3 July 2018
Source:The Spine Journal
Author(s): Bryan S. Lee, Rod Nault, Matthew Grabowski, Benjamin Whiting, Joseph Tanenbaum, Konrad Knusel, Matthew Poturalski, Todd Emch, Thomas E. Mroz, Michael P. Steinmetz
BACKGROUND CONTEXTRoutine use of magnetic resonance imaging (MRI) as a diagnostic tool in lumbar stenosis is becoming more prevalent due to the aging population. Currently there is no clinical guideline to clarify the utility of repeat MRI in patients with lumbar stenosis, without instability, neurological deficits, or disc herniation.PURPOSETo evaluate the utility of routine use of MRI as a diagnostic tool in lumbar stenosis, and to help formulate clinical guidelines on the appropriate use of preoperative imaging for lumbar stenosisSTUDY DESIGN/SETTINGRetrospective radiographic analysisPATIENT SAMPLERetrospective chart review was performed to review patients with lumbar stenosis, who underwent lumbar decompression without fusion from 2011 to 2015 at a single institution.OUTCOME MEASURESPreviously established stenosis grading systems were used to measure and compare the initial and the subsequent repeat lumbar MRI's performed preoperatively. If patients were found to have a moderate or severe grade change, and if the surgical plan was altered due to such exacerbated radiographic findings, then their grade changes were considered clinically meaningful.METHODSWe identified patients with lumbar stenosis without radiographic instability or neurological deficits, who had at least two preoperative lumbar MRI's performed and underwent decompressive surgeries. At each pathologic disc level, the absolute value of the change in grade for central/lateral recess stenosis, right foraminal stenosis, and left foraminal stenosis from the first preoperative MRI to the repeated MRI was calculated. These change data were then used to calculate the mean and median changes in each of the three types of stenosis for each pathologic disc level. Identical calculations were carried out for the subsample of patients who only underwent discectomy or had a discectomy included as part of their surgery.RESULTSAmong the 103 patients who met the inclusion criteria, 37 of those patients had more than one level surgically addressed, and a total of 161 lumbar levels were reviewed. Among the subset of patients that had any grade change, the majority of the grades only had a mild change of 1 (36 out of 42 patients, 85.7%, 95% confidence interval [CI]: 73.1%-94.1%); there was a moderate grade change of 2 in two patients (4.8%, CI: 0.8%-14.0%), and a severe change of 3 in one patient (2.4%, CI: 0.2%-10.1%). There were three patients with decreased grade change (7.1%, CI: 1.8%-17.5%). All clinically meaningful grade changes were from the subset of patients who had only discectomy or discectomy as part of the procedure. Lastly, both patients that had a clinically meaningful grade change had their MRI's performed at an interval of greater than 360 days.CONCLUSIONSThe radiographic evaluation of the utility of routinely repeated MRI's in lumbar stenosis without instability, neurological deficits, or disc herniations demonstrated that there were no significant changes found in the repeated MRI in the preoperative setting, especially if the MRI's were performed less than one year apart. The results of the present study can help to standardize the diagnostic evaluation of lumbar stenosis and to formulate clinical guidelines on the appropriate use of preoperative imaging for lumbar stenosis patients.



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Consensus on Molecular Subtypes of High-grade Serous Ovarian Carcinoma

Purpose: The majority of ovarian carcinomas are of high-grade serous histology, which is associated with poor prognosis. Surgery and chemotherapy are the mainstay of treatment, and molecular characterization is necessary to lead the way to targeted therapeutic options. To this end, various computational methods for gene expression-based subtyping of high-grade serous ovarian carcinoma (HGSOC) have been proposed, but their overlap and robustness remain unknown. Experimental Design: We assess three major subtype classifiers by meta-analysis of publicly available expression data, and assess statistical criteria of subtype robustness and classifier concordance. We develop a consensus classifier that represents the subtype classifications of tumors based on the consensus of multiple methods, and outputs a confidence score. Using our compendium of expression data, we examine the possibility that a subset of tumors are unclassifiable based on currently proposed subtypes. Results: HGSOC subtyping classifiers exhibit moderate pairwise concordance across our data compendium (58.9%-70.9%, p < 10-5) and are associated with overall survival in a meta-analysis across datasets (p < 10-5). Current subtypes do not meet statistical criteria for robustness to re-clustering across multiple datasets (Prediction Strength < 0.6). A new subtype classifier is trained on concordantly classified samples to yield a consensus classification of patient tumors that correlates with patient age, survival, tumor purity, and lymphocyte infiltration. Conclusion: A new consensus ovarian subtype classifier represents the consensus of methods, and demonstrates the importance of classification approaches for cancer that do not require all tumors to be assigned to a distinct subtype.



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Final Report of a Phase I Trial of Olaparib with Cetuximab and Radiation for Heavy Smoker Patients with Locally Advanced Head and Neck Cancer.

Purpose: Our goal was to evaluate the safety and toxicity of combining a PARP inhibitor, olaparib with cetuximab and fractionated intensity modulated radiation therapy for patients with locally advanced head and neck cancer and heavy smoking histories. Experimental Design: Patients with ≥10 pack/year history of smoking were treated with olaparib at doses ranging from 25 mg-200 mg orally twice daily (BID) beginning ~10 days prior to initiation of and with concurrent radiation (69.3 Gy in 33 fractions) using a TITE-CRM model. Cetuximab was administered starting ~5 days prior to radiation per standard of care. Results: A total of 16 patients were entered onto the study with 15 evaluable for acute toxicity. The most common treatment-related Grade 3-4 side effects were radiation dermatitis and mucositis (38% and 69%, respectively). The maximum tolerated dose was determined to be 50 mg PO BID, but the RP2D was deemed to be 25 mg PO BID. At a median follow up of 26 months, the actuarial median overall survival was 37 months but was not reached for other endpoints. Two-year overall survival, progression free survival, local control, and distant control rates were 72%, 63%, 72%, 79%, respectively. Patients who continued to smoke during therapy experienced higher recurrence rates. MYCand KMT2Awere identified as potential correlatives of response on gene amplification and mutational analysis. Conclusion: Olaparib at 25 mg oral BID with concurrent cetuximab and radiation was well tolerated with reduced dermatitis within the radiation field. Responses rates were promising for this high-risk population.



https://ift.tt/2KrzGii

Parallel Accumulation of Tumor Hyaluronan, Collagen and Other Drivers of Tumor Progression

Purpose:The tumor microenvironment (TME) evolves to support tumor progression. One marker of more aggressive malignancy is hyaluronan (HA) accumulation. Here we characterize biological and physical changes associated with HA accumulating (HA-high) tumors. Experimental Design:We used immunohistochemistry, in vivo imaging of tumor pH, and microdialysis to characterize the TME of HA-high tumors, including tumor interstitial pressure (tIP), vascular structure, hypoxia, tumor perfusion by doxorubicin, pH, content of collagen and smooth muscle actin (α-SMA). A novel method was developed to measure real-time tumor-associated soluble cytokines and growth factors. We also evaluated biopsies of murine and pancreatic cancer patients to investigate HA and collagen content, important contributors to drug resistance. Results:In immunodeficient and immunocompetent mice, increasing tumor HA content is accompanied by increasing collagen content, tIP, vascular collapse, hypoxia, and increased metastatic potential, as reflected by increased α-SMA. In vivo treatment of HA-high tumors with PEGylated recombinant human hyaluronidase (PEGPH20) dramatically reversed these changes and depleted stores of VEGF-A165, suggesting that PEGPH20 may also diminish the angiogenic potential of the TME. Finally, we observed in xenografts and in pancreatic cancer patients a coordinated increase in HA and collagen tumor content. Conclusions: The accumulation of HA in tumors is associated with high tIP, vascular collapse, hypoxia, and drug resistance. These findings may partially explain why more aggressive malignancy is observed in the HA-high phenotype. We have shown that degradation of HA by PEGPH20 partially reverses this phenotype and leads to depletion of tumor-associated VEGF-A165. These results encourage further clinical investigation of PEGPH20.



https://ift.tt/2MOntkH

Combined CDK4/6 and pan-mTOR inhibition is synergistic against intrahepatic cholangiocarcinoma

Purpose: Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer type, lacking effective therapies and associated with a dismal prognosis. Palbociclib is a selective CDK4/6 inhibitor, which has been shown to suppress cell proliferation in many experimental cancer models. Recently, we demonstrated that pan-mTOR inhibitors, such as MLN0128, effectively induce apoptosis, while having limited efficacy in restraining proliferation of ICC cells. Here, we tested the hypothesis that Palbociclib, due to its ant-proliferative properties in many cancer types, might synergize with MLN0128 to impair ICC growth. Experimental Design: Human ICC cell lines and the AKT/YapS127A ICC mouse model were used to test the therapeutic efficacy of Palbociclib and MLN0128, either alone or in combination. Results: Administration of Palbociclib suppressed in vitro ICC cell growth by inhibiting cell cycle progression. Concomitant administration of Palbociclib and MLN0128 led to a pronounced, synergistic growth constraint of ICC cell lines. Furthermore, while treatment with Palbociclib or MLN0128 alone resulted in tumor growth reduction in AKT/YapS127A mice, a remarkable tumor regression was achieved when the two drugs were administered simultaneously. Mechanistically, Palbociclib was found to potentiate MLN0128 mTOR inhibition activity, whereas MLN0128 prevented the upregulation of cyclin D1 induced by Pa1bociclib treatment. Conclusions:Our study indicates the synergistic activity of Palbociclib and MLN0128 in inhibiting ICC cell proliferation. Thus, combination of CDK4/6 and mTOR inhibitors might represent a novel, promising, and effective therapeutic approach against human ICC.



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Mast cell activation and KSHV infection in Kaposi sarcoma

Purpose: Kaposi sarcoma (KS) is a vascular tumor initiated by infection of endothelial cells (ECs) with KS-associated herpesvirus (KSHV). KS is dependent on sustained pro-inflammatory signals provided by intra-lesional leukocytes and continued infection of new ECs. However, the sources of these cytokines and infectious virus within lesions are not fully understood. Here, mast cells (MCs) are identified as pro-inflammatory cells within KS lesions that are permissive for, and activated by, infection with KSHV. Experimental Design: Three MC lines were used to assess permissivity to infection and to evaluate MC activation following infection. Biopsies from 31 AIDS-KS cases and 11 AIDS controls were evaluated by immunohistochemistry for the presence of MCs in KS lesions, assessment of activation state, and KSHV infection. Plasma samples from 26 AIDS-KS, 13 classic KS, and 13 healthy adults were evaluated for levels of MC granule contents tryptase and histamine. Results: In culture, MCs supported KSHV infection and infection induced MC degranulation. Within KS lesions MCs were closely associated with spindle cells. MC activation was extensive within KS patients, reflected by elevated circulating levels of tryptase and N-methylhistamine. One patient with clinical signs of extensive MC activation was treated with antagonists of MC-derived pro-inflammatory mediators, which resulted in rapid and durable regression of AIDS-KS lesions. Conclusions: Using complimentary in vitro and in vivo studies we identify MCs as a potential long-lived reservoir for KSHV and a source of pro-inflammatory mediators within the lesion microenvironment. Additionally, we identify MC antagonists as a promising novel therapeutic approach for KS.



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The epigenomic landscape of pituitary adenomas reveals specific alterations and differentiates among acromegaly, Cushing's disease and endocrine-inactive subtypes

Purpose Pituitary adenomas (PAs) are one of the most common benign neoplasms of the central nervous system. Although emerging evidence suggests roles for both genetic and epigenetic factors in tumorigenesis, the degree to which these factors contribute to disease remains poorly understood. Experimental Design A multi-platform analysis was performed to identify the genomic and epigenomic underpinnings of disease among the three major subtypes of surgically-resected PAs in 48 patients: growth hormone (GH)-secreting (n=17), adrenocorticotropic hormone (ACTH)-secreting (n=13, including 3 silent-ACTH adenomas), and endocrine-inactive (n=18). Whole-exome sequencing was used to profile the somatic mutational landscape, whole-transcriptome sequencing was used to identify disease specific patterns of gene expression, and array-based DNA methylation profiling was used to examine genome-wide patterns of DNA methylation. Results Recurrent single nucleotide and small indel somatic mutations were infrequent among the three adenoma subtypes. However, somatic copy number alterations (SCNAs) were identified in all three PA subtypes. Methylation analysis revealed adenoma subtype-specific DNA methylation profiles, with GH-secreting adenomas being dominated by hypomethylated sites. Likewise, gene expression patterns revealed adenoma subtype-specific profiles. Integrating DNA methylation and gene expression data revealed that hypomethylation of promoter regions are related with increased expression of GH1 and SSTR5 genes in GH-secreting adenomas and POMCgene in ACTH-secreting adenomas. Finally, multispectral IHC staining of immune-related proteins showed abundant expression of PD-L1among all three adenoma subtypes. Conclusions Taken together, these data stress the contribution of epigenomic alterations to disease specific etiology among adenoma subtypes and highlight potential targets for future immunotherapy-based treatments.



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Paclitaxel Sensitivity of Ovarian Cancer can be enhanced by knocking down Pairs of Kinases that regulate MAP4 Phosphorylation and Microtubule Stability

Purpose: Most ovarian cancer patients receive paclitaxel chemotherapy, but less than half respond. Pre-treatment microtubule stability correlates with paclitaxel response in ovarian cancer cell lines. Microtubule stability can be increased by depletion of individual kinases. As microtubule stability can be regulated by phosphorylation of microtubule associated proteins (MAPs), we reasoned that depletion of pairs of kinases that regulate phosphorylation of MAPs could induce microtubule stabilization and paclitaxel sensitization. Experimental Design: Fourteen kinases known to regulate paclitaxel sensitivity were depleted individually in 12 well-characterized ovarian cancer cell lines before measuring proliferation in the presence or absence of paclitaxel. Similar studies were performed by depleting all possible pairs of kinases in 6 ovarian cancer cell lines. Pairs that enhanced paclitaxel sensitivity across multiple cell lines were studied in depth in cell culture and two xenograft models. Results: Transfection of siRNA against 10 of the 14 kinases enhanced paclitaxel sensitivity in at least 6 of 12 cell lines. Dual knockdown of IKBKB/STK39 or EDN2/TBK1 enhanced paclitaxel sensitivity more than silencing single kinases. Sequential knockdown was superior to concurrent knockdown. Dual silencing of IKBKB/STK39 or EDN2/TBK1 stabilized microtubules by inhibiting phosphorylation of p38 and MAP4, inducing apoptosis and blocking cell cycle more effectively than silencing individual kinases. Knockdown of IKBKB/STK39 or EDN2/TBK1 enhanced paclitaxel sensitivity in two ovarian xenograft models. Conclusions: Sequential knockdown of dual kinases increased microtubule stability by decreasing p38-mediated phosphorylation of MAP4 and enhanced response to paclitaxel in ovarian cancer cell lines and xenografts, suggesting a strategy to improve primary therapy.



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Comparison of longitudinal CA125 algorithms as a first line screen for ovarian cancer in the general population

Purpose: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening(UKCTOCS) women in the multimodal (MMS) arm had a serum CA125 test (first-line), with those at increased risk, having repeat CA125/ultrasound (second-line test). CA125 was interpreted using the 'Risk of Ovarian Cancer Algorithm'(ROCA). We report on performance of other serial algorithms and a single CA125 threshold as a first line screen in the UKCTOCS dataset. Experimental Design: 50,083 post-menopausal women who attended 346,806 MMS screens were randomly split into training and validation sets, following stratification into cases (ovarian/tubal/peritoneal cancers) and controls. The two longitudinal algorithms, a new serial algorithm, method of mean trends (MMT) and the parametric empirical Bayes (PEB) were trained in the training set and tested in the blinded validation set and the performance characteristics, including that of a single CA125 threshold, were compared. Results The area under receiver operator curve (AUC) was significantly higher (p=0.01) for MMT (0.921) compared to CA125 single threshold (0.884). At a specificity of 89.5%, sensitivities for MMT (86.5%;95%CI:78.4-91.9) and PEB (88.5%;95%CI:80.6-93.4) were similar to that reported for ROCA (sensitivity 87.1%; specificity 87.6%; AUC 0.915) and significantly higher than the single CA125 threshold (73.1%;95%CI:63.6-80.8). Conclusions: These findings from the largest available serial CA125 data set in the general population provide definitive evidence that longitudinal algorithms are significantly superior to simple cut-offs for ovarian cancer screening. Use of these newer algorithms requires incorporation into a multimodal strategy. The results highlight the importance of incorporating serial change in biomarker levels in cancer screening/early detection strategies.



https://ift.tt/2KGO2e8

The Importance of the Double Product in the Six-Minute Walk Test to Predict Myocardial Function

Introduction. The Six-Minute Walk Test (6MWT) is a widely used test to measure the physical performance of patients to assess the effectiveness of treatment, to qualify for rehabilitation, and to evaluate its effects.. Aim. This paper focuses on the assessment of the growth of a double product (DP) during the 6MWT and its diagnostic value in the assessment of patients with heart failure. Material and Methods. The paper has retrospective character. We analyzed medical records of 412 patients hospitalized for cardiac reasons, in whom a 6MWT was performed. The patients were divided into two groups: one with diagnosed heart failure and a control group. Results. The patients with diagnosed heart failure, compared to the control group, were characterized by a shorter walking distance and greater DP increase at equal walking intervals. After distinguishing the group with the preserved and decreased left ventricle ejection fraction, the value of the DP increase was still higher compared to the control group. The mean DP increase corresponding to one meter of walk was the only one that correlated negatively with the left ventricular ejection fraction. Conclusion. The assessment of the increase of the DP during the march test seems to be a better parameter reflecting the efficiency of the myocardium from the distance of the march.

https://ift.tt/2lPqSUN

The Social Media Index as an Indicator of Quality for Emergency Medicine Blogs: A METRIQ Study

Online educational resources such as blogs are increasingly used for education by emergency medicine clinicians. The Social Media Index was developed to quantify their relative impact. The Medical Education Translational Resources: Indicators of Quality (METRIQ) study was conducted in part to determine the association between the Social Media Index score and quality as measured by gestalt and previously derived quality instruments.

https://ift.tt/2u28Tyc

Emergency Department Urinary Tract Infections Caused by Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae: Many Patients Have No Identifiable Risk Factor and Discordant Empiric Therapy Is Common

Community-onset urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae, which are resistant to ceftriaxone and usually coresistant to fluoroquinolones, are increasing worldwide. We investigate and describe in detail UTIs caused by ESBL-producing Enterobacteriaceae in our emergency department (ED), and determine the proportion that occurred in patients without health care–associated risk factors and who received discordant initial antibiotic therapy.

https://ift.tt/2lTaJh0

Point-of-Care Ultrasound Assessment of Bladder Fullness for Female Patients Awaiting Radiology-Performed Transabdominal Pelvic Ultrasound in a Pediatric Emergency Department: A Randomized Controlled Trial

Radiology-performed transabdominal pelvic ultrasound, used to evaluate female patients with suspected pelvic pathology in the pediatric emergency department (ED), is often delayed by the need to fill the bladder. We seek to determine whether point-of-care ultrasound assessment of bladder fullness can predict patient readiness for transabdominal pelvic ultrasound more quickly than patient sensation of bladder fullness.

https://ift.tt/2lTaBhw

Selection of Intravenous Fluids

Fluid resuscitation is one of the mainstays of shock management, and there has been tremendous interest in the choice of intravenous fluids. At present, isotonic crystalloid solutions are favored over colloid solutions. Among isotonic crystalloid solutions, 0.9% "normal" saline solution is perhaps the most widely prescribed medication in the United States. In clinical practice, the alternatives to 0.9% saline solution are balanced salt solutions that contain a physiologic amount of chloride and lactate or acetate as the base equivalent (Table 1).

https://ift.tt/2lSTs7V

Child and Parental Perspectives on Communication and Decision Making in Pediatric CKD: A Focus Group Study

Effective communication and shared decision making improve quality of care and patient outcomes but can be particularly challenging in pediatric chronic disease because children depend on their parents and clinicians to manage complex health care and developmental needs. We aimed to describe the perspectives of children with chronic kidney disease (CKD) and their parents with regard to communication and decision making.

https://ift.tt/2z8D24N

A foodborne acute gastroenteritis outbreak caused by GII.P16-GII.2 norovirus in a boarding high school, Beijing, China: a case–control study

In December 2017, an acute gastroenteritis outbreak involving 61 students occurred in a boarding high school in Beijing, China. We conducted an outbreak investigation immediately in order to determine the caus...

https://ift.tt/2KsQmpC

Coping strategies among nurses in South-west Ethiopia: descriptive, institution-based cross-sectional study

This study aimed to describe coping strategies for job stress among nurses working in Jimma Zone public hospitals, South-west Ethiopia. The study conducted from March to April 2014 through census using English...

https://ift.tt/2IPMcmb

Student performance on the Test of Scientific Literacy Skills (TOSLS) does not change with assignment of a low-stakes grade

Response-validated multiple-choice assessments are used in college courses to assess student learning gains. The ability of a test to accurately reflect student learning gains is highly dependent on the studen...

https://ift.tt/2KsQ9CQ

Sero-prevalence of hepatitis B virus infection and associated factors among health care workers and medical waste handlers in primary hospitals of North-west Ethiopia

The aim of this cross-sectional study was to determined the sero-prevalence of HBV infection and associated factors among health care workers and medical waste handlers in primary hospitals of North-west Ethio...

https://ift.tt/2IOLBkM

Modes of mechanical ventilation vary between hospitals and intensive care units within a university healthcare system: a retrospective observational study

As evidence-based guidance to aid clinicians with mechanical ventilation mode selection is scant, we sought to characterize the epidemiology thereof within a university healthcare system and hypothesized that ...

https://ift.tt/2KsPYra

T-Cell Receptor Excision Circles in HIV-Exposed, Uninfected Newborns Measured During a National Newborn Screening Program for Severe Combined Immunodeficiency

Severe combined immunodeficiency screening by measuring T-receptor excision circles at birth allows evaluation of the impact of various maternal conditions on newborn immunity. The slight decrease observed in a French cohort of newborns to HIV-infected mothers can be explained by the confounding factors of prematurity and African descent.

https://ift.tt/2KGZ3w4

Association Between Video Laryngoscopy and Adverse Tracheal Intubation-Associated Events in the Neonatal Intensive Care Unit

The effect of video laryngoscopy on adverse events during neonatal tracheal intubation is unknown. In this single site retrospective cohort study, video laryngoscopy was independently associated with decreased risk for adverse events during neonatal intubation.

https://ift.tt/2IPYqLm

Predictor of multidrug resistant tuberculosis in southwestern part of Ethiopia: a case control study

Curable disease tuberculosis is becoming incurable or difficult to treat due to drug resistance. Multi drug resistance tuberculosis is a major health problem for less developed countries. Development of drug r...

https://ift.tt/2KybfQB

Gliadin effect on the oxidative balance and DNA damage: An in-vitro, ex-vivo study

Gliadins are involved in gluten-related disorders and are responsible for the alteration of the cellular redox balance. It is not clear if the gliadin-related oxidative stress can induce DNA damage in enterocytes.

https://ift.tt/2NpmoRx

Neuropilin-1 (NRP-1) upregulated by IL-6/STAT3 signalling contributes to invasion in pancreatic neuroendocrine neoplasms

Although the upregulation of Neuropilin-1 (NRP-1) is associated with many solid tumours, its role in pancreatic neuroendocrine neoplasms (pNEN) has not been well elucidated. The aim of this study was to investigate the role of NRP-1 in improving treatment and determining the prognosis of pNEN. In this study, the expression of NRP-1 in pNEN tissue samples and pNEN cell line BON1 was analysed by Western blot, polymerase chain reaction (PCR) and immunocytochemistry upon exposure to interleukin-6 (IL-6).

https://ift.tt/2lQaun1

Conflicting IDH1/IDH2, ATRX, and 1p/19q results in diffuse gliomas: a commentary

Valeria Barresi, MD, PhD vbarresi@unime.it (See Fig..)

https://ift.tt/2zaxczI

Elevated DSN1 expression is associated with poor survival in patients with hepatocellular carcinoma

Dosage suppressor of Nnf1 (DSN1) is a component of the kinetochore protein complex that is required for proper chromosome segregation. Some studies have explored that DSN1 is related to colorectal cancer progression. However, the role of DSN1 in hepatocellular carcinoma (HCC) remains unknown. This study aimed to explore DSN1 expression in HCC tissues and investigated DSN1 functions in HCC cells. We obtained data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to analyze DSN1 expression in HCC.

https://ift.tt/2lT1Hk6

Atypical mitoses are present in otherwise classical pleomorphic lipomas

Dear Editor,

https://ift.tt/2u2PJZ7

Clonality assessment of multifocal lung adenocarcinoma by pathology evaluation and molecular analysis

The aim of this study was to explore morphologic and molecular features distinguishing between multifocal lung adenocarcinoma (MLA) and intrapulmonary metastases (IM). Sixteen patients with MLAs, a total of 34 tumors, were reviewed. Four approaches were used: (1) array-comparative genomic hybridization (CGH) as a standard clonality assessment; (2) EGFR and KRAS mutational profiles as a supplementary method; (3) comprehensive histologic assessment (CHA) was method I in pathology evaluation; (4) CHA combined with lepidic (scaling) component analysis was method II.

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Atypical mitoses are present in otherwise classical pleomorphic lipomas—reply

To the Editor:

https://ift.tt/2z8YG8W

IgA dominant glomerulonephritis with a membranoproliferative pattern of injury

IgA dominant membranoproliferative glomerulonephritis (MPGN) is a descriptive term for renal biopsies in which differential diagnoses of unusual IgA nephropathy (IgAN), infection-related GN, or other etiologies are considered. We sought to understand clinical and pathologic features of this finding. Native kidney biopsies with IgA dominant immune deposits and diffuse MPGN features without significant exudative features or subepithelial deposits were retrospectively reviewed. Two groups (n=27, 33 biopsies) were identified, patients with chronic liver disease and those without.

https://ift.tt/2lPYW2Y

Exploration of BRAFV600E as a diagnostic adjuvant in the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

The non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) are distinguished from classical papillary thyroid carcinoma with predominantly follicular architecture (CPTCPFA) by distinct histomorphologic and molecular features. CPTCPFA frequently harbor the oncogenic variant BRAFV600E while NIFTP and EFVPTC are largely RAS-driven. CPTCPFA have rare papillae and intranuclear pseudoinclusions that may distinguish them from NIFTP or EFVPTC.

https://ift.tt/2u2OZTP

Eps8, a therapeutic potential target for cancer

Dear Editor,

https://ift.tt/2lOjuJg

Targeted gene sequencing of lynch syndrome-related and sporadic endometrial carcinomas

About one third of endometrial carcinomas (ECs), mainly of endometrioid histology, harbor the mismatch repair (MMR) defects and microsatellite instability (MSI). Among these, ECs arising in women with Lynch Syndrome (LS) account for a large proportion. To date, no somatic genetic analyses have been published comparing LS-ECs with sporadic ECs. In this work, we examined the mutational profiles of a well-characterized series of sporadic and LS-related ECs, performing exonic targeted sequencing of 16 genes mainly involved in MSI ECs.

https://ift.tt/2z7Lz7T

Hepatocellular Carcinoma Invading the Gastric Antrum



https://ift.tt/2u4Qu3C

Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism

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https://ift.tt/2tQmut2

Association between Mismatch Negativity and Voxel-Based Brain Volume in Schizophrenia

Mismatch negativity (MMN), a type of event-related potential (ERP), is generated when a discernable change occurs in a series of repetitive standard stimuli (Naatanen et al., 1978). MMN represents the pre-attentive process of auditory discrimination and is associated with the function of auditory memory and involuntary attention shifting (Naatanen et al., 1979, Javitt et al., 1995, Naatanen et al., 2007). MMN deficit is extensively observed in schizophrenia patients (Shelley et al., 1991, Javitt et al., 1993, Umbricht et al., 2005).

https://ift.tt/2IPHxR2

Reply to “Clinical Practice Guidelines or Clinical Research Guidelines?”

We thank our esteemed clinical colleagues Bagić et al. (2018) for their interest in our paper "IFCN-endorsed practical guidelines for clinical magnetoencephalography (MEG)" (Hari et al. 2018). We hereby respectfully respond to the criticism that our paper has (1) a confusing title and (2) poorly-weighted contents.

https://ift.tt/2NoWA7W

Clinical Practice Guidelines or Clinical Research Guidelines?

We write in regard to the recent publication, "IFCN-endorsed practical guidelines for clinical magnetoencephalography (MEG)", by Hari et al. (2018) We find the title misleading and the content, though extensive, inadequate for guidelines in "clinical magnetoencephalography", as practiced. Our concerns follow:

https://ift.tt/2IQhwRG

Successful liver-directed gene delivery by ERCP-guided hydrodynamic injection (with videos)

A simple, safe, targeted and efficient in vivo DNA delivery system is necessary for clinical-grade liver targeted gene therapy in humans. Intravascular hydrodynamic gene delivery has been investigated in large animal models but translation to humans has been hampered by its technical challenges, invasiveness and potential for significant cardiovascular adverse events. We posited that intrabiliary delivery of DNA plasmids via ERCP-guided hydrodynamic injection overcomes these obstacles.

https://ift.tt/2KK1RbJ

Impact of whole lung irradiation on survival outcome in patients with lung relapsed Ewing sarcoma

Whole lung irradiation (WLI) demonstrated potential improvements in survival outcomes in patients with isolated lung relapse of a Ewing sarcoma (EwS), and it additionally appears to be tolerated and safe for both pediatric and young adult patients. The primary tumor site and response of pulmonary lesions to chemotherapy are significant prognostic factors for survival following WLI. Without a randomized prospective analysis, the WLI should be considered for treating pulmonary relapsed EwS.

https://ift.tt/2z3LBO2

High Blood Pressure During Pregnancy and Development of Risk Factors for Cardiovascular Disease



https://ift.tt/2NkKufX

Hypertensive Disorders of Pregnancy and Maternal Cardiovascular Disease Risk Factor Development An Observational Cohort Study

Background:
Women with a history of hypertensive disorders of pregnancy (HDP) are nearly twice as likely to develop cardiovascular disease (CVD) as those who are normotensive during pregnancy. However, the emergence of CVD risk factors after HDP is less well-understood.
Objective:
To identify associations between HDP and maternal CVD risk factors and chart the trajectory of risk factor development after pregnancy.
Design:
Observational cohort study.
Setting:
United States.
Participants:
58 671 parous NHS II (Nurses' Health Study II) participants who did not have CVD or risk factors of interest at baseline.
Measurements:
Women were followed for self-reported physician diagnosis of chronic hypertension and hypercholesterolemia and confirmed type 2 diabetes mellitus (T2DM) from their first birth through 2013; mean follow-up ranged from 25 to 32 years across these end points. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs, with adjustment for prepregnancy confounders.
Results:
Compared with women who were normotensive during pregnancy, those with gestational hypertension (2.9%) or preeclampsia (6.3%) in their first pregnancy had increased rates of chronic hypertension (HRs, 2.8 [95% CI, 2.6 to 3.0] and 2.2 [CI, 2.1 to 2.3], respectively), T2DM (HRs, 1.7 [CI, 1.4 to 1.9] and 1.8 [CI, 1.6 to 1.9], respectively), and hypercholesterolemia (HRs, 1.4 [CI, 1.3 to 1.5] and 1.3 [CI, 1.3 to 1.4], respectively). Although these women were more likely to develop CVD risk factors throughout follow-up, the relative risk for chronic hypertension was strongest within 5 years after their first birth. Recurrence of HDP further elevated risks for all end points.
Limitation:
Participants self-reported HDP.
Conclusion:
Women with HDP in their first pregnancy had increased rates of chronic hypertension, T2DM, and hypercholesterolemia that persisted for several decades. These women may benefit from lifestyle intervention and early screening to reduce lifetime risk for CVD.
Primary Funding Source:
National Institutes of Health.

https://ift.tt/2tZ7JDA

Women's Cardiovascular Health After a Hypertensive Disorder of Pregnancy

In this issue, Stuart and colleagues, using data from the Nurses' Health Study II, report associations between a history of a first pregnancy complicated by a hypertensive disorder of pregnancy and physician-diagnosed hypertension, hypercholesterolemia, and type 2 diabetes over the course of 3 decades after pregnancy. The editorialist discusses the findings and the need to invest in research on this topic to reduce the burden of cardiovascular disease in women.

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Recurrent Renal Cysts in a Transplanted Kidney



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Marijuana Use, Respiratory Symptoms, and Pulmonary Function A Systematic Review and Meta-analysis

Background:
The health effects of smoking marijuana are not well-understood.
Purpose:
To examine the association between marijuana use and respiratory symptoms, pulmonary function, and obstructive lung disease among adolescents and adults.
Data Sources:
PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library from 1 January 1973 to 30 April 2018.
Study Selection:
Observational and interventional studies published in English that reported pulmonary outcomes of adolescents and adults who used marijuana.
Data Extraction:
Four reviewers independently extracted study characteristics and assessed risk of bias. Three reviewers assessed strength of evidence. Studies of similar design with low or moderate risk of bias and sufficient data were pooled.
Data Synthesis:
Twenty-two studies were included. A pooled analysis of 2 prospective studies showed that marijuana use was associated with an increased risk for cough (risk ratio [RR], 2.04 [95% CI, 1.02 to 4.06]) and sputum production (RR, 3.84 [CI, 1.62 to 9.07]). Pooled analysis of cross-sectional studies (1 low and 3 moderate risk of bias) showed that marijuana use was associated with cough (RR, 4.37 [CI, 1.71 to 11.19]), sputum production (RR, 3.40 [CI, 1.99 to 5.79]), wheezing (RR, 2.83 [CI, 1.89 to 4.23]), and dyspnea (RR, 1.56 [CI, 1.33 to 1.83]). Data on pulmonary function and obstructive lung disease were insufficient.
Limitation:
Few studies were at low risk of bias, marijuana exposure was limited in the population studied, cohorts were young overall, assessment of marijuana exposure was not uniform, and study designs varied.
Conclusion:
Low-strength evidence suggests that smoking marijuana is associated with cough, sputum production, and wheezing. Evidence on the association between marijuana use and obstructive lung disease and pulmonary function is insufficient.
Primary Funding Source:
None. (PROSPERO: CRD42017059224)

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Chemical composition, antioxidant, antimicrobial and Antiproliferative activities of essential oil of Mentha spicata L. (Lamiaceae) from Algerian Saharan atlas

Mentha spicata (M. spicata) is a member of Lamiaceae that spreads mainly in the temperate and sub-temperate zones of the world. It is considered as a rich source of essential oils, which is widely used in pharmac...

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10-hydroxy-2-decenoic acid of royal jelly exhibits bactericide and anti-inflammatory activity in human colon cancer cells

Royal jelly (RJ), the exclusive food for the larva of queen honeybee, is regarded as the novel supplement to promote human health. The function of RJ may be attributed to its major and unique fatty acid, 10-hy...

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Reducing antibiotic use for uncomplicated urinary tract infection in general practice by treatment with uva-ursi (REGATTA) – a double-blind, randomized, controlled comparative effectiveness trial

Uncomplicated urinary tract infections (UTI) are common in general practice and usually treated with antibiotics. This contributes to increasing resistance rates of uropathogenic bacteria. A previous trial sho...

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Cytotoxic properties of the anthraquinone derivatives isolated from the roots of Rubia philippinensis

Cancer is one of the most frequently occurring diseases and is the second leading cause of death worldwide. In this study, anthraquinone derivatives (Compounds 1–5) were evaluated for their anti-cancer potenti...

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Antibacterial interactions, anti-inflammatory and cytotoxic effects of four medicinal plant species

The constant emergence of antibiotic resistant species and the adverse side effects of synthetic drugs are threatening the efficacy of the drugs that are currently in use. This study was aimed at investigating...

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Associations Between Gun Shows and Firearm Deaths and Injuries



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Implications of Nine Risk Prediction Models for Selecting Ever-Smokers for Computed Tomography Lung Cancer Screening

Background:
Lung cancer screening guidelines recommend using individualized risk models to refer ever-smokers for screening. However, different models select different screening populations. The performance of each model in selecting ever-smokers for screening is unknown.
Objective:
To compare the U.S. screening populations selected by 9 lung cancer risk models (the Bach model; the Spitz model; the Liverpool Lung Project [LLP] model; the LLP Incidence Risk Model [LLPi]; the Hoggart model; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 [PLCOM2012]; the Pittsburgh Predictor; the Lung Cancer Risk Assessment Tool [LCRAT]; and the Lung Cancer Death Risk Assessment Tool [LCDRAT]) and to examine their predictive performance in 2 cohorts.
Design:
Population-based prospective studies.
Setting:
United States.
Participants:
Models selected U.S. screening populations by using data from the National Health Interview Survey from 2010 to 2012. Model performance was evaluated using data from 337 388 ever-smokers in the National Institutes of Health–AARP Diet and Health Study and 72 338 ever-smokers in the CPS-II (Cancer Prevention Study II) Nutrition Survey cohort.
Measurements:
Model calibration (ratio of model-predicted to observed cases [expected–observed ratio]) and discrimination (area under the curve [AUC]).
Results:
At a 5-year risk threshold of 2.0%, the models chose U.S. screening populations ranging from 7.6 million to 26 million ever-smokers. These disagreements occurred because, in both validation cohorts, 4 models (the Bach model, PLCOM2012, LCRAT, and LCDRAT) were well-calibrated (expected–observed ratio range, 0.92 to 1.12) and had higher AUCs (range, 0.75 to 0.79) than 5 models that generally overestimated risk (expected–observed ratio range, 0.83 to 3.69) and had lower AUCs (range, 0.62 to 0.75). The 4 best-performing models also had the highest sensitivity at a fixed specificity (and vice versa) and similar discrimination at a fixed risk threshold. These models showed better agreement on size of the screening population (7.6 million to 10.9 million) and achieved consensus on 73% of persons chosen.
Limitation:
No consensus on risk thresholds for screening.
Conclusion:
The 9 lung cancer risk models chose widely differing U.S. screening populations. However, 4 models (the Bach model, PLCOM2012, LCRAT, and LCDRAT) most accurately predicted risk and performed best in selecting ever-smokers for screening.
Primary Funding Source:
Intramural Research Program of the National Institutes of Health/National Cancer Institute.

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Annals for Educators - 3 July 2018



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Clinical Implications of Revised Pooled Cohort Equations for Estimating Atherosclerotic Cardiovascular Disease Risk

Background:
The 2013 pooled cohort equations (PCEs) are central in prevention guidelines for cardiovascular disease (CVD) but can misestimate CVD risk.
Objective:
To improve the clinical accuracy of CVD risk prediction by revising the 2013 PCEs using newer data and statistical methods.
Design:
Derivation and validation of risk equations.
Setting:
Population-based.
Participants:
26 689 adults aged 40 to 79 years without prior CVD from 6 U.S. cohorts.
Measurements:
Nonfatal myocardial infarction, death from coronary heart disease, or fatal or nonfatal stroke.
Results:
The 2013 PCEs overestimated 10-year risk for atherosclerotic CVD by an average of 20% across risk groups. Misestimation of risk was particularly prominent among black adults, of whom 3.9 million (33% of eligible black persons) had extreme risk estimates (<70% or >250% those of white adults with otherwise-identical risk factor values). Updating these equations improved accuracy among all race and sex subgroups. Approximately 11.8 million U.S. adults previously labeled high-risk (10-year risk ≥7.5%) by the 2013 PCEs would be relabeled lower-risk by the updated equations.
Limitations:
Updating the 2013 PCEs with data from modern cohorts reduced the number of persons considered to be at high risk. Clinicians and patients should consider the potential benefits and harms of reducing the number of persons recommended aspirin, blood pressure, or statin therapy. Our findings also indicate that risk equations will generally become outdated over time and require routine updating.
Conclusion:
Revised PCEs can improve the accuracy of CVD risk estimates.
Primary Funding Source:
National Institutes of Health.

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Comparison of Five Major Guidelines for Statin Use in Primary Prevention



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ESPACOMP Medication Adherence Reporting Guideline (EMERGE)

Research on assessing or managing medication adherence applies approaches from observational, interventional, and implementation science that spans many disciplines and demands coherent conceptualization, valid methods, appropriate analyses, and complete and accurate reporting. To ensure such reporting, the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) Medication Adherence Reporting Guideline (EMERGE) recommends standard reporting approaches based on an accepted taxonomy.This guideline is derived from a literature review, a reactive Delphi study with 26 medication adherence experts from many countries and disciplines, and feedback from ESPACOMP members. It is designed to supplement existing guidelines for health research reporting and is structured around 4 minimum reporting criteria and 17 items reflecting best reporting practice. By enhancing and harmonizing research reporting, EMERGE aims to advance research and, ultimately, patient outcomes.

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Bronchial Thermoplasty for Severe Asthmatic Cough



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Machine Learning and Evidence-Based Medicine

Machine learning, which converts complex data into algorithms, challenges the traditional epidemiologic approach of evidence-based medicine. This commentary discusses intersections between these approaches, including their differences, strengths, and limitations, and suggests areas of reconciliation.

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Comparison of Five Major Guidelines for Statin Use in Primary Prevention



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Firearms and Dementia: Clinical Considerations

Many support limiting firearm access for persons whose mental illness would place them or others at heightened risk, but less attention has been paid to progressive cognitive impairment and firearm access. For persons with dementia, discussions about firearm access strongly parallel discussions about driving. This commentary discusses when persons with dementia need to "give up the keys," whether they are to a gun safe or a car, and how to do so.

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Emergency Room



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Physician Burnout in the Electronic Health Record Era: Are We Ignoring the Real Cause?

The widespread adoption of electronic health records (EHRs) has been perceived as driving physician dissatisfaction and burnout. The authors of this essay present data comparing EHR use in other countries with that in the United States and offer a possible explanation of, and solutions to, a root cause of dissatisfaction with EHRs.

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Annals Graphic Medicine - Finding the Funny: Everything



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Defining, Estimating, and Communicating Overdiagnosis in Cancer Screening

The toll of inadequate health care is well-substantiated, but recognition is mounting that "too much" is also possible. Overdiagnosis represents one harm of too much medicine, but the concept can be confusing: It is often conflated with related harms (such as overtreatment, misclassification, false-positive results, and overdetection) and is difficult to measure because it cannot be directly observed. Because the U.S. Preventive Services Task Force (USPSTF) issues screening recommendations aimed largely at healthy persons, it has a particular interest in understanding harms related to screening, especially but not limited to overdiagnosis. In support of the USPSTF, the authors summarize the knowledge and provide guidance on defining, estimating, and communicating overdiagnosis in cancer screening. To improve consistency, thinking, and reporting about overdiagnosis, they suggest a specific definition. The authors articulate how variation in estimates of overdiagnosis can arise, identify approaches to estimating overdiagnosis, and describe best practices for communicating the potential for harm due to overdiagnosis.

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Identifying Patients for Whom Lung Cancer Screening Is Preference-Sensitive A Microsimulation Study

Background:
Many health systems are exploring how to implement low-dose computed tomography (LDCT) screening programs that are effective and patient-centered.
Objective:
To examine factors that influence when LDCT screening is preference-sensitive.
Design:
State-transition microsimulation model.
Data Sources:
Two large randomized trials, published decision analyses, and the SEER (Surveillance, Epidemiology, and End Results) cancer registry.
Target Population:
U.S.-representative sample of simulated patients meeting current U.S. Preventive Services Task Force criteria for screening eligibility.
Time Horizon:
Lifetime.
Perspective:
Individual.
Intervention:
LDCT screening annually for 3 years.
Outcome Measures:
Lifetime quality-adjusted life-year gains and reduction in lung cancer mortality. To examine the effect of preferences on net benefit, disutilities (the "degree of dislike") quantifying the burden of screening and follow-up were varied across a likely range. The effect of varying the rate of false-positive screening results and overdiagnosis associated with screening was also examined.
Results of Base-Case Analysis:
Moderate differences in preferences about the downsides of LDCT screening influenced whether screening was appropriate for eligible persons with annual lung cancer risk less than 0.3% or life expectancy less than 10.5 years. For higher-risk eligible persons with longer life expectancy (roughly 50% of the study population), the benefits of LDCT screening overcame even highly negative views about screening and its downsides.
Results of Sensitivity Analysis:
Rates of false-positive findings and overdiagnosed lung cancer were not highly influential.
Limitation:
The quantitative thresholds that were identified may vary depending on the structure of the microsimulation model.
Conclusion:
Identifying circumstances in which LDCT screening is more versus less preference-sensitive may help clinicians personalize their screening discussions, tailoring to both preferences and clinical benefit.
Primary Funding Source:
None.

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Precision Screening for Lung Cancer: Risk-Based but Not Always Preference-Sensitive?

Caverly and colleagues' modeling analysis explored the importance of disutilities in the lung cancer screening decision. The editorialist discusses the unavoidable tensions among the various goals of screening, the role of patient preferences, and how physicians can incorporate Caverly and colleagues' findings into their discussions with patients about lung cancer screening.

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Associations Between Gun Shows and Firearm Deaths and Injuries



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Improving Implementation of Lung Cancer Screening With Risk Prediction Models

Katki and colleagues compared the performance of 9 lung cancer risk models in a representative sample of the U.S. population and investigated the similarities and differences in the populations of ever-smokers selected for screening by each model. The editorialist discusses issues that will require attention if the models are to be implemented in routine clinical practice.

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Comparison of Five Major Guidelines for Statin Use in Primary Prevention



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When Given a Lemon, Make Lemonade: Revising Cardiovascular Risk Prediction Scores

Yadlowsky and colleagues evaluated 2 approaches for improving the pooled cohort equations to estimate cardiac risk. The editorialists discuss the findings and the need to develop increasingly accurate tools for cardiac risk estimation in specific patient populations.

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Group B streptococcal colonization in mothers and infants in western China: prevalences and risk factors

The epidemiology of maternal and infant Group B streptococcus (GBS) colonization is poorly understood in China. The aim of this study is to explore the prevalence and risk factors associated with maternal and ...

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The inflammatory response and neuronal injury in Streptococcus suis meningitis

Many of the currently used models of bacterial meningitis have limitations due to direct inoculation of pathogens into the cerebrospinal fluid or brain and a relatively insensitive assessment of long-term sequ...

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Antibiotic resistance and molecular characterization of the hydrogen sulfide-negative phenotype among diverse Salmonella serovars in China

Among 2179 Salmonella isolates obtained during national surveillance for salmonellosis in China from 2005 to 2013, we identified 46 non-H2S-producing strains originating from different sources.

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Tuberculous pneumonia-induced severe ARDS complicated with DIC in a female child: a case of successful treatment

Tuberculous (TB) pneumonia can induce acute respiratory distress syndrome (ARDS). Although TB pneumonia is one of the causes of disease and death among children worldwide, the literature on TB pneumonia-induce...

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Does discovery of differentially culturable M tuberculosis really demand a new treatment paradigm? Longitudinal analysis of DNA clearance from sputum

According to the traditional tuberculosis (TB) treatment paradigm, the initial doses of treatment rapidly kill most Mycobacterium tuberculosis (Mtb) bacilli in sputum, yet many more months of daily treatment are ...

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Toluidine Blue Staining of Resin-Embedded Sections for Evaluation of Peripheral Nerve Morphology

Here we present a protocol to visualize fine structures of peripheral nerves by obtaining and staining 1-2 µm sections with toluidine blue

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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease

Circulating microRNAs have shown promise as biomarkers for cardiovascular diseases and acute myocardial infarctions. In this study, we describe a protocol for miRNA extraction, reverse transcription, and digital PCR for the absolute quantification of miRNAs in the serum of patients with cardiovascular disease.

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Analysis of Beta-cell Function Using Single-cell Resolution Calcium Imaging in Zebrafish Islets

Beta-cell functionality is important for blood-glucose homeostasis, which is evaluated at single-cell resolution using a genetically encoded reporter for calcium influx.

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Working >45 Hours Tied to Higher Diabetes Risk in Women

TUESDAY, July 3, 2018 -- For women, working 45 hours or more per week is associated with increased risk of diabetes, according to a study published online July 2 in BMJ Open Diabetes Research & Care. Mahée Gilbert-Ouimet, Ph.D., from the...

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CVD Risk Up With Hypertensive Disorders of Pregnancy

TUESDAY, July 3, 2018 -- Women with hypertensive disorders of pregnancy (HDP) in their first pregnancy have increased rates of chronic hypertension, type 2 diabetes mellitus, and hypercholesterolemia, according to a study published online July 3 in...

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American Academy of Pediatrics Warns Against Using Fireworks

TUESDAY, July 3, 2018 -- The American Academy of Pediatrics (AAP) has issued a warning about fireworks safety. Fireworks can cause serious burns, blindness, scars, and death. Even sparklers can cause serious burns to users and bystanders, the AAP...

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Smoking Marijuana May Be Tied to Cough, Sputum Production

TUESDAY, July 3, 2018 -- Smoking marijuana seems to be associated with increased risk of cough, sputum production, and wheezing, according to a review published online July 3 in the Annals of Internal Medicine. Mehrnaz Ghasemiesfe, M.D., from the...

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Effective Marketing Methods Offered for Primary Care Doctors

TUESDAY, July 3, 2018 -- Marketing is important for physicians, and effective methods include internet marketing, speaking engagements, and print materials, according to an article published in Medical Economics. Marketing is increasingly important...

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Dynamics of Brain Volume Loss Vary With MS Progression

TUESDAY, July 3, 2018 -- Brain volume loss (BVL) has nonlinear dynamics and limited reproducibility as a marker of therapeutic response in multiple sclerosis (MS), according to a study published online July 2 in JAMA Neurology. Magí Andorra, from...

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AMA Adopts Policy to Cut Sugar Sweetened Drink Consumption

TUESDAY, July 3, 2018 -- At the annual meeting of the American Medical Association (AMA), a policy was adopted to reduce the consumption of sugar-sweetened beverages (SSBs) as a way to reduce the amount of sugar that Americans consume. The new...

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Automated Bone Scan Index Prognostic for Prostate Cancer

TUESDAY, July 3, 2018 -- The automated Bone Scan Index (aBSI) is an independent prognostic imaging biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC), according to a study published online May 17 in JAMA...

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Future Outlook Tied to Risk of Weapon Violence in Male Teens

TUESDAY, July 3, 2018 -- Positive future orientation is associated with reduced odds of weapon-related violence perpetration among teenage males from low-resource neighborhoods, according to a research letter published online July 2 in JAMA...

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What to know about bone grafts

Doctors use bone grafts in the treatment of a variety of health issues, including fractures, bone infections, spinal fusions, tumors, and joint problems. In this article, learn about the different types of bone grafts and replacement materials. We also cover the possible risks, complications, and the recovery process.

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Small Talk May Not Be as Bad as Previously Thought

People who engage in more substantive conversations tend to be happier, according to research published in Psychological Science, a journal of the Association for Psychological Science. The research also shows that idle small talk is not necessarily negatively related to well-being, contrary to previous findings, said study coauthor Matthias Mehl, a professor of psychology at the University of Arizona.

The new research revisits a small study of 79 college students that Mehl published in 2010, which suggested that more meaningful conversations were linked to greater happiness, while more small talk was linked to unhappiness.

The new study, with a larger and more diverse sample size of 486 people, confirms that quality conversations are indeed linked to greater happiness, but found that small talk seems to have no relationship with happiness one way or the other.

The results hold true for both introverts and extroverts, Mehl said.

"We do not think anymore that there is an inherent tension between having small talk and having substantive conversations. Small talk didn't positively contribute to happiness, and it didn't negatively contribute to it," said Mehl, who carried out the work alongside lead author Anne Milek, who was a postdoctoral researcher in Mehl's lab from 2016 to 2017.

"With this study, we wanted to find out whether it is primarily the quantity or the quality of our social encounters that matters for one's well-being," said Milek, who is now a senior research scientist at the University of Zurich in Switzerland.

The researchers' findings are based on an analysis of four separate studies, in which snippets of audio were collected from participants' daily interactions. The study participants included college students; breast cancer survivors and their partners; recently divorced adults; and healthy adults participating in a meditation intervention.

Upon waking until bedtime, participants in each study wore what is called the EAR, or Electronically Activated Recording, device, which is set to turn on intermittently for short periods of time throughout the day to capture candid moments of daily interactions. The EAR was developed by Mehl at the UA to help psychologists capture behavioral data.

The research team coded the conversations recorded by the EAR to determine whether they were substantive.

"We define small talk as a conversation where the two conversation partners walk away still knowing equally as much – or little – about each other and nothing else," Mehl said. "In substantive conversation, there is real, meaningful information exchanged. Importantly, it could be about any topic – politics, relationships, the weather – it just needs to be at a more than trivial level of depth."

Study participants also completed surveys designed to measure their life satisfaction, as well as assess their personality.

Overall, study participants who engaged in a greater number of substantive conversations were happier, regardless of whether they had more introverted or extroverted personalities.

"We expected that personality might make a difference, for example that extroverts might benefit more from social interactions than introverts or that substantive conversations might be more closely linked to well-being for introverts than for extroverts, and were very surprised that this does not seem to be the case," Milek said.

"Conversation quantity and quality are related to well-being," said Mehl.

"We replicated that people who spend a lot of time alone are less satisfied with their lives and have lower well-being," Mehl said. "People who spend more time interacting and have more meaningful, substantive conversations are more satisfied. The happy life is social, rather than solitary, and meaningfully so."

Although small talk didn't have any direct link to participants' well-being, it may still be important, in that it can help lay the groundwork for more substantive conversations, Mehl said.

"I think of it like this: In every pill, there's an inactive ingredient, and it's a nice metaphor, because you cannot have the pill without the inactive ingredient," Mehl said. "We all understand that small talk is a necessary component to our social lives. You cannot usually walk up to a stranger and jump right into a deep, existential conversation because of social norms."

While the study establishes a link between substantive conversations and happiness, it's hard to say whether having more substantive conversations actually makes people happier, or if happier people have more substantive conversations, Mehl said. That's an area for future research.

"I would like to experimentally 'prescribe' people a few more substantive conversations," he said, "and see whether that does something to their happiness."

Coauthors on the research include Emily A. Butler, Allison M. Tackman, Deanna M. Kaplan, and David Sbarra of the University of Arizona; Charles L. Raison of the University of Wisconsin-Madison; and Simine Vazire of the University of California, Davis.

A. Milek's work on this article was supported by the Swiss National Science Foundation (P2ZHP1_164959). The research was supported by National Institutes of Health Grants 3R01AT004698, 5R01AT004698, R01HD069498, and R03CA137975.

All data and materials have been made publicly available via the Open Science Framework. The complete Open Practices Disclosure for this article is available online. This article has received badges for Open Data and Open Materials.



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