Αρχειοθήκη ιστολογίου

Δευτέρα 2 Απριλίου 2018

Accuracy and trending ability of the fourth-generation FloTrac/Vigileo System™ in patients undergoing abdominal aortic aneurysm surgery

Abstract

Purpose

The fourth-generation FloTrac/Vigileo™ improved its algorithm to follow changes in systemic vascular resistance index (SVRI). This revision may improve the accuracy and trending ability of CI even in patients who undergo abdominal aortic aneurysm (AAA) surgery which cause drastic change of SVRI by aortic clamping. The purpose of this study is to elucidate the accuracy and trending ability of the fourth-generation FloTrac/Vigileo™ in patients with AAA surgery by comparing the FloTrac/Vigileo™-derived CI (CIFT) with that measured by three-dimensional echocardiography (CI3D).

Methods

Twenty-six patients undergoing elective AAA surgery were included in this study. CIFT and CI3D were determined simultaneously in eight points including before and after aortic clamp. We used CI3D as the reference method.

Results

In the Bland–Altman analysis, CIFT had a wide limit of agreement with CI3D showing a percentage error of 46.7%. Subgroup analysis showed that the percentage error between CO3D and COFT was 56.3% in patients with cardiac index < 2.5 L/min/m2 and 28.4% in patients with cardiac index ≥ 2.5 L/min/m2. SVRI was significantly higher in patients with cardiac index < 2.5 L/min/m2 (1703 ± 330 vs. 2757 ± 798; p < 0.001). The tracking ability of fourth generation of FloTrac/Vigileo™ after aortic clamp was not clinically acceptable (26.9%).

Conclusions

The degree of accuracy of the fourth-generation FloTrac/Vigileo™ in patients with AAA surgery was not acceptable. The tracking ability of the fourth-generation FloTrac/Vigileo™ after aortic clamp was below the acceptable limit.



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Effective Removal of Toxic Heavy Metal Ions from Aqueous Solution by CaCO 3 Microparticles

Abstract

Heavy metals are a common contaminant in water supplies and pose a variety of serious health risks to nearby human populations. A promising approach to heavy metal decontamination is the sequestration of heavy metal ions in porous materials; however, current technologies involve materials which can be difficult to synthesize, are high-cost, or are themselves potentially toxic. Herein, we demonstrate that rapidly synthesized calcium carbonate (CaCO3) microparticles can effectively remove high quantities of Pb2+, Cd2+, and Cu2+ ions (1869, 1320, and 1293 mg per gram of CaCO3 microparticles, respectively) from aqueous media. The CaCO3 microparticles were characterized with powder X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and Brunauer–Emmett–Teller (BET) N2 sorption–desorption. It was found that the Ca2+ ions of the microparticles were replaced by the heavy metal ions, leading to partially recrystallized nanoparticles of new compositional phases such as cerussite (PbCO3). The adsorption, surface dissolution/re-precipitation, and nucleation/crystal growth mechanisms were determined by investigating the Ca2+ released, along with the changes to particle morphology and crystal structure. Importantly, this study demonstrates that the porous CaCO3 microparticles performed well in a system with multiple heavy metal ion species: 100% of Cu2+, 97.5% of Pb2+, and 37.0% Cd2+ were removed from an aqueous solution of all cations with initial individual metal concentrations of 50 mg/L and 1.5 g/L of CaCO3 microparticles. At this concentration, the CaCO3 microparticles significantly outperformed activated carbon. These results help to establish CaCO3 microparticles as a promising low-cost and scalable technology for removing heavy metal ions from contaminated water.

Graphical abstract



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Frequency of awake bruxism behaviours in the natural environment. A 7‐day, multiple‐point observation of real‐time report in healthy young adults

Journal of Oral Rehabilitation, EarlyView.


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Microglial Inflammasome Activation in Penetrating Ballistic-Like Brain Injury

Journal of Neurotrauma, Ahead of Print.


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The Effect of Electromagnetic Fields on Post-Operative Pain and Locomotor Recovery in Dogs with Acute, Severe Thoracolumbar Intervertebral Disc Extrusion: A Randomized Placebo-Controlled, Prospective Clinical Trial

Journal of Neurotrauma, Ahead of Print.


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MCC950, the Selective Inhibitor of Nucleotide Oligomerization Domain (NOD)-Like Receptor Protein-3 Inflammasome, Protects Mice against Traumatic Brain Injury

Journal of Neurotrauma, Ahead of Print.


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Cancers, Vol. 10, Pages 103: Role of Gene Therapy in Pancreatic Cancer—A Review

Cancers, Vol. 10, Pages 103: Role of Gene Therapy in Pancreatic Cancer—A Review

Cancers doi: 10.3390/cancers10040103

Authors: Mizuho Sato-Dahlman Keith Wirth Masato Yamamoto

Mortality from pancreatic ductal adenocarcinoma (PDAC) has remained essentially unchanged for decades and its relative contribution to overall cancer death is projected to only increase in the coming years. Current treatment for PDAC includes aggressive chemotherapy and surgical resection in a limited number of patients, with median survival of optimal treatment rather dismal. Recent advances in gene therapies offer novel opportunities for treatment, even in those with locally advanced disease. In this review, we summarize emerging techniques to the design and administration of virotherapy, synthetic vectors, and gene-editing technology. Despite these promising advances, shortcomings continue to exist and here will also be highlighted those approaches to overcoming obstacles in current laboratory and clinical research.



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Long-term Outcome in Extracranial-Intracranial Bypass Surgery for Severe Steno-occlusive Disease of Intracranial Internal Carotid or Middle Cerebral Artery

Publication date: Available online 3 April 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Kok Ann Colin Teo, Tseng Tsai Yeo, Vijay K Sharma
ObjectivesWe report the long-term outcome and rates of recurrent cerebral ischemic events in our cohort of carefully selected patients after STA-MCA bypass for severe steno-occlusive disease of intracranial ICA or MCA with exhausted cerebral vasodilatory reserve.Patients and MethodsIn this retrospective study, we reviewed the hospital records for all patients who underwent direct superficial temporal artery-middle cerebral artery bypass surgery at our institution from January 2010 to August 2017. Patients were included in the study if they presented with transient ischemic attack or non-disabling stroke due to a severe steno-occlusive lesions of the intracranial internal carotid artery or middle cerebral artery with abnormal cerebral vasodilatory reserve on imaging. The overall event rate is defined as transient ischemic attack, acute ischemic stroke, peri-operative stroke or death.Results69 patients were included in the study. The median age of cohort was 57 years (inter-quartile range 36 -78). Median follow up period in our study was 73 months (range 2 to 90 months). The overall event rate post-treatment during the follow up period is 20.2%. In contrast, previous studies have showed that patients who underwent best medical therapy had a higher recurrent ischemic stroke rate over a 2 to 3-year period.ConclusionThis study suggests that carefully selected patients with severe steno-occlusive disease and significantly abnormal cerebral hemodynamic reserve who undergo extracranial-intracranial bypass surgery, may benefit from long-term prevention of symptomatic cerebral ischemic events.



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Factors associated with extension of the scheduled time for spine surgery

Publication date: Available online 3 April 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Kazuyoshi Kobayashi, Kei Ando, Kenyu Ito, Mikito Tsushima, Masayoshi Morozumi, Satoshi Tanaka, Masaaki Machino, Kyotaro Ota, Naoki Ishiguro, Shiro Imagama
ObjectivesAdherence to scheduled times in surgery is important in hospital management. However, sudden surgical changes or unexpected intraoperative problems may lead to prolongation of operative times. The purpose of this study was to investigate operative times in spinal surgery and to identify causes of delays during surgery.Patients and MethodsA retrospective review of 488 cases of spinal surgery was performed to investigate operations prolonged for >2 hours and to identify factors associated with prolongation.ResultsThere were 250 cases without a delay, and 144, 64, and 30 with delays of <1 h, 1 to 2 h, and >2 h, respectively. Delays >2 h were caused by interruptions due to loss of transcranial motor-evoked potential (Tc-MEP) signals in spinal cord monitoring (n = 15), reinsertion due to screw misplacement (n = 5), intraoperative pathology procedures (n = 5), extension of fusion range with instrumentation (n = 3), and complete resection of an intramedullary tumor (n = 2). Surgeries with delays >2 h (n = 30) had greater rates of scheduled surgery for >5 h (40% vs. 23%; P < 0.05), instrumentation use (70% vs. 47%; P < 0.05), reoperation (33% vs. 7%; P < 0.01%), and estimated blood loss (EBL) (1573 vs. 435 ml; P < 0.01), compared to all other surgeries (n = 458). In multivariate logistic regression, reoperation (HR 3.15, 95% CI 1.52-6.55; p < 0.01) and EBL ≥ 1000 ml (HR 3.35, 95% CI 1.56-7.18; p < 0.01) were significantly associated with prolongation of surgery by >2 h.ConclusionInformation suggesting potential prolongation of surgery should be shared with all medical staff. Reliable surgical techniques and hemostasis may also reduce delays in surgery.



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Is rivaroxaban associated with higher morbidity and mortality in patients with traumatic head injuries? A retrospective cohort study comparing rivaroxaban, no anticoagulation, and phenprocoumon

Publication date: Available online 3 April 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Thorsten Jentzsch, Rudolf M. Moos, Valentin Neuhaus, Kariem Hussein, Jan Farei-Campagna, Burkhardt Seifert, Hans-Peter Simmen, Clément M.L. Werner, Georg Osterhoff
ObjectivesThe use of new anticoagulants potentially carries the risk of increased intracranial bleeding, but there is a lack of evidence. The aim of this study was to investigate whether the morbidity and mortality differs in head trauma patients depending on the type of anticoagulation.Patients and methodsA retrospective cohort study was conducted in 2009–2014. Based on sex, age, and Glasgow-Coma Scale (GCS), patients that received rivaroxaban were matched to two control groups, one that received no anticoagulant and another one that received phenprocoumon. The primary outcome was mortality. Among others, secondary outcome variables were the length of stay (LOS) at the hospital and presence of an intracranial injury.ResultsSixty-nine patients and 23 patients per group were analyzed. The characteristics of patients did not differ significantly across groups. There were no significant differences between groups for the primary and secondary outcomes. Two patients died in the rivaroxaban group (one of them likely due to head trauma), while one patient died in the phenprocoumon group (likely not due to head trauma), and no patient died in the no anticoagulatoin group (p = 0.36). The LOS at the hospital was similar (5.0, 4.0, and 5.0 days; p = 0.94). An intracranial injury was observed in a similar number of patients in all groups (n = 11, n = 10, and n = 8; p = 0.75).ConclusionAlthough limited in size, this study did not observe significant outcome differences in patients with traumatic head injuries, who received rivaroxaban, no anticoagulant or phenprocoumon. Although not significant, the only death likely due to head trauma in the study occurred in the rivaroxaban group. Larger studies are needed before clinical application of these findings.



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Comparison of the clinical efficacy of craniotomy and craniopuncture therapy for the early stage of moderate volume spontaneous intracerebral haemorrhage in basal ganglia: using the CTA spot sign as an entry criterion

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Publication date: Available online 3 April 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Chunyan Ge, Wangmiao Zhao, Hong Guo, Zhaosheng Sun, Wanzeng Zhang, Xiaowei Li, Xuehui Yang, Jinrong Zhang, Dongxin Wang, Yi Xiang, Jianhui Mao, Wenchao Zhang, Hao Guo, Yazhao Zhang, Jianchao Chen
ObjectivesSurgical treatment is widely used for haematoma removal in spontaneous intracerebral haemorrhage (ICH) patients, but there is controversy about the selection of surgical methods. The CT angiography (CTA) spot sign has been proven to be a promising factor predicting haematoma expansion and is recommended as an entry criterion for haemostatic therapy in patients with ICH. This trial was designed to evaluate the clinical efficacy of two surgical methods (haematoma removal by craniotomy and craniopuncture combined with urokinase infusion) for patients in the early stage (≤6h from symptom onset) of spontaneous ICH with a moderate haematoma volume (30 ml – 60 ml).Patients and MethodsFrom January 2012 to July 2017, 196 eligible patients treated in our institution were enrolled according to the inclusion criteria. The patients were divided into the CTA spot sign positive type and CTA spot sign negative type according to the presence or absence of the CTA spot sign. For each type, the patients were randomly assigned to two groups, i.e., the craniotomy group, in which patients underwent craniotomy with haematoma removal, and the craniopuncture group, in which patients underwent minimally invasive craniopuncture combined with urokinase infusion therapy. Neurological function was evaluated with the Scandinavian Stroke Scale (SSS) at day 14. The disability level and the activities of daily living were assessed using a modified Rankin Scale (mRS) and Barthel Index (BI) at day 90. Case fatalities were recorded at day 14 and 90. Complications were recorded during hospitalization.ResultsFor the CTA spot sign positive type, the craniotomy group had a higher SSS than that in the craniopuncture group (P<0.05) at day 14. The rebleeding rate was higher in the craniopuncture group than that in the craniotomy group (P<0.05) during hospitalization. The craniotomy group had a lower mRS than that in the craniopuncture group (P<0.01) and had a higher BI than that in the craniopuncture group (P<0.05) at day 90. There was no statistically significant difference in the fatality rate between the two groups. For the CTA spot sign negative type, there were no significant differences in the SSS, mRS, BI, fatality rate and complication rate between the two groups.ConclusionICH can be divided into the CTA spot sign positive and negative type according to the presence or absence of the CTA spot sign. For the CTA spot sign positive type, patients can benefit from craniotomy with haematoma removal, which can reduce the postoperative rebleeding rate and improve the prognosis. For the CTA spot sign negative type, both craniotomy and craniopuncture are applicable. Considering simple procedure and minor surgical injury, craniopuncture can be a more reasonable choice.



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RNF126 as a Biomarker of a Poor Prognosis in Invasive Breast Cancer and CHEK1 Inhibitor Efficacy in Breast Cancer Cells

Purpose: (i) To investigate the expression of the E3 ligase, RNF126, in human invasive breast cancer and its links with breast cancer outcomes; and (ii) to test the hypothesis that RNF126 determines the efficacy of inhibitors targeting the cell-cycle checkpoint kinase, CHEK1.

Experimental Design: A retrospective analysis by immunohistochemistry (IHC) compared RNF126 staining in 110 invasive breast cancer and 78 paired adjacent normal tissues with clinicopathologic data. Whether RNF126 controls CHEK1 expression was determined by chromatin immunoprecipitation and a CHEK1 promoter driven luciferase reporter. Staining for these two proteins by IHC using tissue microarrays was also conducted. Cell killing/replication stress induced by CHEK1 inhibition was evaluated in cells, with or without RNF126 knockdown, by MTT/colony formation, replication stress biomarker immunostaining and DNA fiber assays.

Results: RNF126 protein expression was elevated in breast cancer tissue samples. RNF126 was associated with a poor clinical outcome after multivariate analysis and was an independent predictor. RNF126 promotes CHEK1 transcript expression. Critically, a strong correlation between RNF126 and CHEK1 proteins was identified in breast cancer tissue and cell lines. The inhibition of CHEK1 induced a greater cell killing and a higher level of replication stress in breast cancer cells expressing RNF126 compared to RNF126 depleted cells.

Conclusions: RNF126 protein is highly expressed in invasive breast cancer tissue. The high expression of RNF126 is an independent predictor of a poor prognosis in invasive breast cancer and is considered a potential biomarker of a cancer's responsiveness to CHEK1 inhibitors. CHEK1 inhibition targets breast cancer cells expressing higher levels of RNF126 by enhancing replication stress. Clin Cancer Res; 24(7); 1629–43. ©2018 AACR.



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High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma

Purpose: Development of extranodal extension (ENE) has been associated with poor survival in patients with oral cavity squamous cell carcinoma (OSCC). Here, we sought to confirm the role of ENE as a poor prognostic factor, and identify genomic and epigenetic markers of ENE in order to develop a predictive model and improve treatment selection.

Experimental Design: An institutional cohort (The University of Texas MD Anderson Cancer Center) was utilized to confirm the impact of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE containing tissue. OSCC data from The Cancer Genome Atlas (TCGA) were analyzed for the presence of molecular events associated with nodal and ENE status.

Results: ENE was associated with decreased overall and disease-free survival. Mutation of the TP53 gene was the most common event in ENE+ OSCC. The frequency of TP53 mutation in ENE+ tumors was higher compared with ENE tumors and wild-type (WT) TP53 was highly represented in pN0 tumors. pN+ENE+ patients had the highest proportion of high-risk TP53 mutations. Both primary tumors (PT) and lymph nodes with ENE (LN) exhibited a high rate of TP53 mutations (58.8% and 58.8%, respectively) with no significant change in allele frequency between the two tissue sites.

Conclusions: ENE is one of the most significant markers of OSCC OS and DFS. There is a shift toward a more aggressive biological phenotype associated with high-risk mutations of the TP53 gene. Prospective clinical trials are required to determine whether TP53 mutational status can be used for personalized treatment decisions. Clin Cancer Res; 24(7); 1727–33. ©2018 AACR.



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Personalized Chemosensitivity Assays for Mesothelioma: Are They Worth the Effort?

Cell lines formed from an individual's tumor can be used to predict response to specific therapies and determine genomic predictors. For mesothelioma, where chemotherapy remains the backbone of current therapeutic paradigms, such assays could be used to treat patients with the most effective agents specific to their "chemical profile." Clin Cancer Res; 24(7); 1513–5. ©2018 AACR.

See related article by Schunselaar et al., p. 1761



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Survival of Cancer Stem-Like Cells Under Metabolic Stress via CaMK2{alpha}-mediated Upregulation of Sarco/Endoplasmic Reticulum Calcium ATPase Expression

Purpose: Cancer cells grow in an unfavorable metabolic milieu in the tumor microenvironment and are constantly exposed to metabolic stress such as chronic nutrient depletion. Cancer stem-like cells (CSC) are intrinsically resistant to metabolic stress, thereby surviving nutrient insufficiency and driving more malignant tumor progression. In this study, we aimed to demonstrate the potential mechanisms by which CSCs avoid Ca2+-dependent apoptosis during glucose deprivation.

Experimental Design: We investigated cell viability and apoptosis under glucose deprivation, performed genome-wide transcriptional profiling of paired CSCs and parental cells, studied the effect of calcium/calmodulin-dependent protein kinase 2 alpha (CaMK2α) gene knockdown, and investigated the role of nuclear factor kappa B (NFB) in CSCs during time-dependent Ca2+-mediated and glucose deprivation–induced apoptosis. We also observed the effect of combined treatment with 2-deoxy-d-glucose, a metabolic inhibitor that mimics glucose deprivation conditions in mouse xenograft models, and thapsigargin, a specific inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA).

Results: We demonstrated the coordinated upregulation of SERCA in CSCs. SERCA, in turn, is transcriptionally regulated by CaMK2α via NFB activation. Combined treatment with 2-deoxy-d-glucose and thapsigargin, a specific inhibitor of SERCA, significantly reduced tumor growth compared with that in untreated control animals or those treated with the metabolic inhibitor alone.

Conclusions: The current study provides compelling evidence that CaMK2α acts as a key antiapoptosis regulator in metabolic stress-resistant CSCs by activating NFB. The latter induces expression of SERCA, allowing survival in glucose-deprived conditions. Importantly, our combination therapeutic strategy provides a novel approach for the clinical application of CSC treatment. Clin Cancer Res; 24(7); 1677–90. ©2017 AACR.



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Glycogen Phosphorylase: A Novel Biomarker in Doxorubicin-Induced Cardiac Injury

Extracellular vesicles containing glycogen phosphorylase, brain/heart (PYGB) have been demonstrated as a sensitive biomarker for normal cardiac injuries for patients after chemotherapy. Oxidative stress was suggested to be the mechanism behind the chemotherapy-induced tissue damage and augmented with mitochondrial antioxidant could be an effective means of early intervention. Clin Cancer Res; 24(7); 1516–7. ©2018 AACR.

See related article by Yarana et al., p. 1644



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Highlights of This Issue



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Immunotherapy of Hepatocellular Carcinoma: Facts and Hopes

Treatment of patients with hepatocellular carcinoma (HCC) in the advanced stage remains a great challenge, with very few drugs approved. After decades of failure of immune therapies, immune checkpoint inhibitors have emerged as potentially effective treatments for patients with HCC in the advanced stage. Immune checkpoints, including human cancer, cytotoxic T-lymphocyte protein 4 (CTLA-4), and programmed cell death protein 1 (PD-1), are surface proteins expressed in a variety of immune cells and mostly provide immunosuppressive signals. Monoclonal antibodies able to block these molecules have shown antitumor activity against a wide spectrum of human cancers. Clinical experience with checkpoint inhibitors in HCC includes early trials with the anti–CTLA-4 agent tremelimumab and a large phase II trial with the anti–PD-1 agent nivolumab. The latter has shown strong activity particularly as second-line therapy, both in terms of tumor response and patient survival. At least three topics should be the focus of future research: (i) the search for activity in patients at less-advanced stages, including the adjuvant treatment of patients with resectable or ablatable tumors; (ii) the enhanced efficacy of combination therapies, including particularly the combination with those targeted and locoregional therapies that may have a synergistic effect or act upon mechanisms of primary or acquired resistance to checkpoint inhibitors; and (iii) the identification of clinical features and serum or tissue biomarkers that would allow a better patient selection for individual treatments. Hopefully, ongoing trials will help to design better treatments in the future. Clin Cancer Res; 24(7); 1518–24. ©2017 AACR.



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Establishing a Preclinical Multidisciplinary Board for Brain Tumors

Purpose: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies. It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors. Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials.

Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC). Extensive drug repurposing screens, pharmacokinetic, pharmacodynamic, and efficacy studies were used to triage active compounds for combination preclinical trials with "standard-of-care" surgery and radiotherapy.

Results: Mouse models displayed distinct patterns of response to surgery, irradiation, and chemotherapy that varied with tumor subtype. Repurposing screens identified 3-hour infusions of gemcitabine as a relatively nontoxic and efficacious treatment of SEP and CPC. Combination neurosurgery, fractionated irradiation, and gemcitabine proved significantly more effective than surgery and irradiation alone, curing one half of all animals with aggressive forms of SEP.

Conclusions: We report a comprehensive preclinical trial platform to assess the therapeutic activity of conventional and novel treatments among rare brain tumor subtypes. It also enables the development of complex, combination treatment regimens that should deliver optimal trial designs for clinical testing. Postirradiation gemcitabine infusion should be tested as new treatments of SEP and CPC. Clin Cancer Res; 24(7); 1654–66. ©2018 AACR.



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A First-in-Human Phase I Study of Subcutaneous Outpatient Recombinant Human IL15 (rhIL15) in Adults with Advanced Solid Tumors

Purpose: Preclinical data established IL15 as a homeostatic factor and powerful stimulator of NK and CD8+ T-cell function, the basis for clinical testing.

Experimental Design: A first-in-human outpatient phase I dose escalation trial of subcutaneous (SC) rhIL15 was conducted in refractory solid tumor cancer patients. Therapy consisted of daily (Monday–Friday) subcutaneous injections of rhIL15 for two consecutive weeks (10 total doses/cycle). Clinical response was assessed by RECIST. Pharmacokinetics of rhIL15 and immune biomarkers were evaluated.

Results: Nineteen patients were treated with rhIL15 at dose levels of 0.25, 0.5, 1, 2, and 3 mcg/kg/day. Fourteen patients completed ≥ 2 cycles of therapy that was well tolerated. One serious adverse event (SAE), grade 2 pancreatitis, required overnight hospitalization. Enrollment was halted after a patient receiving 3 mcg/kg/day developed a dose-limiting SAE of grade 3 cardiac chest pain associated with hypotension and increased troponin. No objective responses were observed; however, several patients had disease stabilization including a renal cell carcinoma patient who continued protocol treatment for 2 years. The treatment induced profound expansion of circulating NK cells, especially among the CD56bright subset. A proportional but less dramatic increase was found among circulating CD8+ T cells with maximal 3-fold expansion for the 2 and 3 mcg/kg patients.

Conclusions: SC rhIL15 treatment was well tolerated, producing substantial increases in circulating NK and CD8+ T cells. This protocol establishes a safe outpatient SC rhIL15 regimen of 2 mcg/kg/day dosing amenable to self-injection and with potential as a combination immunotherapeutic agent. Clin Cancer Res; 24(7); 1525–35. ©2017 AACR.



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IDH1/2 Mutations Sensitize Acute Myeloid Leukemia to PARP Inhibition and This Is Reversed by IDH1/2-Mutant Inhibitors

Purpose: Somatic mutations in IDH1/2 occur in approximately 20% of patients with myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2MUT enzymes produce D-2-hydroxyglutarate (D2HG), which associates with increased DNA damage and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor cells. Whether this also holds true for IDH1/2MUT AML is not known.

Experimental Design: Well-characterized primary IDH1MUT, IDH2MUT, and IDH1/2WT AML cells were analyzed for DNA damage and responses to daunorubicin, ionizing radiation, and PARP inhibitors.

Results: IDH1/2MUT caused increased DNA damage and sensitization to daunorubicin, irradiation, and the PARP inhibitors olaparib and talazoparib in AML cells. IDH1/2MUT inhibitors protected against these treatments. Combined treatment with a PARP inhibitor and daunorubicin had an additive effect on the killing of IDH1/2MUT AML cells. We provide evidence that the therapy sensitivity of IDH1/2MUT cells was caused by D2HG-mediated downregulation of expression of the DNA damage response gene ATM and not by altered redox responses due to metabolic alterations in IDH1/2MUT cells.

Conclusions: IDH1/2MUT AML cells are sensitive to PARP inhibitors as monotherapy but especially when combined with a DNA-damaging agent, such as daunorubicin, whereas concomitant administration of IDH1/2MUT inhibitors during cytotoxic therapy decrease the efficacy of both agents in IDH1/2MUT AML. These results advocate in favor of clinical trials of PARP inhibitors either or not in combination with daunorubicin in IDH1/2MUT AML. Clin Cancer Res; 24(7); 1705–15. ©2018 AACR.



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First-in-Human Phase I Study of Single-agent Vanucizumab, A First-in-Class Bispecific Anti-Angiopoietin-2/Anti-VEGF-A Antibody, in Adult Patients with Advanced Solid Tumors

Purpose: Vanucizumab is an investigational antiangiogenic, first-in-class, bispecific mAb targeting VEGF-A and angiopoietin-2 (Ang-2). This first-in-human study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of vanucizumab in adults with advanced solid tumors refractory to standard therapies.

Experimental Design: Patients received escalating biweekly (3–30 mg/kg) or weekly (10–30 mg/kg) intravenous doses guided by a Bayesian logistic regression model with overdose control.

Results: Forty-two patients were treated. One dose-limiting toxicity, a fatal pulmonary hemorrhage from a large centrally located mediastinal mass judged possibly related to vanucizumab, occurred with the 19 mg/kg biweekly dose. Arterial hypertension (59.5%), asthenia (42.9%), and headache (31%) were the most common toxicities. Seventeen (41%) patients experienced treatment-related grade ≥3 toxicities. Toxicity was generally higher with weekly than biweekly dosing. A MTD of vanucizumab was not reached in either schedule. Pharmacokinetics were dose-linear with an elimination half-life of 6–9 days. All patients had reduced plasma levels of free VEGF-A and Ang-2; most had reductions in KTRANS (measured by dynamic contrast-enhanced MRI). Two patients (renal cell and colon cancer) treated with 30 mg/kg achieved confirmed partial responses. Ten patients were without disease progression for ≥6 months. A flat-fixed 2,000 mg biweekly dose (phamacokinetically equivalent to 30 mg/kg biweekly) was recommended for further investigation.

Conclusions: Biweekly vanucizumab had an acceptable safety and tolerability profile consistent with single-agent use of selective inhibitors of the VEGF-A and Ang/Tie2 pathway. Vanucizumab modulated its angiogenic targets, impacted tumor vascularity, and demonstrated encouraging antitumor activity in this heterogeneous population. Clin Cancer Res; 24(7); 1536–45. ©2017 AACR.



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Downregulation of DNMT3A by miR-708-5p Inhibits Lung Cancer Stem Cell-like Phenotypes through Repressing Wnt/{beta}-catenin Signaling

Purpose: Lung cancer is the leading cause of cancer-related death in the world, and emerging evidences suggest that lung cancer stem cells (CSC) are associated with its poor prognosis, tumor recurrence, and therapy resistance. Here we reveal a novel role for miR-708-5p in inhibiting lung CSC–like features.

Experimental Design: Phenotypic effects of miR-708-5p on the lung CSC–like properties were examined by in vitro sphere formation assay and in xenografted animal models. Immunoblotting, dual luciferase reporter, and immunocytochemistry were performed to determine the target of miR-708-5p. DNA methylation of CDH1 promoter region was tested using bisulfate sequencing. Genome-wide miRNA sequencing data of 990 patients from The Cancer Genome Atlas (TCGA) dataset and 148 patients from China cohort were analyzed to excavate the pathogenic implications of miR-708-5p.

Results: Expression of miR-708-5p inhibits the CSC traits of NSCLC cells in vitro while antagonizing miR-708-5p promotes tumorigenesis in vivo. miR-708-5p directly suppresses the translation of DNMT3A, which results in a substantial reduction of global DNA methylation and the upregulated expression of tumor suppressor CDH1. The upregulation of CDH1 decreased the activity of Wnt/β-catenin signaling and then impaired the stemness characteristics of NSCLC cells. Clinically, patients with high miR-708-5p expression show significantly better survival and lower recurrence. Furthermore, miR-708-5p has a promising potential to apply to differentiating histologic subtypes in NSCLC.

Conclusions: Our findings support that miR-708-5p suppresses NSCLC initiation, development, and stemness through interfering DNMT3A-dependent DNA methylation. miR-708-5p may function as a novel diagnostic and prognostic biomarker in NSCLC. Clin Cancer Res; 24(7); 1748–60. ©2017 AACR.



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Laser Treatment of Congenital Melanocytic Naevi

Laser treatment of congenital melanocytic naevi is controversial, with varying results and unknown effect on malignancy risk. This review examined the efficacy and safety of laser therapy for CMN.
The British Journal of Dermatology

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Trends in the Implementation of Active Surveillance for Low-Risk Papillary Thyroid Microcarcinomas at Kuma Hospital: Gradual Increase and Heterogeneity in the Acceptance of This New Management Option

Thyroid, Ahead of Print.


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Quantitative Analysis of the Benefits and Risk of Thyroid Nodule Evaluation in Patients ≥70 Years Old

Thyroid, Ahead of Print.


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Seasonal Changes in Serum TSH Concentrations Observed from Big Data Obtained During Six Consecutive Years from 2010 to 2015 at a Single Hospital in Japan

Thyroid, Ahead of Print.


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Atmospheric and geogenic CO2 within the crown and root of spruce (Picea abies L. Karst.) growing in a mofette area

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Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): D. Vodnik, A. Thomalla, M. Ferlan, T. Levanič, K. Eler, N. Ogrinc, C. Wittmann, H. Pfanz
Mofettes are often investigated in ecology, either as extreme sites, natural analogues to future conditions under climate change, or model ecosystems for environmental impact assessments of carbon capture and storage systems. Much of this research, however, inadequately addresses the complexity of the gas environment at these sites, mainly focusing on aboveground CO2-enrichment. In the current research, the gaseous environment of Norway spruce (Picea abies (L) Karst.) trees growing at the Stavešinske slepice mofette (NE Slovenia) were studied by measuring both soil ([CO2]soil) and atmospheric CO2 concentrations ([CO2]air). Within the studied site (800 m2), soil CO2 enrichment was spatially heterogeneous; about 25% of the area was characterized by very high [CO2]soil (>40%) and hypoxic conditions. Aboveground gas measurements along vertical profiles not only revealed substantially elevated [CO2]air close to the ground (height up to 1.5 m), but also in the upper heights (20–25 m; crown layer). On the basis δ13C of CO2, it was shown that elevated CO2 relates to a geogenic source. Trees grown in high [CO2]soil were characterized by decreased radial growth; the δ13C of their wood was less negative than in trees growing in normal soil. Unfavorable gaseous soil conditions should generally be accepted as being by far the most important factor affecting (i.e. disturbing) the growth of mofette trees.



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Aerosol optical properties and radiative effects: Assessment of urban aerosols in central China using 10-year observations

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Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Ming Zhang, Yingying Ma, Wei Gong, Boming Liu, Yifan Shi, ZhongYong Chen
Poor air quality episodes are common in central China. Here, based on 10 years of ground-based sun-photometric observations, aerosol optical and radiative forcing characteristics were analyzed in Wuhan, the biggest metropolis in central China. Aerosol optical depth (AOD) in the last decade declined significantly, while the Ångström exponent (AE) showed slight growth. Single scattering albedo (SSA) at 440 nm reached the lowest value (0.87) in winter and highest value (0.93) in summer. Aerosol parameters derived from sun-photometric observations were used as input in a radiative transfer model to calculate aerosol radiative forcing (ARF) on the surface in ultraviolet (UV), visible (VIS), near-infrared (NIR), and shortwave (SW) spectra. ARFSW sustained decreases (the absolute values) over the last 10 years. In terms of seasonal variability, due to the increases in multiple scattering effects and attenuation of the transmitted radiation as AOD increased, ARF in summer displayed the largest value (−73.94 W/m2). After eliminating the influence of aerosol loading, the maximum aerosol radiative forcing efficiency in SW range (ARFESW) achieved a value of −64.5 W/m2/AOD in April. The ARFE change in each sub-interval spectrum was related to the change in SSA and effective radius of fine mode particles (Refff), that is, ARFE increased with the decreases in SSA and Refff. The smallest contribution of ARFENIR to ARFESW was 34.11% under strong absorbing and fine particle conditions, and opposite results were found for the VIS range, whose values were always over 51.82%. Finally, due to the serious air pollution and frequency of haze day, aerosol characteristics in haze and clear days were analyzed. The percentage of ARFENIR increased from 35.71% on clear-air days to 37.63% during haze periods, while both the percentage of ARFEUV and ARFENIR in ARFESW kept decreasing. The results of this paper should help us to better understand the effect of aerosols on solar spectral radiation and to develop improved the aerosol models over central China.



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“Hanger” in Intubation and Laryngoscopy

Abstract

Achieving an adequate exposure in laryngoscopy is an extremely tedious task for the operating surgeon, especially for the anterior commissure lesions. Various maneuvers have been described to overcome this difficulty, but failed in providing an adequate exposure leading to a poor outcome. To create a device that can deliver uniform pressure over the laryngeal cartilage and succeed in providing an adequate exposure of the glottic lesion. A total of 44 patients were included in the study, divided into two groups containing 22 patients each. The distance at the level of anterior commissure from the superior border of the distal end of the laryngoscope was noted and compared. Group A subjected to digital cricoid pressure showed a mean distance of 9.09 of exposure with variance of 1.22 and Group B subjected to cricoid pressure with the cricoid catapult showed a mean distance of 11.76 with variance of 1.59. The groups were statistically analyzed using Anova Test and the test was found to be very significant (p < 0.0001). The catapult is made of a hanger defining its economics, which has a vital role in difficult intubations especially in anterior placed larynx, short neck and obese patients, also succeeds in providing an adequate exposure of the glottic lesion, (especially the anterior commissure) by delivering uniform pressure over the laryngeal cartilage, leading to a superior operative outcome.



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Stapes Surgery Teaching Tool: A Simple and Stable Technique

Abstract

Stapedotomy followed by placement of a piston prosthesis is the mainstay for surgical management of otosclerosis primarily undertaken to improve hearing in patients. Although a simple and elegant procedure, prosthesis placement in stapes surgery is difficult to master. Improper surgical technique or improper placement of prosthesis may result in complications which may require revision surgery. We here describe a training technique that is simple, inexpensive, improves the skills and can be done using easily available materials such as a disposable syringe, stapler pin and micro-forceps. Regular practice with this training module minimizes surgical time and can even be done just prior to the surgery, however, this is not a substitute for temporal bone dissections.



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Bilateral Foreign Body Bronchus

Abstract

Foreign body of aerodigestive tract is one of the most common emergency which all the otolaryngologists do come across in the pediatric patients. Among the airway and digestive tract foreign bodies, airway foreign bodies always possess major risk. Only 47% cases will give a probable positive history. Most of the time the airway foreign bodies are radiolucent. Apart from the indirect signs like hyperinflation, collapse or pneumothorax there are no direct evidences regarding the type and number of foreign bodies on radiographs. The chances of having multiple foreign bodies in the same bronchus or in both the bronchi are not remote. Babies presenting with foreign bodies in bilateral bronchus have graver prognosis than the babies with unilateral foreign bodies. Here we want to share our experience in managing 7 cases of bilateral foreign body bronchus.



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Incidence and Treatment Outcomes of Post Traumatic BPPV in Traumatic Brain Injury Patients

Abstract

The aim of this study is to assess the incidence of post traumatic BPPV and evaluate its treatment outcomes in mild and moderate traumatic head injury patients. The study population consisted of 128 patients (89 male:39 female) who were admitted with head and neck injury (Motor Vehicle Accident, Blow to the head, Fall from Height, Whiplash injury) as inpatients in Department of Neurosurgery in Tertiary care hospital in Kerala during a 2 month period from 1st April 2014 to 31st May 2014. The age range was 10–70 years and mean 39.8 with standard deviation 15.5. All cases were evaluated and serially followed up to a period of 6 months in Department of Otorhinolaryngology. In our study, the number of patients with mild injuries (Glasgow coma scale 13–15) were 108 and moderate injury (Glasgow coma scale 9–12) were 20. We found out that post traumatic BPPV was found to be 17% of the traumatic brain injury patients. All patients were treated with particle re-positioning maneuvers and were followed up for a period of 6 months. Recurrence were reported in 9 (40.9%) patients. In these patients re positioning maneuvers were repeated.



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Effectiveness of Over-The-Counter Intranasal Preparations: A Randomized Trial

Abstract

To compare the effectiveness of over-the-counter normal saline with nasal decongestant drops for the symptomatic relief of nasal congestion, and to determine if nasal drops used alone are effective in the treatment of patients suffering from nasal congestion. Prospective, randomized double blinded study. Otorhinolaryngology Outpatient Department. Patients suffering from nasal congestion and similar symptoms such as nasal discharge, dryness, crusting, sneezing, itching and loss of smell. Resolution of symptoms based on visual analog scale and objective findings on anterior rhinoscopy. Chi-square test was done for comparison between the saline and decongestant groups. Subgroup analysis was done for patients on additional medication such as antibiotics. The p value is 0.701671 for the effectiveness of saline against that of decongestant, thus no significant difference exists between them for the relief of nasal congestion. The p value is 0.007497 for those on antibiotics and those that were treated only with nasal drops, thus showing a significant difference (level of significance being p < 0.05). The effectiveness of both nasal saline and decongestant drops in bringing about relief of nasal congestion is similar, and both of them may also cause headache though the mechanism is not well understood from this study. Relief might be primarily obtained with the help of oral medication and not the use of nasal drops.

Level of evidence: Single-center randomized trial, level II b.



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Management of complex pediatric laryngotracheal stenosis with skin graft reconstruction.

https:--linkinghub.elsevier.com-ihub-ima Related Articles

Management of complex pediatric laryngotracheal stenosis with skin graft reconstruction.

Int J Pediatr Otorhinolaryngol. 2018 May;108:46-48

Authors: Bowe SN, Wentland CJ, Sandhu GS, Hartnick CJ

Abstract
OBJECTIVES: For pediatric patients with laryngotracheal stenosis, the ultimate goal is creation of a safe, functional airway. Unfortunately, wound healing in a hollow structure can complicate repair attempts, leading to restenosis. Herein, we present our experience using skin-grafting techniques in two complex pediatric laryngotracheal stenosis cases, leading to successful decannulation or speech production.
METHODS: A chart review was performed examining the evaluation and management of two pediatric patients with laryngotracheal stenosis despite prior reconstructive attempts. Patient history, bronchoscopic evaluation, intra-operative technique, post-operative management, treatment outcomes, and complications were noted. Harvesting and preparation of the split-thickness skin grafts (STSG) proceeded in a similar manner for each case. Stenting material varied based on the clinical scenario.
RESULTS: Using this technique, our patient with a Type 3 glottic web achieved substantial improvement in exercise tolerance, as well as vocal strength and quality. In addition, our aphonic patient could vocalize for the first time since her laryngotracheal injury.
CONCLUSIONS: Temporary endoluminal stenting with skin graft lining can reproduce epithelial continuity and provide "biological inhibition" to enhance the wound healing process. When previous reconstructive efforts have failed, use of STSG can be considered in the management of complex pediatric laryngotracheal stenosis.

PMID: 29605364 [PubMed - in process]



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The Need for Neddylation: A Key to Achieving NED in Uveal Melanoma

The ability of uveal melanoma cells to enter and exit dormancy plays a fundamental role in the development of metastatic disease.  Neddylation blockade is a promising strategy to prolong tumor dormancy via impaired angiogenesis and prevent the establishment of metastases via elimination of cancer stem-like cells.



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Renin-angiotensin system inhibitors to mitigate cancer treatment-related adverse events

Treatment-related side effects are a major clinical problem in cancer treatment. They lead to reduced compliance to therapy as well as increased morbidity and mortality. Well-known are the sequelae of chemotherapy on the heart, especially in childhood cancer survivors. Therefore, measures to mitigate the adverse events of cancer therapy may improve health and quality of life in cancer patients, both in short and long term. The renin angiotensin system (RAS) affects all hallmarks of cancer, and blockage of the RAS is associated with an improved outcome in several cancer types. There is also increasing evidence that inhibition of the RAS might be able to alleviate or even prevent certain types of cancer treatment related adverse effects. In this review, we summarize the potential of RAS inhibitors to mitigate cancer treatment related adverse events, with a special emphasis on chemotherapy-induced cardiotoxicity, radiation injury, and arterial hypertension.



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Potential of quantitative SEPT9 and SHOX2 methylation in plasmatic circulating cell-free DNA as auxiliary staging parameter in colorectal cancer: a prospective observational cohort study

Potential of quantitative SEPT9 and SHOX2 methylation in plasmatic circulating cell-free DNA as auxiliary staging parameter in colorectal cancer: a prospective observational cohort study

Potential of quantitative <i>SEPT9</i> and <i>SHOX2</i> methylation in plasmatic circulating cell-free DNA as auxiliary staging parameter in colorectal cancer: a prospective observational cohort study, Published online: 03 April 2018; doi:10.1038/s41416-018-0035-8

Potential of quantitative SEPT9 and SHOX2 methylation in plasmatic circulating cell-free DNA as auxiliary staging parameter in colorectal cancer: a prospective observational cohort study

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CD163 is required for protumoral activation of macrophages in human and murine sarcoma

Recent findings have shown the significance of CD163-positive macrophages in tumor progression, yet there have been few studies on the function of CD163 in macrophages. Here we uncover the role of CD163 in macrophage activation using CD163-deficient mice and human samples. We detected CD163 in 62 undifferentiated pleomorphic sarcoma samples, in which a high percentage of CD163-positive macrophages was associated with decreased overall survival and higher histological grade. We observed macrophage-induced tumor cell proliferation in co-cultures of human monocyte-derived macrophages and leiomyosarcoma (TYLMS-1) and myxofibrosarcoma (NMFH-1) cell lines, which was abrogated by silencing of CD163. Tumor development of sarcoma (MCA205 and LM8) cells in CD163-deficient mice was significantly abrogated in comparison to WT mice. Co-culture with WT peritoneal macrophages significantly increased proliferation of MCA205 cells but decreased in the presence of CD163-deficient macrophages. Production of IL-6 and CXCL2 in CD163-deficient macrophages was suppressed in comparison to WT macrophages, and overexpression of CD163 in CD163-deficient macrophages induced production of IL-6 and CXCL2. Silencing of IL-6 but not CXCL2 abrogated macrophage-induced proliferation of MCA205 cells. Taken together, our results show that CD163 is involved in protumoral activation of macrophages and subsequent development and progression of tumors in mice and humans.

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Network modeling of microRNA-mRNA interactions in neuroblastoma tumorigenesis identifies miR-204 as a direct inhibitor of MYCN

Neuroblastoma is a pediatric cancer of the sympathetic nervous system where MYCN amplification is a key indicator of poor prognosis. However, mechanisms by which MYCN promotes neuroblastoma tumorigenesis are not fully understood. In this study, we analyzed global miRNA and mRNA expression profiles of tissues at different stages of tumorigenesis from TH-MYCN transgenic mice, a model of MYCN-driven neuroblastoma. Based on a Bayesian learning network model in which we compared pre-tumor ganglia from TH-MYCN+/+ mice to age-matched wild-type controls, we devised a predicted miRNA-mRNA interaction network. Among the miRNA-mRNA interactions operating during human neuroblastoma tumorigenesis, we identified miR-204 as a tumor suppressor miRNA that inhibited a subnetwork of oncogenes strongly associated with MYCN-amplified neuroblastoma and poor patient outcome. MYCN bound to the miR-204 promoter and repressed miR-204 transcription. Conversely, miR-204 directly bound MYCN mRNA and repressed MYCN expression. miR-204 overexpression significantly inhibited neuroblastoma cell proliferation in vitro and tumorigenesis in vivo. Together these findings identify novel tumorigenic miRNA gene networks and miR-204 as a tumor suppressor that regulates MYCN expression in neuroblastoma tumorigenesis.

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Biospecimen Education Among Pacific Islanders in Southern California

Abstract

Despite increasing rates of cancer, biospecimen donations for cancer research remains low among Pacific Islanders (PIs). To address this disparity, researchers partnered with PI community organizations to develop and test a theory-based culturally tailored educational intervention designed to raise awareness about the issues surrounding biospecimen research. A total of 219 self-identified PI adults in Southern California were recruited to participate in a one-group pre-post design study. Participants completed questionnaires that assessed their knowledge and attitude regarding biospecimen research before and after viewing an educational video and receiving print materials. Results showed that participants' overall knowledge and attitude increased significantly from pre-test to post-test (p < .0001). Over 98% of participants also reported that they would be willing to donate at least one type of biospecimen sample. Efforts such as these that utilize culturally tailored education interventions may be instrumental in improving biospecimen donation rates in the PI community as well as other minority populations.



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Precision of EM Simulation Based Wireless Location Estimation in Multi-Sensor Capsule Endoscopy

In this paper, we compute and examine two-way localization limits for an RF endoscopy pill as it passes through an individuals gastrointestinal (GI) tract. We obtain finite-difference time-domain and finite element method-based simulation results position assessment employing time of arrival (TOA). By means of a 3-D human body representation from a full-wave simulation software and lognormal models for TOA propagation from implant organs to body surface, we calculate bounds on location estimators in three digestive organs: stomach, small intestine, and large intestine. We present an investigation of the causes influencing localization precision, consisting of a range of organ properties; peripheral sensor array arrangements, number of pills in cooperation, and the random variations in transmit power of sensor nodes. We also perform a localization precision investigation for the situation where the transmission signal of the antenna is arbitrary with a known probability distribution. The computational solver outcome shows that the number of receiver antennas on the exterior of the body has higher impact on the precision of the location than the amount of capsules in collaboration within the GI region. The large intestine is influenced the most by the transmitter power probability distribution.

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Mastication Evaluation With Unsupervised Learning: Using an Inertial Sensor-Based System

There is a direct relationship between the prevalence of musculoskeletal disorders of the temporomandibular joint and orofacial disorders. A well-elaborated analysis of the jaw movements provides relevant information for healthcare professionals to conclude their diagnosis. Different approaches have been explored to track jaw movements such that the mastication analysis is getting less subjective; however, all methods are still highly subjective, and the quality of the assessments depends much on the experience of the health professional. In this paper, an accurate and non-invasive method based on a commercial low-cost inertial sensor (MPU6050) to measure jaw movements is proposed. The jaw-movement feature values are compared to the obtained with clinical analysis, showing no statistically significant difference between both methods. Moreover, We propose to use unsupervised paradigm approaches to cluster mastication patterns of healthy subjects and simulated patients with facial trauma. Two techniques were used in this paper to instantiate the method: Kohonen's Self-Organizing Maps and K-Means Clustering. Both algorithms have excellent performances to process jaw-movements data, showing encouraging results and potential to bring a full assessment of the masticatory function. The proposed method can be applied in real-time providing relevant dynamic information for health-care professionals.

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S16-2. Strategy in anesthetic management for intraoperative neuromonitoring

The development of postoperative functional dysfunction can have an impact on the length of hospital stay, total medical costs, and necessity of dependency. To maintain functional integrity, neuromonitoring including motor evoked potential (MEP), sensory evoked potential, and visual evoked potential, has been conducted during the operation. Anesthetic management is usually based on the maintenance of MEP, which is most susceptible to suppression by anesthetic agents. MEP is indicated for craniotomy, spine surgery and aortic surgery, in which the technique for stimulation and recording can vary on types of surgery.

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Potential of quantitative SEPT9 and SHOX2 methylation in plasmatic circulating cell-free DNA as auxiliary staging parameter in colorectal cancer: a prospective observational cohort study



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Sleep assessment in aging adults with type 2 diabetes: Agreement between actigraphy and sleep diaries

Actigraphy and sleep diaries have been widely used to evaluate various sleep parameters. However, their agreement in diabetes patients remains unclear. The objective of this study was to examine the agreement between sleep outcomes measured by actigraphy and sleep diaries in aging adults with type 2 diabetes (T2D).

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DNA methylation of the BRD2 promoter is associated with juvenile myoclonic epilepsy in Caucasians

Epilepsia, EarlyView.


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Bicycle helmets are protective against facial injuries, including facial fractures: a meta-analysis

Cycling is a popular activity. However there are risks associated with cycling, including facial injury. Helmets are often worn to prevent head injury. Evidence for their protection against facial injury is limited. This meta-analysis investigated the effect of bicycle helmets on the incidence of facial injury. The PubMed/MEDLINE, Google Scholar, and Cochrane Library databases were searched. Studies included were observational and involved adult participants. Paediatric studies, studies on helmet legislation, and those combining facial injuries with other injury types were excluded.

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Clefts of the lip and palate: is the Internet a trustworthy source of information for patients?

Great numbers of patients use the Internet to obtain information and familiarize themselves with medical conditions. However, the quality of Internet-based information on clefts of the lip and palate has not yet been examined. The goal of this study was to assess the quality of Internet-based patient information on orofacial clefts. Websites were evaluated based on the modified Ensuring Quality Information for Patients (EQIP) instrument (36 items). Three hundred websites were identified using the most popular search engines.

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O-1-13. Diagnosis of lumbar radiculopathy using magnetospinography

We previously reported noninvasive visualization of neural activities in the lumbar spine using magnetospinography (MSG). We report here MSG findings of a patient with lumbar radiculopathy.

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The Dantastic Mr Tox & Howard Episode 1 – Primum, Non Nocere

A discussion of the ongoing opioid epidemic.

EMCrit Project by Tox & Hound.



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Issue Cover (April 2018)

European Journal of Neuroscience, Volume 47, Issue 7, Page i-iii, April 2018.


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Issue Information

Journal of Anatomy, Volume 232, Issue 5, Page i-ii, May 2018.


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Movement of anterior teeth using clear aligners: a three-dimensional, retrospective evaluation

Clear aligner treatment offers several advantages, but the available literature shows that some kind of tooth movements are unpredictable. In addition, the majority of the studies are focused on one clear alig...

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Risk and incidence of perioperative deep vein thrombosis in patients undergoing gastric cancer surgery

Abstract

Background and purpose

Venous thromboembolism (VTE) is a potentially fatal perioperative complication. Understanding the risk factors for deep vein thrombosis (DVT) and initiating appropriate prophylaxis is pivotal for reducing the risk of VTE. The purpose of this study was to clarify the perioperative risk factors for DVT in patients undergoing surgery for gastric cancer.

Methods

We reviewed the findings of lower limb ultrasonography performed in 160 patients who underwent gastrectomy for gastric cancer.

Results

The preoperative and postoperative incidence of DVT was 4.4% (7/160) and 7.2% (11/153), respectively. All postoperative DVTs were of the distal type, whereas preoperative DVTs were of the proximal (n = 3) and distal type (n = 4). None of the patients suffered symptomatic VTE. Multivariate analysis indicated that depth of invasion and D-dimer concentration were independent risk factors for preoperative DVT and that gender and performance status were risk factors for postoperative DVT. Receiver operating characteristic analysis revealed that the optimal cut-off D-dimer concentration was 1.4 μg/mL.

Conclusions

The incidence of perioperative DVT was low for patients undergoing gastric cancer surgery. Therefore, the risk-stratified application of perioperative pharmacologic thromboprophylaxis is thought to be more appropriate than routine pharmacologic thromboprophylaxis for Japanese patients undergoing surgery for gastric cancer.



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Fluoride varnish versus glutaraldehyde for hypersensitive teeth: a randomized controlled trial, meta-analysis and trial sequential analysis

Abstract

Objective

Reports indicate Gluma and Duraphat are commonly used in-office agents to treat hypersensitive teeth. Considering this, the aim of this paper is to compare Gluma and Duraphat using a randomized controlled trial, meta-analysis collating evidences from previous studies and trial sequential analysis.

Materials and methods

Thirty-eight participants were randomized. Hypersensitivity and visual analog scale (VAS) scores were recorded at baseline, 5 min and 7 days. Oral health-related quality of life (OHIP) questionnaire was administered at baseline and 7 days. Statistical analysis was performed to identify significant differences between the variables. For the meta-analysis, electronic data bases were searched and eligible data was extracted and analysed using RevMan 5.0. Trial sequential analysis was performed using O'Brien-Fleming boundary approach for the primary outcome.

Results

Both agents caused significant reduction in hypersensitivity and VAS score at 5 min and 7 days in the randomized trial with no superiority. The quality of life significantly improved in patients treated with both the agents. Four studies including the present trial in meta-analysis and trial sequential analysis indicated that Gluma produced significant reduction in VAS scores at 7 days.

Conclusion

Gluma produces significant reduction in hypersensitivity at 7 days post treatment compared with Duraphat. There is definite lack of evidence on the long-term effect of these agents.

Clinical relevance

This paper provides strong evidence on the use of Gluma for hypersensitive teeth. This also is a way forward to future research on long-term effects, adverse effects and cost-effectiveness studies.



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Aging‐related prognosis analysis of definitive radiotherapy for very elderly esophageal cancer

Cancer Medicine, EarlyView.


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An analysis of the effect of statins on the risk of Non‐Hodgkin's Lymphoma in the Women’s Health Initiative cohort

Cancer Medicine, EarlyView.


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Regulation of NCAPG by miR‐99a‐3p (passenger strand) inhibits cancer cell aggressiveness and is involved in CRPC

Cancer Medicine, EarlyView.


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Comparison of Immunohistochemistry and Direct Sequencing Methods for Identification of the BRAF V600E Mutation in Papillary Thyroid Carcinoma

Abstract

Background

BRAFV600E mutation is the most common somatic variant in papillary thyroid carcinoma (PTC) and is associated with aggressive prognostic factors. The conventional detection method for BRAF mutations is polymerase chain reaction followed by Sanger sequencing. Recently, an immunohistochemistry (IHC) method using a BRAFV600E-specific antibody (VE1) has been developed and widely adopted in the clinics; however, there is a lack of evidence regarding the comparability of the IHC and Sanger sequencing methods.

Methods

Our institution began using the BRAFV600E IHC test in January 2013. We retrospectively analyzed 697 samples that were tested using both the IHC and sequencing methods, and evaluated their concordance.

Results

BRAF mutation was detected in 90.0% (627/697) of samples using IHC and 83.4% (581/697) of samples using direct sequencing. The diagnostic parameters of IHC compared with Sanger sequencing were as follows: 100% sensitivity (581/581), 60.3% specificity (70/116), 92.7% positive predictive value (581/627), and 100% negative predictive value (70/70). No false negative results were recorded using IHC. The overall concordance rate between the two methods was 93.4% (651/697). Discordant results were found in 46 samples (6.6%), 29 of which were from cases with small tumors (< 6 mm), 8 were from cases with low tumor cellularity, and 9 were specimens yielding low-quality DNA.

Conclusions

IHC using the VE1 antibody is a reliable and highly sensitive method for detecting the BRAFV600E mutation in classic PTC.



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Prevalence and Prognostic Significance of Extramural Venous Invasion in Patients with Locally Advanced Esophageal Cancer

Abstract

Background

Extramural venous invasion (EMVI) is a known adverse prognostic factor in patients with colorectal carcinoma. The prevalence and significance of EMVI in esophageal cancer (EC) patients is still unclear.

Methods

From a prospectively maintained database, we retrospectively reviewed the resection specimens of patients with pathologic locally advanced (pT3/T4/N0-3) EC who were treated with curative intent between 2000 and 2015. Patients with previous malignancies and gastroesophageal junction (type II/III) tumors were excluded. Included were 81 patients who underwent surgery alone and 37 patients who underwent neoadjuvant chemoradiotherapy (nCRT). EMVI was assessed on hematoxylin and eosin slides and confirmed or excluded by additional Elastica van Gieson staining. Survival was analyzed using a multivariable Cox regression.

Results

EMVI was present in 23.5% (n = 19) of patients in the surgery-alone group and 21.6% (n = 8) of patients in the nCRT group. The prevalence of EMVI after surgery alone was significantly high in squamous cell carcinomas and among tumors located in the mid-esophagus, as well as those with lymphovascular invasion (p < 0.05). After nCRT, the presence of EMVI was significantly high in tumors with lymphovascular and perineural tumor growth (p = 0.034). EMVI status was an independent adverse prognostic factor for disease-free survival [hazard ratio (HR) 7.0, 95% confidence interval (CI) 2.3–21.8; p =0.001] and overall survival (HR 6.5, 95% CI 2.2–19.1; p = 0.001) in the surgery-alone group for node-positive tumors.

Conclusions

In this study of locally advanced > pT3/N0-3 EC patients, EMVI was present in 23.5% of patients in the surgery-alone group and in 21.6% of patients after nCRT. EMVI was an independent adverse prognostic factor in patients after surgery alone.



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The relationship between physician and cancer patient when initiating adjuvant treatment and its association with sociodemographic and clinical variables

Abstract

Purpose

The aim of this study was to analyze differences in physician and patient satisfaction in shared decision-making (SDM); patients' emotional distress, and coping in subjects with resected, non-metastatic cancer.

Methods

602 patients from 14 hospitals in Spain were surveyed. Information was collected regarding physician and patient satisfaction with SDM, participants' emotional distress and coping, as well as patient sociodemographic and clinical characteristics by means of specific, validated questionnaires.

Results

Overall, 11% of physicians and 19% of patients were dissatisfied with SDM; 22% of patients presented hopelessness or anxious preoccupation as coping strategies, and 56% presented emotional distress. By gender, female patients showed a higher prevalence of dissatisfaction with SDM (23 vs 14%), anxious preoccupation (26 vs 17%), and emotional distress (63 vs 44%) than males. Hopelessness was more prevalent in individuals with stage III disease than those with stages I–II (28 vs 18%).

Conclusion

Physicians must be mindful of the importance of emotional support and individual characteristics when communicating treatment options, benefits, and adverse effects of each alternative to oncological patients.



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Comparison of Immunohistochemistry and Direct Sequencing Methods for Identification of the BRAF V600E Mutation in Papillary Thyroid Carcinoma

Abstract

Background

BRAFV600E mutation is the most common somatic variant in papillary thyroid carcinoma (PTC) and is associated with aggressive prognostic factors. The conventional detection method for BRAF mutations is polymerase chain reaction followed by Sanger sequencing. Recently, an immunohistochemistry (IHC) method using a BRAFV600E-specific antibody (VE1) has been developed and widely adopted in the clinics; however, there is a lack of evidence regarding the comparability of the IHC and Sanger sequencing methods.

Methods

Our institution began using the BRAFV600E IHC test in January 2013. We retrospectively analyzed 697 samples that were tested using both the IHC and sequencing methods, and evaluated their concordance.

Results

BRAF mutation was detected in 90.0% (627/697) of samples using IHC and 83.4% (581/697) of samples using direct sequencing. The diagnostic parameters of IHC compared with Sanger sequencing were as follows: 100% sensitivity (581/581), 60.3% specificity (70/116), 92.7% positive predictive value (581/627), and 100% negative predictive value (70/70). No false negative results were recorded using IHC. The overall concordance rate between the two methods was 93.4% (651/697). Discordant results were found in 46 samples (6.6%), 29 of which were from cases with small tumors (< 6 mm), 8 were from cases with low tumor cellularity, and 9 were specimens yielding low-quality DNA.

Conclusions

IHC using the VE1 antibody is a reliable and highly sensitive method for detecting the BRAFV600E mutation in classic PTC.



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Prevalence and Prognostic Significance of Extramural Venous Invasion in Patients with Locally Advanced Esophageal Cancer

Abstract

Background

Extramural venous invasion (EMVI) is a known adverse prognostic factor in patients with colorectal carcinoma. The prevalence and significance of EMVI in esophageal cancer (EC) patients is still unclear.

Methods

From a prospectively maintained database, we retrospectively reviewed the resection specimens of patients with pathologic locally advanced (pT3/T4/N0-3) EC who were treated with curative intent between 2000 and 2015. Patients with previous malignancies and gastroesophageal junction (type II/III) tumors were excluded. Included were 81 patients who underwent surgery alone and 37 patients who underwent neoadjuvant chemoradiotherapy (nCRT). EMVI was assessed on hematoxylin and eosin slides and confirmed or excluded by additional Elastica van Gieson staining. Survival was analyzed using a multivariable Cox regression.

Results

EMVI was present in 23.5% (n = 19) of patients in the surgery-alone group and 21.6% (n = 8) of patients in the nCRT group. The prevalence of EMVI after surgery alone was significantly high in squamous cell carcinomas and among tumors located in the mid-esophagus, as well as those with lymphovascular invasion (p < 0.05). After nCRT, the presence of EMVI was significantly high in tumors with lymphovascular and perineural tumor growth (p = 0.034). EMVI status was an independent adverse prognostic factor for disease-free survival [hazard ratio (HR) 7.0, 95% confidence interval (CI) 2.3–21.8; p =0.001] and overall survival (HR 6.5, 95% CI 2.2–19.1; p = 0.001) in the surgery-alone group for node-positive tumors.

Conclusions

In this study of locally advanced > pT3/N0-3 EC patients, EMVI was present in 23.5% of patients in the surgery-alone group and in 21.6% of patients after nCRT. EMVI was an independent adverse prognostic factor in patients after surgery alone.



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Explaining Discrepancies Between the Digit Triplet Speech-in-Noise Test Score and Self-Reported Hearing Problems in Older Adults

Purpose
The purpose of this study is to determine which demographic, health-related, mood, personality, or social factors predict discrepancies between older adults' functional speech-in-noise test result and their self-reported hearing problems.
Method
Data of 1,061 respondents from the Longitudinal Aging Study Amsterdam were used (ages ranged from 57 to 95 years). Functional hearing problems were measured using a digit triplet speech-in-noise test. Five questions were used to assess self-reported hearing problems. Scores of both hearing measures were dichotomized. Two discrepancy outcomes were created: (a) being unaware: those with functional but without self-reported problems (reference is aware: those with functional and self-reported problems); (b) reporting false complaints: those without functional but with self-reported problems (reference is well: those without functional and self-reported hearing problems). Two multivariable prediction models (logistic regression) were built with 19 candidate predictors. The speech reception threshold in noise was kept (forced) as a predictor in both models.
Results
Persons with higher self-efficacy (to initiate behavior) and higher self-esteem had a higher odds to being unaware than persons with lower self-efficacy scores (odds ratio [OR] = 1.13 and 1.11, respectively). Women had a higher odds than men (OR = 1.47). Persons with more chronic diseases and persons with worse (i.e., higher) speech-in-noise reception thresholds in noise had a lower odds to being unaware (OR = 0.85 and 0.91, respectively) than persons with less diseases and better thresholds, respectively. A higher odds to reporting false complaints was predicted by more depressive symptoms (OR = 1.06), more chronic diseases (OR = 1.21), and a larger social network (OR = 1.02). Persons with higher self-efficacy (to complete behavior) had a lower odds (OR = 0.86), whereas persons with higher self-esteem had a higher odds to report false complaints (OR = 1.21). The explained variance of both prediction models was small (Nagelkerke R 2 = .11 for the unaware model, and .10 for the false complaints model).
Conclusions
The findings suggest that a small proportion of the discrepancies between older individuals' results on a speech-in-noise screening test and their self-reports of hearing problems can be explained by the unique context of these individuals. The likelihood of discrepancies partly depends on a person's health (chronic diseases), demographics (gender), personality (self-efficacy to initiate behavior and to persist in adversity, self-esteem), mood (depressive symptoms), and social situation (social network size). Implications are discussed.

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“To Be Quite Honest, If It Wasn't for Videogames I Wouldn't Have a Social Life at All”: Motivations of Young Adults With Autism Spectrum Disorder for Playing Videogames as Leisure

Purpose
Leisure activities are underutilized as a context for intervention in the field of speech-language pathology despite the fact that leisure can be an important context for skill development. The current study investigated the perceptions of individuals with autism spectrum disorder (ASD) who play videogames as their primary leisure activity regarding the role of videogames in their lives and their motivations for playing videogames.
Method
Qualitative interview methodology was used to investigate the experiences of 10 18–24-year-olds with ASD. Information was collected about the role of videogames in the lives of adolescents and young adults with ASD and the perceived benefits of playing videogames.
Results
Results indicated the participants perceived playing videogames to have a positive impact on their lives and their development. The motivations for playing videogames described are similar to those reported by typically developing populations.
Conclusions
Videogaming is a popular leisure pursuit for adolescents and young adults with and without ASD. Speech-language pathologists should consider how videogame play may be a useful context for teaching new communication, social, and language.

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Optimal Surgery for Mid-Transverse Colon Cancer: Laparoscopic Extended Right Hemicolectomy Versus Laparoscopic Transverse Colectomy

Abstract

Background

Although the feasibility and safety of laparoscopic surgery for transverse colon cancer have been shown by the recent studies, the optimal laparoscopic approach for mid-transverse colon cancer is controversial.

Methods

We retrospectively analyzed the data of patients with the mid-transverse colon cancer at our institutions between January 2007 and April 2017. Thirty-eight and 34 patients who received extended right hemicolectomy and transverse colectomy, respectively, were enrolled.

Results

There were no significant differences in operating time, blood loss, and hospital stay between the two groups. Postoperative complications developed in 10 of 34 patients (29.4%; wound infection: 2 cases, anastomotic leakage: 2 cases, bowel obstruction: 1 case, incisional hernia: 2 cases, others: 3 cases) for the transverse colectomy group and in 4 of 38 patients (10.5%; wound infection: 1 case, anastomotic leakage: 0 case, bowel obstruction: 2 cases, incisional hernia: 0 case, others: 1 case) for the extended right hemicolectomy group (P = 0.014). Although the median number of harvested #221 and #222 LNs was similar between the two groups (6 vs. 8, P = 0.710, and 3 vs. 2, P = 0.256, respectively), that of #223 was significantly larger in extended right hemicolectomy than in transverse colectomy (3 vs. 1, P = 0.038). The 5-year disease-free and overall survival rates were 92.4 and 90.3% for the extended right hemicolectomy group, and 95.7 and 79.6% for the transverse colectomy group (P = 0.593 and P = 0.638, respectively).

Conclusions

Laparoscopic extended right hemicolectomy and laparoscopic transverse colectomy offer similar oncological outcomes for mid-transverse colon cancer. Laparoscopic extended right hemicolectomy might be associated with fewer postoperative complications.



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Analysis of Early and Long-Term Oncologic Outcomes After Converted Laparoscopic Resection Compared to Primary Open Surgery for Rectal Cancer

Abstract

Background

Laparoscopic rectal resection (LRR) for cancer is a challenging procedure, with conversion to open surgery being reported in up to 30% of cases. Since only a few studies with short follow-up have compared converted LRR and open RR (ORR), it is unclear if conversion to open surgery should be prevented by preferring an open approach in those patients with preoperatively known risk factors for conversion. The aim of this study was to compare early postoperative outcomes and long-term survival after completed LRR, converted LRR or ORR for non-metastatic rectal cancer.

Methods

A prospective database of consecutive curative LRRs and ORRs for rectal cancer was reviewed. Patients undergoing LRR who required conversion (CONV group) were compared with those who had primary open rectal surgery (OPEN group) and completed LRR (LAP group). A multivariate analysis was performed to identify predictors of poor survival.

Results

A total of 537 patients were included in the study: 272 in the LAP group, 49 in the CONV group and 216 in the OPEN group. There were no significant differences in perioperative morbidity, mortality and length of hospital stay between the three groups. Five-year overall survival and disease-free survival rates did not significantly differ between LAP, CONV and OPEN patients: 83.9 versus 77.8 versus 81% (P = 0.398) and 74.5 versus 62.9 versus 72.7% (P = 0.145), respectively. Similar 5-year OS and DFS rates were observed between patients who had converted LRR for locally advanced tumor or for non-tumor-related reasons: 81.2 versus 80.8% (P = 0.839) and 62.5 versus 63.7% (P = 0.970), respectively. Poor grade of tumor differentiation, lymphovascular invasion and a lymph node ratio of 0.25 or greater, but not conversion, were independently associated with poorer survival.

Conclusion

Conversion to open surgery does not impair short-term outcomes and does not jeopardize 5-year survival in patients with rectal cancer when compared to primary open surgery.



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#FOAMtox

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Time for Toxicologists to Stop Dogging It by Meghan Spyres & Jeff Lapoint     Free Open Access Medical Education (FOAM), a term coined by Chris Nickson and Mike Cadogan in 2012, has been defined as a collection of free web-based resources, primarily made up of blogs and podcasts. They also defined it as a […]

EMCrit Project by Tox & Hound.



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Increased cortisol metabolism in women with pregnancy-related hypertension

Abstract

Purpose

The diminished function of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) was found in placentae from preeclamptic pregnancies. Here, we examine the overall maternal glucocorticoid balance in pregnancy-related hypertension. We aim to answer the question if the functions of primary enzymes involved in cortisol metabolism: 11β-HSD1 and 11β-HSD2 and 5-reductases (both 5α- and 5β) are altered in the course of hypertensive pregnancy.

Methods

We determined plasma and urinary cortisol and cortisone as well as their urinary tetrahydro- and allo-tetrahydrometabolites, both in free and conjugated forms in samples obtained from 181 Polish women in the third trimester of pregnancy. We compared steroid profiles in women with preeclampsia (PE), gestational hypertension (GH), chronic hypertension (CH) and in normotensives (controls).

Results

We found significant differences in glucocorticoid balance in pregnancy-related hypertension. Plasma cortisol to cortisone was significantly lower in PE than in controls (3.00 vs. 4.79; p < 0.001). Increased function of renal 11β-HSD2 in PE and GH was manifested by significantly lower urinary free cortisol to cortisone ratio (0.169 and 0.206 vs. 0.277 in controls; p < 0.005). Markedly enhanced metabolism of cortisol was observed in pregnancy-related hypertension, with no significant alterations in CH, and the changes were more clearly expressed in PE than in GH.

Conclusions

The glucocorticoid balance in PE and GH is shifted towards decreasing cortisol concentration either due to intensified conversion to cortisone or enhanced production of tetrahydro and allo-tetrahydrometabolites.



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SAGES Mini Med School: inspiring high school students through exposure to the field of surgery

Abstract

Objective

The SAGES Mini Med School (SMMS) was designed to expose high school students to the field of surgery through mentoring, knowledge transfer, and hands-on experience with simulation. The objective of this paper is to profile the evolutionary development, performance metrics, and satisfaction queries of this innovative effort.

Methods

Sixty-one high school students, grades 9–12, took part in the (SMMS) program during the 2015 SAGES Annual Congress. The students completed a surgical skills lab session where they attempted tasks associated with the development of open surgical and laparoscopic skills. The lab included a warm-up with the validated Super Monkey Ball video game, Top Gun Pea Drop task, FLS Peg Transfer task, open knot tying station, and open instrument tie station.

Results

The following are the results of the surgical skills lab. For the Super Monkey Ball task, 60 students participated with an average score of 73.0 s (SD = 53.9; range 59.1–87.0; median = 74). Sixty students participated in the Surgeons Knot and Pea Drop tasks with average times of 26.6 s (SD = 19.3; range 21.7–31.6; median = 21.0) and 113.8 s (SD = 65.9; range 96.6–131.0; median = 101.0), respectively. Sixty students participated in the Instrument Tie and 56 students participated in the Peg Transfer stations with average times of 51.7 s (SD = 34.5; range 42.8–60.6; median = 39.5) and 173.1 s (SD = 25.0; range 166.4–179.8; median = 180.0), respectively. 51 (83.6%) agreed that the Mini Med School made them more likely to consider a career in medicine. When asked if the program made them more likely to consider a career in surgery 42 (68.8%) agreed. All 61 respondents (100%) said that they would recommend the program to others.

Conclusions

The SMMS program showed that the students had an excellent aptitude for the performance of validated surgical subtasks with high satisfaction, and increased consideration of a career in medicine/surgery. Long-term studies are needed to evaluate the impact on workforce recruitment.



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Long-term oncologic outcomes after laparoscopic versus open rectal cancer resection: a high-quality population-based analysis in a Southern German district

Abstract

Background

An increasing number of rectal carcinoma resections in Germany and worldwide are performed laparoscopically. The recently published COLOR II trial demonstrated the oncologic safety of this surgical approach. It remains unclear whether these findings can be transferred to clinical practice.

Patients and methods

This population-based retrospective cohort study aimed to evaluate 5-year overall, relative, disease-free, and local recurrence-free survival of rectal cancer patients treated by open surgery and laparoscopy. Data from a southern German region of 1.1 million inhabitants were collected by an official clinical cancer registry. All primary non-metastatic rectal adenocarcinoma cases with surgery between 2004 and 2013 were eligible for inclusion. To compare survival rates, Kaplan–Meier analyses, relative survival models, and multivariate Cox regression were applied; a sensitivity analysis assessed bias by exclusion.

Results

Finally, 1507 patients with a median follow-up time of 7.1 years were included. Of these patients, 28.4% underwent laparoscopic procedures, with an increasing rate over time. Patients with tumors of the upper or middle rectum, younger patients, and patients of specialized colorectal cancer centers were more likely to undergo laparoscopy. After 5 years, 80.4% of laparoscopy patients were still alive, compared to 68.6% in the open group (p < 0.001). Moreover, laparoscopy was associated with superior local recurrence-free survival rates. This advantage was also significant in multivariate analysis (HR 0.70, 95% CI 0.52–0.92).

Conclusion

Laparoscopic rectal cancer surgery can be considered safe in daily clinical practice. This should be confirmed by future studies outside the setting of randomized trials.



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Feasibility of adapting the fundamentals of laparoscopic surgery trainer box to endoscopic skills training tool

Abstract

Background

The fundamentals of laparoscopic surgery (FLS) training box is a validated tool, already accessible to surgical trainees to hone their laparoscopic skills. We aim to investigate the feasibility of adapting the FLS box for the practice and assessment of endoscopic skills. This would allow for a highly available, reusable, low-cost, mechanical trainer.

Methods

The design and development process was based on a user-centered design, which is a combination of the design thinking method and cognitive task analysis. The process comprises four phases: empathy, cognitive, prototyping/adaptation, and end user testing. The underlying idea was to utilize as many of the existing components of FLS training to maintain simplicity and cost effectiveness while allowing for the practice of clinically relevant endoscopic skills. A sample size of 18 participants was calculated to be sufficient to detect performance differences between experts and trainees using a two tailed t test with alpha set at 0.05, standard deviation of 5.5, and a power of 80%.

Results

Adaptation to the FLS box included two fundamental attachments: a front panel with an insertion point for an endoscope and a shaft which provides additional support and limits movement of the scope. The panel also allows for mounting of retroflexion tasks. Six endoscopic tasks inspired by FLS were designed (two of which utilize existing FLS components). Pilot testing with 38 participants showed high user's satisfaction and demonstrated that the trainer was robust and reliable. Task performance times was able to discriminate between trainees and experts for all six tasks.

Conclusions

A mechanical, reusable, low-cost adaptation of the FLS training box for endoscopic skills is feasible and has high user satisfaction. Preliminary testing shows that the simulator is able to discriminate between trainees and experts. Following further validation, this adaptation may act as a supplement to the FES program.



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Characteristics of menstrual versus non-menstrual migraine during pregnancy: a longitudinal population-based study

Migraine is a common headache disorder that affects mostly women. In half of these, migraine is menstrually associated, and ranges from completely asymptomatic to frequent pain throughout pregnancy.

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Editorial Board

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4





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Table of Contents

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4





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Response to Letter to the Editor regarding “Effects of respiratory training on heart rate variability and baroreflex sensitivity in individuals with chronic spinal cord injury”

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4
Author(s): Bonnie E. Legg Ditterline, Sevda C. Asian, David C. Randall, Susan J. Harkema, Camilo Castillo, Alexander V. Ovechkin




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Editors' Selections From This Issue: Volume 99 / Number 4 / April 2018

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4





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Archives of Physical Medicine and Rehabilitation Supplements

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4





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Masthead

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4





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Correction

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4





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Prediction of Falls in Subjects Suffering From Parkinson Disease, Multiple Sclerosis, and Stroke

Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4
Author(s): Ettore Beghi, Elisa Gervasoni, Elisabetta Pupillo, Elisa Bianchi, Angelo Montesano, Irene Aprile, Michela Agostini, Marco Rovaris, Davide Cattaneo
ObjectiveTo compare the risk of falls and fall predictors in patients with Parkinson disease (PD), multiple sclerosis (MS), and stroke using the same study design.DesignMulticenter prospective cohort study.SettingInstitutions for physical therapy and rehabilitation.ParticipantsPatients (N=299) with PD (n=94), MS (n=111), and stroke (n=94) seen for rehabilitation.InterventionsNot applicable.Main Outcome MeasuresFunctional scales were applied to investigate balance, disability, daily performance, self-confidence with balance, and social integration. Patients were followed for 6 months. Telephone interviews were organized at 2, 4, and 6 months to record falls and fall-related injuries. Incidence ratios, Kaplan-Meier survival curves, and Cox proportional hazards models were used.ResultsOf the 299 patients enrolled, 259 had complete follow-up. One hundred and twenty-two patients (47.1%) fell at least once; 82 (31.7%) were recurrent fallers and 44 (17.0%) suffered injuries; and 16%, 32%, and 40% fell at 2, 4, and 6 months. Risk of falls was associated with disease type (PD, MS, and stroke in decreasing order) and confidence with balance (Activities-specific Balance Confidence [ABC] scale). Recurrent fallers were 7%, 15%, and 24% at 2, 4, and 6 months. The risk of recurrent falls was associated with disease type, high educational level, and ABC score. Injured fallers were 3%, 8%, and 12% at 2, 4, and 6 months. The only predictor of falls with injuries was disease type (PD).ConclusionsPD, MS, and stroke carry a high risk of falls. Other predictors include perceived balance confidence and high educational level.



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Effects of Respiratory Training on Heart Rate Variability and Baroreflex Sensitivity in Individuals with Chronic Spinal Cord Injury

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4
Author(s): Cameron M. Gee, Christopher R. West




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Correction

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4





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Correction

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4





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Return to Play After Injuries: A Survey on the Helpfulness of Various Forms of Assistance in the Shared Decision-Making Process in Semiprofessional Athletes in Germany

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Publication date: April 2018
Source:Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 4
Author(s): Daniel Niederer, Jan Wilke, Lutz Vogt, Winfried Banzer
ObjectiveTo assess how different decision-guiding factors, such as health- and performance-related stakeholders, as well as evidence-based guidelines, support the process-oriented final positive return-to-play (RTP) decision of head coaches responsible for semiprofessional sport teams.DesignCross-sectional survey.SettingTeam sport.ParticipantsA survey consisting of questions on the importance of different decision-guiding factors used when making the RTP decision after injuries was administered to and completed by head coaches (N=238) of semiprofessional players' teams.InterventionsNot applicable.Main Outcome MeasuresWith respect to helpfulness in the RTP decision-making process, the coaches rated both the importance of the opinions of physicians, physiotherapists, strength and conditioning coaches, and the athletes themselves, and the importance of the general and injury-specific RTP guidelines.ResultsOur survey revealed that the head coaches rely on physicians and physiotherapists to a large extent, to the athletes and to themselves to a medium extent, and to strength and conditioning coaches and RTP guidelines to a small but still relevant extent. The coaches' efforts to seek a shared decision-making process in RTP are, hence, partially evident.ConclusionsA multitude of actuators intervene when making the RTP decision. The professionalization of the RTP process in semiprofessional sports includes the athletes themselves, the head coaches, the (external) physicians, the (external) physiotherapists, and the strength and conditioning coaches based on general RTP decision-making models and specific criteria related to injury type, sports type, level, and playing position. The development of awareness and implementation strategies of RTP models should be subject to further research.



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