Ιατρικά Άρθρα Αλέξανδρος Γ. Σφακιανάκης: 12/19/17

Τρίτη 19 Δεκεμβρίου 2017

Soft Tissue Sarcoma Response to Two Cycles of Neoadjuvant Chemotherapy

Publication date: Available online 19 December 2017
Source:Academic Radiology
Author(s): Jennifer L. Favinger, Daniel S. Hippe, Darin J. Davidson, Saeed Elojeimy, Eira S. Roth, Antoinette W. Lindberg, Alice S. Ha
Rationale and ObjectivesWhen soft tissue sarcomas are treated with neoadjuvant chemotherapy, the number of cycles of chemotherapy is usually dependent on the tumor's initial response. Popular methods to assess tumor response include Response Evaluation Criteria in Solid Tumors (RECIST) criteria, which rely solely on tumor size, and maximum standardized uptake value (SUVmax) reduction in positron emission tomography (PET), which requires an expensive and high radiation test. We hypothesized that contrast-enhanced magnetic resonance imaging (MRI) may offer a good alternative by providing additional information beyond tumor size.Materials and MethodsFollowing IRB approval, a retrospective review identified patients with soft tissue sarcomas who underwent both PET and MRI before and after two cycles of neoadjuvant chemotherapy. Five readers independently examined the MRI exams for: changes in size, T2 or T1 signal, necrosis and degree of enhancement. Readers then made a subjective binary assessment of tumor response to therapy. Each reader repeated the anonymized randomized reading at least 2 weeks apart. 18 F-FDG PET exams were interpreted by a nuclear medicine specialist. The maximum standardized uptake values (SUVmax) for pre and post-chemotherapy exams were compared. Intra- and inter-reader agreement was assessed using Cohen's kappa and Light's kappa, respectively. .ResultsTwenty cases were selected for this multireader study, of which 9 (45%) were responders and 11 were nonresponders by SUVmax. Using all MRI criteria, 43% were classified as responders based on MRI and 1.5% were classified as responders by RECIST criteria. Using PET as the reference, the sensitivity and the specificity of the MRI diagnosis for response using all findings were 50% and 63%, respectively. There was fair to moderate intrareader (kappa = 0.37) and inter-reader (kappa = 0.48) agreement for the MRI diagnosis of response. None of the individual MRI signal characteristics were significantly different between the PET responders and nonresponders. Additionally, no MRI findings were significantly different between those with and without good clinical responses.ConclusionBy our assessment, there is a poor correlation between tumor response by RECIST criteria and PET SUVmax. In addition, varying MR features did not help in diagnosing tumor response. Imaging of tumor response remains a challenging area that requires further research.

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Long-term quality of life in inoperable non-small cell lung cancer patients treated with conventionally fractionated compared to hyperfractionated accelerated radiotherapy – Results of the randomized CHARTWEL trial

To evaluate the quality of life (QoL) of patients with inoperable non-small cell lung cancer treated with conventionally fractionated radiotherapy (CF) vs. continuous hyperfractionated accelerated radiotherapy weekend-less (CHARTWEL).

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Genotype-driven phase I study of weekly irinotecan in combination with capecitabine-based neoadjuvant chemoradiation for locally advanced rectal cancer

We aimed to identify the maximum tolerated dose (MTD) of weekly irinotecan in combination with capecitabine-based neoadjuvant chemoradiation according to the UGT1A1∗28 genotype in patients with locally advanced rectal cancer.

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Predicting hypoxia status using a combination of contrast-enhanced computed tomography and [18F]-Fluorodeoxyglucose positron emission tomography radiomics features

Hypoxia is a known prognostic factor in head and neck cancer. Hypoxia imaging PET radiotracers such as 18F-FMISO are promising but not widely available. The aim of this study was therefore to design a surrogate for 18F-FMISO based on 18F-FDG PET and contrast-enhanced CT radiomics features, and to study its performance in the context of hypoxia-based patient stratification.

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Prospect of robotic assistance for fully automated brachytherapy seed placement into skull base: Experimental validation in phantom and cadaver

Publication date: Available online 18 December 2017
Source:Radiotherapy and Oncology
Author(s): Jian-Hua Zhu, Jing Wang, Yong-Gui Wang, Meng Li, Xiao-Jing Liu, Chuan-Bin Guo
Background and purposeTo investigate the feasibility and accuracy of robot-assisted brachytherapy for skull base tumours.Material and methodsA custom robot system was tested on both phantom and cadaveric specimen. Cone beam CT (CBCT) images were transferred to the graphical user interface (GUI) for planning trajectories and the data were sent to the robot control unit. Following registration, the puncture needle was inserted into the target by the robot under navigation guidance, and seeds were implanted. Placement error was instantly displayed on the GUI; the result was verified after postoperative image scanning.ResultsA total of 150 seeds (100 for phantom experiments, 50 for cadaveric studies) were deposited by the robot system. In phantom experiments the mean placement error was 0.57 ± 0.21 mm (measured by the navigation system) vs. 1.41 ± 0.38 mm (measured by image fusion) (p < 0.001); in cadaveric studies the corresponding figures were 0.60 ± 0.30 mm vs. 2.48 ± 0.32 mm (p < 0.001). There was no significant difference for comparison of accuracy test in phantom experiments (p = 0.173) as well as in cadaveric studies (p = 0.354). Accuracy was better in the phantom experiment than in cadaveric studies (p < 0.001).ConclusionsThe performance of robot-assisted skull base brachytherapy is feasible and accurate. Dosimetric coverage will need to be demonstrated in further studies.

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Long-term quality of life in inoperable non-small cell lung cancer patients treated with conventionally fractionated compared to hyperfractionated accelerated radiotherapy – Results of the randomized CHARTWEL trial

Publication date: Available online 19 December 2017
Source:Radiotherapy and Oncology
Author(s): Marlene Hechtner, Mechthild Krause, Jochem König, Steffen Appold, Beate Hornemann, Susanne Singer, Michael Baumann
Background and purposeTo evaluate the quality of life (QoL) of patients with inoperable non-small cell lung cancer treated with conventionally fractionated radiotherapy (CF) vs. continuous hyperfractionated accelerated radiotherapy weekend-less (CHARTWEL).Material and methodsThe largest monocentric subgroup of the phase III CHARTWEL trial was analyzed up to three years after randomization. QoL was assessed with the European Organization for Research and Treatment of Cancer QoL Core Questionnaire (QLQ-C30) and lung cancer module (QLQ-LC13) and compared using linear mixed models. QoL interrelations with recurrence, metastasis, and death were explored by multi-state modeling.Results160 patients (98%) provided at least one QoL assessment. Average treatment differences of CF vs. CHARTWEL over three years were −5.4 points (95%CI [−13.6,2.8], p = 0.19) in global QoL, 11.9 ([2.8,21.0], p = 0.01) in fatigue, 13.4 ([3.5,23.3], p = 0.009) in pain, 10.5 ([1.3,19.6], p = 0.03) in dyspnea, and 5.2 ([−2.7,13.0], p = 0.19) in dysphagia. At 12 months, the probabilities of being disease-free with good, good or moderate, any global QoL, or alive were 5.1%, 20.3%, 34.2%, 54.4% under CF and 10.4%, 21.0%, 37.5%, 65.3% under CHARTWEL.ConclusionsOver three years, QoL was similar or more favorable under CHARTWEL compared to CF. Modeling QoL together with disease states provided additional insight into treatment comparisons.

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Spontaneous regression of an idiopathic arteriovenous fistula of the right vertebral artery

Abstract

A previously healthy 53-year-old male presented with a 2-month history of pulsatile tinnitus, worsening headaches, and neck pain. Given the clinical symptoms, a workup was initiated to assess for a vascular etiology such as a dural arteriovenous fistula.

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Mechanical Thrombectomy in Basilar Artery Occlusion

Abstract

Background

Mechanical thrombectomy (MT) of basilar artery occlusions (BAO) is a subject of debate. We investigated the clinical outcome of MT in BAO and predictors of a favorable outcome.

Material and Methods

A total of 104 MTs of BAO (carried out between 2010 and 2016) were analyzed. Favorable outcome as a modified Rankin scale (mRS) ≤ 2 at 90 days was the primary endpoint. The influence of the following variables on outcome was investigated: number of detectable posterior communicating arteries (PcoAs), patency of basilar tip, completeness of BAO and posterior circulation Alberta Stroke Program early computed tomography score (PC-ASPECTS). Secondary endpoints were technical periprocedural parameters including symptomatic intracranial hemorrhage (sICH).

Results

The favorable clinical outcome at 90 days was 25% and mortality was 43%. The rate of successful reperfusion, i.e. modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was 82%. Presence of bilateral PcoAs (area under the curve, AUC: 0.81, odds ratio, OR: 4.2, 2.2–8.2; p < 0.0001), lower National Institute of Health Stroke Scale (NIHSS) on admission (AUC: 0.74, OR: 2.6, 1.3–5.2; p < 0.01), PC-ASPECTS ≥ 9 (AUC: 0.72, OR: 4.2, 1.5–11.9; p < 0.01), incomplete BAO (AUC: 0.66, OR: 2.6, 1.4–4.8; p < 0.001), and basilar tip patency (AUC: 0.66, OR: 2.5, 1.3–4.8; p < 0.01) were associated with a favorable outcome. Stepwise logistic regression analysis revealed that the strongest predictors of favorable outcome at 90 days were bilateral PcoAs, low NIHSS on admission, and incomplete BAO (AUC: 0.923, OR: 7.2, 3–17.3; p < 0.0001).

Conclusion

The use of MT for BAO is safe with high rates of successful reperfusion. Aside from baseline NIHSS and incomplete vessel occlusion, both known predictors of favorable outcome in anterior circulation events, we found that collateral flow based on the presence or absence of PcoAs had a decisive prognostic impact.

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Percutaneous Treatment of Scalp Arteriovenous Fistulas by Direct Puncture and Polydocanol Sclerotherapy

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Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer.

Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer.

J Clin Oncol. 2017 Dec 18;:JCO2017750232

Authors: Molenaar RJ, Sidana S, Radivoyevitch T, Advani AS, Gerds AT, Carraway HE, Angelini D, Kalaycio M, Nazha A, Adelstein DJ, Nasr C, Maciejewski JP, Majhail NS, Sekeres MA, Mukherjee S

Abstract
Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

PMID: 29252123 [PubMed - as supplied by publisher]

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In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Ĉerenkov imaging.

http:--linkinghub.elsevier.com-ihub-imag

In vivo fate tracking of degradable nanoparticles for lung gene transfer using PET and Ĉerenkov imaging.

Biomaterials. 2016 Aug;98:53-63

Authors: Black KC, Ibricevic A, Gunsten SP, Flores JA, Gustafson TP, Raymond JE, Samarajeewa S, Shrestha R, Felder SE, Cai T, Shen Y, Löbs AK, Zhegalova N, Sultan DH, Berezin M, Wooley KL, Liu Y, Brody SL

Abstract
Nanoparticles (NPs) play expanding roles in biomedical applications including imaging and therapy, however, their long-term fate and clearance profiles have yet to be fully characterized in vivo. NP delivery via the airway is particularly challenging, as the clearance may be inefficient and lung immune responses complex. Thus, specific material design is required for cargo delivery and quantitative, noninvasive methods are needed to characterize NP pharmacokinetics. Here, biocompatible poly(acrylamidoethylamine)-b-poly(dl-lactide) block copolymer-based degradable, cationic, shell-cross-linked knedel-like NPs (Dg-cSCKs) were employed to transfect plasmid DNA. Radioactive and optical beacons were attached to monitor biodistribution and imaging. The preferential release of cargo in acidic conditions provided enhanced transfection efficiency compared to non-degradable counterparts. In vivo gene transfer to the lung was correlated with NP pharmacokinetics by radiolabeling Dg-cSCKs and performing quantitative biodistribution with parallel positron emission tomography and Čerenkov imaging. Quantitation of imaging over 14 days corresponded with the pharmacokinetics of NP movement from the lung to gastrointestinal and renal routes, consistent with predicted degradation and excretion. This ability to noninvasively and accurately track NP fate highlights the advantage of incorporating multifunctionality into particle design.

PMID: 27179433 [PubMed - indexed for MEDLINE]

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Comparative Study of Clarithromycin- versus Metronidazole-Based Triple Therapy as First-Line Eradication for Helicobacter pylori

Introduction: Clarithromycin (CAM)-based triple therapy comprising proton pump inhibitors and amoxicillin is administered as first-line eradication treatment against Helicobacter pylori infection. However, the eradication rate achieved with CAM-based triple therapy has decreased to H. pylori eradication. Methods:H. pylori-positive patients were treated with CAM-based triple therapy comprising esomeprazole and amoxicillin (EAC group) or with MNZ-based triple therapy comprising esomeprazole and amoxicillin (EAM group). Results:H. pylori eradication rates achieved in the intention-to-treat (ITT) and per protocol (PP) analyses were 70.6 and 72.7%, respectively, in the EAC group. Eradication rates obtained via ITT and PP analyses were 91.7 and 94.3%, respectively, in the EAM group. In the EAC group, eradication rates were significantly lower in patients harboring CAM-resistant strains than in those harboring CAM-sensitive strains. In contrast, eradication rates were comparable between patients harboring CAM-resistant strains and those harboring CAM-sensitive strains in the EAM group. Conclusion: MNZ-based triple therapy consisting of esomeprazole and amoxicillin is superior to CAM-based triple therapy containing esomeprazole and amoxicillin as first-line eradication treatment against H. pylori.
Oncology 2017;93(suppl 1):15-19

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Computer-Aided Diagnosis Based on Convolutional Neural Network System for Colorectal Polyp Classification: Preliminary Experience

Background and Aim: Computer-aided diagnosis (CAD) is becoming a next-generation tool for the diagnosis of human disease. CAD for colon polyps has been suggested as a particularly useful tool for trainee colonoscopists, as the use of a CAD system avoids the complications associated with endoscopic resections. In addition to conventional CAD, a convolutional neural network (CNN) system utilizing artificial intelligence (AI) has been developing rapidly over the past 5 years. We attempted to generate a unique CNN-CAD system with an AI function that studied endoscopic images extracted from movies obtained with colonoscopes used in routine examinations. Here, we report our preliminary results of this novel CNN-CAD system for the diagnosis of colon polyps. Methods: A total of 1,200 images from cases of colonoscopy performed between January 2010 and December 2016 at Kindai University Hospital were used. These images were extracted from the video of actual endoscopic examinations. Additional video images from 10 cases of unlearned processes were retrospectively assessed in a pilot study. They were simply diagnosed as either an adenomatous or nonadenomatous polyp. Results: The number of images used by AI to learn to distinguish adenomatous from nonadenomatous was 1,200:600. These images were extracted from the videos of actual endoscopic examinations. The size of each image was adjusted to 256 × 256 pixels. A 10-hold cross-validation was carried out. The accuracy of the 10-hold cross-validation is 0.751, where the accuracy is the ratio of the number of correct answers over the number of all the answers produced by the CNN. The decisions by the CNN were correct in 7 of 10 cases. Conclusion: A CNN-CAD system using routine colonoscopy might be useful for the rapid diagnosis of colorectal polyp classification. Further prospective studies in an in vivo setting are required to confirm the effectiveness of a CNN-CAD system in routine colonoscopy.
Oncology 2017;93(suppl 1):30-34

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Clinical Significance of Bmi1 Expression in Inflammatory Bowel Disease

Background: Although the stem cell marker Bmi1 is overexpressed in many malignancies, its role in inflammation-associated cancer is unclear. Colitis-associated cancer (CAC) is caused by chronic intestinal inflammation and often results from refractory inflammatory bowel disease (IBD). Methods: To assess the involvement of Bmi1 in the development of CAC, we analyzed the gene expression of colon tissues collected from 111 patients with IBD and CAC. Results: In the colonic mucosa of patients with ulcerative colitis, the expression of Bmi1 correlated significantly with the expression of inflammatory cytokines such as IL-6, IL-17, IL-23, and tumor necrosis factor α (TNF-α). In the colonic mucosa of patients with Crohn's disease, the expression of Bmi1 correlated significantly with the expression of TNF-α and IL-23. The expression of Bmi1 was enhanced in the colonic mucosae of refractory IBD, suggesting that Bmi1 expression might be related to increased cancer risk. In addition, patients with high Bmi1 expression showed significantly lower response rates upon subsequent anti-TNF-α therapy as compared to patients with low Bmi1 expression. In human CAC specimens, the expression of Bmi1 was upregulated in nontumor tissues as well as tumors. Conclusions: Bmi1 expression is related to a refractory clinical course of IBD and upregulated in refractory IBD and CAC. Measurement of Bmi1 expression is a promising approach for the advanced treatment and personalized management of IBD patients.
Oncology 2017;93(suppl 1):20-26

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The Feasibility of 18-mm-Diameter Colonic Stents for Obstructive Colorectal Cancers

Objectives: This study aimed to evaluate the characteristics and the feasibility of 18-mm-diameter stents for obstructive colorectal cancer, comparing the clinical courses with 22- mm-diameter stents. Methods: We retrospectively compared 33 consecutive cases treated with 18-mm-diameter stents (bridge to surgery [BTS] in 25, palliative therapy [PAL] in 8) with 27 consecutive cases treated with 22-mm-diameter stents (BTS in 21, PAL in 6) for obstructive colorectal cancer between May 2013 and November 2015 in our institution. Results: There were no significant differences between the 18-mm and 22-mm groups in technical success rates (97 and 96%, respectively) and clinical success rates (100 and 100%, respectively). As a BTS, the rates of complications and stoma formation were not significantly different between groups. For PAL, although the rates of complications and stent patency were similar, stent occlusion occurred in 1 patient (12.5%) in the 18-mm group. Conclusions: The 18-mm-diameter stents were similarly effective when compared with 22-mm-diameter stents. Because 18-mm-diameter stents are easy to handle and produce less mechanical stress, they have the potential to decrease the perforation rate and mitigate the stent's impact on the tumors. 18-mm-diameter stents can be useful and safe, especially as a BTS.
Oncology 2017;93(suppl 1):43-48

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Prophylactic Suturing Closure Is Recommended after Endoscopic Treatment of Colorectal Tumors in Patients with Antiplatelet/Anticoagulant Therapy

The prophylactic closure of mucosal defects after endoscopic resection is known to prevent postoperative bleeding in colorectal lesions. However, closure of large mucosal defects is difficult with conventional clips only, and several closure techniques have been previously described; use of an Endoloop, 8-ring loop, or loop clip and a small incision around the mucosal defect. Given that the prophylactic closure requires much cost and time, the application should be limited to high-risk cases. Medication of antithrombotics or antiplatelet agents would be one of the reasonable indications for prophylactic closure of mucosal defects after endoscopic resection of colorectal tumors.
Oncology 2017;93(suppl 1):27-29

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Characterization of Pancreatic Tumors with Quantitative Perfusion Analysis in Contrast-Enhanced Harmonic Endoscopic Ultrasonography

Objectives: This study evaluated whether quantitative perfusion analysis with contrast-enhanced harmonic (CH) endoscopic ultrasonography (EUS) characterizes pancreatic tumors, and compared the hemodynamic parameters used to diagnose pancreatic carcinoma. Methods: CH-EUS data from pancreatic tumors of 76 patients were retrospectively analyzed. Time-intensity curves (TIC) were generated to depict changes in signal intensity over time, and 6 parameters were assessed: baseline intensity, peak intensity, time to peak, intensity gain, intensity at 60 s (I₆₀), and reduction rate. These parameters were compared between pancreatic carcinomas (n = 41), inflammatory pseudotumors (n = 14), pancreatic neuroendocrine tumors (n = 14), and other tumors (n = 7). All 6 TIC parameters and subjective analysis for diagnosing pancreatic carcinoma were compared. Results: Values of peak intensity and I₆₀ were significantly lower and time to peak was significantly longer in the groups with pancreatic carcinomas than in the other 3 tumor groups (p p 60, time to peak, and reduction rate, were 0.817, 0.664, 0.810, 0.751, 0.845, 0.777, and 0.725, respectively. I₆₀ was the most accurate parameter for differentiating pancreatic carcinomas from the other groups, giving values of sensitivity/specificity of 92.7/68.6% when optimal cutoffs were chosen. Conclusions: In pancreatic carcinomas, TIC patterns were markedly different from the other tumor types, with I₆₀ being the most accurate diagnostic parameter. Quantitative perfusion analysis is useful for differentiating pancreatic carcinomas from other pancreatic tumors.
Oncology 2017;93(suppl 1):55-60

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Viruses, Vol. 9, Pages 390: How Human Papillomavirus Replication and Immune Evasion Strategies Take Advantage of the Host DNA Damage Repair Machinery

Viruses, Vol. 9, Pages 390: How Human Papillomavirus Replication and Immune Evasion Strategies Take Advantage of the Host DNA Damage Repair Machinery

Viruses doi: 10.3390/v9120390

Authors: Valentina Bordignon Enea Di Domenico Elisabetta Trento Giovanna D’Agosto Ilaria Cavallo Martina Pontone Fulvia Pimpinelli Luciano Mariani Fabrizio Ensoli

The DNA damage response (DDR) is a complex signalling network activated when DNA is altered by intrinsic or extrinsic agents. DDR plays important roles in genome stability and cell cycle regulation, as well as in tumour transformation. Viruses have evolved successful life cycle strategies in order to ensure a chronic persistence in the host, virtually avoiding systemic sequelae and death. This process promotes the periodic shedding of large amounts of infectious particles to maintain a virus reservoir in individual hosts, while allowing virus spreading within the community. To achieve such a successful lifestyle, the human papilloma virus (HPV) needs to escape the host defence systems. The key to understanding how this is achieved is in the virus replication process that provides by itself an evasion mechanism by inhibiting and delaying the host immune response against the viral infection. Numerous studies have demonstrated that HPV exploits both the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and rad3-related (ATR) DDR pathways to replicate its genome and maintain a persistent infection by downregulating the innate and cell-mediated immunity. This review outlines how HPV interacts with the ATM- and ATR-dependent DDR machinery during the viral life cycle to create an environment favourable to viral replication, and how the interaction with the signal transducers and activators of transcription (STAT) protein family and the deregulation of the Janus kinase (JAK)–STAT pathways may impact the expression of interferon-inducible genes and the innate immune responses.

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quality of care; +40 new citations

40 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

quality of care

These pubmed results were generated on 2017/12/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Estrogenic Endocrine Disruption in Switzerland: Assessment of Fish Exposure and Effects

Estrogenic exposure has been reported to occur in Swiss rivers, and there is concern that reduced reproductive health, caused by disturbances of the endocrine system, may contribute to the observed decline in brown trout catch. Consequently, we aimed to determine if disturbances of the endocrine system do occur in wild brown trout (Salmo trutta) in Switzerland and, in the affirmative case, if these might affect trout population status. Our first task was to characterize the estrogenicity of Swiss midland rivers that receive effluents from sewage treatment plants (STP). Next, we performed a set of laboratory and field exposure experiments aimed at elucidating how estrogens affect sexual development and reproductive parameters as estrogen-sensitive targets in the life cycle of brown trout. Subsequently, we assessed the demographic status of brown trout populations in the field which were exposed to the cumulative impact of estrogen-active compounds and other stressors. Finally, we integrated the data into a life-cycle model to predict potential population-level consequences of the (xeno)estrogenic exposure. The estrogenicity of 18 Swiss midland rivers was characterized bioanalytically by applying the YES bioassay to water samples and by measuring plasma vitellogenin (VTG) levels in resident brown trout. Generally, estrogenic contamination of the rivers appears to occur only locally and at comparatively low levels (0.2–2 ng/l 17β-estradiol equivalents). In laboratory experiments, potential disruptive effects of estrogens on gonadal differentiation and reproduction of brown trout were investigated. The estrogen-sensitive window of brown trout gonad differentiation was found to differ from other salmonid species. Feminisation of the developing gonads occurred only after exposure to rather high estrogen concentrations. Analysis of VTG mRNA levels indicated that the yolk may accumulate environmental estrogens and act as a long-term reservoir. The experiments to study the effects of prolonged estrogen exposure on reproduction of mature brown trout showed that, while VTG was induced at low concentrations (20 ng/l estrone (E1), 2 ng/l 17β-estradiol (E2) and 400 ng/l 4-nonylphenol (NP)), effects on reproductive parameters such as fertility became evident only at the higher dose (100 ng/l estrone, 10 ng/l 17β-estradiol and 4000 ng/l 4-nonylphenol). For the field study, the river Lützelmurg (Canton Thurgau) was selected as our study site. This river is impacted by the estrogen-active effluents of one sewage treatment plant (STP). Estrogenic levels in the river were found to be highly variable over time, but showed a distinct difference between sites upstream and downstream from the STP effluent – a difference which was also reflected by the VTG levels of caged and resident brown trout. From the brown trout demographic data, it is evident that factors other than estrogen exposure, including habitat quality, strongly influence population structure. The results from the modelling supported this finding and showed that the trout population in the Lützelmurg is likely to be more sensitive to changes of survival rates in the first winter and beyond than to changes in early life stage survival or reproductive parameters. From the overall results of our project, we conclude that a significant influence of estrogenic contamination on brown trout population densities in the majority of Swiss rivers appears not to be likely.

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Procalcitonin

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Procalcitonin and Other Biomarkers for the Assessment of Disease Severity and Guidance of Treatment in Bacterial Infections

The ambiguities of clinical signs and the limitations of current microbial techniques for the diagnosis of bacterial infections - and to grade their severity – are well known. The use of biomarkers provides a novel, complementary approach to diagnose infection, and to estimate treatment response and the outcome of patients. In most infections, a true “gold standard” for diagnosis does not exist, thus the measurement of biomarkers, specifically the “hormokine” procalcitonin (PCT) in a clearly defined setting, has been shown to significantly improve the diagnostic certainty and also to reduce the utilization of antimicrobial therapy. For prognostic assessment, other promising biomarkers (e.g. adrenomedullin) have demonstrated high predictive potential to estimate the risk for mortality in the short and long term, and other adverse outcomes. A critical appraisal of the advantages and limitations of biomarkers in different clinical situations is mandatory. Herein, the present authors discuss the current data on the use of PCT and other biomarkers for the diagnosis, treatment guidance, and prognostic assessment of bacterial infections, and their potential role in the overall assessment of patients with sepsis.

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Discontinuous Versus In-Continuity Neck Dissection in Squamous Cell Carcinoma of the Tongue and Floor of the Mouth: Comparing the Rates of Locoregional Recurrence.

Discontinuous Versus In-Continuity Neck Dissection in Squamous Cell Carcinoma of the Tongue and Floor of the Mouth: Comparing the Rates of Locoregional Recurrence.

J Oral Maxillofac Surg. 2017 Nov 23;:

Authors: Wang HC, Zheng Y, Pang P, Li RW, Qi ZZ, Sun CF

Abstract
PURPOSE: To date, consensus has not been reached on which treatment modality, that is, in-continuity neck dissection or discontinuous neck dissection, is more appropriate for managing patients with squamous cell carcinoma (SCC) of the tongue and floor of the mouth. This study aimed to perform a meta-analysis to compare discontinuous neck dissection with in-continuity neck dissection as a treatment modality for SCC of the tongue and floor of the mouth.
MATERIALS AND METHODS: The PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched for articles that compared discontinuous neck dissection with in-continuity neck dissection in SCC of the tongue and floor of the mouth until March 1, 2017. The predictor variable was whether discontinuous neck dissection or in-continuity neck dissection was performed in each group. The primary outcome variable was the incidence of locoregional recurrence. Two authors individually extracted the data and assessed the study quality. The meta-analysis was performed using Stata (version 13.0; StataCorp, College Station, TX).
RESULTS: We included 8 studies with 796 patients in our meta-analysis. The results showed that in-continuity neck dissection had a statistically significantly lower incidence of locoregional recurrence than discontinuous neck dissection (random-effects model: relative risk, 0.459; 95% confidence interval, 0.240 to 0.877; P = .019). Because significant heterogeneity among studies (I2 = 74.5%, P < .001) was found in the heterogeneity evaluation, a separate analysis was performed. However, the results still showed that in-continuity neck dissection had a statistically significantly lower rate of locoregional recurrence than discontinuous neck dissection in patients with T2 and T3 SCC of the tongue and floor of the mouth (fixed-effects model: relative risk, 0.281; 95% confidence interval, 0.183 to 0.433; P < .001).
CONCLUSIONS: Compared with discontinuous neck dissection, in-continuity neck dissection can significantly reduce the rate of locoregional recurrence in patients with SCC of the tongue and floor of the mouth.

PMID: 29247622 [PubMed - as supplied by publisher]

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A systematic review of validated sinus surgery simulators.

A systematic review of validated sinus surgery simulators.

Clin Otolaryngol. 2017 Dec 16;:

Authors: Stew B, Kao SS, Dharmawardana N, Ooi EH

Abstract
BACKGROUND: Simulation provides a safe and effective opportunity to develop surgical skills. A variety of endoscopic sinus surgery (ESS) simulators have been described in the literature. Validation of these simulators allows for effective utilisation in training.
OBJECTIVE OF REVIEW: To conduct a systematic review of the published literature to analyse the evidence for validated ESS simulation.
SEARCH STRATEGY: Pubmed, Embase, Cochrane and Cinahl were searched from inception of the databases to January 11th , 2017.
EVALUATION METHOD: 12,516 articles were retrieved of which 10,112 were screened following the removal of duplicates. 38 full text articles were reviewed after meeting the search criteria. Evidence of face, content, construct, discriminant and predictive validity was extracted.
RESULTS: 20 articles were included in the analysis describing 12 ESS simulators. 11 of these simulators had undergone validation; 3 virtual reality, 7 physical bench models and 1 cadaveric simulator. 7 of the simulators were shown to have face validity, 7 had construct validity and 1 had predictive validity. None of the simulators demonstrated discriminate validity.
CONCLUSION: This systematic review demonstrates that a number of ESS simulators have been comprehensively validated. Many of the validation processes, however, lack standardisation in outcome reporting, thus limiting a meta-analysis comparison between simulators. This article is protected by copyright. All rights reserved.

PMID: 29247602 [PubMed - as supplied by publisher]

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American Thyroid Association ultrasound system for the initial assessment of thyroid nodules: Use in stratifying the risk of malignancy of indeterminate lesions.

American Thyroid Association ultrasound system for the initial assessment of thyroid nodules: Use in stratifying the risk of malignancy of indeterminate lesions.

Head Neck. 2017 Dec 16;:

Authors: Trimboli P, Deandrea M, Mormile A, Ceriani L, Garino F, Limone PP, Giovanella L

Abstract
BACKGROUND: The ultrasound risk stratification system of the American Thyroid Association (ATA) is frequently adopted in clinical practice. Here, we evaluated its performance in a series of nodules with indeterminate fine-needle aspiration cytology (FNAC) report.
METHODS: Indeterminate thyroid nodules diagnosed at 2 medical centers were retrospectively screened, ultrasound images were reevaluated, and lesions were classified according to the ATA. Single ultrasound parameters were also analyzed.
RESULTS: One hundred seventy-three indeterminate lesions were included with 24.8% of malignancy. The high suspicion class showed a cancer rate (75%) significantly (P < .001) higher than that recorded in the other categories (16.8%). Between ultrasound parameters, halo and microcalcifications were the most sensitive and specific ones. The most accurate receiver operating characteristic (ROC)-derived cutoff of nodule's diameter was >4.1 cm. At multivariate analysis, only the ATA class of high suspicion and size >4.1 cm were significantly associated with cancer (odds ratios [ORs] 19.4 and 5.4, respectively).
CONCLUSION: The ATA ultrasound system is reliable in the risk stratification of indeterminate thyroid lesions.

PMID: 29247582 [PubMed - as supplied by publisher]

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Modulation of the Tumor Microenvironment by Epstein-Barr virus Latent Membrane Protein-1 in Nasopharyngeal Carcinoma.

Modulation of the Tumor Microenvironment by Epstein-Barr virus Latent Membrane Protein-1 in Nasopharyngeal Carcinoma.

Cancer Sci. 2017 Dec 16;:

Authors: Yoshizaki T, Kondo S, Endo K, Nakanishi Y, Aga M, Kobayashi E, Hirai N, Sugimoto H, Hatano M, Ueno T, Ishikawa K, Wakisaka N

Abstract
Latent membrane protein 1 (LMP1) is a primary oncogene encoded by the Epstein-Barr virus, and various portions of LMP1 are detected in nasopharyngeal carcinoma (NPC) tumor cells. LMP1 has been extensively studied since the discovery of its transforming property in 1985. LMP1 promotes cancer cell growth during NPC development and facilitates the interaction of cancer cells with surrounding stromal cells for invasion, angiogenesis, and immune modulation. LMP1 is detected in 100% of pre-invasive NPC tumors and in approximately 50% of advanced NPC tumors. Moreover, a small population of LMP1-expressing cells in advanced NPC tumor tissue is proposed to orchestrate NPC tumor tissue maintenance and development through cancer stem cells and progenitor cells. Recent studies suggest that LMP1 activity shifts according to tumor development stage, but still has a pivotal role during all stages of NPC development. This article is protected by copyright. All rights reserved.

PMID: 29247573 [PubMed - as supplied by publisher]

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Oropharynx-directed ipsilateral irradiation for p16-positive squamous cell carcinoma involving the cervical lymph nodes of unknown primary origin.

Oropharynx-directed ipsilateral irradiation for p16-positive squamous cell carcinoma involving the cervical lymph nodes of unknown primary origin.

Head Neck. 2017 Dec 16;:

Authors: Chen AM, Meshman J, Hsu S, Yoshizaki T, Abemayor E, John MS

Abstract
BACKGROUND: The purpose of this study was to present our findings on the use of limited-field, oropharynx-directed ipsilateral irradiation for p16-positive squamous cell carcinoma of unknown primary origin.
METHODS: Between April 2011 and January 2016, 25 patients with a histological diagnosis of p16-positive squamous cell carcinoma were selectively irradiated to the ipsilateral oropharynx and cervical neck for tumors of unknown primary origin. The dose to the oropharynx ranged from 54-60 Gy (median 60 Gy) in 30-33 fractions. Concurrent cisplatin-based chemotherapy was administered to 8 patients (32%).
RESULTS: The actuarial 2-year estimates of locoregional control, progression-free survival, and overall survival were 91%, 87%, and 92%, respectively. One patient failed in the contralateral neck. There was no grade 3 + toxicity in either the acute or late setting.
CONCLUSION: Oropharynx-directed, ipsilateral radiation results in disease control that compares favorably with historical controls treated by comprehensive mucosal and bilateral neck radiation.

PMID: 29247568 [PubMed - as supplied by publisher]

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Presenting symptoms and long term survival in Head and Neck cancer.

Presenting symptoms and long term survival in Head and Neck cancer.

Clin Otolaryngol. 2017 Dec 15;:

Authors: Douglas CM, Ingarfield K, McMahon AD, Savage SA, Conway DI, MacKenzie K

Abstract
OBJECTIVES: To assess how type and number of symptoms are related to survival in head and neck cancer patients.
DESIGN: Patients were followed-up for over 10 years from the Scottish Audit of Head and Neck Cancer; (national cohort of head and neck cancer patients in Scotland 1999 - 2001). September 2013, cohort was linked to national mortality data. First, second and third presenting symptoms were recorded at diagnosis.
SETTING: National prospective audit - Scotland.
PARTICIPANTS: A subset of 1589 patients, from the original cohort of 1895, who had cancer arising from one of the four main subsites; larynx, oropharynx, oral cavity and hypopharynx.
MAIN OUTCOME MEASURES: Median survival in relation to patients' presenting symptoms.
RESULTS: 1146 (72%) males and 443 (28%) females, mean age at diagnosis 64 years (13 - 95). There was a significant difference in survival in relation to the number of the patient's presenting symptoms; one symptom had a median survival of 5.3 years compared with 1.1 years for three symptoms. Patients who presented with weight loss had a median survival of 0.8 years, compared to 4.2 years if they did not (p<0.001). Patients who presented with hoarseness had a median survival of 5.9 years compared to 2.6 years without (p<0.001). There was no significant difference in long term survival for patients who presented with an ulcer, compared to those that did not (p=0.105).
CONCLUSIONS: This study highlights the importance of patients' presenting symptoms, giving valuable information in highlighting appropriate "red flag" symptoms and subsequent treatment planning and prognosis. This article is protected by copyright. All rights reserved.

PMID: 29247495 [PubMed - as supplied by publisher]

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End-of-life care pathway of head and neck cancer patients: single-institution experience.

End-of-life care pathway of head and neck cancer patients: single-institution experience.

Eur Arch Otorhinolaryngol. 2017 Dec 15;:

Authors: Heinonen T, Loimu V, Saarilahti K, Saarto T, Mäkitie A

Abstract
BACKGROUND: Studies on palliative care of head and neck cancer (HNC) patients are scarce although the affected patient population is quite large.
OBJECTIVE: To evaluate the role of a specialised palliative-care pathway of HNC patients.
PATIENTS AND METHODS: Data on all HNC patients who were treated at the Helsinki University Hospital Palliative Care Center during 1 year were retrospectively reviewed. The analysis comprised 60 patients (49 males; mean age 67 years; range 28-88). All patients had a minimum follow-up of 1 year or until death.
RESULTS: Fifty-nine (98%) out of the 60 patients died during the follow-up period. Median survival after diagnosis was 11 months (range 3 weeks-11.9 years) and after withholding disease-specific therapies 3 months (range 0-16). Thirty-three (55%) patients received palliative radiotherapy, 27 (45%) had PEG tube and 17 (28%) tracheostomy. Thirty-seven (66%) patients visited an emergency department (ED) (median 1.3 visits; range 0-6) and 21 (35%) were hospitalised at the university hospital during the palliative period. The most common severe complications were infection (also the most common reason for ED visits and hospitalisation), bleeding (four massive airway bleedings with one death), delirium and airway obstruction (one emergency tracheostomy). Twelve (35%) out of the 34 patients who were referred to specialised home care died at home as compared with three (12%) out of the 26 patients not supported by a specialised home-care team.
CONCLUSIONS: Severe complications leading to an emergency unit visit and hospitalisation are common among HNC patients in their relatively short palliative period reflecting the need for early-integrated palliative care. Collaboration with a specialised palliative home-care team seems to increase end-of-life care at home.

PMID: 29247265 [PubMed - as supplied by publisher]

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Periosteal desmoid tumour: a rare finding in the oral cavity.

Periosteal desmoid tumour: a rare finding in the oral cavity.

BMJ Case Rep. 2017 Dec 14;2017:

Authors: Shruti S, Bavle RM, Konda P, Venugopal R

Abstract
A 55-year-old female patient reported with an intraoral well-localised asymptomatic swelling on the right side of the mandible in relation to the right mandibular first molar along with a history of trauma 6 months back. Panoramic radiograph revealed normal trabecular bone pattern in relation to the lesion. The lesion was excised along with the associated buccal cortical plate and tooth. The microscopic examination revealed a well-circumscribed lesion consisting of spindle cells arranged in storiform pattern associated with the buccal cortical plate. The key feature to note was presence of reactive periosteum, which was in continuum with the lesion. Immunohistochemistry (IHC) revealed faint nuclear positivity for β-catenin. The above findings led to our diagnosis of periosteal desmoid, which is rarely reported in the head-and-neck region. The major challenge in the diagnosis of such lesions is good clinicopathological correlation as the differential diagnosis of spindle-cell lesions is vast and needs IHC confirmation.

PMID: 29246931 [PubMed - in process]

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Development and Validation of a Predictive Radiomics Model for Clinical Outcomes in Stage I Non-small Cell Lung Cancer.

Development and Validation of a Predictive Radiomics Model for Clinical Outcomes in Stage I Non-small Cell Lung Cancer.

Int J Radiat Oncol Biol Phys. 2017 Nov 15;:

Authors: Yu W, Tang C, Hobbs BP, Li X, Koay EJ, Wistuba II, Sepesi B, Behrens C, Rodriguez Canales J, Parra Cuentas ER, Erasmus JJ, Court LE, Chang JY

Abstract
PURPOSE: To develop and validate a radiomics signature that can predict the clinical outcomes for patients with stage I non-small cell lung cancer (NSCLC).
METHODS AND MATERIALS: We retrospectively analyzed contrast-enhanced computed tomography images of patients from a training cohort (n = 147) treated with surgery and an independent validation cohort (n = 295) treated with stereotactic ablative radiation therapy. Twelve radiomics features with established strategies for filtering and preprocessing were extracted. The random survival forests (RSF) method was used to build models from subsets of the 12 candidate features based on their survival relevance and generate a mortality risk index for each observation in the training set. An optimal model was selected, and its ability to predict clinical outcomes was evaluated in the validation set using predicted mortality risk indexes.
RESULTS: The optimal RSF model, consisting of 2 predictive features, kurtosis and the gray level co-occurrence matrix feature homogeneity2, allowed for significant risk stratification (log-rank P < .0001) and remained an independent predictor of overall survival after adjusting for age, tumor volume and histologic type, and Karnofsky performance status (hazard ratio [HR] 1.27; P < 2e-16) in the training set. The resultant mortality risk indexes were significantly associated with overall survival in the validation set (log-rank P = .0173; HR 1.02, P = .0438). They were also significant for distant metastasis (log-rank P < .05; HR 1.04, P = .0407) and were borderline significant for regional recurrence on univariate analysis (log-rank P < .05; HR 1.04, P = .0617).
CONCLUSIONS: Our radiomics model accurately predicted several clinical outcomes and allowed pretreatment risk stratification in stage I NSCLC, allowing the choice of treatment to be tailored to each patient's individual risk profile.

PMID: 29246722 [PubMed - as supplied by publisher]

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Functional Outcomes After De-escalated Chemoradiation Therapy for Human Papillomavirus-Positive Oropharyngeal Cancer: Secondary Analysis of a Phase 2 Trial.

Functional Outcomes After De-escalated Chemoradiation Therapy for Human Papillomavirus-Positive Oropharyngeal Cancer: Secondary Analysis of a Phase 2 Trial.

Int J Radiat Oncol Biol Phys. 2017 Nov 06;:

Authors: Hegde JV, Shaverdian N, Felix C, Wang PC, Veruttipong D, Hsu S, Riess JW, Rao SD, Daly ME, Chen AM

Abstract
PURPOSE: To analyze functional outcomes for patients treated on a phase 2 trial of de-escalated chemoradiation therapy for human papillomavirus-positive oropharyngeal cancer.
METHODS AND MATERIALS: Patient eligibility included p16-positive, stage III or IV oropharyngeal squamous cell carcinoma and a Zubrod performance status of 0 to 1. Treatment was induction chemotherapy with paclitaxel, 175 mg/m2, and carboplatin, area under the curve (AUC) of 6 mg/ml/min, for 2 cycles every 21 days, followed by concurrent paclitaxel, 30 mg/m2, every 7 days with dose-reduced radiation therapy of 54 or 60 Gy. Trends in body weight and body mass index (BMI) were analyzed with gastrostomy tube and narcotic use rates. Functional outcomes were assessed using the University of Washington Quality of Life Scale and the Functional Assessment of Cancer Therapy-Head and Neck Scale.
RESULTS: Forty-five patients were registered, of whom 40 were evaluable. Only 1 patient had a BMI deemed unhealthy at the completion of treatment. For the 15 patients (38%) with a normal BMI (18-25 kg/m2) before treatment, recovery back to baseline occurred at approximately 18 months (average BMI, 23.2 kg/m2 vs 22.3 kg/m2; P=.09). In 2 patients (5%), gastrostomy tubes were placed during treatment. No patient was enteral feeding tube-dependent at 6 months after treatment. Ninety-five percent of patients tolerated a normal regular diet at last follow-up.
CONCLUSIONS: De-escalated chemoradiation therapy may improve functional outcomes as indicated by the relatively low incidence of gastrostomy tube placement and long-term dysphagia. In patients with a normal BMI prior to chemoradiation therapy, BMI recovered to baseline levels.

PMID: 29246721 [PubMed - as supplied by publisher]

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Development of one control and one tumor-specific induced pluripotent stem cell line from laryngeal carcinoma patient.

Development of one control and one tumor-specific induced pluripotent stem cell line from laryngeal carcinoma patient.

Stem Cell Res. 2017 Dec;25:283-285

Authors: Zhang Y, Zhu J, Dai Y, Wang L, Liu R

Abstract
Skin fibroblasts and tumor fibroblasts were extracted from a 64-year old male patient clinically diagnosed with laryngeal carcinoma. Control and tumor specific induced pluripotent stem cells were reprogrammed with 5 reprogramming factors, Klf-4, c-Myc, Oct-4, Sox-2, and Lin-28, using the messenger RNA reprogramming system. The transgene-free iPSC lines showed pluripotency, confirmed by immunofluorescence staining. The iPSC lines also showed normal karyotype, and could form embryoid bodies in vitro and differentiate into the 3 germ layers in vivo. This in vitro cellular model can be used to study the oncogenesis and pathogenesis of laryngeal carcinoma.

PMID: 29246575 [PubMed - in process]

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Reliability of High-speed Videoendoscopic Ratings of Essential Voice Tremor and Adductor Spasmodic Dysphonia.

Reliability of High-speed Videoendoscopic Ratings of Essential Voice Tremor and Adductor Spasmodic Dysphonia.

J Voice. 2017 Dec 12;:

Authors: Parker LA, Kunduk M, Fink DS, McWhorter A

Abstract
OBJECTIVES: The main objectives of this study were to (1) examine intrarater and inter-rater reliabilities in perceptual ratings of vocal fold vibratory patterns and supraglottic characteristics for essential vocal tremor and adductor spasmodic dysphonia (AdSD) using high-speed videoendoscopy (HSV), and (2) to investigate the specificity of the parameters in differentiating these two voice disorders.
METHODS: HSV recordings of 34 cases diagnosed with essential vocal tremor, AdSD, or AdSD with vocal tremor were evaluated blindly by two voice speech pathologists. The two raters examined all HSV video segments twice across nine supraglottic and vocal fold vibratory characteristics for inter-rater and intrarater reliabilities. A separate consensus rating was then developed, with the results analyzed to explore differentiation.
RESULTS: Raters demonstrated moderate intrarater reliability with mean Spearman's rho correlation coefficients of 0.68 (rater 1) and 0.73 (rater 2). Moderate inter-rater reliability for the two raters was seen across all parameters with a mean Cohen's kappa coefficient of 0.51. Raters showed higher intrarater and inter-rater reliabilities for supraglottic parameters. Only the presence of tremor differentiated between the two voice disorders in cases with a consistent diagnosis.
CONCLUSIONS: The high level of concomitance between vocal tremor and AdSD may affect subjective perceptual analysis of supraglottic and vocal fold vibratory patterns. Results indicate similar global involvement of supraglottic laryngeal structures for both vocal tremor and AdSD.

PMID: 29246397 [PubMed - as supplied by publisher]

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Interleukin 1 gene polymorphism and susceptibility to disease.

Interleukin 1 gene polymorphism and susceptibility to disease.

Immunol Rev. 2018 Jan;281(1):40-56

Authors: Khazim K, Azulay EE, Kristal B, Cohen I

Abstract
The Interleukin 1 (IL-1) family plays a central role in the generation and regulation of inflammatory responses, in both innate and adaptive immunity. Although the IL-1 molecules are traditionally considered to be classical proinflammatory cytokines, their functions are not restricted to inflammation, and they have also been shown to play a key role in a wide range of additional physiological and pathological functions, including learning modulation, sleep, pregnancy, depression, appetite, hematopoiesis, metabolism, and many others. Since their effect as cytokines and regulators of inflammation is so pleiotropic, any shift of the biological balance between agonistic and antagonistic signals has the potential to cause disease. Here, we consider the genetic influence of interleukin-1 gene polymorphism in the context of susceptibility to human diseases. We review known single nucleotide polymorphisms (SNP) of IL-1 genes linked to human diseases, and suggest how exploring biological effects of IL-1 gene cluster polymorphism may lead to new directions in understanding and diagnostic of disease and effective treatment.

PMID: 29247999 [PubMed - in process]

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Effects of exercise training on restless legs syndrome, depression, sleep quality and fatigue among hemodialysis patients: A systematic review and meta-analysis.

Effects of exercise training on restless legs syndrome, depression, sleep quality and fatigue among hemodialysis patients: A systematic review and meta-analysis.

J Pain Symptom Manage. 2017 Dec 13;:

Authors: Song YY, Hu RJ, Diao YS, Chen L, Jiang XL

Abstract
CONTEXT: Hemodialysis patients experience a heavy symptom burden that leads to a decreased quality of life. Pharmacological treatment is effective but costly and has adverse effects. Exercise is a promising approach for symptom management, but the effect of exercise on restless legs syndrome, depression, sleep quality and fatigue in hemodialysis patients is still uncertain.
OBJECTIVES: This meta-analysis was conducted to identify whether exercise training is beneficial in the treatment of the symptoms of restless legs syndrome, depression, poor sleep quality, and fatigue in patients receiving hemodialysis.
METHODS: A systematic search of PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science was conducted to identify randomized controlled trials (RCTs) comparing exercise training with routine care on restless legs syndrome, depression, sleep quality and fatigue among hemodialysis patients. Quality assessment was conducted using the Cochrane risk of bias tool, and RevMan (5.3) was used to analyze the data.
RESULTS: Fifteen RCTs met our inclusion criteria were included. The pooled effect size showed that exercise training was effective on restless legs syndrome (P<0.001), depression (P<0.001) and fatigue (P<0.001). However, effect size combinations for sleep quality were not performed due to the sensitivity analysis results.
CONCLUSIONS: Exercise training may help hemodialysis patients to reduce the severity of restless legs syndrome, depression, and fatigue. More high-quality RCTs with larger samples and comparative RCTs focused on different exercise regimens are needed.

PMID: 29247753 [PubMed - as supplied by publisher]

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Sleep on a high heat capacity mattress increases conductive body heat loss and slow wave sleep.

Sleep on a high heat capacity mattress increases conductive body heat loss and slow wave sleep.

Physiol Behav. 2017 Dec 13;:

Authors: Kräuchi K, Fattori E, Giordano A, Falbo M, Iadarola A, Aglì F, Tribolo A, Mutani R, Cicolin A

Abstract
Environmental temperature can strongly affect sleep. The habitual sleep phase is usually located between evening decline and morning rise of the circadian rhythm of core body temperature (CBT). However, the thermophysiological mechanisms promoting or disturbing sleep are not yet fully understood. The purpose of this study was to examine the effects of a high heat capacity mattress (HHCM) on CBT, skin temperatures and sleep in comparison to a conventional low heat capacity mattress (LHCM). Based on the higher heat capacity of HHCM an increase in conductive body heat loss enhances the nocturnal decline in CBT can be expected. Based on previous findings this may then be accompanied by an increase in slow wave sleep (SWS). The mattresses were studied in a randomized single-blind crossover design in fifteen healthy young men (Age: 26.9±2.1yr, BMI: 22.2±0.4kg/m2) by overnight in laboratory standard video-polysomnography in a temperature stabilized setting. CBT, room temperature, and skin and mattress surface temperatures were continuously recorded in order to get information about inner and outer body heat flow. Additionally, subjective sleep quality was estimated by visual analogue scale. In comparison to LHCM sleep on HHCM exhibited a selective increase in SWS (16%, p<0.05), increased subjective sleep quality and sleep stability [reduced cyclic alternating pattern (CAP) rate; 5.3%, p<0.01]. Additionally, analyses of the sleep stages showed in the second part of the night a significant increase in SWS and a decrease in REMS. In addition, HHCM induced a greater reduction in CBT (maximally by -0.28°C), reduced the increase in proximal skin temperatures on the back (PROBA; maximally by -0.98°C), and delayed the increase in mattress surface temperature (maximal difference LHCM-HHCM: 6.12°C). Thus, the CBT reduction can be explained by an increase in conductive heat loss to the mattress via proximal back skin regions. Regression analysis identified PROBA as the critical variable to predict inner conductive heat transfer from core to shell and SWS. In conclusion, the study expands the previous findings that a steeper nocturnal decline in CBT increases SWS and subjective sleep quality, whereas inner conductive heat transfer could be identified as the crucial thermophysiological variable, and not CBT.

PMID: 29247670 [PubMed - as supplied by publisher]

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Spectrum Of Symptoms In Women Diagnosed With Endometriosis During Adolescence Versus Adulthood.

Spectrum Of Symptoms In Women Diagnosed With Endometriosis During Adolescence Versus Adulthood.

Am J Obstet Gynecol. 2017 Dec 13;:

Authors: DiVasta AD, Vitonis AF, Laufer MR, Missmer SA

Abstract
BACKGROUND: Endometriosis symptoms often start at a young age, and the time between symptom onset and endometriosis diagnosis can be several years. It is not clear if symptoms experienced by adolescents differ from adults. Better understanding may shorten the often lengthy delay in diagnosis.
OBJECTIVE: To further elucidate the symptom presentation of adolescents as compared to adults to determine if differences existed based upon age at surgical diagnosis that could impact time to diagnosis.
STUDY DESIGN: This investigation was a cross-sectional study at enrollment within a longitudinal cohort of adolescents and women with endometriosis. The population-based cohort was recruited from two tertiary care centers and the surrounding communities. Participants included adolescents (diagnosed ≤18y, n=295) and adults (diagnosed >18y, n=107) with surgically-confirmed endometriosis who were enrolled into The Women's Health Study: From Adolescence to Adulthood. Participants completed an expanded version of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (WERF EPHect) standard clinical questionnaire including items regarding menstrual history, associated symptoms, and pain. Chi-square or Fisher's exact tests were applied to categorical data, and Wilcoxon rank sum tests to continuous data.
RESULTS: Most participants (90%) experienced moderate-severe menstrual pain. On average, 3 doctors were seen before diagnosis, regardless of age at presentation (range 0-25). Time from symptoms to diagnosis averaged 2y for adolescents and 5y for adults (p<0.001). More adolescents (50%) than adults (33%) reported pain starting at menarche (p=0.002) and nausea accompanying pain (69% vs. 53%, p=0.01). Non-cyclic, general pelvic pain was prevalent. Half of participants reported relief of their general pelvic pain after a bowel movement. Pain interfered with work/school, daily activities, exercise, and sleep to a moderate-extreme degree; difficulties were similar by age at diagnosis.
CONCLUSIONS: Pelvic pain was severe, non-cyclical, and negatively impacted quality of life. At our tertiary care centers, symptoms of endometriosis did not differ between women surgically diagnosed during adolescence compared to those diagnosed as adults. Adolescents had more nausea and symptom onset at menarche. Multi-year delays in diagnosis were common. Clinicians should be aware of these alternate symptom patterns, and include endometriosis in their differential diagnosis for both adolescent and young adult women experiencing non-cyclic pelvic pain and nausea.

PMID: 29247637 [PubMed - as supplied by publisher]

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Psychosocial impacts of hybrid closed-loop systems in the management of diabetes: a review.

Psychosocial impacts of hybrid closed-loop systems in the management of diabetes: a review.

Diabet Med. 2017 Dec 16;:

Authors: Farrington C

Abstract
There is a pressing need for new treatment regimens that enable improved glycaemic control and reduced diabetes self-management burdens. Closed-loop, or artificial pancreas, systems represent one of the most promising avenues in this regard. Closed-loop systems connect wearable continuous glucose monitor (CGM) sensors to smartphone- or tablet-mounted algorithms that process and model CGM data to deliver precise and frequently updated doses of fast-acting insulin (and glucagon in dual-hormone systems) to users via wearable pumps. Recent studies have demonstrated that closed-loop systems offer significant benefit in terms of improved glycaemic control. However, less attention has been paid to the psychosocial impact on users of closed-loop systems. This article reviews recent research on psychosocial aspects of closed-loop usage in light of preceding research on user experience of currently available technologies such as insulin pumps and CGM sensors. The small, but growing body of research in this field reports generally positive user experience and a number of experienced benefits including: reassurance and reduced anxiety, improved sleep and confidence, and 'time off' from diabetes demands. However, these benefits are counterbalanced by important challenges, ranging from variable levels of trust to concerns about physical bulk, technical glitches and difficulties incorporating closed-loop systems into everyday life. Future research should explore psychosocial aspects of closed-loop usage in more diverse groups and with regard to clinicians, as well as users, to ensure that the clinical benefits of closed-loop systems are realized at scale in routine medical care. This article is protected by copyright. All rights reserved.

PMID: 29247547 [PubMed - as supplied by publisher]

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Nocturnal activation of melatonin receptor type 1 signaling modulates diurnal insulin sensitivity via regulation of PI3K activity.

Nocturnal activation of melatonin receptor type 1 signaling modulates diurnal insulin sensitivity via regulation of PI3K activity.

J Pineal Res. 2017 Dec 16;:

Authors: Owino S, Sánchez-Bretaño A, Tchio C, Cecon E, Karamitri A, Dam J, Jockers R, Piccione G, Noh HL, Kim T, Kim JK, Baba K, Tosini G

Abstract
Recent genetic studies have highlighted the potential involvement of melatonin receptor 1 (MT1 ) and melatonin receptor 2 (MT2 ) in the pathogenesis of type 2 diabetes. Here we report that mice lacking MT1 (MT1 KO) tend to accumulate more fat mass than WT mice and exhibit marked systemic insulin resistance. Additional experiments revealed that the main insulin signaling pathway affected by the loss of MT1 was the activation of phosphatidylinositol-3-kinase (PI3K). Transcripts of both catalytic and regulatory subunits of PI3K were strongly down-regulated within MT1 KO mice. Moreover, the suppression of nocturnal melatonin levels within WT mice, by exposing mice to constant light, resulted in impaired PI3K activity and insulin resistance during the day, similar to what was observed in MT1 KO mice. Inversely, administration of melatonin to WT mice exposed to constant light, was sufficient and necessary to restore insulin mediated PI3K activity and insulin sensitivity. Hence our data demonstrate that the activation of MT1 signaling at night modulates insulin sensitivity during the day via the regulation of the PI3K transcription and activity. Lastly we provide evidence that decreased expression of MTNR1A (MT1 ) in the liver of diabetic individuals is associated with poorly controlled diabetes. This article is protected by copyright. All rights reserved.

PMID: 29247541 [PubMed - as supplied by publisher]

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Impact of obstructive sleep apnea on cardiovascular outcomes in patients with acute symptomatic pulmonary embolism: Rationale and methodology for the POPE study.

Impact of obstructive sleep apnea on cardiovascular outcomes in patients with acute symptomatic pulmonary embolism: Rationale and methodology for the POPE study.

Clin Cardiol. 2017 Dec 16;:

Authors: Mañas E, Barbero E, Chiluiza D, García A, Morillo R, Barrios D, Martínez-García MÁ, Albalat A, Cano I, Jiménez D, POPE Investigators

Abstract
In normotensive patients with acute symptomatic pulmonary embolism (PE), the effect of undiagnosed obstructive sleep apnea (OSA) on cardiovascular (CV) outcomes lacks clarity. The Prognostic Significance of Obstructive Sleep Apnea in Patients With Acute Symptomatic Pulmonary Embolism (POPE) study is a multicenter, observational study designed to prospectively assess the prognostic significance of concomitant OSA in hemodynamically stable outpatients with acute symptomatic PE. Adult patients with acute stable PE are eligible. Recruited patients undergo an overnight sleep study using a level III portable diagnostic device within 7 days (and preferably within 48 hours) of diagnosis of PE. The sleep tracings are analyzed by a certified sleep technologist and audited by a sleep physician, both of whom are blinded to other study data. The patients are divided into 2 groups based on apnea-hypopnea index (AHI): OSA (AHI ≥15) and non-OSA (AHI <15) groups. The study uses a composite of PE-related death, CV death, clinical deterioration requiring an escalation of treatment, or nonfatal CV events (recurrent venous thromboembolism, acute myocardial infarction, or stroke) within 30 days after the diagnosis of PE as the primary outcome. The projected sample size of 225 patients will provide 80% power to test the hypothesis that OSA will increase the primary outcome from 7% in the non-OSA group to 20% in the OSA group, with α ≤0.05. The trial results will be important to understand the burden and CV effects of OSA in PE patients.

PMID: 29247523 [PubMed - as supplied by publisher]

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Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

Epilepsia. 2017 Dec 15;:

Authors: Klein P, Dingledine R, Aronica E, Bernard C, Blümcke I, Boison D, Brodie MJ, Brooks-Kayal AR, Engel J, Forcelli PA, Hirsch LJ, Kaminski RM, Klitgaard H, Kobow K, Lowenstein DH, Pearl PL, Pitkänen A, Puhakka N, Rogawski MA, Schmidt D, Sillanpää M, Sloviter RS, Steinhäuser C, Vezzani A, Walker MC, Löscher W

Abstract
The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of specific hypotheses about epileptogenesis and its prevention or modification. Acquired human epilepsies with different etiologies share some features with animal models. We identify these commonalities and discuss their relevance to the development of successful epilepsy prevention or disease modification strategies. Risk factors for developing epilepsy that appear common to multiple acute injury etiologies include intracranial bleeding, disruption of the blood-brain barrier, more severe injury, and early seizures within 1 week of injury. In diverse human epilepsies and animal models, seizures appear to propagate within a limbic or thalamocortical/corticocortical network. Common histopathologic features of epilepsy of diverse and mostly focal origin are microglial activation and astrogliosis, heterotopic neurons in the white matter, loss of neurons, and the presence of inflammatory cellular infiltrates. Astrocytes exhibit smaller K+ conductances and lose gap junction coupling in many animal models as well as in sclerotic hippocampi from temporal lobe epilepsy patients. There is increasing evidence that epilepsy can be prevented or aborted in preclinical animal models of acquired epilepsy by interfering with processes that appear common to multiple acute injury etiologies, for example, in post-status epilepticus models of focal epilepsy by transient treatment with a trkB/PLCγ1 inhibitor, isoflurane, or HMGB1 antibodies and by topical administration of adenosine, in the cortical fluid percussion injury model by focal cooling, and in the albumin posttraumatic epilepsy model by losartan. Preclinical studies further highlight the roles of mTOR1 pathways, JAK-STAT3, IL-1R/TLR4 signaling, and other inflammatory pathways in the genesis or modulation of epilepsy after brain injury. The wealth of commonalities, diversity of molecular targets identified preclinically, and likely multidimensional nature of epileptogenesis argue for a combinatorial strategy in prevention therapy. Going forward, the identification of impending epilepsy biomarkers to allow better patient selection, together with better alignment with multisite preclinical trials in animal models, should guide the clinical testing of new hypotheses for epileptogenesis and its prevention.

PMID: 29247482 [PubMed - as supplied by publisher]

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Asthma Mimickers: Approach to Differential Diagnosis.

Asthma Mimickers: Approach to Differential Diagnosis.

Indian J Pediatr. 2017 Dec 16;:

Authors: Ramamurthy MB

Abstract
The airway of a child can be easily obstructed because of its small size and there are myriad conditions that may obstruct it. Though asthma is the most common condition causing reversible obstruction of the airway; there are a large number of conditions which can obstruct the airway both reversibly and irreversibly. These asthma mimics can present as clinical problems from the neonatal period through adolescence. This article presents an overview of the clinical situations that must be kept in mind when the child presents with subtly unusual clinical features or a deviant course. This is followed by a brief description of the common mimickers along with clinical clues to their diagnosis. Clinicians will need a high index of suspicion for diagnosing these conditions. Prompt recognition and optimal case management and referral will ensure the best outcomes in these children.

PMID: 29247425 [PubMed - as supplied by publisher]

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Patient and physician perspectives on the impact of health-related quality of life in Mexican patients with ANCA-associated vasculitis.

Patient and physician perspectives on the impact of health-related quality of life in Mexican patients with ANCA-associated vasculitis.

Rheumatol Int. 2017 Dec 15;:

Authors: Hinojosa-Azaola A, Jiménez-González A, Alcocer-Castillejos N

Abstract
The objective of this study is to describe aspects of health-related quality of life (HRQOL) in Mexican patients with antineutrophil cytoplasmic-associated vasculitis (AAV). Cross-sectional comparison study includes patients with established AAV and a comparison group with rheumatoid arthritis (RA), chronic kidney disease (CKD), and healthy subjects. Variables considered were: socio-demographic data, comorbidities, laboratory, disease activity, damage, and Physician's and Patient's Global Assessment (PhGA and PtGA). The following measurements were done: Pittsburg sleep quality index, Multidimesional Fatigue Inventory (MFI-20), Hospital Anxiety and Depression Scale, Short Form 36 questionnaire (SF-36), and Health Assessment Questionnaire. 60 patients with AAV were included, median age 54 years, and 60% female. Significant differences were found only in the bodily pain domain of the SF-36 (p = 0.01). Aspects of disease relevant for AAV patients were: fatigue and lack of energy; visual abnormalities; neuropathy; renal impairment; arthritis, and sinusitis. Greater total score on MFI-20 (p < 0.001) and worse PtGA (p = 0.01) were associated with worse physical health. Higher PhGA values were associated with worse physical quality of life (p = 0.01). Greater fatigue score (p = 0.002), greater anxiety-depression score (p = 0.005), and worse PtGA (p = 0.01) were associated with worse mental health quality of life. No differences were found in prevalence of sleep impairment, anxiety, depression, or disability between groups. AAV patients experienced more general and physical fatigue (p < 0.0001), and reduced activity (p = 0.01) than healthy subjects, but similar to RA and CKD patients. Vasculitis has negative effects on patients' physical and mental HRQOL.

PMID: 29247347 [PubMed - as supplied by publisher]

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Decrease of perforin positive CD3+γδ-T cells in patients with obstructive sleep disordered breathing.

Decrease of perforin positive CD3+γδ-T cells in patients with obstructive sleep disordered breathing.

Sleep Breath. 2017 Dec 15;:

Authors: Staats R, Rodrigues R, Barros A, Bacelar-Nicolau L, Aguiar M, Fernandes D, Moreira S, Simões A, Silva-Santos B, Rodrigues JV, Barbara C, de Almeida AB, Moita LF

Abstract
INTRODUCTION: Sleep related breathing disorders (SRBD) cause sleep fragmentation, intermittent hypoxia or a combination of both leading to homeostasis perturbations, including in the immune system. We investigated whether SRBD patients with or without intermittent hypoxia show substantial differences in perforin and granzyme-B positive peripheral blood lymphocytes.
METHODS: A total of 87 subjects were included and distributed as follows: 24 controls (C), 19 patients with respiratory effort related arousals due to increased upper airway resistance (UAR) without hypoxic events, 24 obese patients with obstructive sleep apnea (OSA) (oOSA), and 20 without obesity (noOSA). After polysomnographic recording, we analyzed in fasting blood samples routine hematologic and biochemical parameters and the percentage of lymphocytes containing the proteins perforin and granzyme-B (GrB). Kruskal-Wallis tests and a posteriori multiple comparisons were applied for statistical analysis of results.
RESULTS: Perforin-positive γδ-cells revealed significant differences between groups (p = 0.017), especially between the Control group and the oOSA (p-value = 0.04); the remaining SRBD groups also showed differences from the control (C vs UAR: p = 0.08; C vs noOSA = 0.09), but they did not raise to statistical significance. There were no differences among the SRBD groups. Granzyme-B cells were decreased in SRBD patients, but the differences were not statistically significant. No additional statistical significant result was found in the other investigated lymphocyte subsets.
CONCLUSIONS: Obstructive sleep-disordered breathing is associated with a decrease in perforin-positive CD3+γδ-T cells. Although this finding was detected in lean patients without intermittent hypoxia, the reduction was only statistically significant in obese patients with severe OSA. Because CD3+γδ-T cells play an important role in the control of tumor cells, our findings are directly relevant for the study of the association of OSA and cancer.

PMID: 29247296 [PubMed - as supplied by publisher]

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The predictive value of drug-induced sleep endoscopy for CPAP titration in OSA patients.

The predictive value of drug-induced sleep endoscopy for CPAP titration in OSA patients.

Sleep Breath. 2017 Dec 15;:

Authors: Lan MC, Hsu YB, Lan MY, Huang YC, Kao MC, Huang TT, Chiu TJ, Yang MC

Abstract
PURPOSE: The aim of this study was to identify possible upper airway obstructions causing a higher continuous positive airway pressure (CPAP) titration level, utilizing drug-induced sleep endoscopy (DISE).
METHODS: A total of 76 patients with obstructive sleep apnea (OSA) underwent CPAP titration and DISE. DISE findings were recorded using the VOTE classification system. Polysomnographic (PSG) data, anthropometric variables, and patterns of airway collapse during DISE were analyzed with CPAP titration levels.
RESULTS: A significant association was found between the CPAP titration level and BMI, oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and neck circumference (NC) (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively, by Spearman correlation). Patients with concentric collapse of the velum or lateral oropharyngeal collapse were associated with a significantly higher CPAP titration level (P < 0.001 and P = 0.043, respectively, by nonparametric Mann-Whitney U test; P < 0.001 and P = 0.004, respectively, by Spearman correlation). No significant association was found between the CPAP titration level and any other collapse at the tongue base or epiglottis.
CONCLUSIONS: By analyzing PSG data, anthropometric variables, and DISE results with CPAP titration levels, we can better understand possible mechanisms resulting in a higher CPAP titration level. We believe that the role of DISE can be expanded as a tool to identify the possible anatomical structures that may be corrected by oral appliance therapy or surgical intervention to improve CPAP compliance.

PMID: 29247295 [PubMed - as supplied by publisher]

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Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD): follow-up interviews on patient-centred outcomes.

Salford Lung Study in chronic obstructive pulmonary disease (SLS COPD): follow-up interviews on patient-centred outcomes.

NPJ Prim Care Respir Med. 2017 Dec 15;27(1):66

Authors: Doward L, Svedsater H, Whalley D, Crawford R, Leather D, Lay-Flurrie J, Bosanquet N

Abstract
This study investigated patient perceptions, experiences and management of COPD throughout the SLS COPD study. Follow-up interviews were conducted with 400 patients who completed SLS COPD; a mixed-methods approach was used to collect quantitative and qualitative information. Structured interviews using closed-ended questions were conducted with 360 patients, detailing aspects of background/lifestyle information and COPD. Extended interviews containing open-ended questions on perceptions of COPD and quality of life (QoL) in addition to the closed-ended questions were completed by 40 further patients. Participants also completed the Adherence Starts with Knowledge-12 (ASK-12) and the COPD and Asthma Sleep Impact Scale (CASIS) questionnaire. Quantitative data were analysed descriptively; qualitative data were analysed using qualitative description. The participants (n = 400) were reasonably representative of the SLS COPD population; mean age was 66.2 years. Breathlessness was the most commonly recalled symptom of/associated with COPD (88.5% of patients) and was the symptom that changed the most (improved, 26.8%/worsened, 20.9%) throughout the study. Participants' daily functioning and activities were most affected by symptoms of/associated with COPD, followed by relationships and psychological issues. 66.5% of participants experienced exacerbations, 60.5% of whom reported self-management as their first treatment strategy (taking antibiotics, resting and/or corticosteroids). Qualitative analysis revealed COPD symptoms, breathlessness in particular, to have a significant impact on mobility and in turn QoL. In conclusion, breathlessness was cited in these interviews as the COPD symptom with the greatest impact on participants' daily functioning, activities and self-care. The findings provided significant additional knowledge to the SLS COPD study findings.

PMID: 29247229 [PubMed - in process]

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Prostaglandin D2 metabolite in urine is an index of food allergy.

Prostaglandin D2 metabolite in urine is an index of food allergy.

Sci Rep. 2017 Dec 15;7(1):17687

Authors: Maeda S, Nakamura T, Harada H, Tachibana Y, Aritake K, Shimosawa T, Yatomi Y, Murata T

Abstract
Food allergy is immediate hypersensitive reactions to ingested foods. Since early diagnosis is effective for disease control, development of an objective diagnostic index is required. Using mediator-lipidomics, we found that levels of the urinary prostaglandin D2 (PGD2) metabolite, tetranor-PGDM, reflected the severity of the allergic symptoms and intestinal mast cell hyperplasia in mice. Repeated oral challenges with ovalbumin promoted allergic symptoms in sensitized mice. Particularly, the allergic mice presented with increased numbers of intestinal mast cells, which strongly expressed hematopoietic PGD synthase (H-PGDS). The levels of urinary tetranor-PGDM increased as the disease progressed. Treatment with a mast cell inactivator or an anti-inflammatory steroid attenuated these symptoms and decreased the tetranor-PGDM urinary levels. The levels of urinary tetranor-PGDM did not correlate with the disease severity in murine models of colitis, asthma, or allergic dermatitis. Furthermore, we have shown that urinary levels of tetranor-PGDM were significantly higher in patients with food allergy than those in healthy volunteers and patients with other types of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis. These findings suggest that urinary tetranor-PGDM is a useful diagnostic index of food allergy in both mice and humans.

PMID: 29247205 [PubMed - in process]

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Association of sleep duration and quality with blood lipids: a systematic review and meta-analysis of prospective studies.

Association of sleep duration and quality with blood lipids: a systematic review and meta-analysis of prospective studies.

BMJ Open. 2017 Dec 14;7(12):e018585

Authors: Kruisbrink M, Robertson W, Ji C, Miller MA, Geleijnse JM, Cappuccio FP

Abstract
OBJECTIVES: To assess the longitudinal evidence of the relationships between sleep disturbances (of quantity and quality) and dyslipidaemia in the general population and to quantify such relationships.
SETTING: Systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
METHODS: We performed a systematic search of PubMed and Embase (up to 9 September 2017), complemented with manual searches, of prospective population studies describing the association between sleep duration and quality and the incidence of dyslipidaemias. Relative risks (95% CIs) were extracted and pooled using a random effects model. Subgroup analyses by lipid type were performed. Heterogeneity and publication bias were also assessed. Quality was assessed with Downs and Black score.
PARTICIPANTS: Studies were included if they were prospective, had measured sleep quantity and/or quality at baseline and either incident cases of dyslipidaemia or changes in blood lipid fractions assessed prospectively.
PRIMARY OUTCOME MEASURES: Incidence of dyslipidaemia and changes in lipid fractions. Dyslipidaemia was defined as a high total cholesterol, triglycerides, low-density lipoprotein cholesterol or low high-density lipoprotein cholesterol compared with the reference group.
RESULTS: Thirteen studies were identified (eight using sleep duration, four sleep quality and one both). There was heterogeneity in the sleep quality aspects and types of lipids assessed. Classification of sleep duration (per hour/groups) also varied widely. In the pooled analysis of sleep duration (6 studies, 16 cohort samples; 30 033 participants; follow-up 2.6-10 years), short sleep was associated with a risk of 1.01 (95% CI 0.93 to 1.10) of developing dyslipidaemia, with moderate heterogeneity (I2=56%, P=0.003) and publication bias (P=0.035). Long sleep was associated with a risk of 0.98 (95% CI 0.87 to 1.10) for dyslipidaemia, with heterogeneity (I2=63%, P<0.001) and no significant publication bias (P=0.248).
CONCLUSION: The present analysis was unable to find supportive evidence of a significant relationship between sleep duration and the development of dyslipidaemia. However, heterogeneity and small number of studies limit the interpretation.
PROSPERO REGISTRATION NUMBER: CRD42016045242.

PMID: 29247105 [PubMed - in process]

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Prospective study of restless legs syndrome and total and cardiovascular mortality among women.

Prospective study of restless legs syndrome and total and cardiovascular mortality among women.

Neurology. 2017 Dec 15;:

Authors: Li Y, Li Y, Winkelman JW, Walters AS, Han J, Hu FB, Gao X

Abstract
OBJECTIVE: We prospectively examined whether women with physician-diagnosed restless legs syndrome (RLS) had a higher risk of total and cardiovascular disease (CVD) mortality relative to those without RLS.
METHODS: The current study included 57,417 women (mean age 67 years) from the Nurses' Health Study without cancer, renal failure, and CVD at baseline (2002). Main outcomes were total and CVD mortality. We used the Cox proportional hazards model to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CVD-specific mortality based on RLS status, adjusting for age, presence of major chronic diseases, and other potential confounders.
RESULTS: We documented 6,448 deaths during 10 years of follow-up. We did not observe a significant association between presence of physician-diagnosed RLS and high risk of total mortality (adjusted HR 1.15, 95% CI 0.98-1.34). When cause-specific mortality was studied, participants with RLS had a significantly higher risk of CVD mortality (adjusted HR 1.43, 95% CI 1.02-2.00) relative to those without RLS after adjustment for potential confounders. Longer duration of RLS diagnosis was significantly associated with a higher risk of CVD mortality (p for trend = 0.04). Excluding participants with common RLS comorbidities strengthened the association between RLS and total (adjusted HR 1.43, 95% CI 1.03-1.97) and CVD mortality (adjusted HR 2.27, 95% CI 1.21-4.28). However, we did not find a significant association between RLS and mortality due to cancer and other causes.
CONCLUSIONS: Women with RLS had a higher CVD mortality rate, which may not be fully explained by common co-occurring disorders of RLS.

PMID: 29247069 [PubMed - as supplied by publisher]

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Sleep restriction undermines cardiovascular adaptation during stress, contingent on emotional stability.

Sleep restriction undermines cardiovascular adaptation during stress, contingent on emotional stability.

Biol Psychol. 2017 Dec 12;132:125-132

Authors: Lü W, Hughes BM, Howard S, James JE

Abstract
Sleep loss is associated with increased cardiovascular disease, but physiological mechanisms accounting for this relationship are largely unknown. One possible mechanism is that sleep restriction exerts effects on cardiovascular stress responses, and that these effects vary between individuals. Emotional stability (ES) is a personality trait pertinent to sleep restriction and stress responding. However, no study to date has explored how ES and sleep-restriction interactively affect cardiovascular stress responses or processes of adaptation during stress. The present study sought to investigate the association between ES and impact of sleep restriction on cardiovascular function during stress, with particular regard to the trajectory of cardiovascular function change across time. Ninety female university students completed a laboratory vigilance stress task while undergoing continuous cardiovascular (SBP, DBP, HR, SV, CO, TPR) monitoring, after either a night of partial sleep restriction (40% of habitual sleep duration) or a full night's rest. Individuals high in ES showed stable and adaptive cardiovascular (SBP, SV, CO) responses throughout stress exposure, regardless of sleep. In contrast, individuals low in ES exhibited cardiovascular adaptation during stress exposure while rested, but disrupted adaption while sleep-restricted. These findings suggest that sleep-restriction undermines healthful cardiovascular adaptation to stress for individuals low in ES.

PMID: 29246812 [PubMed - as supplied by publisher]

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Πληροφορίες

Τρίτη 19 Δεκεμβρίου 2017

Abstract

Abstract

Background

Material and Methods

Results

Conclusion

Δημοφιλείς αναρτήσεις