Head and Neck Diseases by Alexandros G.Sfakianakis: 01/27/18

Σάββατο 27 Ιανουαρίου 2018

Corrigendum to “Hodgkin Lymphoma Cell Lines Are Characterized by a Specific miRNA Expression Profile.” Neoplasia 2009, Feb;11(2):167-176

Publication date: February 2018
Source:Neoplasia, Volume 20, Issue 2
Author(s): J.H. Gibcus, L.P. Tan, G. Harms, R.N. Schakel, D. de Jong, T. Blokzijl, P. Möller, S. Poppema, B.J. Kroesen, A. van den Berg

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c-RAF Ablation Induces Regression of Advanced Kras/Trp53 Mutant Lung Adenocarcinomas by a Mechanism Independent of MAPK Signaling

Publication date: Available online 27 January 2018
Source:Cancer Cell
Author(s): Manuel Sanclemente, Sarah Francoz, Laura Esteban-Burgos, Emilie Bousquet-Mur, Magdolna Djurec, Pedro P. Lopez-Casas, Manuel Hidalgo, Carmen Guerra, Matthias Drosten, Monica Musteanu, Mariano Barbacid
A quarter of all solid tumors harbor KRAS oncogenes. Yet, no selective drugs have been approved to treat these malignancies. Genetic interrogation of the MAPK pathway revealed that systemic ablation of MEK or ERK kinases in adult mice prevent tumor development but are unacceptably toxic. Here, we demonstrate that ablation of c-RAF expression in advanced tumors driven by Kras^G12V/Trp53 mutations leads to significant tumor regression with no detectable appearance of resistance mechanisms. Tumor regression results from massive apoptosis. Importantly, systemic abrogation of c-RAF expression does not inhibit canonical MAPK signaling, hence, resulting in limited toxicities. These results are of significant relevance for the design of therapeutic strategies to treat K-RAS mutant cancers.

Graphical abstract

Teaser

Sanclemente et al. generate oncogenic Kras mice that allow inducible deletion of Raf1, encoding c-RAF, and/or Braf in established Kras^G12V or Kras^G12V;Trp53^−/− lung tumors. They show that systemic c-RAF ablation has limited toxicity and leads to significant tumor regression without having an impact on MAPK activity.

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Tumor Architecture and Notch Signaling Modulate Drug Response in Basal Cell Carcinoma

Publication date: Available online 27 January 2018
Source:Cancer Cell
Author(s): Markus Eberl, Doris Mangelberger, Jacob B. Swanson, Monique E. Verhaegen, Paul W. Harms, Marcus L. Frohm, Andrzej A. Dlugosz, Sunny Y. Wong
Hedgehog (Hh) pathway inhibitors such as vismodegib are highly effective for treating basal cell carcinoma (BCC); however, residual tumor cells frequently persist and regenerate the primary tumor upon drug discontinuation. Here, we show that BCCs are organized into two molecularly and functionally distinct compartments. Whereas interior Hh⁺/Notch⁺ suprabasal cells undergo apoptosis in response to vismodegib, peripheral Hh⁺⁺⁺/Notch⁻ basal cells survive throughout treatment. Inhibiting Notch specifically promotes tumor persistence without causing drug resistance, while activating Notch is sufficient to regress already established lesions. Altogether, these findings suggest that the three-dimensional architecture of BCCs establishes a natural hierarchy of drug response in the tumor and that this hierarchy can be overcome, for better or worse, by modulating Notch.

Graphical abstract

Teaser

Eberl et al. show that in mouse basal cell carcinoma models, interior Hh⁺/Notch⁺ suprabasal cells undergo apoptosis in response to vismodegib, whereas peripheral Hh⁺⁺⁺/Notch⁻ basal cells survive throughout treatment. Modulating Notch overcomes the drug response hierarchy established by tumor architecture.

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Graphene Oxide Elicits Membrane Lipid Changes and Neutrophil Extracellular Trap Formation

Publication date: Available online 27 January 2018
Source:Chem
Author(s): Sourav P. Mukherjee, Beatrice Lazzaretto, Kjell Hultenby, Leon Newman, Artur F. Rodrigues, Neus Lozano, Kostas Kostarelos, Per Malmberg, Bengt Fadeel
Understanding the biological interactions of graphene-based materials is important for the safe use of these materials. Previous studies have explored the interaction between graphene oxide (GO) and macrophages but not the impact of GO on neutrophils, key cells of the immune system. Here, we synthesized GO sheets with differing lateral dimensions and showed by using an array of analytical and imaging techniques, including transmission and scanning electron microscopy, confocal microscopy, and time-of-flight secondary ion mass spectroscopy (ToF-SIMS), that GO elicited the formation of neutrophil extracellular traps (NETs). ToF-SIMS revealed pronounced perturbations of plasma membrane lipids, including a decrease in cholesterol and increased levels of oxidized cholesterol species. The induction of NETs was size dependent and associated with the production of mitochondrial reactive oxygen species and calcium influx. Importantly, antioxidant treatment reduced the production of NETs. These studies provide evidence that a previously undescribed biological effect of GO manifests through direct effects on membrane lipids.

Graphical abstract

Teaser

Graphene oxide (GO) is a promising material for a variety of biomedical and other applications. The increasing use of GO necessitates careful assessment of potential health hazards. Using primary neutrophils as a model, Mukherjee et al. show that GO elicits neutrophil extracellular traps. Furthermore, by using ToF-SIMS, the authors noted pronounced perturbations of plasma membrane lipids in cells exposed to GO.

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Adverse Prognostic Factors of Advanced Esophageal Cancer in Patients Undergoing Induction Therapy with Docetaxel, Cisplatin and 5-Fluorouracil

Background/Aim: The purpose of this study was to identify adverse prognostic factors for patients with advanced esophageal cancer undergoing chemotherapy with docetaxel, cisplatin and 5-fluorouracil (DCF). Patients and Methods: The study cohort comprised of 45 patients with advanced esophageal cancer who underwent induction DCF therapy followed by esophagectomy or chemoradiotherapy. Treatment outcomes and factors affecting early recurrence and death were analyzed. Results: Overall 3-year survival was 61.4%, and 3-year disease-free survival was 44.7%. Clinically evident lymph node metastasis and clinical stage were associated with recurrence within 1 year and death within 2 years. Low maximum standardized uptake value (SUV_max) after induction DCF therapy and small decreases in SUV_max from pre- to post-DCF therapy were also predictors of recurrence and poor prognosis. Conclusion: Induction DCF therapy may be ineffective for advanced-stage esophageal cancer and clinical lymph node metastasis (≥N2, ≥stage IIIB). Moreover, small decreases in SUV_max DCF therapy are associated with early disease relapse and death.

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Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis

Background: In ulcerative colitis (UC), the majority of colorectal carcinomas (CRC) arise in the vast colorectal mucosal domain built with mucus-producing goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny, spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the four reported cases of colonic carcinoma developing in GALT mucosa in UC, searching for possible precursor lesions connected with the evolution of these tumours. Materials and Methods: The clinical history, age, gender, endoscopic descriptions, and the pathology (localization, gross and histological descriptions of the luminal surface) of the four UC-GALT carcinomas reported in the literature were reviewed. Results: The luminal surface in three out of the four carcinomas revealed conventional (tubular/villous) adenomas or high-grade dysplasia. All four UC-GALT-carcinomas were detected at an early stage (T1N0). Conclusion: GALT carcinomas do occur, albeit infrequently, in patients with UC. The finding that three out of the four GALT carcinomas on record were covered by conventional adenomas or by high-grade dysplasia strongly suggests that non-invasive conventional neoplasias might often precede GALT carcinomas in UC.

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Tandem Affinity Purification and Nano HPLC-ESI-MS/MS Reveal Binding of Vitamin D Receptor to p53 and other New Interaction Partners in HEK 293T Cells

While nuclear cofactors that contribute to vitamin D receptor (VDR)-mediated gene transcription, including retinoid X receptors, nuclear co-activators and co-repressors, have been extensively investigated, little is known about cytoplasmic VDR-binding partners and the physiological relevance of their interaction. To gain new insight into this topic, we isolated whole-cell protein extracts of 1,25-dihydroxyvitamin D₃ stimulated and UV-B-irradiated vs. non-irradiated HEK 293T cells transfected with a plasmid called pURB VDR C-Term TAP tag. VDR complex was purified by tandem affinity purification (TAP). The nuclear tumor-suppressor protein p53 and its negative regulator novel INHAT repressor (NIR), in addition to 43 other nuclear or cytoplasmatic VDR binding partners, were identified using nano high-performance liquid chromatography–electrospray ionization tandem mass spectrometric analysis. VDR binding to p53 was confirmed by western blot analysis. Future studies are required to further elucidate the functional significance of these interactions.

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Effects of Combined Treatment with Vitamin D and COX2 Inhibitors on Breast Cancer Cell Lines

Background: Vitamin D is known for its anticancer potential. Prostaglandin E₂ (PGE₂) is a proliferative and inflammation-activating agent. The production of PGE₂ is dependent on the activity of cyclooxygenase-2 (COX2). A link between vitamin D and PGE₂ metabolism was shown recently. Materials and Methods: In MDA-MB-231 and MCF-7 breast cancer cell lines, we investigated the influence of calcitriol and the COX2 inhibitor celecoxib on cell growth via the MTT test, as well as on the protein and mRNA expression of COX2 using western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Results: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX2 inhibitor celecoxib and even more strongly by their combination. Moreover, calcitriol inhibited COX2 protein expression in MDA-MB-231 cells, as well as COX2 mRNA expression in both cell lines. Conclusion: The combination of calcitriol and celecoxib demonstrated a synergistic growth-inhibitory effect in breast cancer cell lines.

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Partial Body UV Exposure in Chronic Kidney Disease and Extrarenal Vitamin D Metabolism

Background/Aim: Exposure of the skin to sunshine is the major natural source of vitamin D. In order to imitate this natural production of vitamin D for patients with chronic kidney disease, hemodialysis patients were exposed three times a week to radiation of the front part of both legs to normalize the vitamin D status. Patients and Methods: Partial body UVB irradiation was performed during the routine dialysis session. Twenty-two patients took part, with a mean age of 61.7 (range=35-81) years. Results: Serum levels of 25(OH)D₃ and 1,25(OH)₂D₃ increased into the mid normal range. Intact parathyroid hormone decreased by 25% and osteocalcin by 45%. 24-Hour blood-pressure monitoring demonstrated decreases in systolic and diastolic blood pressure. Conclusion: Partial body exposure to UVB radiation normalized not only the serum level of 25(OH)D₃, but also that of 1,25(OH)₂D₃, which resulted in a significant decrease in parathyroid hormone, osteocalcin levels, and also in blood pressure. Sunshine imitating UVB exposure utilizes the capacity of the skin to convert extrarenally vitamin D₃ to 25(OH)D₃ and 1,25(OH)₂D₃.

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Vitamin D Status, Supplementation and Cardiovascular Disease

This review was conducted to assess the dose–response relationship between vitamin D and cardiovascular disease (CVD) outcomes in humans: Prospective cohort studies indicate a multivariable-adjusted non-linear increase in CVD events at levels of circulating 25-hydroxyvitamin D [25(OH)D] of less than 50 nmol/l. However, Mendelian randomization studies do not support these findings. Although meta-analyses of randomized controlled trials (RCTs) do not rule out small beneficial vitamin D effects on surrogate parameters of CVD risk, such as arterial stiffness, at vitamin D doses equivalent to 1,000-5,333 IU daily, other meta-analyses of RCTs show no reduction in CVD events by vitamin D supplementation. Notably, some cohort studies and a recent RCT provide evidence for harmful effects of vitamin D on CVD outcomes at 25(OH)D levels in excess of 100 nmol/l. In conclusion, more studies in individuals with a deficient 25(OH)D level (i.e. <30 nmol/l) are needed, but caution is necessary regarding supplementation with vitamin D doses achieving a 25(OH)D level which exceeds 100 nmol/l.

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The Winding Path Towards an Inverse Relationship Between Sun Exposure and All-cause Mortality

For a long time, skin cancer has been known to be related to extensive UV exposure. New emerging data have, however, shown low UV exposure/low vitamin D levels to be related to increased mortality rate due to skin cancer. In addition, low sun exposure habits in regions of low solar intensity have been shown to be a major risk factor for all-cause mortality in the same range as that for smoking. This is mainly due to lower all-cause mortality due to cardiovascular disease (CVD) and non-CVD/non-cancer disease among women with active sun exposure. Women with active sun exposure habits were estimated to have a 1- to 2-year longer life-expectancy during the Melanoma in Southern Sweden study interval. These findings are in line with those to be expected from an evolutionary perspective and research findings, but in opposition to present guidelines and recommendations.

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Solarium Use and Risk for Malignant Melanoma: Meta-analysis and Evidence-based Medicine Systematic Review

Background: There is an ongoing debate whether solarium use (indoor tanning/artificial UV) may increase the risk for primary cutaneous malignant melanoma. Aim: A systematic literature search was conducted using MEDLINE and ISI Web of Science. Included studies were critically assessed regarding their risk of bias, and methodological shortcomings. Levels of evidence and grades of recommendation were determined according to guidelines of the Oxford Centre for Evidence-Based Medicine. Summary risk estimates and 95% confidence intervals for four different outcomes (ever exposure, exposure at younger age, high/low exposure vs. non-exposure) were derived from random-effects meta-analyses to account for possible heterogeneity across studies. Results: Two cohort and twenty-nine case–control studies were eligible. Overall, quality of included studies was poor as a result of severe limitations, including possible recall and selection bias, and due to lack of interventional trials. Summary risk estimates suggested a weak association (odds ratio (OR)=1.19, 95% confidence interval (CI)=1.04-1.35, p=0.009) for ever-exposure to UV radiation from a solarium with melanoma risk. However, sensitivity analyses did not show an association for studies from Europe (OR=1.10; 95%CI=0.95-1.27, p=0.218), studies with low risk of bias (OR=1.15; 95%CI=0.94-1.41, p=0.179), and studies conducted after 1990 (OR 1.09; 95%CI=0.93-1.29, p=0.295). Moreover, moderate associations were found for first exposure to UV radiation from a solarium at younger age (<25 years) and high exposure (>10 sessions in lifetime) with melanoma risk. However, for all outcomes analyzed, overall study quality and resulting levels of evidence (3a–) and grades of recommendation (D) were low due to lack of interventional studies and severe limitations including unobserved or unrecorded confounding. Conclusion: Current scientific knowledge is mainly based on observational studies with poor quality data, which report associations but do not prove causality. At present, there is no convincing evidence that moderate/responsible solarium use increases melanoma risk.

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Xeroderma Pigmentosum - Facts and Perspectives

Ultraviolet (UV)-induced DNA lesions are almost exclusively removed by the nucleotide excision repair (NER) pathway, which is essential for prevention of skin cancer development. Patients with xeroderma pigmentosum (XP) are extremely sun sensitive due to a genetic defect in components of the NER cascade. They present with first signs of premature skin aging at an early age, with a considerably increased risk of developing UV-induced skin cancer. XP belongs to the group of DNA repair defective disorders that are mainly diagnosed in the clinic and in hindsight confirmed at the molecular level. Unfortunately, there are no causative treatment options for this rare, autosomal-recessive disorder, emphasizing the importance of an early diagnosis. Subsequently, UV-protective measures such as the reduction of exposure to environmental UV and regular skin cancer screenings should be undertaken to substantially improve prognosis as well as the disease course.

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Photocarcinogenesis and Skin Cancer Prevention Strategies: An Update

UV radiation is acknowledged as the primary cause of photocarcinogenesis and therefore contributes to the development of skin cancer entities such as squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. Typical DNA photoproducts and indirect DNA damage caused by reactive oxygen species are the result of UV radiation. UV-induced DNA damage is repaired by nucleotide excision repair, which consequently counteracts the development of mutations and skin carcinogenesis. Tumour-suppressor genes are inactivated by mutation and growth-promoting pathways are activated leading to disruption of cell-cycle progression. Depending on the skin cancer entity, some genes are more frequently affected than others. In BCC mutations in Patched or Smoothened are common and affect the Sonic hedgehog pathway. In SCC, cell regulator protein p53 (TP53) mutations are prevalent, as well as mutations of the epidermal growth factor receptor (EGFR), cyclin-dependent kinase 2A (CDKN2A), Rat sarcoma (RAS), or the tyrosine kinase Fyn (FYN). UV-induced mutations in TP53 and CDKN2A are frequent in melanoma. UV-induced inflammatory processes also facilitate photocarcinogenesis. Recent studies showed a connection between photocarcinogenesis and citrus consumption, phytochemicals, alcohol consumption, hormone replacement therapy, as well as oral contraceptive use. Preventative measures include adequate use of sun protection and skin cancer screening at regular intervals, as well as the use of chemopreventative agents.

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The Impact of UV-dose, Body Surface Area Exposed and Other Factors on Cutaneous Vitamin D Synthesis Measured as Serum 25(OH)D Concentration: Systematic Review and Meta-analysis

Background/Aim: To optimize public health campaigns concerning UV exposure, it is important to characterize factors that influence UV-induced cutaneous vitamin D production. This systematic review and meta-analysis investigated the impact of different individual and environmental factors including exposed body surface area (BSA), UVB dose and vitamin D status, on serum 25(OH)D concentration. Materials and Methods: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses, and Meta-analysis of Observational studies in Epidemiology guidelines, a systematic literature search was conducted (MEDLINE; 01/1960-07/2016) investigating the impact of these factors on vitamin D status after artificial UV exposure as main outcome measure. Summary mean differences [and 95% confidence interval (CI)] were derived from random-effects meta-analysis to account for possible heterogeneity across studies. Meta-regression was conducted to account for impact of UVB dose, baseline 25(OH)D level and BSA. Results: We identified 15 studies, with an estimated mean 25(OH)D rise per standard erythema dose (SED) of 0.19 nmol/l (95% CI 0.11-0.26 nmol/l). Results from meta-regression suggest a significant impact of UV dose and baseline 25(OH)D concentration on serum 25(OH)D level (p<0.01). Single UVB doses between 0.75 and 3 SED resulted in the highest rise of serum 25(OH)D per dose unit. BSA exposed had a smaller, non-proportional, not significant impact. Partial BSA exposure resulted in relatively higher rise compared to whole-body exposure (e.g. exposure of face and hands caused an 8-fold higher rise of serum 25(OH)D concentration/SED/1% BSA compared to whole-body exposure). Our findings support previous reports, estimating that the half-life of serum 25(OH)D varies depending on different factors. Conclusion: Our results indicate that partial BSA exposure (e.g. 10%) with moderate UV doses (e.g. 1 SED) is effective in generating or maintaining a healthy vitamin D status. However, due to limitations that include possible confounding factors such as skin type, which could not be considered, these findings should be interpreted with caution.

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A Review of the Evidence Supporting the Vitamin D-Cancer Prevention Hypothesis in 2017

The vitamin D–cancer prevention hypothesis has been evaluated through several types of studies, including geographical ecological studies related to indices of solar ultraviolet-B (UVB) dose (the primary source of vitamin D for most people), observational studies related to UVB exposure or serum 25-hydroxyvitamin D [25(OH)D] concentrations, laboratory studies of mechanisms, and clinical trials. Each approach has strengths and limitations. Ecological studies indirectly measure vitamin D production and incorporate the assumption that vitamin D mediates the effect of UVB exposure. Findings from observational studies with long follow-up times are affected by changing 25(OH)D concentrations over time. Most clinical trials have been poorly designed and conducted, based largely on guidelines for pharmaceutical drugs rather than on nutrients. However, three clinical trials do support the hypothesis. In general, the totality of the evidence, as evaluated using Hill's criteria for causality in a biological system, supports the vitamin D–cancer prevention hypothesis.

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Vitamin D: Current Guidelines and Future Outlook

Vitamin D is of public health interest because its deficiency is common and is associated with musculoskeletal diseases, as well as extraskeletal diseases, such as cancer, cardiovascular diseases, and infections. Several health authorities have reviewed the existing literature and published nutritional vitamin D guidelines for the general population. There was a wide consensus that serum 25-hydroxyvitamin D [25(OH)D] concentration should be used to assess vitamin D status and intake, and that musculoskeletal, and not extraskeletal, effects of vitamin D should be the basis for nutritional vitamin D guidelines. Recommended target levels for 25(OH)D range from 25 to 50 nmol/l (10 to 20 ng/ml), corresponding to a vitamin D intake of 400 to 800 International Units (10 to 20 μg) per day. It is of concern that significant sections of the general population do not meet these recommended vitamin D levels. This definitely requires action from a public health perspective.

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Fibrinogen Levels Are Associated with Lymph Node Involvement and Overall Survival in Gastric Cancer Patients

Background/Aim: Combination of perioperative chemotherapy with gastrectomy with D2 lymphadenectomy improves long-term survival in patients with gastric cancer. The aim of this study was to investigate the predictive value of preoperative levels of CRP, albumin, fibrinogen, neutrophil-to-lymphocyte ratio and routinely used tumor markers (CEA, CA 19-9, CA 72-4) for lymph node involvement. Materials and Methods: This retrospective study was conducted in 136 patients who underwent surgery between 2007 and 2015. Bivariable and multivariable analyses were performed in order to identify important characteristics associated with the risk of lymph node involvement. Kaplan-Meier survival curves and log-rank tests were used to compare overall survival. Results: Lymph node involvement was significantly affected by preoperative fibrinogen (p=0.008) and albumin (p=0.023). Poor clinical condition, T and N staging and fibrinogen level above 3.5 g/l were significantly associated with worse overall survival. Conclusion: Preoperative fibrinogen and albumin levels are significantly associated with lymphoid metastases in patients with gastric cancer.

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A Critical Appraisal of the Recent Reports on Sunbeds from the European Commission's Scientific Committee on Health, Environmental and Emerging Risks and from the World Health Organization

The European Commission's Scientific Committee on Health, Environmental and Emerging Risks and the World Health Organization recently published reports which concluded that a large proportion of melanoma and non-melanoma skin cancer is attributable to sunbed use, and that there is no need to use sunbeds as there are no health benefits and they are not needed to achieve an optimal vitamin D level. The overall conclusion from both bodies was that there is no safe limit for UV irradiance from sunbeds. We are, however, deeply concerned that these assessments appear to be based on an incomplete, unbalanced and non-critical evaluation of the literature. Therefore, we rebut these conclusions by addressing the incomplete analysis of the adverse health effects of UV and sunbed exposure (what is 'safe'?) and the censored representation of beneficial effects, not only but especially from vitamin D production. The stance taken by both agencies is not sufficiently supported by the data and in particular, current scientific knowledge does not support the conclusion sunbed use increases melanoma risk.

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Image Quality Assessment of 2D versus 3D T2WI and Evaluation of Ultra-high b-Value (b=2,000 mm/s2) DWI for Response Assessment in Rectal Cancer

Aim: The purpose of this IRB-approved, retrospective study was to compare image quality between 2D and high-resolution 3D, T2-weighted (T2WI) magnetic resonance imaging (MRI) sequences and to investigate the additional value of ultra-high b-value diffusion-weighted imaging (DWI; b=2,000 mm/s²) for both rectal cancer staging and evaluating treatment response. Materials and Methods: From 12 February to 24 August 2016, 26 consecutive patients (22 males, four females; mean age: 61.9±14.0 years) with histologically-proven rectal cancer. In total 31 examinations [12 prior to and 19 after chemoradiation (CRT)] were included. The patients underwent pelvic MRI on a 3.0-T scanner (Magnetom Skyra, Erlangen, Germany). Three radiologists (3, 4, and 5 years of experience in MRI, respectively) independently assessed all images and rated the image quality of DWI (b=800 mm/s²), apparent diffusion coefficient map, DWI (b=2,000 mm/s²), 3D sagittal T2WI, 3D axial T2WI, 2D sagittal T2WI, and 2D axial T2WI of each patient, respectively. In addition, signal intensity ratios (SIR) were calculated between rectal cancer and obturator internus muscle (background) in all patients after CRT on DWI (b=2,000 mm/s²) and correlated with histopathological regression grade (RG). Results: Tumor delineation was significantly better by 2D T2WI than 3D T2WI both before and after CRT (before CRT: Z=–3.2, p=0.02; after CRT: Z=–4.408, p<0.001; all: Z=–5.192; p<0.001) and was the preferred method, although image quality ratings were not significantly different (3D sagittal: 4.00±0.48; 2D sagittal: 4.03±0.34, p=0.713; 3D axial: 3.85±0.61, 2D axial: 3.78±0.64, p=0.537). Independent t-test showed significantly higher SIR between those with RG 1 or 2 (moderate response: mean score=2.02) and those with RG 3+4 (good response: mean score=0.8) (t=3.044, p=0.011). In those with RG 4 (complete response), SIR of b2000 was 0.946 compared to a 1.41 average of the whole cohort. In two patients, tumor was invisible on b2000 following CRT (RG 3 and 4, respectively). Interobserver agreement was mostly good (≥0.6) regarding image quality assessment, except for poor agreement (=0.4) in DWI (b2000) between the two less-experienced readers. Conclusion: In conclusion, 3D T2WI might be useful for evaluating response to neoadjuvant therapy in a comprehensive, cost-effective protocol, where 2D imaging seems to be preferable. In addition, DWI (b2000) may be beneficial in assessing both the primary and the residual tumor after CRT in rectal cancer and SIR may be helpful in assessing response to CRT.

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Prognostic Significance of NSCLC and Response to EGFR-TKIs of EGFR-Mutated NSCLC Based on PD-L1 Expression

Background/Aim: Recent clinical trials have shown that immune checkpoint blockades that target either PD-1 or PD-L1 yield remarkable responses in a subgroup of patients with non-small cell lung cancer (NSCLC). Materials and Methods: We retrospectively examined, by immunohistochemical analysis, 211 NSCLC samples. Using 32 independent samples, we also evaluated PD-L1 expression in NSCLC patients with EGFR gene mutations treated by EGFR-TKIs. Results: Overall survival of PD-L1-positive stages I-III NSCLC and stage I NSCLC and stages I-III squamous cell carcinoma (SQ) were significantly shorter than those of PD-L1-negative NSCLC (p<0.01 and p=0.02 and p=0.01, respectively). In stage I NSCLC and stages I-III SQ, PD-L1 expression was found to be independent predictor of death after multivariate analysis. Response to EGFR-TKIs was not significantly different between PD-L1-positive and PD-L1-negative NSCLC patients with EGFR mutations. Conclusion: PD-L1 expression was a significant independent predictor of poor outcome in NSCLC patients.

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Intensity and Pattern of Enhancement on CESM: Prognostic Significance and its Relation to Expression of Podoplanin in Tumor Stroma - A Preliminary Report

Background/Aim: It is possible that the degree of enhancement on contrast-enhanced spectral mammography (CESM), a new diagnostic method, might provide prognostic information for breast cancer patients. Therefore, in a group of 82 breast cancer patients, we analyzed the prognostic significance of degree and pattern of enhancement on CESM as well as its relation to: (a) breast cancer immunophenotype (based on ER/PR/HER2 status) (b) podoplanin expression in cancer stroma (lymphatic vessel density plus podoplanin-positivity of cancer-associated fibroblasts), and (c) other histological parameters. Materials and Methods: For each tumor the intensity of enhancement on CESM was qualitatively assessed as strong or weak/medium, while the pattern – as homogenous and heterogenous. Results: Herein we report, for the first time, that strong and heterogenous enhancement on CESM was related to unfavorable disease-free survival of breast cancer patients (p=0.005). Moreover, the strong enhancement was more frequent in large and node-positive tumors (pT>1, pN>0) (p=0.002), as well as in carcinomas with podoplanin-sparse stroma (p=0.008). Conclusion: Intensity and pattern of enhancement on CESM might provide (together with the results of other diagnostic imaging methods) not only the confirmation of presence or absence of tumor, but also prognostic information.

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Applying the Ts of referred otalgia to a cohort of 226 patients

Abstract

Referred or secondary otalgia is the complaint of ear pain arising from pathology of non-otologic locations with which the ear shares common neural pathways. The pain can present in various degrees of intensity and characteristics while severity is not proportional to the seriousness of the underlying cause^1,2.

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Superiorly Curved Scalp Incision for Implantation of Magnetic Transcutaneous Bone Conduction Devices: Multicentre Experience of 60 patients

Abstract

The authors describe the use of superiorly curved scalp Incision for Implantation of Magnetic Transcutaneous Bone Conduction Devices

They describe a new technical aspect to minimise numbness issues in a series of 60 patients from two tertiary referral centres.

An inferiorly-based flap design will help to preserve branches of the great auricular and lesser occipital nerves, which normally sacrificed with the original technique.

Superiorly curved scalp Incision will be suitable for subsequent retroauricular incision that is used in auricular reconstruction in microtia patients.

These easily reproducible technical modification comfortable be used safely for Implantation of Magnetic Transcutaneous Bone Conduction Devices, especially patients with auricular dysplasia where auricular reconstruction is planned

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Intracranial suppurative complications of ear, nose and throat infections: a single-centre cohort study of 65 patients

Abstract

In the Picardie region of northern France, the prevalence of intracranial suppurative complications (particularly empyema) of ear, nose and throat infections seems to have increased over the last 10 to 15 years.

Three possible reasons for the increased incidence in this region are the inappropriate use of antibiotics, low socioeconomic status, and poor access to high-quality healthcare.

Intracranial complications affect both sexes and all ages.

If a patient suffering from sinusitis or (especially) otitis media complains of headache, the possible presence of an intracranial suppurative complication must be always be considered and should prompt immediate medical imaging (a cranial CT scan and MRI) for confirmation of the diagnosis.

Early diagnosis and multidisciplinary pharmacological and surgical management (focused on the intracranial complication) should enable complete recovery in more than three quarters of these cases

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A Retrospective Case Series of 1773 patients

Abstract

A peritonsillar abscess (PTA) is a collection of pus between the pharyngeal musculature and palatine tonsil capsule. It is the most common deep space infection of the head and neck region and the most common indication for acute ORL hospital admission ¹. Causative microorganisms include Gram negative rods, Gram positive cocci and anaerobes ². Usual treatment is aspiration +/- incision and drainage of PTA, but there is practice variation based on geographical location ³.

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Loop-Mediated Isothermal Amplification test for the diagnosis of pertussis in Japan

Publication date: 1 February 2018
Source:Vaccine, Volume 36, Issue 6
Author(s): Nobutoshi Nawa

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Response to the letter by Dr. Nawa, Loop-Mediated isothermal amplification test for the diagnosis of pertussis in Japan

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Publication date: 1 February 2018
Source:Vaccine, Volume 36, Issue 6
Author(s): Hideyuki Ikematsu, Naoki Kawai, Shigehiro Yajima

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Editorial Board/Aims and Scope

Publication date: 1 February 2018
Source:Vaccine, Volume 36, Issue 6

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Self-assembling protein nanoparticles with built-in flagellin domains increases protective efficacy of a Plasmodium falciparum based vaccine

Publication date: 1 February 2018
Source:Vaccine, Volume 36, Issue 6
Author(s): Stephen A. Kaba, Christopher P. Karch, Labdhi Seth, Karen M.B. Ferlez, Casey K. Storme, Danielle M. Pesavento, Paige Y. Laughlin, Elke S. Bergmann-Leitner, Peter Burkhard, David E. Lanar
To eliminate the problems associated with the use of extraneous adjuvants we have designed a Self-Assembling Protein Nanoparticle (SAPN) containing epitopes from the Plasmodium falciparum circumsporozoite protein (PfCSP) (designated FMP014) and portions of the TLR5 agonist flagellin (designated FMP014D0D1) as an intrinsic adjuvant. By combining different molar ratios of FMP014 to FMP014D0D1 monomers before self-assembly, we generated multiple nanoparticles and investigated their biophysical characteristics, immunogenicity and protective efficacy. Immunization with the construct formulated with the ratio 58:2 of FMP014 to FMP014D0D1 had the highest protective efficacy against a challenge with a transgenic P. berghei sporozoite expressing PfCSP. Increasing the proportion of flagellin per particle resulted in an inverse relationship with levels of both antibody titers and protection. The cytokine profiles of the various immunization groups were evaluated and quantitative amounts of the cytokines IL-2, IFN-γ, IL-12/p70 (Th1); IL4, IL5 (Th2); TNF-α, IL1β, IL-6, KC/GRO (pro-inflammatory), and IL-10 (immunomodulatory) were measured. The relationship of the cytokines to each other revealed a strong immunomodulatory effect depending on the proportion of flagellin in the construct. Our results demonstrate that SAPNs with flagellin may be a promising strategy for the development and delivery of a safe vaccine for infectious diseases.

http://ift.tt/2FmYZei

Vascular Reconstruction in a Neonate after Iatrogenic Injury during Cardiac Catheterization

Summary: As technology and interventional techniques continue to evolve, both the volume and complexity of cardiac catheterizations will increase, leading to a rise in the number of complications. One of the most morbid complications of cardiac catheterization is vascular injury. We report the case of a 31-day-old, 3.0-kg infant with hypoplastic left heart syndrome who experienced a left common iliac artery disruption during cardiac catheterization resulting in a retroperitoneal hemorrhage. The extent of the vascular injury combined with the vessel caliber posed a technically challenging surgical scenario. Ultimately, the vascular supply to the left lower extremity was reconstructed by the plastic surgery team with a reverse autologous vein graft. To our knowledge, this multidisciplinary approach with the involvement of plastic surgery represents a unique case.

http://ift.tt/2DF87KS

No Vertical Scar Breast Weight Transfer

Summary: Women desire beautiful breasts that are functional, pain free, and without foreign material. Vertical scars, insufficient elevation, inadequate upper pole fullness, nipple numbness, and loss of breast feeding are undesirable. Relieving pain attributed to enlarged breasts has required significant tissue removal. Software analysis of chest images, physical measurements, and desires are combined to generate a surgical blueprint. The breast is divided horizontally into two components preserving the neurovascular supply and major lactiferous ducts. The skin flap cephalad to the areola provides external coverage. The areola remains attached to a deepithelialized mound, which is rotated into a cone. Dermal straps originating from the base of the cone are looped through the pectoralis major muscle and the cone repeatedly. Weight transfer to the pectoralis major muscles eliminates pain in 54% and decreases pain in 38%. Incisions are concealed at the areola cutaneous junction and in the shadow of the breast. Upper pole fullness increased in 86% without implants or fat transfer. Nipple sensation was increased in 37% and unchanged in 44%. Overall results were excellent in 50% and good in 36%. Complications consisted of dog-ears, periareolar infection, and fat necrosis. No patient required a return to the operation room. Combing computer-aided design with plastic surgical principles creates beautiful, functional breasts without foreign material. Vertical scars are avoided, and weight transfer relieves pain.

http://ift.tt/2EdzuNp

upper respiratory tract infection; +47 new citations

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upper respiratory tract infection

These pubmed results were generated on 2018/01/27

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.

http://ift.tt/2njgKDZ

[Papillomavirus, could we speak about cancer and prevention?]

[Papillomavirus, could we speak about cancer and prevention?]

Bull Cancer. 2018 Jan 16;:

Authors: Pernot S, Pavie J, Péré H, Menard M, Hurel S, Cochand-Priollet B, Bats AS, Badoual C

PMID: 29373106 [PubMed - as supplied by publisher]

http://ift.tt/2nfG4M4

Home Non-Invasive Ventilation for COPD: How, Who and When?

Home Non-Invasive Ventilation for COPD: How, Who and When?

Arch Bronconeumol. 2018 Jan 19;:

Authors: Murphy PB, Hart N

Abstract
Patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure have high levels of morbidity and mortality. The clinical efficacy of long term home oxygen therapy has been well documented in this patient group but despite the efficacy of non-invasive ventilation (NIV) during acute decompensated respiratory failure the addition of home NIV has been associated with equivocal results. The physiological efficacy of home NIV to improve gas exchange in chronic stable hypercapnic respiratory failure has been proven in small studies but larger clinical trials failed to translate this into clinical efficacy. Criticisms of early clinical trials include the use of marginally hypercapnic patients and failure to demonstrate effective delivery of home NIV. When considering recent trial data it is important to clearly evaluate the patient phenotype and timing and delivery of NIV. Recent data supports the delivery of home NIV in patients with chronic hypercapnia (PaCO2>7kPa or 50mmHg) and the frequent or infrequent exacerbator phenotype. Importantly in the frequent exacerbator the timing of the assessment needs to be in the recovery phase, 2-4 weeks after resolution of acute acidosis, to delineate transient from persistent hypercapnia. In patient with persistent hypercapnia NIV must be titrated to achieve control of sleep disordered breathing with the aim of improving daytime respiratory failure. Furthermore there are observational data to support the use of home positive airway pressure therapy (NIV or continuous positive airway pressure; CPAP) in patients with COPD and obstructive sleep apnoea (OSA) both with and without hypercapnia.

PMID: 29371025 [PubMed - as supplied by publisher]

http://ift.tt/2FnCJ4j

Comprehensive circRNA expression profile and construction of circRNA-associated ceRNA network in fur skin

Abstract

Circular RNA (circRNA), a class of non-coding RNAs, is a new group of RNAs that are related to tumorigenesis. The role of circRNAs in various diseases has been already highlighted. However, the expression levels and functions of circRNAs related to the melanocytes in the skin are poorly understood. RNA sequence was performed to analyze the expression profiles of circRNAs in black fur skin and white fur skin during different differentiation stages and investigate the relevant metabolism mechanisms. Differentially expressed circRNAs were detected using empirical Bayes sequencing (EBSeq) and then verified through the quantitative real-time PCR method. The EQSeq analysis of circRNAs identified 11 downregulated and 32 upregulated circRNAs in the embryo of black fur skin and white fur skin, as well as 21 downregulated and 17 upregulated circRNA in the postnatal stage. A circRNA–microRNA (miRNA)– messenger RNA (mRNA) network was established to predict the circRNA targets. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to enrich the mRNA data further. Results showed that the specific mRNAs mainly involved in the transcription- related GOs, especially GO:0042802, GO:0005080 and GO:0032403, demonstrate their specific actions in transcriptional regulation. In the circRNA–miRNA–mRNA network, the most enriched GO terms of the mRNAs were pigmentation, protein autophosphorylation, and protein complex. Therefore, the circRNA–miRNA–mRNA pathway may reveal novel mechanisms for pigmentation, and circRNAs may serve as candidates in pigmentation.

http://ift.tt/2BxhjPM

Excellent Prognosis of Central Lymph Node Recurrence-Free Survival for cN0M0 Papillary Thyroid Carcinoma Patients Who Underwent Routine Prophylactic Central Node Dissection.

Excellent Prognosis of Central Lymph Node Recurrence-Free Survival for cN0M0 Papillary Thyroid Carcinoma Patients Who Underwent Routine Prophylactic Central Node Dissection.

World J Surg. 2018 Jan 25;:

Authors: Ito Y, Miyauchi A, Masuoka H, Fukushima M, Kihara M, Miya A

Abstract
INTRODUCTION: In Japan, prophylactic central node dissection (p-CND) for papillary thyroid carcinoma (PTC) has been routinely performed in many institutions, including ours (Kuma Hospital, Japan). We evaluated the recurrence to a central lymph node in patients with cN0M0 PTC who underwent routine p-CND.
MATERIALS AND METHODS: We enrolled 4301 patients with cN0M0 PTC who underwent an initial surgery between 1987 and 2005 (median age 51 years). The postoperative follow-up periods ranged from 4 to 362 months (median 164 months). Only 15 patients underwent radioactive iodine (RAI) ablation (≥30 mCi) after total or near total thyroidectomy.
RESULTS: Of the 4301 patients with N0M0 PTC who underwent p-CND, 2548 (59%) were diagnosed as pN1a on postoperative pathological examination. To date, only 52 cases (1.2%) showed recurrence to a central lymph node. The 10-year and 20-year central node recurrence-free survival rates were excellent at 99.1 and 98.2%, respectively. On multivariate analysis, age ≥55 years, significant extrathyroid extension, tumor size >2 cm, and ≥5 pathologically confirmed central node metastases (but not the presence of central node metastasis) independently affected central node recurrence.
CONCLUSIONS: Under the situation of routine p-CND, the central node recurrence-free survival of cN0M0 PTC is excellent. However, future studies, including double-arm studies from Japan, should examine whether the omission of p-CND cN0M0 PTC is appropriate without RAI ablation in consideration of various factors, including the pros and cons of p-CND.

PMID: 29372373 [PubMed - as supplied by publisher]

http://ift.tt/2rJDJh2

Scatter Correction of Septal Penetration for 123I-IMP Cerebral Blood Flow SPECT Adding Radioactivity from the Outside of Field of View-Comparison between Simulation-based and Multi-window Scatter Corrections.

Scatter Correction of Septal Penetration for 123I-IMP Cerebral Blood Flow SPECT Adding Radioactivity from the Outside of Field of View-Comparison between Simulation-based and Multi-window Scatter Corrections.

Nihon Hoshasen Gijutsu Gakkai Zasshi. 2017;73(10):1028-1038

Authors: Yamanaga T, Katayama Y, Nakama S, Kakimi A, Nagahata T, Kishimoto K, Ichida T, Higashiyama S, Kawabe J, Shiomi S

Abstract
PURPOSE: The N-Isopropyl-p-[123I] Iodoamphetamine (123I-IMP) SPECT imaging reduces the image quality and quantitative accuracy due to scatter and septal penetration occurred by radioactive uptake from outside of the field of view such as the lungs. We evaluated the influence of scatter and septal penetration using phantom-simulated radioactivity from outside of the field of view, and subsequently compared the effect of scatter and septal penetration corrections between the simulation-based effective scatter source estimation (ESSE) method and the multi-window method (ellipse approximation method).
METHODS: We used the phantom filled with 10 and 25 kBq/mL for the brain and lung parts corresponding to radioactive concentration in the clinical study. The SPECT images were acquired with and without lung phantom using low-energy high-resolution (LEHR) and cardiac high-resolution (CHR) collimators. We quantitatively evaluated a brain phantom by count analysis and coefficient of variation as reference data without lung phantom simulated the radioactivity from outside of the field of view, and compared between two scatter corrections by each collimator.
RESULTS: The brain count in cerebral base with the ESSE method using LEHR collimator was higher than that of the ellipse approximation method. The whole brain count with the ellipse approximation method using CHR collimator shows 28.8% lower than the ESSE method, so that it suggests that the ellipse approximation method for LEHR collimator and the ESSE method for CHR collimator was close to reference counts. The coefficient of variation of the ESSE method was lower than that of the ellipse approximation method for both two collimators.
CONCLUSIONS: It was possible to correct the scatter and penetration from outside the field of view with high accuracy, by using the ellipse approximation method with LEHR collimator and the ESSE method with CHR collimator.

PMID: 29057774 [PubMed - indexed for MEDLINE]

http://ift.tt/2DBSe89

Endoluminal Vacuum Therapy (E-Vac): A Treatment Option in Oesophagogastric Surgery.

Endoluminal Vacuum Therapy (E-Vac): A Treatment Option in Oesophagogastric Surgery.

World J Surg. 2018 Jan 25;:

Authors: Pournaras DJ, Hardwick RH, Safranek PM, Sujendran V, Bennett J, Macaulay GD, Hindmarsh A

Abstract
BACKGROUND: Leaks from the upper gastrointestinal tract often pose a management challenge, particularly when surgical treatment has failed or is impossible. Vacuum therapy has revolutionised the treatment of wounds, and its role in enabling and accelerating healing is now explored in oesophagogastric surgery.
METHODS: A piece of open cell foam is sutured around the distal end of a nasogastric tube using a silk suture. Under general anaesthetic, the foam covered tip is placed endoscopically through the perforation and into any extra-luminal cavity. Continuous negative pressure (125 mmHg) is then applied. Re-evaluation with change of the negative pressure system is performed every 48-72 h depending on the clinical condition. Patients are fed enterally and treated with broad-spectrum antibiotics and anti-fungal medication until healing, assessed endoscopically and/or radiologically, is complete.
RESULTS: Since April 2011, twenty one patients have been treated. The cause of the leak was postoperative/iatrogenic complications (14 patients) and ischaemic/spontaneous perforation (seven patients). Twenty patients (95%) completed treatment successfully with healing of the defect and/or resolution of the cavity and were subsequently discharged from our care. One patient died from sepsis related to an oesophageal leak after withdrawing consent for further intervention following a single endoluminal vacuum (E-Vac) treatment. In addition, two patients who were successfully treated with E-Vac for their leak subsequently died within 90 days of E-Vac treatment from complications that were not associated with the E-Vac procedure. In two patients, E-Vac treatment was complicated by bleeding. The median number of E-Vac changes was 7 (range 3-12), and the median length of hospital stay was 35 days (range 23-152).
CONCLUSIONS: E-Vac therapy is a safe and effective treatment for upper gastrointestinal leaks and should be considered alongside more established therapies. Further research is now needed to understand the mechanism of action and to improve the ease with which E-Vac therapy can be delivered.

PMID: 29372375 [PubMed - as supplied by publisher]

http://ift.tt/2rGX7v7

Cysto-cholecystostomy: A More Physiological Procedure for Hepatic Cysts with Biliary Communications and Cystic Dilatations of Main Intrahepatic Ducts.

Cysto-cholecystostomy: A More Physiological Procedure for Hepatic Cysts with Biliary Communications and Cystic Dilatations of Main Intrahepatic Ducts.

World J Surg. 2018 Jan 25;:

Authors: Diao M, Li L, Cheng W

Abstract
OBJECTIVE: Hepatic cysts with biliary communications (HC) and cystic dilatations of main intrahepatic ducts (CIHD) can cause biliary obstruction, cholestasis, stone formation, cholangitis, liver damage and carcinoma. Conventionally, Roux-Y cysto-jejunostomy is employed to manage these conditions. However, it is technically demanding and may be complicated with major biliary disruption and bacteria migration from intestine to intrahepatic duct. We have carried out laparoscopic cysto-cholecystostomies for HC with biliary communication and CIHD and evaluated outcomes.
METHODS: Twenty patients with HC (n = 10) or CIHD (n = 10) who successfully underwent laparoscopic cysto-cholecystostomies in our center, between September 2010 and March 2017, were reviewed.
RESULTS: The mean age of the patients at surgery was 2.06 and 2.23 years for HC and CIHD groups, respectively. Eighteen patients were symptomatic, with abdominal pain, fever, vomiting and jaundice. Laboratory results showed abnormal liver functions in 8 patients. Pathological results verified hepatic cellular damages in 8 patients. The mean operative time was 0.97 and 0.92 h for HC and CIHD patients, respectively. The median follow-up duration was 27 months (1-54 months) and 35 months (1-79 months) for HC and CIHD groups, respectively. No patient developed bile leak, anastomotic stenosis, stone formation or cholangitis. Liver function normalized postoperatively.
CONCLUSIONS: Laparoscopic cysto-cholecystostomy is a simpler and more physiological surgical alternative for managing HC with biliary communication and CIHD.

PMID: 29372374 [PubMed - as supplied by publisher]

http://ift.tt/2GoWfPc

Excellent Prognosis of Central Lymph Node Recurrence-Free Survival for cN0M0 Papillary Thyroid Carcinoma Patients Who Underwent Routine Prophylactic Central Node Dissection.

Excellent Prognosis of Central Lymph Node Recurrence-Free Survival for cN0M0 Papillary Thyroid Carcinoma Patients Who Underwent Routine Prophylactic Central Node Dissection.

World J Surg. 2018 Jan 25;:

Authors: Ito Y, Miyauchi A, Masuoka H, Fukushima M, Kihara M, Miya A

PMID: 29372373 [PubMed - as supplied by publisher]

http://ift.tt/2rJDJh2

Surgery for Hepatocellular Carcinoma in Patients with Child-Pugh B Cirrhosis: Hepatic Resection Versus Living Donor Liver Transplantation.

Surgery for Hepatocellular Carcinoma in Patients with Child-Pugh B Cirrhosis: Hepatic Resection Versus Living Donor Liver Transplantation.

World J Surg. 2018 Jan 25;:

Authors: Harimoto N, Yoshizumi T, Fujimoto Y, Motomura T, Mano Y, Toshima T, Itoh S, Harada N, Ikegami T, Uchiyama H, Soejima Y, Maehara Y

Abstract
BACKGROUND: Liver transplantation has been established as the optimal treatment for hepatocellular carcinoma in cirrhotic patients, but hepatic resection is also effective in patients with well-preserved liver function. Determining the suitable surgical treatment for patients with Child-Pugh class B cirrhosis is a more difficult challenge.
METHODS: We retrospectively compared the results of hepatic resection and living donor liver transplantation for hepatocellular carcinoma in 137 patients with Child-Pugh class B cirrhosis. The procedures were performed at Kyushu University Hospital from April 2014 through October 2016.
RESULTS: Patients who underwent hepatic resection were significantly older and had better liver function, larger tumor size, smaller number of tumors, and less surgical stress compared with patients who underwent living donor liver transplantation. The overall survival rate and the recurrence-free survival rate in patients with transplantation were significantly better than that in patients with resection. The multivariate analysis showed that recurrent hepatocellular carcinoma and microvascular invasion were significant prognostic factors for both overall and recurrence-free survival in the hepatic resection group. In the group with protein induced by vitamin K absence or antagonist-II ≥300 mAU/mL, both the overall survival curve and the recurrence-free survival curve in patients with living donor liver transplantation were not significantly different from those in patients with hepatic resection.
CONCLUSIONS: Living donor liver transplantation for hepatocellular carcinoma in patients with Child-Pugh class B cirrhosis was favorable under the condition of protein induced by vitamin K absence or antagonist-II <300 mAU/mL in selected recipients and donors. Hepatic resection for recurrent hepatocellular carcinoma and excessive blood loss should be avoided in patients with Child-Pugh class B cirrhosis.

PMID: 29372372 [PubMed - as supplied by publisher]

http://ift.tt/2GmBjIn

Laryngeal Manipulation for Dysphagia with Muscle Tension Dysphonia.

Laryngeal Manipulation for Dysphagia with Muscle Tension Dysphonia.

Dysphagia. 2018 Jan 25;:

Authors: DePietro JD, Rubin S, Stein DJ, Golan H, Noordzij JP

Abstract
The purpose of the article is to describe the use of laryngeal manipulation as a treatment for dysphagia resulting from excessive paralaryngeal muscle tension and to identify the patients likely to have symptomatic improvement. This is a retrospective single-center case series. A retrospective review identified patients from 2007 to 2013 with laryngeal manipulation for muscle tension dysphagia in an academic Otolaryngology practice. Subjects with dysphagia not attributable to an anatomic cause who attended therapy at least one time were included in the study. The primary outcome of the study was subjective improvement in dysphagia symptoms (yes/no) during follow-up. Symptoms, demographic information, treatment, and response to therapy were recorded. The Kruskal-Wallis test was used for analysis of continuous variables, while a Chi-squared test or fisher's exact test was used for analysis of all categorical variables. Forty-four subjects were included, consisting of 37 women and 7 men. Subjective improvement in dysphagia was seen in 34 subjects (77.3%). No significant differences were seen in improvement based on gender (p = 0.3223), race (p = 0.4317), number of sessions with a speech pathologist (p = 0.3198), or presenting symptoms including hoarseness (p = 0.0853), pain (p = 1.000), globus (p = 0.2834), and cough (p = 1.000). We found subjective improvement with laryngeal manipulation as reported during follow-up visits to clinic among individuals with muscle tension dysphagia. Patient age, presenting symptoms, and number of therapy sessions were not found to be significantly associated with resolution of symptoms.

PMID: 29372358 [PubMed - as supplied by publisher]

http://ift.tt/2EfLjCy

In situ analysis of gelatinolytic activity in human dentin.

In situ analysis of gelatinolytic activity in human dentin.

Acta Histochem. 2018 Jan 16;:

Authors: Stape THS, Tjäderhane L, Tezvergil-Mutluay A, Da Silva WG, Dos Santos Silva AR, da Silva WJ, Marques MR

Abstract
Matrix metalloproteinases (MMPs) such as gelatinases are differentially expressed in human tissues. These enzymes cleave specific substrates involved in cell signaling, tissue development and remodeling and tissue breakdown. Recent evidences show that gelatinases are crucial for normal dentin development and their activity is maintained throughout the entire tooth function in the oral cavity. Due to the lack of information about the exact location and activity of gelatinases in mature human dentin, the present study was designed to examine gelatinolytic levels in sound dentin. In situ zymography using confocal microscopy was performed on both mineralized and demineralized dentin samples. Sites presenting gelatinase activity were identified throughout the entire biological tissue pursuing different gelatinolytic levels for distinct areas: predentin and dentinal tubule regions presented higher gelatinolytic activity compared to intertubular dentin. Dentin regions with higher gelatinolytic activity immunohistochemically were partially correlated with MMP-2 expression. The maintenance of gelatinolytic activity in mature dentin may have biological implications related to biomineralization of predentin and tubular/peritubular dentinal regions, as well as regulation of defensive mechanisms of the dentin-pulp complex.

PMID: 29373132 [PubMed - as supplied by publisher]

http://ift.tt/2ncBqyr

Melanoma of the Sinonasal Tract: Value of a Septate Pattern on Precontrast T1-Weighted MR Imaging.

Melanoma of the Sinonasal Tract: Value of a Septate Pattern on Precontrast T1-Weighted MR Imaging.

AJNR Am J Neuroradiol. 2018 Jan 25;:

Authors: Kim YK, Choi JW, Kim HJ, Kim HY, Park GM, Ko YH, Cha J, Kim ST

Abstract
BACKGROUND AND PURPOSE: Various tumors of the sinonasal tract can exhibit high signal intensity on T1WI. The purpose of this study was to determine the value of a septate pattern on precontrast T1WI for diagnosing sinonasal melanoma.
MATERIALS AND METHODS: Retrospectively, 3 observers independently reviewed MR images of 31 histologically proved sinonasal melanomas with special attention to the presence or absence of a septate pattern on precontrast T1WI, defined as alternating hyperintense and hypointense striations on precontrast T1WI. For comparison, we evaluated the prevalence of a septate pattern on precontrast T1WI in 106 nonmelanomatous sinonasal malignant tumors with 16 different histologic types. We also tried to identify the histopathologic features responsible for the septate pattern on precontrast T1WI.
RESULTS: Twenty-seven (87.1%) of 31 sinonasal melanomas showed hyperintense foci on T1WI, among which a septate pattern on precontrast T1WI was seen in 23 (74.2%), while 22 (20.8%) of 106 nonmelanomatous malignant tumors demonstrated hyperintense foci on T1WI, among which only 3 (2.8%) showed a septate pattern on precontrast T1WI. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of a septate pattern on precontrast T1WI for the diagnosis of sinonasal melanoma were 74%, 97%, 88%, 93%, and 92%, respectively. Although limited due to the retrospective nature, 4 of 23 histologically reviewed sinonasal melanomas revealed an uneven distribution of melanin with alternating melanin and fibrous bands within the tumors.
CONCLUSIONS: A septate pattern on precontrast T1WI might be an adjunctive imaging finding for the diagnosis of sinonasal melanoma. This might be attributed histologically to an uneven distribution of melanin and hemorrhage within the tumors.

PMID: 29371259 [PubMed - as supplied by publisher]

http://ift.tt/2Gm7J60

Quantitative Susceptibility Mapping of the Thalamus: Relationships with Thalamic Volume, Total Gray Matter Volume, and T2 Lesion Burden.

Quantitative Susceptibility Mapping of the Thalamus: Relationships with Thalamic Volume, Total Gray Matter Volume, and T2 Lesion Burden.

AJNR Am J Neuroradiol. 2018 Jan 25;:

Authors: Chiang GC, Hu J, Morris E, Wang Y, Gauthier SA

Abstract
BACKGROUND AND PURPOSE: Both thalamic iron deposition and atrophy have been reported in patients with multiple sclerosis compared with healthy controls, but how they are related is unclear. The purpose of this study was to understand the pathophysiologic basis for this iron deposition.
MATERIALS AND METHODS: Ninety-five patients with relapsing-remitting multiple sclerosis underwent 3T MR imaging with a standardized protocol that included quantitative susceptibility mapping to measure iron concentration and a 3D T1 echo-spoiled gradient-echo sequence to obtain thalamic volumes. Volumes of interest were manually delineated on the quantitative susceptibility map to encompass both thalami. Multivariate regression analyses were performed to identify the association between thalamic susceptibility and volume. Associations between thalamic susceptibility and total gray matter volume, cortical thickness, and T2 lesion volume were also assessed.
RESULTS: The relative susceptibility of the thalamus was associated with T2 lesion volume (P = .015) and was higher in the presence of enhancing lesions (P = .013). The relative susceptibility of the thalami was not associated with thalamic volumes, total gray matter volumes, or cortical thickness (P > .05).
CONCLUSIONS: Iron levels in the thalami are associated with T2 lesion burden and the presence of enhancing lesions, but not with thalamic or gray matter volumes, suggesting that iron accumulation is associated with white matter inflammation rather than gray matter neurodegeneration.

PMID: 29371258 [PubMed - as supplied by publisher]

http://ift.tt/2Bw4qpj

Early Hemodynamic Response Assessment of Stereotactic Radiosurgery for a Cerebral Arteriovenous Malformation Using 4D Flow MRI.

Early Hemodynamic Response Assessment of Stereotactic Radiosurgery for a Cerebral Arteriovenous Malformation Using 4D Flow MRI.

AJNR Am J Neuroradiol. 2018 Jan 25;:

Authors: Li CQ, Hsiao A, Hattangadi-Gluth J, Handwerker J, Farid N

Abstract
Brain AVMs treated with stereotactic radiosurgery typically demonstrate a minimum latency period of 1-3 years between treatment and nidus obliteration. Assessment of treatment response is usually limited to evaluation of AVM nidus structural changes using conventional MR imaging and MRA techniques. This report describes the use of 4D Flow MRI to also measure radiation-induced hemodynamic changes in a Spetzler-Martin grade III AVM, which were detectable as early as 6 months after treatment.

PMID: 29371257 [PubMed - as supplied by publisher]

http://ift.tt/2nfy2CN

Comparison of Blood Oxygenation Level-Dependent fMRI and Provocative DSC Perfusion MR Imaging for Monitoring Cerebrovascular Reserve in Intracranial Chronic Cerebrovascular Disease.

Comparison of Blood Oxygenation Level-Dependent fMRI and Provocative DSC Perfusion MR Imaging for Monitoring Cerebrovascular Reserve in Intracranial Chronic Cerebrovascular Disease.

AJNR Am J Neuroradiol. 2018 Jan 25;:

Authors: Thulborn KR, Atkinson IC, Alexander A, Singal M, Amin-Hanjani S, Du X, Alaraj A, Charbel FT

Abstract
BACKGROUND AND PURPOSE: Loss of hemodynamic reserve in intracranial cerebrovascular disease reduces blood oxygenation level-dependent activation by fMRI and increases asymmetry in MTT measured by provocative DSC perfusion MR imaging before and after vasodilation with intravenous acetazolamide. The concordance for detecting hemodynamic reserve integrity has been compared.
MATERIALS AND METHODS: Patients (n = 40) with intracranial cerebrovascular disease and technically adequate DSA, fMRI and provocative DSC perfusion studies were retrospectively grouped into single vessels proximal to and distal from the circle of Willis, multiple vessels, and Moyamoya disease. The vascular territories were classified as having compromised hemodynamic reserve if the expected fMRI blood oxygenation level-dependent activation was absent or if MTT showed increased asymmetry following vasodilation. Concordance was examined in compromised and uncompromised vascular territories of each group with the Fischer exact test and proportions of agreement.
RESULTS: Extensive leptomeningeal collateral circulation was present in all cases. Decreased concordance between the methods was found in vascular territories with stenosis distal to but not proximal to the circle of Willis. Multivessel and Moyamoya diseases also showed low concordance. A model of multiple temporally displaced arterial inputs from leptomeningeal collateral flow demonstrated that the resultant lengthening MTT mimicked compromised hemodynamic reserve despite being sufficient to support blood oxygenation level-dependent contrast.
CONCLUSIONS: Decreased concordance between the 2 methods for assessment of hemodynamic reserve for vascular disease distal to the circle of Willis is posited to be due to well-developed leptomeningeal collateral circulation providing multiple temporally displaced arterial input functions that bias the perfusion analysis toward hemodynamic reserve compromise while blood oxygenation level-dependent activation remains detectable.

PMID: 29371256 [PubMed - as supplied by publisher]

http://ift.tt/2BycoOn

Nonsphericity Index and Size Ratio Identify Morphologic Differences between Growing and Stable Aneurysms in a Longitudinal Study of 93 Cases.

Nonsphericity Index and Size Ratio Identify Morphologic Differences between Growing and Stable Aneurysms in a Longitudinal Study of 93 Cases.

AJNR Am J Neuroradiol. 2018 Jan 25;:

Authors: Chien A, Xu M, Yokota H, Scalzo F, Morimoto E, Salamon N

Abstract
BACKGROUND AND PURPOSE: Recent studies have strongly associated intracranial aneurysm growth with increased risk of rupture. Identifying aneurysms that are likely to grow would be beneficial to plan more effective monitoring and intervention strategies. Our hypothesis is that for unruptured intracranial aneurysms of similar size, morphologic characteristics differ between aneurysms that continue to grow and those that do not.
MATERIALS AND METHODS: From aneurysms in our medical center with follow-up imaging dates in 2015, ninety-three intracranial aneurysms (23 growing, 70 stable) were selected. All CTA images for the aneurysm diagnosis and follow-up were collected, a total of 348 3D imaging studies. Aneurysm 3D geometry for each imaging study was reconstructed, and morphologic characteristics, including volume, surface area, nonsphericity index, aspect ratio, and size ratio were calculated.
RESULTS: Morphologic characteristics were found to differ between growing and stable groups. For aneurysms of <3 mm, nonsphericity index (P < .001); 3-5 mm, nonsphericity index (P < .001); 5-7 mm, size ratio (P = .003); >7 mm, volume (P < .001); surface area (P < .001); and nonsphericity index (P = .002) were significant. Within the anterior communicating artery, the nonsphericity index (P = .008) and, within the posterior communicating artery, size ratio (P = .004) were significant. The nonsphericity index receiver operating characteristic area under the curve was 0.721 for discriminating growing and stable cases on the basis of initial images.
CONCLUSIONS: Among aneurysms with similar sizes, morphologic characteristics appear to differ between those that are growing and those that are stable. The nonsphericity index, in particular, was found to be higher among growing aneurysms. The size ratio was found to be the second most significant parameter associated with growth.

PMID: 29371255 [PubMed - as supplied by publisher]

http://ift.tt/2nhfaTY

Local Glioma Cells Are Associated with Vascular Dysregulation.

Local Glioma Cells Are Associated with Vascular Dysregulation.

AJNR Am J Neuroradiol. 2018 Jan 25;:

Authors: Bowden SG, Gill BJA, Englander ZK, Horenstein CI, Zanazzi G, Chang PD, Samanamud J, Lignelli A, Bruce JN, Canoll P, Grinband J

Abstract
BACKGROUND AND PURPOSE: Malignant glioma is a highly infiltrative malignancy that causes variable disruptions to the structure and function of the cerebrovasculature. While many of these structural disruptions have known correlative histopathologic alterations, the mechanisms underlying vascular dysfunction identified by resting-state blood oxygen level-dependent imaging are not yet known. The purpose of this study was to characterize the alterations that correlate with a blood oxygen level-dependent biomarker of vascular dysregulation.
MATERIALS AND METHODS: Thirty-two stereotactically localized biopsies were obtained from contrast-enhancing (n = 16) and nonenhancing (n = 16) regions during open surgical resection of malignant glioma in 17 patients. Preoperative resting-state blood oxygen level-dependent fMRI was used to evaluate the relationships between radiographic and histopathologic characteristics. Signal intensity for a blood oxygen level-dependent biomarker was compared with scores of tumor infiltration and microvascular proliferation as well as total cell and neuronal density.
RESULTS: Biopsies corresponded to a range of blood oxygen level-dependent signals, ranging from relatively normal (z = -4.79) to markedly abnormal (z = 8.84). Total cell density was directly related to blood oxygen level-dependent signal abnormality (P = .013, R2 = 0.19), while the neuronal labeling index was inversely related to blood oxygen level-dependent signal abnormality (P = .016, R2 = 0.21). The blood oxygen level-dependent signal abnormality was also related to tumor infiltration (P = .014) and microvascular proliferation (P = .045).
CONCLUSIONS: The relationship between local, neoplastic characteristics and a blood oxygen level-dependent biomarker of vascular function suggests that local effects of glioma cell infiltration contribute to vascular dysregulation.

PMID: 29371254 [PubMed - as supplied by publisher]

http://ift.tt/2Fnrclx

Comparison of MR Imaging and Dual-Energy CT for the Evaluation of Cartilage Invasion by Laryngeal and Hypopharyngeal Squamous Cell Carcinoma.

Comparison of MR Imaging and Dual-Energy CT for the Evaluation of Cartilage Invasion by Laryngeal and Hypopharyngeal Squamous Cell Carcinoma.

AJNR Am J Neuroradiol. 2018 Jan 25;:

Authors: Kuno H, Sakamaki K, Fujii S, Sekiya K, Otani K, Hayashi R, Yamanaka T, Sakai O, Kusumoto M

Abstract
BACKGROUND AND PURPOSE: Dual-energy CT can distinguish iodine-enhanced tumors from nonossified cartilage and has been investigated for evaluating cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinomas. In this study, we compared the diagnostic accuracy of MR imaging and of a combination of weighted-average and iodine overlay dual-energy CT images in detecting cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinomas, in particular thyroid cartilage invasion.
MATERIALS AND METHODS: Fifty-five consecutive patients who underwent 3T MR imaging and 128-slice dual-energy CT for preoperative initial staging of laryngeal or hypopharyngeal squamous cell carcinomas were included. Two blinded observers evaluated laryngeal cartilage invasion on MR imaging and dual-energy CT using a combination of weighted-average and iodine-overlay images. Pathologic findings of surgically resected specimens were used as the reference standard for evaluating sensitivity, specificity, and the areas under the receiver operating characteristic curve of both modalities for cartilage invasion by each type of cartilage and for all cartilages together. Sensitivity and specificity were compared using the McNemar test and generalized linear mixed models.
RESULTS: Dual-energy CT showed higher specificity than MR imaging for diagnosing all cartilage together (84% for MR imaging versus 98% for dual-energy CT, P < .004) and for thyroid cartilage (64% versus 100%, P < .001), with a similar average area under the curve (0.94 versus 0.95, P = .70). The sensitivity did not differ significantly for all cartilages together (97% versus 81%, P = .16) and for thyroid cartilage (100% versus 89%, P = .50), though there was a trend toward increased sensitivity with MR imaging.
CONCLUSIONS: Dual-energy CT showed higher specificity and acceptable sensitivity in diagnosing laryngeal cartilage invasion compared with MR imaging.

PMID: 29371253 [PubMed - as supplied by publisher]

http://ift.tt/2DG6Nvs

Looking Deep into the Eye-of-the-Tiger in Pantothenate Kinase-Associated Neurodegeneration.

Looking Deep into the Eye-of-the-Tiger in Pantothenate Kinase-Associated Neurodegeneration.

AJNR Am J Neuroradiol. 2018 Jan 25;:

Authors: Lee JH, Gregory A, Hogarth P, Rogers C, Hayflick SJ

Abstract
BACKGROUND AND PURPOSE: A detailed delineation of the MR imaging changes in the globus pallidus in pantothenate kinase-associated neurodegeneration will be helpful for diagnosis and monitoring of patients. The aim of this study was to determine the morphologic spectrum of the "eye-of-the-tiger" sign and the topographic pattern of iron deposition in a group of patients with pantothenate kinase-associated neurodegeneration.
MATERIALS AND METHODS: Seventy-four MR imaging scans from 54 individuals with PANK2 mutations were analyzed for signal patterns in the globus pallidus. Sixteen SWI data from 15 patients who underwent 1.5T (n = 7), 3T (n = 7), and 7T (n = 2) MR imaging were included to visualize the iron topography.
RESULTS: The linear hyperintensity alongside the medial border of the globus pallidus was the earliest T2 signal change. This finding was evident before SWI changes from iron deposition became visible. T2WI performed in early childhood mostly showed isolated hyperintense signal. In adult patients, marked signal reduction within an earlier hyperintense center resulting from iron accumulation led to the loss of signal difference between the central and surrounding areas. Signal hypointensity on SWI progressed from the medial to the lateral portion of the globus pallidus with increasing age. The fiber connections between the medial globus pallidus and the anteromedial aspect of the substantia nigra and subthalamic nucleus were markedly hypointense on SWI.
CONCLUSIONS: In pantothenate kinase-associated neurodegeneration, the globus pallidus MR imaging changes using SWI develop as region-specific and age-dependent phenomena. Signal inhomogeneity was observed across the globus pallidus in pantothenate kinase-associated neurodegeneration and should be considered when determining the concentration of iron.

PMID: 29371252 [PubMed - as supplied by publisher]

http://ift.tt/2BwsJmU

Intravoxel Incoherent Motion MR Imaging in the Differentiation of Benign and Malignant Sinonasal Lesions: Comparison with Conventional Diffusion-Weighted MR Imaging.

Intravoxel Incoherent Motion MR Imaging in the Differentiation of Benign and Malignant Sinonasal Lesions: Comparison with Conventional Diffusion-Weighted MR Imaging.

AJNR Am J Neuroradiol. 2018 Jan 25;:

Authors: Xiao Z, Tang Z, Qiang J, Wang S, Qian W, Zhong Y, Wang R, Wang J, Wu L, Tang W, Zhang Z

Abstract
BACKGROUND AND PURPOSE: Intravoxel incoherent motion is a promising method for the differentiation of sinonasal lesions. This study aimed to evaluate the value of intravoxel incoherent motion in the differentiation of benign and malignant sinonasal lesions and to compare the diagnostic performance of intravoxel incoherent motion with that of conventional DWI.
MATERIALS AND METHODS: One hundred thirty-one patients with histologically proved solid sinonasal lesions (56 benign and 75 malignant) who underwent conventional DWI and intravoxel incoherent motion were recruited in this study. The diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values derived from intravoxel incoherent motion and ADC values derived from conventional DWI were measured and compared between the 2 groups using the Student t test. Receiver operating characteristic curve analysis, logistic regression analysis, and 10-fold cross-validation were performed to evaluate the diagnostic performance of single-parametric and multiparametric models.
RESULTS: The mean ADC and D values were significantly lower in malignant sinonasal lesions than in benign sinonasal lesions (both P < .001). The mean f value was higher in malignant lesions than in benign lesions (P = .003). Multiparametric models can significantly improve the cross-validated areas under the curve for the differentiation of sinonasal lesions compared with single-parametric models (all corrected P < .05 except the D value). The model of D+f provided a better diagnostic performance than the ADC value (corrected P < .001).
CONCLUSIONS: Intravoxel incoherent motion appears to be a more effective MR imaging technique than conventional DWI in the differentiation of benign and malignant sinonasal lesions.

PMID: 29371251 [PubMed - as supplied by publisher]

http://ift.tt/2neQOKG

Short Takes

Publication date: Available online 17 January 2018
Source:Pediatric Neurology
Author(s): Steven G. Pavlakis

http://ift.tt/2rEI19o

Cosmetics, Vol. 5, Pages 15: Development of a Natural Anti-Age Ingredient Based on Quercus pubescens Willd. Leaves Extract—A Case Study

Cosmetics, Vol. 5, Pages 15: Development of a Natural Anti-Age Ingredient Based on Quercus pubescens Willd. Leaves Extract—A Case Study

Cosmetics doi: 10.3390/cosmetics5010015

Authors: Hortense Plainfossé Pauline Burger Stéphane Azoulay Anne Landreau Grégory Verger-Dubois Xavier Fernandez

Consumers pay more and more attention not just to the safety and health aspects of ingredients entering their cosmetics' formulations, but also to their potency, origin, processing, ethical value and environmental footprint. Sustainability of the supply chain, preservation of biodiversity, as well as greener extraction techniques are hence very popular with consumers. Consumers are primarily concerned by the efficacy of the cosmetic products they use and continuously scrutinize product labels, so marketing arguments need to be based on rigorous testing and reliable results to support claims (anti-age, anti-pollution, etc.) displayed on the product's packaging. As a result, the increasing demand for natural ingredients with assessed bioactivities has profoundly modified the strategies adopted by cosmetic professionals to innovate in terms of actives. Sourcing and developing new natural cosmetic actives is a long-term procedure that is thoroughly described in the present paper, via the example of the design of both liquid and solid ingredients based on Quercus pubescens Willd. leaves extract, for which anti-age properties were assessed by a combination of in vitro assays.

http://ift.tt/2rI3iPL

Magnetic nanoparticles: recent developments in drug delivery system.

Magnetic nanoparticles: recent developments in drug delivery system.

Drug Dev Ind Pharm. 2018 Jan 25;:1-10

Authors: Xiong F, Huang S, Gu N

Abstract
Nanostructured functional materials have demonstrated their great potentials in medical applications, attracting increasing attention because of the opportunities in cancer therapy and the treatment of other ailments. This article reviews the problems and recent advances in the development of magnetic NPs for drug delivery.

PMID: 29370711 [PubMed - as supplied by publisher]

http://ift.tt/2Bwsvw4

Discordant Analytical Results Caused by Biotin Interference on Diagnostic Immunoassays in a Pediatric Hospital.

Discordant Analytical Results Caused by Biotin Interference on Diagnostic Immunoassays in a Pediatric Hospital.

Ann Clin Lab Sci. 2017 Sep;47(5):638-640

Authors: Ali M, Rajapakshe D, Cao L, Devaraj S

Abstract
Recent studies have reported that biotin interferes with certain immunoassays. In this study, we evaluated the analytical interference of biotin on immunoassays that use streptavidin-biotin in our pediatric hospital. We tested the effect of different concentrations of biotin (1.5-200 ng/ml) on TSH, Prolactin, Ferritin, CK-MB, β-hCG, Troponin I, LH, FSH, Cortisol, Anti-HAV antibody (IgG and IgM), assays on Ortho Clinical Diagnostic Vitros 5600 Analyzer. Biotin (up to 200 ng/mL) did not significantly affect Troponin I and HAV assays. Biotin (up to 12.5 ng/ml) resulted in <10% bias in CK-MB, β-hCG, AFP, Cortisol, Ferritin assays and biotin >6.25 ng/mL significantly affected TSH (>20% bias) assay. Prolactin was significantly affected even at low levels (Biotin 1.5 ng/mL). Thus, we recommend educating physicians about biotin interference in common immunoassays and adding an electronic disclaimer.

PMID: 29066495 [PubMed - indexed for MEDLINE]

http://ift.tt/2nkfEb0

Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults.

Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults.

Cancer Epidemiol Biomarkers Prev. 2017 Feb;26(2):261-269

Authors: Howe CG, Liu X, Hall MN, Ilievski V, Caudill MA, Malysheva O, Lomax-Luu AM, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Costa M, Gamble MV

Abstract
BACKGROUND: Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation.
METHODS: We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMC) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults. Sex-specific associations between several blood OCM indices (folate, vitamin B12, choline, betaine, homocysteine) and PTHMs were examined at baseline using regression models, adjusted for multiple tests by controlling for the false discovery rate (PFDR). We also evaluated the effects of folic acid supplementation (400 μg/d for 12 weeks), compared with placebo, on PTHMs.
RESULTS: Associations between choline and H3K36me2 and between vitamin B12 and H3K79me2 differed significantly by sex (Pdiff < 0.01 and <0.05, respectively). Among men, plasma choline was positively associated with H3K36me2 (PFDR < 0.05), and among women, plasma vitamin B12 was positively associated with H3K79me2 (PFDR < 0.01). Folic acid supplementation did not alter any of the PTHMs examined (PFDR = 0.80).
CONCLUSIONS: OCM indices may influence PTHMs in a sex-dependent manner, and folic acid supplementation, at this dose and duration, does not alter PTHMs in PBMCs.
IMPACT: This is the first study to examine the influences of OCM indices on PTHMs in a population that may have increased susceptibility to cancer development due to widespread exposure to arsenic-contaminated drinking water and a high prevalence of hyperhomocysteinemia. Cancer Epidemiol Biomarkers Prev; 26(2); 261-9. ©2016 AACR.

PMID: 27765800 [PubMed - indexed for MEDLINE]

http://ift.tt/2DHn7w3

Probiotic supplementation can positively affect anxiety and depressive symptoms: a systematic review of randomized controlled trials.

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

Probiotic supplementation can positively affect anxiety and depressive symptoms: a systematic review of randomized controlled trials.

Nutr Res. 2016 Sep;36(9):889-898

Authors: Pirbaglou M, Katz J, de Souza RJ, Stearns JC, Motamed M, Ritvo P

Abstract
Gastrointestinal microbiota, consisting of microbial communities in the gastrointestinal tract, play an important role in digestive, metabolic, and immune functioning. Preclinical studies on rodents have linked behavioral and neurochemical changes in the central nervous system with deficits or alterations in these bacterial communities. Moreover, probiotic supplementation in rodents has been shown to markedly change behavior, with correlated changes in central neurochemistry. While such studies have documented behavioral and mood-related supplementation effects, the significance of these effects in humans, especially in relation to anxiety and depression symptoms, are relatively unknown. Thus, the purpose of this paper was to systematically evaluate current literature on the impact of probiotic supplementation on anxiety and depression symptoms in humans. To this end, multiple databases, including Medline, PsycINFO, PubMed, Scopus, and Web of Science were searched for randomized controlled trials published between January 1990 and January 2016. Search results led to a total of 10 randomized controlled trials (4 in clinically diagnosed and 6 in non-clinical samples) that provided limited support for the use of some probiotics in reducing human anxiety and depression. Despite methodological limitations of the included trials and the complex nature of gut-brain interactions, results suggest the detection of apparent psychological benefits from probiotic supplementation. Nevertheless a better understanding of developmental, modulatory, and metagenomic influences on the GI microbiota, specifically as they relate to mood and mental health, represent strong priorities for future research in this area.

PMID: 27632908 [PubMed - indexed for MEDLINE]

http://ift.tt/2nfSvXx

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD2 production in UVR-exposed human skin: a randomised controlled study.

http:--media.wiley.com-assets-7315-19-Wi

Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD2 production in UVR-exposed human skin: a randomised controlled study.

Exp Dermatol. 2016 Dec;25(12):962-968

Authors: Pilkington SM, Gibbs NK, Costello P, Bennett SP, Massey KA, Friedmann PS, Nicolaou A, Rhodes LE

Abstract
Langerhans cells (LCs) are sentinels of skin's immune system, their loss from epidermis contributing to UVR suppression of cell-mediated immunity (CMI). Omega-3 polyunsaturated fatty acids show potential to reduce UVR suppression of CMI in mice and humans, potentially through modulation of LC migration. Our objectives were to examine whether eicosapentaenoic acid (EPA) ingestion influences UV-mediated effects on epidermal LC numbers and levels of immunomodulatory mediators including prostaglandin (PG)D2 , which is expressed by LC. In a double-blind randomised controlled study, healthy individuals took 5-g EPA-rich (n=40) or control (n=33) lipid for 12 weeks; UVR-exposed and unexposed skin samples were taken pre- and postsupplementation. Epidermal LC numbers were assessed by immunofluorescence for CD1a, and skin blister fluid PG and cytokines were quantified by LC-MS/MS and Luminex assay, respectively. Presupplementation, UVR reduced mean (SEM) LC number/mm2 from 913 (28) to 322 (40) (P<.001), and mean PGD2 level by 37% from 8.1 (11.6) to 5.1 (5.6) pg/μL; P<.001), while IL-8 level increased (P<.001). Despite confirmation of EPA bioavailability in red blood cells and skin in the active group, no between-group effect of EPA was found on UVR modulation of LC numbers, PGD2 or cytokine levels postsupplementation. Thus, no evidence was found for EPA reduction of photoimmunosuppression through an impact on epidermal LC numbers. Intriguingly, UVR exposure substantially reduced cutaneous PGD2 levels in humans, starkly contrasting with reported effects of UVR on other skin PG. Lowered PGD2 levels could reflect LC loss from the epidermis and/or altered dendritic cell activity and may be relevant for phototherapy of skin disease.

PMID: 27572109 [PubMed - indexed for MEDLINE]

http://ift.tt/2DJrE1b

Randomized controlled trials: who fails run-in?

https:--s3-service-broker-live-ddda94b7-

https:--www.ncbi.nlm.nih.gov-corehtml-pm

Randomized controlled trials: who fails run-in?

Trials. 2016 Jul 29;17:374

Authors: Rees JR, Mott LA, Barry EL, Baron JA, Figueiredo JC, Robertson DJ, Bresalier RS, Peacock JL

Abstract
BACKGROUND: Early identification of participants at risk of run-in failure (RIF) may present opportunities to improve trial efficiency and generalizability.
METHODS: We conducted a partial factorial-design, randomized, controlled trial of calcium and vitamin D to prevent colorectal adenoma recurrence at 11 centers in the United States. At baseline, participants completed two self-administered questionnaires (SAQs) and a questionnaire administered by staff. Participants in the full factorial randomization (calcium, vitamin D, both, or neither) received a placebo during a 3-month single-blinded run-in; women electing to take calcium enrolled in a two-group randomization (calcium with vitamin D, or calcium alone) and received calcium during the run-in. Using logistic regression models, we examined baseline factors associated with RIF in three subgroups: men (N = 1606) and women (N = 301) in the full factorial randomization and women in the two-group randomization (N = 666).
RESULTS: Overall, 314/2573 (12 %) participants failed run-in; 211 (67 %) took fewer than 80 % of their tablets (poor adherence), and 103 (33 %) withdrew or were uncooperative. In multivariable models, 8- to 13-fold variation was seen by study center in odds of RIF risk in the two largest groups. In men, RIF decreased with age (adjusted odds ratio [OR] per 5 years 0.85 [95 % confidence interval, CI; 0.76-0.96]) and was associated with being single (OR 1.65 [95 % CI; 1.10-2.47]), not graduating from high school (OR 2.77 [95 % CI; 1.58-4.85]), and missing SAQ data (OR 1.97 [1.40-2.76]). Among women, RIF was associated primarily with health-related factors; RIF risk was lower with higher physical health score (OR 0.73 [95 % CI; 0.62-0.86]) and baseline multivitamin use (OR 0.44 [95 % CI; 0.26-0.75]). Women in the 5-year colonoscopy surveillance interval were at greater risk of RIF than those with 3-year follow-up (OR 1.91 [95 % CI; 1.08-3.37]), and the number of prescription medicines taken was also positively correlated with RIF (p = 0.03). Perceived toxicities during run-in were associated with 12- to 29-fold significantly increased odds of RIF.
CONCLUSIONS: There were few common baseline predictors of run-in failure in the three randomization groups. However, heterogeneity in run-in failure associated with study center, and missing SAQ data reflect potential opportunities for intervention to improve trial efficiency and retention.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT00153816 . Registered September 2005.

PMID: 27474021 [PubMed - indexed for MEDLINE]

http://ift.tt/2nkFJXQ

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Σάββατο 27 Ιανουαρίου 2018

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