An Unusual Combination: KRAS and BRAF Co-mutated Metastatic Colorectal Cancer

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Advances of Molecular Targeted Therapy in Gastric Cancer

Abstract

Background

Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life.

Discussion

In the treatment of human epidermal growth factor receptor 2 (HER2)-positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances.

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ACTH-Producing Pancreatic Neuroendocrine Tumor Presenting with Severe Hypokalemic Alkalosis: A Case Report

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Liposarcoma of Hypopharynx and Esophagus: a Unique Entity?

Abstract

Purpose

Liposarcoma is the most common soft tissue sarcoma in adults. It represents approximately 20 % of all mesenchymal malignancies. It most frequently involves retroperitoneum, trunk, and extremities. Hypopharyngeal and esophageal localization of liposarcoma is extremely rare.

Methods

We performed a systematic review of literature and reported 26 and 33 cases of hypopharyngeal and esophageal liposarcoma. We analyzed natural history, imaging features, histology, treatment, and prognosis, with a specific focus to similarities and differences between tumors of hypopharynx and esophagus.

Results

Hypopharyngeal and esophageal liposarcomas have more similarities than differences. Incidence has a peak at 6th and 7th decades. The diagnostic procedures are barium swallow, endoscopic examination, and CT/MR imaging. Well-differentiated liposarcoma represents the most frequent histological subtype. Surgical excision is the main treatment. Endoscopic resection can be useful for pedunculated tumors of hypopharynx and cervical esophagus. Differences between hypopharyngeal and esophageal liposarcoma are represented by local recurrence rate (greater for hypopharyngeal tumors), number of giant tumors, and time to recurrence (greater for esophageal tumors). Finally, liposarcomas of distal esophagus need more extended approaches.

Conclusions

Liposarcomas of hypopharynx and cervical esophagus could be considered a unique pathological entity, with similar features and treatment options. Survival rate is dependent on histological type and location. Local recurrence is common, especially for hypopharyngeal liposarcoma, while the risk of lymph node or distant metastasis is very low. Patients should undergo regular examinations to rule out local recurrence, also for a long time, especially for esophageal tumors.

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Giant Prolapsed Anorectal Malignant Melanoma

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Stool Investigations for Colorectal Cancer Screening: From Occult Blood Test to DNA Analysis

Abstract

Purpose

We report an update of current methods for colorectal cancer (CRC) screening based on fecal sample analysis.

Methods

A systematic review of the literature was performed in MEDLINE, EMBASE, and Science Direct electronic databases.

Results

Blood in the stools is the first and most used strategy. Fecal occult blood test (FOBT) and fecal immunochemical test (FIT) are the main methods. Both are economic, easy to perform with high specificity, and low sensitivity. Based on CRC multi-step process with genetic and epigenetic alterations in large bowel cell DNA, single mutations or panels of alterations have been detected. These tests have the advantage of a marked improvement of the sensitivity when compared to fecal blood. However, high costs, poor availability, and correct choice of marker panel represent the major limits. A specific sDNA panel including aberrantly methylated BMP3 and NDRG4 promoter regions, mutant k-ras and β-actin (a reference gene for human DNA quantity), and an immunochemical assay for human hemoglobin has been recently approved by Food and Drug Administration. Novel promising biomarkers for CRC screening are represented by microRNAs (miRNAs), a group of 18-25 nucleotide non-coding RNA molecules that regulate gene expression. Reports on these fecal biomarkers are case-control studies, and each of them evaluates single miRNAs or multi-target panels. On the other hand, some fecal proteins have been studied as possible CRC screening markers, even though they demonstrated poor results. Finally, alterations of estrogen receptor-beta (i.e., dramatic reduction in the early stage of CRC) have been demonstrated in tissue samples.

Conclusions

Specific investigations are warranted in order to add further noninvasive markers to the panel of CRC screening tools.

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Sporadic Gastric Hyperplastic Polyposis with Superimposed Multifocal Adenocarcinoma, an Extremely Rare Case Report and Review of the Literature

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Olfaction in Chronic Rhinosinusitis

Abstract

Olfactory dysfunction is a frequent complaint in chronic rhinosinusitis patients and has a significant impact on quality of life. Therefore, it is essential that clinicians are aware of the importance of olfactory dysfunction in chronic rhinosinusitis (CRS) patients and know how to deal with it. Notably, the evaluation of olfactory function (i.e., using psychophysical testing) and imagery of olfactory bulb play an important role in the evaluation of patients and give essential information about the "baseline" olfactory function. Because the high impact of olfactory function on quality of life and medical and/or surgical treatment should be proposed to patients. However, it remains difficult to predict the outcome of treatment as well as long-term efficacy. The first section of this review is dedicated to the assessment of olfactory function. Secondly, we will discuss the etiopathology of olfactory dysfunction in CRS with and without nasal polyps. Finally, we will review literature findings about the efficacy of different treatments on olfactory function.

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Higher levels of TIMP-1 expression are associated with a poor prognosis in triple-negative breast cancer

Abstract

Background

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional protein that can directly regulate apoptosis and metastasis. In this study, we investigated the functional and molecular mechanisms by which TIMP-1 influences triple-negative breast cancer (TNBC).

Methods

The expression level of TIMP-1 in breast cancer tissues was analyzed using the ONCOMINE microarray database. The overall survival of patients with distinct molecular subtypes of breast cancer stratified by TIMP-1 expression levels was evaluated using Kaplan–Meier analysis. Bisulfate sequencing PCR (BSP) was used to analyze the methylation status of the TIMP-1 promoter. Real-time-PCR (RT-PCR), Western blot and ELISA assays were used to evaluate gene and protein expression in cell lines and human tissue specimens. In addition, TIMP-1 function was analyzed using a series of in vitro and in vivo assays with cells in which TIMP-1 was inhibited using RNAi or neutralizing antibodies.

Results

We found that serum TIMP-1 levels were strongly enhanced in patients with TNBC and that elevated TIMP-1 levels were associated with a poor prognosis in TNBC. However, TIMP-1 levels were not significantly associated with overall survival in other subtypes of breast cancer or in the overall population of breast cancer patients. We also report the first evidence that the TIMP-1 promoter is hypomethylated in TNBC cell lines compared with non-TNBC cell lines, suggesting that aberrant TIMP-1 expression in TNBC results from reduced DNA methylation. RNAi-mediated silencing of TIMP-1 in TNBC cells induced cell cycle arrest at the G1 phase and reduced cyclin D1 expression. In addition, mechanistic analyses revealed that the p-Akt and p-NF-κB signaling pathways, but not the GSK-3β and MAPK1/2 pathways, are associated with TIMP-1 overexpression in TNBC cells. Moreover, neutralizing antibodies against TIMP-1 significantly decreased the rate of tumor growth in vivo.

Conclusions

Our findings suggest that TIMP-1 is a biomarker indicative of a poor prognosis in TNBC patients and that targeting TIMP-1 may provide an attractive therapeutic intervention specifically for triple-negative breast cancer patients.

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Exploiting aberrant mRNA expression in autism for gene discovery and diagnosis

Abstract

Autism spectrum disorder (ASD) is characterized by substantial phenotypic and genetic heterogeneity, which greatly complicates the identification of genetic factors that contribute to the disease. Study designs have mainly focused on group differences between cases and controls. The problem is that, by their nature, group difference-based methods (e.g., differential expression analysis) blur or collapse the heterogeneity within groups. By ignoring genes with variable within-group expression, an important axis of genetic heterogeneity contributing to expression variability among affected individuals has been overlooked. To this end, we develop a new gene expression analysis method—aberrant gene expression analysis, based on the multivariate distance commonly used for outlier detection. Our method detects the discrepancies in gene expression dispersion between groups and identifies genes with significantly different expression variability. Using this new method, we re-visited RNA sequencing data generated from post-mortem brain tissues of 47 ASD and 57 control samples. We identified 54 functional gene sets whose expression dispersion in ASD samples is more pronounced than that in controls, as well as 76 co-expression modules present in controls but absent in ASD samples due to ASD-specific aberrant gene expression. We also exploited aberrantly expressed genes as biomarkers for ASD diagnosis. With a whole blood expression data set, we identified three aberrantly expressed gene sets whose expression levels serve as discriminating variables achieving >70 % classification accuracy. In summary, our method represents a novel discovery and diagnostic strategy for ASD. Our findings may help open an expression variability-centered research avenue for other genetically heterogeneous disorders.

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Comparison and evaluation of biomechanical, electrical, and biological methods for assessment of damage to tissue collagen

Abstract

In regard to evaluating tissue banking methods used to preserve or otherwise treat (process) soft allograft tissue, current tests may not be sufficiently sensitive to detect potential damage inflicted before, during, and after processing. Using controlled parameters, we aim to examine the sensitivity of specific biomechanical, electrical, and biological tests in detecting mild damage to collagen. Fresh porcine pulmonary heart valves were treated with an enzyme, collagenase, and incubated using various times. Controls received no incubation. All valves were cryopreserved and stored at −135 °C until being rewarmed for evaluation using biomechanical, permeability, and cell viability tests. Statistically significant time dependent changes in leaflet ultimate stress, (p = 0.006), permeability (p = 0.01), and viability (p ≤ 0.02, four different days of culture) were found between heart valves subjected to 0–15 min of collagenase treatment (ANOVA). However, no statistical significance was found between the tensile modulus of treated and untreated valves (p = 0.07). Furthermore, the trends of decreasing and increasing ultimate stress and viability, respectively, were somewhat inconsistent across treatment times. These results suggest that permeability tests may offer a sensitive, quantitative assay to complement traditional biomechanical and viability tests in evaluating processing methods used for soft tissue allografts, or when making changes to current validated methods. Multiple test evaluation may also offer insight into the mechanism of potential tissue damage such as, as is the case here, reduced collagen content and increased tissue porosity.

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Cartilage storage at 4 °C with regular culture medium replacement benefits chondrocyte viability of osteochondral grafts in vitro

Abstract

Maintenance of articular cartilage allografts in culture media is a common method of tissue storage; however, the technical parameters of graft storage remain controversial. In this study, we examined the optimal temperature and culture medium exchange rate for the storage of osteochondral allografts in vitro. Cylindrical osteochondral grafts (n = 120), harvested from the talar joint surface of ten Boer goats, were randomly classified into four groups and stored under the following conditions: Group A1 was maintained at 4 °C in culture medium that was refreshed every 2 days; Group A2 was maintained at 4 °C in the same culture medium, without refreshing; Group B1, was maintained at 37 °C in culture medium that was refreshed every 2 days; Group B2, was maintained at 37 °C in the same culture medium, without refreshing. Chondrocyte viability in the grafts was determined by ethidium bromide/fluorescein diacetate staining on days 7, 21, and 35. Proteoglycan content was measured by Safranin-O staining. Group A1 exhibited the highest chondrocyte survival rates of 90.88 %, 88.31 % and 78.69 % on days 7, 21, and 35, respectively. Safranin O staining revealed no significant differences between groups on days 21 and 35. These results suggest that storage of osteochondral grafts at 4 °C with regular culture medium replacement should be highly suitable for clinical application.

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Linezolid-induced thrombocytopenia in two patients with renal dysfunction

2016-04-30T05-39-45Z
Source: Cukurova Medical Journal
Engin Melek, Bahriye Atmış, Aysun Karabay Bayazıt, Ali Anarat.
Linezolid is an oxazolidinone antibiotic, active against gram positive bacteria that are resistant to other antibiotics including glycopeptides. Thrombocytopenia is an adverse effect of linezolid. Although various risk factors have been suggested, the mechanisms behind this side effect are largely unknown. Here, we report two adolescents with the diagnosis of chronic kidney disease who developed thrombocytopenia following treatment with linezolid. Our purpose in highlighting these cases is to increase the clinical awareness concerning this side effect of linezolid. While it is well known that thrombocytopenia may develop during linezolid treatment, it is relatively unknown that patients with renal dysfunction have an increased risk for the development of thrombocytopenia compared to patients without renal dysfunction.


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Psoralen and Isopsoralen Ameliorate Sex Hormone Deficiency-Induced Osteoporosis in Female and Male Mice

Osteoporosis is a systemic skeletal disease, which is characterized by a systemic destruction of bone mass and microarchitecture. With life standard improved, the treatment of osteoporosis attracted more attention. The aim of this study is to verify the osteoprotective effect of psoralen and isopsoralen in females and males. Female and male mice were divided into 7 groups in this study: control group (sham-operation), model group (by ovariectomy or orchidectomy), positive control group (females given estradiol valerate; males given alendronate sodium), psoralen groups (10 mg/kg and 20 mg/kg), and isopsoralen groups (10 mg/kg and 20 mg/kg). After administration of psoralen and isopsoralen for 8 weeks, osteoporosis was ameliorated with increasing bone strength and improving trabecular bone microstructure as indicated by CT scan and pathology. Serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRACP), osteocalcin (OC), and C-terminal cross-linking telopeptides of type I collagen (CTX-1) were examined. Decreased TRACP and increased ALP/TRACP suggested restoring from bone destruction. These results suggest that psoralen and isopsoralen may be used as good natural compounds for the treatment of osteoporosis in males, as well as females.

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Neuroinfection as a Mask of Lung Cancer: A Case Series

Introduction. The diagnosis of lung cancer may still be difficult due to the fact that the first symptoms very often mimic symptoms of other diseases. Case Presentation. In this paper we present two cases, in which initial diagnosis of neuroinfection delayed proper diagnosis. Conclusion. Based on our experience we concluded that neurological symptoms in the area endemic for tick-borne diseases suggesting neuroinfection require careful differential diagnosis. Moreover, neurological symptoms in heavy smokers may be associated with metastases of lung cancer.

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Research and Responsibility

Publication date: Available online 29 April 2016
Source:Academic Radiology
Author(s): Annemarie Relyea-Chew




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Clinical Decision Support at the Point-of-Order Entry: An Education Simulation Pilot with Medical Students

Publication date: Available online 29 April 2016
Source:Academic Radiology
Author(s): Marc H. Willis, L. Alexandre Frigini, Jay Lin, David M. Wynne, Karla A. Sepulveda
Rationale and ObjectivesWe have been called to reform radiology undergraduate medical education (UME) curricula. Clinically available clinical decision support provides an opportunity to improve education regarding appropriate imaging utilization, patient safety, and cost-effective care.Material and MethodsWe created an education simulation portal utilizing integrated clinical decision support. The portal was then piloted with 34 volunteer medical students at our institution in a blended learning environment. A program assessment was performed utilizing the results from a qualitative survey, pre-test, and post-test.ResultsThe large majority of medical students felt this supplemental education resource should be included in our UME curriculum (85.29%). All students perceived value in the education simulation portal. The students performed significantly better on the post-test in multiple categories (overall P <.0001), including Choosing Wisely topics (P = .0207).ConclusionsBased on our program assessment from this pilot program, we believe this innovative educational resource has significant potential to fill curricular gaps in radiology UME curricula. This platform is scalable and can be further customized to fill needs across the continuum of medical education.



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Feasibility of automated proton therapy plan adaptation for head and neck tumors using cone beam CT images

Abstract

Background

Intensity modulated proton therapy (IMPT) of head and neck (H&N) tumors may benefit from plan adaptation to correct for the dose perturbations caused by weight loss and tumor volume changes observed in these patients. As cone beam CT (CBCT) is increasingly considered in proton therapy, it may be possible to use available CBCT images following intensity correction for plan adaptation. This is the first study exploring IMPT plan adaptation on CBCT images corrected and delineated by deformable image registration of the planning CT (pCT) to the CBCT, yielding a virtual CT (vCT).

Methods

A Morphons algorithm was used to deform the pCTs and corresponding delineations of 9 H&N cancer patients to a weekly CBCT acquired within ±3 days of a control replanning CT scan (rpCT). The IMPT treatment plans were adapted using the vCT and the adapted and original plans were recalculated on the rpCT for dose/volume parameter evaluation of the impact of adaptation.

Results

On the rpCT, the adapted plans were equivalent to the original plans in terms of target volumes D ₉₅ and V ₉₅, but showed a significant reduction of D ₂ in these volumes. OAR doses were mostly equivalent or reduced. In particular, the adapted plans did not reduce parotid gland D _mean, but the dose to the optical system. For three patients the spinal cord or brain stem received higher, though well below tolerance, maximum dose. Subsequent tightening of the treatment planning constraints for these OARs on new vCT-adapted plans did not degrade target coverage and yielded pCT equivalent plans on the vCT.

Conclusions

An offline automated procedure to generate an adapted IMPT plan on CBCT images was developed and investigated. When evaluating the adapted plan on a control rpCT we observed reduced D ₂ in target volumes as major improvement. OAR sparing was only partially improved by the procedure. Despite potential limitations in the accuracy of the vCT approach, an improved quality of the adapted plans could be achieved.

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Safety of Monopolar Electrocautery in Patients With Cochlear Implants.

Safety of Monopolar Electrocautery in Patients With Cochlear Implants.

Ann Otol Rhinol Laryngol. 2016 Apr 28;

Authors: Tien DA, Woodson EA, Anne S

Abstract
OBJECTIVE: The outcomes of 2 patients with cochlear implants (CIs) who underwent adenotonsillectomy (AT) with inadvertent use of monopolar cautery are presented. The safety data regarding monopolar cautery use in CI recipients is also reviewed.
STUDY DESIGN: This is a retrospective case series of 2 CI recipients that underwent AT with monopolar cautery and literature review of electrocautery safety in the setting of CI.
RESULTS: Two patients with CIs underwent AT with use of monopolar cautery inadvertently by surgeons that do not routinely perform cochlear implants as part of his or her clinical practice. Patient 1 was a 9-year-old female who had AT for obstructive sleep apnea (OSA) after undergoing unilateral CI for profound congenital sensorineural hearing loss (SNHL) 8 years ago. Patient 2 was a 7-year-old female who underwent AT for OSA 4 months after undergoing unilateral CI for congenital SNHL. Both patients had no immediate signs of complications with their CI use postoperatively. Both patients demonstrated unchanged postoperative neural response telemetry and behavioral audiometric testing. Patient 1 continues to have no CI-related complications 3.5 years after the procedure. Patient 2 has been followed for at least 3 months by audiometric testing and 10 months by otolaryngologist with no CI-related complications.
CONCLUSION: Although animal and cadaveric studies suggest that monopolar cautery may be safely used in patients with cochlear implants, there have been no in vivo human studies that have evaluated the risk to the patient or implant. This is a report of a small, unintended experience with 2 patients, both of whom exhibit no complications or changes to CI function thus far.

PMID: 27126654 [PubMed - as supplied by publisher]

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Budget Impact Analysis of Veterans Affairs Medical Foster Homes versus Community Living Centers.

Budget Impact Analysis of Veterans Affairs Medical Foster Homes versus Community Living Centers.

Popul Health Manag. 2016 Apr 29;

Authors: Sutton BS, Pracht É, Williams AR, Alemi F, Williams AE, Levy C

Abstract
The objectives were to determine whether and by what amounts the US Department of Veterans Affairs (VA) use of Medical Foster Homes (MFH) rather than Community Living Centers (CLC) reduced budget impacts to the VA. This was a retrospective, matched, case-control study of veterans residing in MFH or CLC in the VA health care system from 2008 to 2012. Administrative data sets, nearest neighbor matching, generalized linear models, and a secondary analysis were used to capture and analyze budget impacts by veterans who used MFH or CLC exclusively in 2008-2012. Controls of 1483 veterans in CLC were matched to 203 cases of veterans in MFH. Use of MFH instead of CLC reduced budget impacts to the VA by at least $2645 per veteran per month. A secondary analysis of the data using different matching criteria and statistical methods produced similar results, demonstrating the robustness of the estimates of budget impact. When the average out-of-pocket payments made by MFH residents, not made by CLC residents, were included in the analysis, the net reduction of budget impact ranged from $145 to $2814 per veteran per month or a savings of $1740 to $33,768 per veteran per year. Even though outpatient costs of MFH are higher, much of the reduced budget impact of MFH use arises from lower inpatient or hospital costs. Reduced budget impacts on the VA system indicate that expansion of the MFH program may be cost-effective. Implications for further research are suggested. (Population Health Management 20xx;xx:xxx-xxx).

PMID: 27128142 [PubMed - as supplied by publisher]

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Factors Associated with Myelosuppression Related to Low-Dose Methotrexate Therapy for Inflammatory Rheumatic Diseases.

Factors Associated with Myelosuppression Related to Low-Dose Methotrexate Therapy for Inflammatory Rheumatic Diseases.

PLoS One. 2016;11(4):e0154744

Authors: Mori S, Hidaka M, Kawakita T, Hidaka T, Tsuda H, Yoshitama T, Migita K, Ueki Y

Abstract
OBJECTIVE: Severe myelosuppression is a serious concern in the management of rheumatic disease patients receiving methotrexate (MTX) therapy. This study was intended to explore factors associated with the development of MTX-related myelosuppression and its disease severity.
METHODS: We retrospectively examined a total of 40 cases of MTX-related myelosuppression that had been filed in the registries of participating rheumatology and hematology divisions. Data before onset were compared with those of 120 controls matched for age and sex. Cytopenia was graded according to the National Cancer Institute criteria for adverse events. Data before and at onset were compared between the severe and non-severe groups.
RESULTS: Non-use of folic acid supplements, concurrent medications, and low renal function were significantly associated with the development of myelosuppression (p < 0.001, p < 0.001, and p = 0.002, respectively). In addition, significantly lower MTX dosages, higher blood cell counts, and lower hemoglobin levels were seen in the myelosuppression group (p < 0.001). No patients exhibited leukocytopenia, neutropenia, or thrombocytopenia in routine blood monitoring taken within the past month. One-fourth developed myelosuppression within the first two months (an early-onset period). Myelosuppression was severe in approximately 40% of patients. Hypoalbuminemia and non-use of folic acid supplements were significantly associated with the severity of pancytopenia (p = 0.001 and 0.008, respectively). Besides these two factors, early onset and the use of lower doses of MTX were significantly associated with the severity of neutropenia (p = 0.003, 0.007, 0.003, and 0.002, respectively).
CONCLUSIONS: Myelosuppression can occur abruptly at any time during low-dose MTX therapy, but severe neutropenia is more likely to occur in the early-onset period of this therapy. Contrary to our expectations, disease severity was not dependent on MTX doses. Serum albumin levels and folic acid supplementation are the important factors affecting the severity of MTX-related pancytopenia and neutropenia.

PMID: 27128679 [PubMed - as supplied by publisher]

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Quantifying short-term and long-term health benefits of attaining ambient fine particulate pollution standards in Guangzhou, China

Publication date: July 2016
Source:Atmospheric Environment, Volume 137
Author(s): Hualiang Lin, Tao Liu, Jianpeng Xiao, Weilin Zeng, Xing Li, Lingchuan Guo, Yanjun Xu, Yonghui Zhang, Michael G. Vaughn, Erik J. Nelson, Zhengmin (Min) Qian, Wenjun Ma
In 2012, Chinese Environmental Bureau modified its National Ambient Air Quality Standards to include fine particulate matter (PM2.5). Recent air pollution monitoring data shows that numerous locations have exceeded this standard, which may have resulted in avoidable adverse health effects. For example, among the 74 Chinese cities with PM2.5 monitoring data in 2013, only three cities attained the annual air quality standard (35 μg/m³). This study aimed to quantify the potential short- and long-term health benefits from achieving the Chinese ambient air quality standard and WHO's air quality objectives. A generalized additive model was used to estimate the short-term association of mortality with changes in daily PM2.5 concentrations, based on which we estimated the potential premature mortality reduction that would have been achieved during the period of 2012–2015 if the daily air quality standard had been met in Guangzhou, China; we also estimated the avoidable deaths if attaining the annual air quality standard using the relative risk obtained from a previous cohort study. During the study period, there were 160 days exceeding the national daily PM2.5 standard (75 μg/m³) in Guangzhou, and the annual average concentration (47.7 μg/m³) was higher than the air quality standard of 35 μg/m³. Significant associations between PM2.5 and mortality were observed. An increase of 10 μg/m³ in PM2.5 was associated with increases in daily death counts of 0.95% (95% CI: 0.56%, 1.34%) in natural mortality, 1.31% (95% CI: 0.75%, 1.87%) in cardiovascular mortality, and 1.06% (95% CI: 0.19%, 1.94%) in respiratory mortality. The health benefits of attaining the national daily air quality standard of PM2.5 (75 μg/m³) would have prevented 143 [95% confidence interval (CI): 84, 203] fewer natural deaths, including 84 (95% CI: 48, 121) fewer cardiovascular deaths and 27 (95% CI: 5, 49) fewer respiratory deaths. Had the annual PM2.5 levels been reduced to 35 μg/m³, an estimated 3875 (95% CI: 1852, 6074) natural deaths, 2378 (95% CI: 800, 4230) cardiovascular deaths, and 227 (95% CI: -437, 1033) respiratory deaths could have been prevented. Even greater substantial mortality reductions could be achieved if the WHO's air quality objectives were met. Our study suggests that air pollution is significantly associated with mortality in Guangzhou, and more stringent air quality standards would significantly reduce air pollution-related premature mortality.



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Theoretical model for diffusive greenhouse gas fluxes estimation across water-air interfaces measured with the static floating chamber method

Publication date: July 2016
Source:Atmospheric Environment, Volume 137
Author(s): Shangbin Xiao, Chenghao Wang, Richard Jeremy Wilkinson, Defu Liu, Cheng Zhang, Wennian Xu, Zhengjian Yang, Yuchun Wang, Dan Lei
Aquatic systems are sources of greenhouse gases on different scales, however the uncertainty of gas fluxes estimated using popular methods are not well defined. Here we show that greenhouse gas fluxes across the air-water interface of seas and inland waters are significantly underestimated by the currently used static floating chamber (SFC) method. We found that the SFC CH4 flux calculated with the popular linear regression (LR) on changes of gas concentration over time only accounts for 54.75% and 35.77% of the corresponding real gas flux when the monitoring periods are 30 and 60 min respectively based on the theoretical model and experimental measurements. Our results do manifest that nonlinear regression models can improve gas flux estimations, while the exponential regression (ER) model can give the best estimations which are close to true values when compared to LR. However, the quadratic regression model is proved to be inappropriate for long time measurements and those aquatic systems with high gas emission rate. The greenhouse gases effluxes emitted from aquatic systems may be much more than those reported previously, and models on future scenarios of global climate changes should be adjusted accordingly.



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Complete Remission of Acute Myeloid Leukemia following Cisplatin Based Concurrent Therapy with Radiation for Squamous Cell Laryngeal Cancer.

Related Articles

Complete Remission of Acute Myeloid Leukemia following Cisplatin Based Concurrent Therapy with Radiation for Squamous Cell Laryngeal Cancer.

Case Rep Hematol. 2016;2016:8581421

Authors: Mody MD, Gill HS, Higgins KA, Saba NF, Kota VK

Abstract
Acute myeloid leukemia (AML) is a myeloid disorder with several established treatment regimens depending on patient and leukemic factors. Cisplatin is known to have strong leukemogenic potential and is rarely used even as salvage therapy in relapsed or refractory AML. We present a patient simultaneously diagnosed with AML and squamous cell carcinoma of the larynx, who was found to be in complete remission from AML following treatment with cisplatin based chemoradiotherapy for his laryngeal cancer.

PMID: 27127664 [PubMed]

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Usefulness of radiologic examinations for diagnosing level VI lymph node metastasis in patients with laryngohypopharyngeal carcinoma.

Related Articles

Usefulness of radiologic examinations for diagnosing level VI lymph node metastasis in patients with laryngohypopharyngeal carcinoma.

Eur Arch Otorhinolaryngol. 2016 Apr 28;

Authors: Park HS, Chung EJ, Park MW, Bae SH, Jung SY, Kim HS, Yoon DY, Rho YS

Abstract
The aim of this study was to estimate the usefulness of imaging modalities for diagnosing level VI lymph node metastasis in patients with laryngohypopharyngeal cancer. A retrospective review of 138 patients with squamous cell carcinoma of the larynx or hypopharynx who underwent central compartment neck dissection (CCND) was performed. Level VI metastasis occurred in 29 of 138 (21 %) patients. CT accuracy and sensitivity for level VI lymph node was 85.5 and 48.3 %, respectively. Respective values for MRI, US, and PET were 84.4 and 41.4 %, 87.7 and 44.8 %, and 81.2 and 34.5 %. CT combined with US demonstrated the best result in sensitivity (51.7 %) and negative predictive value (NPV) (88.1 %) compared to those of other imaging techniques. CT combined with US could improve sensitivity and NPV compared to CT or US alone. Considering cost-effectiveness and the highest results in all parameters compared to those of other combinations of imaging techniques, CT combined with US could be the best preoperative imaging modalities for evaluating laryngohypopharyngeal cancer. However, these imaging techniques are not absolutely reliable methods for detecting occult metastasis in the level VI due to high false-negative rates. Elective CCND should be considered in indicated patients (>N2b, T4), even if physical examinations and the radiologic findings of level VI nodes are negative.

PMID: 27126335 [PubMed - as supplied by publisher]

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Drug delivery system of basic fibroblast growth factor using gelatin hydrogel for restoration of acute vocal fold scar.

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Drug delivery system of basic fibroblast growth factor using gelatin hydrogel for restoration of acute vocal fold scar.

Auris Nasus Larynx. 2016 Apr 25;

Authors: Kobayashi T, Mizuta M, Hiwatashi N, Kishimoto Y, Nakamura T, Kanemaru SI, Hirano S

Abstract
OBJECTIVE: There continue to be therapeutic challenges in the management of vocal fold scarring. We previously showed that basic fibroblast growth factor (bFGF) injection has therapeutic potential for vocal fold scarring. However, the working time of bFGF is relatively short, and multiple injections were required in many cases to obtain the regenerative effect. An efficacious delivery system for bFGF has yet to be established. We designed a method of sustained drug delivery system (DDS) of bFGF by using a gelatin hydrogel. Hydrogel has been developed for targeted delivery and controlled release of bFGF. Hydrogel of the particle type is also injectable and commercially available. The current study aims to investigate the effects of a single injection of bFGF-DDS on acute vocal fold scarring using a canine model.
METHODS: Vocal folds from eight beagles were unilaterally scarred by stripping the lamina propria. One month later, hydrogels (0.5ml) containing 10μg of bFGF were injected into the scarred vocal folds of four beagles (FGF-hydrogel group). Saline (0.5ml) was injected into the other four beagles (sham group). Vibratory and histological examination of excised larynges was performed 5 months after treatment. Comparative analysis between the current data and our previous data with repeated injection of bFGF solution was also completed.
RESULTS: Vibratory examination demonstrated significantly improved vibration in the bFGF hydrogel-treated group. Histological examination of the bFGF hydrogel group showed restoration of hyaluronic acid in the lamina propria as compared to sham. Comparison between the DDS system and our previous bFGF solution injection indicated better effects of the DDS system on vibratory amplitude.
CONCLUSION: A single injection of bFGF hydrogel has regenerative effects on acute vocal fold scarring, which is at least similar to repeated injection of bFGF solution.

PMID: 27126068 [PubMed - as supplied by publisher]

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Heads Up: a pilot trial of a psychological intervention to improve nutrition in head and neck cancer patients undergoing radiotherapy.

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Heads Up: a pilot trial of a psychological intervention to improve nutrition in head and neck cancer patients undergoing radiotherapy.

Eur J Cancer Care (Engl). 2016 Apr 28;

Authors: Britton B, Baker A, Clover K, McElduff P, Wratten C, Carter G

Abstract
Malnutrition in head and neck cancer (HNC) patients is common and associated with poorer radiotherapy outcomes including increased mortality. This pilot trial investigates the feasibility and effectiveness of a psychological intervention to improve nutritional status, depression and mortality in HNC patients undergoing radiotherapy. Fifty-nine intervention patients received motivational interviewing and cognitive behavioural therapy compared to 70 historical controls who received treatment as usual. Participants were assessed for nutrition, depression and mortality. There were no significant differences between groups in nutritional status, depression or mortality. Subgroup analyses among patients at greater nutritional risk (cancers of the oral cavity, pharynx, larynx) revealed a potentially clinically important reduction on the PG-SGA and lower mortality (31% of controls vs. 16% intervention; P = 0.03) in favour of the intervention condition. Potential benefits in nutritional status and in mortality in this pilot trial of a psychological intervention among HNC patients at high nutritional risk suggest that a larger randomised controlled trial is warranted.

PMID: 27125571 [PubMed - as supplied by publisher]

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Cricothyroidotomy catheters: an investigation of mechanisms of failure and the effect of a novel intracatheter stylet.

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Cricothyroidotomy catheters: an investigation of mechanisms of failure and the effect of a novel intracatheter stylet.

Anaesthesia. 2016 Jan;71(1):39-43

Authors: Hebbard PD, Ul Hassan I, Bourke EK

Abstract
Emergency catheter cricothyroidotomy often fails. Case reports have concentrated on kinking and displacement of the catheter as the major causes. We investigated catheter tip penetration of the trachea. Using insertion angles of 90°, 75°, 60°, 45° and 30° we advanced 14 G intravenous catheters into fresh isolated sheep tracheas during high pressure oxygen insufflation. At all angles, the catheter tip became blocked by pushing into the mucosa with submucosal gas injection on one or more attempts. Full thickness rupture with extratracheal gas also occurred on insertions at 90° and 60°. We then tested a Luer-mounted prototype wire stylet which remains in situ during insufflation. Using the same methodology, the stylet was able to be placed and prevented blockage at all angles of insertion. Mucosal trauma and submucosal gas injection occurred on insertions at 90° and 75°. Our results should guide further stylet design.

PMID: 26507099 [PubMed - indexed for MEDLINE]

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Laryngeal reconstruction with a sternohyoid muscle flap after supracricoid laryngectomy: postoperative respiratory and swallowing evaluation.

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Laryngeal reconstruction with a sternohyoid muscle flap after supracricoid laryngectomy: postoperative respiratory and swallowing evaluation.

Otolaryngol Head Neck Surg. 2014 Nov;151(5):824-9

Authors: Yu Y, Wang XL, Xu ZG, Wu YH

Abstract
OBJECTIVE: To compare postoperative respiratory and swallowing functions between patients who underwent classic supracricoid laryngectomy (SCL) and those who underwent SCL with laryngeal reconstruction using the sternohyoid muscle.
STUDY DESIGN: Prospective study.
SETTING: National cancer center.
SUBJECTS AND METHODS: Forty-four patients who consecutively underwent SCL for laryngeal squamous cell carcinoma from December 2009 to March 2011 were included. Postoperative parameters including the mean tracheostomy decannulation time, tracheostomy decannulation rate at 6 months, mean nasogastric tube (NGT) removal time, degree of dysphagia at 3 months, and survival time after surgery were evaluated.
RESULTS: Twenty-one patients underwent classic SCL (group A), and 23 underwent SCL with laryngeal reconstruction (group B). After a median follow-up period of 37 months (range, 3-44 months), group A had a significantly longer mean decannulation time (120.05 ± 109.38 days vs 33.43 ± 22.60 days, respectively; P < .01) and NGT removal time (37.30 ± 29.97 days vs 17.22 ± 10.95 days, respectively; P < .01) than group B. Swallowing function after 6 months was significantly better in group B than in group A (P = .004). The decannulation rate after 6 months was significantly higher in group B than in group A (95.7% vs 66.7%, respectively; P = .036). The 3-year disease-free survival rate was not significantly different between group A and group B (95.2% vs 95.7%, respectively; P = .961).
CONCLUSION: Laryngeal reconstruction using a sternohyoid muscle flap seems to improve quality of life in the early postoperative period after SCL.

PMID: 25205642 [PubMed - indexed for MEDLINE]

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High specificity of a novel Zika virus ELISA in European patients after exposure to different flaviviruses.

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High specificity of a novel Zika virus ELISA in European patients after exposure to different flaviviruses.

Euro Surveill. 2016 Apr 21;21(16)

Authors: Huzly D, Hanselmann I, Schmidt-Chanasit J, Panning M

Abstract
The current Zika virus (ZIKV) epidemic in the Americas caused an increase in diagnostic requests in European countries. Here we demonstrate high specificity of the Euroimmun anti-ZIKV IgG and IgM ELISA tests using putative cross-reacting sera of European patients with antibodies against tick-borne encephalitis virus, dengue virus, yellow fever virus and hepatitis C virus. This test may aid in counselling European travellers returning from regions where ZIKV is endemic.

PMID: 27126052 [PubMed - in process]

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Objective quantification of the vocal fold vascular pattern: comparison of narrow band imaging and white light endoscopy.

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Objective quantification of the vocal fold vascular pattern: comparison of narrow band imaging and white light endoscopy.

Eur Arch Otorhinolaryngol. 2016 Apr 28;

Authors: Pliske G, Voigt-Zimmermann S, Glaßer S, Arens C

Abstract
No clinical standard procedure has yet been defined to quantify the vascular pattern of vocal folds. Subjective classification trials have shown a lot of promise. Narrow band imaging (NBI) as an endoscopic imaging tool is useful, because it shows the vascular structure clearer than white light endoscopy (WL) alone. Endoscopic images of 74 human vocal folds (NBI and WL) were semi-automatically evaluated after image processing with respect to pixels of vessels and mucosa by the software MeVisLab. The ratios of vessel/mucosa pixels were compared. Using NBI, more vocal fold vessels are visible compared with WL alone (p = 0.000). There may be a difference between the right and left vocal folds due to the handedness of the examiner (p = 0.033) without any interaction between the method (NBI/WL) and the side (right/left) (p = 0.467). MeVisLab is a suitable tool for the objective quantification of the vessel/mucosa ratio for NBI and WL endoscopic images. NBI is an appropriate endoscopic tool for examination of diseases of vocal folds with changes in the vascular pattern. There is evidence that the handedness of the examiner may have an influence on the quality of the examination between the right and left vocal folds.

PMID: 27126337 [PubMed - as supplied by publisher]

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Efficacy and tolerability of an ectoine mouth and throat spray compared with those of saline lozenges in the treatment of acute pharyngitis and/or laryngitis: a prospective, controlled, observational clinical trial.

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Efficacy and tolerability of an ectoine mouth and throat spray compared with those of saline lozenges in the treatment of acute pharyngitis and/or laryngitis: a prospective, controlled, observational clinical trial.

Eur Arch Otorhinolaryngol. 2016 Apr 28;

Authors: Müller D, Lindemann T, Shah-Hosseini K, Scherner O, Knop M, Bilstein A, Mösges R

Abstract
The aim of this observational trial was to evaluate the efficacy and tolerability of a mouth and throat spray containing ectoine in the treatment of acute pharyngitis and/or laryngitis. The outcome was compared with control treatment using saline lozenges. This study was designed as a prospective, controlled, non-randomized, observational multicenter clinical trial and was conducted in Germany. The study population consisted of 95 patients. The decision for treatment with either spray or lozenges was based on the patients' preference for pharyngeal or oral application. Investigators assessed symptoms specific to acute pharyngitis/laryngitis and determined the pharyngitis symptom score. Both patients and investigators evaluated the tolerability and efficacy of the treatment applied. Treatment with the spray showed higher efficacy, 1.95 ± 0.81 versus 1.68 ± 0.67 (investigators) and 1.97 ± 0.88 versus 1.57 ± 0.69 (patients, p < 0.05). Treatment with the spray resulted in significantly greater reduction of cervical lymph node swelling (p < 0.05), ∆ spray = 0.44 ± 0.62, ∆ lozenges = 0.21 ± 0.62. The lozenges showed some advantage in relieving cough, ∆ lozenges = 0.62 ± 0.94 versus ∆ spray = 0.44 ± 0.85. Both patients and investigators rated the tolerability of both medical devices as "good" to "very good". Adverse events of mild to moderate severity were either possibly related or not related to the medical devices used. No serious adverse events occurred. Taken together, while the tolerability was consistent in both treatment groups, the ectoine-based spray showed superior efficacy in treating acute pharyngitis and/or laryngitis.

PMID: 27126336 [PubMed - as supplied by publisher]

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Usefulness of radiologic examinations for diagnosing level VI lymph node metastasis in patients with laryngohypopharyngeal carcinoma.

Related Articles

Usefulness of radiologic examinations for diagnosing level VI lymph node metastasis in patients with laryngohypopharyngeal carcinoma.

Eur Arch Otorhinolaryngol. 2016 Apr 28;

Authors: Park HS, Chung EJ, Park MW, Bae SH, Jung SY, Kim HS, Yoon DY, Rho YS

Abstract
The aim of this study was to estimate the usefulness of imaging modalities for diagnosing level VI lymph node metastasis in patients with laryngohypopharyngeal cancer. A retrospective review of 138 patients with squamous cell carcinoma of the larynx or hypopharynx who underwent central compartment neck dissection (CCND) was performed. Level VI metastasis occurred in 29 of 138 (21 %) patients. CT accuracy and sensitivity for level VI lymph node was 85.5 and 48.3 %, respectively. Respective values for MRI, US, and PET were 84.4 and 41.4 %, 87.7 and 44.8 %, and 81.2 and 34.5 %. CT combined with US demonstrated the best result in sensitivity (51.7 %) and negative predictive value (NPV) (88.1 %) compared to those of other imaging techniques. CT combined with US could improve sensitivity and NPV compared to CT or US alone. Considering cost-effectiveness and the highest results in all parameters compared to those of other combinations of imaging techniques, CT combined with US could be the best preoperative imaging modalities for evaluating laryngohypopharyngeal cancer. However, these imaging techniques are not absolutely reliable methods for detecting occult metastasis in the level VI due to high false-negative rates. Elective CCND should be considered in indicated patients (>N2b, T4), even if physical examinations and the radiologic findings of level VI nodes are negative.

PMID: 27126335 [PubMed - as supplied by publisher]

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Elements: in this month's issue.

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Elements: in this month's issue.

QJM. 2016 May;109(5):291

Authors: Donnelly SC

PMID: 27126927 [PubMed - in process]

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Long QT Syndrome Leading to Multiple Cardiac Arrests After Posaconazole Administration in an Immune-Compromised Patient with Sepsis: An Unusual Case Report.

Long QT Syndrome Leading to Multiple Cardiac Arrests After Posaconazole Administration in an Immune-Compromised Patient with Sepsis: An Unusual Case Report.

Am J Case Rep. 2016;17:295-300

Authors: Panos G, Velissaris D, Karamouzos V, Matzaroglou C, Tylianakis M

Abstract
BACKGROUND We present the case of a septic patient with severe immunodeficiency, who developed QT interval prolongation followed by episodes of lethal cardiac arrhythmia. Cardiac events occurred after posaconazole administration, incriminating posaconazole use, alone or in combination with voriconazole, as the culpable agent. CASE REPORT A 26-year-old female patient underwent orthopedic surgery to remove ectopic calcifications in her left hip joint. On the first post-operative day she became septic due to a surgical wound infection. Despite being treated according to the therapeutic protocols for sepsis, no clinical improvement was noticed and further assessment revealed an underlying immunodeficiency. Considering the underlying immunodeficiency and to that point poor clinical response, an antifungal agent was added to the antibiotic regiment. Following discontinuation of multiple antifungal agents due to adverse effects, posaconazole was administered. Posaconazole oral intake was followed by episodes of bradycardia and QT interval prolongation. The patient suffered continuous incidents of cardiac arrest due to polymorphic ventricular tachycardia (torsades des pointes) that degenerated to lethal ventricular fibrillation. Posaconazole was immediately discontinued and a temporary pacemaker was installed. The patient finally recovered without any neurological deficit, and was discharged in a good clinical status. CONCLUSIONS Close cardiac monitoring is recommended in cases where posaconazole administration is combined with coexisting risk factors, as they may lead to severe ECG abnormalities and cardiac arrhythmias such as long QT interval syndrome and torsades de pointes. Posaconazole interactions with medications metabolized via the CYP3A4 pathway should be considered an additional risk factor for lethal cardiac incidents.

PMID: 27125217 [PubMed - in process]

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A Simplified Approach to Measure the Effect of the Microvasculature in Diffusion-weighted MR Imaging Applied to Breast Tumors: Preliminary Results.

A Simplified Approach to Measure the Effect of the Microvasculature in Diffusion-weighted MR Imaging Applied to Breast Tumors: Preliminary Results.

Radiology. 2016 Apr 29;:151630

Authors: Teruel JR, Goa PE, Sjøbakk TE, Østlie A, Fjøsne HE, Bathen TF

Abstract
Purpose To evaluate the relative change of the apparent diffusion coefficient (ADC) at low- and medium-b-value regimens as a surrogate marker of microcirculation, to study its correlation with dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging-derived parameters, and to assess its potential for differentiation between malignant and benign breast tumors. Materials and Methods Ethics approval and informed consent were obtained. From May 2013 to June 2015, 61 patients diagnosed with either malignant or benign breast tumors were prospectively recruited. All patients were scanned with a 3-T MR imager, including diffusion-weighted imaging (DWI) and DCE MR imaging. Parametric analysis of DWI and DCE MR imaging was performed, including a proposed marker, relative enhanced diffusivity (RED). Spearman correlation was calculated between DCE MR imaging and DWI parameters, and the potential of the different DWI-derived parameters for differentiation between malignant and benign breast tumors was analyzed by dividing the sample into equally sized training and test sets. Optimal cut-off values were determined with receiver operating characteristic curve analysis in the training set, which were then used to evaluate the independent test set. Results RED had a Spearman rank correlation of 0.61 with the initial area under the curve calculated from DCE MR imaging. Furthermore, RED differentiated cancers from benign tumors with an overall accuracy of 90% (27 of 30) on the test set with 88.2% (15 of 17) sensitivity and 92.3% (12 of 13) specificity. Conclusion This study presents promising results introducing a simplified approach to assess results from a DWI protocol sensitive to the intravoxel incoherent motion effect by using only three b values. This approach could potentially aid in the differentiation, characterization, and monitoring of breast pathologies. (©) RSNA, 2016 Online supplemental material is available for this article.

PMID: 27128662 [PubMed - as supplied by publisher]

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The prevalence of dysphagia among adults in the United States.

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The prevalence of dysphagia among adults in the United States.

Otolaryngol Head Neck Surg. 2014 Nov;151(5):765-9

Authors: Bhattacharyya N

Abstract
OBJECTIVE: To determine the prevalence of dysphagia, reported etiologies, and impact among adults in the United States.
STUDY DESIGN: Cross-sectional analysis of a national health care survey.
SUBJECTS AND METHODS: The 2012 National Health Interview Survey was analyzed, identifying adult cases reporting a swallowing problem in the preceding 12 months. In addition to demographic data, specific data regarding visits to health care professionals for swallowing problems, diagnoses given, and severity of the swallowing problem were analyzed. The relationship between swallowing problems and lost workdays was assessed.
RESULTS: An estimated 9.44 ± 0.33 million adults (raw N = 1554; mean age, 52.1 years; 60.2% ± 1.6% female) reported a swallowing problem (4.0% ± 0.1%). Overall, 22.7% ± 1.7% saw a health care professional for their swallowing problem, and 36.9% ± 0.1.7% were given a diagnosis. Women were more likely than men to report a swallowing problem (4.7% ± 0.2% versus 3.3% ± 0.2%, P < .001). Of the patients, 31.7% and 24.8% reported their swallowing problem to be a moderate or a big/very big problem, respectively. Stroke was the most commonly reported etiology (422,000 ± 77,000; 11.2% ± 1.9%), followed by other neurologic cause (269,000 ± 57,000; 7.2% ± 1.5%) and head and neck cancer (185,000 ± 40,000; 4.9% ± 1.1%). The mean number of days affected by the swallowing problem was 139 ± 7. Respondents with a swallowing problem reported 11.6 ± 2.0 lost workdays in the past year versus 3.4 ± 0.1 lost workdays for those without a swallowing problem (contrast, +8.1 lost workdays, P < .001).
CONCLUSION: Swallowing problems affect 1 in 25 adults, annually. A relative minority seek health care for their swallowing problem, even though the subjective impact and associated workdays lost with the swallowing problem are significant.

PMID: 25193514 [PubMed - indexed for MEDLINE]

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Pedicled adipofascial infraclavicular flap: Elevation technique and its use for maintaining neck contour and vessel coverage after radical and modified radical neck dissection.

Pedicled adipofascial infraclavicular flap: Elevation technique and its use for maintaining neck contour and vessel coverage after radical and modified radical neck dissection.

Head Neck. 2016 Apr 29;

Authors: Yoo J, Low TH, Tam S, Partridge A, MacNeil SD, Nichols AC, Fung K

Abstract
BACKGROUND: The pedicled adipofascial infraclavicular flap (ICF) is based on the anterior perforator of the supraclavicular artery and supplies the fasciocutaneous tissue of the upper chest. This flap may be used to address neck contour defects and vessel coverage after radical and modified radical neck dissections (MRNDs).
METHODS: We described the pedicled adipofascial ICF elevation technique and its use immediately after neck dissections in order to maintain soft tissue volume and vessel coverage. A video of the operation is provided.
RESULTS: Our results demonstrated satisfactory neck contours with adequate volume replacement, great vessel coverage, and little donor-site morbidity.
CONCLUSION: The pedicled adipofascial ICF is a technically straightforward operation with broad possible applications in head and neck surgery. It may be useful to provide vascularized soft-tissue coverage and maintain neck contour after neck dissections. © 2016 Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 27126378 [PubMed - as supplied by publisher]

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Peri-implant bony overgrowth as a cause of revision surgery in auditory osseointegrated implantation

Publication date: July 2016
Source:International Journal of Pediatric Otorhinolaryngology, Volume 86
Author(s): Jared J. Tompkins, Dana K. Petersen, Daniel D. Sharbel, Brian J. McKinnon, C. Bruce MacDonald
Implantation of auditory osseointegrated implants, also known as bone-anchored hearing systems (BAHS), represents a surgical option for select pediatric patients aged 5 years or older with hearing loss. Functional indications in this patient population include conductive or mixed hearing loss. Common complications of implantation include skin infections, chronic skin irritation, hypertrophic skin overgrowth, and loose abutments. In a case series of 15 pediatric patients, we discovered an unexpectedly high skin-related complication rate requiring surgical revision of 53%. During revision surgery, we discovered 5 patients who exhibited significant bony overgrowth at the abutment site, a complication infrequently noted in past literature.



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Response Assessment in Pediatric Neuro-Oncology: Implementation and Expansion of the RANO Criteria in a Randomized Phase II Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

Response Assessment in Pediatric Neuro-Oncology: Implementation and Expansion of the RANO Criteria in a Randomized Phase II Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

AJNR Am J Neuroradiol. 2016 Apr 28;

Authors: Jaspan T, Morgan PS, Warmuth-Metz M, Sanchez Aliaga E, Warren D, Calmon R, Grill J, Hargrave D, Garcia J, Zahlmann G

Abstract
Determination of tumor response to treatment in neuro-oncology is challenging, particularly when antiangiogenic agents are considered. Nontumoral factors (eg, blood-brain barrier disruption, edema, and necrosis) can alter contrast enhancement independent of true tumor response/progression. Furthermore, gliomas are often infiltrative, with nonenhancing components. In adults, the Response Assessment in Neuro-Oncology (RANO) criteria attempted to address these issues. No such guidelines exist yet for children. The ongoing randomized phase II trial, A Study of Avastin (bevacizumab) in Combination With Temolozomide (TMZ) and Radiotherapy in Paediatric and Adolescent Patients With High-Grade Glioma (HERBY), will establish the efficacy and safety of the antiangiogenic agent bevacizumab for the first-line treatment of newly diagnosed high-grade glioma in children (n = 121 patients, enrollment complete). The primary end point is event-free survival (tumor progression/recurrence by central review, second primary malignancy, or death). Determination of progression or response is based on predefined clinical and radiographic criteria, modeled on the RANO criteria and supported by expert pseudoprogression review and the use of standardized imaging protocols. The HERBY trial will also compare conventional MR imaging (T1-weighted and T2/fluid-attenuated inversion recovery sequences) with conventional MR imaging plus diffusion/perfusion imaging for response assessment. It is anticipated that HERBY will provide new insights into antiangiogenic-treated pediatric brain tumors. HERBY will also investigate the practicality of obtaining adequate quality diffusion/perfusion scans in a trial setting, and the feasibility of implementing standard imaging protocols across multiple sites. To date, 61/73 (83.6%) patients with available data have completed diffusion-weighted imaging (uptake of other nonconventional techniques has been limited). Harmonization of imaging protocols and techniques may improve the robustness of pediatric neuro-oncology studies and aid future trial comparability.

PMID: 27127006 [PubMed - as supplied by publisher]

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MR Imaging of the Pituitary Gland and Postsphenoid Ossification in Fetal Specimens.

MR Imaging of the Pituitary Gland and Postsphenoid Ossification in Fetal Specimens.

AJNR Am J Neuroradiol. 2016 Apr 28;

Authors: Mehemed TM, Fushimi Y, Okada T, Kanagaki M, Yamamoto A, Okada T, Takakuwa T, Yamada S, Togashi K

Abstract
BACKGROUND AND PURPOSE: A thorough knowledge of fetal growth and development is key to understanding both the normal and abnormal fetal MR imaging findings. We investigated the size and signal intensity of the normal pituitary gland and the intrasphenoidal ossification around the Rathke pouch in formalin-fixed fetuses on MR imaging.
MATERIALS AND METHODS: Thirty-two fetuses with undamaged brains were included in this study (mean age, 19.93 weeks; age range, 12-31 weeks). Visual inspection of the pituitary and ossification around the Rathke pouch in the sphenoid bone or the postsphenoid ossification was conducted. The extent of pituitary and postsphenoid ossification, pituitary/pons signal ratio, and postsphenoidal ossification/sphenoid bone signal ratio was compared according to gestational age.
RESULTS: The pituitary gland was identified as a hyperintense intrasellar structure in all cases, and postsphenoid ossification was identified as an intrasphenoidal hyperintense area in 27 of the 32 cases (84%). The mean pituitary/pons signal ratio was 1.13 ± 0.18 and correlated weakly with gestational age (R(2) = 0.243), while the mean postsphenoid ossification/sphenoid bone signal ratio was 2.14 ± 0.56 and did not show any increase with gestational age (R(2) = 0.05). No apparent change in the size of pituitary hyperintensity was seen with gestational age (R(2) = 0.001). Postsphenoid ossification showed an increase in size with gestational age (R(2) = 0.307).
CONCLUSIONS: The fetal pituitary gland was hyperintense on T1-weighted images and the pituitary/pons ratio and extent of postsphenoid ossification correlated weakly with gestational age.

PMID: 27127005 [PubMed - as supplied by publisher]

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Intervention versus Aggressive Medical Therapy for Cognition in Severe Asymptomatic Carotid Stenosis.

Intervention versus Aggressive Medical Therapy for Cognition in Severe Asymptomatic Carotid Stenosis.

AJNR Am J Neuroradiol. 2016 Apr 28;

Authors: Lin CJ, Chang FC, Chou KH, Tu PC, Lee YH, Lin CP, Wang PN, Lee IH

Abstract
BACKGROUND AND PURPOSE: Asymptomatic carotid stenosis of ≥70% increases the incidence of microembolism and/or chronic hypoperfusion, which may consequently impair neurocognition and brain connections. We sought controlled evidence for any cognitive benefit of aggressive medical therapy and combined carotid revascularization.
MATERIALS AND METHODS: Patients with asymptomatic, unilateral, ≧70% stenosis of the extracranial ICA chose either aggressive medical therapy alone or in combination with carotid artery stent placement in this nonrandomized controlled study. They were examined with a battery of neuropsychological tests, structural MR imaging, DTI, and resting-state fMRI before and 3 months after treatment.
RESULTS: Forty patients were included with 15 in the medical group and 25 in the stent-placement group. Among them, 13 and 21 in the respective groups completed neuroimaging follow-up. The baseline characteristics and the changes in cognitive performance during 3 months showed no differences between treatment groups. Nevertheless, compared with the medical group, the stent-placement group showed subjective dizziness alleviation (P = .045) and a small increase in fractional anisotropy at the splenium of the corpus callosum and the posterior periventricular white matter ipsilateral to carotid artery stent placement. Moreover, only the stent-placement group showed interval improvement in immediate memory and visuospatial performance, which was accompanied by an increase of functional connectivity at the insular cortex of the dorsal attention network and the medial prefrontal cortex of the default mode network.
CONCLUSIONS: Both aggressive medical therapy alone and combined carotid revascularization in ≧70% asymptomatic carotid stenosis similarly preserved cognition during 3-month follow-up, though the latter had the potential for dizziness alleviation and cognitive and connectivity enhancement.

PMID: 27127004 [PubMed - as supplied by publisher]

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Uremic Encephalopathy: MR Imaging Findings and Clinical Correlation.

Uremic Encephalopathy: MR Imaging Findings and Clinical Correlation.

AJNR Am J Neuroradiol. 2016 Apr 28;

Authors: Kim DM, Lee IH, Song CJ

Abstract
BACKGROUND AND PURPOSE: Uremic encephalopathy is a metabolic disorder in patients with renal failure. The purpose of this study was to describe the MR imaging findings of uremic encephalopathy.
MATERIALS AND METHODS: This study retrospectively reviewed MR imaging findings in 10 patients with clinically proved uremic encephalopathy between May 2005 and December 2014. Parameters evaluated were lesion location and appearance; MR signal intensity of the lesions on T1WI, T2WI, and T2 fluid-attenuated inversion recovery images; the presence or absence of restricted diffusion on diffusion-weighted images and apparent diffusion coefficient maps; and the reversibility of documented signal-intensity abnormalities on follow-up MR imaging.
RESULTS: MR imaging abnormalities accompanying marked elevation of serum creatinine (range, 4.3-11.7 mg/dL) were evident in the 10 patients. Nine patients had a history of chronic renal failure with expansile bilateral basal ganglia lesions, and 1 patient with acute renal failure had reversible largely cortical lesions. Two of 6 patients with available arterial blood gas results had metabolic acidosis. All basal ganglia lesions showed expansile high signal intensity (lentiform fork sign) on T2WI. Varied levels of restricted diffusion and a range of signal intensities on DWI were evident and were not correlated with serum Cr levels. All cortical lesions demonstrated high signal intensity on T2WI. Four patients with follow-up MR imaging after hemodialysis showed complete resolution of all lesions.
CONCLUSIONS: The lentiform fork sign is reliable in the early diagnosis of uremic encephalopathy, regardless of the presence of metabolic acidosis. Cytotoxic edema and/or vasogenic edema on DWI/ADC maps may be associated with uremic encephalopathy.

PMID: 27127003 [PubMed - as supplied by publisher]

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Application of Blood-Brain Barrier Permeability Imaging in Global Cerebral Edema.

Application of Blood-Brain Barrier Permeability Imaging in Global Cerebral Edema.

AJNR Am J Neuroradiol. 2016 Apr 28;

Authors: Ivanidze J, Kallas ON, Gupta A, Weidman E, Baradaran H, Mir D, Giambrone A, Segal AZ, Claassen J, Sanelli PC

Abstract
BACKGROUND AND PURPOSE: Blood-brain barrier permeability is not routinely evaluated in the clinical setting. Global cerebral edema occurs after SAH and is associated with BBB disruption. Detection of global cerebral edema using current imaging techniques is challenging. Our purpose was to apply blood-brain barrier permeability imaging in patients with global cerebral edema by using extended CT perfusion.
MATERIALS AND METHODS: Patients with SAH underwent CTP in the early phase after aneurysmal rupture (days 0-3) and were classified as having global cerebral edema or nonglobal cerebral edema using established noncontrast CT criteria. CTP data were postprocessed into blood-brain barrier permeability quantitative maps of PS (permeability surface-area product), K(trans) (volume transfer constant from blood plasma to extravascular extracellular space), Kep (washout rate constant of the contrast agent from extravascular extracellular space to intravascular space), VE (extravascular extracellular space volume per unit of tissue volume), VP (plasmatic volume per unit of tissue volume), and F (plasma flow) by using Olea Sphere software. Mean values were compared using t tests.
RESULTS: Twenty-two patients were included in the analysis. Kep (1.32 versus 1.52, P < .0001), K(trans) (0.15 versus 0.19, P < .0001), VP (0.51 versus 0.57, P = .0007), and F (1176 versus 1329, P = .0001) were decreased in global cerebral edema compared with nonglobal cerebral edema while VE (0.81 versus 0.39, P < .0001) was increased.
CONCLUSIONS: Extended CTP was used to evaluate blood-brain barrier permeability in patients with SAH with and without global cerebral edema. Kep is an important indicator of altered blood-brain barrier permeability in patients with decreased blood flow, as Kep is flow-independent. Further study of blood-brain barrier permeability is needed to improve diagnosis and monitoring of global cerebral edema.

PMID: 27127002 [PubMed - as supplied by publisher]

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Tractography at 3T MRI of Corpus Callosum Tracts Crossing White Matter Hyperintensities.

Tractography at 3T MRI of Corpus Callosum Tracts Crossing White Matter Hyperintensities.

AJNR Am J Neuroradiol. 2016 Apr 28;

Authors: Reginold W, Itorralba J, Luedke AC, Fernandez-Ruiz J, Reginold J, Islam O, Garcia A

Abstract
BACKGROUND AND PURPOSE: The impact of white matter hyperintensities on the diffusion characteristics of crossing tracts is unclear. This study used quantitative tractography at 3T MR imaging to compare, in the same individuals, the diffusion characteristics of corpus callosum tracts that crossed white matter hyperintensities with the diffusion characteristics of corpus callosum tracts that did not pass through white matter hyperintensities.
MATERIALS AND METHODS: Brain T2 fluid-attenuated inversion recovery-weighted and diffusion tensor 3T MR imaging scans were acquired in 24 individuals with white matter hyperintensities. Tractography data were generated by the Fiber Assignment by Continuous Tracking method. White matter hyperintensities and corpus callosum tracts were manually segmented. In the corpus callosum, the fractional anisotropy, radial diffusivity, and mean diffusivity of tracts crossing white matter hyperintensities were compared with the fractional anisotropy, radial diffusivity, and mean diffusivity of tracts that did not cross white matter hyperintensities. The cingulum, long association fibers, corticospinal/bulbar tracts, and thalamic projection fibers were included for comparison.
RESULTS: Within the corpus callosum, tracts that crossed white matter hyperintensities had decreased fractional anisotropy compared with tracts that did not pass through white matter hyperintensities (P = .002). Within the cingulum, tracts that crossed white matter hyperintensities had increased radial diffusivity compared with tracts that did not pass through white matter hyperintensities (P = .001).
CONCLUSIONS: In the corpus callosum and cingulum, tracts had worse diffusion characteristics when they crossed white matter hyperintensities. These results support a role for white matter hyperintensities in the disruption of crossing tracts.

PMID: 27127001 [PubMed - as supplied by publisher]

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Use of prucalopride for chronic constipation: a systematic review and meta-analysis of published randomized, controlled trials.

Use of prucalopride for chronic constipation: a systematic review and meta-analysis of published randomized, controlled trials.

J Neurogastroenterol Motil. 2016 Apr 29;

Authors: Sajid MS, Hebbar M, Baig MK, Li A, Philipose Z

Abstract
This article highlights the role of prucalopride in the management of chronic constipation based upon the principles of meta-analysis using data reported in the published randomized, controlled trials. Sixteen randomized, controlled trials on 3943 patients reported the effectiveness of prucalopride in patients with chronic constipation. Prucalopride successfully increased the frequency of spontaneous bowel movements per week in all variable doses of 1 mg (standardized mean difference, 0.42 [95% CI, 0.18-0.66; P = 0.006]), 2 mg (standardized mean difference, 0.34 [95% CI, 0.11-0.56; P = 0.003]), and 4 mg (standardized mean difference, 0.33 [95% CI, 0.22-0.44; P = 0.00001]). The risks of adverse events or side effects such as headache, abdominal cramps, excessive flatulence, dizziness, diarrhoea, and rash were higher (odds ratio, 1.70 [95% CI, 1.27 to -2.27; P = 0.0004]) in prucalopride group. Prucalopride is clinically a beneficial pharmacotherapy for chronic constipation and its routine use may be considered in patients with chronic simple laxative-resistant constipation.

PMID: 27127190 [PubMed - as supplied by publisher]

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Editorial board

Publication date: July 2016
Source:Journal of Environmental Radioactivity, Volumes 158–159





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A hearing self-reported survey in people over 80 years of age in China by hearing handicap inventory for the elderly-complete version vs screening version.

A hearing self-reported survey in people over 80 years of age in China by hearing handicap inventory for the elderly-complete version vs screening version.

Acta Otolaryngol. 2016 Apr 29;:1-9

Authors: Liu XY, Han Y, Yang SM

Abstract
CONCLUSION: HHIE-S can be a useful tool in investigating hearing loss among people over 80 years old, with the same validity as HHIE.
OBJECTIVE: To investigate the effect of hearing loss on the quality-of-life in people over 80 years of age in China, and to compare the results of the Chinese mandarin version Hearing Handicap Inventory for the Elderly (HHIE) and its screening version (HHIE-S).
METHODS: Eighty-four people over 80 years participated in the study. Both HHIE and HHIE-S were completed, and the hearing handicap degrees were rated according to HHIE scores and HHIE-S scores, respectively. Results obtained by HHIE and HHIE-S were compared. Multi-factor analysis of variance was used to analyze the impact of eight factors on hearing handicap in the oldest old people over 80 years of age, including age, noise exposure, ear surgery, infection, ototoxic drugs use, cardiovascular and cerebrovascular diseases, diabetes, and tumors.
RESULTS: Both HHIE and HHIE-S revealed 48 subjects (57.1%) with no self-perceived hearing problem, and 36 subjects (42.9%) with hearing handicap. No statistical difference was found between results of the functional hearing handicap rating by HHIE and HHIE-S (Chi-square = 1.532, p = 0.465). The HHIE and HHIE-S were in agreement with each other (kappa = 0.772, p < 0.001). All the eight factors had no significance on both HHIE and HHIE-S scores (p > 0.05), except noise exposure on S-score of HHIE-S (p = 0.032), and the R-squares of these factors were less than 5%.

PMID: 27126678 [PubMed - as supplied by publisher]

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[Evidence and Lack of Evidence in the Treatment of Tinnitus].

[Evidence and Lack of Evidence in the Treatment of Tinnitus].

Laryngorhinootologie. 2016 Apr;95(S 01):S155-S191

Authors: Hesse G

Abstract
A broad variety of therapeutic regimen is proposed, introduced and sold against tinnitus, but most of these approaches lack scientific validation and evidence. Up to date a causal, tinnitus eliminating therapy is not available. Most probably this will not be possible at all, as the mechanism of tinnitus generation are multiple and include peripheral as well as central or cortical reactions. Like in fashion and design however, therapeutic medical interventions against tinnitus come in waves again and again over the last decades, without being able to prove lasting and scientifically evident effects.This review presents, discusses and assesses almost all available therapies regarding their evidence. Evidence should include besides external evidence through publications and available data also internal evidence, e.g. including experience of the therapist and needs of the patients.Almost all interventions that try to influence the inner ear or the auditory cortex either pharmaceutically or by direct stimulation or modulation do not reach evidence. However, there are procedures that have proven to be effective and show at least certain degrees of evidence with proven strength of effect. These are habituation therapies and psychotherapeutic interventions like cognitive behavioural therapy, especially when they are combined with concrete measures to improve auditory perception like hearing-aids, cochlear implants or hearing-therapy.

PMID: 27128400 [PubMed - as supplied by publisher]

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Bilateral internal auditory canal gangliogliomas mimicking neurofibromatosis Type II.

Bilateral internal auditory canal gangliogliomas mimicking neurofibromatosis Type II.

Surg Neurol Int. 2016;7:39

Authors: Hooten KG, Oliveria SF, Sadrameli SS, Gandhi S, Yachnis AT, Lewis SB

Abstract
BACKGROUND: Gangliogliomas are rare low grade, typically well-differentiated, tumors that are composed of mature ganglion cells and neoplastic glial cells. These tumors can appear at virtually any location along the neuroaxis but classically occur in the temporal lobe of young patients. In a small number of cases, gangliogliomas have presented as masses in the brainstem or involving cranial nerves. With the exception of vestibular schwannomas, bilateral tumors in the region of the internal auditory canal (IAC) or cerebellopontine angle (CPA) are exceedingly rare.
CASE DESCRIPTION: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma.
DESCRIPTION: We report a case of a 58-year-old male who presented with hearing loss, tinnitus, and vertigo. Initial magnetic resonance imaging revealed bilateral nonenhancing IAC/CPA tumors. Based on this finding, a presumptive diagnosis of neurofibromatosis Type II was made, which was initially managed conservatively with close observation. He returned for follow-up with worsening vertigo and tinnitus, thus prompting the decision to proceed with surgical resection of the symptomatic mass. Intriguingly, pathological study demonstrated a WHO Grade I ganglioglioma.
CONCLUSION: This is the first reported case of bilateral IAC/CPA gangliogliomas. When evaluating bilateral IAC/CPA lesions with unusual imaging characteristics, ganglioglioma should be included in the differential diagnosis.

PMID: 27127704 [PubMed]

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Detection and adequacy evaluation of erythrocyte glutathione transferase on levels of circulating toxins in hemodialysis patients.

Detection and adequacy evaluation of erythrocyte glutathione transferase on levels of circulating toxins in hemodialysis patients.

Artif Cells Nanomed Biotechnol. 2016 Apr 28;:1-4

Authors: Yin R, Qiu H, Zuo H, Cui M, Zhai N, Zheng H, Zhang D, Huo P, Hong M

Abstract
To explore detection and adequacy evaluation of erythrocyte glutathione S transferase (GST) on levels of circulating toxins in hemodialysis patients in Qinhuangdao region in China, this study divided 84 cases of long-term, end-stage hemodialysis patients into 2 groups: one group of 33 cases of adequate hemodialysis (spKt/V ≥ 1.3) and another group of 51 cases of inadequate hemodialysis (spKt/V < 1.3), according to the urea index value of the unit chamber model (spKt/V). Another 50 cases of subjects found healthy by a physical examination were taken as the control group, and the differences in the related clinical and biochemical indexes of the 3 groups were compared and analyzed. The levels of GST, creatinine, high sensitivity C-reactive protein (hs-CRP), transferrin saturation (TSAT), parathyroid hormone (PTH), interleukin-2,6,8 (IL-2,6,8) and tumor necrosis factor-a (TNF-a) in the hemodialysis group were significantly higher than those in the control group (P < 0.05), and GST, IL-2, 6, 8, and TNF-a levels in the inadequate hemodialysis group were significantly higher than in the adequate hemodialysis group (P < 0.05). Pearson's relevant analysis showed that the levels of GST and spKt/V, IL-2, IL-6, IL-8, and TNF-a have a positive correlation (P < 0.05), and they have no correlation with levels of creatinine, hs-CRP, TSAT, and PHT (P > 0.05). There were 23 patients with levels of spKt/V ≥ 1.3 after adjusting the dialysis solution for 51 cases of inadequate hemodialysis patients, and the GST level after the adjustment was significantly lower than that before the adjustment, but still higher than that in the adequate dialysis group. This concludes that the maintenance of hemodialysis in patients has certain relevance on spKt/V and associated inflammatory factors. Through the study, it can be determined that GST can effectively respond to adequate hemodialysis, which has a guiding significance on adjusting the blood dialysis solution in clinical practice.

PMID: 27121915 [PubMed - as supplied by publisher]

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The role of professional learning communities for beginning teachers' learning outcomes and intention to leave the job

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A novel approach to an efficient LED on SOI

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Novelty low-cost integrated photonic biosensor using broadband source and on-chip spectral filter

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Design of an electronically tunable laser diode integrated on the SOI platform

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On-chip axicon for light sheet microscopy

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Si and SiN biophotonic Technology Platform, Applied to Biosensing, Spectroscopy, and Lens-Free Imaging

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Low optical loss ohmic contacts on heavily doped n-type InGaAs for InP membrabes devices

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Trametinib in metastatic melanoma.

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Trametinib in metastatic melanoma.

Expert Rev Anticancer Ther. 2015;15(7):749-60

Authors: Chopra N, Nathan PD

Abstract
The treatment of metastatic melanoma is rapidly changing. In 2002, the BRAF mutation was described in over 50% of melanomas and led to the first BRAF inhibitor, vemurafenib, being approved for clinical use in 2011. Clinical responses are often rapid but duration of response is limited due to the development of resistance. MEK is the next downstream target from BRAF in the MAP kinase pathway. Trametinib was the first MEK inhibitor to be approved for clinical use in 2013. Preclinical studies demonstrated a delay in resistance and a reduction in cutaneous toxicity by combined BRAF and MEK inhibition. Here, we review the rationale for clinical development of trametinib and give an update on recent clinical trials of trametinib alone and in combination with braf inhibition in melanoma.

PMID: 26107021 [PubMed - indexed for MEDLINE]

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Invadopodia: a new therapeutic target to block cancer metastasis.

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Invadopodia: a new therapeutic target to block cancer metastasis.

Expert Rev Anticancer Ther. 2015;15(7):733-5

Authors: Stoletov K, Lewis JD

Abstract
Cancer cells become dangerous when they acquire the ability to invade through physical barriers in the body and disseminate to distant sites. Recent evidence has demonstrated that cancer cells utilize specialized structures called invadopodia, unique protrusions that concentrate proteases such as matrix metalloproteinases (MMPs), to escape blood vessels during the process of extravasation. Perhaps most exciting is the fact that inhibition of invadopodia through genetic or pharmacological means reduces the ability of cancer cells to extravasate and effectively blocks metastasis. This opens the door for the development of novel therapies targeting invadopodia and cancer metastasis.

PMID: 26098830 [PubMed - indexed for MEDLINE]

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Panobinostat: a novel pan-deacetylase inhibitor for the treatment of relapsed or relapsed and refractory multiple myeloma.

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Panobinostat: a novel pan-deacetylase inhibitor for the treatment of relapsed or relapsed and refractory multiple myeloma.

Expert Rev Anticancer Ther. 2015;15(7):737-48

Authors: Richardson PG, Laubach JP, Lonial S, Moreau P, Yoon SS, Hungria VT, Dimopoulos MA, Beksac M, Alsina M, San-Miguel JF

Abstract
Outcomes for patients with multiple myeloma (MM) have improved significantly over the past decade. Despite these advances, MM remains incurable and an unmet medical need remains for patients who are relapsed and/or refractory. Panobinostat is a potent, oral pan-deacetylase inhibitor that elicits anti-myeloma activity through epigenetic modulation of gene expression and disruption of protein metabolism. Preclinical data demonstrated that panobinostat has synergistic effects on myeloma cells when combined with bortezomib and dexamethasone. In a Phase III clinical trial evaluating bortezomib and dexamethasone in combination with panobinostat or placebo in patients with relapsed or relapsed and refractory MM (PANORAMA 1), panobinostat led to a significant increase in median progression-free survival. Panobinostat is currently under regulatory review with a recent accelerated approval granted for the treatment of relapsed disease, in which both bortezomib and immunomodulatory drugs have failed. Here, we summarize the preclinical, pharmacokinetic and clinical data for panobinostat in MM.

PMID: 26051506 [PubMed - indexed for MEDLINE]

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Maintenance therapy in non-small cell lung cancer.

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Maintenance therapy in non-small cell lung cancer.

Expert Rev Anticancer Ther. 2015;15(7):839-46

Authors: Genestreti G, Di Battista M, Cavallo G, Bartolotti M, Brandes AA

Abstract
Several randomized trials have investigated the role of maintenance treatment for patients with advanced non-small cell lung cancer (NSCLC) not progressed after completion of first-line chemotherapy, with good performance score (PS) and no persistent chemotherapy-induced toxicity. Two separate strategies have been developed: the immediate use of non-cross-resistant drug (switch maintenance or early second-line therapy) or the continuation of platinum partner alone (continuation maintenance) or in combination with other drug (combination maintenance). Here we discuss how the benefits demonstrated in these studies may change clinical practice (in terms of potential toxicity and costs) and reflect on factors that may identify subgroups of patients who might benefit from maintenance therapy in general, and which maintenance therapy specifically.

PMID: 26027675 [PubMed - indexed for MEDLINE]

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Use of angiotensin-converting enzyme inhibitors in the prophylaxis of anthracycline or trastuzumab-related cardiac dysfunction: preclinical and clinical considerations.

Related Articles

Use of angiotensin-converting enzyme inhibitors in the prophylaxis of anthracycline or trastuzumab-related cardiac dysfunction: preclinical and clinical considerations.

Expert Rev Anticancer Ther. 2015;15(7):829-37

Authors: Abdel-Rahman O, Alorabi M

Abstract
Cardiac toxicity is one of the most important long-term toxicities experienced by cancer survivors so that survival rate due to anticancer therapy may be negatively affected due to cardiac complications. Thus, the search for novel methods to lower the incidence of treatment-related cardiotoxicity is a priority for all cancer-related disciplines. In this review, we provide an overview of the available preclinical and clinical data evaluating the role of angiotensin-converting enzyme inhibitors in the prophylaxis of cardiac dysfunction secondary to anthracyclines and trastuzumab use. The available clinical data suggest some degree of protective utility for the use of some angiotensin-converting enzyme inhibitors against anthracycline-related cardiotoxicity while the data are scarce with regard to a similar role for patients receiving trastuzumab.

PMID: 26013380 [PubMed - indexed for MEDLINE]

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Novel approaches to pediatric leukemia treatment.

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Novel approaches to pediatric leukemia treatment.

Expert Rev Anticancer Ther. 2015;15(7):811-28

Authors: Thomas X

Abstract
Despite remarkable improvements in the treatment of pediatric acute leukemia (AL) over the last decades, relapse still carries a poor prognosis with significant morbidity and mortality. Novel targeted therapies are currently being investigated in an attempt to reduce adverse events and improve survival outcomes. This review summarizes recent data from the literature regarding advances in drug discovery based on biological evidence and the novel targeted drug therapies for childhood AL. Significant challenges still remain for novel drug development in childhood AL. However, first results combined with a large number of new agents currently being investigated are very encouraging. Furthermore, therapeutic advances will depend upon combination strategies using the specific action of each agent and their complementary effects on leukemia cells.

PMID: 26004287 [PubMed - indexed for MEDLINE]

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Risk of oral and gastrointestinal mucosal injury in patients with solid tumors treated with everolimus, temsirolimus or ridaforolimus: a comparative systematic review and meta-analysis.

Related Articles

Risk of oral and gastrointestinal mucosal injury in patients with solid tumors treated with everolimus, temsirolimus or ridaforolimus: a comparative systematic review and meta-analysis.

Expert Rev Anticancer Ther. 2015;15(7):847-58

Authors: Abdel-Rahman O, Fouad M

Abstract
BACKGROUND: The authors performed a systematic review and meta-analysis of diarrhea and stomatitis associated with the use of everolimus, temsirolimus or ridaforolimus in patients with solid tumors.
PATIENTS AND METHODS: Eligible studies included randomized trials of patients with solid tumors on everolimus, temsirolimus or ridaforolimus, describing the events of diarrhea and stomatitis.
RESULTS: After exclusion of ineligible studies, a total of 18 clinical trials including 8143 patients were considered eligible for the meta-analysis. The relative risk ratios of all-grade diarrhea and stomatitis were 1.94 (95% CI: 1.6-2.36; p < 0.00001) and 3.54 (95% CI: 2.59-4.84; p < 0.00001), respectively, while the relative risk ratios of high-grade diarrhea and stomatitis were 3.49 (95% CI: 2.39-5.09; p < 0.00001) and 6.98 (95% CI: 4.76-10.26; p < 0.00001), respectively. On subgroup analysis, there was no statistically significant difference between everolimus and temsirolimus in the risk of relevant adverse events.
CONCLUSIONS: This meta-analysis demonstrated that regimens containing everolimus, temsirolimus or ridaforolimus for the treatment of solid tumors are associated with a significantly increased risk of all-grade and high-grade diarrhea and stomatitis. Close clinical monitoring is required when administering these drugs.

PMID: 25994247 [PubMed - indexed for MEDLINE]

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