Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity.

Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity.

J Radiat Res. 2015 Dec 24;

Authors: Chen J, Wang Y, Mei Z, Zhang S, Yang J, Li X, Yao Y, Xie C

Abstract
Lung fibrosis may be associated with Type-2 polarized inflammation. Herein, we aim to investigate whether radiation can initiate a Type-2 immune response and contribute to the progression of pulmonary fibrosis in tumor-bearing animals. We developed a tumor-bearing mouse model with Lewis lung cancer to receive either radiation therapy alone or radiation combined with Th1 immunomodulator unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotide (CpG-ODN). The Type-2 immune phenotype in tumors and the histological grade of lung fibrosis were evaluated in mice sacrificed three weeks after irradiation. Mouse lung tissues were analyzed for hydroxyproline and the expression of Type-1/Type-2 key transcription factors (T-bet/GATA-3). The concentration of Type-1/Type-2 cytokines in serum was measured by cytometric bead array. Lung fibrosis was observed to be more serious in tumor-bearing mice than in normal mice post-irradiation. The fibrosis score in irradiated tumor-bearing mice on Day 21 was 4.33 ± 0.82, which was higher than that of normal mice (2.00 ± 0.63; P < 0.05). Hydroxyproline and GATA-3 expression were increased in the lung tissues of tumor-bearing mice following irradiation. CpG-ODN attenuated fibrosis by markedly decreasing GATA-3 expression. Serum IL-13 and IL-5 were elevated, whereas INF-γ and IL-12 expression were decreased in irradiated tumor-bearing mice. These changes were reversed after CpG-ODN treatment. Thus, Type-2 immunity in tumors appeared to affect the outcome of radiation damage and might be of interest for future studies on developing approaches in which Type-1-related immunotherapy and radiotherapy are used in combination.

PMID: 26703457 [PubMed - as supplied by publisher]

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Meningiomas With Rhabdoid Features Lacking Other Histologic Features of Malignancy: A Study of 44 Cases and Review of the Literature.

Meningiomas With Rhabdoid Features Lacking Other Histologic Features of Malignancy: A Study of 44 Cases and Review of the Literature.

J Neuropathol Exp Neurol. 2016 Jan;75(1):44-52

Authors: Vaubel RA, Chen SG, Raleigh DR, Link MJ, Chicoine MR, Barani I, Jenkins SM, Aleff PA, Rodriguez FJ, Burger PC, Dahiya S, Perry A, Giannini C

Abstract
The behavior of rhabdoid meningiomas otherwise lacking malignant features remains unknown as most of the originally reported aggressive cases showed anaplastic histologic features independently of rhabdoid phenotype. We studied 44 patients with rhabdoid meningiomas lacking anaplastic features. Median age at diagnosis was 48.6 years (range 10-79). Location was supratentorial in 28 (63.6%), skull base in 15 (34.1%), and spinal in 1 (2.3%). Tumor grade was otherwise World Health Organization grade I (n = 22, 50%) or II (n = 22, 50%). Rhabdoid cells represented <20% of the tumor in 12 cases (27.3%), 20% to 50% in 18 (40.9%), and >50% in 14 (31.8%). Median clinical follow-up, available for 38 patients, was 5.0 years (range 0.17-14.2). Recurrence occurred in 9 patients (5-year recurrence-free survival, 73.7%) with a significantly higher risk in subtotally resected tumors (p = 0.043). Rhabdoid cell percentage was not associated with recurrence. Six patients died (4 of disease, 2 of unclear causes); 5-year overall survival was 86.7%, a mortality in excess of that expected in grade I-II meningiomas but much lower than originally reported. Review of 50 similar previously reported cases confirmed our findings. We suggest that rhabdoid meningiomas be graded analogously to nonrhabdoid tumors, with caution that some may still behave aggressively and close follow-up is recommended.

PMID: 26705409 [PubMed - in process]

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Additional Prone 18F-FDG PET/CT Acquisition to Improve the Visualization of the Primary Tumor and Regional Lymph Node Metastases in Stage II/III Breast Cancer.

Additional Prone 18F-FDG PET/CT Acquisition to Improve the Visualization of the Primary Tumor and Regional Lymph Node Metastases in Stage II/III Breast Cancer.

Clin Nucl Med. 2015 Dec 22;

Authors: Teixeira SC, Koolen BB, Vogel WV, Wesseling J, Stokkel MP, Vrancken Peeters MT, van der Noort V, Rutgers EJ, Valdés Olmos RA

Abstract
PURPOSE: To prospectively compare prone and supine acquired F-FDG PET/CT for visualization of primary tumors and regional lymph nodes in stage II/III breast cancer patients.
MATERIALS AND METHODS: One hundred ninety-eight patients were included consecutively from August 2010 to April 2012. One hour after administration of 180-240 MBq F-FDG, PET/CT images of the thorax were firstly acquired in prone position. Subsequently, a standard PET/CT in supine position from skull base to thighs was made. Both sets of images were tested in a univariate and a multivariate analysis for the number of lesions per breast or lymph node (LN) region and anatomical mismatch between PET and CT images.
RESULTS: Images in prone position showed less compression of breast tissue, more primary tumor (PT) multifocality (P < 0.001) and more avid axillary LNs (P < 0.001) compared with supine position. Anatomical mismatch of the axillary LN metastases was found more often on supine PET/CT images compared with prone (P = 0.004). Prone images showed a smaller PT functional volume compared with supine position (P < 0.001).
CONCLUSIONS: Prone position PET/CT improved the visualization of PT multifocality and the number of detected axillary lymph nodes. Therefore, it is a valuable addition to standard supine PET/CT in the protocol for locoregional assessment in stage II/III breast cancer patients.

PMID: 26704731 [PubMed - as supplied by publisher]

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The role of radiosurgery in the management of benign head and neck tumors.

The role of radiosurgery in the management of benign head and neck tumors.

World Neurosurg. 2015 Dec 15;

Authors: Park HH, Hong CK, Jung HH, Chang WS, Kim CH, Lee WS, Lee SC, Park YG, Chang JH

Abstract
OBJECTIVE: Head and neck tumors are a heterogeneous group and often invade the skull base. Various radiation techniques can be used for these tumors when surgery is unavailable. This study investigated the indications for gamma knife radiosurgery (GKRS) in benign head and neck tumors.
METHODS: Thirty-seven lesions in 35 patients were treated with GKRS for schwannoma, juvenile nasal angiofibroma, choroidal hemangioma and pleomorphic adenoma. The median follow-up period was 43.0 months (range, 12.2-174.1 months).
RESULTS: Tumor control was achieved in 35 of 37 lesions (94.6%) at last follow-up after GKRS. Thirty-four lesions (91.9%) decreased, 1 lesion (2.7%) remained stable and 2 lesions (5.4%) increased in size. Clinically, 15 cases (40.5%) showed improvement, 17 cases (45.9%) were stable, 1 case (2.7%) experienced deterioration and 4 cases (10.8%) developed new symptoms. Four of the 5 cases that exhibited deterioration or new symptoms eventually improved.
CONCLUSION: GKRS is a reasonable alternative to surgery that can effectively control tumor growth and preserve functions of the head and neck in primary, residual or recurrent benign head and neck tumors.

PMID: 26704197 [PubMed - as supplied by publisher]

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Patient and treatment-related risk factors for osteoradionecrosis of the jaw in patients with head and neck cancer.

Patient and treatment-related risk factors for osteoradionecrosis of the jaw in patients with head and neck cancer.

Oral Surg Oral Med Oral Pathol Oral Radiol. 2015 Oct 22;

Authors: Raguse JD, Hossamo J, Tinhofer I, Hoffmeister B, Budach V, Jamil B, Jöhrens K, Thieme N, Doll C, Nahles S, Hartwig ST, Stromberger C

Abstract
OBJECTIVE: The purpose of this study was to evaluate risk factors for and the incidence of osteoradionecrosis (ORN) of the jaw in patients with head and neck cancer.
STUDY DESIGN: This study was a retrospective analysis of the risk for ORN and outcome for 149 of 540 patients with head and neck cancer of the oral cavity (65%), oropharynx (26%), or other head and neck sites (9%) treated with radiotherapy between 2004 and 2009. ORN was graded according to Late Effects of Normal Tissues/Somatic Objective Management Analytic Scale (LENT/SOMA) criteria.
RESULTS: Within a median follow-up of 41 months (95% confidence interval: 27.4-54.6), 38 patients (25.5%) had developed ORN, 37 patients (25%) had a local recurrence, and 53 patients (36%) had died. The median time to diagnosis of ORN was 14.5 months (range: 3-80), and 79% were diagnosed within 2 years of RT. Eleven of these patients had undergone previous mandibular surgery. Univariate significant risk factors for ORN were any comorbidity, poor oral hygiene, pre-radiotherapy osteotomy, close tumor-to-bone proximity, post-radiotherapy dentoalveolar surgery (DAS), DAS without sufficient wound closure, alcohol consumption, and denture pressure sores. In multivariate analysis, comorbidities, pre-radiotherapy mandibular surgery, poor oral hygiene, and insufficient DAS remained significant.
CONCLUSIONS: Reducing the risk of ORN calls for maintaining optimal oral hygiene, ensuring good denture fit, receiving proper training in DAS, and helping patients to stop drinking and smoking.

PMID: 26703417 [PubMed - as supplied by publisher]

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Response to Madans et al. Comments on Sabariego et al. Measuring Disability: Comparing the Impact of Two Data Collection Approaches on Disability Rates. Int. J. Environ. Res. Public Health, 2015, 12, 10329-10351.

Response to Madans et al. Comments on Sabariego et al. Measuring Disability: Comparing the Impact of Two Data Collection Approaches on Disability Rates. Int. J. Environ. Res. Public Health, 2015, 12, 10329-10351.

Int J Environ Res Public Health. 2015;13(1)

Authors: Sabariego C, Oberhauser C, Posarac A, Bickenbach J, Kostanjsek N, Chatterji S, Officer A, Coenen M, Chhan L, Cieza A

Abstract
We greatly appreciate and wish to thank Madans, Mont and Loeb for the issues they raise in their Comment [1] on our paper "Measuring Disability: Using the WHO Model Disability Survey to Address the Impact of Screeners on Disability Rates" [2]. [...].

PMID: 26703704 [PubMed - in process]

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Low-level laser therapy ameliorates disease progression in a mouse model of multiple sclerosis.

Low-level laser therapy ameliorates disease progression in a mouse model of multiple sclerosis.

Autoimmunity. 2015 Dec 24;:1-11

Authors: Gonçalves ED, Souza PS, Lieberknecht V, Fidelis GS, Barbosa RI, Silveira PC, de Pinho RA, Dutra RC

Abstract
Multiple sclerosis (MS) is an autoimmune demyelinating inflammatory disease characterized by recurrent episodes of T cell-mediated immune attack on central nervous system (CNS) myelin, leading to axon damage and progressive disability. The existing therapies for MS are only partially effective and are associated with undesirable side effects. Low-level laser therapy (LLLT) has been clinically used to treat inflammation, and to induce tissue healing and repair processes. However, there are no reports about the effects and mechanisms of LLLT in experimental autoimmune encephalomyelitis (EAE), an established model of MS. Here, we report the effects and underlying mechanisms of action of LLLT (AlGaInP, 660 nm and GaAs, 904 nm) irradiated on the spinal cord during EAE development. EAE was induced in female C57BL/6 mice by immunization with MOG35-55 peptide emulsified in complete Freund's adjuvant. Our results showed that LLLT consistently reduced the clinical score of EAE and delayed the disease onset, and also prevented weight loss induced by immunization. Furthermore, these beneficial effects of LLLT seem to be associated with the down-regulation of NO levels in the CNS, although the treatment with LLLT failed to inhibit lipid peroxidation and restore antioxidant defense during EAE. Finally, histological analysis showed that LLLT blocked neuroinflammation through a reduction of inflammatory cells in the CNS, especially lymphocytes, as well as preventing demyelination in the spinal cord after EAE induction. Together, our results suggest the use of LLLT as a therapeutic application during autoimmune neuroinflammatory responses, such as MS.

PMID: 26703077 [PubMed - as supplied by publisher]

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[Detection of aspiration of nasopharyngeal secretion and the relationship between the aspiration of nasopharyngeal secretion and the incidence of pneumonia].

[Detection of aspiration of nasopharyngeal secretion and the relationship between the aspiration of nasopharyngeal secretion and the incidence of pneumonia].

Zhonghua Jie He He Hu Xi Za Zhi. 2015 Jul;38(7):511-5

Authors: Liu N, Zheng Z, Chen P, Hou P, Wang X, Li H, Chen R

Abstract
OBJECTIVE: To establish a method to detect aspiration of nasopharyngeal secretion and to explore the relationship between aspiration of nasopharyngeal secretion and pneumonia.
METHOD: Thirty-two patients with pulmonary infection [(30 males, 2 females; mean age (73±8) years] were recruited from the First Affiliated Hospital of Guangzhou Medical University during the period between June 2014 and August 2014, and 9 age-matched healthy volunteers [(7 males, 2 females; mean age (73±6) years] as the control group. A dose of 74.0 MBq (99)Tc(m)-sulfur colloid was diluted in 12 ml of saline, and then the mixture was dripped into the nasal pharynx of volunteers by 24 ml/h. Dynamic imaging from the mouth to the stomach was acquired by SPECT/CT. Two experienced physicians assessed all examination results and reached consensus for final diagnosis. Radioactivity detected at either the bronchi or within the lung fields was reported as positive for aspiration.
RESULTS: In the test group, 19 of 32 patients with pneumonia had a history of suffering from upper respiratory tract symptoms such as runny or blocked nose, and 21 of 32 patients were detected to have aspiration. However, none of the healthy people had aspiration (χ(2)=9.624, P=0.002). In 21 patients with pneumonia, 14 showed respiratory aspirations in areas corresponding to the lesions, i.e. bilateral lungs, the right lung and the left lung in 6/10, 6/8, and 2/3 cases respectively (P=0.067).
CONCLUSION: (99)Tc(m)-sulfur colloid imaging is effective to detect the aspiration of nasopharyngeal secretions in the elderly people. Besides, the incidence rate of aspiration in the patients was higher than that in healthy people, which suggests that aspiration of nasopharyngeal secretion is the cause of pulmonary infection.

PMID: 26703017 [PubMed - in process]

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Individual Benefit vs Societal Effect of Antibiotic Prescribing for Preschool Children With Recurrent Wheeze.

Related Articles

Individual Benefit vs Societal Effect of Antibiotic Prescribing for Preschool Children With Recurrent Wheeze.

JAMA. 2015 Nov 17;314(19):2027-9

Authors: Cohen RT, Pelton SI

PMID: 26575058 [PubMed - indexed for MEDLINE]

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Extra-pulmonary tuberculosis and Xpert® MTB/RIF: all about meta-analyses?

Related Articles

Extra-pulmonary tuberculosis and Xpert® MTB/RIF: all about meta-analyses?

Int J Tuberc Lung Dis. 2015 Mar;19(3):254

Authors: O'Grady J, Kik SV, Ferrara G

PMID: 25686127 [PubMed - indexed for MEDLINE]

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Table of Contents.

Table of Contents.

Chem Senses. 2016 Jan;41(1):NP

Authors:

PMID: 26703082 [PubMed - in process]

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Subscriptions.

Subscriptions.

Chem Senses. 2016 Jan;41(1):NP

Authors:

PMID: 26703081 [PubMed - in process]

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Editorial Board.

Editorial Board.

Chem Senses. 2016 Jan;41(1):NP

Authors:

PMID: 26703080 [PubMed - in process]

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Cover.

Cover.

Chem Senses. 2016 Jan;41(1):NP

Authors:

PMID: 26703079 [PubMed - in process]

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Editor-in-Chief's Note - Thank you to Reviewers.

Editor-in-Chief's Note - Thank you to Reviewers.

Chem Senses. 2016 Jan;41(1):95-6

Authors:

PMID: 26703078 [PubMed - in process]

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[Radiosensitivity and/or radioresistance of head and neck cancers: Biological angle].

[Radiosensitivity and/or radioresistance of head and neck cancers: Biological angle].

Bull Cancer. 2015 Dec 15;

Authors: Guy JB, Rancoule C, Méry B, Espenel S, Wozny AS, Simonet S, Vallard A, Alphonse G, Ardail D, Rodriguez-Lafrasse C, Magné N

Abstract
Radiation therapy is a cornerstone of head and neck cancer management. Technological improvements in recent years in radiation therapy, with intensity-modulated techniques, reinforce even more its role. However, both local and locoregional relapses are still observed. Understanding biological mechanisms of treatment resistance is a topic of major interest. From the cancer cell itself, its ability to repair and proliferate, its microenvironment and oxygenation conditions, migratory and invasive capacity, to biological parameters related to the patient, there are many mechanisms involving radiosensitivity and/or radioresistance of head and neck cancer. The present study explores the main biological mechanisms involved in radiation resistance of head and neck cancer, and describes promising therapeutic approaches.

PMID: 26702507 [PubMed - as supplied by publisher]

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[Cancer stem cells: Radiotherapeutic features and therapeutic targets].

[Cancer stem cells: Radiotherapeutic features and therapeutic targets].

Bull Cancer. 2015 Dec 15;

Authors: Méry B, Rancoule C, Guy JB, Espenel S, Wozny AS, Simonet S, Vallard A, Alphonse G, Ardail D, Rodriguez-Lafrasse C, Magné N

Abstract
Recent evidences suggest that many types of cancers contain a cell population presenting stem cell properties. While the great majority of tumor cells are destined to differentiate, and eventually stop dividing, only a minority population of cells, termed cancer stem cells (CSCs), possesses extensive self-renewal capability and can recapitulate tumor pathophysiology in an immune-compromised animal model. Tumor initiating cells have been identified and isolated in many tumor types including brain, colon and prostate. They are virtually resistant to radiation and may contribute to treatment resistance and recurrence. Therefore, therapies specifically targeting CSCs will likely be needed for complete tumor eradication. The present study reviews published reports identifying the mechanisms of radioresistance of CSCs and potential targets based on the pathways of self-renewal. Further elucidation of pathways that regulate CSCs may provide insights into the development of novel innovative therapies.

PMID: 26702506 [PubMed - as supplied by publisher]

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Rapid exacerbation of neuromyelitis optica after rituximab treatment.

Rapid exacerbation of neuromyelitis optica after rituximab treatment.

J Clin Neurosci. 2015 Dec 15;

Authors: Dai Y, Lu T, Wang Y, Fang L, Li R, Kermode AG, Qiu W

Abstract
Studies have shown the efficacy of immunosuppressants against neuromyelitis optica (NMO). Rituximab is recommended as an off-label prescription to treat refractory NMO. However, we describe two such patients who were suboptimally responsive to rituximab and whose symptoms worsened after treatment. Our cautionary cases highlight that in a small proportion of patients with refractory NMO, rituximab may either fail or induce rapid relapse of NMO. This suggests we need to consider new treatment strategies for refractory NMO.

PMID: 26704780 [PubMed - as supplied by publisher]

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Cytokine Patterns and Endotypes in Acute and Chronic Rhinosinusitis

Abstract

Since rhinosinusitis is an inflammatory disease, cytokines as key regulators of inflammation play a central role in its pathophysiology. In acute rhinosinusitis, several proinflammatory cytokines of different types have been identified. Initial information about the involvement of the inflammasome in rhinosinusitis has been gained, but this area remains open for more detailed research. Although it has been accepted now that chronic rhinosinusitis (CRS) needs to be differentiated into CRS with and without nasal polyps, it has become clear that this distinction is insufficient to clearly define subgroups with uniform pathophysiology and cytokine patterns. While Th1-cytokines are mostly found in CRSsNP and Th2 cytokines in CRSwNP, there is a substantial overlap, and several other cytokines have also been detected. Attempts to identify CRS endotypes based on cytokines are ongoing but not yet generally accepted. Despite the central role of cytokines in rhinosinusitis, no specific cytokine-targeted therapies are currently available, and only very few studies have specifically addressed the effects of such biologicals in rhinosinusitis.

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Recurrent Fevers for the Pediatric Immunologist: It’s Not All Immunodeficiency

Abstract

Autoinflammatory diseases are disorders of the innate immune system, characterized by systemic inflammation independent of infection and autoreactive antibodies or antigen-specific T cells. Similar to immunodeficiencies, these immune dysregulatory diseases have unique presentations, genetics, and available therapies. Given the presentation of fevers, rashes, and mucosal symptoms in many of the disorders, the allergist/immunologist is the appropriate medical home for these patients: to appropriately rule out immunodeficiencies, evaluate for allergic disease, and diagnose and treat recurrent fever disorders. However, many practicing physicians are unfamiliar with the clinical presentation, diagnosis, and treatment of autoinflammatory disorders. This review will focus on understanding the signs and symptoms of classic autoinflammatory disorders, introduce newly described monogenic and polygenic disorders, and address the approach to the patient with recurrent fevers to distinguish autoinflammation from immunodeficiency and autoimmunity.

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Clinical significance of OCT4 and SOX2 protein expression in cervical cancer

Abstracts

Background

Cancer stem cell markers have become a major research focus because of their relationship with radiation or chemotherapy resistance in cancer therapy. Cancer stem cell markers including OCT4 and SOX2 have been found in various solid tumors. Here, we investigate the expression and clinical significance of OCT4 and SOX2 in cervical cancer.

Methods

To define the clinical significance of OCT4 and SOX2 expression, we performed immunohistochemistry for OCT4 and SOX2 on 305 normal cervical epithelium samples, 289 cervical intraepithelial neoplasia samples, and 161 cervical cancer cases and compared the data with clinicopathologic factors, including survival rates of patients with cervical cancer.

Results

OCT4 and SOX2 expression was higher in cervical cancer than normal cervix (both p < 0.001). OCT4 overexpression was associated with lymphovascular space invasion (p = 0.045), whereas loss of SOX2 expression was correlated with large tumor size (p = 0.015). Notably, OCT4 and SOX2 were significantly co-expressed in premalignant cervical lesions, but not in malignant cervical tumor. OCT4 overexpression showed worse 5-year disease-free and overall survival rates (p = 0.012 and p = 0.021, respectively) when compared to the low-expression group, while SOX2 expression showed favorable overall survival (p = 0.025). Cox regression analysis showed that OCT4 was an independent risk factor (hazard ratio = 11.23, 95 % CI, 1.31 - 95.6; p = 0.027) for overall survival while SOX2 overexpression showed low hazard ratio for death (hazard ratio = 0.220, 95 % CI, 0.06–0.72; p = 0.013).

Conclusions

These results suggest that OCT4 overexpression and loss of SOX2 expression are strongly associated with poor prognosis in patients with cervical cancer.

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Low-power photodynamic therapy induces survival signaling in perihilar cholangiocarcinoma cells

Abstract

Background

Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways).

Methods

To assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm²). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo.

Results

PDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic.

Conclusions

PDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways.

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Value of cephalic part of lateral crus in functional rhinoplasty.

Value of cephalic part of lateral crus in functional rhinoplasty.

Eur Arch Otorhinolaryngol. 2015 Dec 24;

Authors: Sazgar AA, Amali A, Peyvasty MN

Abstract
Reshaping of the nasal tip is the most difficult part of rhinoplasty. Over the years, there have been many advances in the field of rhinoplasty, including tip plasty. The goal of these continuous refinements in existing procedures has been to improve both aesthetic and functional outcomes. The cephalic part of the lateral crus of the lower lateral cartilage is what mainly contributes to nasal tip deformity. Various surgical techniques have been reported that used the cephalic part of lateral crus to refine the nasal tip and preserve alar integrity and nasal breathing function. In this review article, we have attempted to show the evolution of these methods while focusing on development of approaches that are basic for "modern rhinoplasty" and presenting our personal preferences. We have also endeavored to categorize these methods and clarify some misconceptions and inaccuracies in their descriptions.

PMID: 26704927 [PubMed - as supplied by publisher]

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Fatal Liver Cyst Rupture Due to Anabolic Steroid Use: A Case Presentation.

Fatal Liver Cyst Rupture Due to Anabolic Steroid Use: A Case Presentation.

Am J Forensic Med Pathol. 2015 Dec 23;

Authors: Hansma P, Diaz FJ, Njiwaji C

Abstract
Liver cysts are commonly found incidentally from imaging scans or at autopsy. These benign neoplasms vary in size and represent a heterogeneous group of disorders, for which the demographics, risk factors, apparent inciting event, clinical presentation, and outcome are varied. Complications that can develop from a liver cyst include development of spontaneous hemorrhage, infection, and/or obstruction. Although the etiology of liver cysts varies, fatal rupture of a hemorrhagic liver cyst due to anabolic steroid use is a rare occurrence. In fact, there are few reported cases in journal literature. We report a case of a fatal liver cyst rupture with resultant hemoperitoneum in the presence of anabolic steroid (stanozolol) use.

PMID: 26704022 [PubMed - as supplied by publisher]

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Colorectal carcinoma in pediatric patients: A comparison with adult tumors, treatment and outcomes from the National Cancer Database.

Colorectal carcinoma in pediatric patients: A comparison with adult tumors, treatment and outcomes from the National Cancer Database.

J Pediatr Surg. 2015 Dec 1;

Authors: Poles GC, Clark DE, Mayo SW, Beierle EA, Goldfarb M, Gow KW, Goldin A, Doski JJ, Nuchtern JG, Vasudevan SA, Langer M

Abstract
BACKGROUND: Pediatric colorectal cancer (CRC) is rare. Comparison with adult CRC tumors, management, and outcomes may identify opportunities for improvement in pediatric CRC care.
STUDY DESIGN: CRC patients in the National Cancer Data Base from 1998 to 2011, were grouped into Pediatric (≤21years), early onset adult (22-50) and older adult (>50) patients. Groups were compared with χ(2) and survival analysis.
RESULTS: A total of 918 pediatric (Ped), 157,779 early onset adult (EA), and 1,304,085 older adults (OA) were identified (p<0.01 for all comparisons). Patients ≤50 presented more frequently with stage 3 and 4 disease (Ped: 62.0%, EA: 49.7%, OA: 37.3%) and rectal cancer (Ped: 23.6%, EA: 27.5%, OA: 19.2%). Pediatric histology was more likely signet ring, mucinous, and poorly differentiated. Initial treatment was usually surgery, but patients ≤50 were more likely to have radiation (Ped: 15.1%, EA: 18.6%, and OA: 9.2%) and chemotherapy (Ped: 42.0%, EA: 38.2%, and OA: 22.7%). Children and older adults showed poorer overall survival at 5years when compared to early onset adults. Adjusting for covariates, age ≤21 was a significant predictor of mortality for colon and rectal cancers (colon HR: 1.22, rectal HR: 1.69).
CONCLUSIONS: This is the largest cohort of pediatric CRC patients, revealing more aggressive tumor histology and behavior in children, particularly in rectal cancer. Despite standard oncologic treatment, age ≤21 was a significant predictor of mortality. This is likely owing to worse tumor biology rather than treatment disparities and may signal the need for different therapeutic strategies.

PMID: 26703433 [PubMed - as supplied by publisher]

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Solitary fibrous tumor of the breast: a case report and review of the literature.

Solitary fibrous tumor of the breast: a case report and review of the literature.

J Med Ultrason (2001). 2016 Jan;43(1):125-8

Authors: Rhee SJ, Ryu JK, Han SA, Won KY

Abstract
Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that can be benign or malignant. SFTs have been most often documented in the pleura. Recently, involvement of extrapleural sites such as the abdomen, musculoskeletal soft tissue, upper respiratory tract, mediastinum, and head and neck were reported. Less than 15 cases of SFT of the breast have been reported. Here, we report a case of a pathologically proven SFT of the breast and review the literature on the radiologic findings. US imaging showed an oval, well-circumscribed, hypoechoic solid mass. A solitary fibrous tumor of the breast is a very rare lesion.

PMID: 26703178 [PubMed - in process]

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A Life-Threatening Mediastinal Hematoma After Central Venous Port System Implantation.

A Life-Threatening Mediastinal Hematoma After Central Venous Port System Implantation.

Am J Case Rep. 2015;16:904-907

Authors: Sarach J, Zschokke I, Melcher GA

Abstract
BACKGROUND We report a case of surgical central venous port system implantation using Seldinger's technique with a life-threatening mediastinal hematoma due to the perforation of the superior vena cava. CASE REPORT A 68-year-old woman was admitted to our institution for port implantation. Open access to the cephalic vein and 2 punctures of the right subclavian vein were unsuccessful. Finally, the port catheter could be placed into the superior vena cava using Seldinger's technique. As blood aspiration via the port catheter was not possible, fluoroscopy was performed, revealing mediastinal contrast extravasation without contrasting the venous system. A new port system could be placed in the correct position without difficulties. After extubation, the patient presented with severe respiratory distress and required consecutive cardiopulmonary resuscitation and reintubation. The CT scan showed a significant hematoma in the lower neck and posterior mediastinum with tracheal compression. We assumed a perforation of the superior vena cava with the tip of the guidewire using Seldinger's technique. Long-term intensive treatment with prolonged ventilation and tracheotomy was necessary. The port system had to be subsequently explanted due to infection. CONCLUSIONS Mediastinal hematoma is a rare but life-threatening complication associated with central venous catheterization using Seldinger's technique. Perforation occurs most often during central venous catheterization in critical care. Mediastinal hematoma is an example of a mechanical complication occurring after central venous catheterization, which has been described only a few times in the literature to date. This case highlights the importance of awareness of possible, rare, life-threatening complications during port implantation, mostly performed in multimorbid patients by surgeons in training.

PMID: 26703924 [PubMed - as supplied by publisher]

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Predictive Soft Tissue Airway Volume Analysis in Mandibular Distraction: Pushing The Envelope in Surgical Planning for Obstructive Sleep Apnea.

Predictive Soft Tissue Airway Volume Analysis in Mandibular Distraction: Pushing The Envelope in Surgical Planning for Obstructive Sleep Apnea.

J Craniofac Surg. 2015 Dec 16;

Authors: Mhlaba JM, Chen ML, Bandla HP, Baroody FM, Reid RR

Abstract
Three-dimensional computed tomography has been used in both preoperative planning of mandibular distraction osteogenesis and in the evaluation of postoperative resolution of tongue-based airway obstruction. The authors present a case report using software to predict postdistraction airway volume during virtual surgical planning (VSP) of mandibular distraction osteogenesis in a 7 year old. The predicted increase in airway volume derived from VSP was 33.57% (1716 mm preoperatively to 2292 mm postvirtual distraction). Based on the three-dimensional computed tomography, the actual airway volume increased to 2211 mm postoperatively, a 28.85% increase.The implications of this advancing technology are far-reaching. An illustrative case is presented herein to demonstrate the efficacy of the airway prediction and its limitations. The authors believe that, with continued investigation, this novel approach may be a standard feature of all VSP sessions for the treatment of tongue-based airway obstruction.

PMID: 26703061 [PubMed - as supplied by publisher]

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MicroR-140-5p suppresses tumor cell migration and invasion by targeting ADAM10-mediated Notch1 signaling pathway in hypopharyngeal squamous cell carcinoma.

MicroR-140-5p suppresses tumor cell migration and invasion by targeting ADAM10-mediated Notch1 signaling pathway in hypopharyngeal squamous cell carcinoma.

Exp Mol Pathol. 2015 Dec 15;

Authors: Jing P, Sa N, Liu X, Liu X, Xu W

Abstract
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides that negatively regulate gene expression at the post-transcriptional level. Downexpression of miR-140-5p was reported in some human cancers, and combined with a reduction of cell migration and invasion, suggesting that miR-140-5p functions as a tumor suppressor. However, little is known about the expression and function of miR-140-5p in hypopharyngeal squamous cell carcinoma(HSCC). In this research, we found that miR-140-5p was significantly downregulated in HSCC tissues and correlated to tumor classification and lymph node metastasis. Restoration of miR-140-5p suppressed the migration and invasion of FaDu cells, and decreased the protein expression levels of ADAM10. Furthermore, the luciferase reporter assay revealed that miR-140-5p was directly bound to ADAM10 mRNA and knockdown of ADAM10 could inhibit FaDu cells migration and invasion and reduced the protein expression levels of and Notch1 intracellular domain (NICD1). Of note, knockdown of Notch1 could inhibit the migration and invasion of FaDu cells and rescued the effect of miR-140-5p inhibitor in FaDu cells. Taken together, our study demonstrate that miR-140-5p suppresses tumor migration and invasion by inhibiting ADAM10-mediated Notch1 signaling pathway and suggest that miR-140-5p could have potential therapeutic applications in HSCC.

PMID: 26704053 [PubMed - as supplied by publisher]

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Total rhinectomy, a clinical review of nine cases.

Total rhinectomy, a clinical review of nine cases.

Ir J Med Sci. 2015 Dec 24;

Authors: Subramaniam T, Lennon P, O'Neill JP, Kinsella J, Timon C

Abstract
INTRODUCTION: A large proportion of malignancies involving the external nose can be managed with limited resection and local autologous reconstruction or, in some cases, radiotherapy as primary or adjuvant treatment. We highlight a small cohort of patients undergoing total rhinectomy for advanced nasal malignancies.
METHODS: A retrospective review of all patients undergoing total rhinectomy in our institution from 2006 to 2014 was undertaken. We reviewed patient demographics, surgical management, adjuvant treatment, histology, reconstruction and outcomes.
RESULTS: Nine patients underwent total rhinectomy over an 8-year period, three of whom were being treated for recurrent disease. Eight patients had squamous cell carcinoma (SCC) and a single patient had an angiosarcoma. Two patients completed adjuvant radiotherapy. Seven patients underwent nasal prosthetic rehabilitation. All nine patients are alive and disease free at latest follow-up.
CONCLUSION: Total rhinectomy is an uncommon procedure usually undertaken for extensive nasal malignancy. Nasal prosthetic rehabilitation is a viable method of reconstruction.

PMID: 26702623 [PubMed - as supplied by publisher]

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Resection of Intraventricular Tumors in Children by Purely Endoscopic Means.

Resection of Intraventricular Tumors in Children by Purely Endoscopic Means.

World Neurosurg. 2015 Dec 15;

Authors: Hidalgo ET, Ali A, Weiner HL, Harter DH

PMID: 26704210 [PubMed - as supplied by publisher]

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"My Mind Is Doing It All": No "Brake" to Stop Speech Generation in Jargon Aphasia.

"My Mind Is Doing It All": No "Brake" to Stop Speech Generation in Jargon Aphasia.

Cogn Behav Neurol. 2015 Dec;28(4):229-41

Authors: Robinson GA, Butterworth B, Cipolotti L

Abstract
OBJECTIVE: To study whether pressure of speech in jargon aphasia arises out of disturbances to core language or executive processes, or at the intersection of conceptual preparation.
BACKGROUND: Conceptual preparation mechanisms for speech have not been well studied. Several mechanisms have been proposed for jargon aphasia, a fluent, well-articulated, logorrheic propositional speech that is almost incomprehensible.
METHODS: We studied the vast quantity of jargon speech produced by patient J.A., who had suffered an infarct after the clipping of a middle cerebral artery aneurysm. We gave J.A. baseline cognitive tests and experimental word- and sentence-generation tasks that we had designed for patients with dynamic aphasia, a severely reduced but otherwise fairly normal propositional speech thought to result from deficits in conceptual preparation.
RESULTS: J.A. had cognitive dysfunction, including executive difficulties, and a language profile characterized by poor repetition and naming in the context of relatively intact single-word comprehension. J.A.'s spontaneous speech was fluent but jargon. He had no difficulty generating sentences; in contrast to dynamic aphasia, his sentences were largely meaningless and not significantly affected by stimulus constraint level.
CONCLUSIONS: This patient with jargon aphasia highlights that voluminous speech output can arise from disturbances of both language and executive functions. Our previous studies have identified three conceptual preparation mechanisms for speech: generation of novel thoughts, their sequencing, and selection. This study raises the possibility that a "brake" to stop message generation may be a fourth conceptual preparation mechanism behind the pressure of speech characteristic of jargon aphasia.

PMID: 26705270 [PubMed - in process]

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Factors Associated With Patient-perceived Hoarseness in Spasmodic Dysphonia Patients.

Factors Associated With Patient-perceived Hoarseness in Spasmodic Dysphonia Patients.

J Voice. 2015 Dec 15;

Authors: Hu A, Hillel A, Meyer T

Abstract
OBJECTIVES/HYPOTHESIS: The American Academy of Otolaryngology-Head and Neck Surgery Clinical Practice Guidelines on Hoarseness distinguishes between hoarseness, which is a symptom perceived by the patient, and dysphonia, which is a diagnosis made by the clinician. Our objective was to determine factors that are associated with patient-perceived hoarseness in spasmodic dysphonia (SD) patients.
STUDY DESIGN: Retrospective study.
METHODS: Adductor SD patients who presented for botulinum toxin injections from September 2011 to June 2012 were recruited. The main outcome variable, Voice Handicap Index-10 (VHI-10), was used to quantify patient-perceived hoarseness. Clinical data, Hospital Anxiety and Depression Scale (HADS), and VHI-10 were collected. Clinician-perceived dysphonia was measured by a speech-language pathologist with Consensus Auditory Perceptual Evaluation of Voice (CAPE-V). Statistical analysis included univariate analyses and multiple linear regression.
RESULTS: One hundred thirty-nine SD patients had VHI-10 score of 26.0 ± 7.2 (mean ± standard deviation), disease duration of 10.5 + 7.0 years, CAPE-V overall score of 43.2 ± 21.8, HADS anxiety score of 6.7 ± 3.8, and HADS depression score of 3.6 ± 2.8. In univariate analyses, there were positive correlations (P < 0.05) between VHI-10 and female gender, CAPE-V overall, older age, HADS anxiety, and depression. There was no correlation with professional voice use and disease duration. In multiple linear regression (R(2) = 0.178, P < 0.001), age, HADS anxiety, female gender, and CAPE-V were significant.
CONCLUSIONS: Older age, higher anxiety levels, female gender, and clinician-perceived dysphonia are associated with higher levels of patient-perceived hoarseness in SD patients. Hoarseness is a very personal symptom. Multiple factors determine its self-perception.

PMID: 26704415 [PubMed - as supplied by publisher]

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Scleroderma dermal microvascular endothelial cells exhibit defective response to pro-angiogenic chemokines.

Scleroderma dermal microvascular endothelial cells exhibit defective response to pro-angiogenic chemokines.

Rheumatology (Oxford). 2015 Dec 24;

Authors: Tsou PS, Rabquer BJ, Ohara RA, Stinson WA, Campbell PL, Amin MA, Balogh B, Zakhem G, Renauer PA, Lozier A, Arasu E, Haines GK, Kahaleh B, Schiopu E, Khanna D, Koch AE

Abstract
OBJECTIVES: Angiogenesis plays a critical role in SSc (scleroderma). The aim of this study was to examine the expression of growth-regulated protein-γ (Gro-γ/CXCL3), granulocyte chemotactic protein 2 (GCP-2/CXCL6) and their receptor CXCR2 in endothelial cells (ECs) isolated from SSc skin and determine whether these cells mount an angiogenic response towards pro-angiogenic chemokines. The downstream signalling pathways as well as the pro-angiogenic transcription factor inhibitor of DNA-binding protein 1 (Id-1) were also examined.
METHODS: Skin biopsies were obtained from patients with dcSSc. ECs were isolated via magnetic positive selection. Angiogenesis was measured by EC chemotaxis assay.
RESULTS: Gro-γ/CXCL3 and GCP-2/CXCL6 were minimally expressed in both skin types but elevated in SSc serum. Pro-angiogenic chemokine mRNA was greater in SSc ECs than in normal ECs. SSc ECs did not migrate to vascular endothelial growth factor (VEGF), Gro-γ/CXCL3, GCP-2/CXCL6 or CXCL16. The signalling pathways stimulated by these chemokines were also dysregulated. Id-1 mRNA in SSc ECs was lower compared with normal ECs, and overexpression of Id-1 in SSc ECs increased their ability to migrate towards VEGF and CXCL16.
CONCLUSION: Our results show that SSc ECs are unable to respond to pro-angiogenic chemokines despite their increased expression in serum and ECs. This might be due to the differences in the signalling pathways activated by these chemokines in normal vs SSc ECs. In addition, the lower expression of Id-1 also decreases the angiogenic response. The inability of pro-angiogenic chemokines to promote EC migration provides an additional mechanism for the impaired angiogenesis that characterizes SSc.

PMID: 26705326 [PubMed - as supplied by publisher]

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Hypothesis: Metalloproteinase Inhibitors Decrease Risks of Cardiovascular Disease.

Hypothesis: Metalloproteinase Inhibitors Decrease Risks of Cardiovascular Disease.

J Cardiovasc Pharmacol Ther. 2015 Dec 24;

Authors: Lizotte-Waniewski M, Brew K, Hennekens CH

Abstract
The hypothesis that matrix metalloproteinase (MMP) inhibitors reduce risks of cardiovascular disease in humans is plausible, unproven, and difficult to test, due, in part, to differences in specificity and route of administration. Endogenous tissue inhibitors of metalloproteinases (TIMPs) are tight-binding, protein inhibitors that function in vivo and can be engineered to enhance specificity for desired targets. Nonetheless, TIMPs have been difficult to test, in part, because their secondary functions, including cell growth promotion and angiogenesis, raise concerns about side effects and they cannot be delivered orally. In contrast, doxycycline and other chemically modified tetracyclines are broad-spectrum, reversible MMP inhibitors with lower affinity but can be taken orally and have US Food and Drug Administration approval. The completed phase 2 randomized trials in humans of MMP inhibitors have methodologic limitations but generally show no significant benefits with adverse effects. At present, the principal research challenge is to achieve a better understanding of the complexities of biological functions of MMPs and subsequently to conduct large-scale phase 3 trials.

PMID: 26703451 [PubMed - as supplied by publisher]

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In vivo monitoring of the anti-angiogenic therapeutic effect of the pan-deacetylase inhibitor panobinostat by small animal PET in a mouse model of gastrointestinal cancers.

In vivo monitoring of the anti-angiogenic therapeutic effect of the pan-deacetylase inhibitor panobinostat by small animal PET in a mouse model of gastrointestinal cancers.

Nucl Med Biol. 2016 Jan;43(1):27-34

Authors: Maschauer S, Gahr S, Gandesiri M, Tripal P, Schneider-Stock R, Kuwert T, Ocker M, Prante O

Abstract
INTRODUCTION: Deacetylase inhibitors have recently been established as a novel therapeutic approach to solid and hematologic cancers and have also been demonstrated to possess anti-angiogenic properties. Although these compounds show a good efficacy in vitro and in vivo, no data on monitoring and predicting treatment response are currently available. We therefore investigated the effect of the pan-deacetylase inhibitor panobinostat (LBH589) on gastrointestinal cancer models and the suitability of 2-[(18)F]FGlc-RGD as a specific agent for imaging integrin αvβ3 expression during tumor angiogenesis using small animal positron emission tomography (PET).
METHODS: The effect of panobinostat on cell viability in vitro was assessed with a label-free impedance based real-time analysis. Nude mice bearing HT29 and HepG2 tumors were treated with daily i.p. injections of 10mg/kg panobinostat for 4weeks. During this time, tumor size was determined with a calliper and mice were repeatedly subjected to PET imaging. Tumor tissues were analyzed immunohistochemically with a focus on proliferation and endothelial cell markers (Ki-67, Meca-32) and by Western blot applying specific markers of apoptosis.
RESULTS: In vitro, panobinostat inhibited the proliferation of HepG2 and HT29 cells. Contrary to the situation in HepG2 tumors in vivo, where panobinostat treatment is known to reduce proliferation and vascularization resulting in a decreased tumor growth, HT29 tumors did not show any effect on these parameters. We demonstrated by Western blotting, that panobinostat induced apoptosis in HT29 tumors in vivo. Longitudinal PET imaging studies in HepG2 tumor-bearing mice using 2-[(18)F]FGlc-RGD demonstrated that the standard uptake value (SUVmax) in HepG2 tumors was significantly decreased by 39% at day 7 after treatment. The comparative PET study using HT29 tumor-bearing animals did not reveal any response of the tumors to panobinostat treatment.
CONCLUSIONS: Small-animal PET imaging using 2-[(18)F]FGlc-RGD was successfully applied to the non-invasive monitoring of the HepG2-tumor response to panobinostat in nude mice early after begin of treatment. Thus, PET imaging of angiogenesis using 2-[(18)F]FGlc-RGD could be a valuable tool to monitor panobinostat therapy in further preclinical studies.
ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: When successfully translated to the clinical surrounding, PET imaging of angiogenesis could therefore facilitate therapy planning and monitoring of therapy success with panobinostat in hepatocellular carcinoma.

PMID: 26702784 [PubMed - in process]

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Is change in blood pressure a biomarker of pazopanib and sunitinib efficacy in advanced/metastatic renal cell carcinoma?

Is change in blood pressure a biomarker of pazopanib and sunitinib efficacy in advanced/metastatic renal cell carcinoma?

Eur J Cancer. 2015 Dec 14;53:96-104

Authors: Goldstein D, Rosenberg JE, Figlin RA, Townsend RR, McCann L, Carpenter C, Pandite L

Abstract
AIM: Pazopanib, an oral antiangiogenic agent, is associated with improved outcomes in patients with metastatic renal cell carcinoma. In this retrospective analysis, we explore hypertension, an on-target adverse event, as a predictive marker.
METHODS: Data from the pazopanib arm of the phase III COMPARZ trial (NCT00720941) comprised the test set. Pooled data from phase II (NCT00244764) and III (NCT00334282) pazopanib trials comprised the validation set. Data from the sunitinib arm of COMPARZ were analysed separately. Measures of efficacy were response rate, progression-free survival (PFS), and overall survival (OS). Mean arterial blood pressure (MAP) was the primary metric, and systolic hypertension (S-HTN) and diastolic hypertension (D-HTN) were secondary metrics; 4- and 12-week landmark analyses were performed.
RESULTS: Analyses revealed no significant associations at the landmarks between response and MAP. We observed a trend towards improved PFS with S-HTN at week 4 (hazard ratio [HR] = 0.79, P = 0.060) and week 12 (HR = 0.75, P = 0.073) among pazopanib-treated patients in COMPARZ. This trend was not confirmed at week 12 in the validation set or in sunitinib-treated patients. In the test set, there was a trend towards increased OS in patients with S-HTN by week 4 (HR = 0.76, P = 0.062) and with D-HTN by week 4 (HR = 0.71, P = 0.016) but not by week 12. No significant differences in OS were observed in sunitinib-treated patients for S-HTN or D-HTN.
CONCLUSION: Neither hypertension nor any blood pressure elevation above baseline was associated with efficacy outcomes of pazopanib or sunitinib. Accordingly, management of tyrosine kinase inhibitor-induced hypertension is unlikely to compromise outcome.

PMID: 26702763 [PubMed - as supplied by publisher]

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The anti-angiogenic herbal extract from Melissa officinalis inhibits adipogenesis in 3T3-L1 adipocytes and suppresses adipocyte hypertrophy in high fat diet-induced obese C57BL/6 J mice.

The anti-angiogenic herbal extract from Melissa officinalis inhibits adipogenesis in 3T3-L1 adipocytes and suppresses adipocyte hypertrophy in high fat diet-induced obese C57BL/6 J mice.

J Ethnopharmacol. 2015 Dec 15;

Authors: Woo S, Yoon M, Kim J, Hong Y, Kim MY, Shin SS, Yoon M

Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Melissa officinalis L. (Labiatae; lemon balm) has been used traditionally and contemporarily as an anti-stress herb. Current hypotheses suggest that not only chronic stress promotes angiogenesis, but angiogenesis also modulates adipogenesis and obesity. Because the herbal extract ALS-L1023 from Melissa officinalis L. (Labiatae; lemon balm) has an anti-angiogenic activity, we hypothesized that ALS-L1023 could inhibit adipogenesis and adipocyte hypertrophy.
MATERIALS AND METHODS: ALS-L1023 was prepared by a two-step organic solvent fractionation from Melissa officinalis. The effects of ALS-L1023 on adipogenesis in 3T3-L1 adipocytes and adipocyte hypertrophy in high fat diet (HFD)-fed obese mice were measured using in vivo and in vitro approaches.
RESULTS: ALS-L1023 inhibited angiogenesis in a dose-dependent manner in the HUVEC tube formation assay in vitro. Treatment of cells with ALS-L1023 inhibited lipid accumulation and adipocyte-specific gene expression caused by troglitazone or MDI differentiation mix. ALS-L1023 reduced mRNA expression of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9) in differentiated cells. In contrast, mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) increased. Protease activity, as measured by zymography, showed that activity of MMP-2 and MMP-9 decreased in ALS-L1023-treated cells. ALS-L1023 also inhibited MMP-2 and MMP-9 reporter gene expression in the presence of the MMP inducer phorbol 12-myristate 13-acetate. An in vivo study showed that ALS-L1023 not only decreased adipose tissue mass and adipocyte size, but also reduced mRNA levels of adipose tissue angiogenic factors and MMPs in HFD-fed obese mice.
CONCLUSIONS: These results suggest that the anti-angiogenic herbal extract ALS-L1023 suppresses adipogenesis and adipocyte hypertrophy, and this effect may be mediated by inhibiting angiogenesis and MMP activities. Thus, by curbing adipogenesis, anti-angiogenic ALS-L1023 yields a possible therapeutic choice for the prevention and treatment of human obesity and its associated conditions.

PMID: 26702505 [PubMed - as supplied by publisher]

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Delayed Hemorrhage Following Treatment of Brain Arteriovenous Malformations (AVMs).

Delayed Hemorrhage Following Treatment of Brain Arteriovenous Malformations (AVMs).

World Neurosurg. 2015 Dec 15;

Authors: Yang W, Hung A, Caplan JM, Braileanu M, Wang JY, Colby GP, Coon AL, Tamargo RJ, Huang J

Abstract
OBJECT: The risk of delayed hemorrhage, occurring greater than 2 years following treatment in brain arteriovenous malformations (AVM) is rarely reported. In this study, we compare the risk of delayed hemorrhage across different treatment modalities.
METHODS: We performed a retrospective chart review of treated patients with a single intracranial AVM seen at our institution from 1990-2013. Delayed hemorrhage was defined as hemorrhage occurring at least 2 years after last treatment. Survival analysis was used to assess risk of delayed hemorrhage by treatment modalities.
RESULTS: Our study included 420 patients. Spetzler-Martin grades were: I(12.6%), II(36.2%), III(32.6%), IV(15.0%), V(3.6%). Average follow-up time is 5.1 years. Twenty-two patients (5.2%) were found to have 28 delayed hemorrhages. Average interval between last treatment and delayed hemorrhage is 7.6 years, with the longest being 24.2 years. Proportions of delayed hemorrhages by treatment modalities were: surgery ± embolization (group I, 9.1%), radiosurgery ± embolization (group II, 63.6%), embolization only (group III, 22.7%) and surgery + radiosurgery ± embolization (group IV, 4.5%). Annualized hemorrhage risk after 2 years for each treatment group was: group I(0.4%), group II(1.2%), group III(3.7%), group IV(1.7%). Survival analysis demonstrated lowest risk of delayed hemorrhage for group 1 (p < 0.01).
CONCLUSIONS: This study is the first to compare the risk of delayed hemorrhage across different treatment modalities. Surgical resection is associated with the lowest risk for delayed hemorrhage compared to other treatment modalities. Patients with partially embolized AVMs should seek timely definitive treatment to reduce the risk of delayed hemorrhage.

PMID: 26704216 [PubMed - as supplied by publisher]

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Evaluating Preoperative Models: A Methodological Contribution.

Evaluating Preoperative Models: A Methodological Contribution.

World Neurosurg. 2015 Dec 15;

Authors: Fasel JH, Uldin T, Vaucher P, Beinemann J, Stimec B, Schaller K

PMID: 26704215 [PubMed - as supplied by publisher]

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A case of moyamoya disease with a transient neurological deterioration associated with subcortical low intensity on fluid-attenuated inversion recovery magnetic resonance images after bypass surgery.

A case of moyamoya disease with a transient neurological deterioration associated with subcortical low intensity on fluid-attenuated inversion recovery magnetic resonance images after bypass surgery.

World Neurosurg. 2015 Dec 15;

Authors: Tanioka S, Shiba M, Umeda Y, Sano T, Maeda M, Suzuki H

Abstract
BACKGROUND: Moyamoya disease is often treated by revascularization surgery. In this report, we first describe a case of moyamoya disease, which repeatedly showed a transient subcortical low intensity (SCLI) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance images postoperatively.
CASE DESCRIPTION: A 59-year-old woman presenting with repeated transient ischemia underwent right superficial temporal artery to middle cerebral artery anastomosis with encephalo-duro-myo-synangiosis. After the operation, the patient had a transient neurological deterioration. MRI findings were not particular apart from SCLI and sulcal hyperintensity on FLAIR images, but no abnormalities in cerebral blood flow on SPECT and no abnormalities on electroencephalogram were found. Symptoms improved in a few days, and SCLI on FLAIR images disappeared in a few months. Thereafter, when the left-sided bypass surgery was performed, similar findings occurred in the left cerebral hemisphere.
CONCLUSIONS: The mechanisms of transient SCLI on FLAIR images remain unclear, but this finding appears to be associated with a postoperative transient neurological deterioration.

PMID: 26704214 [PubMed - as supplied by publisher]

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Can Serum glucose level in early admission, predict outcome in patints with severe head trauma ?

Can Serum glucose level in early admission, predict outcome in patints with severe head trauma ?

World Neurosurg. 2015 Dec 15;

Authors: Salehpour F, Bazzazi AM, Aghazadeh J, Abbasivash R, Forouhideh Y, Mirzaei F, Naseri Alavi SA

Abstract
BACKGROUND: Traumatic brain Injury is a major general health concern. This study aims to evaluate possible relationship between serum level of glucose during admission and outcome of patients with severe traumatic brain injury.
METHODS: In this prospective study, 80 patients with severe traumatic brain injury were recruited from emergency department of Urmia Imam Khomeini hospital. Serum level of glucose was measured at the time of admission and its correlation was investigated with Glasgow Coma Scale (GCS) score (admission, 24h, 48h, 1week, and discharge) and Glasgow Outcome Score (GOS). The value of admission serum glucose was compared between expired and discharged patients, as well.
RESULTS: Eighty patients with severe head trauma, 71 males (88%) and 9 females (11.2%) with a mean age of 31.71±15.66 were enrolled into the study. The inhospital mortality rate was 25% (n=20). There was no significant correlation between serum glucose level and GCS score (at different intervals) or GOS. The mean serum level of glucose was comparable between expired and discharged cases (186.10±51.36 vs. 187.98±76.03 mg/dl, respectively; p=0.91).
CONCLUSION: Apparently, admission serum glucose is not a significant indicator of outcome in patients with severe head trauma.

PMID: 26704213 [PubMed - as supplied by publisher]

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Subacute Posttraumatic Ascending Myelopathy after an Incomplete Spinal Cord injury from Gunshot Wound to the Spine - Case Report and Review of the Literature.

Subacute Posttraumatic Ascending Myelopathy after an Incomplete Spinal Cord injury from Gunshot Wound to the Spine - Case Report and Review of the Literature.

World Neurosurg. 2015 Dec 15;

Authors: Miller BA, Roy AK, Boucher A, Pradilla G, Ahmad FU

PMID: 26704212 [PubMed - as supplied by publisher]

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Perspective of Value-Based Management of Spinal Disorders in Brazil.

Perspective of Value-Based Management of Spinal Disorders in Brazil.

World Neurosurg. 2015 Dec 15;

Authors: Teles AR, Righesso O, Gullo MC, Ghogawala Z, Falavigna A

PMID: 26704211 [PubMed - as supplied by publisher]

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Simulation in Neurosurgery - a brief review and commentary.

Simulation in Neurosurgery - a brief review and commentary.

World Neurosurg. 2015 Dec 15;

Authors: Cobb MI, Taekman JM, Zomorodi AR, Gonzalez LF, Turner DA

Abstract
Neurosurgery is one of the most technically demanding and liable of all medical professionals. More than 75% of neurosurgical errors deemed as preventable and technical in nature. Yet in a specialty that requires such high level of technical expertise, with large consequences for error, there are even fewer opportunities for residents in training to practice on the most complicated cases. Although there is no replacement for actual experiences in the operating room, inter-personal mentorship, coaching, and training, there is room to supplement residency education through simulation. Here we review the evidence to support surgical simulation, describe the strengths and weaknesses of existing technologies in direct neurosurgery specific and indirect simulation applications, and advocate for the development of more neurosurgery specific applications using emerging kinetic technologies.

PMID: 26704209 [PubMed - as supplied by publisher]

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Outcome of microscopic Transsphenoidal Surgery in Cushing's disease: a case series of 96 patients.

Outcome of microscopic Transsphenoidal Surgery in Cushing's disease: a case series of 96 patients.

World Neurosurg. 2015 Dec 15;

Authors: Shirvani M, Motiei-Langroudi R, Sadeghian H

PMID: 26704208 [PubMed - as supplied by publisher]

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A dissecting aneurysm of the distal medial lenticulostriate artery: Case report.

A dissecting aneurysm of the distal medial lenticulostriate artery: Case report.

World Neurosurg. 2015 Dec 15;

Authors: Saito A, Kon H, Nakamura T, Sasaki T

Abstract
BACKGROUND: Medial lenticulostriate artery (MLSA) aneurysms are rare; to our knowledge only 2 cases without an association with Moyamoya disease have been documented. We treated a ruptured dissecting aneurysm of the distal MLSA surgically using a tube retractor.
CASE DESCRIPTION: A 66-year-old woman suffered sudden-onset consciousness disturbance. Computed tomography showed diffuse subarachnoid hemorrhage and a dense intraventricular hematoma associated with acute hydrocephalus. She underwent emergent ventricular drainage. Angiography revealed a 3-mm distal MLSA aneurysm. On repeat angiographs the aneurysm had not disappeared. As the stenotic, narrow structure of the proximal portion of the MLSA disallowed the endovascular approach we performed direct surgery via the transventricular approach using a tube retractor. The aneurysm on the intraventricular surface of the anterior horn of the lateral ventricle adjacent to the caudate nucleus was exposed. We resected the aneurysm under transcranial motor-evoked potential monitoring because neck clipping would have endangered the patency of the MLSA. Her postoperative course was uneventful. The pathological diagnosis was ruptured dissecting aneurysm.
CONCLUSIONS: There is no definitive strategy to treat distal MLSA aneurysms. Our experience illustrates that natural healing of the vessel wall cannot be expected in all cases. Therefore, less invasive direct surgical- as well as endovascular treatment should not be ruled out in patients with ruptured distal MLSA aneurysms.

PMID: 26704207 [PubMed - as supplied by publisher]

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Preoperative embolization of spinal tumors: A systematic review and meta-analysis.

Preoperative embolization of spinal tumors: A systematic review and meta-analysis.

World Neurosurg. 2015 Dec 15;

Authors: Griessenauer CJ, Salem M, Hendrix P, Foreman PM, Ogilvy CS, Thomas AJ

Abstract
BACKGROUND: Spinal tumors are referred for preoperative embolization to minimize intraoperative blood loss and facilitate surgical resection.
OBJECTIVE: To perform a systematic review and meta-analysis and provide comprehensive data on embolization technique, efficacy, and complications.
METHODS: A systematic review of PubMed articles was performed with the following inclusion criteria: original studies, studies of ≥ 10 patients (except Onyx due to scarcity of available data), embolization through vascular access, and reporting of the embolic agent used. Additionally the manuscript needed to contain at least one of the following variables: demographics, tumor type, location, vascularity, degree of devascularization, complications, time to operation, type of operation, estimated blood loss (EBL), and use of blood transfusion.
RESULTS: Thirty-seven studies with a total of 1,305 patients met inclusion criteria. Renal cell carcinoma was the most commonly embolized tumor comprising 47.4% (95% CI 39.4 - 55.4) of all tumor embolizations. The rate of complete devascularization for all tumor types was 68.3% (95% CI 60.0 - 76.6). There was a significant decrease in operative EBL in more recently published studies as compared to earlier studies, however, the rate of complete embolization remained stable. Polyvinyl alcohol (PVA) and Onyx(®) were associated with similar EBL and rates of complete embolization. The overall complication rate was 3.1% (95% CI 1.2 - 4.9).
CONCLUSIONS: The rapid evolution of neurointervention and spinal tumor embolization has made scientific inquiry and definitive conclusion on the safety and efficacy of the practice difficult. The data supporting the procedure is fragmented and largely based on a multitude of retrospective studies utilizing varying techniques. Review of the available literature support embolization of spinal tumors as a safe and efficacious treatment adjunct prior to surgery.

PMID: 26704206 [PubMed - as supplied by publisher]

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Clinical Experience with Pedunculopontine Nucleus Stimulation in Conditions with Nigro-Striatal Disconnection.

Clinical Experience with Pedunculopontine Nucleus Stimulation in Conditions with Nigro-Striatal Disconnection.

World Neurosurg. 2015 Dec 15;

Authors: Rowe J, Khan A, Romanowski C, Isaac C, Khan S, Mair R, Aziz T, Yianni J

PMID: 26704205 [PubMed - as supplied by publisher]

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World Health Organization Grade I Convexity Meningiomas: Study on Outcomes, Complications and Recurrence Rates.

World Health Organization Grade I Convexity Meningiomas: Study on Outcomes, Complications and Recurrence Rates.

World Neurosurg. 2015 Dec 15;

Authors: Nanda A, Bir SC, Konar S, Maiti TK, Bollam P

Abstract
BACKGROUND: The clinical significance of the Simpson grading system of extent of meningioma resection and its role as a predictor for recurrence of World Health Organization (WHO) grade I meningiomas has been questioned in the past, as microsurgery and knowledge of pathological details have advanced.
METHODS: Clinical and radiological information of 112 patients with WHO grade I convexity meningiomas who underwent surgery over the past 20 years was retrospectively reviewed.
RESULTS: The recurrence rate in grade 0-I resection group was 2.9%, whereas in grade II-IV resection group, recurrence rate was 31% (p=0.0001). In Cox regression analysis, Simpson grade 0-I resection was revealed as a significant predictor of RFS (p=0.021). The hazard ratio for recurrence after II-IV resection was 10.98 times higher than grade 0- I. Like Simpson grading of resection, a similar trend of recurrence (grade I, 1.6% vs. grade II-IV, 28%, p=0.0001) was observed in Shinshu grade of resection. In univariate analysis, female gender and using of neuronavigation were also identified as independent predictors of RFS after resection of WHO grade I meningiomas. Six months after surgery, using of anti-epileptic medication was less in grade 0-I compared to other grades.
CONCLUSION: When histological grade is fixed, Simpson's grading system is the prime predictor for recurrence of meningioma after resection. Grade 0-I resection is also beneficial to cut off anti-epileptic medication in patients with convexity meningiomas. Although complete tumor resection (grade 0-I) is the goal, surgical approach should be tailored to each patient depending on the risks and surgical morbidity.

PMID: 26704204 [PubMed - as supplied by publisher]

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