Real-Time Estimation of Core Infarct in Angiography Using Collateral Flow

Background and Purpose: In order to attribute a diagnostic value to angiographic runs performed before revascularization, we aimed at developing a regional evaluation of leptomeningeal collateral flow that can be used to detect and predict infarction when performing stroke endovascular procedures. Materials and Methods: We evaluated all consecutive patients treated for occlusions in the anterior circulation in our center between 2009 and 2013, with MRI imaging performed before the endovascular procedure. Two readers performed an evaluation of collateral circulation in 5 cortical regions based on the vascular anatomy. Regional scores were correlated with the presence of infarction in the same cortical sector on pretreatment and follow-up imaging. Global collateral scores for each patient were correlated with infarct volumes. Results: In 89 patients with 408 cortical regions, we found a significant correlation between the degree of zonal collateral flow and the absence of infarction in the same zone on pretreatment imaging. In a subgroup of 37 recanalized patients (Thrombolysis in Cerebral Infarction scale 3) with 173 cortical zones, retrograde collateral flow to the proximal M4 segment predicted the absence of infarction within the same zone on follow-up imaging (positive predictive value 88.7%). We found good inter-rater agreement for the presence of collateral flow to the M4 proximal segment or further – k = 0.77 (p = 0.05, 95% CI 0.66-0.88). Global collateral scores correlated with infarct volume on initial imaging; all patients with scores ≥4 had infarct volumes ≤70 ml, whereas all patients with global collateral scores ≤1 had infarct volumes ≥70 ml. Conclusion: Anatomic collateral flow evaluation using the angiographic runs performed during stroke endovascular procedures can provide a real-time estimation of the volume and location of core infarct. For each cortical region, good collateral flow is associated with the absence of infarct on pre-treatment imaging, and is predictive of the absence of infarct on follow-up imaging in recanalized patients.
Cerebrovasc Dis 2016;41:177-186

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Dysregulation of protein methyltransferases in human cancer: an emerging target class for anticancer therapy

Abstract

Protein methylation is one of the important post-translational modifications. Although its biological and physiological functions were unknown for a long time, we and others have characterized a number of protein methyltransferases, which unveils the critical functions of protein methylation in various cellular processes, in particular, in epigenetic regulation. In addition, it had been believed that protein methylation is an irreversible phenomenon, but through identification of a variety of protein demethylases, protein methylation is now considered to be dynamically regulated as resemble to protein phosphorylation. A large amount of evidence indicated that protein methylation has a pivotal role in post-translational modification of histone proteins as well as non-histone proteins and is involved in various processes of cancer development and progression. Since dysregulation of this modification has been observed frequently in various types of cancer, small-molecule inhibitors targeting protein methyltransferases and demethylases have been actively developed as anti-cancer drugs, for some of which clinical trials have just been started. In this review, we discuss the biological and physiological importance of protein methylation in human cancer, especially focusing on the significance of protein methyltransferases as emerging targets for anticancer therapy.

This article is protected by copyright. All rights reserved.

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Viruses, Vol. 8, Pages 16: Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC

Rhinoviruses (RVs) and respiratory enteroviruses (EVs) are leading causes of upper respiratory tract infections and among the most frequent infectious agents in humans worldwide. Both are classified in the Enterovirus genus within the Picornaviridae family and they have been assigned to seven distinct species, RV-A, B, C and EV-A, B, C, D. As viral infections of public health significance, they represent an important financial burden on health systems worldwide. However, the lack of efficient antiviral treatment or vaccines against these highly prevalent pathogens prevents an effective management of RV-related diseases. Current advances in molecular diagnostic techniques have revealed the presence of RV in the lower respiratory tract and its role in lower airway diseases is increasingly reported. In addition to an established etiological role in the common cold, these viruses demonstrate an unexpected capacity to spread to other body sites under certain conditions. Some of these viruses have received particular attention recently, such as EV-D68 that caused a large outbreak of respiratory illness in 2014, respiratory EVs from species C, or viruses within the newly-discovered RV-C species. This review provides an update of the latest findings on clinical and fundamental aspects of RV and respiratory EV, including a summary of basic knowledge of their biology.

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Knee Pain 101

CNN interviews an orthopedic surgeon at Emory: Mild injury as a child leads to chronic changes as we get older:

Posted at Clinical Cases and Images. Stay updated and subscribe, follow us on Twitter and connect on Facebook.

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Illustrated tributes to David Bowie carry the news of musician’s death – Dezeen

Dezeen

Illustrated tributes to David Bowie carry the news of musician's death Dezeen Following the death of legendary musician David Bowie, illustrators and graphic designers are posting their images interpreting his iconic style and flamboyant fashion. Bowie died yesterday aged 69 after a 18-month battle with cancer, sparking a global … and more »

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Cortical Superficial Siderosis in Memory Clinic Patients: Further Evidence for Underlying Cerebral Amyloid Angiopathy

Background: Cerebral amyloid angiopathy (CAA) is associated with many cases of spontaneous symptomatic lobar intracerebral haemorrhage in older individuals and is emerging as an important contributor to cognitive impairment. Cortical superficial siderosis (cSS) is an increasingly recognized haemorrhagic neuroimaging manifestation of CAA. We sought to investigate its prevalence and its association with underlying CAA among memory clinic patients. Methods: We included consecutive eligible patients who presented to the out-patient memory clinic at the Massachusetts General Hospital from 2007 to 2010 and had appropriate MRI, including blood-sensitive sequences. We analyzed the prevalence and topography of cSS according to demographic, clinical, APOE and MRI data. Results: Our cohort consisted of 339 memory clinic patients: Alzheimer's disease (n = 86); mild cognitive impairment (n = 162); vascular dementia/mixed dementia (n = 18); other dementia/undetermined (n = 42); and subjective cognitive complains (n = 31). cSS was detected in 10 patients (3%; 95% CI 1.4-5.4): in 7 cases cSS was focal and in 3 cases, it was disseminated. In multivariable logistic regression analysis, the presence of cSS was associated with lobar microbleeds (OR 1.08; 95% CI 1.03-1.13; p = 0.001, per each additional microbleed) and severe white matter hyperintensities (Fazekas score 5-6, OR 4.43; 95% CI 1.21-26.28; p = 0.028) after adjusting for age. These associations were not influenced by the clinical diagnosis. In patients with APOE data, the APOE ε4/ε4 genotype was overrepresented among subjects with vs. without cSS. In the subgroup of patients with probable CAA (n = 68; 9 with cSS) based on the presence of strictly lobar microbleeds, cSS was also associated with a higher prevalence of severe white matter hyperintensities (66.7 vs. 10.2%; p = 0.001), high centrum semiovale perivascular spaces burden (88.9 vs. 52.4%; p = 0.041) and higher counts of lobar microbleeds (median 13; IQR 10-36 vs. median 1; IQR 1-2; p Conclusions: Our data provide further evidence supporting the hypothesis that cSS is a manifestation of advanced CAA in memory clinic populations. Future longitudinal studies should explore any direct effect of cSS on cognition or haemorrhage risk and disease progression.
Cerebrovasc Dis 2016;41:156-162

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Frequency and Risk Factors for Cerebral Arterial Disease in a HIV/AIDS Neuroimaging Cohort

Background: Infection with HIV predisposes patients to a myriad of neurologic disorders, including cerebrovascular disease. The pathophysiology is likely multifactorial, with proposed mechanisms including infectious vasculitis, HIV-induced endothelial dysfunction and adverse effects of combination antiretroviral therapy (cART). Epidemiologic data on clinically evident cerebral vasculopathy in HIV-infected adults is scarce, even though stroke hospitalizations are rising in this patient population. Methods: A total of 6,298 HIV-infected adults (San Francisco General Hospital, 2000-2013) were screened to generate a cohort of patients with dedicated neuroimaging of the intra- and extracranial cerebral vasculature. We extracted information regarding the extent of HIV disease (including serial viral load and CD4 counts), cardiovascular disease risk factors and exposure to cART (cross-referenced with pharmacy records) and performed multivariate logistic regression analysis to identify predictors of vasculopathy. Results: Of 144 patients, 55 patients (38.2%) had radiographic evidence of cerebral vasculopathy. Twenty (13.9%) had a vasculopathy characterized by vessel dolichoectasia and intracranial aneurysm formation. Thirty-five patients (24.3%) had intra- and or extracranial stenosis/occlusion. cART use (OR 2.27, 95% CI 1.03-5) and tobacco abuse (OR 2.35, 95% CI 1.04-5.25) were independently associated with the development of any vasculopathy, whereas cART use was also an independent risk factor for the stenosis/occlusion subtype specifically (OR 2.87, 95% CI 1.11-7.45). Conclusions: There was a high frequency of cerebral arterial disease in this neuroimaging cohort of HIV/AIDS patients. A history of cART use and a history of tobacco abuse were independent risk factors for vasculopathy, though these findings should be confirmed with large-scale prospective studies.
Cerebrovasc Dis 2016;41:170-176

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Real-Time Estimation of Core Infarct in Angiography Using Collateral Flow

Background and Purpose: In order to attribute a diagnostic value to angiographic runs performed before revascularization, we aimed at developing a regional evaluation of leptomeningeal collateral flow that can be used to detect and predict infarction when performing stroke endovascular procedures. Materials and Methods: We evaluated all consecutive patients treated for occlusions in the anterior circulation in our center between 2009 and 2013, with MRI imaging performed before the endovascular procedure. Two readers performed an evaluation of collateral circulation in 5 cortical regions based on the vascular anatomy. Regional scores were correlated with the presence of infarction in the same cortical sector on pretreatment and follow-up imaging. Global collateral scores for each patient were correlated with infarct volumes. Results: In 89 patients with 408 cortical regions, we found a significant correlation between the degree of zonal collateral flow and the absence of infarction in the same zone on pretreatment imaging. In a subgroup of 37 recanalized patients (Thrombolysis in Cerebral Infarction scale 3) with 173 cortical zones, retrograde collateral flow to the proximal M4 segment predicted the absence of infarction within the same zone on follow-up imaging (positive predictive value 88.7%). We found good inter-rater agreement for the presence of collateral flow to the M4 proximal segment or further – k = 0.77 (p = 0.05, 95% CI 0.66-0.88). Global collateral scores correlated with infarct volume on initial imaging; all patients with scores ≥4 had infarct volumes ≤70 ml, whereas all patients with global collateral scores ≤1 had infarct volumes ≥70 ml. Conclusion: Anatomic collateral flow evaluation using the angiographic runs performed during stroke endovascular procedures can provide a real-time estimation of the volume and location of core infarct. For each cortical region, good collateral flow is associated with the absence of infarct on pre-treatment imaging, and is predictive of the absence of infarct on follow-up imaging in recanalized patients.
Cerebrovasc Dis 2016;41:177-186

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Viruses, Vol. 8, Pages 15: Dynamic Viral Glycoprotein Machines: Approaches for Probing Transient States That Drive Membrane Fusion

The fusion glycoproteins that decorate the surface of enveloped viruses undergo dramatic conformational changes in the course of engaging with target cells through receptor interactions and during cell entry. These refolding events ultimately drive the fusion of viral and cellular membranes leading to delivery of the genetic cargo. While well-established methods for structure determination such as X-ray crystallography have provided detailed structures of fusion proteins in the pre- and post-fusion fusion states, to understand mechanistically how these fusion glycoproteins perform their structural calisthenics and drive membrane fusion requires new analytical approaches that enable dynamic intermediate states to be probed. Methods including structural mass spectrometry, small-angle X-ray scattering, and electron microscopy have begun to provide new insight into pathways of conformational change and fusion protein function. In combination, the approaches provide a significantly richer portrait of viral fusion glycoprotein structural variation and fusion activation as well as inhibition by neutralizing agents. Here recent studies that highlight the utility of these complementary approaches will be reviewed with a focus on the well-characterized influenza virus hemagglutinin fusion glycoprotein system.

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How does your garden grow? For cancer patients, small gardens could bring big benefits

Dr Phelps discusses her recently published article on a feasibility study involving breast cancer patients tending "garden bowls". The aim was to find out whether the well-known benefits of nature, sometimes known as ecotherapy, could be captured…

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Use of pulsed dye laser treatments in patients with vocal fold mucosal bridges with sulcus vocalis-our experience of five cases

Abstract

Larger and thicker mucosal bridges are usually associated with severe dysphonia, surgical excision is the currently preferred treatment.

Surgical excision of mucosal bridges may decrease vocal fold bulk and result in subsequent postoperative glottal incompetence.

PDL can make a cleavage plane between the epithelium and the superficial lamina propria by denaturing the anchoring fibers of lamina lucida of the basement membrane, and this plane allows en-bloc and easy peeling of the medial epithelium of the mucosal bridge. In addition, epithelium overlying the sulcus can be vapourized or denatured by direct contact with the PDL fibres. Therefore, approximation between the de-epithelized mucosal bridge and the PDL-treated sulcus bed can be accomplished easily with preservation of the lamina propria of vocal folds.

PDL may induce additional restoration of lamina propria by physiologic tissue remodeling on the accompanying sulcus vocalis with mucosal bridge

PDL glottoplasty with the PDL-assisted mucosal bridge undermining technique can be an effective and safe technique, and be advised for obviating the loss of bulk due to surgical resection of the mucosal bridge.

This article is protected by copyright. All rights reserved.

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Thrombolysis in Stroke Patients with Isolated Aphasia

Background: Data about evolution of aphasia following stroke are rare and controversial especially following fibrinolysis. The aim of this study was to describe the early clinical patterns of isolated aphasia in consecutive stroke patients with or without thrombolysis. Methods: Clinical and radiological data of consecutive stroke patients were routinely entered in prospective registry. Patients were considered aphasic when NIHSS (National Institutes of Health Stroke Scale) item 9 >0. 'Isolated aphasia' was defined by aphasic patients without motor limb deficit. We created a 'composite language score' obtained by summing the NIHSS items 1b, 1c and 9, which reflects language-processing ability. Recovery of functions was evaluated as measured by global NIHSS, composite language score and language screening test (LAST) at baseline, H24 and day 7 (D7). 'Mild deficit' was defined as global NIHSS Results: A total of 100 consecutive patients met study criteria for isolated aphasia. Twenty-five underwent thrombolysis and 75 did not. There was no difference between the 2 groups concerning demographic characteristics, involved territories and presence of arterial occlusion, initial median NIHSS, composite language and LAST scores at entrance. Evolution was significantly better in thrombolysed patient for the 3 testings: NIHSS, composite language score and LAST at D7 (respective p = 0.0002; p = 0.01 and p = 0.004). Similar results were found when we focused on the subgroups of patients with initial 'mild' deficits (p = 0.01; p = 0.0003 and p = 0.007). No symptomatic hemorrhagic transformation occurred following thrombolysis. Conclusion: These data strongly suggest that thrombolysis is safe and effective in patients with 'isolated aphasia,' even if the global NIHSS score is Cerebrovasc Dis 2016;41:163-169

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Microorganisms, Vol. 4, Pages 8: Extremophiles in an Antarctic Marine Ecosystem

Recent attempts to explore marine microbial diversity and the global marine microbiome have indicated a large proportion of previously unknown diversity. However, sequencing alone does not tell the whole story, as it relies heavily upon information that is already contained within sequence databases. In addition, microorganisms have been shown to present small-to-large scale biogeographical patterns worldwide, potentially making regional combinations of selection pressures unique. Here, we focus on the extremophile community in the boundary region located between the Polar Front and the Southern Antarctic Circumpolar Current in the Southern Ocean, to explore the potential of metagenomic approaches as a tool for bioprospecting in the search for novel functional activity based on targeted sampling efforts. We assessed the microbial composition and diversity from a region north of the current limit for winter sea ice, north of the Southern Antarctic Circumpolar Front (SACCF) but south of the Polar Front. Although, most of the more frequently encountered sequences were derived from common marine microorganisms, within these dominant groups, we found a proportion of genes related to secondary metabolism of potential interest in bioprospecting. Extremophiles were rare by comparison but belonged to a range of genera. Hence, they represented interesting targets from which to identify rare or novel functions. Ultimately, future shifts in environmental conditions favoring more cosmopolitan groups could have an unpredictable effect on microbial diversity and function in the Southern Ocean, perhaps excluding the rarer extremophiles.

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Prognostic factors for re-mobilization using plerixafor and granulocyte colony-stimulating factor (G-CSF) in patients with malignant lymphoma or multiple myeloma previously failing mobilization with G-CSF with or without chemotherapy: the Korean multicenter retrospective study

Abstract

Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has been shown to improve the rates of successful peripheral blood stem cell (PBSC) mobilization in patients with malignant lymphoma or multiple myeloma (MM) who experienced prior failure of PBSC mobilization. We evaluated the mobilization results of re-mobilization using plerixafor and G-CSF in insufficiently mobilizing patients. Forty-four patients with lymphoma (n = 29) or MM (n = 15) were included in the study. The median age was 50 (range, 24–64) years. Previous mobilization regimens were chemotherapy with G-CSF (n = 28), including cyclophosphamide with G-CSF (n = 15), and G-CSF only (n = 16). All patients with lymphoma achieved at least partial response (PR) before the mobilization, including 13 complete responses (CRs). Eleven patients with MM achieved at least PR and four patients with MM were in stable disease before mobilization. The median number of apheresis was 3 (range, 1–6). The median yield of PBSC collections was 3.41 (0.13–38.11) × 106 CD34+ cells/kg. Thirty-four (77.3 %) patients had successful collections defined as at least 2 × 106 CD34+ cells/kg. The rate of successful collections was not different between the two underlying diseases (79.3 % in lymphoma and 73.3 % in MM). Of the entire cohort, 38 (86.4 %) of patients went on to receive an autologous transplant. Previous long-term use of high-risk drugs (>4 cycles use of alkylating agents, platinum-containing agents, or thalidomide) (HR 10.8, 95 % CI 1.1–110.0, P = 0.043) and low platelet count (<100 × 109/L) 1 day before the first apheresis (HR 27.9, 95 % CI 2.9–273.7, P = 0.004) were independent prognostic factors for predicting failure of PBSC re-mobilization using plerixafor and G-CSF. In conclusion, re-mobilization using plerixafor and G-CSF showed a success rate of 77.3 % in patients with lymphoma or MM who experienced prior failure of PBSC mobilization, and the majority of them underwent autologous transplant. Therefore, plerixafor-based re-mobilization was an effective method in poor mobilizers.

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Cortical Superficial Siderosis in Memory Clinic Patients: Further Evidence for Underlying Cerebral Amyloid Angiopathy

Background: Cerebral amyloid angiopathy (CAA) is associated with many cases of spontaneous symptomatic lobar intracerebral haemorrhage in older individuals and is emerging as an important contributor to cognitive impairment. Cortical superficial siderosis (cSS) is an increasingly recognized haemorrhagic neuroimaging manifestation of CAA. We sought to investigate its prevalence and its association with underlying CAA among memory clinic patients. Methods: We included consecutive eligible patients who presented to the out-patient memory clinic at the Massachusetts General Hospital from 2007 to 2010 and had appropriate MRI, including blood-sensitive sequences. We analyzed the prevalence and topography of cSS according to demographic, clinical, APOE and MRI data. Results: Our cohort consisted of 339 memory clinic patients: Alzheimer's disease (n = 86); mild cognitive impairment (n = 162); vascular dementia/mixed dementia (n = 18); other dementia/undetermined (n = 42); and subjective cognitive complains (n = 31). cSS was detected in 10 patients (3%; 95% CI 1.4-5.4): in 7 cases cSS was focal and in 3 cases, it was disseminated. In multivariable logistic regression analysis, the presence of cSS was associated with lobar microbleeds (OR 1.08; 95% CI 1.03-1.13; p = 0.001, per each additional microbleed) and severe white matter hyperintensities (Fazekas score 5-6, OR 4.43; 95% CI 1.21-26.28; p = 0.028) after adjusting for age. These associations were not influenced by the clinical diagnosis. In patients with APOE data, the APOE ε4/ε4 genotype was overrepresented among subjects with vs. without cSS. In the subgroup of patients with probable CAA (n = 68; 9 with cSS) based on the presence of strictly lobar microbleeds, cSS was also associated with a higher prevalence of severe white matter hyperintensities (66.7 vs. 10.2%; p = 0.001), high centrum semiovale perivascular spaces burden (88.9 vs. 52.4%; p = 0.041) and higher counts of lobar microbleeds (median 13; IQR 10-36 vs. median 1; IQR 1-2; p Conclusions: Our data provide further evidence supporting the hypothesis that cSS is a manifestation of advanced CAA in memory clinic populations. Future longitudinal studies should explore any direct effect of cSS on cognition or haemorrhage risk and disease progression.
Cerebrovasc Dis 2016;41:156-162

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Use of pulsed dye laser treatments in patients with vocal fold mucosal bridges with sulcus vocalis-our experience of five cases

Abstract

Larger and thicker mucosal bridges are usually associated with severe dysphonia, surgical excision is the currently preferred treatment.

Surgical excision of mucosal bridges may decrease vocal fold bulk and result in subsequent postoperative glottal incompetence.

PDL can make a cleavage plane between the epithelium and the superficial lamina propria by denaturing the anchoring fibers of lamina lucida of the basement membrane, and this plane allows en-bloc and easy peeling of the medial epithelium of the mucosal bridge. In addition, epithelium overlying the sulcus can be vapourized or denatured by direct contact with the PDL fibres. Therefore, approximation between the de-epithelized mucosal bridge and the PDL-treated sulcus bed can be accomplished easily with preservation of the lamina propria of vocal folds.

PDL may induce additional restoration of lamina propria by physiologic tissue remodeling on the accompanying sulcus vocalis with mucosal bridge

PDL glottoplasty with the PDL-assisted mucosal bridge undermining technique can be an effective and safe technique, and be advised for obviating the loss of bulk due to surgical resection of the mucosal bridge.

This article is protected by copyright. All rights reserved.

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Toxic epidermal necrolysis in adult T cell leukemia/lymphoma treated with mogamulizumab

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Frequency and Risk Factors for Cerebral Arterial Disease in a HIV/AIDS Neuroimaging Cohort

Background: Infection with HIV predisposes patients to a myriad of neurologic disorders, including cerebrovascular disease. The pathophysiology is likely multifactorial, with proposed mechanisms including infectious vasculitis, HIV-induced endothelial dysfunction and adverse effects of combination antiretroviral therapy (cART). Epidemiologic data on clinically evident cerebral vasculopathy in HIV-infected adults is scarce, even though stroke hospitalizations are rising in this patient population. Methods: A total of 6,298 HIV-infected adults (San Francisco General Hospital, 2000-2013) were screened to generate a cohort of patients with dedicated neuroimaging of the intra- and extracranial cerebral vasculature. We extracted information regarding the extent of HIV disease (including serial viral load and CD4 counts), cardiovascular disease risk factors and exposure to cART (cross-referenced with pharmacy records) and performed multivariate logistic regression analysis to identify predictors of vasculopathy. Results: Of 144 patients, 55 patients (38.2%) had radiographic evidence of cerebral vasculopathy. Twenty (13.9%) had a vasculopathy characterized by vessel dolichoectasia and intracranial aneurysm formation. Thirty-five patients (24.3%) had intra- and or extracranial stenosis/occlusion. cART use (OR 2.27, 95% CI 1.03-5) and tobacco abuse (OR 2.35, 95% CI 1.04-5.25) were independently associated with the development of any vasculopathy, whereas cART use was also an independent risk factor for the stenosis/occlusion subtype specifically (OR 2.87, 95% CI 1.11-7.45). Conclusions: There was a high frequency of cerebral arterial disease in this neuroimaging cohort of HIV/AIDS patients. A history of cART use and a history of tobacco abuse were independent risk factors for vasculopathy, though these findings should be confirmed with large-scale prospective studies.
Cerebrovasc Dis 2016;41:170-176

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Myelodysplastic syndrome with del (5q) and JAK2 V617F mutation transformed to acute myeloid leukaemia with complex karyotype

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Acute myeloid leukemia with t(3;8)(q26;q24) complicated by diabetes insipidus

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Use of pulsed dye laser treatments in patients with vocal fold mucosal bridges with sulcus vocalis-our experience of five cases

Abstract

Larger and thicker mucosal bridges are usually associated with severe dysphonia, surgical excision is the currently preferred treatment.

Surgical excision of mucosal bridges may decrease vocal fold bulk and result in subsequent postoperative glottal incompetence.

PDL can make a cleavage plane between the epithelium and the superficial lamina propria by denaturing the anchoring fibers of lamina lucida of the basement membrane, and this plane allows en-bloc and easy peeling of the medial epithelium of the mucosal bridge. In addition, epithelium overlying the sulcus can be vapourized or denatured by direct contact with the PDL fibres. Therefore, approximation between the de-epithelized mucosal bridge and the PDL-treated sulcus bed can be accomplished easily with preservation of the lamina propria of vocal folds.

PDL may induce additional restoration of lamina propria by physiologic tissue remodeling on the accompanying sulcus vocalis with mucosal bridge

PDL glottoplasty with the PDL-assisted mucosal bridge undermining technique can be an effective and safe technique, and be advised for obviating the loss of bulk due to surgical resection of the mucosal bridge.

This article is protected by copyright. All rights reserved.

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Microorganisms, Vol. 4, Pages 8: Extremophiles in an Antarctic Marine Ecosystem

Recent attempts to explore marine microbial diversity and the global marine microbiome have indicated a large proportion of previously unknown diversity. However, sequencing alone does not tell the whole story, as it relies heavily upon information that is already contained within sequence databases. In addition, microorganisms have been shown to present small-to-large scale biogeographical patterns worldwide, potentially making regional combinations of selection pressures unique. Here, we focus on the extremophile community in the boundary region located between the Polar Front and the Southern Antarctic Circumpolar Current in the Southern Ocean, to explore the potential of metagenomic approaches as a tool for bioprospecting in the search for novel functional activity based on targeted sampling efforts. We assessed the microbial composition and diversity from a region north of the current limit for winter sea ice, north of the Southern Antarctic Circumpolar Front (SACCF) but south of the Polar Front. Although, most of the more frequently encountered sequences were derived from common marine microorganisms, within these dominant groups, we found a proportion of genes related to secondary metabolism of potential interest in bioprospecting. Extremophiles were rare by comparison but belonged to a range of genera. Hence, they represented interesting targets from which to identify rare or novel functions. Ultimately, future shifts in environmental conditions favoring more cosmopolitan groups could have an unpredictable effect on microbial diversity and function in the Southern Ocean, perhaps excluding the rarer extremophiles.

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Molecular Targeted Therapy Approaches for BRAF Wild-Type Melanoma

Molecular Targeted Therapy Approaches for BRAF Wild-Type Melanoma:

Abstract

Patients with metastatic melanoma have historically had dismal outcomes. The last several years has seen the emergence of effective immune and targeted therapies for metastatic melanoma. Targeted therapies have primarily impacted the 40–50 % of patients with BRAF ^V600 mutated melanoma. The remainder of patients with advanced melanoma harbor a wide spectrum of mutations other than BRAF ^V600 that are associated with unique pathophysiological, prognostic, and therapeutic implications. The treatment of this subset of patients is a challenging problem. In recent years, preclinical and early clinical studies have suggested that inhibitors of mitogen activated protein kinase (MAPK) pathway and parallel signaling networks may have activity in treatment of BRAF ^V600 wild-type (WT) melanoma. In this review, we will discuss available and developing therapies for BRAF WT patients with metastatic melanoma, particularly focusing on molecular targeted options for various genetically defined melanoma subsets.

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Central nervous system germinoma

Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation:

Abstract

CNS germinomas have an excellent prognosis with radiation therapy alone. However, in children, volume and dose of CNS radiation are associated with neurocognitive and neuroendocrine sequelae. Our objective was to determine long-term outcomes of our cohort who received chemotherapy and reduced radiation. This retrospective cohort study analyzed treatment and outcome of intracranial germinoma patients consecutively treated at Sick Kids, Toronto, Canada, from January 2000 to December 2013. 24 children (13 male, 11 female; median age 13.36 years) were identified. Median follow up was 61 months (range 1–144 months). Tumor location was suprasellar (n = 9), bifocal (8), pineal (6), and basal ganglia (1). Three children showed dissemination on imaging. 2/24 had only elevated serum human chorionic gonadotropin, 3/24 only elevated lumbar cerebrospinal fluid (CSF) hCG, and 2/24 had both elevated serum and lumbar CSF hCG. 23/24 children completed treatment and received multi-agent chemotherapy followed by either ventricular radiation (2340–2400 cGy) (n = 9), ventricular radiation + boost (1600 cGy) (n = 8), whole brain (2340 cGy) (n = 3), focal (4000 cGy) (n = 2) or craniospinal radiation (2340 cGy) (n = 1). Five-year progression free and overall survival was 96 and 100 % respectively. 8/24 patients with ventricular radiation ± boost (2340/4000 cGy) displayed stable full scale intelligence quotient over a mean interval of 3 years following radiation, but showed declined processing speed. In this limited experience, excellent 5-year overall survival rates were achieved with chemotherapy followed by reduced whole ventricular radiation even if ventricular radiation was delivered without boost.

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Initial classification of pediatric hearing impairment using behavioral measures of early prelingual auditory development

10.3109/14992027.2015.1120891<br/>Siyu Liang

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Decision-making and outcomes of hearing help-seekers: A self-determination theory perspective

10.3109/14992027.2015.1120893<br/>Jason Ridgway

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Initial classification of pediatric hearing impairment using behavioral measures of early prelingual auditory development

10.3109/14992027.2015.1120891<br/>Siyu Liang

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Decision-making and outcomes of hearing help-seekers: A self-determination theory perspective

10.3109/14992027.2015.1120893<br/>Jason Ridgway

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Primary melanocytic tumors of the central nervous system

Targeted next generation sequencing reveals unique mutation profile of primary melanocytic tumors of the central nervous system:

Abstract

Melanocytic tumors originating in the central nervous system (MT-CNS) are rare tumors that generally have a favorable prognosis, however malignant tumors do occur. Pathogenetically MT-CNS are not well characterized. Similar to uveal melanoma and blue nevi, they frequently harbor activating GNAQ or GNA11 mutations. Rare NRAS mutations have also been reported. Other mutations have not yet been described. We analyzed 19 MT-CNS, 7 uveal melanomas and 19 cutaneous melanomas using a targeted next generation sequencing approach analyzing 29 genes known to be frequently mutated in other melanocytic tumors (in particular uveal and cutaneous melanomas). In concordance with previous studies, cutaneous melanoma samples showed frequent NRAS or BRAF mutations, as well as mutations in other genes (e.g. NF1, RAC1, PIK3CA, ARID1A). Metastasized uveal melanomas exhibited mutations in GNAQ, GNA11 and BAP1. In contrast, MT-CNS almost exclusively demonstrated mutations in GNAQ (71 %) or GNA11 (12 %). Interestingly both GNA11 mutations identified were detected in MT-CNS diagnosed as intermediate grade melanocytomas which also recurred. One of these recurrent cases also harbored an inactivating BAP1 mutation and was found to have lost one copy of chromosome 3. Our findings show that while MT-CNS do have GNAQ or GNA11 mutations, they rarely harbor other recurrent mutations found in uveal or cutaneous melanomas. Considering chromosome 3 and BAP1 loss are robust markers of poor prognosis in uveal melanoma, it will prove interesting to determine whether these genomic alterations are also of prognostic significance in MT-CNS.

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Fully automatic segmentation of left atrium and pulmonary veins in late gadolinium-enhanced MRI: Towards objective atrial scar assessment

Purpose

To realize objective atrial scar assessment, this study aimed to develop a fully automatic method to segment the left atrium (LA) and pulmonary veins (PV) from late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI). The extent and distribution of atrial scar, visualized by LGE-MRI, provides important information for clinical treatment of atrial fibrillation (AF) patients.

Materials and Methods

Forty-six AF patients (age 62 ± 8, 14 female) who underwent cardiac MRI prior to RF ablation were included. A contrast-enhanced MR angiography (MRA) sequence was acquired for anatomy assessment followed by an LGE sequence for LA scar assessment. A fully automatic segmentation method was proposed consisting of two stages: 1) global segmentation by multiatlas registration; and 2) local refinement by 3D level-set. These automatic segmentation results were compared with manual segmentation.

Results

The LA and PVs were automatically segmented in all subjects. Compared with manual segmentation, the method yielded a surface-to-surface distance of 1.49 ± 0.65 mm in the LA region when using both MRA and LGE, and 1.80 ± 0.93 mm when using LGE alone (P < 0.05). In the PV regions, the distance was 2.13 ± 0.67 mm and 2.46 ± 1.81 mm (P < 0.05), respectively. The difference between automatic and manual segmentation was comparable to the interobserver difference (P = 0.8 in LA region and P = 0.7 in PV region).

Conclusion

We developed a fully automatic method for LA and PV segmentation from LGE-MRI, with comparable performance to a human observer. Inclusion of an MRA sequence further improves the segmentation accuracy. The method leads to automatic generation of a patient-specific model, and potentially enables objective atrial scar assessment for AF patients. J. Magn. Reson. Imaging 2016.

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Fully automatic segmentation of left atrium and pulmonary veins in late gadolinium-enhanced MRI: Towards objective atrial scar assessment

Purpose

To realize objective atrial scar assessment, this study aimed to develop a fully automatic method to segment the left atrium (LA) and pulmonary veins (PV) from late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI). The extent and distribution of atrial scar, visualized by LGE-MRI, provides important information for clinical treatment of atrial fibrillation (AF) patients.

Materials and Methods

Forty-six AF patients (age 62 ± 8, 14 female) who underwent cardiac MRI prior to RF ablation were included. A contrast-enhanced MR angiography (MRA) sequence was acquired for anatomy assessment followed by an LGE sequence for LA scar assessment. A fully automatic segmentation method was proposed consisting of two stages: 1) global segmentation by multiatlas registration; and 2) local refinement by 3D level-set. These automatic segmentation results were compared with manual segmentation.

Results

The LA and PVs were automatically segmented in all subjects. Compared with manual segmentation, the method yielded a surface-to-surface distance of 1.49 ± 0.65 mm in the LA region when using both MRA and LGE, and 1.80 ± 0.93 mm when using LGE alone (P < 0.05). In the PV regions, the distance was 2.13 ± 0.67 mm and 2.46 ± 1.81 mm (P < 0.05), respectively. The difference between automatic and manual segmentation was comparable to the interobserver difference (P = 0.8 in LA region and P = 0.7 in PV region).

Conclusion

We developed a fully automatic method for LA and PV segmentation from LGE-MRI, with comparable performance to a human observer. Inclusion of an MRA sequence further improves the segmentation accuracy. The method leads to automatic generation of a patient-specific model, and potentially enables objective atrial scar assessment for AF patients. J. Magn. Reson. Imaging 2016.

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Magnetic resonance lymphangiography: How to prove it?

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Magnetic resonance lymphangiography: How to prove it?

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Hydrogen Sulfide Donor Potentiates Radiotherapy

Hydrogen Sulfide Donor Potentiates Radiotherapy:

Hydrogen sulfide (H₂S) is the last gaseous transmitter identified in mammals, and previous studies have reported disparate conclusions regarding the implication of H₂S in cancer progression. In the present study, we hypothesized that sodium hydrosulfide (NaHS), a fast H₂S-releasing donor, might interfere with the mitochondrial respiratory chain of tumor cells, increase tumor oxygenation, and potentiate the response to irradiation. Using electron paramagnetic resonance (EPR) oximetry, we found a rapid increase in tumor pO₂ after NaHS administration (0.1 mmol/kg) in two human tumor models (breast MDA-MB-231 and cervix SiHa), an effect that was due to a decreased oxygen consumption and an increased tumor perfusion. Tumors irradiated 15 minutes after a single NaHS administration were more sensitive to irradiation compared with those that received irradiation alone (increase in growth delay by 50%). This radiosensitization was due to the oxygen effect, as the increased growth delay was abolished when temporarily clamped tumors were irradiated. In contrast, daily NaHS injection (0.1 mmol/kg/day for 14 days) did not provide any effect on tumor growth in vivo. To understand these paradoxical data, we analyzed the impact of external factors on the cellular response to NaHS. We found that extracellular pH had a dramatic effect on the cell response to NaHS, as the proliferation rate (measured in vitro by BrdU incorporation) was increased at pH = 7.4, but decreased at pH = 6.5. Overall, our study highlights the complex role of environmental components in the response of cancer cells to H₂S and suggests a new approach for the use of H₂S donors in combination with radiotherapy. Mol Cancer Ther; 15(1); 154–61. ©2015 AACR.

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KillerRed-Based Oncolytic Photodynamic Therapy

KillerRed-Based Oncolytic Photodynamic Therapy:

Photodynamic therapy (PDT) is a minimally invasive antitumor therapy that eradicates tumor cells through a photosensitizer-mediated cytotoxic effect upon light irradiation. However, systemic administration of photosensitizer often makes it difficult to avoid a photosensitive adverse effect. The red fluorescent protein KillerRed generates reactive oxygen species (ROS) upon green light irradiation. Here, we show the therapeutic potential of a novel tumor-specific replicating photodynamic viral agent (TelomeKiller) constructed using the human telomerase reverse transcriptase (hTERT) promoter. We investigated the light-induced antitumor effect of TelomeKiller in several types of human cancer cell lines. Relative cell viability was investigated using an XTT assay. The in vivo antitumor effect was assessed using subcutaneous xenografted tumor and lymph node metastasis models. KillerRed accumulation resulted in ROS generation and apoptosis in light-irradiated cancer cells. Intratumoral injection of TelomeKiller efficiently delivered the KillerRed protein throughout the tumors and exhibited a long-lasting antitumor effect with repeated administration and light irradiation in mice. Moreover, intratumorally injected TelomeKiller could spread into the regional lymph node area and eliminate micrometastasis with limited-field laser irradiation. Our results suggest that KillerRed has great potential as a novel photosensitizer if delivered with a tumor-specific virus-mediated delivery system. TelomeKiller-based PDT is a promising antitumor strategy to efficiently eradicate tumor cells. Mol Cancer Ther; 15(1); 199–208. ©2015 AACR.

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Ang-(1-7) Inhibits Proliferation of NPC Cells

Ang-(1-7) Inhibits Proliferation of NPC Cells:

Angiotensin-(1-7) [Ang-(1-7)] is an endogenous, heptapeptide hormone acting through the Mas receptor (MasR), with antiproliferative and antiangiogenic properties. Recent studies have shown that Ang-(1-7) has an antiproliferative action on lung adenocarcinoma cells and prostate cancer cells. In this study, we report that MasR levels were significantly upregulated in nasopharyngeal carcinoma (NPC) specimens and NPC cell lines. Viral vector–mediated expression of Ang-(1-7) dramatically suppressed NPC cell proliferation and migration in vitro. These effects were completely blocked by the specific Ang-(1-7) receptor antagonist A-779, suggesting that they are mediated by the Ang-(1-7) receptor Mas. In this study, Ang-(1-7) not only caused a significant reduction in the growth of human nasopharyngeal xenografts, but also markedly decreased vessel density, suggesting that the heptapeptide inhibits angiogenesis to reduce tumor size. Mechanistic investigations revealed that Ang-(1-7) inhibited the expression of the proangiogenic factors VEGF and PlGF. Taken together, the data suggest that upregulation of MasR could be used as a diagnostic marker of NPC and Ang-(1-7) may be a novel therapeutic agent for nasopharyngeal cancer therapy because it exerts significant antiangiogenic activity. Mol Cancer Ther; 15(1); 37–47. ©2015 AACR.

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AKT Inhibition Promotes Cancer Cell Survival

AKT Inhibition Promotes Cancer Cell Survival:

Small molecule inhibitors of AKT (v-akt murine thymoma viral oncogene homolog) signaling are being evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with subtherapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multiscale, molecular snapshot of this "AKT^low" cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously upregulate a host of other proteins and metabolites posttranscriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. Mol Cancer Ther; 15(1); 142–53. ©2015 AACR.

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Melanoma Patient-Reported Quality of Life Outcomes Following Sentinel Lymph Node Biopsy, Completion Lymphadenectomy, and Adjuvant Interferon: Results from the Sunbelt Melanoma Trial

Melanoma Patient-Reported Quality of Life Outcomes Following Sentinel Lymph Node Biopsy, Completion Lymphadenectomy, and Adjuvant Interferon: Results from the Sunbelt Melanoma Trial:

Abstract

Background

Quality of life (QOL) and physical condition (PC) outcomes after sentinel lymph node biopsy (SLNB), completion lymph node dissection (CLND), and adjuvant therapy with interferon alfa-2b (IFN) were evaluated in this study.

Methods

Self-reported QOL and PC scores were evaluated in patients enrolled in a prospective, multicenter, randomized, clinical trial evaluating adjuvant IFN. After SLN biopsy, patients with a positive SLN underwent CLND then were randomized to adjuvant IFN or observation. QOL and PC scores were compared between patients who underwent SLNB alone, CLND without IFN, and CLND with IFN. Time to return to baseline QOL and PC scores reported at the time of SLNB was recorded and compared.

Results

There were statistically significant differences in time to return to baseline QOL (p = 0.0018) and PC (p = 0.0018) scores across the three treatment groups. The time to return to baseline QOL and PC scores was similar for SLND and CLND alone. Differences in time to return to baseline QOL and PC were sustained when stratified by recurrence status but did not differ significantly for different lymph node regions. There was a delay in return to baseline QOL and PC condition scores that was sustained beyond the cessation of IFN therapy.

Conclusions

CLND is well-tolerated with a similar effect on self-reported QOL outcomes in both the short- and long-term compared with SLNB alone. IFN therapy is associated with worse QOL outcomes compared with SLNB and CLND, an effect that may be sustained following cessation of adjuvant IFN.

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Tumour-induced osteomalacia

Tumour-induced osteomalacia: a literature review and a case report:

Abstract

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterised by severe hypophosphataemia and osteomalacia, with renal phosphate wasting that occurs in association with tumour. The epidemiology likewise aetiology is not known. The clinical presentation of TIO includes bone fractures, bone and muscular pains, and sometimes height and weight loss. TIO may be associated with mesenchymal tumours which may be benign or malignant in rare cases. Mesenchymal tumour itself may be related to fibroblast growth factor 23 (FGF23), which is responsible for hypophosphataemia and phosphaturia occurring in this paraneoplastic syndrome. Hypophosphataemia, phosphaturia and elevated alkaline phosphatase are the main laboratory readings that may lead to more precise investigations and better diagnosis. Finding the tumour can be a major diagnostic challenge and may involve total body magnetic resonance imaging, computed tomography and scintigraphy using radiolabelled somatostatin analogue. The treatment of choice for TIO is resection of a tumour with a wide margin to insure complete tumour removal, as recurrences of these tumours have been reported. We provide here an overview on the current available TIO case reports and review the best practices that may lead to earlier recognition of TIO and the subsequent treatment thereof, even though biochemical background and the long-term prognosis of the disease are not well understood. This review also includes a 4-year-long history of a patient that featured muscular pains, weakness and multiple stress fractures localised in the hips and vertebra with subsequent recovery after tumour resection. Because the occurrence of such a condition is rare, it may take years to correctly diagnose the disease, as is reported in this case report.

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Predicting prognosis in papillary thyroid cancer

Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer:

Abstract

Papillary thyroid cancer (PTC) often presents as multifocal tumor;, however, whether multifocality is associated with poor prognosis remains controversial. The aims of this retrospective study were to identify the characteristics of PTC with multifocal tumors and evaluate the association between the location and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as three groups: N1 (solitary tumor), N2 (2 or more foci within unilateral lobe of thyroid), and N3 (bilateral tumors, at least one tumor focus for each lobe of thyroid). We analyzed the differences of clinicopathologic features and clinical outcomes among the three groups. Cox regression model was used to assess the relation between the different locations of multifocal tumors and prognosis. Although the differences of clinicopathologic features such as the size of tumor, extrathyroidal extension, and cervical lymph node metastasis were not significant among the three groups, the bilateral-multifocality was proved to be an independent risk factor for neck recurrence (hazard ratio (HR) = 4.052, 95 % confidence interval (CI) 2.070–7.933), distant metastasis (HR = 3.860, 95 % CI 1.507–9.884), and cancer death (HR = 7.252, 95 % 2.189–24.025). In addition, extrathyroidal extension (HR = 2.291, 95 % CI 1.185–4.427) and older age >45 years (HR = 6.721, 95 % CI 2.300–19.637) were also significant predictors for neck recurrence and cancer death, respectively. Therefore, bilateral-multifocality as an indicator for more extensive tumor location could be used to assess the risk of recurrence and mortality in PTC. Given the poor prognosis associated with bilateral-multifocality and other risk factors, aggressive therapy and intensive follow-up were recommended for PTC patients with them.

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Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer

Bilaterality weighs more than unilateral multifocality in predicting prognosis in papillary thyroid cancer:

Abstract

Papillary thyroid cancer (PTC) often presents as multifocal tumor;, however, whether multifocality is associated with poor prognosis remains controversial. The aims of this retrospective study were to identify the characteristics of PTC with multifocal tumors and evaluate the association between the location and prognosis. We reviewed the medical records of 496 patients who underwent total thyroidectomy for PTC. Patients were classified as three groups: N1 (solitary tumor), N2 (2 or more foci within unilateral lobe of thyroid), and N3 (bilateral tumors, at least one tumor focus for each lobe of thyroid). We analyzed the differences of clinicopathologic features and clinical outcomes among the three groups. Cox regression model was used to assess the relation between the different locations of multifocal tumors and prognosis. Although the differences of clinicopathologic features such as the size of tumor, extrathyroidal extension, and cervical lymph node metastasis were not significant among the three groups, the bilateral-multifocality was proved to be an independent risk factor for neck recurrence (hazard ratio (HR) = 4.052, 95 % confidence interval (CI) 2.070–7.933), distant metastasis (HR = 3.860, 95 % CI 1.507–9.884), and cancer death (HR = 7.252, 95 % 2.189–24.025). In addition, extrathyroidal extension (HR = 2.291, 95 % CI 1.185–4.427) and older age >45 years (HR = 6.721, 95 % CI 2.300–19.637) were also significant predictors for neck recurrence and cancer death, respectively. Therefore, bilateral-multifocality as an indicator for more extensive tumor location could be used to assess the risk of recurrence and mortality in PTC. Given the poor prognosis associated with bilateral-multifocality and other risk factors, aggressive therapy and intensive follow-up were recommended for PTC patients with them.

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Fully automatic segmentation of left atrium and pulmonary veins in late gadolinium-enhanced MRI: Towards objective atrial scar assessment

Purpose

To realize objective atrial scar assessment, this study aimed to develop a fully automatic method to segment the left atrium (LA) and pulmonary veins (PV) from late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI). The extent and distribution of atrial scar, visualized by LGE-MRI, provides important information for clinical treatment of atrial fibrillation (AF) patients.

Materials and Methods

Forty-six AF patients (age 62 ± 8, 14 female) who underwent cardiac MRI prior to RF ablation were included. A contrast-enhanced MR angiography (MRA) sequence was acquired for anatomy assessment followed by an LGE sequence for LA scar assessment. A fully automatic segmentation method was proposed consisting of two stages: 1) global segmentation by multiatlas registration; and 2) local refinement by 3D level-set. These automatic segmentation results were compared with manual segmentation.

Results

The LA and PVs were automatically segmented in all subjects. Compared with manual segmentation, the method yielded a surface-to-surface distance of 1.49 ± 0.65 mm in the LA region when using both MRA and LGE, and 1.80 ± 0.93 mm when using LGE alone (P < 0.05). In the PV regions, the distance was 2.13 ± 0.67 mm and 2.46 ± 1.81 mm (P < 0.05), respectively. The difference between automatic and manual segmentation was comparable to the interobserver difference (P = 0.8 in LA region and P = 0.7 in PV region).

Conclusion

We developed a fully automatic method for LA and PV segmentation from LGE-MRI, with comparable performance to a human observer. Inclusion of an MRA sequence further improves the segmentation accuracy. The method leads to automatic generation of a patient-specific model, and potentially enables objective atrial scar assessment for AF patients. J. Magn. Reson. Imaging 2016.

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Geographic variation in human papillomavirus-related oropharyngeal cancer: Data from four multinational randomized trials.

Geographic variation in human papillomavirus-related oropharyngeal cancer: Data from four multinational randomized trials.

Head Neck. 2016 Jan 8;

Authors: Mehanna H, Franklin N, Compton N, Robinson M, Powell N, Biswas-Baldwin N, Paleri V, Hartley A, Fresco L, Al-Booz H, Junor E, El-Hariry I, Roberts S, Harrington K, Ang KK, Dunn J, Woodman C

Abstract
BACKGROUND: There are variations in the proportions of head and neck cancers caused by the human papillomavirus (HPV) between countries and regions. It is unclear if these are true variations or due to different study designs and assays.
METHODS: We tested formalin-fixed paraffin-embedded diagnostic biopsies for p16 immunohistochemistry and HPV-DNA (by polymerase chain reaction [PCR] and in situ hybridization [ISH]) using validated protocols on samples from 801 patients with head and neck cancer recruited prospectively between 2006 and 2011 in 4 randomized controlled trials (RCTs).
RESULTS: Twenty-one percent of patients (170 of 801) showed both HPV-DNA and p16-positivity, detected almost exclusively in oropharyngeal cancer (55%; 15 of 302); and only 1% of the patients (5 of 499) with nonoropharyngeal cancer were HPV positive. HPV-positive oropharyngeal cancer differed between Western and Eastern Europe (37%, 155 of 422 vs 6%, 8 of 144; p < .0001) and between Western Europe and Asia (37% vs 2%; 4 of 217; p < .0001). Other independent determinants of HPV positivity were tumor site and smoking.
CONCLUSION: This is the first study to establish geographic variability as an independent risk factor in HPV-positive oropharyngeal cancer prevalence, with higher prevalence in Western Europe. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 26749143 [PubMed - as supplied by publisher]

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Geographic variation in human papillomavirus-related oropharyngeal cancer: Data from four multinational randomized trials.

Geographic variation in human papillomavirus-related oropharyngeal cancer: Data from four multinational randomized trials.

Head Neck. 2016 Jan 8;

Authors: Mehanna H, Franklin N, Compton N, Robinson M, Powell N, Biswas-Baldwin N, Paleri V, Hartley A, Fresco L, Al-Booz H, Junor E, El-Hariry I, Roberts S, Harrington K, Ang KK, Dunn J, Woodman C

Abstract
BACKGROUND: There are variations in the proportions of head and neck cancers caused by the human papillomavirus (HPV) between countries and regions. It is unclear if these are true variations or due to different study designs and assays.
METHODS: We tested formalin-fixed paraffin-embedded diagnostic biopsies for p16 immunohistochemistry and HPV-DNA (by polymerase chain reaction [PCR] and in situ hybridization [ISH]) using validated protocols on samples from 801 patients with head and neck cancer recruited prospectively between 2006 and 2011 in 4 randomized controlled trials (RCTs).
RESULTS: Twenty-one percent of patients (170 of 801) showed both HPV-DNA and p16-positivity, detected almost exclusively in oropharyngeal cancer (55%; 15 of 302); and only 1% of the patients (5 of 499) with nonoropharyngeal cancer were HPV positive. HPV-positive oropharyngeal cancer differed between Western and Eastern Europe (37%, 155 of 422 vs 6%, 8 of 144; p < .0001) and between Western Europe and Asia (37% vs 2%; 4 of 217; p < .0001). Other independent determinants of HPV positivity were tumor site and smoking.
CONCLUSION: This is the first study to establish geographic variability as an independent risk factor in HPV-positive oropharyngeal cancer prevalence, with higher prevalence in Western Europe. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck, 2016.

PMID: 26749143 [PubMed - as supplied by publisher]

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Management of CSF leakage after microsurgery for vestibular schwannoma via the middle cranial fossa approach.

Management of CSF leakage after microsurgery for vestibular schwannoma via the middle cranial fossa approach.

Eur Arch Otorhinolaryngol. 2016 Jan 9;

Authors: Scheich M, Ginzkey C, Ehrmann-Müller D, Shehata-Dieler W, Hagen R

Abstract
Microsurgery is one of the primary current standard options for the treatment of vestibular schwannoma (VS). Especially the middle cranial fossa (MCF) approach is a safe and efficacious technique for the preservation of hearing and facial nerve function in small VS. Postoperative complications are rare, although a leakage of cerebrospinal fluid (CSF) is common. The aim of this study was to analyze postoperative CSF leaks and to describe strategies for postoperative treatment. Between October 2005 and May 2012, 148 patients suffering from VS and selected for microsurgery via the MCF approach were treated in our department. Postoperative CSF leakage occurred in 19 patients. We found a leakage via the Eustachian tube into the nasopharynx in 18 patients and one case of incisional leakage. In 13 cases leaking stopped within 5 days by conservative management including bed rest and intravenous (i.v) antibiotics. Five patients needed lumbar drainage (LD) and only two patients had to undergo revision surgery to seal and pack the mastoid. Analyzed risk factors were age, gender, tumor size and pneumatization of the mastoid. Only the latter showed a significant influence on CSF leakage. We could demonstrate that a stepwise strategy is needed for successful treatment of CSF leaks.

PMID: 26749560 [PubMed - as supplied by publisher]

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Patterns and surgical significance of facial nerve branching within the parotid gland in 43 cases

Abstract

Purpose

Different patterns of facial nerve branching within the parotid gland were detected, and these anatomical variations may affect the treatment approaches and outcomes of surgery. The aim of this study was to identify the patterns of facial nerve branching with the parotid gland and their importance in surgical procedures.

Materials and methods

A total of 43 patients undergoing surgical treatments of parotid lesions were included in this study. Each patient's demographic data and type of operation were recorded. In addition, the courses of the facial nerve within the gland were classified into six types according to their branching patterns and communication.

Results

In all of the patients, the facial nerve consisted of one trunk separated into two divisions. Branching type III was the most common variety found (30.2 %) followed by type II (23.2 %), while type V represented the least frequent pattern (4.6 %).

Conclusion

It is essential for surgeons to become familiar with the different types of nerve morphologies in order to avoid morbidity and preserve the facial nerve during surgery. Variations and anastomosis can explain the different consequences of facial nerve injury that may occur after parotid surgery.

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Patterns and surgical significance of facial nerve branching within the parotid gland in 43 cases

Abstract

Purpose

Different patterns of facial nerve branching within the parotid gland were detected, and these anatomical variations may affect the treatment approaches and outcomes of surgery. The aim of this study was to identify the patterns of facial nerve branching with the parotid gland and their importance in surgical procedures.

Materials and methods

A total of 43 patients undergoing surgical treatments of parotid lesions were included in this study. Each patient's demographic data and type of operation were recorded. In addition, the courses of the facial nerve within the gland were classified into six types according to their branching patterns and communication.

Results

In all of the patients, the facial nerve consisted of one trunk separated into two divisions. Branching type III was the most common variety found (30.2 %) followed by type II (23.2 %), while type V represented the least frequent pattern (4.6 %).

Conclusion

It is essential for surgeons to become familiar with the different types of nerve morphologies in order to avoid morbidity and preserve the facial nerve during surgery. Variations and anastomosis can explain the different consequences of facial nerve injury that may occur after parotid surgery.

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Simulation-based otolaryngology – head and neck surgery boot camp: ‘how I do it’

Research Articles
C J Chin, C A Chin, K Roth, B W Rotenberg, K Fung
The Journal of Laryngology Otology, FirstView Article(s), 7 pages

Abstract

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Self-stability of C60 nanocapsules with radio-iodide content and its interaction with calcium atoms.

Self-stability of C60 nanocapsules with radio-iodide content and its interaction with calcium atoms.

J Mol Model. 2016 Jan;22(1):28

Authors: Valderrama A, Reynoso R, Gómez RW, Marquina V

Abstract
This paper inquires the C60 capabilities to contain radio-iodide ((131)I2) molecules. The encapsulation conditions are investigated applying first principles method to simulate with geometric optimizations and molecular dynamics at 310 K and atmospheric pressure. We find that the n(131)I2@C60 system, where n = 1, 2, 3…, is stable if the content does not exceed three molecules of radio-iodide. The application of density functional theory allows us to determine that, the nanocapsules content limit is related with the amount of charge that is transferred from the iodine (131)I2 molecules to the carbon atoms in the fullerene surface. The Mulliken population analysis reveals that the excess of charge increases the repulsive forces between atoms and the bond length average in the C60 structure. The weakened bonds easily break and will critically damage the encapsulation properties. Additionally, we test the interaction nanocapsules with different amounts of radioactive iodine diatomic molecules content with calcium atoms, and find that only the fullerene containing one radioactive iodine diatomic molecule was able to interact with up to nine atoms of calcium without disrupting or cracking. Other fullerenes with two and three radio iodine diatomic molecules cannot resist the interaction with a single calcium atom without cracking or being broken. Graphical Abstract Instability of 3(131)I2@C60 Ca.

PMID: 26748925 [PubMed - as supplied by publisher]

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Patterns and surgical significance of facial nerve branching within the parotid gland in 43 cases

Abstract

Purpose

Different patterns of facial nerve branching within the parotid gland were detected, and these anatomical variations may affect the treatment approaches and outcomes of surgery. The aim of this study was to identify the patterns of facial nerve branching with the parotid gland and their importance in surgical procedures.

Materials and methods

A total of 43 patients undergoing surgical treatments of parotid lesions were included in this study. Each patient's demographic data and type of operation were recorded. In addition, the courses of the facial nerve within the gland were classified into six types according to their branching patterns and communication.

Results

In all of the patients, the facial nerve consisted of one trunk separated into two divisions. Branching type III was the most common variety found (30.2 %) followed by type II (23.2 %), while type V represented the least frequent pattern (4.6 %).

Conclusion

It is essential for surgeons to become familiar with the different types of nerve morphologies in order to avoid morbidity and preserve the facial nerve during surgery. Variations and anastomosis can explain the different consequences of facial nerve injury that may occur after parotid surgery.

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