Head and Neck Diseases by Alexandros G.Sfakianakis: 11/08/16

Τρίτη 8 Νοεμβρίου 2016

Rhabdomyolysis in a Hospitalized 16-Year-Old Boy: A Rarely Reported Underlying Cause

Rhabdomyolysis can occur because of multiple causes and account for 7% of all cases of acute kidney injury annually in the United States. Identification of specific cause can be difficult in many cases where multiple factors could potentially cause rhabdomyolysis. We present a case of 16-year-old male who had seizures and was given levetiracetam that resulted in rhabdomyolysis. This side effect has been rarely reported previously and like in our case diagnosis may be delayed.

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Persistent Tachypnea and Alveolar Hemorrhage in an Infant: An Unexpected Etiology

Persistent tachypnea and failure to thrive during infancy have a broad differential diagnosis which includes pulmonary and cardiovascular disorders. Diffuse alveolar hemorrhage (DAH) is a rare entity in children. DAH requires an extensive work-up as certain conditions may need chronic therapy. Cardiovascular disorders are included in the etiology of DAH. We present a case of an 8-month-old female with a moderate, restrictive patent ductus arteriosus (PDA) admitted to the hospital with respiratory distress and failure to thrive. An extensive work-up into tachypnea including multiple echocardiograms did not find an etiology. Open lung biopsy was performed and consistent with pulmonary hypertension. After closure of the PDA, patient's tachypnea improved, and she was discharged home with periodic follow-up showing a growing, thriving child. When an infant presents with tachypnea, a respiratory viral illness is often a common cause. The diagnosis of persistent tachypnea requires further investigation. Echocardiography, although readily available, may not always be sensitive in detecting clinically significant pulmonary hypertension. A clinician must have a heightened index of suspicion to proceed in evaluating for causes of tachypnea with a nonrespiratory etiology.

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Is There a Role for Opportunistic Infection Prophylaxis in Pemphigus? An Expert Survey

Abstract

Background

Opportunistic infections (OIs) are a dreaded adverse effect of immunosuppressive therapy, leading to the use of opportunistic infection prophylaxis (OIP) in many immunosuppressed conditions. However, guidelines for OIP in pemphigus are lacking.

Objective

Our objective was to evaluate the approach of leading pemphigus experts towards OIP.

Methods

We conducted an online survey of OIP trends.

Results

The survey was completed by 33 experts. Prior to initiation of immunosuppressive therapy, 75% routinely screened for hepatitis viruses, and at least half screened for HIV or tuberculosis. Most experts (76%) prescribed OIP but to <10% of their patients, and the most frequent drugs of choice were sulfamethoxazole/trimethoprim and acyclovir. Most experts agreed that treatment with three or more immunosuppressive agents or a previous history of OIs would lead to the use of OIP that was then discontinued with cessation of immunosuppression. The arguments against OIP were the lack of evidence for its necessity and concern about side effects or emergence of resistant pathogens. The surveyed experts treated patients with severe disease in a tertiary care setting, which may have led to an overestimation of the use of OIP. Infectious disease specialists were not included.

Conclusion

Substantial disparities exist in approaches to OIP for patients with pemphigus, including the decision to treat, type of treatment, and risk stratification among pemphigus experts.

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Real-time Simultaneous DKG and 2D DKG Using High-speed Digital Camera

For the evaluation of voice disorders, direct observation of vocal cord vibration is important. Among the various methods, laryngeal videostroboscopy (LVS) is widely used, but it was not a true image because it collects images from different cycles. In contrast, high-speed videoendoscopy and videokymography have much higher frame rates and can assess functional and mobility disorders.

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The Effectiveness of Low-Level Light Therapy in Attenuating Vocal Fatigue

Low-level light therapy (LLLT) is effective in reducing inflammation, promoting wound healing, and preventing tissue damage, but has not yet been studied in the treatment of voice disorders. The objective of this study was to investigate the possible effectiveness of LLLT in attenuating symptoms of vocal fatigue created by a vocal loading task as measured by acoustic, aerodynamic, and self-reported vocal effort.

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Effect of Levodopa + Carbidopa on the Laryngeal Electromyographic Pattern in Parkinson Disease

Vocal impairment is one of the main debilitating symptoms of Parkinson disease (PD). The effect of levodopa on vocal function remains unclear.

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Acoustic and Auditory Perception Effects of the Voice Therapy Technique Finger Kazoo in Adult Women

This study aimed to verify and to correlate acoustic and auditory-perceptual measures of glottic source after the performance of finger kazoo (FK) technique.

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Reply

Publication date: November–December 2016
Source:The Journal of Allergy and Clinical Immunology: In Practice, Volume 4, Issue 6
Author(s): Paul J. Turner, Audrey DunnGalvin, Jonathan O'B Hourihane

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Evaluation of known and novel inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a fluorescence imaging plate reader assay

Publication date: Available online 7 November 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Iman Azimi, Jack U. Flanagan, Ralph J. Stevenson, Marco Inserra, Irina Vetter, Gregory R. Monteith, William A. Denny
The Orai1 Ca²⁺ permeable ion channel is an important component of store operated Ca²⁺ entry (SOCE) in cells. It's over-expression in basal molecular subtype breast cancers has been linked with poor prognosis, making it a potential target for drug development. We pharmacologically characterised a number of reported inhibitors of SOCE in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader (FLIPR) assay, and show that the rank order of their potencies in this assay is the same as those reported in a wide range of published assays. The assay was also used in a screening project seeking novel inhibitors. Following a broad literature survey of classes of calcium channel inhibitors we used simplified ligand structures to query the ZINC on-line database, and following two iterations of refinement selected a novel Orai1-selective dichlorophenyltriazole hit compound. Analogues of this were synthesized and evaluated in the FLIPR assay to develop structure-activity relationships (SAR) for the three domains of the hit; triazole (head), dichlorophenyl (body) and substituted phenyl (tail). For this series, the results suggested the need for a lipophilic tail domain and an out-of-plane twist between the body and tail domains.

Graphical abstract

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Discovery of 4-chloro-2-(2,4-dichloro-6-methylphenoxy)-1-methyl-7-(pentan-3-yl)-1H-benzimidazole, a novel CRF1 receptor antagonist

Publication date: Available online 8 November 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Michiyo Mochizuki, Takuto Kojima, Katsumi Kobayashi, Etsuo Kotani, Yuji Ishichi, Naoyuki Kanzaki, Hideyuki Nakagawa, Teruaki Okuda, Yohei Kosugi, Takahiko Yano, Yuu Sako, Maiko Tanaka, Kazuyoshi Aso
Compound 1 exhibits potent binding inhibition activity against a corticotropin-releasing factor 1 (CRF1) receptor (IC50 = 9.5 nM) and in vitro antagonistic activity (IC50 = 88 nM) but is rapidly metabolized by human hepatic microsomes (182 μL/min/mg). Here we identified metabolically stable compounds with potent CRF binding inhibitory activity. Structure–activity relationship (SAR) studies considering in vitro metabolic stability revealed that 4-chloro-2-(2,4-dichloro-6-methylphenoxy)-1-methyl-7-(pentan-3-yl)-1H-benzimidazole 24d was more stable in human microsomes (87 μL/min/mg) than compound 1. Compound 24d demonstrated potent CRF binding inhibitory activity (IC50 = 4.1 nM), in vitro antagonistic activity (IC50 = 44 nM), and slow dissociation from the CRF1 receptor. Orally administered compound 24d (6–24 μmol/kg) showed ex vivo CRF1 receptor binding in the rat pituitary, olfactory bulb, and frontal cortex and suppressed stress-induced adrenocorticotropic hormone (ACTH) secretion. In this report, we discuss SAR studies on the metabolic stability as well as CRF binding inhibitory activity of the benzimidazole series as CRF1 receptor antagonists and the pharmacological profiles of compound 24d.

Graphical abstract

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Reply

Comparison of allergens collected from furnace filters and vacuum floor dust

Publication date: Available online 7 November 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Ryan Allenbrand, Charles S. Barnes, Mubeen Mohammed, Luke Gard, Freddy Pacheco, Kevin Kennedy, Anita DiDonna, Jay Portnoy, Chitra Dinakar

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Adrenal insufficiency associated with long-term use of inhaled steroid in asthma

Publication date: Available online 7 November 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Inseon S. Choi, Da-Woon Sim, Seung-Hoon Kim, Jin-Woo Wui
BackgroundWe previously reported that as many as one third of hospitalized patients with asthma treated with a low to medium daily dose of inhaled steroids (ICSs) for an average of 4.5 years showed adrenal insufficiency (AI).ObjectiveTo re-examine this issue in consecutive outpatients with asthma because of possible subject selection bias.MethodsOne hundred twenty-one consecutive adult patients with asthma under ICS treatment for at least 6 months underwent a rapid adrenocorticotrophic hormone stimulation test. AI was defined as a morning serum cortisol level no higher than 3 μg/dL or lower than 18 μg/dL before and after administration of 250 μg of adrenocorticotrophic hormone.ResultsThe mean durations of ICS use in the short-term (less than the median) and long-term (at least the median) users were 3.8 and 11.5 years, respectively. The proportion of subjects affected by AI tended to increase with the increasing cumulative dose of ICS (short-term users at a low to medium daily dose: mean cumulative dose 502 mg [15 of 34, 44.1%]; short-term users at a high dose of 941 mg [16 of 26, 61.5%]; long-term users at a low to medium dose of 1,077 mg [25 of 41, 61.0%]; long-term users at a high dose of 2,805 mg [13 of 20, 65.0%]), although not significantly. In short-term users, daily and cumulative ICS doses were significantly related to serum cortisol levels 60 minutes after taking adrenocorticotrophic hormone (r = −0.300 and −0.287, respectively; P < .05).ConclusionA large number of patients with asthma might have AI even with low- to medium-dose ICS treatment when ICSs are administered over a long period. Thus, it is essential that patients with asthma under ICS treatment be checked for AI much more frequently.

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Meta-analysis of the association between asthma and serum levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol

Publication date: Available online 7 November 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Jiayu Peng, Ying Huang
BackgroundThe reported associations of blood lipid profiles with asthma are ambiguous.ObjectiveTo explore the association between asthma and the serum levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C).MethodsA systematic search was performed in the PubMed, MEDLINE, Cochrane Library, and Chinese Biomedical Literature databases.Study SelectionTen studies were identified. We divided these studies into 2 subgroups according to age: children (<18 years old) and adults (≥18 years old).ResultsIn children, the asthma group had lower HDL-C levels (weighted mean difference, −3.44; 95% confidence interval [CI], −5.83 to −1.04; P = .005) compared with the nonasthma group, whereas the serum levels of LDL-C in these 2 groups were not statistically different. In contrary, in adults, the asthma group had higher LDL-C levels (weighted mean difference, 8.95; 95% confidence interval, 3.55–14.35; P = .001) compared with the nonasthma group, whereas the HDL-C levels were not statistically different.ConclusionThere is a significant association between asthma and the serum levels of HDL-C and LDL-C. Moreover, this association differs in children and adults.

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Primary Cutaneous Adenoid Cystic Carcinoma with MYB aberrations, report of three cases and comprehensive review of the literature

Abstract

Adenoid cystic carcinoma (ACC) is a relatively rare slow growing and often-aggressive epithelial-myoepithelial neoplasm that arises in multiple organs including the skin. The t(6;9) (q22-23;p23-24) translocation, resulting in a MYB-NFIB gene fusion has been found in ACCs from the salivary glands and other organs. Recently, MYB aberrations occurring in a subset (40%) of primary cutaneous ACC (PCACC) examples was described. Herein, we report 3 additional cases of PCACC harboring MYB aberrations. The tumors presented in 3 males aged 43, 81 and 55 years old and affected the extremities in the first 2 patients and the scalp in the third one. None of the patients had history of prior or concurrent ACC elsewhere. Lesions exhibited the classic ACC morphology of nests of basaloid cells arranged in cribriform and adenoid patterns. Sentinel lymph node biopsy was performed in two cases with one case showing lymph node positivity. Fluorescence in situ hybridization with break-apart probes for MYB and NFIB loci revealed that 2 cases showed MYB rearrangements while one case showed loss of one MYB signal. None of the cases showed NFIB rearrangements. We contribute with 3 additional cases of PCACC exhibiting MYB aberrations, the apparent driving genetic abnormality in these tumors.

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Diffusion restriction in the corticospinal tracts and the corpus callosum in neonates after cerebral insult

Publication date: Available online 7 November 2016
Source:Brain and Development
Author(s): Monika Bekiesinska-Figatowska, Agnieszka Duczkowska, Sylwia Szkudlinska-Pawlak, Marek Duczkowski, Jaroslaw Madzik, Astra Cabaj, Katarzyna Krupa, Pawel Peczkowski, Hanna Bragoszewska
BackgroundIn neonatal brains diffusion restriction, which is not limited to the region of insult, but is also found in distant locations from it seems to be a frequent finding, called pre-Wallerian degeneration.ObjectivesThe purpose of this study was to describe these findings and to estimate the frequency of their occurrence with an attempt to determine their clinical significance.Methods125 brain MRI examinations of neonates with confirmed brain damage performed or consulted in our Institute were retrospectively reviewed, focusing on the presence of restricted diffusion in corticospinal tracts (CST) and corpus callosum (CC). Apparent diffusion coefficients (ADC) were measured in callosal splenium and compared to normal neonatal brains.ResultsRestricted diffusion was found in 21 newborns (16.8%): in 4 in CST (3.2%), in 5 in CC (4.0%), in 12 in both (9.6%). Mean ADC value in CC was 0.638, standard deviation (SD): 0.211μm²/s and in the control group 0.995, SD: 0.162μm²/s (p=0,001).ConclusionsNeonatal brain MRI should be searched for DWI abnormalities which are not rare and require careful studying of ADC maps. Diffusion restriction in the corpus callosum and/or corticospinal tracts below the region of insult should not be mistaken for acute ischemia as it most likely reflects early phase of secondary neuronal degeneration called pre-Wallerian degeneration. This finding helps in prognostication and guides the management of the affected neonates.

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Readability Of Online Resources For Rhinoplasty

According to the American Society of Plastic Surgeons (ASPS), in 2009 more than 250,000 rhinoplasties were performed in the United States, making it one of the more popular aesthetic procedures. For patients, the decision to have a rhinoplasty is not made lightly and most patients thoroughly research the procedure as well as their surgeon in advance. There is no substitute for a consultation with a medical professional yet the decision-making process is often influenced by information found online.

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Collective cell migration of thyroid carcinoma cells: a beneficial ability to override unfavourable substrates

Abstract

Purpose

Tumor cell invasion and metastasis are life threatening events. Invasive tumor cells tend to migrate as collective sheets. In the present in vitro study we aimed to (i) assess whether collective tumor cells gain benefits in their migratory potential compared to single cells and (ii) to identify its putative underlying molecular mechanisms.

Methods

The migratory potential of single and collective carcinoma cells was assessed using video time lapse microscopy and cell migration assays in the absence and presence of seven potential gap junction inhibitors or the Rac1 inhibitor Z62954982. The perturbation of gap junctions was assessed using a dye diffusion assay. In addition, LDH-based cytotoxicity and RT-PCR-based expression analyses were performed.

Results

Whereas single breast, cervix and thyroid carcinoma cells were virtually immobile on unfavourable plastic surfaces, we found that they gained pronounced migratory capacities as collectives under comparable conditions. Thyroid carcinoma cells, that were studied in more detail, were found to express specific subsets of connexins and to form active gap junctions as revealed by dye diffusion analysis. Although all potential gap junction blockers suppressed intercellular dye diffusion in at least one of the cell lines tested, only two of them were found to inhibit collective cell migration and none of them to inhibit single cell migration. In the presence of the Rac1 inhibitor Z62954982 collective migration, but not single cell migration, was found to be reduced up to 20 %.

Conclusions

Our data indicate that collective migration enables tumor cells to cross otherwise unfavourable substrate areas. This capacity seems to be independent of intercellular communication via gap junctions, whereas Rac1-dependent intracellular signalling seems to be essential.

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Targeting CXCR4 and FAK reverses doxorubicin resistance and suppresses invasion in non-small cell lung carcinoma

Abstract

Background

Current high lung cancer mortality rates are mainly due to the occurrence of metastases and therapeutic resistance. Therefore, simultaneous targeting of these processes may be a valid approach for the treatment of this type of cancer. Here, we assessed relationships between CXC chemokine receptor type 4 (CXCR4) and focal adhesion kinase (FAK) gene expression levels and expression levels of the drug resistance-related genes ABCB1 and ABCC1, and tested the potential of CXCR4 and FAK inhibitors to reverse doxorubicin (DOX) resistance and to decrease the invasive capacity of non-small cell lung carcinoma (NSCLC) cells.

Methods

qRT-PCR was used for gene expression analyses in primary lung tissue samples obtained from 30 NSCLC patients and the human NSCLC-derived cell lines NCI-H460, NCI-H460/R and COR-L23. MTT, flow cytometry, cell death and β-galactosidase activity assays were used to assess the in vitro impact of CXCR4 and FAK inhibitors on DOX sensitivity. In addition, invasion and gelatin degradation assays were used to assess the in vitro impact of the respective inhibitors on metastasis-related processes in combination with DOX treatment.

Results

We found that ABCB1 over-expression was significantly associated with CXCR4 and FAK over-expression, whereas ABCC1 over-expression was associated with increased FAK expression. We also found that CXCR4 and FAK inhibitors strongly synergized with DOX in reducing cell viability, arresting the cell cycle in the S or G₂/M phases and inducing senescence. Additionally, we found that DOX enhanced the anti-invasive potential of CXCR4 and FAK inhibitors by reducing gelatin degradation and invasion.

Conclusions

From our data we conclude that targeting of CXCR4 and FAK may overcome ABCB1 and ABCC1-dependent DOX resistance in NSCLC cells and that simultaneous treatment of these cells with DOX may potentiate the anti-invasive effects of CXCR4 and FAK inhibitors.

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Erratum to: An update on peripheral ossifying fibroma: case report and literature review

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Mast Cell Clonal Disorders: Classification, Diagnosis and Management

Abstract

Mast cell clonal disorders are characterized by the clonal proliferation of pathological mast cells as a result of somatic mutations in the KIT gene, most commonly the D816V mutation. Accumulation and degranulation of these cells causes a wide variety of symptoms. Mast cell clonal disorders can be divided into mastocytosis and monoclonal mast cell activation syndrome, depending of the level of clonality. The severity of mastocytosis varies from an indolent variant with a good prognosis, to an aggressive condition with short life expectancy. Diagnosis is based on demonstration of clonality and accumulation in the skin and in extracutaneous tissues. Treatment is highly individualized, and is based on the severity of the condition. Treatment of patients with indolent systemic mastocytosis is aimed at reducing symptoms, using histamine H1 and H2 receptor antagonists as a starting point. In addition, associated conditions such as osteoporosis must be treated. Treatment of advanced systemic mastocytosis is aimed at reducing mast cell load through cytoreductive therapy. The choice of such therapy depends on the KIT mutational status. Though currently there is no curative treatment available, promising new therapies such as midostaurin are emerging that have demonstrated success in reducing symptoms and improving quality of life.

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Severe Hiatal Hernia as a Cause of Failure to Thrive Discovered by Transthoracic Echocardiogram

A newborn infant with failure to thrive presented for murmur evaluation on day of life three due to a harsh 3/6 murmur. During the evaluation, a retrocardiac fluid filled mass was seen by transthoracic echocardiogram. The infant was also found to have a ventricular septal defect and partial anomalous pulmonary venous return. Eventually, a large hiatal hernia was diagnosed on subsequent imaging. The infant ultimately underwent surgical repair of the hiatal hernia at a tertiary care facility. Hiatal hernias have been noted as incidental extracardiac findings in adults, but no previous literature has documented hiatal hernias as incidental findings in the pediatric population.

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Vitamin C enhances substantially formation of 5-hydroxymethyluracil in cellular DNA

Publication date: Available online 8 November 2016
Source:Free Radical Biology and Medicine
Author(s): Martyna Modrzejewska, Maciej Gawronski, Magdalena Skonieczna, Ewelina Zarakowska, Marta Starczak, Marek Foksinski, Joanna Rzeszowska-Wolny, Daniel Gackowski, Ryszard Olinski
The most plausible mechanism behind active demethylation of 5-methylcytosine involves TET proteins which participate in oxidation of 5-methylcytosine to 5-hydroxymethylcytosine; the latter is further oxidized to 5-formylcytosine and 5-carboxycytosine. 5-Hydroxymethyluracil can be also generated from thymine in a TET-catalyzed process. Ascorbate was previously demonstrated to enhance generation of 5-hydroxymethylcytosine in cultured cells. The aim of this study was to determine the levels of the abovementioned TET-mediated oxidation products of 5-methylcytosine and thymine after addition of ascorbate, using an isotope-dilution automated online two-dimensional ultra-performance liquid chromatography with electrospray ionization tandem mass spectrometry. Intracellular concentration of ascorbate was determined by means of ultra-performance liquid chromatography with UV detection. Irrespective of its concentration in culture medium (10 µM-100 µM) and inside the cell, ascorbate stimulated a moderate (2- to 3-fold) albeit persistent (up to 96-h) increase in the level of 5-hydroxymethylcytosine. However, exposure of cells to higher concentrations of ascorbate (100µM or 1mM) stimulated a substantial increase in 5-formylcytosine and 5-carboxycytosine levels. Moreover, for the first time we demonstrated a spectacular (up to 18.5-fold) increase in 5-hydroxymethyluracil content what, in turn, suggests that TET enzymes contributed to the presence of the modification in cellular DNA. These findings suggest that physiological concentrations of ascorbate in human serum (10–100µM) are sufficient to maintain a stable level of 5-hydroxymethylcytosine in cellular DNA. However, markedly higher concentrations of ascorbate (ca. 100µM in the cell milieu or ca. 1mM inside the cell) were needed to obtain a sustained increase in 5-formylcytosine, 5-carboxycytosine and 5-hydroxymethyluracil levels. Such feedback to elevated concentrations of ascorbate may reflect adaptation of the cell to environmental conditions.

Graphical abstract

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MTH1 as a nucleotide pool sanitizing enzyme: friend or foe?

Publication date: Available online 7 November 2016
Source:Free Radical Biology and Medicine
Author(s): Yusaku Nakabeppu, Eiko Ohta, Nona Abolhassani
8-Oxo-7,8-dihydroguanine (GO) can originate as 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP), an oxidized form of dGTP in the nucleotide pool, or by direct oxidation of guanine base in DNA. Accumulation of GO in cellular genomes can result in mutagenesis or programmed cell death, and is thus minimized by the actions of MutT homolog-1 (MTH1) with 8-oxo-dGTPase, OGG1 with GO DNA glycosylase and MutY homolog (MUTYH) with adenine DNA glycosylase. Studies on Mth1/Ogg1/Mutyh-triple knockout mice demonstrated that the defense systems efficiently minimize GO accumulation in cellular genomes, and thus maintain low incidences of spontaneous mutagenesis and tumorigenesis. Mth1/Ogg1-double knockout mice increased GO accumulation in the genome, but exhibited little susceptibility to spontaneous tumorigenesis, thus revealing that accumulation of GO in cellular genomes induces MUTYH-dependent cell death. Cancer cells are exposed to high oxidative stress levels and accumulate a high level of 8-oxo-dGTP in their nucleotide pools; cancer cells consequently express increased levels of MTH1 to eliminate 8-oxo-dGTP, indicating that increased expression of MTH1 in cancer cells may be detrimental for cancer patients. Mth1/Ogg1-double knockout mice are highly vulnerable to neurodegeneration under oxidative conditions, while transgenic expression of human MTH1 efficiently prevents neurodegeneration by avoiding GO accumulation in mitochondrial genomes of neurons and/or nuclear genomes of microglia, indicating that increased expression of MTH1 may be beneficial for neuronal tissues.

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Efficacy and safety of wet wrap therapy for patients with atopic dermatitis: a systematic review and meta-analysis

Abstract

Background

Wet wrap therapy (WWT) consists of topical steroids administered under a layer of wet cotton bandages or garments. Several trials with WWT have reported promising results in atopic dermatitis (AD). However, no systematic review and meta-analysis on its efficacy and safety has been published.

Objectives

To systematically review the literature on WWT in AD to assess its efficacy and safety.

Methods

We included randomized controlled trials among patients of all ages with a diagnosis of AD based on predefined criteria or performed by a dermatologist. Electronic searches were performed from 1970 to March 30, 2016, in the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and the WHO International Clinical Trials Registry. Selection of studies and data extraction was performed independently by two researchers, and discrepancies were resolved by consensus.

Results

6 trials comparing WWT against topical steroids in children or adults with AD were included. Sample sizes ranged from 19 to 51 patients. Results on clinical severity and quality of life were reported incompletely and proved heterogeneous across studies. A nonsignificant tendency to increased risk of mild skin infections was observed in those treated with WWT (pooled relative risk 6.35; 95% confidence interval 0.83 to 48.55). The overall grade of quality of evidence for the efficacy and safety outcomes was low.

Conclusions

The evidence that WWT is more effective than conventional treatment with topical steroids in AD is of low quality. Further clinical trials should establish the efficacy of WWT in AD.

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Efficacy and safety of wet wrap therapy for patients with atopic dermatitis: a systematic review and meta-analysis

Abstract

Background

Objectives

To systematically review the literature on WWT in AD to assess its efficacy and safety.

Methods

Results

Conclusions

The evidence that WWT is more effective than conventional treatment with topical steroids in AD is of low quality. Further clinical trials should establish the efficacy of WWT in AD.

http://ift.tt/2fckAwn

Rheumatoid vasculitis: early presentation of rheumatoid arthritis

Rheumatoid vasculitis is a rare and late complication of rheumatoid arthritis and may affect small-to-medium-sized vessels. Here, we report a case of a 49-year-old man who presented with amaurosis fugax in the left eye, symmetric polyarthritis, Raynaud's symptoms and paraesthesia in both lower extremities. The patient subsequently experienced right foot drop, nail fold infracts and gangrene of his right second toe. He was found to have a high titre of rheumatoid factor and treatment with rituximab and high dose of corticosteroids led to significant improvement of his symptoms. This is rare case describing the early onset of rheumatoid vasculitis in a patient with rheumatoid arthritis.

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Primary Mycobacterium tuberculosis infection over insulin injection site

Description

A 36-year-old man had been diagnosed with type 2 diabetes and put on twice daily premixed insulin for severe hyperglycaemia and osmotic symptoms about 3 months prior to his presentation to us. He was injecting himself with U-40 insulin syringe subcutaneously over anterior abdomen with proper technique and regular rotation of the injection sites. After about 2 months after starting insulin he had noticed multiple firm nodules appearing over the injection sites. The nodules were painless, became fluctuant over the course of time and used to burst spontaneously with discharge of pus. He had been put on several courses of oral antibiotics over the previous 2 months without any symptomatic relief. Some of the swellings required incision and drainage of the underlying pus. Gram stain and both aerobic and anaerobic culture of the drained pus were negative on multiple occasions.

A thorough systemic examination did not reveal any abnormality. Complete...

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Persistent spontaneous fungal peritonitis secondary to Candida albicans in a patient with alcoholic cirrhosis and review of the literature

Candida albicans is a common human pathogen. Occasionally, it can cause peritonitis in immunocompromised and postsurgical patients. We report a case of a male patient who presented with abdominal pain and distention. He had a history of end-stage liver disease secondary to alcoholism. His peritoneal fluid culture revealed C albicans, and (1–3)-β-d glucan (BDG) level was elevated. His hospital course was complicated by sepsis and renal failure. He was treated with antifungals for spontaneous fungal peritonitis. Fungal peritonitis should be suspected in patients with chronic liver disease particularly with elevated BDG levels.

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Neurosarcoidosis presenting as a large dural mass lesion

Description

A woman aged 52 years presented with episodic holocranial headaches with recurrent episodes of diminution of vision in the right eye and decreased sensation on the right side of face for the past 1 year. Clinical examination revealed optic atrophy in the right eye and sensory loss on the ophthalmic and maxillary division of the trigeminal nerve. MRI brain revealed extensive nodular enhancement on T1-weighted contrast images predominantly involving the dura around bilateral temporal lobes, right fronto-basal area and bilateral cavernous sinuses (figure 1). CT scan of the chest showed multiple lung nodules and mediastinal lymphadenopathy. Cerebrospinal fluid examination, cryptococcal antigen, vasculitic screen, HIV serology and serum ACE levels were all in normal range.

Figure 1

MRI brain, axial section, T1-weighted image showing contrast enhancement involving the dura around bilateral temporal lobes, right fronto-basal area and bilateral cavernous sinuses.

As MRI...

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Hibernoma: diagnostic and surgical considerations of a rare benign tumour

Hibernoma is a rare, benign tumour of brown fat origin. Less than 250 cases have been reported in the literature. We present a case of a 19-year-old man referred to surgical oncology for evaluation of a large soft tissue mass near the apex of his right scapula. Complete surgical excision was performed, sparing the overlying latissimus dorsi musculature. Surgical pathology revealed findings were consistent with hibernoma, grossly showing a well-encapsulated fluctuant mass measuring 21.4x14.4x5.3 cm, and histologically composed of brown fat adipocytes. The mainstay of treatment is surgical excision of the mass. Primary goals of the operation include complete removal of the mass to prevent recurrence and sparing of adjacent structures as it is a benign, non-invasive tumour. We present a case of a large chest wall hibernoma in a young adult, diagnosed on final pathology after complete surgical excision.

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Critical Review Upon the Role and Potential of Fluorescence and Near-Infrared Imaging and Absorption Spectroscopy in Cancer Related Cells, Serum, Saliva, Urine and Tissue Analysis

During the last years, non-invasive or minimally invasive diagnostic tools in cancer diagnostics have become more important. Many fluorescence spectroscopic methodologies have been established for nearly all different kinds of cancer. The reason therefore is its high sensitivity, low amount of sample required, short testing time, and the suitability for in situ testing. The potential influence factors for cancer diagnostics and the subsequent suitability of the method to different applications are well described. Near-Infrared spectroscopy (NIRS) is based on differences of endogenous chromophores between cancer and normal tissues using either oxyhaemoglobin or deoxy-haemoglobin, lipid or water bands, or a combination of two or more of these diagnostic markers. These marker bands are known to provide the fundamental for the diagnosis of several cancers and the spectroscopic setup can be applied for the analysis of cells, urine and tissue. For the preparation of this review the literature published during the last fifteen years has been taken into consideration. It will provide an overview on the importance of the fluorescence and NIRS tools in cancer analysis giving hints about how these techniques can play a crucial role in cancer diagnosis, treatment decisions and therapy. The two techniques, fluorescence and near-infrared spectroscopy (NIRS) are faced to each other and individual advantages and/or drawbacks are discussed. Finally, it will be taken into consideration; how the synergistic combination of different approaches can give additional information related to development and progression stages of cancer. 

http://ift.tt/2cjYrvG

Brain-metastatic Breast Cancer: Clinical Considerations and Pharmacological Approaches

Despite constant advances on breast cancer knowledge, the metastatic disease resulting from the spreading of this disease is still a challenge. This scenario is particularly critical in the more aggressive subtypes, as HER2-amplified and triple negative breast cancers, when often occurs the invasion of central nervous system (CNS) structures. In this situation, the survival of patients is drastically reduced, and the number of sequels and functional impairment is huge due to the small therapeutic arsenal available. In this context, it is necessary to understand the mechanisms involved in the process of metastasis of breast cancer to CNS, and how this process affects anatomically important structures for its functioning. This review aims to point out some mechanisms enrolled in the spread of breast cancer to CNS, discuss the clinical impact of such metastatisation and address the critical aspects related to the treatment of this condition.

http://ift.tt/2fz3Rli

Myeloproliferative Disease: An Unusual Cause of Raynaud’s Phenomenon and Digital Ischaemia

We describe a 59-year-old female who presented with ischaemic digits, preceded by a 6-month history of Raynaud's phenomenon affecting her fingers and toes. There were no clinical or laboratory features of primary vasculitis or connective tissue disease, Doppler imaging was normal, and bloods were unremarkable aside from a platelet count of 786 × 109/L (150–400) and white cells of 16 × 109/L (4–11). In view of the thrombocytosis a JAK2 mutation assay was requested which confirmed a JAK2 V617F mutation, suggesting essential thrombocytosis (ET) as the cause. She received treatment with hydroxycarbamide which normalised her platelet count and led to a complete resolution of her Raynaud's symptoms. Raynaud's phenomenon is a rare manifestation of ET. Myeloproliferative disorders such as ET should be considered in the differential diagnosis of Raynaud's phenomenon and vasculitis.

http://ift.tt/2fc65bQ

Axl is required for TGF-β2-induced dormancy of prostate cancer cells in the bone marrow.

Axl is required for TGF-β2-induced dormancy of prostate cancer cells in the bone marrow.

Sci Rep. 2016 Nov 07;6:36520

Authors: Yumoto K, Eber MR, Wang J, Cackowski FC, Decker AM, Lee E, Nobre AR, Aguirre-Ghiso JA, Jung Y, Taichman RS

Abstract
Disseminated prostate cancer (PCa) cells in the marrow survive for years without evidence of proliferation, while maintaining the capacity to develop into metastatic lesions. These dormant disseminated tumor cells (DTCs) may reside in close proximity to osteoblasts, while expressing high levels of Axl, one of the tyrosine kinase receptors for growth arrest specific 6 (Gas6). Yet how Axl regulates DTC proliferation in marrow remains undefined. Here, we explored the impact of the loss of Axl in PCa cells (PC3 and DU145) on the induction of their dormancy when they are co-cultured with a pre-osteoblastic cell line, MC3T3-E1. MC3T3-E1 cells dramatically decrease the proliferation of PCa cells, however this suppressive effect of osteoblasts is significantly reduced by the reduction of Axl expression in PCa cells. Interestingly, expression of both TGF-β and its receptors were regulated by Axl expression in PCa cells, while specific blockade of TGF-β signaling limited the ability of the osteoblasts to induce dormancy of PCa cells. Finally, we found that both Gas6 and Axl are required for TGF-β2-mediated cell growth suppression. Taken together, these data suggest that a loop between the Gas6/Axl axis and TGF-β2 signaling plays a significant role in the induction of PCa cell dormancy.

PMID: 27819283 [PubMed - in process]

http://ift.tt/2fyCSIK

Reconstruction of high resolution MLC leaf positions using a low resolution detector for accurate 3D dose reconstruction in IMRT.

Reconstruction of high resolution MLC leaf positions using a low resolution detector for accurate 3D dose reconstruction in IMRT.

Phys Med Biol. 2016 Dec 7;61(23):N642-N649

Authors: Visser R, Godart J, Wauben DJ, Langendijk JA, Van't Veld AA, Korevaar EW

Abstract
In pre-treatment dose verification, low resolution detector systems are unable to identify shifts of individual leafs of high resolution multi leaf collimator (MLC) systems from detected changes in the dose deposition. The goal of this study was to introduce an alternative approach (the shutter technique) combined with a previous described iterative reconstruction method to accurately reconstruct high resolution MLC leaf positions based on low resolution measurements. For the shutter technique, two additional radiotherapy treatment plans (RT-plans) were generated in addition to the original RT-plan; one with even MLC leafs closed for reconstructing uneven leaf positions and one with uneven MLC leafs closed for reconstructing even leaf positions. Reconstructed leaf positions were then implemented in the original RT-plan for 3D dose reconstruction. The shutter technique was evaluated for a 6 MV Elekta SLi linac with 5 mm MLC leafs (Agility(™)) in combination with the MatriXX Evolution detector with detector spacing of 7.62 mm. Dose reconstruction was performed with the COMPASS system (v2.0). The measurement setup allowed one row of ionization chambers to be affected by two adjacent leaf pairs. Measurements were obtained for various field sizes with MLC leaf position errors ranging from 1.0 mm to 10.0 mm. Furthermore, one clinical head and neck IMRT treatment beam with MLC introduced leaf position errors of 5.0 mm was evaluated to illustrate the impact of the shutter technique on 3D dose reconstruction. Without the shutter technique, MLC leaf position reconstruction showed reconstruction errors up to 6.0 mm. Introduction of the shutter technique allowed MLC leaf position reconstruction for the majority of leafs with sub-millimeter accuracy resulting in a reduction of dose reconstruction errors. The shutter technique in combination with the iterative reconstruction method allows high resolution MLC leaf position reconstruction using low resolution measurements with sub-millimeter accuracy.

PMID: 27819251 [PubMed - in process]

http://ift.tt/2fjERhb

HPV 16 in squamous cell carcinoma of 19th century tonsils.

HPV 16 in squamous cell carcinoma of 19th century tonsils.

Lancet Oncol. 2016 Nov;17(11):e477-e478

Authors: Benmoussa N, Charpentier C, Mariaggi AA, Collin G, Descamps D, Hourseau M, Barry B, Albert S, Picard A, Conan P, Charlier P

PMID: 27819244 [PubMed - in process]

http://ift.tt/2fjDijp

Vemurafenib for BRAF(V600E)-positive metastatic papillary thyroid cancer - Authors' response.

Vemurafenib for BRAF(V600E)-positive metastatic papillary thyroid cancer - Authors' response.

Lancet Oncol. 2016 Nov;17(11):e469

Authors: Brose MS, Singh N

PMID: 27819236 [PubMed - in process]

http://ift.tt/2ehMjN5

Vocal fold mobility alteration reversed after thyroidectomy.

Vocal fold mobility alteration reversed after thyroidectomy.

Autops Case Rep. 2016 Jul-Sep;6(3):53-57

Authors: Miazaki AP, Araújo-Filho VJ, Brandão LG, de Araujo-Neto VJ, Matos LL, Cernea CR

Abstract
The involvement of the inferior or recurrent laryngeal nerve (RLN) in mobility derangement of the vocal folds occurs more frequently due to thyroid malignancy invasion. Although uncommon, the same derangement, which is caused by benign thyroid entities, is also described and reverts to normality after a thyroidectomy in up to 89% of cases. In these cases, the pathogenesis of the vocal cord mobility disturbance is attributed to the direct compression of the RLN by massive thyroid enlargement. The authors describe three cases of patients presenting unilateral vocal cord palsy, which, before surgery, was diagnosed by laryngoscopy concomitantly with large and compressive goiter. Vocal fold mobility became normal after the thyroidectomy in all three cases. Therefore, it is noteworthy that these alterations may present reversibility after appropriate surgical treatment. An early surgical approach is recommended to reduce the nerve injury as much as possible; to preserve the integrity of both RLNs since the nerve function will be restored in some patients.

PMID: 27818960 [PubMed - in process]

http://ift.tt/2eQYe0d

Human papillomavirus-associated small cell carcinoma/neuroendocrine carcinoma of the oropharynx: a report of two cases.

Human papillomavirus-associated small cell carcinoma/neuroendocrine carcinoma of the oropharynx: a report of two cases.

Springerplus. 2016;5(1):1847

Authors: Misawa K, Kawasaki H, Matsuo R, Sugiyama K, Mochizuki D, Endo S, Imai A, Misawa Y, Yamatodani T, Mizuta K, Mineta H

Abstract
INTRODUCTION: Small cell carcinoma/neuroendocrine carcinoma (SCNEC) of the oropharynx is uncommon. Two cases of SCNEC in an 81-year-old woman and in a 54-year-old man are presented here.
CASE DESCRIPTION: We have documented two cases of SCNEC arising in the oropharynx with evidence of high-risk human papillomavirus (HPV) infection. Histologically, both cases were classified as poorly differentiated SCNEC with high nuclear-to-cytoplasmic ratios and nuclear molding. Observations using a transmission electron microscope revealed membrane-bound neuroendocrine granules in some tumor cells. Both tumors expressed high levels of p16, a surrogate marker for high-risk HPV infection. HPV infection was confirmed in both cases using HPV polymerase chain reaction analysis; HPV subtype 16 was identified in one case and HPV subtype 18 in the other.
DISCUSSION AND EVALUATION: SCNEC of the oropharynx is a rare and novel HPV-associated disease with neuroendocrine granules and aggressive clinical behavior.
CONCLUSIONS: Herein, we present two cases of SCNEC, focusing on its histologic features and treatment modalities. More studies are required to elucidate the pathophysiology of HPV-associated SCNEC in different organ systems.

PMID: 27818885 [PubMed - in process]

http://ift.tt/2fyJHKl

Long-term stability of intracortical recordings using perforated and arrayed Parylene sheath electrodes.

Long-term stability of intracortical recordings using perforated and arrayed Parylene sheath electrodes.

J Neural Eng. 2016 Nov 07;13(6):066020

Authors: Hara SA, Kim BJ, Kuo JT, Lee CD, Meng E, Pikov V

Abstract
OBJECTIVE: Acquisition of reliable and robust neural recordings with intracortical neural probes is a persistent challenge in the field of neuroprosthetics. We developed a multielectrode array technology to address chronic intracortical recording reliability and present in vivo recording results.
APPROACH: The 2 × 2 Parylene sheath electrode array (PSEA) was microfabricated and constructed from only Parylene C and platinum. The probe includes a novel three-dimensional sheath structure, perforations, and bioactive coatings that improve tissue integration and manage immune response. Coatings were applied using a sequential dip-coating method that provided coverage over the entire probe surface and interior of the sheath structure. A sharp probe tip taper facilitated insertion with minimal trauma. Fabricated probes were subject to examination by optical and electron microscopy and electrochemical testing prior to implantation.
MAIN RESULTS: 1 × 2 arrays were successfully fabricated on wafer and then packaged together to produce 2 × 2 arrays. Then, probes having electrode sites with adequate electrochemical properties were selected. A subset of arrays was treated with bioactive coatings to encourage neuronal growth and suppress inflammation and another subset of arrays was implanted in conjunction with a virally mediated expression of Caveolin-1. Arrays were attached to a custom-made insertion shuttle to facilitate precise insertion into the rat motor cortex. Stable electrophysiological recordings were obtained during the period of implantation up to 12 months. Immunohistochemical evaluation of cortical tissue around individual probes indicated a strong correlation between the electrophysiological performance of the probes and histologically observable proximity of neurons and dendritic sprouting.
SIGNIFICANCE: The PSEA demonstrates the scalability of sheath electrode technology and provides higher electrode count and density to access a greater volume for recording. This study provided support for the importance of creating a supportive biological environment around the probes to promote the long-term electrophysiological performance of flexible probes in the cerebral cortex. In particular, we demonstrated beneficial effects of the Matrigel coating and the long-term expression of Caveolin-1. Furthermore, we provided support to an idea of using an artificial acellular tissue compartment as a way to counteract the walling-off effect of the astrocytic scar formation around the probes as a means of establishing a more intimate and stable neural interface.

PMID: 27819256 [PubMed - as supplied by publisher]

http://ift.tt/2ehJETu

An adaptive and generalizable closed-loop system for control of medically induced coma and other states of anesthesia.

An adaptive and generalizable closed-loop system for control of medically induced coma and other states of anesthesia.

J Neural Eng. 2016 Nov 07;13(6):066019

Authors: Yang Y, Shanechi MM

Abstract
OBJECTIVE: Design of closed-loop anesthetic delivery (CLAD) systems is an important topic, particularly for medically induced coma, which needs to be maintained for long periods. Current CLADs for medically induced coma require a separate offline experiment for model parameter estimation, which causes interruption in treatment and is difficult to perform. Also, CLADs may exhibit bias due to inherent time-variation and non-stationarity, and may have large infusion rate variations at steady state. Finally, current CLADs lack theoretical performance guarantees. We develop the first adaptive CLAD for medically induced coma, which addresses these limitations. Further, we extend our adaptive system to be generalizable to other states of anesthesia.
APPROACH: We designed general parametric pharmacodynamic, pharmacokinetic and neural observation models with associated guidelines, and derived a novel adaptive controller. We further penalized large steady-state drug infusion rate variations in the controller. We derived theoretical guarantees that the adaptive system has zero steady-state bias. Using simulations that resembled real time-varying and noisy environments, we tested the closed-loop system for control of two different anesthetic states, burst suppression in medically induced coma and unconsciousness in general anesthesia.
MAIN RESULTS: In 1200 simulations, the adaptive system achieved precise control of both anesthetic states despite non-stationarity, time-variation, noise, and no initial parameter knowledge. In both cases, the adaptive system performed close to a baseline system that knew the parameters exactly. In contrast, a non-adaptive system resulted in large steady-state bias and error. The adaptive system also resulted in significantly smaller steady-state infusion rate variations compared to prior systems.
SIGNIFICANCE: These results have significant implications for clinically viable CLAD design for a wide range of anesthetic states, with potential cost-saving and therapeutic benefits.

PMID: 27819255 [PubMed - as supplied by publisher]

http://ift.tt/2eQVlwH

Applying dynamic data collection to improve dry electrode system performance for a P300-based brain-computer interface.

Applying dynamic data collection to improve dry electrode system performance for a P300-based brain-computer interface.

J Neural Eng. 2016 Nov 07;13(6):066018

Authors: Clements JM, Sellers EW, Ryan DB, Caves K, Collins LM, Throckmorton CS

Abstract
OBJECTIVE: Dry electrodes have an advantage over gel-based 'wet' electrodes by providing quicker set-up time for electroencephalography recording; however, the potentially poorer contact can result in noisier recordings. We examine the impact that this may have on brain-computer interface communication and potential approaches for mitigation.
APPROACH: We present a performance comparison of wet and dry electrodes for use with the P300 speller system in both healthy participants and participants with communication disabilities (ALS and PLS), and investigate the potential for a data-driven dynamic data collection algorithm to compensate for the lower signal-to-noise ratio (SNR) in dry systems.
MAIN RESULTS: Performance results from sixteen healthy participants obtained in the standard static data collection environment demonstrate a substantial loss in accuracy with the dry system. Using a dynamic stopping algorithm, performance may have been improved by collecting more data in the dry system for ten healthy participants and eight participants with communication disabilities; however, the algorithm did not fully compensate for the lower SNR of the dry system. An analysis of the wet and dry system recordings revealed that delta and theta frequency band power (0.1-4 Hz and 4-8 Hz, respectively) are consistently higher in dry system recordings across participants, indicating that transient and drift artifacts may be an issue for dry systems.
SIGNIFICANCE: Using dry electrodes is desirable for reduced set-up time; however, this study demonstrates that online performance is significantly poorer than for wet electrodes for users with and without disabilities. We test a new application of dynamic stopping algorithms to compensate for poorer SNR. Dynamic stopping improved dry system performance; however, further signal processing efforts are likely necessary for full mitigation.

PMID: 27819250 [PubMed - as supplied by publisher]

http://ift.tt/2ehINSU

Richter's Type of Incarcerated Obturator Hernia that Presented with a Deep Femoral Abscess: An Autopsy Case Report.

Richter's Type of Incarcerated Obturator Hernia that Presented with a Deep Femoral Abscess: An Autopsy Case Report.

Am J Case Rep. 2016 Nov 07;17:830-833

Authors: Yonekura S, Kodama M, Murano S, Kishi H, Toyoda A

Abstract
BACKGROUND Richter's obturator hernia is a rare abdominal hernia that is difficult to diagnose. The purpose of this case report is to show an unusual presentation of a fatal Richter's obturator hernia that was accompanied by a femoral abscess. CASE REPORT An 89-year-old woman complained of sudden left coxalgia and a gait disorder but no abdominal symptoms. She had no history of trauma or surgery in the inguinal area. Twenty-three days after her first complaint of coxalgia, the patient was admitted in a coma with necrotizing fasciitis in the left inguinal area. The patient died of asystole due to hyperkalemia. During surveillance for the cause of death, a Richter's type of incarcerated obturator hernia was identified at autopsy. The incarcerated small intestine had penetrated into the left obturator foramen to form an abscess that extended into the deep femoral region. CONCLUSIONS Obturator hernia accompanied by femoral abscess is extremely rare, but it should be suspected when a patient with no history of trauma or surgery has a femoral abscess, even in the absence of abdominal symptoms.

PMID: 27818487 [PubMed - in process]

http://ift.tt/2eR0y7E

In Vivo Assessment of Brainstem Depigmentation in Parkinson Disease: Potential as a Severity Marker for Multicenter Studies.

In Vivo Assessment of Brainstem Depigmentation in Parkinson Disease: Potential as a Severity Marker for Multicenter Studies.

Radiology. 2016 Nov 7;:160662

Authors: Schwarz ST, Xing Y, Tomar P, Bajaj N, Auer DP

Abstract
Purpose To investigate the pattern of neuromelanin signal intensity loss within the substantia nigra pars compacta (SNpc), locus coeruleus, and ventral tegmental area in Parkinson disease (PD); the specific aims were (a) to study regional magnetic resonance (MR) quantifiable depigmentation in association with PD severity and (b) to investigate whether imaging- and platform-dependent signal intensity variations can be normalized. Materials and Methods This prospective case-control study was approved by the local ethics committee and the research department of Nottingham University Hospitals. Written informed consent was obtained from all participants before enrollment in the study. Sixty-nine participants (39 patients with PD and 30 control subjects) were investigated with neuromelanin-sensitive MR imaging by using two different 3-T platforms and three differing protocols. Neuromelanin-related volumes of the anterior and posterior SNpc, locus coeruleus, and ventral tegmental area were determined, and normalized neuromelanin volumes were assessed for protocol-dependent effects. Diagnostic test performance of normalized neuromelanin volume was investigated by using receiver operating characteristic analyses, and correlations with the Unified Parkinson's Disease Rating Scale scores were tested. Results Reduction of normalized neuromelanin volume in PD was most pronounced in the posterior SNpc (median, -83%; P < .001), followed by the anterior SNpc (-49%; P < .001) and the locus coeruleus (-37%; P < .05). Normalized neuromelanin volume loss of the posterior and whole SNpc allowed the best differentiation of patients with PD and control subjects (area under the receiver operating characteristic curve, 0.92 and 0.88, respectively). Normalized neuromelanin volume of the anterior, posterior, and whole SNpc correlated with Unified Parkinson's Disease Rating Scale scores (r(2) = 0.25, 0.22, and 0.28, respectively; all P < .05). Conclusion PD-induced neuromelanin loss can be quantified across imaging protocols and platforms by using appropriate adjustment. Depigmentation in PD follows a distinct spatial pattern, affords high diagnostic accuracy, and is associated with disease severity. (©)RSNA, 2016 Online supplemental material is available for this article.

PMID: 27820685 [PubMed - as supplied by publisher]

http://ift.tt/2ehKfEv

Phase II Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma.

Phase II Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma.

Radiology. 2016 Nov 7;:160572

Authors: Wang X, Hu J, Cao G, Zhu X, Cui Y, Ji X, Li X, Yang R, Chen H, Xu H, Liu P, Li J, Li J, Hao C, Xing B, Shen L

Abstract
Purpose To evaluate the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin and 5-fluorouracil for advanced perihilar cholangiocarcinoma (PCC) in this prospective phase II study. Materials and Methods The protocol was approved by the local ethics committee, and all patients gave informed consent. Patients with nonresectable PCC were included in a prospective, open phase II study investigating HAI through interventionally implanted port catheters. HAI consisted of infusions of oxaliplatin 40 mg/m(2) for 2 hours, followed by 5-fluorouracil 800 mg/m(2) for 22 hours on days 1-3 every 3-4 weeks. A maximum of six cycles of HAI were applied for tumor control patients followed by maintenance with oral capecitabine until tumor progression. The primary end points were tumor response and progression-free survival (PFS). The secondary end points were local PFS, overall survival, and adverse events. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the risk factors for survival. Results Between 2012 and 2015, 37 patients were enrolled. The overall response rate was 67.6% (25 of 37), and the disease control rate was 89.2% (33 of 37). Median PFS, local PFS, and overall survival were 12.2, 25.0, and 20.5 months, respectively. All three survival lengths in patients with periductal infiltrating pattern were found to be significantly longer than those in patients with mass-forming pattern (P < .001, hazard ratio < 0.2). Macroscopic growth patterns (P = .018) and number of HAI cycles (P < .001) were independent risk factors of survival. The most frequent adverse events were grades 1 and 2 gastrointestinal side effects and sensory neuropathy in 31 (83.8%) and 28 (75.7%) patients, respectively. Conclusion HAI with oxaliplatin and 5-fluorouracil may be an encouraging treatment choice for advanced PCC due to its high tumor control, survival benefit, and low toxicity, especially in patients with periductal infiltrating pattern. (©) RSNA, 2016.

PMID: 27820684 [PubMed - as supplied by publisher]

http://ift.tt/2eQZ8tG

The Necrosis-Avid Small Molecule HQ4-DTPA as a Multimodal Imaging Agent for Monitoring Radiation Therapy-Induced Tumor Cell Death.

The Necrosis-Avid Small Molecule HQ4-DTPA as a Multimodal Imaging Agent for Monitoring Radiation Therapy-Induced Tumor Cell Death.

Front Oncol. 2016;6:221

Authors: Stammes MA, Maeda A, Bu J, Scollard DA, Kulbatski I, Medeiros PJ, Sinisi R, Dubikovskaya EA, Snoeks TJ, van Beek ER, Chan AB, Löwik CW, DaCosta RS

Abstract
PURPOSE: Most effective antitumor therapies induce tumor cell death. Non-invasive, rapid and accurate quantitative imaging of cell death is essential for monitoring early response to antitumor therapies. To facilitate this, we previously developed a biocompatible necrosis-avid near-infrared fluorescence (NIRF) imaging probe, HQ4, which was radiolabeled with (111)Indium-chloride ((111)In-Cl3) via the chelate diethylene triamine pentaacetic acid (DTPA), to enable clinical translation. The aim of the present study was to evaluate the application of HQ4-DTPA for monitoring tumor cell death induced by radiation therapy. Apart from its NIRF and radioactive properties, HQ4-DTPA was also tested as a photoacoustic imaging probe to evaluate its performance as a multimodal contrast agent for superficial and deep tissue imaging.
MATERIALS AND METHODS: Radiation-induced tumor cell death was examined in a xenograft mouse model of human breast cancer (MCF-7). Tumors were irradiated with three fractions of 9 Gy each. HQ4-DTPA was injected intravenously after the last irradiation, NIRF and photoacoustic imaging of the tumors were performed at 12, 20, and 40 h after injection. Changes in probe accumulation in the tumors were measured in vivo, and ex vivo histological analysis of excised tumors was performed at experimental endpoints. In addition, biodistribution of radiolabeled [(111)In]DTPA-HQ4 was assessed using hybrid single-photon emission computed tomography-computed tomography (SPECT-CT) at the same time points.
RESULTS: In vivo NIRF imaging demonstrated a significant difference in probe accumulation between control and irradiated tumors at all time points after injection. A similar trend was observed using in vivo photoacoustic imaging, which was validated by ex vivo tissue fluorescence and photoacoustic imaging. Serial quantitative radioactivity measurements of probe biodistribution further demonstrated increased probe accumulation in irradiated tumors.
CONCLUSION: HQ4-DTPA has high specificity for dead cells in vivo, potentiating its use as a contrast agent for determining the relative level of tumor cell death following radiation therapy using NIRF, photoacoustic imaging and SPECT in vivo. Initial preclinical results are promising and indicate the need for further evaluation in larger cohorts. If successful, such studies may help develop a new multimodal method for non-invasive and dynamic deep tissue imaging of treatment-induced cell death to quantitatively assess therapeutic response in patients.

PMID: 27818949 [PubMed - in process]

http://ift.tt/2ezKy97

18F-FDG-PET/CT of peritoneal tumors: a pictorial essay.

18F-FDG-PET/CT of peritoneal tumors: a pictorial essay.

Nucl Med Commun. 2016 Nov 3;

Authors: Dubreuil J, Giammarile F, Rousset P, Rubello D, Colletti PM, Glehen O, Skanjeti A

Abstract
Cancer imaging on the peritoneum is quite difficult on PET/CT because of the particular anatomical features of this membrane. The abdominal cavity can be the seat of very different primary or secondary tumoral lesions, with heterogeneous aggressiveness and variable fluorine-18 fluorodeoxyglucose uptake and patterns. We aimed to depict a spectrum of appearances with abnormal fluorine-18 fluorodeoxyglucose uptakes localized on the peritoneum in frequent conditions such as peritoneal carcinomatosis and in rarer disease such as desmoplastic round cell tumor.

PMID: 27820721 [PubMed - as supplied by publisher]

http://ift.tt/2fjD5N3

Harmonic scalpel impact on blood loss and operating time in major head and neck surgery: a randomized clinical trial

Abstract

Background

Long operating time and high blood loss contribute to post-surgical morbidity. Therefore, strategies to reduce these factors should to be tested using robust methods.

The purpose of this study was to evaluate the impact of using the harmonic scalpel on operating time and blood loss in patients undergoing resection for advanced oral cancer (OSCC).

Methods

Thirty-six adult head and neck cancer patients with advanced OSCC requiring primary tumor resection with uni- or bi- lateral selective neck dissection from July 2012 to September 2014 were randomized to either the control group (traditional surgery) or the experimental group (harmonic surgery). Patients older than 18 years who were able to provide informed consent were eligible. Primary outcomes of interest were: intraoperative blood loss (mL) and operative time (minutes) for the ablative part of the surgery.

Results

Mean blood loss in the experimental group was 260 mL versus 403 mL in the control group (p = 0.08). Mean operative time was 140 min in the experimental group and 159 min in the control group (p = 0.2).

Conclusions

In this randomized controlled trial, use of the harmonic scalpel did not effect intraoperative blood loss or OR time in patients undergoing surgery for advanced OSCC.

Trial registration

ClinicalTrials.gov, NCT02017834.

http://ift.tt/2fz55Nu

Harmonic scalpel impact on blood loss and operating time in major head and neck surgery: a randomized clinical trial

Abstract

Background

Long operating time and high blood loss contribute to post-surgical morbidity. Therefore, strategies to reduce these factors should to be tested using robust methods.

The purpose of this study was to evaluate the impact of using the harmonic scalpel on operating time and blood loss in patients undergoing resection for advanced oral cancer (OSCC).

Methods

Results

Conclusions

In this randomized controlled trial, use of the harmonic scalpel did not effect intraoperative blood loss or OR time in patients undergoing surgery for advanced OSCC.

Trial registration

ClinicalTrials.gov, NCT02017834.

http://ift.tt/2fz55Nu

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τρίτη 8 Νοεμβρίου 2016

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Αρχειοθήκη ιστολογίου