OtoRhinoLaryngology News: 03/04/18

Κυριακή 4 Μαρτίου 2018

Detection and Characterization of a Novel Norovirus in Bats, China

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ti3uFR

Development and evolution of tooth renewal in neoselachian sharks as a model for transformation in chondrichthyan dentitions

Abstract

A defining feature of dentitions in modern sharks and rays is the regulated pattern order that generates multiple replacement teeth. These are arranged in labio-lingual files of replacement teeth that form in sequential time order both along the jaw and within successively initiated teeth in a deep dental lamina. Two distinct adult dentitions have been described: alternate, in which timing of new teeth alternates between two adjacent files, each erupting separately, and the other arranged as single files, where teeth of each file are timed to erupt together, in some taxa facilitating similarly timed teeth to join to form a cutting blade. Both are dependent on spatiotemporally regulated formation of new teeth. The adult Angel shark Squatina (Squalomorphii) exemplifies a single file dentition, but we obtained new data on the developmental order of teeth in the files of Squatina embryos, showing alternate timing of tooth initiation. This was based on micro-CT scans revealing that the earliest mineralised teeth at the jaw margin and their replacements in file pairs (odd and even jaw positions) alternate in their initiation timing. Along with Squatina, new observations from other squalomorphs such as Hexanchus and Chlamydoselachus, together with representatives of the sister group Galeomorphii, have established that the alternate tooth pattern (initiation time and replacement order) characterises the embryonic dentition of extant sharks; however, this can change in adults. These character states were plotted onto a recent phylogeny, demonstrating that the Squalomorphii show considerable plasticity of dental development. We propose a developmental-evolutionary model to allow change from the alternate to a single file alignment of replacement teeth. This establishes new dental morphologies in adult sharks from inherited alternate order.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I2Umsb

Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study

Abstract

Purpose

Evidence suggests that the inflammatory state of an atherosclerotic plaque is important in predicting future risk of plaque rupture. This study aims to investigate the feasibility of measuring plaque inflammation in patients with obstructive sleep apnea (OSA) utilizing advanced vascular imaging — hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) with fluorodeoxyglucose (FDG) tracer—before and after continuous positive airway pressure (CPAP).

Methods

Patients with newly diagnosed moderate to severe OSA underwent baseline PET/MRI for assessment of vascular inflammation of the carotid arteries and thoracic aorta prior to initiation of CPAP. Those adherent to CPAP returned for repeat imaging after 3–6 months of CPAP use. Atherosclerotic plaque activity, as measured by arterial wall FDG uptake, was calculated using target-to-background ratios (TBR) before and after CPAP.

Results

Five patients were recruited as part of a focused project. Mean age was 52 years (80% male), and mean apnea-hypopnea index (AHI) was 33. Three patients were objectively adherent with CPAP. In the pre-CPAP phase, all patients had focal FDG uptake in the carotid arteries and aorta. After CPAP, there was an average reduction in TBR of 5.5% (TBR_mean) and 6.2% (TBR_max) in carotid and aortic plaque inflammation, similar in magnitude to the reduction observed with statin therapy alone in non-OSA patients (previously reported by others).

Conclusions

We demonstrate the feasibility of using hybrid PET/MRI to assess atherosclerotic plaque inflammation in patients with OSA before and after CPAP. Use of the vascular PET/MRI platform in patients with OSA may provide better insight into the role of OSA and its treatment in reducing atherosclerotic inflammation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FSmjCk

Endoscopic ultrasound guided brush/fine-needle aspiration cytology: A 15-month study

Background

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become increasingly popular for the diagnosis and staging of gastrointestinal diseases and peri-gastrointestinal lesions. The application of FNA/Brush has dramatically expanded the clinical utility of EUS.

Aims and objective

To evaluate the diagnostic accuracy, study the spectrum of lesions encountered in EUS-FNAC/brush cytology of gastrointestinal and peri-gastrointestinal lesions.

Materials and methods

Total of 124 patients during the period from August 2015 to November 2016 was included in the study. Routine staining was done.

Results

A total of 124 cases were studied with 86% (107 cases) being satisfactory for evaluation. M:F ratio was 1:1.03, mean age of 50.5 years. The most common site was common bile duct (CBD) (37%) followed by lymph node (21%), pancreas (17.7%), esophagus (17%), stomach (3.5%), liver (1.8%), gallbladder (1%), and spleen (1%). In total, 53.4% lesions were benign, in 6.5% atypical cells were seen, 12.1% were suspicious for malignancy, and 28% cases were positive for malignancy. Follow-up was available in 102 cases with cyto-histopathological concordance rate of 90%.

Conclusion

EUS-FNA/Brush is a reliable, sensitive, specific and minimally invasive way to establish a diagnosis. It can be utilized as a pre-operative procedure for the management of many intra-abdominal lesions and prevent unnecessary invasive procedures.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oS9Czd

Tastant-evoked Arc expression in the nucleus of the solitary tract and nodose/petrosal ganglion of the mouse is specific for bitter compounds

Abstract

Despite long and intense research, some fundamental questions regarding representation of taste information in the brain still remain unanswered. This might in part be due to shortcomings of the established methods that limit the researcher either to thorough characterization of few elements or analyze the response of the entirety of neurons to only one stimulus. To overcome these restrictions, we evaluate the use of the immediate early gene Arc as a neuronal activity marker in the early neural structures of the taste pathway, the nodose/petrosal ganglion (NPG) and the nucleus of the solitary tract (NTS). Responses of NPG and NTS neurons were limited to substances that taste bitter to humans and are avoided by mice. Arc expressing cells were concentrated in the rostromedial part of the dorsal NTS suggesting a role in gustatory processing. The use of Arc as a neuronal activity marker has several advantages, primarily the possibility to analyze the response of large numbers of neurons while using more than one stimulus makes Arc an interesting new tool for research in the early stages of taste processing.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oQouyf

Bone vascularized composite allotransplantation model in swine tibial defect: Evaluation of surgical angiogenesis and transplant viability

Introduction

In prior small animal studies, we maintained vascularized bone allotransplant viability without long-term immunotherapy. Instead, an autogenous neoangiogenic circulation is created from implanted vessels, sufficient to maintain bone viability with only 2 weeks immunosupression. Blood flow is maintained despite rejection of the allogeneic vascular pedicle thereafter. We have previously described a large animal (swine) pre-clinical model, reconstructing tibial defects with vascularized tibial allotransplants. In this manuscript, autologous angiogenesis is evaluated in this model and correlated with bone viability.

Materials and methods

Allogeneic tibial segments were transplanted across a major swine leukocyte antigen mismatch. Microvascular repair of the bone VCA pedicle was combined with intraosseous implantation of an autogenous arteriovenous (AV) bundle. The bundle was ligated in group 1 (n = 4), and allowed to perfuse in group 2 (n = 4). Three-drug immunotherapy was given for 2 weeks. At 16 weeks micro-CT angiography quantified neoangiogenic vessel volume. Bone viability, rejection grade, and bone healing were analyzed.

Results

A substantial neoangiogenic circulation developed from the implanted AV-bundle in group 2, with vessel density superior to ligated AV-bundle controls (0.11 ± 0.05 vs. 0.01 ± 0.01, P = .029). Bone allotransplant viability was also significantly enhanced by neoangiogenesis (78.7 ± 4.4% vs. 27.7 ± 5.8%, P = .028) with higher bone healing scores (21.4 ± 2.9 vs. 12.5 ± 3.7, P = .029). Ligated control tibias demonstrated disorganized bone morphology and higher local inflammation (P = .143).

Conclusion

Implantation of autogenous AV bundles into vascularized bone allotransplants resulted in the rapid formation of a neoangiogenic autogenous blood supply in a swine tibia model that maintained bone viability, improved bone healing, and minimized rejection.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FUilJA

Inspiratory muscle weakness, diaphragm immobility and diaphragm atrophy after neck dissection

Abstract

Background

Inspiratory strength after a neck dissection has not been evaluated, and diaphragm function has not been adequately evaluated.

Objective

Evaluate diaphragm mobility and inspiratory strength after neck dissection.

Methods

Prospective data collection of a consecutive series of adult patients submitted to neck dissection for head and neck cancer treatment, in a tertiary referral cancer center, from January to September 2014, with 30 days of follow-up. A total of 43 were studied (recruited 56; excluded 13).

Main outcome measures

Determine diaphragm mobility and inspiratory muscle strength after neck dissection, using diaphragm ultrasound and by measuring maximal inspiratory pressure (MIP) and sniff nasal inspiratory pressure (SNIP).

Results

Thirty patients underwent unilateral neck dissection, and thirteen patients underwent bilateral neck dissection. Diaphragm immobility occurred in 8.9% of diaphragms at risk. For the entire cohort, inspiratory strength decreased immediately after the dissection but returned to preoperative values after 1 month. Except for those with diaphragm immobility, diaphragm mobility remained unchanged after the dissection. One month after the dissection, the diaphragm thickness decreased, indicating diaphragm atrophy.

Conclusions

Immediately after a neck dissection, just a few patients showed diaphragmatic immobility, and there was a transient decrease in inspiratory strength in all individuals. Such findings can increase the risk of postoperative complications in patients with previous lung disease.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fcb7DF

Endoscopic visualization to the anterior surface of the malleus and tensor tympani tendon in congenital cholesteatoma

Abstract

Purpose

This study evaluated the feasibility of endoscopy in exposing the anterior surface of the malleus and tensor tympani tendon (ASMT) in children with congenital cholesteatoma (CC), and investigated the outcomes of hearing, postoperative complications, and residual or recurrent disease in endoscopic surgical approach cases.

Methods

A retrospective case review was performed in one tertiary referral center. Twelve children with CC involving the ASMT were recruited, and their medical records were reviewed. All patients underwent either total endoscopic surgery (n = 3) or endoscope-assisted surgery (n = 9), and Potsic staging was adopted to classify CC according to its severity: stage I (n = 8), stage II (n = 2), and stage III (n = 2). The mean follow-up period was 15.5 ± 2.8 months. The visibility of the ASMT by endoscope assistance, audiological results, surgical and postoperative complications, and recidivism of CC were analyzed.

Results

The ASMT was well visualized by endoscope assistance in all cases. No patient showed hearing deterioration at 3 months after surgery, and none experienced residual or recurrent disease during the follow-up period. Postoperative complications were not observed.

Conclusions

Total endoscopic or endoscope-assisted surgery could help surgeons directly visualize the ASMT in children, with negligible risks of hearing deterioration, postoperative complications, and recurrent disease. Our study might suggest that endoscopic ear surgery should be considered in patients with CC in the ASMT.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FfipT4

Inspiratory muscle weakness, diaphragm immobility and diaphragm atrophy after neck dissection

Abstract

Background

Inspiratory strength after a neck dissection has not been evaluated, and diaphragm function has not been adequately evaluated.

Objective

Evaluate diaphragm mobility and inspiratory strength after neck dissection.

Methods

Main outcome measures

Results

Conclusions

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fcb7DF

Endoscopic visualization to the anterior surface of the malleus and tensor tympani tendon in congenital cholesteatoma

Abstract

Purpose

Methods

Results

Conclusions

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FfipT4

Transcriptome changes induced in vitro by alcohol-containing mouthwashes in normal and dysplastic oral keratinocytes

Abstract

Background

The role of alcohol-containing mouthwash as a risk factor for the development of oral cancer is a subject of conflicting epidemiological evidence in the literature despite alcohol being a recognised carcinogen. The aim of this study was to use in vitro models to investigate mechanistic and global gene expression effects of exposure to alcohol-containing mouthwash.

Methods

Two brands of alcohol-containing mouthwash and their alcohol-free counterparts were used to treat two oral cell lines derived from normal (OKF6-TERT) and dysplastic (DOK) tissues. Genotoxicity was determined by Comet assay. RNA-seq was performed using the Ion Torrent platform. Bioinformatics analysis used R/Bioconductor packages with differential expression using DEseq2. Pathway enrichment analysis used EnrichR with the Wikipathways and Kegg databases.

Results

Both cell lines displayed dose dependent DNA damage in response to acute exposure to ethanol and alcohol-containing mouthwashes as well as alcohol-free mouthwashes reconstituted with ethanol as shown by Comet assay. The transcriptomic effects of alcohol-containing mouthwash exposure were more complex with significant differential gene expression ranging from >2000 genes in dysplastic (DOK) cells to <100 genes in normal (OKF6-TERT) cells. Pathway enrichment analysis in DOK cells revealed alcohol-containing mouthwashes showed common features between the two brands used including DNA damage response as well as cancer associated pathways. In OKF6-TERT cells the most significantly enriched pathways involved inflammatory signalling.

Conclusions

Alcohol-containing mouthwashes are genotoxic in vitro to normal and dysplastic oral keratinocytes and induce widespread changes in gene expression. Dysplastic cells are more susceptible to the transcriptomic effects of mouthwash.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FcI7eQ

Assessment of atherosclerotic plaque activity in patients with sleep apnea using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI): a feasibility study

Abstract

Purpose

Methods

Results

Conclusions

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FSmjCk

Cancers, Vol. 10, Pages 64: The Role of Oncogenic Tyrosine Kinase NPM-ALK in Genomic Instability

Cancers, Vol. 10, Pages 64: The Role of Oncogenic Tyrosine Kinase NPM-ALK in Genomic Instability

Cancers doi: 10.3390/cancers10030064

Authors: Cosimo Lobello Vasilis Bikos Andrea Janikova Sarka Pospisilova

Genomic stability is crucial for cell life and transmitting genetic material is one of the primary tasks of the cell. The cell needs to be able to recognize any possible error and quickly repair it, and thus, cells have developed several mechanisms to detect DNA damage and promote repair during evolution. The DNA damage response (DDR) and DNA repair pathways ensure the control of possible errors that could impair the duplication of genetic information and introduce variants in the DNA. Endogenous and exogenous factors compromise genomic stability and cause dysregulation in the DDR and DNA repair pathways. Cancer cells often impair these mechanisms to overcome cellular barriers (cellular senescence and/or apoptosis), leading to malignancy. NPM (nucleophosmin)-ALK (anaplastic lymphoma kinase) is an oncogenic tyrosine kinase that is involved in the development of anaplastic large cell lymphoma (ALCL). NPM-ALK is known to be involved in the activation of proliferative and anti-apoptotic signaling pathways. New evidence reveals that NPM-ALK translocation also impairs the ability of cells to maintain the genomic stability through both DDR and DNA repair pathways. This review aims to highlight the role of the oncogenic tyrosine kinase NPM-ALK in the cell, and pointing to new possible therapeutic strategies.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tfjEjD

Time Matters: the Toxicity of Zinc Oxide Nanoparticles to Lemna minor L. Increases with Exposure Time

Abstract

The use of zinc oxide nanoparticles (nano-ZnO) has rapidly increased in recent years, and this has triggered the need for versatile toxicity tests that can be used to test a range of different exposure scenarios. Acute exposure studies, using a variety of plant species, have overwhelmingly demonstrated nano-ZnO-induced toxicity, but substantial differences in the degree of phytotoxicity are reported in different studies. Here, we analysed the role of exposure time in determining the variation in phytotoxic effects. Using the model species Lemna minor, the effects of short-term (24 h), standardised (1 week) and chronic (up to 6 weeks) nano-ZnO exposure were compared. Nano-ZnO effects on Lemna minor growth indicators (biomass growth rate, root length), chlorophyll content and photosynthetic efficiency were measured. Rapid inhibitory effects of nano-ZnO on the maximal quantum yield of photosystem II could be measured after just 24-h exposure. Standardised (1 week) experiments revealed phytotoxic effects on Lemna minor biomass growth. More severe inhibitory effects on growth developed gradually over 4 to 6 weeks exposure to nano-ZnO, and these were qualitatively associated with increased zinc content in the plant. Such dynamics of nano-ZnO toxicity have not been elucidated before, and this study emphasises the importance of exposure time in studies of nanoparticle toxicity. We conclude that short-term, standardised experiments can potentially underestimate the environmental phytotoxicity, which may result from chronic exposure to nano-ZnO.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2HZYGsh

Improving Performance of Treatment Wetlands: Evaluation of Supplemental Aeration, Varying Flow Direction, and Phosphorus Removing Filters

Abstract

Pollutant removal was compared among subsurface flow constructed wetland (CW) mesocosms used for dairy farm wastewater treatment. Supplemental aeration, flow direction, and the use of phosphorus-reducing filters (PRFs) were varied among the CWs. The following were compared: (1) vertical flow CWs with and without supplemental aeration, (2) aerated CWs with horizontal and vertical flow directions, (3) single-cell and two-cell treatment systems, and (4) wetland-wetland systems (two CWs in series) and wetland-PRF systems (a CW followed by a PRF). The results from this investigation showed that, first, nearly all treatment strategies, either singly or in pairs, substantially reduced almost all the contaminants we tested. Second, supplemental aeration resulted in higher ammonium-nitrogen (NH₄-N) removal efficiencies in aerated vertical flow CWs, compared to unaerated CWs. However, it caused no further improvement in dissolved reactive phosphorus (DRP), total suspended solids (TSS), E. coli, or BOD₅ removal. Third, there was no difference between aerated horizontal and aerated vertical flow CWs in removal of any of the tested contaminants. Fourth, adding a second stage of treatment significantly improved DRP, TSS, E. coli, and NH₄-N removal, but not BOD₅. Finally, treatment systems with PRFs showed superior performance in DRP and E. coli removal.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oQtoes

Development of a Measurement Tool to Assess Students’ Knowledge and Perceptions About Cancer (SKPaC)

Abstract

Cancer literacy is currently one of the most important dimensions of cancer continuum. Objective assessment of cancer knowledge in populations remains a challenging field to public health entities. Different evaluation tools are currently available; still, some groups remain disregarded due to the absence of validated instruments. Cancer literacy in adolescents and young adults has been clearly overlooked being a subject that requires new tools to be properly studied. To address this topic, we developed a new instrument and field tested it in a classroom environment for internal reliability, construct, and face validity. "Students Knowledge and Perceptions about Cancer questionnaire" was designed in Portuguese language and adapted to the Portuguese context by a multidisciplinary team. The final version of the questionnaire includes 35 items organized in three sections, encompassing knowledge and perceptions about cancer and socio-biographic data. Cancer experts ensured content validity, while tailoring of contents was refined with high school teachers. Test and retest of the instrument showed a good reliability of the scale and construct validity. Also, the clarity of the questionnaire and suitability to proper evaluate cancer knowledge was consistent between test and retest. The Students' Knowledge and Perceptions About Cancer Questionnaire (SKPaC) showed to be a valid tool to assess adolescents' knowledge and perceptions about cancer that can be used in the educational context.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tdlxNw

Nicorandil increased the cerebral blood flow via nitric oxide pathway and ATP-sensitive potassium channel opening in mice

Abstract

Purpose

Nicorandil has dual properties and acts as a nitric oxide donor and an ATP-sensitive potassium (K_ATP) channel opener. Considering its pharmacological profile, nicorandil might exert protective effects on the brain as well as on the heart. The purpose of this study was to directly evaluate the effect of nicorandil on cerebral blood flow (CBF) in mice using a transcranial Doppler method.

Methods

Under general anesthesia, the nicorandil groups received a single-bolus intraperitoneal injection of the respective doses of nicorandil (1, 5, or 10 mg/kg), while the control group received vehicle only. CBF was measured using a transcranial Doppler flowmeter. N^G-nitro-l-arginine methyl ester and glibenclamide were used to elucidate the underlying mechanisms.

Results

A single-bolus injection of 1 mg/kg of nicorandil increased the CBF (11.6 ± 3.6 vs. 0.5 ± 0.7%, p < 0.001) without affecting the heart rate and blood pressure. On the contrary, 5 and 10 mg/kg of nicorandil significantly decreased the cerebral blood flow by decreasing the mean blood pressure below the cerebral autoregulation range. The positive effect of 1 mg/kg of nicorandil on the cerebral blood flow was inhibited by co-administration of either N^G-nitro-l-arginine methyl ester or glibenclamide.

Conclusions

A clinical dose of nicorandil increases CBF without affecting systemic hemodynamics. The positive effect of nicorandil on CBF is most likely caused via both the nitric oxide pathway and K_ATP channel opening.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FfSGJW

Marshaling the Translational Potential of MC1R for Precision Risk Assessment of Melanoma

Melanoma rates have been increasing in the United States, and neither primary (sun protection and avoidance) nor secondary (skin examination) prevention is practiced consistently, even by those with melanoma risk factors. Inherited variation at MC1R is a robust marker for increased risk of melanoma, even among individuals with "sun-resistant" phenotypes. Although MC1R conveys important information about inherited melanoma risk for a broad spectrum of individuals, concerns that MC1R feedback could have negative consequences, including increased distress about melanoma, inappropriate use of health services, and development of a false sense of security, are valid and require empirical examination. The time is right for high-quality research focusing on the translation of MC1R genotype into clinical and public health practice. If studies show MC1R genetic risk screening is effective at motivating behavior change, more melanomas may be detected at earliest stages for which surgical excision is highly curative or a large number of melanomas may be prevented altogether. While other genetic markers for melanoma susceptibility may emerge in the coming years, the burgeoning research agenda on the public health translational potential of MC1R genetic risk screening will inform and usefully advance current and future precision risk assessment of melanoma. Cancer Prev Res; 11(3); 121–4. ©2017 AACR.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FgNcP8

Effects of Black Raspberry on Dibenzo[a,l]Pyrene Diol Epoxide Induced DNA Adducts, Mutagenesis, and Tumorigenesis in the Mouse Oral Cavity

We previously showed that metabolic activation of the environmental and tobacco smoke constituent dibenzo[a,l]pyrene (DB[a,l]P) to its active fjord region diol epoxide (DB[a,l]PDE) is required to induce DNA damage, mutagenesis, and squamous cell carcinoma (SCC) in the mouse oral cavity. In contrast to procarcinogens, which were employed previously to induce SCC, DB[a,l]PDE does not require metabolic activation to exert its biological effects, and thus, this study was initiated to examine, for the first time, whether black raspberry powder (BRB) inhibits postmetabolic processes, such as DNA damage, mutagenesis, and tumorigenesis. Prior to long-term chemoprevention studies, we initially examined the effect of BRB (5% added to AIN-93M diet) on DNA damage in B6C3F1 mice using LC/MS-MS and on mutagenesis in the lacI gene in the mouse oral cavity. We showed that BRB inhibited DB[a,l]PDE-induced DNA damage (P < 0.05) and mutagenesis (P = 0.053) in the oral cavity. Tumor incidence in the oral cavity (oral mucosa and tongue) of mice fed diet containing 5% BRB was significantly (P < 0.05) reduced from 93% to 66%. Specifically, the incidence of benign tumor was significantly (P < 0.001) reduced from 90% to 31% (62% to 28% in the oral cavity and 28% to 2% in the tongue), a nonsignificant reduction of malignant tumors from 52% to 45%. Our preclinical findings demonstrate for the first time that the chemopreventive efficacy of BRB can be extended to direct-acting carcinogens that do not require phase I enzymes and is not just limited to procarcinogens. Cancer Prev Res; 11(3); 157–64. ©2017 AACR.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FSQPft

Targeting Epigenetics to Prevent Obesity Promoted Cancers

Epigenetic changes in DNA and associated chromatin proteins are increasingly being considered as important mediators of the linkage between obesity and cancer. Although multiple agents, targeted at epigenetic changes, are being tested for therapy of established cancers, this issue of Cancer Prevention Research carries two articles demonstrating that the bromodomain inhibitor I-BET-762 can attenuate adipose tissue–promoted cancers. Although I-BET-762 significantly delayed, rather than completely prevented, the onset of adiposity-promoted transformation and malignancy, these experiments provide important proof of principle for the strategies of targeting epigenetic changes to disrupt the obesity–cancer linkage. Because bromodomain proteins represent only one of multiple epigenetic mediators, it is probable that targeting other epigenetic processes, alone or in combination, may serve to even more effectively disrupt the obesity promotion of cancer. Given the magnitude of the current obesity pandemic and its impact on cancer, preventive measures to disrupt this linkage are critically important. Cancer Prev Res; 11(3); 125–8. ©2018 AACR.

See related article by Chakraborty et al., p. 129

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D11pO9

Chemoprevention of Preclinical Breast and Lung Cancer with the Bromodomain Inhibitor I-BET 762

Breast cancer and lung cancer remain the top two leading causes of cancer-related deaths in women. Because of limited success in reducing the high mortality of these diseases, new drugs and approaches are desperately needed. Cancer prevention is one such promising strategy that is effective in both preclinical and clinical studies. I-BET 762 is a new bromodomain inhibitor that reversibly targets BET (bromodomain and extraterminal) proteins and impairs their ability to bind to acetylated lysines on histones, thus interrupting downstream transcription. This inhibitor has anti-inflammatory effects and induces growth arrest in many cancers and is currently under clinical trials for treatment of cancer. However, few studies have investigated the chemopreventive effects of bromodomain inhibitors. Here, we found that I-BET 762 significantly delayed tumor development in preclinical breast and lung cancer mouse models. This drug not only induced growth arrest and downregulated c-Myc, pSTAT3, and pERK protein expression in tumor cells in vitro and in vivo but also altered immune populations in different organs. These results demonstrate the promising potential of using I-BET 762 for cancer prevention and suggest the striking effects of I-BET 762 are the result of targeting both tumor cells and the tumor microenvironment. Cancer Prev Res; 11(3); 143–56. ©2017 AACR.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FSAHKM

A BET Bromodomain Inhibitor Suppresses Adiposity-Associated Malignant Transformation

Almost half a million of all new cancers have been attributed to obesity and epidemiologic evidence implicates visceral adipose tissue (VAT) and high-fat diets (HFD) in increasing cancer risk. We demonstrated that VAT-derived fibroblast growth factor 2 (FGF2) from mice fed an HFD or obese individuals stimulates the malignant transformation of epithelial cells. Mechanism-based strategies to prevent this VAT-enhanced tumorigenesis have not been explored. Clinical studies have indicated that bromodomain inhibitors have considerable potential as therapeutic agents for cancer by inhibiting the activity of several oncogenes, including c-Myc; however, their chemopreventive activity is unknown. We show herein that mice with visceral adiposity have elevated nuclear c-Myc expression in their epidermis. We hypothesized that the bromodomain inhibitor I-BET-762 (I-BET) would have efficacy in the prevention of malignant transformation by VAT and FGF2. We tested this hypothesis using our novel models of VAT-stimulated transformation in vitro and FGF2- stimulated tumor formation in vivo. We found that I-BET significantly attenuates VAT and FGF2-stimulated transformation and inhibits VAT-induced c-Myc protein expression in several skin and breast epithelial cell lines. Moreover, I-BET attenuated tumor growth significantly in FGF2-treated nude mice. Work is ongoing to determine the role of visceral adiposity in c-Myc activity in several tissues and determine the inhibitory effect of I-BET on VAT-promoted tumors in vivo. Cancer Prev Res; 11(3); 129–42. ©2017 AACR.

See related editorial by Berger and Scacheri, p. 125

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CZdymX

Clinical Outcomes after Conservative Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) in Women Ages 21-39 Years

Cervical intraepithelial neoplasia grade 2 (CIN2) frequently regresses, is typically slow-growing, and rarely progresses to cancer. Some women forgo immediate treatment, opting for conservative management (heightened surveillance with cytology and colposcopy), to minimize overtreatment and increased risk of obstetric complications; however, there are limited data examining clinical outcomes in these women. We performed a retrospective cohort analysis of younger women diagnosed with initially untreated CIN1/2, CIN2 and CIN2/3 lesions at Kaiser Permanente Northern California between 2003 and 2015. Clinical outcomes were categorized into five mutually exclusive hierarchical groups: cancer, treated, returned to routine screening, persistent high-grade lesion, or persistent low-grade lesion. Median follow-up for the 2,417 women was 48 months. Six women were diagnosed with cancer (0.2%), all with history of high-grade cytology, and none after a negative cotest. Thirty percent of women were treated, and only 20% returned to routine screening; 50% remained in continued intensive follow-up, of which 86% had either low-grade cytology/histology or high-risk human papillomavirus (HPV) positivity, but not necessarily persistence of a single HPV type. No cancers were detected after a single negative cotest in follow-up. Almost half of initially untreated women did not undergo treatment, but remained by protocol in colposcopy clinic for 2 or more years in the absence of persisting CIN2⁺. Their incomplete return to total negativity was possibly due to sequential new and unrelated low-grade abnormalities. The prolonged colposcopic surveillance currently required to return to routine screening in the absence of persisting CIN2⁺ might not be necessary after a negative cotest.

Significance: Many younger women under conservative management following an initial CIN2 result remain in a clinical protocol of prolonged intensified surveillance without a subsequent diagnosis of CIN2 or more severe diagnoses. More research is needed to determine whether such prolonged management might be unnecessary following a negative cotest for those women with an initial CIN2 but otherwise only low-grade findings. Cancer Prev Res; 11(3); 165–70. ©2018 AACR.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FSVLAJ

HIF1α protein and mRNA expression as a new marker for post mortem interval estimation in human gingival tissue

Abstract

Estimating the post mortem interval (PMI) is still a crucial step in Forensic Pathology. Although several methods are available for assessing the PMI, a precise estimation is still quite unreliable and can be inaccurate. The present study aimed to investigate the immunohistochemical distribution and mRNA expression of hypoxia inducible factor (HIF-1α) in post mortem gingival tissues to establish a correlation between the presence of HIF-1α and the time since death, with the final goal of achieving a more accurate PMI estimation. Samples of gingival tissues were obtained from 10 cadavers at different PMIs (1–3 days, 4–5 days and 8–9 days), and were processed for immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. The results showed a time-dependent correlation of HIF-1α protein and its mRNA with different times since death, which suggests that HIF-1α is a potential marker for PMI estimation. The results showed a high HIF-1α protein signal that was mainly localized in the stratum basale of the oral mucosa in samples collected at a short PMI (1–3 days). It gradually decreased in samples collected at a medium PMI (4–5 days), but it was not detected in samples collected at a long PMI (8–9 days). These results are in agreement with the mRNA data. These data indicate an interesting potential utility of Forensic Anatomy-based techniques, such as immunohistochemistry, as important complementary tools to be used in forensic investigations.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I47TzM

Incomplete and false tract insertions in cochlear implantation: retrospective review of surgical and auditory outcomes

Abstract

Objectives

To evaluate incidence, demographics, surgical, and radiological correlates of incomplete and false tract electrode array insertions during cochlear implantation (CI). To evaluate outcomes in patients with incomplete electrode insertion (IEI).

Study design

Retrospective analysis.

Setting

Otology and skull base center.

Patients and methods

Charts of 18 patients (19 ears) with incomplete or false tract insertions of the electrode array were evaluated who underwent CI, with at least 1 year follow-up (from 470 cases). Demographic findings, etiologies, pre-operative radiologic findings, operative records, post-operative plain radiographic assessment for extent of electrode insertion, and switch-on mapping were evaluated. Audiological outcomes were evaluated using maximum and last recorded vowel, word, sentence, and comprehension scores for patients with IEI.

Results

Incidence of insertional abnormalities was 4.25% with 17 instances of incomplete and 2 cases of insertion into superior semicircular canal. Mean age and duration of deafness were 55.18 ± 4.62 and 22.12 ± 5.71 years. Etiologies in the IEI group were idiopathic, otosclerosis, meningitis, chronic otitis media (COM), temporal bone fractures, and Neurofibromatosis-2. 29.4% cases had cochlear luminal obstruction. Mean radiological and active electrophysiological length of insertion was 20.49 ± 0.66 and 19.49 ± 0.88 mm, respectively. No significant correlation was observed between audiological outcomes and insertional length except in time to achieve maximum word scores (p = 0.04). Age at implantation had significant correlations with last recorded word and comprehension scores at mean follow-up of 42.9 months, and with time to achieve maximum auditory scores.

Conclusions

IEI during cochlear implantation using straight electrodes can occur with or without cochlear luminal obstruction. Age plays an important role in the auditory rehabilitation in this patient subset.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oJfdZp

Incomplete and false tract insertions in cochlear implantation: retrospective review of surgical and auditory outcomes

Abstract

Objectives

Study design

Retrospective analysis.

Setting

Otology and skull base center.

Patients and methods

Results

Conclusions

IEI during cochlear implantation using straight electrodes can occur with or without cochlear luminal obstruction. Age plays an important role in the auditory rehabilitation in this patient subset.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oJfdZp

Can Prostate Imaging Reporting and Data System Version 2 reduce unnecessary prostate biopsies in men with PSA levels of 4–10 ng/ml?

Abstract

Purpose

To explore the value of Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) for predicting prostate biopsy results in patients with prostate specific antigen (PSA) levels of 4–10 ng/ml.

Methods

We retrospectively reviewed multi-parameter magnetic resonance images from 528 patients with PSA levels of 4–10 ng/ml who underwent transrectal ultrasound-guided prostate biopsies between May 2015 and May 2017. Among them, 137 were diagnosed with prostate cancer (PCa), and we further subdivided them according to pathological results into the significant PCa (S-PCa) and insignificant significant PCa (Ins-PCa) groups (121 cases were defined by surgical pathological specimen and 16 by biopsy). Age, PSA, percent free PSA, PSA density (PSAD), prostate volume (PV), and PI-RADS score were collected. Logistic regression analysis was performed to determine predictors of pathological results. Receiver operating characteristic curves were constructed to analyze the diagnostic value of PI-RADS v2 in PCa.

Results

Multivariate analysis indicated that age, PV, percent free PSA, and PI-RADS score were independent predictors of biopsy findings, while only PI-RADS score was an independent predictor of S-PCa (P < 0.05). The areas under the receiver operating characteristic curve for diagnosing PCa with respect to age, PV, percent free PSA, and PI-RADS score were 0.570, 0.430, 0.589 and 0.836, respectively. The area under the curve for diagnosing S-PCa with respect to PI-RADS score was 0.732. A PI-RADS score of 3 was the best cutoff for predicting PCa, and 4 was the best cutoff for predicting S-PCa. Thus, 92.8% of patients with PI-RADS scores of 1–2 would have avoided biopsy, but at the cost of missing 2.2% of the potential PCa cases. Similarly, 83.82% of patients with a PI-RADS score ≤ 3 would have avoided biopsy, but at the cost of missing 3.3% of the potential S-PCa cases.

Conclusions

PI-RADS v2 could be used to reduce unnecessary prostate biopsies in patients with PSA levels of 4–10 ng/ml.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FTG4JA

Complication analysis of complete versus partial coverage of tissue expanders using serratus anterior musculofascial flaps in immediate breast reconstruction

Abstract

Purpose

To prevent tissue expander (TE) exposure following mastectomy flap necrosis in immediate breast reconstruction, the TE is usually covered completely or partially with a musculofascial (MF) flap. This study compares the complications of the two coverage methods.

Methods

We reviewed, retrospectively, 106 cases of immediate TE-based breast reconstruction. The patients were divided into two groups according to whether complete or partial TE coverage was done. In the complete coverage group, the serratus anterior MF flap was dissected and sutured to the pectoralis major muscle to cover the TE completely. In the partial coverage group, the serratus anterior MF flap was not dissected, and the lateral border of the pectoralis major muscle was sutured to the mastectomy skin flaps.

Results

The TEs were covered completely in 60 breasts and partially in 46 breasts. The mastectomy flap necrosis rate was significantly higher in the complete coverage group (p < 0.01), but there was no incidence of TE exposure in either groups. The lateral migration rate was significantly higher in the partial coverage group (p = 0.033). There were no significant differences in the cranial migration rate (p = 0.133).

Conclusions

The complete coverage method is a better option if there is a high risk of mastectomy flap necrosis; however, surgeons should monitor carefully for cranial migration.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FldYZX

Novel condylar repositioning method for 3D-printed models

Abstract

Background

Along with the advances in technology of three-dimensional (3D) printer, it became a possible to make more precise patient-specific 3D model in the various fields including oral and maxillofacial surgery. When creating 3D models of the mandible and maxilla, it is easier to make a single unit with a fused temporomandibular joint, though this results in poor operability of the model. However, while models created with a separate mandible and maxilla have operability, it can be difficult to fully restore the position of the condylar after simulation. The purpose of this study is to introduce and asses the novel condylar repositioning method in 3D model preoperational simulation.

Methods

Our novel condylar repositioning method is simple to apply two irregularities in 3D models. Three oral surgeons measured and evaluated one linear distance and two angles in 3D models.

Results

This study included two patients who underwent sagittal split ramus osteotomy (SSRO) and two benign tumor patients who underwent segmental mandibulectomy and immediate reconstruction. For each SSRO case, the mandibular condyles were designed to be convex and the glenoid cavities were designed to be concave. For the benign tumor cases, the margins on the resection side, including the joint portions, were designed to be convex, and the resection margin was designed to be concave. The distance from the mandibular ramus to the tip of the maxillary canine, the angle created by joining the inferior edge of the orbit to the tip of the maxillary canine and the ramus, the angle created by the lines from the base of the mentum to the endpoint of the condyle, and the angle between the most lateral point of the condyle and the most medial point of the condyle were measured before and after simulations. Near-complete matches were observed for all items measured before and after model simulations of surgery in all jaw deformity and reconstruction cases.

Conclusions

We demonstrated that 3D models manufactured using our method can be applied to simulations and fully restore the position of the condyle without the need for special devices.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FcTXpj

Perspectives on the etiology of chronic rhinosinusitis: An immune barrier hypothesis

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tkmoMG

The efficacy of topical antibiofilm agents in a sheep model of rhinosinusitis

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oHE7Zn

Microarray analysis of distinct gene transcription profiles in non-eosinophilic chronic sinusitis with nasal polyps

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tjep2l

Analysis of T-helper responses and FOXP3 gene expression in patients with Japanese cedar pollinosis

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oGr8au

Pathophysiology of nasal polyposis: The role of desmosomal junctions

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tggsnJ

Olfactory bulb volume in patients with sinonasal disease

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oKek2M

Squamous metaplasia and chronic rhinosinusitis: A clinicopathological study

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2te4ET5

Posttraumatic anosmia secondary to central nervous system injury

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oGr1f4

Postoperative antibiotic care after functional endoscopic sinus surgery

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tciPIk

Sonography versus plain x rays in diagnosis of nasal fractures

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oHWWfg

Acoustic rhinometry of Asian noses

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tjM63w

Balloon catheter dilatation for frontal sinus ostium stenosis in the office setting

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tfEGOO

In vivo laser tissue welding in the rabbit maxillary sinus

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oKW4X9

Attachment-oriented endoscopic surgical strategy for sinonasal inverted papilloma

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tdRNjH

Combined image guidance and intraoperative computed tomography in facilitating endoscopic orientation within and around the paranasal sinuses

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oH8aR6

Construct validation of a low-fidelity endoscopic sinus surgery simulator

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tiNOCk

Analysis of transnasal endoscopic versus transseptal microscopic approach for excision of pituitary tumors

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oNdWAT

Comparison of laryngeal mask with endotracheal tube for anesthesia in endoscopic sinus surgery

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tfEFue

Results of endoscopic maxillary mega-antrostomy in recalcitrant maxillary sinusitis

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2oKW49B

Relationship between mucosal inflammation, computed tomography, and symptomatology in chronic rhinosinusitis without polyps

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2tjekvz

Novel homozygous GBA2 mutation in a patient with complicated spastic paraplegia

Publication date: Available online 3 March 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Giulia Coarelli, Silvia Romano, Lorena Travaglini, Michela Ferraldeschi, Francesco Nicita, Maria Spadaro, Arianna Fornasiero, Marina Frontali, Marco Salvetti, Enrico Bertini, Giovanni Ristori
Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurological disorders characterized primarily by a pyramidal syndrome with lower limb spasticity, which can manifest as pure HSP or associated with a number of neurological or non-neurological signs (i.e., complicated HSPs). The clinical variability of HSPs is associated with a wide genetic heterogeneity, with more than eighty causative genes known. Recently, next generation sequencing (NGS) has allowed increasing genetic definition in such a heterogeneous group of disorders. We report on a 56- year-old man affected by sporadic complicated HSP consisting of a pyramidal syndrome, cerebellar ataxia, congenital cataract, pes cavus, axonal sensory-motor peripheral neuropathy and cognitive decline. Brain MRI showed cerebellar atrophy and thin corpus callosum. By NGS we found a novel homozygous biallelic c.452-1G>C mutation in the b-glucosidase 2 gene (GBA2), known to be causative for autosomal recessive hereditary spastic paraplegia type 46 (SPG46). The rarity of this inherited form besides reporting on a novel mutation, expands the genetic and clinical spectrum of SPG46 related HSP.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fh0OKw

Commentary on letter to editor titled “The clinical value of the RGB value of an image of the interarytenoid area for diagnosis of laryngopharyngeal reflux”

We are thankful to Dr. Zhengcai-Lou and Dr. Zihan-Lou for their interest in our article. It would be our pleasure to take this opportunity to comment on them.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FSA3x3

Virtual reality rehabilitation with functional electrical stimulation improves upper extremity function in patients with chronic stroke: a pilot randomized controlled study

Publication date: Available online 2 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Stephanie Hyeyoung Lee, Ji-Yeong Lee, Mi-Young Kim, Yu-Jin Jeon, Suyoung Kim, Joon-Ho Shin
ObjectiveTo compare virtual reality (VR) combined with functional electrical stimulation (FES) to cyclic FES for improving upper extremity function and health-related quality of life in patients with a chronic stroke.DesignA pilot, randomized, single blinded, controlled trial.SettingStroke rehabilitation inpatient unitParticipantsForty-eight participants with a hemiplegia secondary to a unilateral stroke for >3 months, with a hemiplegic wrist extensor Medical Research Council (MRC) scale score of 1–3.InterventionsFES was applied to the wrist extensors and finger extensors. A virtual-reality(VR) based wearable rehabilitation device was used, combined with FES and virtual activity-based training. The control group received cyclic FES only. Both groups completed 20 sessions, over a 4-week period.Main outcome measuresPrimary outcomes were the change in the Fugl–Meyer Assessment: upper extremity (FMA) and Wolf Motor Function Test (WMFT) scores. Secondary outcomes were the change in the Box and Block test (BB), Jebsen Taylor Hand Function Test (JTT), and Stroke Impact Scale (SIS) scores. Assessments were performed at baseline (T0) and at 2 weeks (T1), 4 weeks (T4), and 8 weeks (T8). Between-group comparisons were evaluated using a repeated measures analysis of variance.ResultsForty-one participants were included in the analysis. Compared to FES alone, VR-FES produced greater increase in FMA–distal score (p=0.011) and marginal improvement in JTT–gross score (p=0.057). VR-FES produced greater, although non-significant, improvements in all other outcome measures, except in the SIS–ADL/IADL score.ConclusionsFES with VR-based rehabilitation may be more effective than cyclic FES to improve distal gross upper extremity function post-stroke.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GZrRdB

Gait Training in Acute Spinal Cord Injury Rehabilitation – Utilization and Outcomes Among Non-Ambulatory Individuals: Findings from the SCIRehab Project

Publication date: Available online 3 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Stephanie Rigot, Lynn Worobey, Michael L. Boninger
ObjectivesTo investigate relation of gait training (GT) during inpatient rehabilitation (IPR) to outcomes of people with traumatic spinal cord injury (SCI).DesignProspective observational study using the SCIRehab database.SettingSix IPR facilities.ParticipantsPatients with new SCI receiving initial rehabilitation (n=1376).InterventionsPatients were divided into groups of who did and did not receive GT. Patients were further subdivided based on their primary mode of mobility as measured by the Functional Independence Measure (FIM).Outcome MeasuresPain rating scales; Patient Health Questionnaire Mood Subscale; Satisfaction with Life Scale (SWLS); and Craig Handicap Assessment and Reporting Technique (CHART).ResultsNearly 58% of all patients received GT, including 33.3% of patients who were primarily using a wheelchair 1-year after discharge from IPR. Those who used a wheelchair and received GT, received significantly less transfer and wheeled mobility training (p<.001). CHART physical independence (p=.002), mobility (p=.024), and occupation (p=.003) scores were significantly worse in patients who used a wheelchair at 1-year and received GT, compared to those who used a wheelchair and did not receive GT in IPR. Older age was also a significant predictor of worse participation as measured by the CHART.ConclusionsA significant percentage of individuals who are not likely to become functional ambulators are spending portions of their IPR stays performing GT, which is associated with less time allotted for other functional interventions. GT in IPR was also associated with participation deficits at 1-year for those who used a wheelchair, implying the potential consequences of opportunity costs, pain, and psychological difficulties of receiving unsuccessful GT. Clinicians should consider this data when deciding to implement gait training during initial inpatient rehabilitation.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Fkk5xD

Effects of Intraneural Injection of Dexmedetomidine in Combination With Ropivacaine in Rat Sciatic Nerve Block

Background and Objectives Dexmedetomidine is known to have neural protection effect via attenuation of inflammatory responses induced by local anesthetics. We investigated whether intraneural dexmedetomidine is effective for attenuating or preventing neural injury resulting from inadvertent intraneural injection of local anesthetic. Methods Rats were randomly divided, and left sciatic nerve was surgically exposed. The rats received no injection (control group) or intraneural injections of 0.2 mL of normal saline (saline group), 0.2 mL of 0.5% ropivacaine (ropivacaine group), or 0.2 mL of 0.5% ropivacaine and 0.5 μg/kg of dexmedetomidine (ropivacaine plus dexmedetomidine group). Interleukin (IL)-6 and IL-1β messenger RNA (mRNA) levels were detected at 60 minutes after intraneural injection in experiment 1 (5 per group). Sensory and motor functions were assessed until the return of normal sensory and motor functions, and histopathological and ultrastructure analysis were performed at 4 weeks after intraneural injection in experiment 2 (8 per group). Results Dexmedetomidine with ropivacaine better enhanced sensory and motor blockade than ropivacaine alone. IL-6 (3.2 ± 1.0 vs 5.9 ± 2.1), IL-1β (1.1 ± 0.1 vs 2.2 ± 0.7) levels, scores of axon and myelinated fiber degeneration (1 [0–2] vs 2 [1–3]), and demyelinated fiber percentages (20.1 ± 10.4 vs 48.3 ± 12.7) were lower in the ropivacaine plus dexmedetomidine group than in the ropivacaine group. No animals showed any signs of permanent neurological deficit. Conclusions Intraneural dexmedetomidine has sensory and motor blockade-enhancing effects, anti-inflammatory properties, and protective effects against neural injury. These findings suggest that dexmedetomidine as an adjuvant has beneficial effects in rat when intraneural injection of local anesthetic occurs. Accepted for publication October 4, 2017. Address correspondence to: Deok-hee Lee, MD, PhD, Department of Anesthesiology and Pain Medicine, College of Medicine, Yeungnam University, 170, Hyeonchung-ro, Nam-gu, Daegu, Republic of Korea (e-mail: dhlee415@ynu.ac.kr). The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FSuA9q

Low-level clonal FGFR2 amplification defines a unique molecular subtype of intrahepatic cholangiocarcinoma in a Chinese population

Publication date: Available online 4 March 2018
Source:Human Pathology
Author(s): Xiao-Hong Pu, Qing Ye, Jun Yang, Hong-Yan Wu, Xi-Wei Ding, Jiong Shi, Liang Mao, Xiang-Shan Fan, Jun Chen, Yu-Dong Qiu, Qin Huang
Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer rarely curable by surgery that is increasing rapidly in incidence. Chromosomal translocations and amplifications of the fibroblast growth factor receptor 2 (FGFR2) locus are present in several kinds of tumors including ICC, but their incidence has not been assessed in Chinese patients. Using break-apart probes and by determining the ratios of FGFR2/chromosome enumeration probe (CEP) 10 double-color probes, we evaluated 122 ICCs for the presence of FGFR2 translocations and amplifications, respectively, by fluorescence in situ hybridization (FISH). We further determined FGFR2 protein expression by immunohistochemistry and analyzed the clinicopathologic records of the patients. Eight tumors (6.6%) had FGFR2 translocations, whereas 15 (12.3%) had low-level FGFR2 amplification. Interestingly, the tumors that showed both translocation and low-level amplification frequently were of the mass-forming (MF) type. Compared with the ICCs with normal FGFR2s, tumors with amplifications secreted less mucus (P = .017) and typically were accompanied by hepatitis B virus infection (P = .004). Tumors with low-level amplification generally were of lower stage (P = .013) and associated with better overall survival (P = .017). As tumors with FGFR2 amplification exhibit different biology from lesions with a normal gene, low-level amplification of FGFR2 may play an important role in tumor progression and may be a marker for targeted therapy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FnBWny

Phosphaturic Mesenchymal Tumor Without Osteomalacia: Additional Confirmation of the “Non-Phosphaturic” Variant, with Emphasis on the Roles of FGF23 Chromogenic in situ Hybridization and FN1-FGFR1 Fluorescence in situ Hybridization

Publication date: Available online 4 March 2018
Source:Human Pathology
Author(s): Kimberley N Sent-Doux, Craig Mackinnon, Jen-Chieh Lee, Andrew L Folpe, Omar Habeeb
Phosphaturic Mesenchymal Tumor (PMT) is a rare, histologically distinctive neoplasm, which classically presents with phosphaturia and tumor-induced osteomalacia (TIO) (i.e., oncogenic osteomalacia). Both the phosphaturia and TIO are due to paraneoplastic production of FGF23 (a phosphatonin) by the neoplastic cells, which are genetically characterized by rearrangements of FN1 (most often with FGFR1 – and less frequently with FGF1). However, rare cases of PMT present without phosphaturia and TIO (i.e., the "non-phosphaturic" variant) – and are therefore much more challenging to diagnose. Here, we report the first case of a genetically confirmed, non-phosphaturic PMT – in which the correct diagnosis was established through a combination of careful histological evaluation, FGF23 chromogenic in situ hybridization (CISH), and fluorescence in situ hybridization (FISH) testing for FN1-FGFR1.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2H5sSRd

Propranolol prevents liver cirrhosis by inhibiting hepatic stellate cell activation mediated by the PDGFR/Akt pathway

Publication date: Available online 4 March 2018
Source:Human Pathology
Author(s): Qian Ding, Zhen Li, Bin Liu, Liping Ling, Xiangguo Tian, Chunqing Zhang
Propranolol is known to reduce portal pressure by decreasing blood flow to the splanchnic circulation and the liver. However, it is unknown if propranolol improves fibrogenesis and sinusoidal remodeling in the cirrhotic liver. The aim of this study was to investigate the therapeutic effects of propranolol on carbon tetrachloride (CCl4)-induced liver fibrosis in a mouse model and the intrinsic mechanisms underlying those effects. In this study, a hepatic cirrhosis mouse model was induced by CCl4 administration for 6weeks. Propranolol was simultaneously administered orally in the experimental group. Liver tissue and blood samples were collected for histological and molecular analyses. LX-2 cells induced by platelet-derived growth factor-BB (PDGF-BB) were used to evaluate the anti-fibrogenic effect of propranolol in vitro. The results showed that treatment of mice with CCl4 induced hepatic fibrosis, as evidenced by inflammatory cell infiltration, collagen deposition and abnormal vascular formation in the liver tissue. All these changes were significantly attenuated by propranolol treatment. Furthermore, we also found that propranolol inhibited PDGF-BB-induced hepatic stellate cell migration, fibrogenesis, and PDGFR/Akt phosphorylation. Taken together, propranolol might prevent CCl4-induced liver injury and fibrosis at least partially through inhibiting the PDGF-BB-induced PDGFR/Akt pathway. The anti-fibrogenic effect of propranolol may support its status as a first-line treatment in patients with chronic liver disease.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FnBW72

Classic biphasic pulmonary blastoma: a case report and review of the literature

Publication date: Available online 3 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Hervé Le Caer

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CZHUWf

Transoral robotic excision of laryngeal papillomas with Flex® Robotic System — A novel surgical approach

Publication date: Available online 3 March 2018
Source:American Journal of Otolaryngology
Author(s): Bernard Tan Wen Sheng, Patrick Wong, Constance Teo Ee Hoon
IntroductionRecurrent respiratory papillomatosis results in hoarseness, stridor and airway obstruction. Management is surgical, with most surgeons using microdebrider or laser. Transoral robotic surgery (TORS) has been successfully utilised for the excision of oropharyngeal malignancies and paediatric airway surgery. This is the first case report of TORS being used for the excision of laryngeal papillomas.Case reportA 36 year old Chinese female was diagnosed with juvenile onset recurrent respiratory papillomatosis. She had 4 previous laryngeal surgeries. She was pregnant in her 2nd trimester and experienced rapid progression of her disease, leading to impending airway compromise. At her latest surgery (2 years ago), poor laryngeal exposure was encountered during laryngoscopy which made the surgery technically challenging. Thus, a flexible robotic system (Flex® Robotic System, Medrobotics Corporation, Raynham, Massachusetts, USA) was utilised with the aim of providing better surgical exposure. During surgery, laryngeal intubation was not possible and her airway was secured with needle cricothyroidotomy followed by tracheotomy. Transoral robotic excision of laryngeal papillomas was performed successfully. Complete excision of obstructing papillomas was achieved with postoperative restoration of airway and voice.DiscussionUtilisation of TORS improved visualisation, dexterity and access. Drawbacks include cost, set up time, requirement for special equipment and advanced training. TORS approach can be considered as an alternative to the usual laryngoscopic technique, especially in cases where difficult anatomy and poor laryngeal exposure is anticipated.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CYxohW

Does blindness affect ocular vestibular evoked myogenic potentials?

Publication date: Available online 3 March 2018
Source:American Journal of Otolaryngology
Author(s): Ali Bayram, Mehmet Kalkan, Nuri Ünsal, Ahmet Kale, Bekir Küçük, Cemil Mutlu
ObjectiveThe aim of the present study was to investigate the influence of blindness on ocular vestibular evoked myogenic potentials (oVEMP) responses.MethodsThirty-one subjects with unilateral blindness (UB group) and 25 age and sex-matched healthy subjects (control group) were recruited for the present study. The oVEMP responses including latency, amplitude and amplitude asymmetry ratio (AR) were measured and compared between the blind side, the contralateral eye of the UB group and the control subjects.ResultsOcular VEMP recordings were obtained from 29 of 31 patients (93.5%) for the blind side of the UB group. There was no significant difference in terms of latency, amplitude and AR value between the blind side and the contralateral eye of the UB group and the control subjects.ConclusionClear oVEMP recordings can be elicited as long as the eyeball and extraocular muscles are preserved in a blind eye.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FQYuL8

Dynamic imaging with sialography combined with sialendoscopy to manage a foreign body in Stensen's duct

Publication date: Available online 3 March 2018
Source:American Journal of Otolaryngology
Author(s): C. Blake Sullivan, Henry Hoffman
ObjectiveWe describe sialography as a dynamic imaging modality useful in establishing the diagnosis and planning for treatment of a parotid gland ductal foreign body.MethodsChart and radiographic imaging review of a 75 year-old male who had obstructive sialadenitis symptoms two years after welding slag pierced the cheek skin and identified as a 'piece of steel stuck in his cheek'.ResultsSialography was used to demonstrate a foreign body adjacent to the parotid gland to indicate its presence as a mobile element within the ductal system associated with marked pre-obstructive duct dilation. Sialendoscopy was used to successfully remove the foreign body.ConclusionsIn selected cases, the management of obstructive sialadenitis can be improved with sialography in permitting dynamic imaging of salivary duct anatomy. Although ultrasound has evolved as a standard component of salivary gland assessment, sialography may complement imaging with ultrasound (or CT as in this case) to offer the highest acuity definition of the salivary ducts.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CXoT77

Commentary on letter to editor titled “The clinical value of the RGB value of an image of the interarytenoid area for diagnosis of laryngopharyngeal reflux”

Publication date: Available online 4 March 2018
Source:American Journal of Otolaryngology
Author(s): Anindya Nayak

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FR8Bzw

Intraoperative Neuromonitoring During Sciatic Nerve Schwanomma Excision: Utility of Evoked Potentials

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2I1bsa1

Technical Aspects of Awake Craniotomy with Mapping for Brain Tumors in a Limited Resource Setting

Publication date: May 2018
Source:World Neurosurgery, Volume 113
Author(s): Rafael Teixeira Magalhaes Leal, Bruno Mendonça Barcellos, Jose Alberto Landeiro
BackgroundBrain tumor surgery near or within eloquent regions is increasingly common and is associated with a high risk of neurologic injury. Awake craniotomy with mapping has been shown to be a valid method to preserve neurologic function and increase the extent of resection. However, the technique used varies greatly among centers. Most count on professionals such as neuropsychologists, speech therapists, neurophysiologists, or neurologists to help in intraoperative patient evaluation. We describe our technique with the sole participation of neurosurgeons and anesthesiologists.MethodsA retrospective review of 19 patients who underwent awake craniotomies for brain tumors between January 2013 and February 2017 at a tertiary university hospital was performed. We sought to identify and describe the most critical stages involved in this surgery as well as show the complications associated with our technique.ResultsPreoperative preparation, positioning, anesthesia, brain mapping, resection, and management of seizures and pain were stages deemed relevant to the accomplishment of an awake craniotomy. Sixteen percent of the patients developed new postoperative deficit. Seizures occurred in 24%. None led to awake craniotomy failure.ConclusionsWe provide a thorough description of the technique used in awake craniotomies with mapping used in our institution, where the intraoperative patient evaluation is carried out solely by neurosurgeons and anesthesiologists. The absence of other specialized personnel and equipment does not necessarily preclude successful mapping during awake craniotomy. We hope to provide helpful information for those who wish to offer function-guided tumor resection in their own centers.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FjJtUf

Cerebellar Peduncle Localized Oligodendroglioma: Case Report and Review of the Literature

Publication date: May 2018
Source:World Neurosurgery, Volume 113
Author(s): Oguz Baran, Omur Kasimcan, Hakan Oruckaptan
BackgroundOligodendrogliomas constitute 5% of all primary brain tumors and are the third most common cancer among intracranial tumors. More than 90% of oligodendrogliomas have supratentorial localization. Oligodendrogliomas arising in cerebellar peduncle are substantially rare, <1%. Up to now, 6 oligodendroglioma cases with cerebellar peduncle localization have been presented. We aimed to discuss our World Health Organization grade II oligodendroglioma case, which originated from cerebellar peduncle in the light of literature.Case DescriptionWe report a case of 43-year-old woman. Her complaints were headache, perioral numbness and gait abnormality. Magnetic resonance imaging revealed cyst-like well-demarcated lesion localized in right cerebellar peduncle. Tumor excision was performed by turning around the tumor.ConclusionIt should be kept in mind that oligodendrogliomas may be present as cerebellar peduncle localized tumors.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2H2LW2I

Next-generation Sequencing Reveals Recurrent Somatic Mutations in Small Cell Neuroendocrine Carcinoma of the Uterine Cervix

Small cell neuroendocrine carcinoma (SCNEC) of the uterine cervix is a rare but extremely aggressive tumor. While high-risk human papillomavirus (HPV) is involved at an early stage of oncogenesis in many tumors, additional driving events have been postulated to facilitate the progression of SCNECs. Identification of oncogenic drivers could guide targeted therapy of this neoplasm. Clinicopathologic features of 10 cervical SCNECs are reported. Analyses included immunohistochemical evaluation of p16, p53, synaptophysin, and chromogranin expression; in situ hybridizations and polymerase chain reaction for high-risk HPV and/or HPV 18; and next-generation sequencing based on a 637-gene panel. The patients ranged in age from 28 to 68 years (mean, 45.6 y; median, 40.5 y). All tumors had diffuse p16 and synaptophysin expression. All but 1 tumor was positive for chromogranin (extent of staining ranged from focal to diffuse). HPV 18 was detected in 6 tumors and HPV 35 in 1 tumor. At least 1 driver mutation was detected in 8 tumors. Four cases harbored TP53 somatic mutations, 3 of which correlated with an aberrant p53 staining pattern. Four PIK3CA mutations (p.G106A, p.N345T, p.E545K, and p.E545D) were detected in 3 tumors, 2 of which also harbored TP53 mutations. Oncogenic driver mutations involving KRAS, Erbb2, c-Myc, NOTCH1, BCL6, or NCOA3 were detected in 4 tumors. Mutations in caretaker tumor suppressors PTEN, RB1, BRCA1, BRCA2, and ARID1B were also identified in 4 tumors that commonly coharbored activating oncogenic mutations. Targeted next-generation gene sequencing identified genetic alterations involving the MAPK, PI3K/AKT/mTOR, and TP53/BRCA pathways in SCNECs. The presence of genetic alterations that are amenable to targeted therapy in SCNECs offers the potential for individualized management strategies for treatment of this aggressive tumor. D.X. and G.Z. contributed equally. Conflicts of Interest and Source of Funding: Career Development Award by the Cervical Cancer SPORE program at Johns Hopkins (D.X.). The remaining authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Deyin Xing, MD, PhD, Department of Pathology, The Johns Hopkins Hospital, Weinberg 2242, 401 N. Broadway, Baltimore, MD 21231 (e-mail: dxing2@jhmi.edu). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CWrZZ1

Intralymphatic Spread is a Rare Finding Associated With Poor Prognosis in Diffuse Large B-Cell Lymphoma With Extranodal Involvements

Intralymphatic spread is common in solid cancers, but has been rarely studied in lymphomas. Review of 635 extranodal specimens from 475 diffuse large B-cell lymphoma (DLBCL) patients revealed intralymphatic spread in 10 surgical resection specimens from 10 patients including 9 de novo DLBCLs and 1 Richter transformation. The prevalence in de novo DLBCL with extranodal involvements was 1.65%. The most common involved site of intralymphatic spread was the gastrointestinal tract, followed by the female genital tract and breasts. Lymphatic vessels, lined by D2-40-positive endothelial cells, were expanded by lymphoma cells, reminiscent of intravascular lymphoma or tumor emboli. None of the involved lymphatic vessels were located in the mucosa. Patients with intralymphatic spread had a trend of lower overall response rate and a trend of higher progressive disease than those without intralymphatic spread. Compared with patients without intralymphatic spread, those patients with intralymphatic spread had a shorter median overall survival (14.3 vs. 96.2 mo; P=0.004) and a shorter median progression-free survival (11.2 vs. 64.2 mo; P=0.01), respectively. Multivariate analyses showed that intralymphatic spread was an independent poor prognostic factor for overall survival (hazard ratio, 3.029; 95% confidence interval, 1.315-6.978; P=0.009), irrespective of the National Comprehensive Cancer Network-International Prognostic Index, B symptoms, and serum albumin levels. Among patients who underwent surgical resection, intralymphatic spread was still an independent prognostic factor. In conclusion, our study demonstrated extranodal intralymphatic spread in DLBCL. Inspiringly, this rare morphologic finding may serve as a new negative prognostic indicator in DLBCL with extranodal involvements. Conflicts of Interest and Source of Funding: Supported by Department of Medical Research, National Taiwan University Hospital (105N-3211 and UN106-016). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Shan-Chi Yu, MD, Department of Pathology, National Taiwan University Hospital, Room 03-104, No. 7, Chung-Shan South Road, Taipei 100, Taiwan (e-mail: b88401002@ntu.edu.tw). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FQg8hZ

Inflammatory Myofibroblastic Tumor Associated With the Placenta: Short Tandem Repeat Genotyping Confirms Uterine Site of Origin

Inflammatory myofibroblastic tumor (IMT) is a neoplasm of intermediate malignant potential that only rarely involves the gynecologic tract. Several cases of IMT arising in various locations including the lung, bladder, trachea, and breast in association with pregnancy have been reported in the literature, and 3 cases involving the placenta have been previously described. We report 2 cases of IMT identified in association with pregnancy; the first was an intrauterine mass delivered entirely separate from the placenta and fetus, and the second was an incidental mass identified within the placental parenchyma following delivery. Short tandem repeat genotyping was used to compare tissue from the tumor and the placenta for both cases. Both tumors were determined to be of maternal origin, confirming that uterine IMTs may present within the placenta or as a separate mass following delivery. This demonstrates the utility of short tandem repeat genotyping in determining the origin of tumors presenting in association with the placenta. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Sarah E. Umetsu, MD, PhD, Department of Pathology, University of California, San Francisco, 505 Parnassus Avenue, Room M551A, Box 0102, San Francisco, CA 94143-0102 (e-mail: sarah.umetsu@ucsf.edu). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CYal75

Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups

Our aim was to investigate whether molecular classification can be used to refine prognosis in grade 3 endometrial endometrioid carcinomas (EECs). Grade 3 EECs were classified into 4 subgroups: p53 abnormal, based on mutant-like immunostaining (p53abn); MMR deficient, based on loss of mismatch repair protein expression (MMRd); presence of POLE exonuclease domain hotspot mutation (POLE); no specific molecular profile (NSMP), in which none of these aberrations were present. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method (Log-rank test) and univariable and multivariable Cox proportional hazard models. In total, 381 patients were included. The median age was 66 years (range, 33 to 96 y). Federation Internationale de Gynecologie et d'Obstetrique stages (2009) were as follows: IA, 171 (44.9%); IB, 120 (31.5%); II, 24 (6.3%); III, 50 (13.1%); IV, 11 (2.9%). There were 49 (12.9%) POLE, 79 (20.7%) p53abn, 115 (30.2%) NSMP, and 138 (36.2%) MMRd tumors. Median follow-up of patients was 6.1 years (range, 0.2 to 17.0 y). Compared to patients with NSMP, patients with POLE mutant grade 3 EEC (OS: hazard ratio [HR], 0.36 [95% confidence interval, 0.18-0.70]; P=0.003; RFS: HR, 0.17 [0.05-0.54]; P=0.003) had a significantly better prognosis; patients with p53abn tumors had a significantly worse RFS (HR, 1.73 [1.09-2.74]; P=0.021); patients with MMRd tumors showed a trend toward better RFS. Estimated 5-year OS rates were as follows: POLE 89%, MMRd 75%, NSMP 69%, p53abn 55% (Log rank P=0.001). Five-year RFS rates were as follows: POLE 96%, MMRd 77%, NSMP 64%, p53abn 47% (P=0.000001), respectively. In a multivariable Cox model that included age and Federation Internationale de Gynecologie et d'Obstetrique stage, POLE and MMRd status remained independent prognostic factors for better RFS; p53 status was an independent prognostic factor for worse RFS. Molecular classification of grade 3 EECs reveals that these tumors are a mixture of molecular subtypes of endometrial carcinoma, rather than a homogeneous group. The addition of molecular markers identifies prognostic subgroups, with potential therapeutic implications. Present address: Douglas A. Levine, MD, New York University Langone Medical Center, New York, NY. Conflicts of Interest and Sources of Funding: Supported in part by the Dutch Cancer Society (KWF-UL2012-5719) (Dr Bosse, Dr Nout) and in part through the NIH/NCI Support Grant P30 CA008748 (Dr Abu-Rustum, Dr Levine, Dr Soslow). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Robert A. Soslow, MD, Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (e-mail: soslowr@mskcc.org). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FRQh9C

Differentiated Vulvar Intraepithelial Neoplasia-like and Lichen Sclerosus-like Lesions in HPV-associated Squamous Cell Carcinomas of the Vulva

Most human papillomavirus (HPV)-associated vulvar squamous cell carcinomas (VSCCs) originate from high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia. However, growing evidence suggests that morphologic studies have limitations in predicting HPV status in vulvar lesions. We aimed to evaluate adjacent intraepithelial lesions in a series of DNA HPV-positive VSCCs, focusing on unusual histologic patterns mimicking differentiated vulvar intraepithelial neoplasia (dVIN) or lichen sclerosus (LS). We identified 326 DNA HPV-positive VSCC with at least 1 cm of skin adjacent to the invasive tumor and analyzed HPV typing, HPV E6*I mRNA, and p16 immunohistochemistry in all cases. A careful histologic evaluation was conducted. A conclusive association with HPV was based on a positive p16 or HPV E6*I mRNA result or both in addition to the HPV DNA, whereas cases negative for both markers were classified as nonconclusively associated with HPV. One hundred twenty-one tumors (37.1%) had normal adjacent skin, 191 (58.6%) had only high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia, and unusual intraepithelial lesions were identified in 14 (4.3%) tumors. Seven cases showed dVIN-like features, 5 showed adjacent LS-like lesion, and in 2 cases dVIN-like and LS-like lesions were identified simultaneously. Six of them were conclusively associated with HPV (3 dVIN-like, 2 LS-like, 1 with combined dVIN/LS-like features). All 6 tumors were associated with HPV16 and were positive for both p16 and HPV mRNA, and p16 was also positive in the dVIN-like and LS-like lesions. In summary, a small subset of VSCCs conclusively associated with HPV may arise on intraepithelial lesions, mimicking precursors of HPV-independent VSCC. Conflicts of Interest and Source of Funding: L.A., S.d.S., and B.Q. have received occasional travel fund to attend scientific meetings from Merck. The remaining authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Jaume Ordi, MD, PhD, Department Pathology, Hospital Clinic, C/Villarroel 136, Barcelona 08036, Spain (e-mail: jordi@clinic.ub.es). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FcKvhL

Histopathologic Features of Postablation Tubal Sterilization Syndrome

Postablation tubal sterilization syndrome (PATSS) is an uncommon complication of endometrial ablation in patients with antecedent tubal ligation characterized by cyclic pelvic pain. Recurrent tubal distention resulting from retrograde menstruation into occluded proximal fallopian tube segments by residual/regenerated cornual endometrial tissue is postulated to be the cause. Reports of PATSS have largely focused on the clinicoradiologic and operative findings. Detailed descriptions of the gross pathologic findings of PATSS are sparse and rarer still are examples in which the histologic manifestations are discussed. Three patients with a history of tubal ligation and subsequent endometrial ablation who underwent hysterectomy and bilateral salpingo-oophorectomy for pelvic pain were identified. A clinical suspicion of PATSS was conveyed to the pathologist at the time of initial pathologic examination in only 2 of the 3 cases. Pathologic findings in all 3 cases were similar and included hematosalpinx of the proximal fallopian tubes, intraluminal hemosiderotic material, mural hemosiderosis, and pseudoxanthomatous salpingitis featuring plical and mural lipofuscin-laden macrophages, along with inactive to attenuated endometrium with variable submucosal myometrial hyalinization/scarring compatible with postablative changes. The pathologic features, in conjunction with the appropriate clinicoradiologic findings, were interpreted as consistent with PATSS. PATSS complicates an estimated 5% to 10% of endometrial ablations, but is likely underreported due to a lack of awareness. Pathologists should consider PATSS in hysterectomy specimens that show postablative endometrial changes accompanied by hematosalpinx and pseudoxanthomatous salpingitis of the proximal segments of ligated fallopian tubes. To our knowledge, this is the first study to depict the histopathologic features of PATSS. Presented in part at the 105th Annual Meeting, United States and Canadian Academy of Pathology, Seattle, WA, in March 2016. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Kelly J. Butnor, MD, Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, 111 Colchester Ave., ACC Bldg., EP2-120, Burlington, VT 05401 (e-mail: kelly.butnor@uvmhealth.org). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FQipda

Renal Interstitial Exhaustion and SGLT2 Blockers

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FdNE0L

Pulse Pressure and Carotid Artery Doppler Velocimetry as Indicators of Maternal Volume Status: A Prospective Cohort Study

BACKGROUND: Narrow pulse pressure has been demonstrated to indicate low central volume status. In critically ill patients, volume status can be qualitatively evaluated using Doppler velocimetry to assess hemodynamic changes in the carotid artery in response to autotransfusion with passive leg raise (PLR). Neither parameter has been prospectively evaluated in an obstetric population. The objective of this study was to determine if pulse pressure could predict the response to autotransfusion using carotid artery Doppler in healthy intrapartum women. We hypothesized that the carotid artery Doppler response to PLR would be greater in women with a narrow pulse pressure, indicating relative hypovolemia. METHODS: Intrapartum women with singleton gestations ≥35 weeks without acute or chronic medical conditions were recruited to this prospective cohort study. Participants were grouped by admission pulse pressure as

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FQwEP6

The Amazing Language of Medicine: Understanding Medical Terms and Their Backstories

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2D10e1y

The Effect of Repeated Versus Initial Procalcitonin Measurements on Diagnosis of Infection in the Intensive Care Setting: A Prospective Observational Study

Procalcitonin (PCT) measurement has been proposed to direct antibiotic use. We examined whether repeated PCT measurements (0, 6, and/or 12 hours) versus the initial measurement only (time 0) increased the sensitivity and specificity of PCT for diagnosing infection in intensive care unit patients. Infection was identified in 67/176 (38%) patients. The sensitivity of repeated versus the initial PCT measurement (with a cutoff value 0.5 ng/mL) was 52/67 (77%; 95% confidence interval [CI], 66%–87%) vs 46/67 (69%; 95% CI, 56%–79%; P = .04) and specificity 60/109 (55%; 95% CI, 45%–65%) vs 59/109 (54%; 95% CI, 44%–64%; P = 1.0). Repeat PCT evaluations over 12 hours did not provide a clinically significant improvement in diagnostic accuracy when compared to the initial single test. Accepted for publication January 17, 2018. P. D. Levin and M. J. Cohen contributed equally to this article. Funding: This study was supported by Brahms and Siemens, which provided the procalcitonin kits at no cost. The authors declare no conflicts of interest. The information in this study was presented in part at the European Society of Intensive Care Medicine (ESICM) 27th Annual Congress, Barcelona, 2014. Reprints will not be available from the authors. Address correspondence to Shmuel Benenson, MD, MSc, Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Center, PO Box 12000, Jerusalem 9112001, Israel. Address e-mail to Benenson@Hadassah.org.il. © 2018 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FRKkcN

Description of a Novel Set-Up for Functional Echocardiographic Assessment of Left Ventricular Performance During Ex Vivo Heart Perfusion

Ex vivo heart perfusion (EVHP) is a new technology aimed at decreasing cold ischemia time and evaluating cardiac function before transplanting a donor heart. In an experimental EVHP swine model, we tested a 3D-printed custom-made set-up to perform surface echocardiography on an isolated beating heart during left ventricular loading. The views obtained at any time point were equivalent to standard transesophageal and transthoracic views. A decrease in left ventricular function during EVHP was observed in all experiments. Accepted for publication December 29, 2017. Funding: This study was supported by the Peter Munk Cardiac Foundation, private donation, and the University of Toronto Anesthesia Merit Award. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Massimiliano Meineri, MD, FASE, Department of Anesthesia, Toronto General Hospital, 200 Elizabeth St EN 3–442, Toronto, ON, M5G 2C4, Canada. Address e-mail to Massimiliano.Meineri@uhn.ca. © 2018 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FdNnLh

The Association of Targeted Cell Salvage Blood Transfusion During Cesarean Delivery With Allogeneic Packed Red Blood Cell Transfusions in a Maternity Hospital in China

BACKGROUND: Autologous transfusion of intraoperative cell salvage blood may be a potential method to decrease the need for allogeneic packed red blood cell transfusions after cesarean delivery, although there are limited data on the benefits of this method. This study evaluated the implementation of targeted intraoperative cell salvage during cesarean delivery in women at increased risk for hemorrhage at the Women's and Children's Hospital in Ningbo, China. METHODS: All women who underwent cesarean delivery >28 weeks of gestation were included in the study. The period before intraoperative cell collection (October 1, 2010, to August 31, 2012, n = 11,322) was compared with the postimplementation period (September 1, 2012, to June 30, 2015, n = 17,456) using an interrupted time series analysis. In the postimplementation period, women suspected to be at increased risk of the need for a blood transfusion (1604, 9.2%) underwent intraoperative cell salvage collection. The primary outcomes were the monthly rate of allogeneic packed red blood cell use and the incidence of clinical manifestation of acute blood transfusion reactions. RESULTS: The mean (standard deviation) estimated monthly allogeneic packed blood cell transfusion rate at the end of the 57-month study was 2.2% ± 0.7% with the implementation compared with 2.7% ± 0.9% without, difference −0.5%, 95% CI, −1.4% to 0.3%; P = .22. The mean number of allogeneic units transfused per patient was 4.1 ± 0.4 units with implementation and 3.9 ± 0.9 units without, difference 0.2, 95% CI, −1.7 to 1.1 units; P = .69. Intraoperative cell salvage blood was reinfused in 757 (47%) and wasted in 847 (53%) cases. The monthly intraoperative allogeneic packed red blood cells use rate was lower after implementation (difference −0.7%, 95% CI, −0.1% to −1.4%; P = .03); however, the monthly postpartum allogeneic packed red blood cell use rate was unchanged (difference −0.2%, 95% CI, −0.4% to 0.7%; P = .56). The clinical manifestation of acute blood transfusion reactions rate was unchanged (difference −2%, 99% CI, −9% to 5%; P = .55) between the periods. CONCLUSIONS: Our findings suggest that targeted intraoperative cell salvage in women undergoing cesarean delivery was associated with less allogeneic blood exposure in the operating room, but not in the postoperative period. Intraoperative cell salvage in targeted cesarean deliveries was not associated with a lesser allogeneic red blood cell exposure over the hospital admission period. The lack of adverse events associated with intraoperative cell salvage supports the safety of intraoperative cell salvage in cesarean delivery. Accepted for publication January 8, 2018. Funding: None. R. J. McCarthy is currently affiliated with the Department of Anesthesiology, Rush University Medical Center, Chicago, Illinois. Conflicts of Interest: See Disclosures at the end of the article. The study was presented at the 2015 Annual Meeting of the American Society of Anesthesiologists, October 24–28, San Diego, CA. Reprints will not be available from the authors. Address correspondence to Robert J. McCarthy, PharmD, Department of Anesthesiology, Rush University Medical Center, 1653 W. Congress Pkwy, Chicago, IL 60612. Address e-mail to robert_j_mccarthy@rush.edu. © 2018 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2FRKfpv

Αρχειοθήκη ιστολογίου

Κυριακή 4 Μαρτίου 2018

Abstract

Abstract

Purpose

Methods

Results

Conclusions

Background

Aims and objective

Materials and methods

Results

Conclusion

Introduction

Materials and methods

Results

Conclusion

Abstract

Background

Objective

Methods

Main outcome measures

Results

Conclusions

Abstract

Purpose

Methods

Results

Conclusions

Abstract

Background

Objective

Methods

Main outcome measures

Results

Conclusions

Abstract

Purpose

Methods

Results

Conclusions

Abstract

Background

Methods

Results

Conclusions

Abstract

Purpose

Methods

Results

Conclusions

Abstract

Abstract

Abstract

Abstract

Purpose

Methods

Results

Conclusions

Abstract

Abstract

Objectives

Study design

Setting

Patients and methods

Results

Conclusions

Abstract

Objectives

Study design

Setting

Patients and methods

Results

Conclusions

Abstract

Purpose

Methods

Results

Conclusions

Abstract