CDKN2BAS gene polymorphisms and the risk of intracranial aneurysm in the Chinese population

CDKN2BAS gene polymorphisms has been shown to correlation with intracranial aneurysm(IA) in the study of foreign people. The study, the author selected the Chinese people as the research object to explore whet...

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

Secondary pallidonigral degeneration mimicking recurrent acute stroke in clinical presentation and magnetic resonance imaging: a case report

Secondary pallidonigral transneuronal degeneration after a remote primary cerebral infarct can mimic recurrent stroke at clinical presentation. We describe a patient with secondary pallidonigral degeneration f...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C5iUhi

Factors Associated With Lack of Vision Improvement in Children With Cortical Visual Impairment

Background: Improvement in vision has been noted in children with cortical visual impairment (CVI), resulting from disparate types of brain injury. The purpose of our study was to determine the risk factors associated with poor recovery of vision in this group of patients. Methods: Case records of children who were born before 2010 with at least 4 follow-up visits for CVI were reviewed for underlying etiologies of CVI, visual acuity (VA), and associated neurological and ophthalmological disorders. VA was assessed in 6 qualitative grades. Changes in VA were recorded as the difference between the grades of VA at presentation and the last follow-up visit. The outcome was calculated as a ratio of actual improvement to potential improvement in grades of qualitative VA. Multiple linear regression determined factors associated with lack of vision improvement in all children and based on etiology. Results: Fifty-three children with CVI were identified. The median age at presentation was 13.6 months (range: 2.9–76.4 months) and the median follow-up was 5.8 years (1.1–16.3 years). CVI resulted from central nervous system (CNS) malformation (9.4%), hypoxic/inflammatory injury (15.1%), seizures (24.5%), and combined causes (51.0%). Vision improvement was noted in 83% of children. Lack of VA improvement was associated with older age at presentation in all children with CVI and within each etiological group except CNS malformation. None of the other investigated variables were associated with poor recovery of VA. Conclusions: Most of the children with CVI showed improvement in vision. Older age at presentation, but not etiology of CVI, was associated with poor improvement in VA. Address correspondence to Swati Handa, FRCS, MCI, Pediatric Ophthalmology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899; E-mail: Handa.swati@kkh.com.sg The authors report 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 full text and PDF versions of this article on the journal's Web site (http://ift.tt/2BFTkP1). © 2017 by North American Neuro-Ophthalmology Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C874TJ

Microvascular replantation of a composite facial avulsion in a 24-month-old child after dog bite

Dog bite injuries are common sources of morbidity with an estimated incidence of 4.5 million bites per year with over 350,000 requiring treatment in the emergency room. Children under the age of 14 are most likely to be affected with a peak age of 5–9 years old. We report a case of a 24-month-old female who sustained a large composite facial avulsion injury from a pit bull dog bite. The avulsed tissue involved a substantial portion of the patient's mid-face, including the entire soft tissue of the nose, upper lip, part of the left cheek, and left oral commissure. Artery-only microvascular replantation was performed because no recipient vein could be identified from the facial defect. Medicinal leech therapy was used for eight days postoperatively to prevent venous congestion. The patient experienced significant blood loss due to leech therapy and required nearly 29 L of blood product replacement. At the last follow up of 8 months postoperatively, the patient was recovering well with significant improvement in function and cosmesis of the mid-face. This case describes a successful artery-only replantation of an avulsive bite injury to the face of a young child. Despite the technical difficulty of cases such as this one, microvascular replantation should be attempted because when successful it provides a superior cosmetic and functional result to other reconstructive techniques.

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

Factors affecting the outcomes of direct pulp capping using Biodentine

Abstract

Introduction

This study aimed to evaluate the prognostic value of factors with regard to the treatment outcome of direct pulp capping using Biodentine (Septodont, Saint-Maur-des-Fossés, France), in permanent teeth in which the pulps were exposed during caries removal.

Methods

Between 2010 and 2014, 112 teeth with deep carious lesions underwent direct pulp capping. The patients were followed up at 2–3 months and 1–1.5 years with a routine examination on both recall visits. Periapical radiographs were taken at 1–1.5 years. Lack of patient complaints, positive reactions to cold and electric testing, no sensitivity to percussion, and no widening of the periapical ligament indicated success. The Fisher exact test was used for statistical analysis. The significance level was P = .05.

Results

Eighty-six teeth were available for 1–1.5 years follow-up. The overall success rate was 82.6%. Only age had a significant effect on the pulpal survival rate: the success rate was 90.9% in patients younger than 40 years and 73.8% in patients 40 years or older (P = .0480). Sex, initial or secondary caries treatment, occlusal or cervical/proximal caries, delayed placement of permanent filling, tooth position, and arch type did not influence the outcome.

Conclusions

A patient's age influenced the outcome of direct pulp capping using this new calcium silicate cement.

Clinical relevance

Asymptomatic vital permanent teeth with cariously exposed pulp can be treated successfully by direct pulp capping using Biodentine.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AbMS1z

Factors affecting the outcomes of direct pulp capping using Biodentine

Abstract

Introduction

This study aimed to evaluate the prognostic value of factors with regard to the treatment outcome of direct pulp capping using Biodentine (Septodont, Saint-Maur-des-Fossés, France), in permanent teeth in which the pulps were exposed during caries removal.

Methods

Between 2010 and 2014, 112 teeth with deep carious lesions underwent direct pulp capping. The patients were followed up at 2–3 months and 1–1.5 years with a routine examination on both recall visits. Periapical radiographs were taken at 1–1.5 years. Lack of patient complaints, positive reactions to cold and electric testing, no sensitivity to percussion, and no widening of the periapical ligament indicated success. The Fisher exact test was used for statistical analysis. The significance level was P = .05.

Results

Eighty-six teeth were available for 1–1.5 years follow-up. The overall success rate was 82.6%. Only age had a significant effect on the pulpal survival rate: the success rate was 90.9% in patients younger than 40 years and 73.8% in patients 40 years or older (P = .0480). Sex, initial or secondary caries treatment, occlusal or cervical/proximal caries, delayed placement of permanent filling, tooth position, and arch type did not influence the outcome.

Conclusions

A patient's age influenced the outcome of direct pulp capping using this new calcium silicate cement.

Clinical relevance

Asymptomatic vital permanent teeth with cariously exposed pulp can be treated successfully by direct pulp capping using Biodentine.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AbMS1z

Beneficial Effects of Exercise Pretreatment in a Sporadic Alzheimer's Rat Model

PURPOSE This study aimed to examine the effects of swimming exercise pretreatment on a streptozotocin (STZ)-induced sporadic Alzheimer's disease rat model and provide an initial understanding of related molecular mechanisms. METHODS Male 2.5-month-old Sprague-Dawley rats were divided into the following 4 groups: a) control, b) swim + vehicle, c) STZ without swim, and d) swim + STZ. The Barnes Maze task and Novel Object Recognition test were used to measure hippocampus-dependent spatial learning and working memory, respectively. Immunofluorescence staining, Western blot analysis, ELISA analysis and related assay kits were used to assess synaptic proteins, inflammatory cytokines, total antioxidant capacity, antioxidant enzymes, amyloid-beta (Aβ) production and tau hyperphosphorylation. RESULTS Behavioral tests revealed that exercise pretreatment could significantly inhibit STZ-induced cognitive dysfunction (p

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iUDl80

PRIME: A Novel Low-Mass, High-Repetition Approach to Improve Function in Older Adults

ABSTRACT Introduction The ability to maintain functional independence in a rapidly aging population results in an increased life expectancy without corresponding increases in health care costs. The accelerated decline in VO2peak after the age of 65 is primarily due to peripheral tissue changes rather than centrally mediated factors. The purpose of this study was to determine if the PRIME (Peripheral Remodeling through Intermittent Muscular Exercise) approach, consisting of a low mass, high repetition/duration skeletal muscle focused training regimen would provide superior functional benefits in participants above 70 years old and at risk for losing functional independence. Methods In this clinical trial, 107 participants were randomized to four weeks of either standard aerobic exercise training (AT) or PRIME [Phase 1]. This was followed by eight weeks of a progressive whole-body aerobic and resistance training (AT+RT) for all participants [Phase 2]. The major outcome measures were cardiorespiratory fitness (peak oxygen consumption-VO2peak), muscular fitness (1 repetition maximal strength -1RM) and physical function (Senior Fitness Test scores-SFT). Results were analyzed under a pro-protocol criterion. Results Thirty-eight PRIME and 38 AT participants completed the 3-month protocols. VO2peak, 1RM, and SFT scores all increased significantly after 12 weeks for both treatment groups (p

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kZ7sj1

Postexercise Fructose-Maltodextrin Ingestion Enhances Subsequent Endurance Capacity

ABSTRACT Purpose Restoring skeletal muscle and hepatic glycogen content during short-term (

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

Composite neuroendocrine tumor and adenocarcinoma of the rectum

Although adenocarcinomas showing neuroendocrine differentiation or those mixed with high-grade neuroendocrine carcinoma (NEC) are sometimes encountered, composite tumors comprising neuroendocrine tumor (NET) G...

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

High riding of brachiocephalic artery: A rare case of pulsatile anterior neck mass

Publication date: Available online 11 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Bao Ling Wong, Shashi Gopalan, Muhammad Nasri Abu Bakar, Ming Huei Wong
Anterior neck swellings are common presentations that are seen in otorhinolaryngology clinics. We presented a rare diagnosis of pulsatile anterior neck swelling where a high riding brachiocephalic artery needs to be considered as a differential diagnosis. This 54-year-old lady presented with anterior neck swelling for one year which appear to be pulsatile, soft and non-tender mass. Ultrasound and Doppler scan, contrast-enhanced computed tomography (CECT) scan revealed that the neck swelling corresponds to the high riding brachiocephalic artery. Hence, ultrasound scan is essential to detect any vascular lesion prior to biopsy or fine needle aspiration cytology as to avoid catastrophic hemorrhage.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jzIne6

Postoperative nausea and vomiting after unrestricted clear fluids before day surgery: A retrospective analysis

BACKGROUND Guidance on pre-operative fluids fasting policy continues to evolve. Current European guidelines encourage the intake of oral fluids up to 2 h before the induction of general anaesthesia. From October 2014, Torbay Hospital Day Surgery Unit commenced an unrestricted fluid policy, encouraging patients to drink clear fluids up until the time of transfer to theatre. OBJECTIVE The aim of this study was to assess the incidence of postoperative nausea and vomiting before and after the change to the unrestricted pre-operative clear oral fluids. DESIGN Retrospective, before and after study. SETTING Single district general hospital between November 2013 and February 2016. PATIENTS A total of 11 500 patients on the day case pathway who were receiving either sedation, general anaesthesia, regional anaesthesia or their combination. The data from these patients were collected routinely. This number of patients represents approximately 78% of all patients before the change in fluids policy and 74% after the change. Exclusions were patients undergoing a termination of pregnancy, or patients undergoing community dental procedures, from whom patient experience data are not collected. INTERVENTION Introduction of a change to the day surgery pathway policy permitting unrestricted clear oral fluids preoperatively until transfer to theatre (from October 2014). MAIN OUTCOME MEASURES Incidence of postoperative nausea and vomiting. RESULTS The rates of nausea within 24 h postoperatively were 270/5192 (5.2%) when patients could not drink within 2 h of surgery, and 179/4724 (3.8%) when patients could drink up until surgery, a relative rate (95% confidence interval) of 0.73 (0.61 to 0.88), P = 0.00074. The corresponding rates of vomiting were 146/5186 (2.8%) and 104/4716 (2.2%), a relative rate (95% confidence interval) of 0.78 (0.61 to 1.00), P = 0.053. CONCLUSION Our data suggest that the liberal consumption of clear fluids before the induction of scheduled day case anaesthesia reduced the rates of postoperative nausea and vomiting. Correspondence to Dr Graham C. McCracken, MB, BCh, BAO, Department of Anaesthetics, Torbay and South Devon NHS Foundation Trust, Lowes Bridge, Torquay TQ2 7AA, Devon, UK E-mail: gmccracken@nhs.net © 2017 European Society of Anaesthesiology

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z2JI2l

Knowledge Translation: the bridging function of Cochrane Rehabilitation

Publication date: Available online 12 December 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Stefano Negrini, Francesca Gimigliano, Chiara Arienti, Carlotte Kiekens
Cochrane Rehabilitation is aimed to ensure that all rehabilitation professionals can apply Evidence Based Clinical Practice and take decisions according to the best and most appropriate evidence in this specific field, combining the best available evidence as gathered by high quality Cochrane systematic reviews, with their own clinical expertise and the values of patients. This mission can be pursued through Knowledge Translation. The aim of this paper is to shortly present what Knowledge Translation is, how and why Cochrane (previously known as Cochrane Collaboration) is trying to reorganize itself in light of Knowledge Translation, and the relevance that this process has for Cochrane Rehabilitation and in the end for the whole world of Rehabilitation.It is well known how it is difficult to effectively apply in everyday life what we would like to do and to apply the scientific knowledge in the clinical field: this is called the "know-do gap". In the field of Evidence Based Medicine, where Cochrane belongs, it has been proven that high quality evidence is not consistently applied in practice. A solution to these problems is the so-called "Knowledge Translation". In this context, Cochrane Rehabilitation is organized to provide the best possible Knowledge Translation in both directions (bridging function), obviously toward the world of rehabilitation (spreading reviews), but also to the Cochrane community (production of reviews significant for rehabilitation). Cochrane is now strongly pushing to improve its KT activities, and this creates a strong base for Cochrane Rehabilitation work, focused not only on spreading the evidence, but also on improving its production to make it more meaningful for the world of rehabilitation.



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

A Cost-Effective, In-House, Positioning and Cutting Guide System for Orthognathic Surgery

Abstract

Introduction

Technological advances in 3D printing can dramatically improve orthognathic surgical planning workflow. Custom positioning and cutting guides enable intraoperative reproduction of pre-planned osteotomy cuts and can result in greater surgical accuracy and patient safety.

Objectives

This short paper describes the use of freeware (some with open-source) combined with in-house 3D printing facilities to produce reliable, affordable osteotomy cutting guides.

Methods

Open-source software (3D Slicer) is used to visualise and segment three-dimensional planning models from imported conventional computed tomography (CT) scans. Freeware (Autodesk Meshmixer ©) allows digital manipulation of maxillary and mandibular components to plan precise osteotomy cuts. Bespoke cutting guides allow exact intraoperative positioning. These are printed in polylactic acid (PLA) using a fused-filament fabrication 3D printer. Fixation of the osteotomised segments is achieved using plating templates and four pre-adapted plates with planned screw holes over the thickest bone. We print maxilla/ mandible models with desired movements incorporated to use as a plating template.

Results

A 3D printer capable of reproducing a complete skull can be procured for £1000, with material costs in the region of £10 per case. Our production of models and guides typically takes less than 24 hours of total print time. The entire production process is frequently less than three days. Externally sourced models and guides cost significantly more, frequently encountering costs totalling £1500–£2000 for models and guides for a bimaxillary osteotomy.

Conclusion

Three-dimensional guided surgical planning utilising custom cutting guides enables the surgeon to determine optimal orientation of osteotomy cuts and better predict the skeletal maxilla/mandible relationship following surgery. The learning curve to develop proficiency using planning software and printer settings is offset by increased surgical predictability and reduced theatre time, making this form of planning a worthy investment.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C4PcZN

A novel technique for superior-based pharyngeal flaps: 10-year results with formal speech outcomes assessment

Publication date: Available online 11 December 2017
Source:American Journal of Otolaryngology
Author(s): Ryan Winters, John Carter, J. Lindhe Guarisco
PurposeDescribe a novel technique for superior-based pharyngeal flaps allowing restoration of bulk to the soft palate and intraoperative fine-tuning of lateral port size, while avoiding midline palate-splitting. Validated speech assessment tools are employed for quantitative analysis.MethodsRetrospective review of all patients who underwent superior-based pharyngeal flap in a 10-year period by a single surgeon. Pittsburgh Weighted Values for Speech Symptoms Associated with VPI and the Goldman-Fristoe Test of Articulation were used for formal speech assessment.Results78 patients met inclusion criteria with clinical data up to 10years postoperatively. 31 patients had congenital velopharyngeal insufficiency (VPI), and the remainder acquired VPI after cleft palate repair or adenoidectomy. 37 patients had a recognized syndrome. All patients noted subjective improvement in nasality, and evaluation with the validated speech assessment tools demonstrated statistically significant improvement in speech. Only one flap takedown was required in a patient with severe midface hypoplasia who developed sleep apnea several years postoperatively.ConclusionsThis technique is successful in congenital and acquired VPI, and in patients with complex craniofacial syndromes. Customization of lateral ports based on preoperative nasopharyngoscopy, and avoidance of a midline palate splitting incision, make this an attractive option for superior-based flap surgery.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jAx4lV

Gastro-pharyngeal reflux and total laryngectomy. Increasing knowledge about its management

Publication date: Available online 11 December 2017
Source:American Journal of Otolaryngology
Author(s): Giuditta Mannelli, Roberto Santoro, Francesco Segala, Elisabetta Surrenti, Oreste Gallo
PurposeInvestigate the incidence, the degree and the effect of gastro-pharyngeal reflux (GPR) in laryngectomised patients.Materials and methodsBehavioral and 24-hour pH- and impedance-monitoring data were prospectively analyzed for 25 laryngectomised patients with no previous history of GER in outpateints' setting. Reflux detected was characterized as either acid, weakly acidic or nonacid. Proximal reflux was found at 15cm above the LES.Results40% of patients presented a pathological number of reflux episodes in the upright position (p<0.0001); 9 of them presented a pathologic bolus exposure time. Bolus exposure at the proximal sphincter was one fourth-fold lower than 5cm above the LES (p=0.3593). There was a prevalence of acid reflux at both sphincters (p<0.0001); liquid reflux was prevalent at the LES (p=0.003) and mixed reflux at the UES (p=0.0001). Median REs was higher than time acid exposure (p=0.0013).ConclusionsPre- and post-surgical reflux investigation could identify preexisting reflux severity and screen potential high-risk cancer patients for postoperative complications. This might allow the early onset of acid suppressive therapy in presence of pathologic findings in high-complication risk cancer patients.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Bg2mWp

Development and characterization of an anthropomorphic breast phantom for permanent breast seed implant brachytherapy credentialing

Publication date: Available online 11 December 2017
Source:Brachytherapy
Author(s): Michael Roumeliotis, Sarah Quirk, Matthew Skarsgard, Tiana Trumpour, Elizabeth Watt, Tyler Meyer
PurposeTo develop an anthropomorphic breast phantom for use in credentialing of permanent breast seed implant brachytherapy.Methods and MaterialsA representative external contour and target volume was used as the basis of mold manufacturing for anthropomorphic breast phantom development. Both target and normal tissue were composed of gel-like materials that provide suitable computed tomography and ultrasound contrast for brachytherapy delivery. The phantoms were evaluated for consistency in construction (target location) and Hounsfield unit (computed tomography contrast). For both target and normal tissue, the speed of sound was measured and compared to the image reconstruction algorithm's expectation value. Five phantoms were imaged preimplant and postimplant to assess interphantom similarity as well as to evaluate the uncertainty in quantifying seed position.ResultsThe average Hounsfield units of the target and normal tissue gels is −146 ± 5 and 23 ± 1, respectively. The average speed of sound of the target and normal tissue gels is 1485 ± 7 m/s and 1558 ± 9 m/s, respectively, resulting in an estimated 0.4 mm uncertainty in image guidance. The registration/deformation uncertainty was determined to be 0.8 mm. The standard combined uncertainty in assessing seed position spatial accuracy, also including a 0.9 mm estimate based on literature for seed localization, is estimated to be 1.3 mm.ConclusionsThe development of the anthropomorphic breast phantom and evaluation of both the consistency as well as overall seed position uncertainty illustrates the suitability of this phantom for use in brachytherapy end-to-end delivery and implant accuracy evaluation. When evaluating a user's implant accuracy, we estimate a standard combined uncertainty of 1.3 mm.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2B7FCqM

Characterizing the impact of adaptive planning on image-guided perineal interstitial brachytherapy for gynecologic malignancies

Publication date: Available online 11 December 2017
Source:Brachytherapy
Author(s): Adam Gladwish, Ananth Ravi, Lisa Barbera, Lucas Mendez, Melanie Davidson, Laura D'Alimonte, David D'Souza, Matt Wronski, Eric Leung
PurposeTo determine the dosimetric impact of organ and implant motion/deformation in the context of adaptive planning in image-guided gynecologic brachytherapy using a 3-fraction transperineal approach.Methods and materialsTwenty-six patients were analyzed. Each patient was treated with three fractions given over a 24-h period using a single insertion. A planning CT scan (±MRI) was acquired before the first fraction. A verification scan was taken within 1 h following the second fraction. A single plan was delivered for Fractions 1 and 2 with an adaptive plan delivered for Fraction 3. Two evaluation frameworks were established. Framework 1 investigated the effects of motion/deformation from both implant and organs. Framework 2 investigated the impact of implant motion/deformation alone. Differences in high-risk clinical target volume (HRCTV) D90%, V100%, and bladder/rectum D2cc were assessed.ResultsFrom implant to verification, the HRCTV D90% and V100% decreased significantly (5.0%, p < 0.01; 3.1%, p < 0.01) and rectal D2cc was significantly higher (12.2%, p = 0.02). Adaptive planning recouped these changes. Implant changes resulted in a reduction in HRCTV dose and coverage, but no significant effect was seen in the bladder or rectum.ConclusionsAdaptive planning represents an important aspect of perineal-based interstitial image-guided brachytherapy given in three fractions; its absence would result in plan degradation.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BBFp0n

Placement of an absorbable rectal hydrogel spacer in patients undergoing low-dose-rate brachytherapy with palladium-103

Publication date: Available online 11 December 2017
Source:Brachytherapy
Author(s): Amandeep S. Taggar, Tomer Charas, Gil'ad N. Cohen, Keeratikarn Boonyawan, Marisa Kollmeier, Sean McBride, Nitin Mathur, Antonio L. Damato, Michael J. Zelefsky
PurposeRates of rectal toxicity after low-dose-rate (LDR) brachytherapy for prostate cancer are dependent on rectal dose, which is associated with rectal distance from prostate and implanted seeds. Placement of a hydrogel spacer between the prostate and rectum has proven to reduce the volume of the rectum exposed to higher radiation dose levels in the setting of external beam radiotherapy. We present our findings with placing a rectal hydrogel spacer in patients following LDR brachytherapy, and we further assess the impact of this placement on dosimetry and acute rectal toxicity.Methods and MaterialsBetween January 2016 and April 2017, 74 patients had placement of a hydrogel spacer, immediately following a Pd-103 seed-implant procedure. Brachytherapy was delivered as follows: as a monotherapy to 26 (35%) patients; as part of planned combination therapy with external beam radiotherapy to 40 (54%) patients; or as a salvage monotherapy to eight (11%) patients. Postoperative MRI was used to assess separation achieved with rectal spacer. Acute toxicity was assessed retrospectively using Radiation Oncology Therapy Group radiation toxicity grading system. Rectal dosimetry was compared with a consecutive cohort of 136 patients treated with seed implantation at our institution without a spacer, using a 2-tailed paired Student's t test (p < 0.05 for statistical significance).ResultsOn average, 11.2-mm (SD 3.3) separation was achieved between the prostate and the rectum. The resultant mean rectal volume receiving 100% of prescribed dose (V100%), dose to 1 cc of rectum (D1cc), and dose to 2 cc of rectum (D2cc) were 0 (SD 0.05 cc), 25.3% (SD 12.7), and 20.5% (SD 9.9), respectively. All rectal dosimetric parameters improved significantly for the cohort with spacer placement as compared with the nonspacer cohort. Mean prostate volume, prostate V100 and dose to 90% of gland (D90) were 29.3 cc (SD 12.4), 94.0% (SD 3.81), and 112.4% (SD 12.0), respectively. Urethral D20, D5cc, and D1cc were 122.0% (SD 17.27), 133.8% (SD 22.8), and 144.0% (SD 25.4), respectively. After completing all treatments, at the time of first the followup, 7 patients reported acute rectal toxicity—6 experiencing Grade 1 rectal discomfort and 1 (with preexisting hemorrhoids) experiencing Grade 1 bleeding.ConclusionsInjection of rectal spacer is feasible in the post-LDR brachytherapy setting and reduces dose to the rectum with minimal toxicity. Prostate and urethral dosimetries do not appear to be affected by the placement of a spacer. Further studies with long-term followup are warranted to assess the impact on reduction of late rectal toxicity.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2B8XMJ5

Reduction Mammoplasty: Intraoperative vs Pathology Weight

Are there discrepancies between intraoperative and pathology reduction mammoplasty breast tissue specimen weights -- and if so, what are the implications for insurance reimbursement?
ePlasty, Open Access Journal of Plastic Surgery

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

Central Mound Mastopexy for the Correction of Tuberous/Tubular Breast Deformity

Summary: Tuberous and tubular breast deformity are well-recognized abnormalities in the plastic surgery community that incur severe physical and psychological consequences in affected patients. Current reconstructive options for the tuberous and tubular breasts favor the use of prosthetic implants and soft-tissue manipulation. We present a case of tuberous and tubular breast deformity treated with a central mound reduction technique and mastopexy with imbricating sutures without the use of prosthetic implants. The patient remained extremely pleased with her results at long-term follow-up. This represents a unique case of successful reconstruction in a patient with a tuberous and tubular breast deformity using a central mound reduction technique with mastopexy and without a prosthetic device.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2j17dDt

Gluteal Black Market Silicone–induced Renal Failure: A Case Report and Literature Review

Summary: Very few cases of successful surgical treatment for renal failure due to gluteal silicone injections have been reported in the literature. The silicone toxicity and subsequent renal failure seem to follow repetitive silicone injections and silicone injections in large quantities. This is a case of a 31-year-old woman who developed renal failure after 6 years of gluteal silicone injections who underwent radical resection of bilateral gluteal regions in an attempt to mitigate her impending complete renal failure. A systematic review of the literature was conducted using PubMed database and with assistance from medical library staff to conduct keyword searches for "Silicone," "Renal failure," "Silicone emboli syndrome," "Silicone granuloma," and "Silicone end organ toxicity." The search results were reviewed by the authors and selected based on the relevance to the case report presented. Extensive literature relating to silicone granulomas and their systemic effects supports the use of steroids for immediate treatment and eventual surgical resection for cure of the various silicone-related end-organ toxicities including renal failure.

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

Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced KRAS-mutated rectal cancer: A phase I/II trial (SAKK 41/08)

Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): Roger von Moos, Dieter Koeberle, Sabina Schacher, Stefanie Hayoz, Ralph C. Winterhalder, Arnaud Roth, György Bodoky, Panagiotis Samaras, Martin D. Berger, Daniel Rauch, Piercarlo Saletti, Ludwig Plasswilm, Daniel Zwahlen, Urs R. Meier, Pu Yan, Paola Izzo, Dirk Klingbiel, Daniela Bärtschi, Kathrin Zaugg
BackgroundKRAS mutation occurs in ∼40% of locally advanced rectal cancers (LARCs). The multitarget tyrosine kinase inhibitor sorafenib has radiosensitising effects and might improve outcomes for standard preoperative chemoradiotherapy in patients with KRAS-mutated LARC.MethodsAdult patients with KRAS-mutated T3/4 and/or N1/2M0 LARC were included in this phase I/II study. The phase I dose-escalation study of capecitabine plus sorafenib and radiotherapy was followed by a phase II study assessing efficacy and safety. Primary end-points were to: establish the maximum tolerated dose of the regimen in phase I; determine the pathologic complete response (pCR) rate in phase II defined as Dworak regression grade 3 and 4.ResultsFifty-four patients were treated at 18 centres in Switzerland and Hungary; 40 patients were included in the single-arm phase II study. Recommended doses from phase I comprised radiotherapy (45 Gy in 25 fractions over 5 weeks) with capecitabine 825 mg/m² twice daily × 33 plus sorafenib 400 mg/d. Median daily dose intensity in phase II was radiotherapy 100%, capecitabine 98.6%, and sorafenib 100%. The pCR rate (Dworak 3/4) was 60% (95% CI, 43.3–75.1%) by central independent pathologic review. Sphincter preservation was achieved in 89.5%, R0 resection in 94.7%, and downstaging in 81.6%. The most common grade 3 toxicities during phase II included diarrhoea (15.0%), skin toxicity outside radiotherapy field (12.5%), pain (7.5%), skin toxicity in radiotherapy field, proctitis, fatigue and cardiac ischaemia (each 5%).ConclusionsCombining sorafenib and standard chemoradiotherapy with capecitabine is highly active in patients with KRAS-mutated LARC with acceptable toxicity and deserves further investigation. http://ift.tt/PmpYKN: NCT00869570.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z2g9hb

Metastatic cutaneous apocrine adenocarcinoma responsive to the programmed cell death protein 1 inhibitor pembrolizumab

Publication date: Available online 11 December 2017
Source:European Journal of Cancer
Author(s): Max Rogatsch, Johannes Schmid, Sigurd Lax, Maximilian Uranitsch, Karin Schmid-Zalaudek, Roberta Giuffrida, Iris Zalaudek




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

Haploinsufficiency of A20 causes autoinflammatory and autoimmune disorders

Publication date: Available online 11 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Tomonori Kadowaki, Hidenori Ohnishi, Norio Kawamoto, Tomohiro Hori, Kenichi Nishimura, Chie Kobayashi, Tomonari Shigemura, Shohei Ogata, Yuzaburo Inoue, Tomoki Kawai, Eitaro Hiejima, Masatoshi Takagi, Kohsuke Imai, Ryuta Nishikomori, Shuichi Ito, Toshio Heike, Osamu Ohara, Tomohiro Morio, Toshiyuki Fukao, Hirokazu Kanegane




from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jQkc8m

Long-term follow up of IPEX syndrome patients after different therapeutic strategies: an international multicenter retrospective study

Publication date: Available online 11 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Federica Barzaghi, Laura Cristina Amaya Hernandez, Benedicte Neven, Silvia Ricci, Zeynep Yesim Kucuk, Jack Bleesing, Zohreh Nademi, Mary Anne Slatter, Erlinda Rose Ulloa, Anna Shcherbina, Anna Roppelt, Austen Worth, Juliana Silva, Alessandro Aiuti, Luis Murguia-Favela, Carsten Speckmann, Magda Carneiro-Sampaio, Juliana Folloni Fernandes, Safa Baris, Ahmet Ozen, Elif Karakoc-Aydiner, Ayca Kiykim, Ansgar Schulz, Sandra Steinmann, Lucia Dora Notarangelo, Eleonora Gambineri, Paolo Lionetti, William Thomas Shearer, Lisa Forbes, Caridad Martinez, Despina Moshous, Stephane Blanche, Alain Fisher, Frank M. Ruemmele, Come Tissandier, M. Ouachee-Chardin, Frédéric Rieux-Laucat, Marina Cavazzana, Waseem Qasim, Barbarella Lucarelli, Michael H. Albert, Ichiro Kobayashi, Laura Alonso, Cristina Diaz De Heredia, Hirokazu Kanegane, Anita Lawitschka, Jong Jin Seo, Marta Gonzalez-Vicent, Miguel Angel Diaz, Rakesh Kumar Goyal, Martin G. Sauer, Akif Yesilipek, Minsoo Kim, Yesim Yilmaz-Demirdag, Monica Bhatia, Julie Khlevner, Erick .J. Richmond Padilla, Silvana Martino, Davide Montin, Olaf Neth, Agueda Molinos-Quintana, Justo Valverde-Fernandez, Arnon Broides, Vered Pinsk, Antje Ballauf, Filomeen Haerynck, Victoria Bordon, Catharina Dhooge, Maria Laura Garcia-Lloret, Robbert G. Bredius, Krzysztof Kałwak, Elie Haddad, Markus Gerhard Seidel, Gregor Duckers, Sung-Yun Pai, Christopher C. Dvorak, Stephan Ehl, Franco Locatelli, Frederick Goldman, Andrew Richard Gennery, Mort J. Cowan, Maria Grazia Roncarolo, Rosa Bacchetta
BackgroundImmunedysregulation Polyendocrinopathy Enteropathy X-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined.ObjectiveTo evaluate disease onset, progression and long-term outcome of the two main treatments in long-term IPEX survivors.MethodsClinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed.ResultsWe confirm neonatal onset with enteropathy, type 1 diabetes (T1D), and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n=58) had a median follow-up of 2.7 years (range: 1 week - 15 years). Patients receiving chronic IS (n=34) had a median follow-up of 4 years (range: 2 months - 25 years). The overall survival (OS) after HSCT was 73.2% (95% confidence interval [CI], 59.4 to 83.0) and after IS was 65.1% (95 % CI, 62.8 to 95.8). The pre-treatment OI score was the only significant predictor of OS after transplant (p=0.035) but not under IS.ConclusionsPatients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source or conditioning regimen.

Graphical abstract

Teaser

This international retrospective multicenter study of patients with long-term IPEX syndrome (n=96) provides data on onset, disease progression, and outcomes after different treatments to inform future therapeutic choices.


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

Efficacy of lentiviral mediated gene therapy in an Omenn syndrome Rag2 mouse model is not hindered by inflammation and immune dysregulation

Publication date: Available online 11 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Valentina Capo, Maria Carmina Castiello, Elena Fontana, Sara Penna, Marita Bosticardo, Elena Draghici, Luigi P. Poliani, Lucia Sergi Sergi, Rosita Rigoni, Barbara Cassani, Monica Zanussi, Paola Carrera, Paolo Uva, Kerry Dobbs, Nicolò Sacchetti, Luigi D. Notarangelo, Niek P. van Til, Gerard Wagemaker, Anna Villa
BackgroundOmenn syndrome (OS) is a rare severe combined immunodeficiency associated with autoimmunity, caused by defects of the lymphoid-specific V(D)J recombination. Most patients carry hypomorphic mutations in recombination activating genes (RAG) 1 or 2. Hematopoietic stem cell (HSC) transplantation is the standard treatment, however gene therapy (GT) may represent a valid alternative, especially for patients lacking a matched donor.ObjectiveTo determine the efficacy of lentiviral vector (LV) mediated GT in the murine model of OS (Rag2^R229Q/R229Q) in correcting immunodeficiency and autoimmunity.MethodsOS Lin^- cells were transduced with a LV encoding the human RAG2 gene and injected into irradiated OS recipients. Control mice were transplanted with wild-type or OS untransduced Lin- cells. Immunophenotype, T-dependent and independent antigen challenges, immune spectratyping, autoantibodies detection and detailed tissue immunohistochemical analyses were performed.ResultsLV-mediated GT allowed immunological reconstitution, although suboptimal as compared to wild type bone marrow transplanted OS mice, in peripheral blood and hematopoietic organs, such as bone marrow, thymus and spleen. We observed in vivo variability in the efficacy of GT correlating with the levels of transduction achieved. Immunoglobulin levels and T cell repertoire normalized and gene corrected mice properly responded to challenges in vivo. Autoimmune manifestations, such as skin infiltration and autoantibodies, dramatically improved in GT mice with a vector copy number/genome higher than 1 in the bone marrow and 2 in the thymus.ConclusionsOur data show that LV-mediated GT for Omenn Syndrome significantly ameliorates the immunodeficiency even in an inflammatory environment.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2kpymg9

An actin cytoskeletal barrier inhibits lytic granule release from Natural Killer cells in Chediak-Higashi syndrome

Publication date: Available online 11 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Aleksandra Gil-Krzewska, Mezida B. Saeed, Anna Oszmiana, Elizabeth R. Fischer, Kathryn Lagrue, William A. Gahl, Wendy J. Introne, John E. Coligan, Daniel M. Davis, Konrad Krzewski
BackgroundChediak-Higashi syndrome (CHS) is a rare disorder caused by biallelic mutations in the LYST gene, resulting in formation of giant lysosomes or lysosome-related organelles in several cell types. The disease is characterized by immunodeficiency and a fatal hemophagocytic lymphohistiocytosis due to impaired function of cytotoxic lymphocytes, mainly Natural Killer (NK) cells.ObjectiveWe sought to determine the underlying biochemical cause of the impaired cytotoxicity of NK cells in CHS.MethodsWe generated a human cell model of CHS, using CRISPR technology. We used a combination of classical techniques to evaluate lysosomal function and cell activity in the model system, and super-resolution microscopy to visualize filamentous (F-)actin and lytic granules in normal and LYST-deficient NK cells.ResultsLoss of LYST function in a human NK cell line, NK92mi, resulted in inhibition of NK cell cytotoxicity and reproduced other aspects of CHS cellular phenotype, including the presence of significantly enlarged lytic granules with defective exocytosis, and impaired integrity of endo-lysosomal compartments. The large granules had an acidic pH, normal activity of lysosomal enzymes, and were positive for the proteins essential for lytic granule exocytosis. Visualization of the actin meshwork openings at the immunological synapse revealed that the cortical actin acts as a barrier for secretion of such large granules at the cell-cell contact site. Decreasing the cortical actin density at the immunological synapse, or decreasing the lytic granule size, restored the ability of LYST-deficient NK cells to degranulate and kill target cells.ConclusionThe cortical actin and granule size play significant roles in NK cell cytotoxic function. The periodicity of sub-synaptic actin is an important factor limiting the release of large lytic granules from CHS NK cells, and could be a novel target for pharmaceutical intervention.

Teaser

The large lytic granules in Chediak-Higashi syndrome NK cells are functional, but the actin meshwork at the immunological synapse is a barrier to their exocytosis, resulting in defective CHS NK cell degranulation and cytotoxicity. Decreasing the cortical actin density, or lytic granule size, restores the ability of LYST-deficient NK cells to degranulate and kill target cells..


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jQk7S6

Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting

Publication date: Available online 11 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Marie-Claire Arrieta, Andrea Arévalo, Leah Stiemsma, Pedro Dimitriu, Martha E. Chico, Sofia Loor, Maritza Vaca, Rozlyn C.T. Boutin, Evan Morien, Mingliang Jin, Stuart E. Turvey, Jens Walter, Laura Wegener Parfrey, Philip J. Cooper, Brett Finlay
BackgroundAsthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment.ObjectiveWe sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting.MethodsWe conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography.ResultsAs previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze.ConclusionsOur findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy.

Graphical abstract

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

Atypical chronic myeloid leukemia: a rare entity with management challenges

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Agkg7i

Survival prediction in pancreatic cancer patients with no distant metastasis: a large-scale population-based estimate

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z2P7GA

Endoscopic and Phoniatric Evaluation in Singing Students

Publication date: Available online 11 December 2017
Source:Journal of Voice
Author(s): Andrea Nacci, Giovanna Baracca, Salvatore Osvaldo Romeo, Maria Denise Cavaliere, Maria Rosaria Barillari, Stefano Berrettini, Francesco Ursino, Bruno Fattori
ObjectivesIn To analyze laryngostroboscopic findings and ENT/phoniatric examination results in a group of singing students and in a control group of non-singing subjects to emphasize the importance of ENT/phoniatric examination and of laryngostroboscopy before taking up singing.Methods56 singing students and 60 healthy euphonic non-singer volunteers were recruited. In each subject a perceptual assessment and a self-assessment (VHI) of the voice were performed. The singing students filled out the Singing-VHI. All subjects underwent flexible fiberoptic endoscopy and laryngostroboscopy. All subjects were evaluated through the Reflux Symptom Index (RSI) and the Reflux Finding Score (RFS).ResultsAt laryngostroboscopy, 60.7% of students presented pathological findings, versus 20% of controls (P < 0.0001). Incomplete glottic closure (35.7% vs. 13.3%), supraglottic hypertonus (16.1% vs. 5%), organic lesions (bilateral nodules, cysts, sulcus vergeture) (17.9% vs. 3.3%), posterior erythema (16.1% vs. 5%) and laryngeal edema (14.3% vs 3.3%) were more frequent in the students. The most common symptoms in singers were phonasthenia (37.5 % vs 6.7%; P =  0.0001) and mucus sensation (17.9% vs. 5%, P = 0.03). S-VHI showed higher values in students with pathological laryngostroboscopy (P < 0.0001). Finally, average RSI and RFS were higher in students.ConclusionsDue to the high percentage of organic and functional voice disorders in singing students, it would be desirable that every subject who is going to start singing underwent an ENT/phoniatric investigation with videostrobolaryngoscopy to ascertain vocal folds healthy condition.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C6hJye

Bamboo Nodes on a Series of 15 Patients: Vocal Fold Lesion as a Sign of Autoimmune Disease and Microphonotrauma

Publication date: Available online 11 December 2017
Source:Journal of Voice
Author(s): Natalie Oker, Aude Julien-Laferrière, Philippe Herman, Gérard Chevaillier
ObjectivesBamboo nodes are band-like submucosal deposits of the middle third of the vocal fold. They are often related to connective tissue disorders, but can also precede them. The aim of this study was to report our experience with conservative treatment of those rare lesions.MethodsThis is a retrospective series of 15 patients consulting for hoarseness and presenting bamboo nodes from 2010 to 2016.ResultsAll patients were women of mean age of 38 years with a moderate or high degree of daily vocal effort. Nine patients (60%) presented with known autoimmune disease at the phoniatric appointment. The other patients (40%) benefited from a systematic biological research for autoimmune disease, which retrieved two poorly symptomatic connective tissue disorders.Patients were clinically improved by speech therapy (53%) or by an optimization or introduction of immunosuppressive treatment (46%). A spontaneous improvement was observed for three patients after voice rest (one after retirement, one after professional change, and last one after resuming professional singing). In our series, no phonosurgery was performed.The vocal profile at last appointment found a moderate Voice Handicap Index at 35.3/120, a low maximum time of phonation at 13.6 seconds, and a high jitter at 1.4, sign of instability of the vibrator.ConclusionThis series emphasizes the importance of diagnosing bamboo nodes in middle-aged female presenting an autoimmune disease. Vice versa for each patient with bamboo nodes, a systematic autoimmune check-up has to be realized to detect a biological asymptomatic autoimmune disease.



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

Pathology of retroperitoneal sarcomas: A brief review

Sarcomas represent a highly heterogeneous group of tumors as reflected in the significant overlap between their histologic phenotypes between the different types, posing diagnostic challenges for the pathologist. Definitive tumor classification is increasingly important because of prognostication and emergence of targeted therapies for some of the sarcoma types. In this review, we highlight pertinent pathologic and molecular aspects of sarcomas common in the retroperitoneum, relevant to the surgical oncologist.

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

Can you tell the difference: round vs anatomical implants – a real-time global ballot

Publication date: Available online 11 December 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): A. Mohan, M. See, J. Farhadi




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

The aetiopathogenesis of capsular contracture: a systematic review of the literature

Publication date: Available online 11 December 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Yara Bachour, Stephan P. Verweij, Susan Gibbs, Johannes C.F. Ket, Marco J.P.F. Ritt, Frank B. Niessen, Margriet G. Mullender
BackgroundCapsular contracture is the most frequent complication after breast augmentation or reconstruction with breast implants. The immune system plays a prominent role in capsular contracture formation, albeit to an unknown extent. Bacterial contamination in situ has been hypothesized to be causative for capsular contracture. How this relates to the immunological processes involved is unknown. This article aims to provide an overview of immunological and bacterial factors involved in development of capsular contracture.MethodsWe undertook a systematic literature review focused on immunological factors and microbiota in relation to capsular contraction around implants. This systematic review was performed in accordance with the PRISMA guidelines. PubMed, EMBASE, and the Cochrane databases were searched from inception up to October 2016. Included studies were assessed for the following variables: subject characteristics, number of capsules, primary indication for surgery, surgical procedure, follow-up or implant duration, study methods, type of antibiotics or medical therapies and outcomes related to microbiota and immunological factors.ResultsData on immunological factors and bacterial contamination was retrieved from 64 included studies. Notably the presence of macrophages and Staphylococcus epidermidis within capsules were often associated with capsular contracture.ConclusionThis review provides a clear overview of the immunological factors associated with capsular contracture and provides a hypothetical immunological model for development of the disease. Furthermore, an overview of bacterial contamination and associations with capsular contracture has been provided. Follow-up research may result in clinical recommendations to prevent capsular contracture. CLINICAL QUESTION



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2l0mwwX

Unexpected Blooming Artifact in Brain Magnetic Resonance Imaging

Abstract Unexpected foreign bodies are occasionally discovered during magnetic resonance imaging (MRI). These are often present unknown to the patient, missed during routine pre-MRI screening and result in unnecessary delay during MRI. The authors present a patient with traumatically embedded foreign body in the scalp that escaped pre-MRI screening and caused susceptibility artifacts during brain MRI. The object was surgically removed to allow the imaging to be completed. Patients with suspicion or history of facial trauma or with dental restorations are referred to concerned specialists for compatibility of hardware, restorations and for assessing risks during MRI due to these. This patient is presented as a reminder for clinicians to probe further during anamnesis and have a high index of suspicion for foreign bodies that may be present even after trivial injuries. Address correspondence and reprint requests to Akilesh Ramasamy, MDS, Department of Dentistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Puducherry, India; E-mail: akident@gmail.com Received 22 April, 2017 Accepted 4 August, 2017 The authors report no conflicts of interest. © 2017 by Mutaz B. Habal, MD.

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

A Three-Dimensional Anthropometric Evaluation of Facial Morphology

Objectives: The aims of this study were to evaluate sexual dimorphism for facial features within Italian and Egyptian populations and to compare the facial morphology by sex between these 2 populations. Materials and Methods: Three-dimensional (3D) facial images were acquired by using the portable 3dMDface System, which captured 259 subjects from 2 population groups of Italian (n = 139) and Egyptian (n = 120). Each population was categorized into male and female groups for evaluation. All subjects in the groups were aged between 18 and 30 years and had no apparent facial anomalies. A total of 23 anthropometric landmarks were identified on the 3D faces of each subject. The independent t test was used to analyze each data set obtained within each subgroup. Results: Egyptian women tend to have distinct facial features when compared with Italian women; they had less prominent eyes, more nasal width, more height of upper and lower faces and more height of upper and lower vermilion lengths. Egyptian and Italian males demonstrated very close facial features. However, Egyptian males had more nasal width, length of alare, and mandibular height. Conclusions: Sexual dimorphism for facial features was presented in both the Italian and Egyptian populations. In addition, there were significant differences in facial morphology between these 2 populations, especially in females. Address correspondence and reprint requests to Dr. Chung How Kau, DDS, MSD, MBA, PhD, MOrth, FDS, FFD, FAMS, Department of Orthodontics, University of Alabama at Birmingham, School of Dentistry, 1919 Seventh Ave. S. Birmingham, AL 35294; E-mail: ckau@uab.edu Received 13 March, 2017 Accepted 14 August, 2017 The authors report no conflicts of interest. © 2017 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2l1EGy9

The Hybrid Technical Management of Large and Complicated Traumatic Arteriovenous Fistula of Preauricular Region

Background: Arteriovenous fistula (AVF) is defined as an abnormal communication between the high flow arterial system and the low flow venous network, which directly connects the arterial feeding vessels and the near draining veins without normal intervening capillary bed. Arteriovenous fistula incurs in preauricular region is exceeding rare. Most of these fistulae occur as a result of an iatrogenic injury, the volume is small, feeding and draining vessels of feeding and draining are simple, and can be cured easily. However, the treatment of the large and complicated AVF after incidental trauma in preauricular region is a challenge even for senior neurosurgeon. In this study, the authors discuss the management of a traumatic AVF through combined therapeutic method of surgical ligation and transarterial embolization. It is fed by ipsilateral superficial temporal artery, internal maxillary artery, posterior auricular artery, and their accessory branches and is drained by ipsilateral common facial vein and external jugular vein. Also the etiology, clinical manifestations, pathology, diagnosis, and management are summarized. Conclusion: Large and complicated traumatic AVF in preauricular region is rare, often due from an injury in maxillofacial region, combined therapy needed. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/OBJ4xP Address correspondence and reprint requests to Jinlong Sun, Shandong Provincial Qianfoshan Hospital, Jinan, China; E-mail: jinlongsun@hotmail.com Received 16 July, 2017 Accepted 19 August, 2017 The authors report no conflicts of interest. © 2017 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2l1Jxj6

Differences in the Alignment Pattern of the Maxillary Dental Arch Following Fixed Orthodontic Treatment in Patients With Bilateral Cleft Lip and Palate: Anteroposterior-Collapsed Arch Versus Transverse-Collapsed Arch

Abstract The purpose of this study was to investigate differences in the alignment pattern of the collapsed maxillary arch following fixed orthodontic treatment (FOT) in bilateral cleft lip and palate (BCLP) patients according to collapse type. Fifteen BCLP patients were divided into Group 1 (anteroposterior-collapsed arch, n = 7) and Group 2 (transverse-collapsed arch, n = 8) according to maxillary arch shape before FOT. Linear and angular variables of lateral cephalograms and dental models were evaluated before (T1) and after FOT (T2), and statistical analysis was performed. In cephalometric measurements at T1, both the groups exhibited retrusive maxillae, a Class III relationship, and lingual inclination of U1-SN. At T2, significant improvement of U1-SN was observed in both the groups (P 

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

Recurrent Lower Eyelid Ectropion After Graft Surgery Using Autogenous Palmaris Longus Tendon

Abstract A 78-year-old male experienced right lower eyelid ectropion following right facial trauma from a fall 5 years ago, for which he underwent autogenous palmaris longus tendon graft surgery at another clinic. Recurrence was noted 3 years after surgery. On first examination, there was outward turning of the lateral half of the right lower eyelid margin. We performed a lateral tarsal strip procedure with removal of the graft. Intraoperatively, the lateral part of the graft was located along the inferior tarsal border, whereas the medial part was located on the tarsal surface. The lateral stump had bifurcated; 1 branch had passed through a bony hole drilled at the base of the rim; and both branches had been ligated together on the rim surface. The medial side had been fixed to the medial canthal tendon. Postoperatively, the apposition of eyelid and ocular surface was good, and the patient experienced no recurrence after 1 year. Address correspondence and reprint requests to Hiromichi Matsuda, MD, Department of Ophthalmology, Daisan Hospital, The Jikei University School of Medicine, 4-11-1 Izumihonchou, Komae, Tokyo 201-8601, Japan; E-mail: thkmmm@yahoo.co.jp Received 21 June, 2017 Accepted 6 October, 2017 The authors report no conflicts of interest. © 2017 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2l1JmUY

Intraoral Pleomorphic Adenoma in Young Patients

Background: Intraoral pleomorphic adenoma (PA) is rare in young individuals, with only single clinical reports or small patient series reported previously. Aim: The aim of this study was to describe the clinicopathological features of PA in 4 patients under 18 years of age, and to discuss the differential diagnosis of pediatric patients presenting with intraoral submucosal nodules. Methods: Between 2000 and 2015, all patients of intraoral PA in patients aged ≤18 years diagnosed in the Oral Pathology Laboratory of the Universidade Federal de Pernambuco, Brazil, were retrieved for the study. Clinical data were recorded from the clinical charts. Histopathological slides stained with hematoxylin and eosin were reviewed to confirm the diagnosis. Results: There were 4 cases of PA in patients aged ≤18 years. All patients in this patient series were males, with a mean age of 16.7 years. Three cases occurred in the palate, and in 1 case, the upper lip was affected. All PAs appeared as a painless, smooth surface, well-circumscribed, and submucosal nodule. All patients were surgically excised and subsequent histopathological analysis revealed well-circumscribed tumors composed of cells that were arranged in ducts within a fibromyxoid stroma. No signs of recurrence were observed in 3 patients after a mean follow-up of 30 months. One patient is lost to follow-up. Conclusion: Although PAs are unusual in young patients, they should be considered in the differential diagnosis of oral submucosal nodules. Address correspondence and reprint requests to Danyel Elias da Cruz Perez, PhD, 4a Travessa Professor Artur de Sá, Departamento de Clínica e Odontologia Preventiva, Universidade Federal de Pernambuco, s/n—Cidade Universitária, CEP: 50740-521, Recife, Pernambuco, Brazil; E-mail: danyel.perez@ufpe.br Received 11 September, 2017 Accepted 8 October, 2017 The authors report no conflicts of interest. © 2017 by Mutaz B. Habal, MD.

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

Osseous Convexity at the Anterior Fontanelle: A Presentation of Metopic Fusion?

Background: Craniosynostosis, or a premature fusion of 1 or more cranial vault sutures, results in characteristic head shape deformities. In previous reports, an osseous prominence at the anterior fontanelle has been suggestive of adjacent suture fusion and local elevation in intracranial pressure (ICP). This prominence has been termed the "volcano" sign, and has been described in the anterior fusion of the sagittal suture and serves as an indication for surgery. Methods: Two patients presented for head shape evaluation with mild metopic ridging and anterior fontanellar osseous convexities consistent with the volcano sign. Low-dose computed tomography imaging was performed in both patients due to concern for underlying craniosynostosis with elevated locoregional ICP. Results: In both patients, imaging was significant for a localized, superior forehead metopic fusion, as well as a bony, convex prominence at the site of the ossified anterior fontanelle. There were no other clinical or radiologic signs or symptoms to suggest elevated ICP. Surgery was not indicated in either patient. Conclusions: Here the authors present 2 patients with osseous convexities at the site of the closed anterior fontanelle without signs or symptoms of elevated ICP, or classic signs of metopic synostosis. The authors hypothesize that this pattern may be due to a form of mechanically induced premature fusion of a normal metopic suture that is focused superiorly at the bregma, with minimal resultant restriction of overall skull growth. This is in contrast to metopic synostosis, which primarily has a sutural pathology and leads to characteristic findings of hypotelorism and trigonocephaly. Address correspondence and reprint requests to John A. Persing, MD, Yale Plastic Surgery, PO Box 208062, New Haven, CT 06510; E-mail: john.persing@yale.edu Received 25 February, 2017 Accepted 9 June, 2017 The authors report no conflicts of interest. © 2017 by Mutaz B. Habal, MD.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2l1JwM4

Devices for adenoma detection rate: Holy Grail or training tool?

A relationship between endoscopists' adenoma detection rate (ADR) at colonoscopy and risk of interval colorectal cancer and colorectal cancer death has been proven.1-3 Since then, ADR became one of the most important performance indicators for colonoscopy, endorsed by several professional societies.4,5 Although ADR depends on adenoma prevalence in the target population,6-8 it is endoscopist performance that best explains observed ADR variability among physicians.9 Four key factors are believed to drive endoscopists' performance in detecting adenomas: knowledge, imaging technology, colonoscopy examination technique, and motivation/nontechnical skills.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BeR6t9

Endoscopic eradication therapy and the test of time

Endoscopic therapy for Barrett's esophagus (BE) has come a long way since 1992, when Brandt and Kauvar1 first demonstrated that BE metaplasia could be ablated by using endoscopically delivered laser irradiation. Early concerns regarding the feasibility and safety of endoscopic therapy were soon allayed, and attention shifted to finding the best endoscopic eradication technique. Endoscopic ablative modalities that have been studied include a variety of laser types, multipolar electrocoagulation, argon plasma coagulation, photodynamic therapy, radiofrequency ablation (RFA), and cryotherapy.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jymU5D

Is it noninferiority?

We have read the article by Park et al entitled "Effect of scheduled second-look endoscopy on peptic ulcer bleeding: a prospective randomized multicenter trial."1 We have some questions and comments regarding the statistical analysis and conclusion of the trial.

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

Instructions for authors

GASTROINTESTINAL ENDOSCOPY publishes original papers reporting investigations and observations relating to endoscopic procedures used in the study and treatment of digestive diseases. All submissions undergo peer review. Submissions may be accompanied by supplemental materials posted to the electronic version of the journal; such materials also will be subject to peer review. Careful adherence to submission guidelines will avoid unnecessary delays, as incomplete submissions will be returned to the authors before initiation of the peer review process.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jxYWY4

Response:

We thank Drs Masao Kobayakawa, Yuki Matsushita, and Hidetaka Okubo1 for their interest and comments on article "Effect of scheduled second-look endoscopy on peptic ulcer bleeding: a prospective randomized multicenter trial."2 The authors have raised some statistical issues, and we appreciate the opportunity to respond and correct the errors of our study.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BeR2JV

Gastroscopy and gastric cancer–related mortality: Time to change recommendations regarding screening?

Gastric cancer is the third most common cause of cancer-related death worldwide,1 and most cases are locally advanced or metastatic at diagnosis. Widespread Helicobacter pylori eradication2 and radiologic or endoscopic screening,3 have been proved to decrease gastric cancer mortality in high-incidence countries. However, in countries with lower incidence, these strategies are probably not cost effective, and there are only recommendations regarding secondary prevention in high-risk patients, such as those with gastric preneoplastic conditions.

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

Unearthing the significance of buried intestinal metaplasia

Pre-cancerous Barrett's esophagus (BE) arises from columnar metaplasia of the squamous mucosa secondary to chronic reflux injury. If untreated, the metaplastic columnar epithelium may undergo a dysplastic transformation and in a subset of patients subsequently progresses to adenocarcinoma. New endoscopic modalities can successfully ablate the Barrett's mucosa to be replaced by neosquamous mucosa while the patients are taking a proton pump inhibitor. Although these advances have a positive impact on the conservation of the esophagus and treatment of early neoplasia, they have uncovered the issue of "buried BE" or "subsquamous intestinal metaplasia (SSIM)." SSIM is defined as the presence of esophageal subepithelial columnar epithelium underlying a restored squamous mucosal lining.

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

Sphincter of Oddi dysfunction: the never-ending story has come to a conclusion

In the late 1970s, during my fellowship in general surgery, my main scientific interest was the evaluation of the sphincter of Oddi status with intraoperative cholangiography during cholecystectomy. At that time, especially in Italy1 and in other locations, many cholecystectomies for gallstones were complemented by transduodenal sphincteroplasty whenever a dilatation of the common bile duct (CBD) or a tapering of the papillary contour was observed by intraoperative cholangiography. We assumed that these features were diagnostic for "papillitis," later more broadly renamed "sphincter of Oddi dysfunction" (SOD).

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

Post-ERCP pancreatitis in patients with type 2 diabetes mellitus

In their recent observational study, Zhao et al1 found similar incidence rates of post-ERCP pancreatitis (PEP) in patients with chronic pancreatitis (CP) versus other biliary diseases, and they reported lower PEP incidence rates as the severity of CP increased. The authors state that they "identified other possible risk and protective factors not examined before. The reduced incidence of PEP in CP patients was correlated with the presence of diabetes mellitus, pancreatic stones, and the use of ESWL (extracorporeal shock wave lithotripsy)." We would like to point out that our group had formerly evaluated the influence of type 2 diabetes mellitus (T2DM) on the short-term adverse events after ERCP in an 11-year (2003-2013) observational study that included 126,885 therapeutic procedures (23,002 [18.1%] in people with T2DM) in the overall Spanish population.

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

Assessment of trainees’ performance in colonoscopy

The international competency-based medical education (CBME) collaborators proposed the following steps in planning a CBME curriculum: "(1) Identify the abilities needed of graduates. (2) Explicitly define the required competencies and their components. (3) Define milestones along a development path for the competencies. (4) Select educational activities, experiences, and instructional methods. (5) Select assessment tools to measure progress along the milestones. (6) Design an outcomes evaluation of the program."1

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jz28m2

Response:

We thank Nicosia and colleagues1 for their comments on our article "Asia-Pacific consensus guidelines for endoscopic management of benign biliary strictures."2 In that article, we highlighted the importance of a multidisciplinary approach to the management of benign biliary strictures (BBSs), not only in the diagnosis but in the treatment as well.2 The selection of treatment approaches to BBSs depends on the clinical setting, the patient's condition and willingness, and the availability of expertise, which mandate a multidisciplinary discussion among different specialties aimed at providing a patient with the appropriate treatment and the most optimal outcome.

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

Early ERCP for severe cholangitis? Of course!

Jean-Martin Charcot (1825-1893), a member of the Faculté de Médicin at the famous Hôpital Salpêtrière in Paris, a neurologist and professor of anatomic pathology, in 1877 brought attention to the "maladies du foie et des voie biliare"1 and the entity of "fièvre intermittente hépatique" characterized by the triad of jaundice, right upper quadrant pain, and fever, which came to be one of his eponymous legacies. This condition later became known as ascending cholangitis, based on the belief that infection always ascended from the duodenum through an incompetent sphincter of Oddi.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jx0aTo

Information for readers

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Be0r4E

Recurrent symptoms after per-oral endoscopic myotomy in achalasia: Redo, dilate, or operate? A call for a tailored approach

We read with interest the study by Van Hoeij et al1 in this issue of Gastrointestinal Endoscopy on the management of recurrent dysphagia symptom in patients who underwent prior per-oral endoscopic myotomy (POEM) in the treatment of achalasia. Since the first published case series by Inoue et al2 in 2010 showing the safety and efficacy of the use of a submucosal tunnel to perform esophageal myotomy, POEM has gained increasing popularity as a first-line therapy for treatment of achalasia. Although response rates of >90% have widely been reported,3-5 there is a subset of patients who fail POEM and develop recurrent symptoms.

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

Response:

We highly appreciate the response from de Miguel-Yanes et al1 about the influence of diabetes mellitus (DM) on the incidence rate of post-ERCP pancreatitis (PEP). Because patients with chronic pancreatitis (CP) are at high risk for the development of DM, it is an important issue with significant implications for clinical practice.2

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Be0mxS

Guidewire cannulation in ERCP: from zero to hero!

For decades biliary cannulation during ERCP was done by lining up and advancing a catheter or a sphincterotome into the ampulla at what one believed was a "good" biliary angle and then gently (or not so gently) injecting contrast. This either resulted in a cholangiogram or a pancreatogram. If the bile duct was accessed, a wire was then advanced through the catheter into the biliary tree, and the procedure moved forward. If the pancreas was accessed, the catheter was pulled out and the maneuver was attempted again (and again and again) until ultimately successful or the biliary tree was not accessed.

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

In upcoming issues...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Be0ihC

Is it safe to wait 10 years after a negative baseline screening colonoscopy result?

Despite guidelines1 that recommend a 10-year interval after a negative screening colonoscopy result in average-risk individuals, many patients receive early examinations.2,3 This could be due to concerns about the adequacy of the baseline examination or to a fear of postcolonoscopy interval colorectal cancer (CRC). Prior studies suggest that if the baseline examination was less than adequate (poor preparation or uncertain cecal intubation), the yield of repeating the examination is high.4 However, in most cases, the baseline examination is adequate, and previous work has suggested that the risk of serious pathologic changes within 10 years is low.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jwZT2O

Continuing Medical Education Exam: January 2018

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Be0duk

Effectiveness of Online Cancer Education for Nurses and Allied Health Professionals; a Systematic Review Using Kirkpatrick Evaluation Framework

Abstract

Embedding online learning within higher education can provide engaging, cost-effective, interactive and flexible education. By evaluating the impact, outcomes and pedagogical influence of online cancer and education, future curricula can be shaped and delivered by higher education providers to better meet learner, health care provider and educational commissioners' requirements for enhanced patient care and service delivery needs. Using the Kirkpatrick's four-level model of educational evaluation, a systematic review of the effectiveness of online cancer education for nurses and allied health professionals was conducted. From 101 articles, 30 papers were included in the review. Educational theory is not always employed. There is an absence of longitudinal studies to examine impact; an absence of reliability and/or validity testing of measures, limited experimental designs taking account of power and few attempts to mitigate bias. There is, however, an emerging innovative use of mobile/spaced learning techniques. Evidence for clinical and educational effectiveness is weak offering insights into experiences and participant perceptions rather than concrete quantitative data and patient-reported outcomes. More pedagogical research is merited to inform effective evaluation of online cancer education, which incorporates and demonstrates a longer-term impact.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ygfxB4

TNM stage at diagnosis is more predictive of prognosis than pathological complete response in young breast cancer treated with neoadjuvant chemotherapy

No abstract available

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

Structural modification of histone deacetylase inhibitors with a phenylglycine scaffold

During the discovery of histone deacetylase inhibitors (HDACIs) as antitumor drugs, a series of potent phenylglycine-based HDACIs were developed. However, further development is restricted by the poor solubility. Therefore, structural modifications were performed in the present study in the development of potent HDACIs with improved pharmacokinetic properties. The synthesized molecules were designed by the substitution of fatty linkers for aromatic linkers, and showed good solubility profiles. Among the compounds derived, molecule HD9 showed a potent enzyme-inhibitory effect (IC50 values of 76 nmol/l) and in-vitro antiproliferative activities (IC50 values of 0.51, 0.83, and 0.76 µmol/l against U937, K562, and HL60 cells, respectively). Molecule HD9 showed selectivity of HDAC3 over HDAC6 in the isoform selectivity assays. Molecular docking studies showed good binding patterns of molecule HD9 to the active site of HDAC3. Results from the present work indicated that molecule HD9 is a promising lead compound for the tumor therapy. Correspondence to Dr Lei Zhang, Department of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang 261053, China Tel: +86 150 9208 5925; fax: +86 053 6846 2014; e-mail: leiqdu@foxmail.com Correspondence to Dr Weiguo Song, Department of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang 261053, China Fax: +86 053 6846 2014 Received February 13, 2017 Accepted November 8, 2017 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jPejs6

Statin-induced cancer cell death can be mechanistically uncoupled from prenylation of RAS family proteins

The statin family of drugs preferentially trigger tumor cell apoptosis by depleting mevalonate pathway metabolites farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), which are used for protein prenylation, including the oncoproteins of the RAS superfamily. However, accumulating data indicate that activation of the RAS superfamily are poor biomarkers of statin sensitivity, and the mechanism of statin-induced tumor-specific apoptosis remains unclear. Here we demonstrate that cancer cell death triggered by statins can be uncoupled from prenylation of the RAS superfamily of oncoproteins. Ectopic expression of different members of the RAS superfamily did not uniformly sensitize cells to fluvastatin, indicating that increased cellular demand for GGPP and FPP cannot explain increased statin sensitivity. While ectopic expression of HRAS increased statin sensitivity, expression of myristoylated HRAS did not rescue this effect. HRAS-induced epithelial-to-mesenchymal transition (EMT) through activation of zinc finger E-box binding homeobox 1 (ZEB1) sensitized tumor cells to the anti-proliferative activity of statins, and induction of EMT by ZEB1 was sufficient to phenocopy the increase in fluvastatin sensitivity; knocking out ZEB1 reversed this effect. Publicly available gene expression and statin sensitivity databases indicated that enrichment of EMT features was associated with increased sensitivity to statins in a large panel of cancer cell lines across multiple cancer types. These results indicate that the anti-cancer effect of statins is independent from prenylation of RAS family proteins and is associated with a cancer cell EMT phenotype.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AL8aEh

Race disparities in the contribution of miRNA isoforms and tRNA-derived fragments to triple-negative breast cancer

Triple-Negative Breast Cancer (TNBC) is a breast cancer subtype characterized by marked differences between White and Black/African-American women. We performed a systems-level analysis on datasets from The Cancer Genome Atlas (TCGA) to elucidate how the expression patterns of messenger RNAs (mRNAs) are shaped by regulatory non-coding RNAs (ncRNAs). Specifically, we studied isomiRs, i.e. isoforms of microRNAs (miRNAs), and tRNA-derived fragments (tRFs). In normal breast tissue, we observed a marked cohesiveness in both the ncRNA and mRNA layers and the associations between them. This cohesiveness was widely disrupted in TNBC: many mRNAs become either differentially expressed or differentially wired between normal breast and TNBC in tandem with isomiR or tRF dysregulation. The affected pathways included energy metabolism, cell signaling and immune responses. Within TNBC, the wiring of the affected pathways with isomiRs and tRFs differed in each race. Multiple isomiRs and tRFs arising from specific miRNA loci (e.g., miR-200c, miR-21, the miR-17/92 cluster, the miR-183/96/182 cluster) and from specific tRNA loci (e.g. the nuclear tRNAGly and tRNALeu, the mitochondrial tRNAVal and tRNAPro) were strongly associated with the observed race disparities in TNBC. We highlight the race-specific aspects of transcriptome wiring by discussing in detail the metastasis-related MAPK and the Wnt/β-catenin signaling pathways, two of the many key pathways that were found differentially wired. In conclusion, by employing a data- and knowledge-driven approach we comprehensively analyzed the normal and cancer transcriptomes to uncover novel key contributors to the race-based disparities of TNBC.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BVS7mF

Coactivation of estrogen receptor and IKK-{beta} induces a dormant metastatic phenotype in ER-positive breast cancer

A growing body of evidence suggests that the inflammatory NFκB pathway is associated with the progression of ER+ tumors to more aggressive stages. However, it is unknown whether NFκB is a driver or a consequence of aggressive ER+ disease. To investigate this question, we developed breast cancer cell lines expressing an inducible, constitutively active form of IκB kinase β (CA-IKKβ), a key kinase in the canonical NFκB pathway. We found that CA-IKKβ blocked E2-dependent cell proliferation in vitro and tumor growth in vivo in a reversible manner, suggesting that IKKβ may contribute to tumor dormancy and recurrence of ER+ disease. Moreover, coactivation of ER and IKKβ promoted cell migration and invasion in vitro and drove experimental metastasis in vivo. Gene expression profiling revealed a strong association between ER and CA-IKKβ-driven gene expression and clinically relevant invasion and metastasis gene signatures. Mechanistically, the invasive phenotype appeared to be driven by an expansion of a basal/stem-like cell population rather than EMT. Taken together, our findings suggest that coactivation of ER and the canonical NFκB pathway promotes a dormant, metastatic phenotype in ER+ breast cancer and implicates IKKβ as a driver of certain features of aggressive ER+ breast cancer.

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

miR-204-5p and miR-211-5p contribute to BRAF inhibitor resistance in melanoma

Melanoma treatment with the BRAF V600E inhibitor vemurafenib (VMF) provides therapeutic benefits but the common emergence of drug resistance remains a challenge. We generated A375 melanoma cells resistant to VMF with the goal of investigating changes in miRNA expression patterns that might contribute to resistance. Increased expression of miR-204-5p and miR-211-5p occurring in VMF-resistant cells was determined to impact VMF response. Their expression was rapidly affected by VMF treatment through RNA stabilization. Similar effects were elicited by MEK and ERK inhibitors but not AKT or Rac inhibitors. Ectopic expression of both miRNA in drug-naive human melanoma cells was sufficient to confer VMF resistance and more robust tumor growth in vivo. Conversely, silencing their expression in resistant cells inhibited cell growth. Joint overexpression of miR-204-5p and miR-211-5p durably stimulated Ras and MAPK upregulation after VMF exposure. Overall, our findings show how upregulation of miR-204-5p and miR-211-5p following VMF treatment enables the emergence of resistance, with potential implications for mechanism-based strategies to improve VMF responses.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BUyDP7

Transcription factor activities enhance markers of drug sensitivity in cancer

Transcriptional dysregulation induced by aberrant Transcription factors (TFs) is a key feature of cancer, but its global influence on drug sensitivity has not been examined. Here we infer the transcriptional activity of 127 TFs through analysis of RNA-seq gene expression data newly generated for 448 cancer cell lines, combined with publicly available datasets to survey a total of 1,056 cancer cell lines and 9,250 primary tumors. Predicted TF activities are supported by their agreement with independent shRNA essentiality profiles and homozygous gene deletions, and recapitulate mutant-specific mechanisms of transcriptional dysregulation in cancer. By analysing cell line responses to 265 compounds, we uncovered numerous TFs whose activity interacts with anti-cancer drugs. Importantly, combining existing pharmacogenomic markers with TF activities often improves the stratification of cell lines in response to drug treatment. Our results, which can be queried freely at dorothea.opentargets.io, offer a broad foundation for discovering opportunities to refine personalised cancer therapies.

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

VEGFR-2-mediated reprogramming of mitochondrial metabolism regulates the sensitivity of acute myeloid leukemia to chemotherapy

Metabolic reprogramming is central to tumorigenesis, but whether chemotherapy induces metabolic features promoting recurrence remains unknown. We established a mouse xenograft model of human acute myeloid leukemia (AML) that enabled chemotherapy-induced regressions of established disease followed by lethal regrowth of more aggressive tumor cells. Human AML cells from terminally ill mice treated with chemotherapy (chemoAML) had higher lipid content, increased lactate production and ATP levels, reduced expression of PPARG coactivator 1α (PGC-1α), and fewer mitochondria than controls from untreated AML animals. These changes were linked to increased vascular endothelial growth factor receptor 2 (VEGFR-2) signaling that counteracted chemotherapy-driven cell death; blocking of VEGFR-2 sensitized chemoAML to chemotherapy (re-)treatment and induced a mitochondrial biogenesis program with increased mitochondrial mass and oxidative stress. Accordingly, depletion of PGC-1α in chemoAML cells abolished such induction of mitochondrial metabolism and chemosensitization in response to VEGFR-2 inhibition. Collectively, this reveals a mitochondrial metabolic vulnerability with potential therapeutic applications against chemotherapy-resistant AML.

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

Genomic and Epigenomic Signatures in Ovarian Cancer Associated with Re-sensitization to Platinum Drugs

DNA methylation aberrations have been implicated in acquired resistance to platinum drugs in ovarian cancer (OC). In this study, we elucidated an epigenetic signature associated with platinum drug re-sensitization that may offer utility in predicting the outcomes of patients who are co-administered a DNA methyltransferase inhibitror. The OC specimens we analyzed were derived from a recent clinical trial that compared the responses of patients with recurrent platinum-resistant OC who received carboplatin plus the DNA methyltransferase inhibitor guadecitabine or a standard of care chemotherapy regimen selected by the treating physician. Tumor biopsies or malignant ascites were collected from patients before treatment (day 1, cycle 1) or after treatment (after 2 cycles) for epigenomic and transcriptomic profiling using the Infinium HumanMethylation450 BeadChip (HM450). We defined 94 gene promoters that were hypomethylated significantly by guadecitabine, with 1659 genes differentially expressed in pre-treatment vs. post-treatment tumors. Pathway analysis revealed that the experimental regimen significantly altered immune re-activation and DNA repair pathways. Progression-free survival correlated with baseline expression levels of 1155 genes involved in 25 networks. In functional investigations in OC cells, engineered upregulation of certain signature genes silenced by promoter methylation (DOK2, miR-293a and others) restored platinum drug sensitivity. Overall, our findings illuminate how inhibiting DNA methylation can sensitize OC cells to platinum drugs, in large part by altering gene expression patterns related to DNA repair and immune activation, with implications for improving the personalized care and survival outcomes of OC patients.

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

LNMICC promotes nodal metastasis of cervical cancer by reprogramming fatty acid metabolism

Cancer spread to lymph nodes (LN) predicts poor survival but underlying mechanisms remain little understood. In this study, we show that overexpression of the long non-coding RNA LNMICC associates with LN metastasis of primary cervical cancer, where it serves as an independent high-risk factor in patient survival. Functional investigations demonstrated that LNMICC promoted LN metastasis by reprogramming fatty acid metabolism, by recruiting the nuclear factor NPM1 to the promoter of the fatty acid binding protein FABP5. We also found that the pro-metastatic effects of LNMICC were directly targeted and suppressed by miR-190. Our results establish a new mechanism of LN metastasis and highlight LNMICC as a candidate prognostic biomarker and therapeutic target in cervical cancer.

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

A2AR adenosine signaling suppresses natural killer cell maturation in the tumor microenvironment.

Extracellular adenosine is a key immunosuppressive metabolite that restricts activation of cytotoxic lymphocytes and impairs anti-tumor immune responses. Here, we show that engagement of A2A adenosine receptor (A2AR) acts as a checkpoint that limits the maturation of natural killer (NK) cells. Both global and NK cell-specific conditional deletion of A2AR enhanced proportions of terminally mature NK cells at homeostasis, following reconstitution, and in the tumor microenvironment. Notably, A2AR-deficient, terminally mature NK cells retained proliferative capacity and exhibited heightened reconstitution in competitive transfer assays. Moreover, targeting A2AR specifically on NK cells also improved tumor control and delayed tumor initiation. Taken together, our results establish A2AR-mediated adenosine signaling as an intrinsic negative regulator of NK cell maturation and anti-tumor immune responses. On the basis of these findings, we propose that administering A2AR antagonists concurrently with NK cell-based therapies may heighten therapeutic benefits by augmenting NK cell-mediated anti-tumor immunity.

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

Downregulating Neuropilin-2 triggers a novel mechanism enabling EGFR-dependent resistance to oncogene-targeted therapies

Neuropilins are a class of cell surface proteins implicated in cell migration and angiogenesis, with aberrant expression in human tumors. Here we show that the expression of Neuropilin-2 (NRP2) controls EGFR protein levels, thereby impinging on intracellular signaling, viability and response to targeted therapies of oncogene-addicted cells. Notably, increased NRP2 expression in EGFR-addicted tumor cells led to downregulation of EGFR protein and tumor cell growth inhibition. Nrp2 also blunted upregulation of an EGFR "rescue" pathway induced by targeted therapy in Met-addicted carcinoma cells. Cancer cells acquiring resistance to MET oncogene-targeted drugs invariably underwent NRP2 loss, a step required for EGFR upregulation. Mechanistic investigations revealed that NRP2 loss activated NFkB and upregulated the EGFR-associated protein KIAA1199/CEMIP, which is known to oppose the degradation of activated EGFR kinase. Notably, KIAA1199 silencing in oncogene-addicted tumor cells improved therapeutic responses and counteracted acquired drug resistance. Our findings define NRP2 as the pivotal switch of a novel broad-acting and actionable pathway controlling EGFR signaling, and driving resistance to therapies targeting oncogene-addiction.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BVdbd9

CDKN2A/p16 deletion in head and neck cancer cells is associated with Cdk2 activation, replication stress, and vulnerability to Chk1 inhibition

Checkpoint kinase inhibitors (CHKi) exhibit striking single agent activity in certain tumors, but the mechanisms accounting for hypersensitivity are poorly understood. We screened a panel of 49 established human head and neck squamous cell carcinoma (HNSCC) cell lines and report that nearly 20% are hypersensitive to CHKi monotherapy. Hypersensitive cells underwent early S-phase arrest at drug doses sufficient to inhibit greater than 90% of Chk1 activity. Reduced rate of DNA replication fork progression and chromosomal shattering were also observed, suggesting replication stress as a root causative factor in CHKi hypersensitivity. To explore genomic underpinnings of CHKi hypersensitivity, comparative genomic analysis was performed between hypersensitive cells and cells categorized as least sensitive because they showed drug IC50 value greater than the cell panel median and lacked early S phase arrest. Novel association between CDKN2A/p16 copy number loss, Cdk2 activation, replication stress and hypersensitivity of HNSCC cells to CHKi monotherapy was found. Restoring p16 in cell lines harboring CDKN2A/p16 genomic deletions alleviated Cdk2 activation and replication stress, attenuating CHKi hypersensitivity. Taken together, our results suggest a biomarker-driven strategy for selecting HNSCC patients who may benefit the most from CHKi therapy.

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

Nkx2-2as suppression contributes to the pathogenesis of Sonic Hedgehog medulloblastoma

Aberrant Hedgehog signaling and excessive activation of the Gli family of transcriptional activators are key drivers of medulloblastoma (MB), the most common human pediatric brain malignancy. MB originates mainly from cerebellar granule neuron progenitors (CGNP), but the mechanisms underlying CGNP transformation remain largely obscure. In this study, we found that suppression of the non-coding RNA Nkx2-2as promotes Sonic Hedgehog (Shh)-potentiated MB development. Nkx2-2as functioned as a competing endogenous RNA (ceRNA) against miR-103 and miR-107, sequestering them and thereby de-repressing their tumor suppressive targets BTG2 and LATS1 and impeding cell division and migration. We also found that Nkx2-2as tethered miR-548m and abrogated its LATS2 targeting activity, Shh signaling impaired Nkx2-2as expression by upregulating the transcriptional repressor FoxD1. In clinical specimens of Shh-subgroup MB we validated coordinated expression of the aforementioned proteins. Notably, exogenous expression of Nkx2-2as suppressed tumorigenesis and prolonged animal survival in MB mouse models. Our findings illuminate the role of non-coding RNAs in Hedgehog signaling and MB occurrence, with implications for identifying candidate therapeutic targets for MB treatment.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ALQ59d

Activation of the Aryl Hydrocarbon Receptor Leads to Resistance to EGFR TKIs in Non-Small-Cell Lung Cancer by Activating Src-Mediated Bypass Signaling

Purpose: The aryl hydrocarbon receptor (AhR) has been generally recognized as a ligand-activated transcriptional factor that responds to xenobiotic chemicals. Recent studies have suggested that the expression of AhR varies widely across different cancer types and cancer cell lines, but its significance in cancer treatment has yet to be clarified. Experimental Design: AhR expression in non-small-cell lung cancer (NSCLC) was determined by Western blotting and IHC staining. In vitro and in vivo functional experiments were performed to determine the effect of AhR on sensitivity to targeted therapeutics. A panel of biochemical assays was used to elucidate the underlying mechanisms. Results: A high AhR protein level indicated an unfavorable prognosis for lung adenocarcinoma. Inhibition of AhR signaling sensitized epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC cells that express high level of endogenous AhR protein. Notably, activation of AhR by pharmacological and molecular approaches rendered EGFR mutant cells resistant to TKIs by restoring PI3K/Akt and MEK/Erk signaling through activation of Src. In addition, we found that AhR acts as a protein adaptor to mediate Jak2-Src interaction, which does not require the canonical transcriptional activity of AhR. Conclusions: Our results reveal a transcription-independent function of AhR and indicate that AhR may act as a protein adaptor that recruits kinases bypassing EGFR and drives resistance to TKIs. Accordingly, targeting Src would be a strategy to overcome resistance to EGFR TKIs in AhR-activated NSCLC.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iTjGW3