Greater Omental Lymph Node Flap for Upper Limb Lymphedema with Lymph Nodes–depleted Patient

Background: The greater omentum is supplied by the right, middle, and left omental arteries, which arise from the right and left gastroepiploic arteries. All or part of the greater omentum can be harvested based on this blood supply for free tissue transfer. It has stimulated new interest in its use as the donor site in the treatment of lymphedema. For patients who have failed other management options or have limited peripheral lymph node donor sites, the greater omental lymph node flap may offer the best chance for lymphedema treatment. Methods: We report a 59-year-old woman with a history of left breast cancer who was treated with left modified radical mastectomy and axillary lymph node dissection and developed left upper extremity Grade IV lymphedema. She received vascularized groin lymph node transfer and lymphaticovenous anastomosis, but the result was not satisfactory. She also had nasopharyngeal cancer that was treated with radiotherapy to the head and neck, making use of the submental lymph nodes flap impossible. Due to a lack of other options of lymph node donor sites, the split greater omental lymph node flap (GOLF) was used. Results: After surgery, it showed an arm circumference reduction of 42.9% above the elbow and 36.4% below the elbow at an 8-month follow-up. There was no intraabdominal complication. Conclusions: The split GOLF has shown good results in a peripheral lymph node–depleted lymphedema patient. Using a laparoscopic technique for flap harvest has less risk of donor site morbidity and hides scarring.

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Chronological Order of Lipofilling during Implant Exchange

No abstract available

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Skin Necrosis Caused by Simple Massage Equipment

No abstract available

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Sickle cell disease and implementation science: A partnership to accelerate advances

Abstract

Sickle cell disease (SCD) results in end organ damage and a shortened lifespan. Both the pathophysiology of the disease and the social determinants of health affect patient outcomes. Randomized controlled trials have been completed among this population and resulted in medical advances; however, the gestation of these advances and the lack of penetrance into clinical practice have limited advancements in clinical improvements for many people with SCD. We discuss the role of implementation science in SCD and highlight the need for this science to shorten the length of time to implement evidence-based care for more people with SCD.

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Care Bundles in Emergency Medicine

Abstract

The ability to make sound clinical decisions in a high stress and often chaotic atmosphere lies at the heart of emergency medicine. This can be a daunting task when one considers the sheer volume of pathology covered under the umbrella of emergency medicine.

This article is protected by copyright. All rights reserved.

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Recent 210Pb, 137Cs and 241Am accumulation in an ombrotrophic peatland from Amsterdam Island (Southern Indian Ocean)

Publication date: September 2017
Source:Journal of Environmental Radioactivity, Volumes 175–176
Author(s): Chuxian Li, Gaël Le Roux, Jeroen Sonke, Pieter van Beek, Marc Souhaut, Nathalie Van der Putten, François De Vleeschouwer
Over the past 50 years, ²¹⁰Pb, ¹³⁷Cs and ²⁴¹Am have been abundantly used in reconstructing recent sediment and peat chronologies. The study of global aerosol-climate interaction is also partially depending on our understanding of ²²²Rn-²¹⁰Pb cycling, as radionuclides are useful aerosol tracers. However, in comparison with the Northern Hemisphere, few data are available for these radionuclides in the Southern Hemisphere, especially in the South Indian Ocean. A peat core was collected in an ombrotrophic peatland from the remote Amsterdam Island (AMS) and was analyzed for ²¹⁰Pb, ¹³⁷Cs and ²⁴¹Am radionuclides using an underground ultra-low background gamma spectrometer. The ²¹⁰Pb Constant Rate of Supply (CRS) model of peat accumulations is validated by peaks of artificial radionuclides (¹³⁷Cs and ²⁴¹Am) that are related to nuclear weapon tests. We compared the AMS ²¹⁰Pb data with an updated ²¹⁰Pb deposition database. The ²¹⁰Pb flux of 98 ± 6 Bq·m⁻²·y⁻¹ derived from the AMS core agrees with data from Madagascar and South Africa. The elevated flux observed at such a remote location may result from the enhanced ²²²Rn activity and frequent rainfall in AMS. This enhanced ²²²Rn activity itself may be explained by continental air masses passing over southern Africa and/or Madagascar. The ²¹⁰Pb flux at AMS is higher than those derived from cores collected in coastal areas in Argentina and Chile, which are areas dominated by marine westerly winds with low ²²²Rn activities. We report a ¹³⁷Cs inventory at AMS of 144 ± 13 Bq·m⁻² (corrected to 1969). Our data thus contribute to the under-represented data coverage in the mid-latitudes of the Southern Hemisphere.



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Amelanotic melanoma in oculocutaneous albinism: a genetic, dermoscopic and reflectance confocal microscopy study

Abstract

Herein we describe the usefulness of a successful combination of dermoscopy and in vivo RCM for the early diagnosis of 3 AM in 2 OCA patients OCA is a group of rare autosomal recessive disorders of pigmentation. It consists in the absence or reduction of melanin in the skin, hair, and eyes due to a partial or total deficit in the activity of tyrosinase(TYR)¹ or other related genes^2,3. Those patients are at higher risk of non melanoma skin cancer, while still debated is their increased risk of melanoma, in particular amelanotic⁴. They usually lack in clinical and dermoscopic pattern, what makes them challenging to be diagnosed, especially at early stage.

This article is protected by copyright. All rights reserved.

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Heterogeneity of trichoscopy findings in dissecting cellulitis of the scalp: correlation to disease activity and duration

Abstract

dissecting cellulitis of the scalp (DCS) is a chronic inflammatory condition characterized by recurrent nodules, abscesses and sinus tract formation.^1-3 It usually starts as a simple folliculitis with occlusion of follicular openings mainly on the scalp vertex or nape, generally followed by perifollicular pustules and painful firm or fluctuant nodules releasing a purulent discharge, either spontaneously or after a gentle pressure.

This article is protected by copyright. All rights reserved.

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The association between psoriasis and coeliac disease

Psoriasis is known to be associated with inflammatory comorbidities. Coeliac disease (CD) is an immune-mediated enteropathy caused by permanent intolerance to dietary gliadin, which is present in wheat, barley, and rye.¹ The disease occurs in predisposed individuals, and is characterized clinically by malabsorption and histologically by villous atrophy and crypt hyperplasia, which improves when the causal antigen is removed through a gluten-free diet.¹ We investigated the relationship between psoriasis and CD in Denmark.

This article is protected by copyright. All rights reserved.

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Aspiration of Aluminum Beverage Can Tab: Case Report and Literature Review

We describe the case of a 16-year-old male who aspirated a beverage can tab resulting in significant functional impairment. Since the introduction of beverage can opening tabs (“pop-tops” or “pull-tabs”) nearly 50 years ago, five cases of their aspiration have been reported in the literature and this is the first case to report tracheal lodgment. We describe the clinical course for this patient including the inadequacy of radiographic evaluation and a significant delay in diagnosis. We highlight unique features of small aluminum foreign bodies that require consideration and mention a potential change in epidemiology associated with evolving product design. Our primary objective is increased awareness among otolaryngologists that radiography is unreliable for diagnosis or localization of small aluminum foreign bodies. The patient history must therefore be incorporated with other imaging modalities and/or endoscopic evaluation. Also, given the marked prevalence of aluminum beverage cans, we suspect that the inadvertent aspiration of can tabs is more common than indicated by the paucity of published reports.

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Recurrent Meningitis

Abstract

Purpose of Review

Recurrent meningitis is a rare clinical scenario that can be self-limiting or life threatening depending on the underlying etiology. This review describes the causes, risk factors, treatment, and prognosis for recurrent meningitis. As a general overview of a broad topic, the aim of this review is to provide clinicians with a comprehensive differential diagnosis to aide in the evaluation and management of a patient with recurrent meningitis.

Recent Findings

New developments related to understanding the pathophysiology of recurrent meningitis are as scarce as studies evaluating the treatment and prevention of this rare disorder. A trial evaluating oral valacyclovir suppression after HSV-2 meningitis did not demonstrate a benefit in preventing recurrences. The data on prophylactic antibiotics after basilar skull fractures do not support their use. Intrathecal trastuzumab has shown promise in treating leptomeningeal carcinomatosis from HER-2 positive breast cancer. Monoclonal antibodies used to treat cancer and autoimmune diseases are new potential causes of drug-induced aseptic meningitis.

Summary

Despite their potential for causing recurrent meningitis, the clinical entities reviewed herein are not frequently discussed together given that they are a heterogeneous collection of unrelated, rare diseases. Epidemiologic data on recurrent meningitis are lacking. The syndrome of recurrent benign lymphocytic meningitis described by Mollaret in 1944 was later found to be closely related to HSV-2 reactivation, but HSV-2 is by no means the only etiology of recurrent aseptic meningitis. While the mainstay of treatment for recurrent meningitis is supportive care, it is paramount to ensure that reversible and treatable causes have been addressed for further prevention.

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Back Pain with Leg Pain

Abstract

Purpose of Review

The clinical diagnostic dilemma of low back pain that is associated with lower limb pain is very common. In relation to back pain that radiates to the leg, the International Association for the Study of Pain (IASP) states: “Pain in the lower limb should be described specifically as either referred pain or radicular pain. In cases of doubt no implication should be made and the pain should be described as pain in the lower limb.”

Recent Findings

Bogduks’ editorial in the journal PAIN (2009) helps us to differentiate and define the terms somatic referred pain, radicular pain, and radiculopathy. In addition, there are other pathologies distal to the nerve root that could be relevant to patients with back pain and leg pain such as plexus and peripheral nerve involvement. Hence, the diagnosis of back pain with leg pain can still be challenging.

Summary

In this article, we present a patient with back and leg pain. The patient appears to have a radicular pain syndrome, but has no neurological impairment and shows signs of myofascial involvement. Is there a single diagnosis or indeed two overlapping syndromes? The scope of our article encompasses the common diagnostic possibilities for this type of patient. A discussion of treatment is beyond the scope of this article and depends on the final diagnosis/diagnoses made.

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Primary Headaches and School Performance—Is There a Connection?

Abstract

Purpose of Review

Headache is a common complaint among children and adolescents. School functioning is one of the most important life domains impacted by chronic pain in children. This review discusses the epidemiological and pathophysiological connections between headaches and school functioning including a suggested clinical approach.

Recent Findings

The connection between recurrent and chronic headache and learning disabilities might be psychosocial (fear of failure) or anatomical (malfunctioning of the frontal and prefrontal areas). Only few population-based and clinical studies were done and good studies are still needed in order to understand the complex relationship better. However, relating to our patients’ learning and school performance, history is crucial when a child with primary headaches is evaluated.

Summary

Learning disabilities seem to have a high prevalence among children with primary headache syndromes especially migraine. The connection between the two is complex and might be either part of a common brain pathophysiology and/or a consequence of poor quality of life.

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Risk stratification of women with false-positive test results in mammography screening based on mammographic morphology and density: A case control study

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Rikke Rass Winkel, My von Euler-Chelpin, Elsebeth Lynge, Pengfei Diao, Martin Lillholm, Michiel Kallenberg, Julie Lyng Forman, Michael Bachmann Nielsen, Wei Yao Uldall, Mads Nielsen, Ilse Vejborg
BackgroundThe long-term risk of breast cancer is increased in women with false-positive (FP) mammography screening results. We investigated whether mammographic morphology and/or density can be used to stratify these women according to their risk of future breast cancerMethodsWe undertook a case-control study nested in the population-based screening programme in Copenhagen, Denmark. We included 288 cases and 288 controls based on a cohort of 4743 women with at least one FP-test result in 1991–2005 who were followed up until 17 April 2008. Film-based mammograms were assessed using the Breast Imaging-Reporting and Data System (BI-RADS) density classification, the Tabár classification, and two automated techniques quantifying percentage mammographic density (PMD) and mammographic texture (MTR), respectively. The association with breast cancer was estimated using binary logistic regression calculating Odds Ratios (ORs) and the area under the receiver operating characteristic (ROC) curves (AUCs) adjusted for birth year and age and invitation round at the FP-screenResultsSignificantly increased ORs were seen for BI-RADS D(density)2-D4 (OR 1.94; 1.30-2.91, 2.36; 1.51-3.70 and 4.01; 1.67-9.62, respectively), Tabár’s P(pattern)IV (OR 1.83; 1.16-2.89), PMD Q(quartile)2-Q4 (OR 1.71; 1.02-2.88, 1.97; 1.16-3.35 and 2.43; 1.41-4.19, respectively) and MTR Q4 (1.97; 1.12-3.46) using the lowest/fattiest category as referenceConclusionAll four methods, capturing either mammographic morphology or density, could segregate women with FP-screening results according to their risk of future breast cancer − using already available screening mammograms. Our findings need validation on digital mammograms, but may inform potential future risk stratification and tailored screening strategies



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Recurrent Meningitis

Abstract

Purpose of Review

Recurrent meningitis is a rare clinical scenario that can be self-limiting or life threatening depending on the underlying etiology. This review describes the causes, risk factors, treatment, and prognosis for recurrent meningitis. As a general overview of a broad topic, the aim of this review is to provide clinicians with a comprehensive differential diagnosis to aide in the evaluation and management of a patient with recurrent meningitis.

Recent Findings

New developments related to understanding the pathophysiology of recurrent meningitis are as scarce as studies evaluating the treatment and prevention of this rare disorder. A trial evaluating oral valacyclovir suppression after HSV-2 meningitis did not demonstrate a benefit in preventing recurrences. The data on prophylactic antibiotics after basilar skull fractures do not support their use. Intrathecal trastuzumab has shown promise in treating leptomeningeal carcinomatosis from HER-2 positive breast cancer. Monoclonal antibodies used to treat cancer and autoimmune diseases are new potential causes of drug-induced aseptic meningitis.

Summary

Despite their potential for causing recurrent meningitis, the clinical entities reviewed herein are not frequently discussed together given that they are a heterogeneous collection of unrelated, rare diseases. Epidemiologic data on recurrent meningitis are lacking. The syndrome of recurrent benign lymphocytic meningitis described by Mollaret in 1944 was later found to be closely related to HSV-2 reactivation, but HSV-2 is by no means the only etiology of recurrent aseptic meningitis. While the mainstay of treatment for recurrent meningitis is supportive care, it is paramount to ensure that reversible and treatable causes have been addressed for further prevention.

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Back Pain with Leg Pain

Abstract

Purpose of Review

The clinical diagnostic dilemma of low back pain that is associated with lower limb pain is very common. In relation to back pain that radiates to the leg, the International Association for the Study of Pain (IASP) states: “Pain in the lower limb should be described specifically as either referred pain or radicular pain. In cases of doubt no implication should be made and the pain should be described as pain in the lower limb.”

Recent Findings

Bogduks’ editorial in the journal PAIN (2009) helps us to differentiate and define the terms somatic referred pain, radicular pain, and radiculopathy. In addition, there are other pathologies distal to the nerve root that could be relevant to patients with back pain and leg pain such as plexus and peripheral nerve involvement. Hence, the diagnosis of back pain with leg pain can still be challenging.

Summary

In this article, we present a patient with back and leg pain. The patient appears to have a radicular pain syndrome, but has no neurological impairment and shows signs of myofascial involvement. Is there a single diagnosis or indeed two overlapping syndromes? The scope of our article encompasses the common diagnostic possibilities for this type of patient. A discussion of treatment is beyond the scope of this article and depends on the final diagnosis/diagnoses made.

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Primary Headaches and School Performance—Is There a Connection?

Abstract

Purpose of Review

Headache is a common complaint among children and adolescents. School functioning is one of the most important life domains impacted by chronic pain in children. This review discusses the epidemiological and pathophysiological connections between headaches and school functioning including a suggested clinical approach.

Recent Findings

The connection between recurrent and chronic headache and learning disabilities might be psychosocial (fear of failure) or anatomical (malfunctioning of the frontal and prefrontal areas). Only few population-based and clinical studies were done and good studies are still needed in order to understand the complex relationship better. However, relating to our patients’ learning and school performance, history is crucial when a child with primary headaches is evaluated.

Summary

Learning disabilities seem to have a high prevalence among children with primary headache syndromes especially migraine. The connection between the two is complex and might be either part of a common brain pathophysiology and/or a consequence of poor quality of life.

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Aspiration of Aluminum Beverage Can Tab: Case Report and Literature Review

We describe the case of a 16-year-old male who aspirated a beverage can tab resulting in significant functional impairment. Since the introduction of beverage can opening tabs (“pop-tops” or “pull-tabs”) nearly 50 years ago, five cases of their aspiration have been reported in the literature and this is the first case to report tracheal lodgment. We describe the clinical course for this patient including the inadequacy of radiographic evaluation and a significant delay in diagnosis. We highlight unique features of small aluminum foreign bodies that require consideration and mention a potential change in epidemiology associated with evolving product design. Our primary objective is increased awareness among otolaryngologists that radiography is unreliable for diagnosis or localization of small aluminum foreign bodies. The patient history must therefore be incorporated with other imaging modalities and/or endoscopic evaluation. Also, given the marked prevalence of aluminum beverage cans, we suspect that the inadvertent aspiration of can tabs is more common than indicated by the paucity of published reports.

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Effects of Long-Term Exposure to Traffic-Related Air Pollution on Lung Function in Children

Abstract

Lung function in early life has been shown to be an important predictor for peak lung function in adults and later decline. Reduced lung function per se is associated with increased morbidity and mortality. With this review, we aim to summarize the current epidemiological evidence on the effect of traffic-related air pollution on lung function in children and adolescents. We focus in particular on time windows of exposure, small airway involvement, and vulnerable sub-groups in the population. Findings from studies published to date support the notion that exposure over the entire childhood age range seems to be of importance for lung function development. We could not find any conclusive data to support evidence of sup-group effects considering gender, sensitization status, and asthma status, although a possibly stronger effect may be present for children with asthma. The long-term effects into adulthood of exposure to air pollution during childhood remains unknown, but current studies suggest that these deficits may be propagated into later life. In addition, further research on the effect of exposure on small airway function is warranted.

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Alopecia Areata: An Update on Treatment Options for Children

Abstract

Pediatric alopecia areata is a spectrum of autoimmune non-scarring alopecia in which some patients lose small patches of hair from their scalp but others lose more or all of the hair from the scalp and body, including eyebrows and eyelashes. Few studies have looked at therapies for this disorder in children, so much of the data are derived from adult literature and describe off-label use of medication. Generally, topical therapies consisting of topical steroids and topical irritating compounds/contact sensitizers are used. Systemic therapies that block the immune system, including Janus kinase (JAK) inhibitors, have also been used in this disease. This paper reviews the data on therapy for alopecia areata in pediatric patients.

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Linking neuroethology to the chemical biology of natural products: interactions between cone snails and their fish prey, a case study

Abstract

From a biological perspective, a natural product can be defined as a compound evolved by an organism for chemical interactions with another organism including prey, predator, competitor, pathogen, symbiont or host. Natural products hold tremendous potential as drug leads and have been extensively studied by chemists and biochemists in the pharmaceutical industry. However, the biological purpose for which a natural product evolved is rarely addressed. By focusing on a well-studied group of natural products—venom components from predatory marine cone snails—this review provides a rationale for why a better understanding of the evolution, biology and biochemistry of natural products will facilitate both neuroscience and the potential for drug leads. The larger goal is to establish a new sub-discipline in the broader field of neuroethology that we refer to as "Chemical Neuroethology", linking the substantial work carried out by chemists on natural products with accelerating advances in neuroethology.

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Oral lichenoid dysplasia and exophytic oral verrucous hyperplasia: Mythical entities of oral pathology

The World Health Organisation (WHO) has replaced the terms oral precancerous lesions and conditions with “Oral potentially malignant disorders (OPMD).” The latter term aptly describes its wide anatomical distribution and emphasizes the fact that not all such disorders turn into malignancy [1]. OPMD presents in various forms ranging from a flat white patch to exophytic verrucous growth. Although most OPMDs have precise definitions and strict diagnostic criteria’s, the existences of a few lesions including oral lichenoid dysplasia (OLD) and exophytic oral verrucous hyperplasia (OVH) are still debated.

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Oral lichenoid dysplasia and exophytic oral verrucous hyperplasia: Mythical entities of oral pathology

The World Health Organisation (WHO) has replaced the terms oral precancerous lesions and conditions with “Oral potentially malignant disorders (OPMD).” The latter term aptly describes its wide anatomical distribution and emphasizes the fact that not all such disorders turn into malignancy [1]. OPMD presents in various forms ranging from a flat white patch to exophytic verrucous growth. Although most OPMDs have precise definitions and strict diagnostic criteria’s, the existences of a few lesions including oral lichenoid dysplasia (OLD) and exophytic oral verrucous hyperplasia (OVH) are still debated.

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Loss of gait control assessed by cognitive-motor dual-tasks: pros and cons in detecting people at risk of developing Alzheimer’s and Parkinson’s diseases

Abstract

Alzheimer’s and Parkinson’s diseases are age-related progressive neurodegenerative diseases of increasing prevalence worldwide. In the absence of curative therapy, current research is interested in prevention, by identifying subtle signs of early-stage neurodegeneration. Today, the field of behavioral neuroscience has emerged as one of the most promising areas of research on this topic. Recently, it has been shown that the exacerbation of gait disorders under dual-task conditions (i.e., simultaneous performance of cognitive and motor tasks) could be a characteristic feature of Alzheimer’s and Parkinson’s diseases. The cognitive-motor dual-task paradigm during walking allows to assess whether (i) executive attention is abnormally impaired in prodromal Alzheimer’s disease or (ii) compensation strategies are used in order to preserve gait function when the basal ganglia system is altered in prodromal Parkinson’s disease. This review aims at (i) identifying patterns of dual-task-related gait changes that are specific to Alzheimer’s and Parkinson’s diseases, respectively, (ii) demonstrating that these changes could potentially be used as prediagnostic markers for disease onset, (iii) reviewing pros and cons of existing dual-task studies, and (iv) proposing future directions for clinical research.

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Protective effects of royal jelly on the histomorphologic, oxidative stress and sperm parameters in Ofloxacin treated rat

Abstract

Royal jelly is produced by worker bees as nutrition for bee larvae and adult queens and has also been shown to have protective effects against antibiotics. The aim of this investigation was to determine protective effect of royal jelly on the reproductive functions of male rats treated with ofloxacin. In this experiment, 32 mature male albino rats were randomly allocated into four groups (n = 8): control, ofloxacin only, royal jelly only, and ofloxacin with royal jelly. The results revealed that ofloxacin alone caused significant decreases (P < 0.05) in follicle-stimulating hormone, luteinizing hormone, testosterone, sperm count, sperm viability, total thiol molecules, and total antioxidant capacity compared to the control group. However, levels of immature sperm, DNA impaired sperm, malondialdehyde and nitric oxide were significantly increased (P < 0.05) in the ofloxacin group compared to the control. In the ofloxacin with royal jelly group, no significant increases or decreases were observed. Royal jelly has protective effects on reproductive function of male rat treated with ofloxacin.

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A rare case of sarcoidosis in accessory spleen

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Sentinel node biopsy status is strongly predictive of survival in cutaneous melanoma: Extended follow-up of Oxford patients from 1998-2014

Sentinel lymph node biopsy (SLNB) is widely used as a key investigatory tool for cutaneous melanoma, with results incorporated into the latest AJCC staging guidelines. We present the results of our extended follow-up of sentinel lymph node biopsy for melanoma over a sixteen-year period.

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Computer generated three-dimensional modeling using passive stereophotogrammetry and structured light scanning for craniomaxillofacial imaging

I read with great interest the useful and insightful manuscript by Knoops et al.1 The authors highlight several techniques for three-dimensional scanning that may be useful for craniomaxillofacial imaging,2,3 and helpfully point out newly available lower-cost approaches to facial scanning which may increase the adoption of this important technology.

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WhatsApp: Improvement tool for surgical team communication

We would like to thank Dr Brewtser et al. for their comments (1) on our recent article entitled “WhatsApp: Improvement tool for surgical team communication”(2). This useful information made us review the Electronic Frontier Foundation (EFF) research and their conclusion about security of different smart phone communication applications (3).

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The Combined Vaginoplasty Technique for Male-to-Female Sex Reassignment Surgery: Operative Approach and Outcomes

Several therapy options exist for male-to-female (MTF) transgenders desiring sex reassignment. Surgery includes numerous different procedures. Of those, vaginoplasty is predominant and aims at providing attractive aesthetics and fully functional genitals.The goal of this study was to present the surgical results of our modified combined vaginoplasty technique in a consecutive patient cohort.

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Innervated dorsoradial perforator free flap: A reliable supermicrosurgery fingertip reconstruction technique

This study demonstrates the use of a modified free innervated DRAP flap utilizing the supermicrosurgery technique for fingertip reconstruction.

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Limitation of ischaemic tissue response in a reconstruction with short ischaemia time during free flap surgery

In free flap surgery, patency of the arterial and venous microvascular anastomoses is a major contributor to flap survival. Extended periods of vascular compromise may lead to ischaemic necrosis, which can only be minimized by tissue reperfusion. However, restoration of blood flow evokes ischaemia reperfusion injury. In this manuscript, a case is presented of a patient who demonstrated a normal oxygenation pattern of a deep inferior epigastric perforator (DIEP) flap. As an ischaemic response can be seen as a sign of temporal vascular compromise, we hypothesize that a short ischaemia time is feasible for tissue viability by eliminating ischaemia reperfusion injury.

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What triggers in trigger finger? The flexor tendons at the Flexor Digitorum Sublimis bifurcation

To define the role of the flexor tendons in trigger finger, a high resolution ultrasound examination was undertaken in 20 trigger fingers and 20 normal contralateral digits in 3 digital postures: full extension, mid flexion and near-full flexion. Precise measurements of diameter and cross sectional area of the combined tendon mass were recorded at 5 clearly defined locations: summit of metacarpal head, proximal lip of proximal phalanx (PP), at 1/8, 1⁄4 and 1/2 length of PP. In the normal tendons, there was an anatomical thickening, not previously appreciated at 1⁄4 length PP, in the region of FDS bifurcation.

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Meta-analysis of the effects of genetic polymorphisms on intervertebral disc degeneration

Abstract

Introduction

Chronic low back pain is a significant public health issue. Both its direct and indirect cost represents tens of billions of US dollars. Although chronic low back pain can be the result of many factors, the predominant cause is disc degeneration. Recent studies have shown genetic involvement in up to 74% of cases. This study aimed to evaluate genetic risk factors of disc degeneration by performing a systematic analysis of association studies. The objective is to provide a guide for practice by assessing the clinical relevance of current information.

Methods and materials

We performed a meta-analysis of 3122 items collected from 6 databases. 74 articles were selected according to our inclusion criteria. 18 (24%) could be grouped into 16 meta-analyses of 16 mutations in 12 genes. The statistics of the meta-analysis were conducted through Revman 5.1 software.

Results

The items included are 10,250 cases and 14,136 controls. The GOLD range from 3.42 to 0.38. Two alleles were significantly associated with disc degeneration: IL-6 rs1800797 and MMP-9 rs17576 and one proved to be protective: IL-6 rs1800795. 13 meta-analyses did not yield significant results and methodological heterogeneity.

Discussion

The results highlight the lack of methodological rigor in most of the studies. The absence of international clinical and radiological classification of early disc degeneration, limits the homogeneity of studies. Understanding which populations are predisposed to this significant public health problem may change our approach to diagnostic and therapeutic methods. This work opens up enormous opportunities to provide a genetic solution and consider new diagnostic and therapeutic means to this public health problem.

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Rate and mode of screw misplacements after 3D-fluoroscopy navigation-assisted insertion and 3D-imaging control of 1547 pedicle screws in spinal levels T10-S1 related to vertebrae and spinal sections

Abstract

Purpose

In the field of spinal surgery, 3D-fluoroscopy navigation-assisted pedicle screw (PS) insertion with intra-operative 3D-image control represents a modern application of contemporary navigation technology. In literature, sectional or vertebral accuracy limitations of this image-guidance approach are not profoundly specified. This observational study explicitly differentiates accuracy rates and misplacement mode between spinal sections and single vertebrae from T10 to S1 using a navigation-assisted approach.

Methods

From February 2011 through July 2015, all 3D-fluoroscopy navigation-assisted, 3D-image controlled PS insertions from T10 to S1 were prospectively recorded and evaluated for PS insertion depth, angulation, and entering-point modifications after intraoperative O-arm control scanning. Major complications requiring revision surgery for neurological damage/major bleedings, and procedure-related unintended violations of anatomical structures were recorded.

Results

In 1547 navigation-assisted PS insertions, thoracolumbar accuracy (96.4%) was significantly higher than sacral accuracy (92.6%, p ≈ 0.007) due to special requirements to exact PS (insertion depth) in S1 (p < 0.001). Vertebrae with modification rates above average were identified (T10, L5-S1) (p < 0.001). Major complications did not occur, anatomical structures were violated in 1.2% (19/1547 PS insertions).

Conclusions

In navigation-assisted O-arm-controlled PS placements, correct PS insertion depths are less easily to achieve than correct trajectory or entering-points, which is important for bicortical PS anchorage in S1. Therefore, post-instrumentation PS control by 3D-imaging or at least intraoperative fluoroscopy is recommended for levels with special requirements to exact PS insertion depths (e.g. S1).

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Obstructive sleep apnea: effect of comorbidities and positive airway pressure on all-cause mortality

Most studies have used cardiovascular and cerebrovascular disease (CVD) end-points to measure the effect of continuous positive airway pressure (CPAP), but pre-diagnostic morbidities involve a range of comorbidities that may influence the consequences of obstructive sleep apnea (OSA). We therefore aimed to evaluate all-cause total mortality after a diagnosis of OSA, the effect of CPAP in women and men, and the potential effect of major comorbidities.

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Acute and painful exacerbation of RLS and PLM induced by opioid interaction - withdrawal syndrome

An 87-year-old, non-demented man with long-standing history of restless legs syndrome (RLS) was admitted to the emergency unit with acute pain and motor restlessness, as well as intense periodic limb movements (PLMs) occurring approximately every 20 seconds, involving the whole body(eg, both legs, arms, and the trunk).

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Dopamine and serotonin levels in cerebrospinal fluid during episodes of Kleine-Levin syndrome

Kleine-Levin syndrome (KLS) is characterized by recurrent episodes of hypersomnia, cognitive disturbances, apathy, derealization, mood disturbances, hyperphagia, hypersexuality and dysautonomia [1]. The etiology of KLS is unknown. Increased dopamine turnover in the cerebrospinal fluid (CSF) was shown in one patient with KLS and was greater in symptomatic than in the asymptomatic period [2]. The dopamine transporter availability decreased in the striatum of a teenager with KLS and was more marked in the symptomatic than in the asymptomatic phase [3].

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Frontal dysfunction in patients with restless legs syndrome performing a visual oddball task: An event-related potential source imaging study

Restless legs syndrome (RLS) is a sensorimotor neurological disorder that is accompanied by the compelling urge to move one’s legs, and unpleasant, disturbing sensations in the legs. Several neuropsychological studies have shown that RLS is associated with deficits in cognitive functions, such as attention, working memory, and frontal executive function, presumably due to abnormal frontal activities. However, the mechanism underlying the cognitive deficits in RLS patients is mostly unknown. To investigate the cortical origin of cognitive dysfunction in RLS, we analyzed the P2 and P3 event-related potential (ERP) components evoked by a visual oddball task using distributed cortical source localization via low-resolution brain electromagnetic tomography (LORETA) algorithm.

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Risk of obstructive sleep apnea among patients with Cushing’s syndrome: A nationwide longitudinal study

Previous studies have demonstrated the association between Cushing’s syndrome (CS), obstructive sleep apnea (OSA), and the risk factors for OSA, but rarely provided the evidence within a large population. Using the Taiwan National Health Insurance Research Database, we attempted to investigate the association between CS and OSA, and to provide persuading evidences.

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Concurrent Focal Fat Sparing and Peritumoral Fat Sparing in Diffuse Fatty Liver Identified on 18F-FDG PETCT and Multiparametric Magnetic Resonance Imaging

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Concurrent Focal Fat Sparing and Peritumoral Fat Sparing in Diffuse Fatty Liver Identified on 18F-FDG PETCT and Multiparametric Magnetic Resonance Imaging

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MiR-1271 Inhibits Cell Growth in Prostate Cancer by Targeting ERG

Abstract

ETS-related gene (ERG) is an oncogene that is commonly found in prostate cancer (PCa). Several miRNAs have been reported to be associated with PCa. This study was undertaken to identify miRNAs that act as a tumor suppressor by targeting ERG. We collected 70 PCa and paired adjacent non-tumor (Adjacent-N) tissues and analyzed ERG expression by immunohistochemistry(IHC). Expression of 6 miRNAs (miR-21,-34a,-96,-125b,-150 and miR-1271) was analyzed by qRT-PCR. Luciferase reporter assay was performed to examine miRNA binding to the 3′-UTR of target genes. The effects of ectopic expression of miRNA on cell growth and MAPK signaling pathway were investigated in in PC-3 and LNCaP cell lines. Among 70 PCa cases, 13 (18.6%) were ERG positive. No significant difference of miR-34a, 96, 125b, and 150 expression was found between PCa and Adjacent-N tissues. Significantly higher level of miR-21 and lower level of miR-1271 expression were found in cancer tissues. Furthermore, miR-1271 was down-regulated in ERG-positive PCa cases (p < 0.05). Based on luciferase reporter assay, we identified ERG gene as a direct target gene for miR-1271. Transfection of a miR-1271 mimics into PC-3 and LNCaP cells repressed the ERG expression and significantly suppressed cell growth. Lastly, ectopic expression of miR-1271 inhibits AKT1, p38gama and CREB kinase activity. Our results suggested that reduced expression of miR-1271 may be involved in the ERG expression and that miR-1271 could be a therapeutic target for ERG-positive prostate cancer patients.

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Faisabilité et tolérance de Sienna+® pour la détection du ganglion sentinelle : étude pilote unicentrique sur 30 cas consécutifs

Publication date: Available online 26 May 2017
Source:Cancer/Radiothérapie
Author(s): N. Ly, M. Sauvan, A. Chillès, J. Ratour, N. Musmesci, R. Rouzier, A. Tardivon, Y.M. Kirova, S. Alran




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Facteurs pronostiques de la ré-irradiation des cancers des voies aérodigestives supérieures : revue de la littérature

Publication date: Available online 27 May 2017
Source:Cancer/Radiothérapie
Author(s): T. Ohnleiter, P. Truntzer, D. Antoni, S. Guihard, A.-M. Elgard, G. Noël
Objectif de l’étudePréciser l’efficacité de la ré-irradiation des cancers des voies aérodigestives supérieures et faire une synthèse des facteurs pronostiques mis en évidence dans les séries de patients publiées.Matériels et méthodesUne recherche des séries originales de ré-irradiation externe des cancers des voies aérodigestives supérieures comprenant au moins dix patients a été réalisée dans la base de données Medline.RésultatsLa survie médiane des patients traités par ré-irradiation exclusive avec ou sans chimiothérapie concomitante est de l’ordre de 11 mois, comparativement à 6 mois pour la chimiothérapie seule, avec de 20 à 40 % de survivants à deux ans. Les taux de survie à 3 ans varient de 40 à 60 % en situation postopératoire. Des effets secondaires de grades 3 ou plus apparaissent chez plus de 50 % des patients. Les facteurs de pronostic favorable liés au patient sont le sexe masculin, un âge jeune, un bon état général et l’absence de maladies associées. Ceux liés à la maladie sont un stade rT et rN bas, une tumeur peu différenciée, une histologie autre qu’un carcinome épidermoïde et une localisation au niveau de cavum, du larynx ou de l’oropharynx. En ce qui concerne le traitement, la chirurgie, une dose de plus de 50 à 60Gy dans un volume petit lors de la ré-irradiation, un intervalle entre le premier traitement et la ré-irradiation de plus de 2 ans et l’utilisation d’une technique innovante sont les facteurs pronostiques les plus souvent mis en évidence. L’utilisation de la chimiothérapie concomitante est souvent associée à une plus forte toxicité, sans pour autant améliorer la probabilité de survie globale, à l’exception des chimiothérapies incorporant du cisplatine chez des patients très sélectionnés.ConclusionsLa ré-irradiation des voies aérodigestives supérieures permet d’obtenir des survies de longue durée. Cependant, compte tenu de la toxicité associée, les patients qui peuvent en bénéficier doivent être rigoureusement sélectionnés en fonction de facteurs pronostiques.PurposeTo specify the effectiveness of head and neck cancer reirradiation and make a synthesis of prognostic factors established by published series of patients.Materials and methodsOriginal series of external reirradiation of head and neck cancer with at least ten patients were sought in Medline database.ResultsExclusive reirradiation with or without concurrent chemotherapy offers 11 months of median overall survival, versus 6 months for chemotherapy alone, and 20 to 40% of the patients are still alive two years after treatment. Postoperative reirradiation allows 3 years overall survival from 40 to 60%. However, side effects of grade 3 or more arise in more than half of patients. Patient-related good prognostic factors are male, young age, good performance status without comorbidities. Those related to the disease are low rT and rN stage, poor differentiation, other than squamous cell carcinomas and a nasopharyngeal, oropharyngeal or laryngeal location. Concerning the treatment, surgical resection, a dose higher than 50 to 60Gy in a smaller-irradiated volume, an interval between the two treatments of more than 2 years and the use of an innovating technology are the most commonly highlighted prognostic factors. Concurrent chemotherapy is often associated with higher toxicity rates, without improving overall survival, unless using cisplatin for selected patients.ConclusionsHead and neck cancer reirradiation achieves long-term survival outcomes. However, regarding to its associated side effects, patients need to be carefully selected based on prognostic factors.



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Cierre endoscópico de las perforaciones septales

Publication date: Available online 27 May 2017
Source:Acta Otorrinolaringológica Española
Author(s): Isam Alobid
IntroducciónEl cierre quirúrgico de las perforaciones septales sintomáticas a menudo conduce a resultados no satisfactorios. El conocimiento de la irrigación vascular es de suma importancia para el éxito.ObjetivoEl manejo de las perforaciones septales constituye un reto para el cirujano. Hay descritas una gran variedad de técnicas quirúrgicas, con distintas vías de abordaje. No existen pruebas científicas que avalen un abordaje en concreto. El objetivo de esta revisión es presentar una guía práctica sobre la técnica de elección para cada caso de perforación septal.DiscusiónLa inspección de la mucosa nasal, el tamaño de la perforación, la localización y, sobre todo, el soporte osteocartilaginoso son los pilares para lograr el éxito de la cirugía. Para los colgajos de deslizamiento o rotación de la mucosa del tabique es fundamental haber estudiado previamente si es posible la elevación del mucopericondrio o mucoperiosteo del septum, de lo contrario, el uso de estos colgajos no estaría indicado. Los colgajos de la pared lateral o del suelo nasal son la alternativa. El colgajo pericraneal podría estar indicado en perforaciones totales o casi totales.ConclusiónEl remanente del septum nasal y el estado del soporte osteocartilaginoso son los factores determinantes en el manejo de las perforaciones septales. Cada caso debe valorarse individualmente y la elección del abordaje se realiza según el tamaño y la localización de la perforación, la calidad de la mucosa, los antecedentes personales, la cirugía previa y la experiencia del cirujano.ObjectiveThe management of septal perforations is a challenge for the surgeon. A wide variety of surgical techniques have been described, with different approaches. There is no scientific evidence to support a particular approach. The objective of this review is to present a practical guide on the technique of choice for each case of septal perforation.DiscussionInspection of the nasal mucosa, the size of the perforation, the location and especially the osteo-cartilaginous support, are the pillars of a successful surgery. For the sliding or rotating flaps of the mucosa of the septum it is essential to know in advance if the elevation of the mucopericondrio or mucoperiosteo of the septum is possible, otherwise the use of these flaps would not be indicated. The flaps of the lateral wall or nasal floor are the alternative. The pericranial flap may be indicated in total or near total perforations.ConclusionThe remnant of the nasal septum and status of osteo-cartilaginous support are the determining factors in the management of septal perforations. Each case should be evaluated individually and the approach chosen according to the size and location of the perforation, mucosal quality, personal history, previous surgery and the experience of the surgeon.



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Autofluorescence spectroscopy for nerve-sparing laser surgery of the head and neck—the influence of laser-tissue interaction

Abstract

The use of remote optical feedback systems represents a promising approach for minimally invasive, nerve-sparing laser surgery. Autofluorescence properties can be exploited for a fast, robust identification of nervous tissue. With regard to the crucial step towards clinical application, the impact of laser ablation on optical properties in the vicinity of structures of the head and neck has not been investigated up to now. We acquired 24,298 autofluorescence spectra from 135 tissue samples (nine ex vivo tissue types from 15 bisected pig heads) both before and after ER:YAG laser ablation. Sensitivities, specificities, and area under curve(AUC) values for each tissue pair as well as the confusion matrix were statistically calculated for pre-ablation and post-ablation autofluorescence spectra using principal component analysis (PCA), quadratic discriminant analysis (QDA), and receiver operating characteristics (ROC). The confusion matrix indicated a highly successful tissue discrimination rate before laser exposure, with an average classification error of 5.2%. The clinically relevant tissue pairs nerve/cancellous bone and nerve/salivary gland yielded an AUC of 100% each. After laser ablation, tissue discrimination was feasible with an average classification accuracy of 92.1% (average classification error 7.9%). The identification of nerve versus cancellous bone and salivary gland performed very well with an AUC of 100 and 99%, respectively. Nerve-sparing laser surgery in the area of the head and neck by means of an autofluorescence-based feedback system is feasible even after ER-YAG laser-tissue interactions. These results represent a crucial step for the development of a clinically applicable feedback tool for laser surgery interventions in the oral and maxillofacial region.

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Mesenchymal stromal cell and osteoblast responses to oxidized titanium surfaces pre-treated with λ = 808 nm GaAlAs diode laser or chlorhexidine: in vitro study

Abstract

Preservation of implant biocompatibility following peri-implantitis treatments is a crucial issue in odontostomatological practice, being closely linked to implant re-osseointegration. Our aim was to assess the responses of osteoblast-like Saos2 cells and adult human bone marrow-mesenchymal stromal cells (MSCs) to oxidized titanium surfaces (TiUnite^®, TiU) pre-treated with a 808 ± 10 nm GaAlAs diode laser operating in non-contact mode, in continuous (2 W, 400 J/cm²; CW) or pulsed (20 kHz, 7 μs, 0.44 W, 88 J/cm²; PW) wave, previously demonstrated to have a strong bactericidal effect and proposed as optional treatment for peri-implantitis. The biocompatibility of TiU surfaces pre-treated with chlorhexidine digluconate (CHX) was also evaluated. In particular, in order to mimic the in vivo approach, TiU surfaces were pre-treated with CHX (0.2%, 5 min); CHX and rinse; and CHX, rinse and air drying. In some experiments, the cells were cultured on untreated TiU before being exposed to CHX. Cell viability (MTS assay), proliferation (EdU incorporation assay; Ki67 confocal immunofluorescence analysis), adhesion (morphological analysis of actin cytoskeleton organization), and osteogenic differentiation (osteopontin confocal immunofluorescence analysis; mineralized bone-like nodule formation) analyses were performed. CHX resulted cytotoxic in all experimental conditions. Diode laser irradiation preserved TiU surface biocompatibility. Notably, laser treatment appeared even to improve the known osteoconductive properties of TiU surfaces. Within the limitations of an in vitro experimentation, this study contributes to provide additional experimental basis to support the potential use of 808 ± 10 nm GaAlAs diode laser at the indicated irradiation setting, in the treatment of peri-implantitis and to discourage the use of CHX.

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Macrophage-derived interleukin-1beta promotes human breast cancer cell migration and lymphatic adhesion in vitro

Abstract

Lymphovascular invasion (LVI), encompassing blood and lymphatic vessel invasion, is an important event in tumourigenesis. Macrophages within the tumour microenvironment are linked to the presence of LVI and angiogenesis. This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1β) in an in vitro model of LVI. IL-1β significantly augmented the adhesion and transmigration of breast cancer cell lines MCF7 and MDA-MB-231 across endothelial cell barriers. MDA-MB-231 and MCF7 showed a higher percentage of adhesion to lymphatic endothelial cells than blood endothelial cells following endothelial cell IL-1β stimulation (P < 0.001 and P < 0.0001, respectively). Supernatants from activated macrophages increased the adhesion of tumour cells to lymphatic and blood endothelium. Secretion of IL-1β was caspase-1 dependent, and treatment with caspase-1 inhibitor reduced IL-1β production by 73% and concomitantly reduced tumour cell adhesion to levels obtained with resting macrophages. Transmigration of MDA-MB-231 cells across blood and lymphatic endothelial monolayers was significantly increased following IL-1β stimulation. Furthermore, supernatants from activated macrophages increased transmigration of MDA-MB-231 cells across endothelial monolayers, which was abolished by caspase-1 inhibition. IL-1β stimulation of tumour cells significantly increased their migratory ability and a significant increase in migration was observed when MDA-MB-231 cells were stimulated with macrophage conditioned media (two of three donors). Results demonstrate that macrophage production of IL-1β plays an important role in the migration of breast cancer cells and their adhesion to, and transmigration across, blood and lymphatic endothelial cells. Results suggest that IL-1β may play a role in the adhesion to lymphatic endothelial cells in particular.

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CD45RA − Foxp3 high regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma

Abstract

Background

Although regulatory T cells (Tregs) are thought to play an important role in immune suppression, their clinical significance in head and neck squamous cell carcinoma (HNSCC) is unclear. A recent study reported Tregs could be divided into functional subsets based on the expression of CD45RA and Foxp3.

Method

The frequency of circulating Treg subsets was analyzed in patients with HNSCC and compared with the frequency in patients with benign tumors. The association of Treg subsets with the frequency of lymphocyte subsets, status of progression, clinical course, and prognosis were also examined.

Results

The frequency of CD4⁺Foxp3⁺ Tregs was comparable between HNSCC patients and age-matched benign tumor patients; however, CD45RA⁻Foxp3^high Tregs were significantly increased in HNSCC patients, in particular those with advanced stage tumors. The high frequency of CD45RA⁻Foxp3^high Tregs correlated with a poor prognosis and the low frequency of CD45RA⁻Foxp3^high Tregs before treatment showed a better clinical outcome, even in patients with advanced stage tumors. CD45RA⁻Foxp3^high Treg numbers were decreased after intensive treatments; however, Treg numbers recovered in the early stages of recurrent cases, even before the clinical manifestation.

Conclusion

CD45RA⁻Foxp3^high Tregs are associated with the clinical course of HNSCC and might be a new target for treatment and an early marker of tumor recurrence in HNSCC patients.

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iSepsis – Introduction to the iSepsis Website

Introduction to ISepsis

EMCrit by Paul Marik.

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Phytoremediation of Jordanian Uranium-Rich Soil Using Sunflower

Abstract

Uranium-contaminated environments pose a risk to human health by means of its transfer to the food chain. Overcoming this issue requires using effective methods to minimize the availability of uranium and other metals in soils. Jordan has a promising project for electricity generation from nuclear power. To move forward with this nuclear project, the Jordan Central Area has been mined for uranium. The expansion of the mining activities in this area led to elevated contents of heavy metal in the surface soil. Phytoremediation efficiency in reducing uranium content from uranium-rich carbonate soil was tested using sunflower plants. Forty-eight sunflower plants were planted in three soil samples containing three different uranium concentrations. The plants were harvested after different planting periods in order to investigate the phytoremediation efficiency over time. The ability of sunflowers to translocate uranium was investigated and the results showed that the translocated amount of uranium to plant increased as the initial concentration of uranium in the soil increased. However, most of the uranium taken up by the sunflower was accumulated in the roots, and only 3% of the uranium concentration in the roots passed to the harvestable shoots. Moreover, the biomass of the plants was not affected by increasing uranium concentration in the plants indicating that sunflower is resistant to radiation and toxicity of uranium at these levels found in the soil.

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Exogenously Applied Citric Acid Enhances Antioxidant Defense and Phytoextraction of Cadmium by Willows ( Salix Spp.)

Abstract

The effect of exogenously applied citric acid (CA) on phytoextraction and antioxidant defense was analyzed using willow species (Salix viminalis, S. alba, and S. matsudana) grown in soil contaminated with cadmium (Cd). Citric acid has been used as a chelating agent for the purpose of accelerating the solubility of Cd in soil and enhancing the phytoextraction of selected plants. Willows were exposed to 6 mg/kg of Cd, following the same with citric acid (20 mM/kg soil). Results revealed a positive effect of citric acid in mobilization of accumulated Cd from roots to shoots and leaves. The addition of citric acid alleviated Cd toxicity by helping plants to overcome oxidative stress, through CA’s chelating properties and the increased activity of antioxidant enzymes. Different protection strategies were evident through modification of activities of antioxidant enzymes such as catalase (CAT), ascorbate-peroxidase (APx), and guaiacol peroxidase (GPx) in young versus mature leaves in plants exposed to Cd. Furthermore, results revealed that addition of citric acid may be beneficial in the reduction of the negative effect of Cd stress on photosynthesis. The efficiency of coupling phytoextraction with the chelating agents represents a good strategy for decreasing damages caused by cadmium and has good potential in decontamination of a polluted environment.

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Comparison of Methodologies for Field Application of Road Dust

Abstract

Road dust impacts almost all terrestrial areas of the planet and may impact vegetation and nearby ecosystems. Therefore, research methods are needed for applying road dust in a controlled manner on targeted areas (e.g. plants). Three dust application methods, sifter, sieve, and sprayer, were investigated for their uniformity in applying dust in a 0.75 m × 0.75 m area. Within the treatment area 196, 37-ml cups were placed in a uniform fashion to collect dust applied at 15.8, 78.8, and 158 g. At the 15.8 and 78.8 g rates, the coefficient of uniformity for each method was >98% indicating a uniform amount of dust applied. At the 158 g rate, the sifter and sieve had coefficient of uniformities >95%, while the sprayer had a significantly lower (p < 0.05) coefficient of uniformity (46%). Although the sifter and sieve were simpler to use and the least expensive options, the sprayer may be more useful when applying dust to larger areas when the exact amount of dust entering and exiting the systems does not need to be controlled. This research is useful to anyone looking to apply road dust or similar sized particulates under controlled field or laboratory conditions.

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Extramedullary plasmacytoma of the ureter in an HIV-positive patient

Abstract

A 45-year-old Japanese man, who was undergoing HIV infection treatment, was aware that he had gross hematuria, and he was diagnosed as having a ureteral tumor by radiographic examination. Therefore, he was referred to our department for further examination and treatment. We considered that the ureteral tumor was a urothelial carcinoma (cT2N0M0) because of the left ureteral tumor and urine cytology results, and thus, laparoscopic ureteronephrectomy was performed. The pathological diagnosis was a solitary extramedullary plasmacytoma (EMP) of the ureter. Currently, he is alive and free of disease at 7 months postoperatively. EMP develops in the nasal cavity, paranasal cavity, gastrointestinal tract, lung, thyroid, eye socket, lymph node, and various organs, but the ureter is an extremely rare site of EMP. In addition, the patient had an HIV infection. To the best of our knowledge, this is the first case of EMP of the ureter in an HIV-positive patient.

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Fluorescent CXCR4 targeting peptide as alternative for antibody staining in Ewing sarcoma

Abstract

Background

Ewing sarcoma is an aggressive, highly metastatic primary bone and soft tissue tumor most frequently occurring in the bone of young adolescents. Patients, especially those diagnosed with a metastatic disease, have a poor overall survival. Chemokine receptor CXCR4 has a key pro-tumorigenic role in the tumor microenvironment of Ewing sarcoma and has been suggested to be involved in the increased metastatic propensity. Earlier studies on CXCR4 protein expression in Ewing sarcoma yielded contradictory results when compared to CXCR4 RNA expression studies. Previously, we demonstrated that CXCR4 expression could be detected in vivo using the fluorescently tagged CXCR4-specific peptide MSAP-Ac-TZ14011. Therefore, we studied the membranous CXCR4 expression in Ewing sarcoma cell lines using MSAP-Ac-TZ14011.

Methods

The CXCR4 membrane expression levels were studied in EWS cell lines by flow cytometry using the hybrid peptide MSAP-Ac-TZ14011 and were correlated to CXCR4 RNA expression levels. The measurements were compared to levels detected using the CXCR4 antibody ab2074 under various cell preparation conditions. In addition, the staining patterns were analyzed by confocal fluorescence microscopy over time.

Results

The hybrid peptide MSAP-Ac-TZ14011 levels showed a strong and better correlation of CXCR4 membrane expression with the CXCR4 RNA expression levels than observed with the anti-CXCR4 antibody ab2074. With the hybrid peptide MSAP-Ac-TZ14011 using live cell confocal microscopy CXCR4 membrane staining and internalization was detected and the signal intensity correlated well with CXCR4 mRNA expression levels.

Conclusions

The fluorescently labeled CXCR4 targeting peptide-based method provides a reliable alternative to antibody staining to study the CXCR4 membrane expression in live cells using either flow cytometry or live cell fluorescence microscopy. The fluorescently tagged CXCR4 targeting peptide could enable in vivo detection of CXCR4 expression in Ewing sarcoma which may help to stratify cases for anti-CXCR4 therapy.

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Glyoxalase 1 expression is associated with an unfavorable prognosis of oropharyngeal squamous cell carcinoma

Abstract

Background

Glyoxalase 1 is a key enzyme in the detoxification of reactive metabolites such as methylglyoxal and induced Glyoxalase 1 expression has been demonstrated for several human malignancies. However, the regulation and clinical relevance of Glyoxalase 1 in the context of head and neck squamous cell carcinoma has not been addressed so far.

Methods

Argpyrimidine modification as a surrogate for methylglyoxal accumulation and Glyoxalase 1 expression in tumor cells was assessed by immunohistochemical staining of tissue microarrays with specimens from oropharyngeal squamous cell carcinoma patients (n = 154). Prognostic values of distinct Glyoxalase 1 staining patterns were demonstrated by Kaplan-Meier, univariate and multivariate Cox proportional hazard model analysis. The impact of exogenous methylglyoxal or a Glyoxalase 1 inhibitor on the viability of two established tumor cell lines was monitored by a colony-forming assay in vitro.

Results

Glyoxalase 1 expression in tumor cells of oropharyngeal squamous cell carcinoma patients was positively correlated with the presence of Argpyrimidine modification and administration of exogenous methylglyoxal induced Glyoxalase 1 protein levels in FaDu and Cal27 cells in vitro. Cal27 cells with lower basal and methylglyoxal-induced Glyoxalase 1 expression were more sensitive to the cytotoxic effect at high methylgyoxal concentrations and both cell lines showed a decrease in colony formation with increasing amounts of a Glyoxalase 1 inhibitor. A high and nuclear Glyoxalase 1 staining was significantly correlated with shorter progression-free and disease-specific survival, and served as an independent risk factor for an unfavorable prognosis of oropharyngeal squamous cell carcinoma patients.

Conclusions

Induced Glyoxalase 1 expression is a common feature in the pathogenesis of oropharyngeal squamous cell carcinoma and most likely represents an adaptive response to the accumulation of cytotoxic metabolites. Oropharyngeal squamous cell carcinoma patients with a high and nuclear Glyoxalase 1 staining pattern have a high risk for treatment failure, but might benefit from pharmacological targeting Glyoxalase 1 activity.

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Tissue Factor Expression Does Not Predict Mortality in Breast Cancer Patients

Background: Tissue factor (TF), the trigger of coagulation, not only initiates thrombus formation, but also elicits tumor growth and invasion in breast cancer. However, the characterization of TF expression in breast cancer tissue and its prognostic value remain unclear. Materials and Methods: Three hundred and three primary breast cancer specimens from the local tumor tissue database were immunostained for TF expression and evaluated semiquantitatively. Tumor characteristics (size, grade, nodal status, and ER expression) as well as patient's survival were assessed. Results: Expression of TF was detected in 99% of specimens with higher expression in invasive lobular than ductal carcinoma (p=0.008). TF expression correlated with ER expression (p<0.0001) and inversely with tumor grade (p=0.006). Survival analysis did not reveal any prognostic impact of TF expression (p=0.966). Conclusion: This study – by analyzing TF expression in the largest cohort of breast cancer patients so far – does not support a prognostic impact of TF expression.

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Circulating Antibodies to Linear Peptide Antigens Derived from ANXA1 and FOXP3 in Lung Cancer

Background: Our previous studies revealed that concentrations of circulating antibodies to annexin A1 (ANXA1) and forkhead-box P3 (FOXP3) increased significantly in patients with non-small cell lung cancer (NSCLC). This study was thus undertaken to replicate our initial findings with different sample sets. Patients and Methods: Antibodies were tested in 108 patients with NSCLC and 216 controls, who were divided into the discovery (49 vs. 108) and validation (60 vs. 108) group based on the time of enrolment. Results: Analysis of the discovery group showed a significant increase in circulating anti-ANXA1 IgG levels in the patient group compared with the control group (p=0.005) but the validation group simply exhibited a trend toward an increase in IgG levels in NSCLC (p=0.238), generating a combined p-value of 0.009. Conclusion: The findings of this study support the notion that circulating IgG antibodies to ANXA1 could be used as a biomarker for early diagnosis of NSCLC but failed to replicate such findings for FOXP3.

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Pancreatic Cancer Stem Cells and Therapeutic Approaches

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest human cancers, with 1-5% 5-year survival rates (~6-month median survival duration) despite therapy; thus, PDAC represents an unmet therapeutic challenge. PDAC is the major histological subtype, comprising 90% of all pancreatic cancers. It is a highly complex and aggressive malignancy, presenting with early local invasion and metastasis, and is resistant to most therapies, all of which are believed to contribute to its extremely poor prognosis. PDAC is characterized by molecular alterations, including mutations of K-RAS (~90% of cases), TP53, transforming growth factor-β, Hedgehog, WNT and NOTCH signaling pathways. Given that cancer stem cells have a crucial role not only in tumor initiation and progression, but also in drug resistance and relapse or recurrence of various cancer types, they may be excellent targets for effective novel therapeutic approaches. Here, we reviewed recent therapeutic strategies targeting pancreatic cancer stem cells using chemotherapeutics and targeted drugs, non-coding RNAs (i.e., siRNA and miRNAs), immunotherapy, and natural compounds.

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Rare Neoplasm Mimicking Neuoroendocrine Pancreatic Tumor: A Case Report of Solitary Fibrous Tumor with Review of the Literature

Background: Solitary fibrous tumors (SFTs) are rare biological entities described mainly in the pleura. To date, in the pancreas, only 14 cases have been reported in the English literature. Case Report: A 52-year-old male was diagnosed incidentally with a suspected neuroendocrine tumor (NET) of the pancreas. He underwent pancreatic enucleation of the mass, which, at final pathology, showed spindle cell proliferation set in a collagenous background and featuring the presence of hemangiopericytoma-like blood. Immunohistochemistry showed cytoplasmic expression of CD34 and nuclear expression of STAT6. As mitotic activity was of 1 mitoses/10 high-power fields (HPFs) a diagnosis of conventional SFT was made. The patient was discharged without major complications and is alive and free of disease after 24 months. Conclusion: SFTs of pancreas are rare tumors, often mimicking pancreatic NET.

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Erdheim-Chester Disease: Comprehensive Review of Molecular Profiling and Therapeutic Advances

The revised 2016 World Health Organization classification introduced Erdheim–Chester disease (ECD) as a provisional entity within the histiocytic and dendritic cell neoplasms separate from the juvenile xanthogranuloma family based on distinct molecular features. However, evolving knowledge regarding the molecular and genetic aberrations in addition to common clinical features of ECD support the classification of ECD together with Langerhans cell histiocytosis (LCH). Accordingly, ECD can be thought of as an inflammatory myeloid clonal disorder based on the detection of various activating mutations along the mitogen activated protein kinase-extracellular signal regulated kinase (MAPK-ERK) pathway with most notable variant being a valine to a glutamic acid substitution at amino acid 600 in the B-rapidly accelerated fibrosarcoma protein (BRAFV600E). In this group, targeted therapy with a B-Raf inhibitor alone or combined with a MAPK-ERK (MEK) inhibitor has shown promising results based on several case reports. Currently, two phase II trials with BRAF inhibitors are underway and could potentially change the standard of care. MEK inhibitors may also be efficacious in ECD harboring mutations in MAP2K1; other potential targetable aberrations include programed cell death receptor 1 and mutations in phosphoinositide 3-kinase.

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The Role of Concomitant Radiation Boost in Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Background/Aim: This study analyzed the impact of concomitant boost on long-term clinical outcomes in locally advanced rectal cancer. Patients and Methods: A total of 141 patients (median age=61 years) were treated with neoadjuvant chemoradiotherapy. Median total dose was 50.4 Gy. Forty-three patients received a concomitant boost. Concurrent chemotherapy consisted of 5-fluorouracil (5-FU), given as a 24-h continuous infusion. Mean follow-up was 83.7 months. Results: The 3, 5-, and 10-year overall survival (OS) rates were 91.9%, 84.6%, and 52.9%, respectively. Recurrence-free survival (RFS) rates at 3, 5, and 10 years were 91.4%, 88.9%, and 79.3%, respectively. Metastasis-free survival (MFS) rates at 3, 5, and 10 years were 84.6%, 75.4%, and 49.9%, respectively. Overall, 9.9% of all patients achieved pathological complete response. Down-staging of T- or N-stage was achieved in 55.1% and 41.5% of patients. Multivariate analysis revealed that female sex (p=0.011), concomitant boost-radiotherapy (p=0.014), and the presence of fewer than five positive lymph nodes (p<0.001) were positive predictors of OS. Fewer than five positive lymph nodes was also a positive predictor for RFS (p=0.019). Female gender (p=0.018) and fewer than five positive lymph nodes (p<0.001) were significant predictors for MFS. Conclusion: Our data support the efficacy of preoperative treatment for rectal cancer in terms of local outcomes. Intensified radiotherapy using a concomitant boost has a positive effect on OS.

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Cancer Tissue Classification, Associated Therapeutic Implications and PDT as an Alternative

Carcinogenesis occurs via mutation of critical genes conferring enhanced survival and protection to the ensuing tissue. Current therapies in use garner success due to their specificity for certain intracellular targets. This particularity, whist beneficial in identifying tumorigenic from normal tissue states, is limited by the variations in geno/phenotypic profiles displayed between tumor tissue types. As such, tissue-specific therapeutic combinations and adjuvants are often required for adequate effect, but present symptomatic complications and occasionally generate secondary carcinogenesis displaying multi-drug resistance (MDR). An accumulation of research over the recent years has suggested that photodynamic therapy (PDT) with macrocycle photosensitizers are a promising alternative. Its administration method and toxicity mechanism present attractive features for potentially overcoming MDR cancers of multiple tissue origins with limited symptomatic onsets. Herein, we highlight these potentials as referenced against existing therapeutics and consider the impact of macrocycle-PDT for broad spectrum application regardless of tumorigenic resistance profiles.

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Neoadjuvant Chemoradiotherapy for Stage II or III Esophageal Squamous Cell Carcinoma

Background/Aim: The goal of this retrospective study was to investigate the efficacy and safety of neoadjuvant chemoradiotherapy (CRT) in patients with Stage II or Stage III esophageal squamous cell carcinoma (SCC). Patients and Methods: Between January 2004 and December 2014, a total of 86 patients underwent surgical resection in conjunction with preoperative CRT for esophageal SCC in our Institute. Results: A pathological complete response was achieved in 38.7% of patients with Stage II cancer and 20% of patients with Stage III. Postoperative complications were observed in 61.3% of Stage II and 76.4% of Stage III patients. The 5-year overall survival rate (OS) was 83.2% in Stage II and 22.8% in Stage III (p=0.0001). The 5-year disease-free survival (DFS) rate was 67.9% in Stage II and 29.9% in Stage III (p=0.0007). Conclusion: Neoadjuvant CRT may improve OS and DFS rates in patients with Stage II esophageal SCC.

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Targeted Therapy in Ovarian Cancer. A Comprehensive Systematic Review of Literature

Background/Aim: We aimed to identify the most effectual groups of targeted therapies for ovarian cancer in recent clinical trials. Materials and Methods: A systematic literature review has been gathered on an inventive study design that comprises of five steps. This involves search for pertinent publications from 2010 to date in various accessible medical data bases, usage of inclusion and exclusion, appraisal of quality of the studies included, abstraction of the relevant data and intelligible amalgamation of the data abridged in an evocative and narrative style. Results: Three types of modalities of targeted-therapy drugs have been identified; angiogenesis inhibition, signal enzymes inhibition and apoptosis induction in the tumor cells. Conclusion: There has been a surge in clinical trials with drugs that specifically target signal enzymes, induce apoptosis and inhibit angiogenesis in site-specific ovarian cancer cells, which could be very promising to design a more efficacious protocol for treating the disease.

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Clinical Relevance of Serum HER2 and Circulating Tumor Cell Detection in Metastatic Breast Cancer Patients

Background/Aim: Presence of circulating tumor cells (CTCs) is associated with impaired survival in metastatic breast cancer (MBC). This study was designed to evaluate whether assessment of serum HER2 (sHER2) levels provide additional prognostic information in MBC. Materials and Methods: Two hundred and fifty-three MBC patients were enrolled in this multicentre trial. CTCs were detected before the start of first- or later-line treatment using the CellSearch system. sHER2 was determined using ELISA. Results: ≥5 CTCs were detected in 122 of 245 evaluable patients (49.8%). One hundred and nineteen of 251 patients (47%) had sHER2 levels above 15 ng/ml. Median overall survival (OS) was 16.3 months in patients with elevated sHER2; median OS in patients with non-elevated sHER2 has not been reached (p=0.001). Patients with ≥5 CTCs were more likely to present with elevated sHER2 (61% vs. 33% in those with <5 CTC; p<0.001). In patients with HER2-negative tumors, elevated sHER2 was associated with shorter OS and PFS; in HER2-positive patients with OS only. Including sHER2, CTC status and established prognostic factors into a multivariate analysis, only the presence of CTCs and higher-line of therapy remained independent predictors of OS. Conclusion: Elevated levels of sHER2 are associated with worse survival, irrespective of the HER2 status of the tumor. However, sHER2 does not provide additional prognostic information in patients with known CTC status.

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Measuring Intragastric Tumor Markers in Gastric Cancer Patients: a Systematic Literature Review on Significance and Reliability

As of 2017, no serum tumor marker has shown high levels of sensitivity or specificity for early detection, classification, staging, prediction and prognosis of patients affected by gastric cancer. In this regard, since 1975 several authors have investigated the gastric juice or gastric lavage of patients with gastric adenocarcinoma in order to determine the concentrations of intragastric tumor markers and discover the perfect antigen for this cancer. To date, however, a systematic review of the literature on intragastric tumor markers is still unreported. After a thorough search, we found important as well as unimportant findings and have come to clearly defined conclusions. We believe that describing the current state of knowledge achieved by the scientific community in this particular field of research could augment information on the complex pathobiology of gastric cancer and entail a deeper understanding of its unpredictable malignant behavior.

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Prognostic Significance of Preoperative Anemia in Patients Undergoing Surgery for Renal Cell Carcinoma: A Meta-analysis

Aim: To better evaluate the association between preoperative anemia and outcomes in patients following radical or partial nephrectomy for renal cell carcinoma (RCC). Materials and Methods: A meta-analysis of hazard ratios (HR) was conducted to measure the association between preoperative anemia and all-cause mortality (ACM), cancer-specific mortality (CSM), and disease recurrence (DR) in patients who underwent surgery for RCC. Results: A total of 14 studies (8,673 patients) met the eligibility criteria. All studies reported survival outcomes using the multivariable Cox proportional hazards model. Pooled results showed that preoperative anemia was associated with increased ACM [HR=2.13, 95% Confidence Interval (CI)=1.48-3.06], CSM (HR=1.91, 95% CI=1.26-2.90), and DR (HR=1.67, 95% CI=1.16-2.40). Conclusion: This meta-analysis indicates that preoperative anemia appears to be associated with earlier recurrence and shorter survival of patients undergoing radical or partial nephrectomy for RCC. Our findings, however, still need to be validated by well-designed prospective studies with larger sample sizes and well-controlled confounding factors.

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3,4,7-O-trimethylquercetin Inhibits Invasion and Migration of Ovarian Cancer Cells

Background/Aim: Methylquercetin, 3,4’,7-O-trimethylquercetin (34’7TMQ), has been reported to inhibit metastasis. Recently, we demonstrated that 34’7TMQ inhibited the in vitro melanoma B16 cell metastatic activity. We evaluated the effect of 34’7TMQ on three ovarian cancer cells (SK-OV-3, CRL11731 and CRL1978). Materials and Methods: Proliferation, migration and invasion were measured in 34’7TMQ-treated ovarian cancer cells by commercially available kits. We also evaluated the expression of proliferating cell nuclear antigen (PCNA), urokinase plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1) and matrix metalloproteinase (MMP)-2 by western blot analysis. Results: 34’7TMQ inhibited ovarian cancer cell migration and invasion without effecting proliferation. Furthermore, 34’7TMQ inhibited the expression of uPA and MMP-2; however, it had no effect on PAI-1 and PCNA. Conclusion: 34’7TMQ significantly regulates the expressions of protein to inhibit metastasis in ovarian cancers, while the regulatory effects of 34’7TMQ vary between different ovarian cancer cell lines.

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Effects of Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios on Survival in Patients with Extrahepatic Cholangiocarcinoma

Background/Aim: As indicators of systemic inflammatory response, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict prognoses for various cancers. This study investigated their prognostic significance in extrahepatic cholangiocarcinoma (ECC). Patients and Methods: We analyzed 120 patients who underwent surgery for ECC between 2000 and 2014. We calculated preoperative NLR and PLR and evaluated their correlations with patients' clinicopathological features and prognosis. Results: Although high NLR was not associated with worse recurrence-free survival (RFS) (hazard ratio (HR)=1.32, p=0.26), cancer-specific survival (CSS) (HR=1.35, p=0.31) and overall survival (OS) (HR=1.19, p=0.52), high PLR was significantly associated with worse RFS (HR=1.85, p=0.01), CSS (HR=2.38, p=0.002) and OS (HR=1.98, p=0.008). In multivariate analysis, high PLR (HR=1.89, p=0.02) and lymph node metastasis (HR=1.78, p=0.03) were independent prognostic factors for OS. A high PLR had more liver recurrences (p=0.04) and recurrences within 1 year (HR=2.38, p=0.02) than low PLR. Conclusion: High preoperative PLR was an independent predictor of poor prognosis for patients with ECC who underwent resections.

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MEK162 Enhances Antitumor Activity of 5-Fluorouracil and Trifluridine in KRAS-mutated Human Colorectal Cancer Cell Lines

Background: Preclinical evidence demonstrates that mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway inhibition increases sensitivity to 5-fluorouracil (5-FU) in colorectal cancer (CRC) cell lines and xenografts. Here, we aimed to investigate how CRC cell sensitivity to this combination is correlated to Kirsten rat sarcoma (KRAS) and proto-oncogene B-rapidly accelerated fibrosarcoma (BRAF) mutation, that are common in CRC and often lead to resistance to chemotherapy. Materials and Methods: Wild-type and mutant KRAS/BRAF human CRC cell lines were treated with escalating doses of 5-FU or trifluridine with MEK162 (MEK1/2 inhibitor) for 72 h. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and synergism expressed by the combination index was calculated using CalcuSyn. Results: Evidence of synergistic antitumor activity was observed for the majority of human CRC cell lines treated with MEK162 plus 5-FU (4/6) or trifluridine (7/9). Synergism was greater in KRAS- or BRAF-mutant cell lines compared to wild-type KRAS/BRAF CRC cell lines. Conclusion: The combination of MEK inhibition and trifluridine is worthwhile advancing in clinical development, particularly for treatment-refractory KRAS- or BRAF-mutated metastatic CRC.

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Serum Levels of IGF-1 and IGFBP-3 in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas

Background/Aim: Head and neck squamous cell carcinoma (HNSCC) includes tumors of various anatomical sites sharing multifactorial etiopathogenesis and generally dismal response to conventional treatment. The objective of this study was to determine the clinical significance of serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in HNSCC. Patients and Methods: A total of 46 patients, with histologically-confirmed diagnosis of HNSCC (21 oropharyngeal, 21 laryngeal, and 4 hypopharyngeal cancers) were enrolled in this study. IGF-1 and IGFBP-3 serum levels were measured by an immunoradiometric assay using commercial kits. The adjustment of serum levels at 60 years of age was performed. Results: Significant differences were found in IGF-1 serum concentrations between patients with p16 positive and p16 negative HNSCC (p=0.0062), with higher IGF-1 levels in p16 positive tumors, between low-grade and high-grade cancers (p=0.0323) only in larynx, with elevated IGF-1 concentrations associated with high-grade and between recurrent and non-recurrent HNSCC (p=0.0354), with lower IGF-1 levels in recurrent tumors. Conclusion: The conflicting results of this study may reflect some abnormality of IGF axis regulation in HNSCC, as well as the influence of other etiological factors (e.g. smoking, HPV infection).

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Structure-Activity Relationship of Niclosamide Derivatives

Background/Aim: Cancer is a leading cause of death. Hence, this study aimed at the optimization of niclosamide derivatives for the development of new potential anticancer agents. Materials and Methods: Niclosamide derivatives were synthesized and tested against a panel of human cancer cells: MDA and MCF7 breast cancer cells, PC3 and DU-145 prostate cancer cells, Hela cervical cancer cells, and HL-60 acute promyelocytic leukemia cells. They were also tested in nuclear factor-ĸappa B (NFĸB), V-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and mitochondria transmembrane potential (MTP) assays. Results: N-(3,5-Bis(trifluoromethyl)phenyl)-5-chloro-2-hydroxybenzamide exhibited the most significant cytotoxicity against HL-60 cells, while 5-chloro-N-(2-chlorophenyl)-2-hydroxybenzamide was the most active in the NFĸB assay and 5-chloro-N-(3,5-difluorophenyl)-2-hydroxybenzamide in the MTP assay. 5-chloro-N-(2-chloro-4-(trifluoromethyl) phenyl)-2-hydroxybenzamide and 5-chloro-2-hydroxy-N-(4-hydroxyphenyl)benzamide inhibited both HL-60 cell proliferation and NFĸB. Conclusion: In-depth study of the most promising compounds is highly encouraged to further develop into potential anticancer agents those derivatives found to be significantly active.

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Concordance of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization Using Tissue Microarray in Breast Cancer

Aim: Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are common methods for assessment of human epidermal growth factor receptor 2 (HER2) in breast cancer. Materials and Methods: In a cohort of 498 consecutive patients with breast cancer, we examined concordance between IHC and FISH for HER2 on tissue microarray (TMA) sections. In a subset of 116 specimens, we examined HER2 concordance from the block used for diagnostics and a randomly-chosen additional block (a proxy of the core biopsy). Results: Overall concordance between both methods on TMA sections was 93.8% and between HER2, determined on diagnostic and additional blocks, was 93.6% for IHC and 98.0% for FISH. Conclusion: Since some cases were discordant, we suggest that both methods be used for HER2 assessment. The lower concordance rate between diagnostic and additional blocks using IHC compared to FISH suggests a greater variability of IHC staining across tumor regions than for FISH results.

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Impact of Small Molecules on {beta}-Catenin and E-Cadherin Expression in HPV16-positive and -negative Squamous Cell Carcinomas

Background: The validation of potential molecular targets in head and neck squamous cell carcinoma (SCC) is mandatory. β-Catenin and E-cadherin are crucial for cancer progression through epithelial–mesenchymal transition. We analyzed the effect of the tyrosine kinase inhibitors nilotinib, dasatinib, erlotinib and gefitinib on β-catenin and E-cadherin expression in SCC with respect to human papillomavirus (HPV) status. Materials and Methods: Expression of β-catenin and E-cadherin in cell lines UMSCC 11A, UMSCC 14C and CERV196 under the influence of tyrosine kinase inhibitors were analyzed by enzyme-linked immunosorbent assay. Results: All agents reduced β-catenin and E-cadherin expression of HPV16-negative cells. Increased E-cadherin expression was observed after treatment with gefitinib and dasatinib in HPV16-positive cells. Conclusion: All substances, nilotinib, dasatinib, erlotinib and gefitinib have a significant impact on β-catenin and E-cadherin expression in both HPV16-positive and HPV16-negative cells in vitro. Alterations of β-catenin and E-cadherin could provide novel insights for future targeted therapies of head and neck SCC.

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Complete Reversion of Familial Adenomatous Polyposis Phenotype Associated with Tacrolimus and Mycophenolate Mofetil Treatment Following Kidney Transplantation

Numerous germline mutations in the adenomatous polyposis coli (APC) tumor-suppressor gene are responsible for development of multiple adenomatous colorectal polyps with their inevitable progression to cancer. Multiple attempts at dietary and pharmacological prevention of colorectal carcinoma development in patients with familial adenomatous polyposis (FAP) have provided conflicting results. Immunosuppressive treatment with tacrolimus is known to be associated with an increased risk of malignancy and should be avoided in patients with high propensity for development of neoplasia. We observed a complete reversion of FAP phenotype in a male teenager carrying a germline mutation in APC gene who underwent a kidney transplant due to end-stage kidney disease secondary to congenital dysplastic kidneys. The patient was treated with tacrolimus and mycophenolate mofetil after transplantation. The possible chemopreventative role of these agents should be evaluated and confirmed in a larger cohort. The elucidation of molecular mechanisms underpinning the observed chemopreventative effect of tacrolimus and mycophenolate mofetil might lead to the development of a novel colorectal cancer therapy.

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Orofacial Pain Biomarkers 2017

Jean-Paul Goulet Description This book provides up-to-date information on all aspects of orofacial pain biomarkers. It opens by presenting background information on clinical phenotypes and the neurobiological substrates underlying chronic... Read more »

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Atlas of Implant Dentistry and Tooth-Preserving Surgery : Prevention and Management of Complications

Zoran Stajcic Description This atlas is unique in comparing the two disciplines of dental implant surgery and tooth-preserving surgery with respect to common procedures, problems, and failures and in providing... Read more »

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Sentinel node biopsy status is strongly predictive of survival in cutaneous melanoma: Extended follow-up of Oxford patients from 1998-2014

Publication date: Available online 27 May 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): David R. Thomson, Milap G. Rughani, Rachel Kuo, Oliver CS. Cassell
IntroductionSentinel lymph node biopsy (SLNB) is widely used as a key investigatory tool for cutaneous melanoma, with results incorporated into the latest AJCC staging guidelines. We present the results of our extended follow-up of sentinel lymph node biopsy for melanoma over a sixteen-year period.MethodsData were collected prospectively from June 1998 to December 2014 from a single tertiary skin cancer referral centre. Chi-squared analysis was used to analyse patient demographics and primary tumour pathology. Survival analysis was conducted using Cox regression models and Kaplan-Meier survival curves.ResultsOver a sixteen-year period 1,527 patients underwent SLNB in 1,609 basins, with 2,876 nodes harvested. 347 patients (23%) had a positive biopsy. The most common primary tumour sites for males was the back (32%); women had a significantly higher number of melanomas occurring on the lower and upper limbs (45% and 26% respectively) [all p<0.0001, Chi-squared]. Mean follow-up time was 4.9 years. Patients with a positive SLNB at diagnosis were significantly more likely to die from melanoma (subhazard ratio 5.59, p=0.000, 95% CI 3.59-8.69). Breslow thickness and ulceration were also significant predictors of melanoma-specific mortality. For patients with a primary Breslow >4.0mm ten-year disease free survival was 52% for SLNB negative and 26% for SLNB positive patients. For Breslow thicknesses of 2.01-4mm these values were 66% and 32% respectively.ConclusionsSentinel lymph node biopsy status is strongly predictive of survival across all thicknesses of primary cutaneous melanoma.



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